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388. Ironing out the Data: Iron Deficiency in Heart Failure with Dr. Robert Mentz20 Aug 202400:12:28

CardioNerds Cofounder Dr. Amit Goyal, Chair of the CardioNerds Heart Failure Committee Dr. Jenna Skowronski, and Episode FIT Lead Dr. Shazli Khan discuss iron deficiency and its impact on heart failure with Dr. Robert Mentz, Chief of Heart Failure at Duke University and principal investigator of the HEART-FID trial. In this case-based discussion, they cover the diagnostic criteria of iron deficiency in heart failure, epidemiology, and strengths and limitations of different iron formulations.  They also review clinical trials examining the impact of iron deficiency on quality of life, heart failure hospitalizations, and mortality. Importantly, they stress the relevance of iron metabolism in heart failure, irrespective of the presence of anemia. They also discuss the approach to addressing outpatient management of iron in heart failure and future directions of research needed in this domain.

Notes were drafted by Dr. Shazli Khan, and Dr. Daniel Ambinder engineered episode audio.

Click here for CME.

This episode was created in collaboration with the Cardiometabolic Health Congress and is supported by an educational grant from American Regent. Please follow the link in the show notes for free CME. All CardioNerds education is planned, produced, and reviewed by CardioNerds.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls – Iron Deficiency in Heart Failure
  • Think about iron deficiency in ALL patients with heart failure and send appropriate diagnostic labs, even if there is no evidence of anemia!
  • Iron deficiency in heart failure has a specific and distinguished definition, defined as a ferritin level of <100 ng/mL, or a ferritin level between 100-300 ng/mL with a transferrin saturation of <20%.
  • Data thus far suggests that treatment of iron deficiency in heart failure results in improved quality of life, as well as a probable reduction in heart failure hospitalizations, and that administration of intravenous iron has a favorable safety profile.
  • Not all formulations of iron are created equal – intravenous iron formulations have been shown to be effective in this population, but oral iron therapy has not.
  • Management of iron deficiency in the outpatient setting is an evolving area of research, but patients should typically receive surveillance labs and additional treatment with IV iron if indicated.
Show notes – Iron Deficiency in Heart Failure

How is iron deficiency in heart failure defined, and how prevalent is iron deficiency in this patient population?

  • Iron deficiency is common in patients with heart failure, with an estimated prevalence of 50-60%.
    • Iron deficiency in heart failure is associated with worse outcomes, including increased hospitalization and mortality and poorer functional status and quality of life.
    • Iron deficiency in heart failure is defined as a ferritin level of <100 ng/mL or a ferritin level of 100-300 ng/mL plus a transferrin saturation of <20%.
    • There is an evolving school of thought that suggests transferrin saturation alone may be the best indicator of iron deficiency in heart failure, but more data are needed.

Importantly, iron deficiency in heart failure can be seen in patients with both reduced and preserved ejection fraction. Which patients should be screened for iron deficiency?

  • There is a class I indication to send iron studies in all patients with heart failure as a part of the initial diagnostic work-up for the underlying etiology of the cardiomyopathy, as well as to assess for the presence of iron deficiency.
    • The presence of anemia is not required to check iron studies, as many patients with iron deficiency in heart failure may not have concomitant anemia.
    • That is, all patients with heart failure should be evaluated for iron deficiency, irrespective of the presence of anemia.

What are the hypothesized mechanisms of iron deficiency in heart failure, and how does iron deficiency impact patients with heart failure?

  • Mechanisms causing iron deficiency in heart failure are multifactorial, including reduced oral intake, reduced gut absorption, reduced iron availability due to sequestration, and increased loss due to higher rates of bleeding.
    • Nutritional variation is one proposed mechanism, as patients living with heart failure tend to take in less iron in their diet, and the iron consumed tends to be less easily absorbed.
    • Due to chronic inflammation, there are increased levels of iron sequestration in cells in patients with heart failure, rendering the available iron stores unable to be used.
    • Patients with chronic heart failure also tend to be on anti-platelet agents and/or anticoagulants (due to often-occurring comorbidities), which may potentially lead to bleeding complications, consequently causing iron deficiency.
    • Iron deficiency has been associated with decreased exercise tolerance and functional status, worse quality of life, and increased risk of heart failure hospitalizations.

What are the key takeaways of the clinical trials done in patients with heart failure and iron deficiency?

  • The FAIR-HF trial published in 2009 demonstrated that treatment with IV ferrous carboxymaltose (FCM) in patients with heart failure led to improved symptoms and quality of life with an acceptable safety profile. These benefits were verified in a follow-up study known as CONFIRM-HF, demonstrating improvement in 6MWT and functional capacity.
    • The AFFIRM-AHF trial investigated IV FCM in patients with iron deficiency and a left ventricular ejection fraction of <50%. It was a neutral trial with no significant improvement in their primary endpoint, a composite of hospitalization and death. The trial did demonstrate the safety of FCM and decreased hospitalizations. Of note, this trial was significantly impacted by the COVID pandemic, which may have affected the results. 
    • The IRONMAN trial was similar in design to AFFIRM-AHF but used a different iron formulation (iron derisomaltose) and had similar findings.
    • The HEART-FID trial was a larger study including 3000 patients with HFrEF investigating treatment with IV ferric carboxymaltose every six months if the patients remained iron deficient. The primary endpoint was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. While it was considered a neutral trial with a p=0.019 with a prespecified significance level of 0.01, it demonstrated a trend to improved mortality and six-minute walk.

Which patients should we treat with iron, and with what formulation? What do the guidelines recommend?

  • Patients who have chronic heart failure on maximally tolerated guideline-directed medical therapy with iron deficiency are candidates for intravenous iron supplementation with the goal of improving quality of life and reducing heart failure hospitalizations.
    • Intravenous iron has been shown to be effective, but oral iron therapy has shown no benefit in trials.
    • Per the updated 2023 ESC guidelines, there is a class IA recommendation to provide intravenous iron supplementation in symptomatic patients with heart failure with reduced and mid-range ejection fraction with iron deficiency to both alleviate HF symptoms and improve quality of life.
    • There is a class IIA recommendation to provide supplementation to reduce heart failure hospitalizations.
    • Surveillance labs in the outpatient setting, combined with continued treatment for persistent iron deficiency, are likely beneficial in patients with heart failure.
References – Iron Deficiency in Heart Failure
  1. Packer M, Anker SD, Butler J, et al. Identification of three mechanistic pathways for iron-deficient heart failure. Eur Heart J. 2024;45(26):2281-2293. doi:10.1093/eurheartj/ehae284. https://academic.oup.com/eurheartj/article/45/26/2281/7668668
  • McDonagh TA, Metra M, Adamo M, et al; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627-3639. doi:10.1093/eurheartj/ehad195. Erratum in: Eur Heart J. 2024;45(1):53. doi:10.1093/eurheartj/ehad613. https://academic.oup.com/eurheartj/article/44/37/3627/7246292?login=false
  • Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015;36(11):657-668. doi:10.1093/eurheartj/ehu385. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359359/
387. Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease with Dr. Antonio Abbate18 Aug 202400:44:29

CardioNerds Cardio-Rheumatology Series Co-Chairs Dr. Rick Ferraro, Dr. Gurleen Kaur, and Episode Lead Dr. Ronaldo Correa discuss “The Role of Inflammation in Cardiovascular Disease” with Dr. Antonio Abbate.

Join the CardioNerds as they kick off the Cardio-Rheumatology series with Dr. Antonio Abbate. In this episode, Dr. Abbate, a leading expert in cardio-immunology, discusses the role of inflammation in cardiovascular disease. We explore the molecular mechanisms linking inflammation to atherosclerosis, the impact of chronic low-grade systemic inflammation on heart disease, and potential therapeutic targets. Dr. Abbate shares insights on how genes and lifestyle factors contribute to inflammation, the use of inflammatory markers in clinical practice, and emerging anti-inflammatory therapies in atherosclerotic cardiovascular disease. Tune in for an enlightening conversation on the intersection of inflammation and cardiovascular health.

Dr. Ronaldo Correa drafted the notes. Episode audio was engineered by Dr. Amit Goyal.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Pearls – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease
  1. Inflammation is key in the pathogenesis and progression of atherosclerosis. Estimating systemic inflammation is part of a comprehensive preventive assessment (primary/secondary).
  2. Patients with autoimmune inflammatory diseases are at a higher risk for cardiovascular events.
  3. C-reactive protein (CRP) can estimate systemic inflammation and help assess residual inflammatory risk in patients with traditional intermediate/low cardiovascular disease, guiding management consideration with lipid-lowering therapy, aspirin, and colchicine.
  4. The pharmacological management of atherosclerosis is evolving beyond primarily lipid-lowering therapies to focus on targeting the underlying residual inflammatory process. Colchicine (inflammasome blocker as an anti-mitotic drug) is approved for use in chronic stable CVD in selected cases, and interleukin pathway blockers, especially IL-1 and IL-6, are under clinical trial investigation.
  5. First things first! Prioritize treating and optimizing traditional risk factors and comorbidities and emphasize lifestyle modifications to reduce cardiovascular disease (control diabetes and hypertension, reduce or cease smoking/alcohol, lose weight, and engage in regular physical activity). They all impact inflammation directly or indirectly
Show notes – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease

Notes: Notes drafted by Dr. Ronaldo Correa.

What is the link between inflammation and cardiovascular atherosclerosis?

  • Inflammation is involved both in the pathogenesis and progression of atherosclerosis.
    • Histopathological coronary atherosclerosis studies have demonstrated the presence of inflammatory mediators as well as a central role of factors of innate immunity such as macrophages and T cells which can interact with vascular smooth muscle cells in the progression of atherosclerotic plaque.
    • Patients with autoimmune inflammatory conditions have earlier and higher cardiovascular event rates (accelerated atherosclerosis due to residual inflammatory risk).
    • Elevated inflammatory markers (for example, high CRP) predict cardiovascular events.

How should inflammation be considered in the context of residual cardiovascular risk?

  • Inflammation may be the inciting factor in atherosclerosis, or it may amplify the process driven primarily by other risk factors. Therefore, treating the comorbidities and traditional CVD contributors is key to reducing the vicious inflammatory cycle.
    • Assessing residual risk using inflammatory markers can assist in management. C-reactive protein (CRP) can estimate systemic inflammation and help assess residual inflammatory risk in patients with traditional intermediate/low cardiovascular disease, guiding management consideration with lipid-targeting therapies, aspirin, and colchicine.
    • Optimizing traditional risk factors, emphasizing appropriate treatment for hypertension, diabetes, dyslipidemia, weight loss, obstructive sleep apnea (OSA), depression, underlying inflammatory conditions, and lifestyle modifications such as consuming a Mediterranean diet, alcohol/smoking reduction/cessation, and getting regular physical activity can help directly and indirectly reduce inflammatory contributors.

How does inflammation contribute to thrombosis, and what are the implications for cardiovascular disease?

  • Inflammation increases the expression of procoagulant factors through the inflammasome pathway, including mediators like IL-6.
    • Proinflammatory changes in endothelial cells, leukocytes, and platelets promote thrombosis.
    • The concept of immunothrombosis has emerged, especially highlighted by conditions like COVID-19.
    • Inflammation-induced thrombosis has significant implications for cardiovascular disease.

What are the key inflammatory pathways involved in atherosclerosis, and what therapeutic targets have emerged?

  • The inflammatory process is complex, and we still have much to learn about it. Three inflammatory therapeutic targets are highlighted: NLRP3 inflammasome, IL-1, and IL-6.
    • Colchicine is an NLRP3 inflammasome blocker that is FDA-approved as an add-on medication for secondary ischemic prevention in patients with stable CAD who remain at higher risk despite optimal medical therapy with aspirin and statin.
    • The CANTOS trial showed a significant reduction in MACE and hsCRP in post-MI patients who received canakinumab (IL-1 inhibitor) as an add-on therapy.
    • The ZEUS trial is investigating Ziltivekimab (an IL-6 inhibitor) for secondary ASCVD prevention. Rilonacept (an IL-1 inhibitor) is FDA-approved for recurrent pericarditis based on the RHAPSODY trial. Ongoing trials are further exploring inflammation-targeting therapies for the treatment of cardiovascular disease.
References – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease

Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?. Nat Rev Cardiol. 2022;19(8):522-542. doi:10.1038/s41569-021-00668-4

Kong P, Cui ZY, Huang XF, Zhang DD, Guo RJ, Han M. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther. 2022;7(1):131. Published 2022 Apr 22. doi:10.1038/s41392-022-00955-7

Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 2020;17(7):387-401. doi:10.1038/s41569-020-0352-5

Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol. 2019;16(3):180-196. doi:10.1038/s41569-018-0106-9

Suero-Abreu GA, Zanni MV, Neilan TG. Atherosclerosis With Immune Checkpoint Inhibitor Therapy: Evidence, Diagnosis, and Management: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2022;4(5):598-615. Published 2022 Dec 20. doi:10.1016/j.jaccao.2022.11.011

Zhao TX, Mallat Z. Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(13):1691-1706. doi:10.1016/j.jacc.2018.12.083

Geovanini GR, Libby P. Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond). 2018;132(12):1243-1252. Published 2018 Jun 21. doi:10.1042/CS20180306

Fragoulis GE, Soulaidopoulos S, Sfikakis PP, Dimitroulas T, D Kitas G. Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction. J Inflamm Res. 2021;14:1915-1931. Published 2021 May 14. doi:10.2147/JIR.S282691

Giles JT, Sattar N, Gabriel S, et al. Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial. Arthritis Rheumatol. 2020;72(1):31-40. doi:10.1002/art.41095

Del Buono MG, Bonaventura A, Vecchié A, et al. Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1. Eur J Clin Invest. 2024;54(2):e14110. doi:10.1111/eci.14110

Abbate A, Toldo S, Marchetti C, Kron J, Van Tassell BW, Dinarello CA. Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease. Circ Res. 2020;126(9):1260-1280. doi:10.1161/CIRCRESAHA.120.315937

Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol. 2024;21(4):219-237. doi:10.1038/s41569-023-00946-3

378. Case Report: Severe Mitral Paravalvular Regurgitation Complicated by Hemolytic Anemia – Duke University26 Jun 202400:19:36

CardioNerds cofounder, Amit Goyal joins Dr. Belal Suleiman, Dr. Nkiru Osude, and Dr. David Elliott from Duke University. They discuss a case of severe mitral paravalvular regurgitation complicated by hemolytic anemia. Expert commentary is provided by Dr. Andrew Wang. Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares.

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Case Media – Severe Mitral Paravalvular Regurgitation Complicated by Hemolytic Anemia – Duke University
288. 2nd Annual Sanjay V. Desai Lecture: The Humanity Deficiency in Medicine with Dr. Melanie Sulistio18 Apr 202301:09:10

The CardioNerds Academy welcomes Dr. Melanie Sulistio to give the 2nd Annual Sanjay V. Desai Lecture in Medical Education to mark the graduation of the 2022 CardioNerds Academy Class. Join us as Dr. Sulistio and CardioNerds Academy Program Director Dr. Tommy Das discuss the humanity deficiency in medicine, and how the practice of compassionate assumption can lead us to be better physicians for our patients, our colleagues, our learners, and ourselves. Credit to rising CardioNerds Academy chiefs Dr. Rawan Amir, Dr. Kate Wilcox, Dr. Alaa Diab, and Dr. Gurleen Kaur for their terrific acting in this episode. Audio editing by CardioNerds academy internPace Wetstein.

Dr. Sanjay V Desai serves as the Chief Academic Officer, The American Medical Association and is the former Program Director of the Osler Medical Residency at The Johns Hopkins Hospital.

Dr. Melanie Sulistio is an Associate Professor of Medicine in the Division of Cardiology at the University of Texas Southwestern. Additionally, she is an Associate Dean for Student Affairs and Distinguished Teaching Professor at the University of Texas Southwestern Medical School and co-chairs the ACC Internal Medicine Residency Program. She has a passion for medical education and promoting humanity in medicine, and is actively involved in the work of teaching communication skills that encompass meaningful care, discussions with patients, and difficult conversations with colleagues.

Relevant disclosures: None

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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287. Case Report: When Tumors Take Your Breath Away – University of Oklahoma College of Medicine14 Apr 202300:47:09

CardioNerds join Dr. Samid Muhammad Farooqui, Dr. Hiba Hammad, and Dr. Syed Talal Hussain, from the University of Oklahoma Pulmonary and Critical Care Medicine Fellowship Program, in Oklahoma City. The fellows will take us in a fascinating discussion of a case of rapidly progressing dyspnea and pulmonary hypertension in a patient with metastatic breast cancer. They will then reveal an interesting etiology of pulmonary hypertension, where the secret was on the wedge! University of Oklahoma faculty and expert in pulmonary hypertension and right ventricular physiology, Dr. Roberto J. Bernardo provides the E-CPR for this episode. Audio editing by CardioNerds Academy InternDr. Christian Faaborg-Andersen.

A septuagenarian female, with a past medical history of metastatic breast adenocarcinoma, presented to the hospital with worsening dyspnea over a period of 3 weeks. She was found to be in rapidly progressive hypoxic respiratory failure with unremarkable chest x-ray, CTA chest, and V/Q scan. Transthoracic echocardiogram revealed elevated RVSP and a subsequent right heart catheterization showed pre-capillary pulmonary hypertension with a low cardiac index. She was treated for rapidly progressive RV dysfunction with inotropic support and inhaled pulmonary vasodilators until she decided to pursue comfort measures. Wedge cytology came back positive for malignant cells, confirming a diagnosis of Pulmonary Tumoral Thrombotic Microangiopathy (PTTM).

CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Case Media – When Tumors Take Your Breath Away – University of Oklahoma College of Medicine Pearls – When Tumors Take Your Breath Away – University of Oklahoma College of Medicine
  1. Pulmonary arterial hypertension (PAH) is a progressive disorder of the pulmonary vasculature, characterized by progressive obliteration and remodeling of the pulmonary circulation, resulting in increased pulmonary vascular resistance and increased right ventricular (RV) wall stress, abnormal right ventricular mechanics, and eventually RV dysfunction and death.
  2. Pulmonary hypertension (PH) is divided into pre-capillary and post-capillary profiles, where pre-capillary PH is hemodynamically characterized by a mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) ≥ 3 Woods Units (WU), and post-capillary PH is defined as mPAP > 20 mmHg, PAWP ≥ 15 mmHg, and PVR can be either < 3 WU (isolated post-capillary PH) or ≥ 3 WU (combined pre- and post-capillary PH). Pulmonary arterial hypertension (PAH) falls under the pre-capillary PH profile.
  3. Dyspnea on exertion is the most common manifestation of PH, and the most common initial complain. Other symptoms and physical findings such as venous congestion, peripheral edema, signs of RV dysfunction or syncope present later in the disease course. As such, PH has to be considered in the differential diagnosis of dyspnea, especially in cases of undifferentiated or unexplained dyspnea.
  4. PAH is a chronic but progressive condition, where symptoms progress over the course of months to years. Subacute or rapidly progressive forms of PH (symptoms rapidly worsening over the course of weeks) should warrant consideration for alternative etiologies (i.e., pulmonary embolism or a different cardiopulmonary disorder as the main driver of symptoms), or unique rapidly progressive phenotypes of PAH such as pulmonary tumor thrombotic microangiopathy (PTTM).
  5. PH in the setting of malignancy warrants special consideration, where the pulmonary vascular disorder could be related to venous thromboembolic disease, external compression of the pulmonary vasculature (if the tumor directly compresses mediastinal structures), related to chemotherapeutic agents (such as tyrosine kinase inhibitors) or thoracic radiotherapy (ie. fibrosing mediastinitis), or related to tumor emboli per se, such as in PTTM. PTTM is a unique manifestation of PH in the setting of malignancy, known to be rapidly progressive, associated with poor RV adaptation, and almost universally fatal. The confirmatory testing of PTTM is by pathology (autopsy), although as in our case, sometimes tumor cells can be identified during cytology of pulmonary artery wedge samples.
Show Notes – When Tumors Take Your Breath Away – University of Oklahoma College of Medicine

1. How do you approach dyspnea?

  • Dyspnea is a subjective sensation of uncomfortable breathing. It can be caused by pathologies in cardiac, pulmonary, neuromuscular systems as well as in systemic illnesses. Dyspnea is also a manifestation of psychogenic disorders.
  • Presentation of dyspnea can be divided into acute and chronic forms and the etiology can be identified by a thorough evaluation.
  • A detailed history and physical exam can help identify the organ system involved. Certain physical signs can be suggestive of the culprit organ system e.g., lower extremity edema in congestive heart failure, increased antero-posterior diameter of the chest in obstructive lung disease, etc. Imaging modalities can be very helpful in determining the cause of dyspnea. Chest radiographs, CT scans of the chest, and echocardiograms can help identify the etiology of dyspnea. Additionally, other testing like pulmonary functions tests can be used too.

2. What are the different Pulmonary Hypertension groups?

Pulmonary Hypertension (PH) is divided into 5 main groups in the WHO classification, as follows:

Group I Pulmonary Arterial Hypertension (PAH)   Idiopathic, heritable, drugs, congenital heart disease, liver disease, connective tissue disease, toxins, anorexigens among other causes Group II PH due to Left Heart Disease Left sided heart failure, valvular pathology Group III PH due to Lung Disease COPD, Interstitial Lung Disease, Sleep Apnea Group IV PH due to Chronic Thromboembolic Disease Pulmonary emboli Group V PH due to Other Causes Sarcoidosis, ESRD, Sickle Cell Anemia, Chronic Hemolytic Anemia, Certain Metabolic Disorders

3. How do you approach a patient with Pulmonary Hypertension?

  • The goal is to discover an identifiable etiology for proper classification of pulmonary hypertension according to the WHO groups, in order to guide prognostication and management.
  • A thorough history and physical exam is the first step in the diagnosis of pulmonary hypertension. Exertional dyspnea is the most common presenting symptom. Due to the nonspecific symptoms, there is often a delay in the diagnosis. Other symptoms include chest pain, fatigue, edema. In severe cases, patients may have syncopal episodes.
  • Physical Exam findings concerning for pulmonary hypertension include signs of volume overload (i.e., edema, elevated JVP). Cardiac auscultation may reveal a loud P2 component.
  • Laboratory workup includes basic assessment of hematology along with testing for HIV and serological markers of connective tissue diseases. Biomarkers of cardiovascular system like BNP are important in identification and prognostication of pulmonary hypertension.
  • Radiological studies like chest radiographs, CT scans of the chest and ventilation/perfusion scans of the lung are used to identify pulmonary pathologies and the presence of thromboembolic disease respectively.
  • Echocardiographic assessments are important for diagnosis and assessment of pulmonary hypertension. It allows for the assessment of the left side as well as a detailed analysis of the right side which has diagnostic and prognostic value.
  • Finally, the gold standard for diagnosis is a right heart catheterization, which allows for accurate measurements of the pressure in the different chambers of the heart and allows for the phenotyping of pulmonary hypertension.

4. What are the considerations for Pulmonary Hypertension etiologies in patient with malignancy? How is Pulmonary Tumoral Thrombotic Microangiopathy diagnosed?

  • Pulmonary hypertension in a patient with malignancy requires special attention.
  • Apart from the common reasons for pulmonary hypertension, use of chemotherapeutic agents has been associated with the development of pulmonary arterial hypertension, particularly with Tyrosine Kinase Inhibitors.
  • Pulmonary Veno-Occlusive Disease (PVOD) can be precipitated by the use of many chemotherapeutic agents especially alkylating agents.
  • Detrimental effects of chemotherapeutic agents on myocytes can cause Group II pulmonary hypertension.
  • Chemotherapy and radiation therapy induced lung damage can also cause Group III pulmonary hypertension. 
  • Large tumors may directly compress mediastinal structures causing elevated pulmonary pressures due to external compression. 
  • In patients with adenocarcinoma, tumoral thrombotic microangiopathy can result in sub-acute pulmonary hypertension known as Pulmonary Tumoral Thrombotic Microangiopathy (PTTM).
  • PTTM results in rapid clinical deterioration and hence requires a high suspicion of index. It is mostly diagnosed postmortem, but can be diagnosed by performing wedge cytology.

5. What is the prognosis of PTTM and how is it treated?

  • PTTM carries a grave prognosis. It causes accelerated occlusion of pulmonary arteries resulting in acute to subacute pulmonary hypertension and ensuing RV dysfunction and failure.
  • The mainstay of treatment relies on pulmonary vasodilation and slowing the growth of malignant cells.
  • Pulmonary vasodilators, especially endothelin receptor antagonists, have been reported to be used.
  • Imatinib, a tyrosine kinase inhibitor, has been reported to be used with some improvement in survival. 
References –
  1. Vonk Noordegraaf A, Chin KM, Haddad F, et al. Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update. Eur Respir J. Jan 2019;53(1):1801900. doi:10.1183/13993003.01900-2018. Link:
  2. Bernardo RJ, Haddad F, Couture EJ, et al. Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction. Cardiovasc Diagn Ther. Oct 2020;10(5):1580-1603. doi:10.21037/cdt-20-479.
  3. Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. The European respiratory journal. 2019;53(1):1801913-1801913. doi:10.1183/13993003.01913-2018.
  4. Dumitrescu D, Sitbon O, Weatherald J, Howard LS. Exertional dyspnoea in pulmonary arterial hypertension. Eur Respir Rev. Sep 30 2017;26(145)doi:10.1183/16000617.0039-2017.
  5. Buser M, Felizeter-Kessler M, Lenggenhager D, Maeder MT. Rapidly progressive pulmonary hypertension in a patient with pulmonary tumor thrombotic microangiopathy. Am J Respir Crit Care Med. Mar 15 2015;191(6):711-2. doi:10.1164/rccm.201501-0004IM.
  6. Price LC, Wells AU, Wort SJ. Pulmonary tumour thrombotic microangiopathy. Lippincott Williams and Wilkins; 2016. p. 421-428.
  7. Price LC, Seckl MJ, Dorfmüller P, Wort SJ. Tumoral pulmonary hypertension. European Respiratory Review. 2019;28(151)doi:10.1183/16000617.0065-2018.
  8. Shah AT, Bernardo RJ, Berry GJ, Kudelko K, Wakelee HA. Two Cases of Pulmonary Tumor Thrombotic Microangiopathy Associated with ROS1-Rearranged Non-Small-Cell Lung Cancer. Clin Lung Cancer. Mar 2021;22(2):e153-e156. doi:10.1016/j.cllc.2020.09.020.
  9. Godbole RH, Saggar R, Kamangar N. Pulmonary tumor thrombotic microangiopathy: a systematic review. Pulm Circ. Apr-Jun 2019;9(2):2045894019851000. doi:10.1177/2045894019851000
286. Guidelines: 2021 ESC Cardiovascular Prevention – Question #21 with Dr. Noreen Nazir11 Apr 202300:07:09

The following question refers to Section 4.4 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Maryam Barkhordarian, answered first by medicine resident Dr. Ahmed Ghoneem, and then by expert faculty Dr. Noreen Nazir.

Dr. Nazir is Assistant Professor of Clinical Medicine at the University of Illinois at Chicago, where she is the director of cardiac MRI and the preventive cardiology program.

The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association.



Question #21

Ms. J is a 57-year-old woman with a past medical history of myocardial infarction resulting in ischemic cardiomyopathy, heart failure with reduced ejection fraction, and major depressive disorder who presents today for follow-up. She reports feeling extremely overwhelmed lately due to multiple life stressors. She is on appropriate cardiovascular GDMT agents and is not prescribed any medications for her mood disorder.

True or false: in addition to psychotherapy for stress management, it is appropriate to consider Ms. J for anti-depressant SSRI pharmacotherapy at this time to improve cardiovascular outcomes.

A True B False



Answer #21

Explanation The correct answer is FALSE.

An ESC class 3 recommendation states that SSRIs, SNRIs, and tricyclic antidepressants are not recommended in patients with heart failure and major depression; this is based on data suggesting potential lack of SSRI efficacy for reducing depression or cardiovascular events, as well as safety data indicating an association between SSRI use and increased risk of CV events and all-cause as well as cardiovascular mortality among HF patients. Mental health disorders are associated with worse outcomes in patients with ASCVD and appropriate treatment effectively reduces stress symptoms and improves quality of life. Nonpharmacologic modalities of treatment (exercise therapy, psychotherapy, collaborative care) should be considered before pharmacotherapy to improve cardiovascular outcomes in patients with heart failure.

Of note, the ESC suggests SSRI treatment be considered for patients with coronary heart disease (without HF) and moderate-to-severe major depression based on data that SSRI treatment is associated with lower rates of CHD readmission (RR 0.63), all-cause mortality (RR 0.56), and the composite endpoint of all-cause mortality/MI/PCI (HR 0.69) vs. no treatment. This is a class 2a recommendation.

ESC also gives a class 2a recommendation to consider referral to psychotherapeutic stress management for individuals with stress and ASCVD to improve CV outcomes and reduce stress symptoms.

The ACC/AHA guidelines do not provide focused recommendations regarding mental health considerations in patients with elevated cardiovascular risk.

Main Takeaway It is important to consider mental health treatment in patients with ASCVD as mental disorders are associated with increased CVD risk and poor patient prognosis, and data support that mental health interventions can improve overall and CVD outcomes, as well as improve quality of life. Guideline Loc. Section 4.4

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285. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #15 with Dr. Ileana Pina11 Apr 202300:10:57

The following question refers to Section 10.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Western Michigan University medical student and CardioNerds Intern Shivani Reddy, answered first by Boston University cardiology fellow and CardioNerds Ambassador Dr. Alex Pipilas, and then by expert faculty Dr. Ileana Pina.

Dr. Pina is Professor of Medicine and Quality Officer for the Cardiovascular Line at Thomas Jefferson University, Clinical Professor at Central Michigan University, and Adjunct Professor of Biostats and Epidemiology at Case Western University. She serves as Senior Fellow and Medical Officer at the Food and Drug Administration’s Center for Devices and Radiological Health.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.



Question #15

Mrs. Framingham is a 65-year-old woman who presents to her cardiologist’s office for stable angina and worsening dyspnea on minimal exertion. She has a history of non-insulin dependent type 2 diabetes mellitus and hypertension. She is taking metformin, linagliptin, lisinopril, and amlodipine. Blood pressure is 119/70 mmHg. Labs are notable for a hemoglobin of 14.2 mg/dL, iron of 18 mcg/dL, ferritin 150 ug/L, transferrin saturation 15%, and normal creatine kinase. An echocardiogram shows reduced left ventricular ejection fraction of 25%. Coronary angiography shows obstructive lesions involving the proximal left anterior descending, left circumflex, and right coronary arteries. In addition to optimizing GDMT, which of the following are recommendations for changes in management?

A

Anticoagulation, percutaneous revascularization, and IV iron

B

A change in her diabetic regimen, percutaneous revascularization, and PO iron

C

A change in her diabetic regimen, surgical revascularization, and IV iron

D

A change in her diabetic regimen, medical treatment alone for CAD, and PO iron

E

Anticoagulation and surgical revascularization



Answer #15

Explanation

The correct answer is C – a change in her diabetic regimen, surgical treatment and IV iron.

Multimorbidity is common in patients with heart failure. More than 85% of patients with HF also have at least 2 additional chronic conditions, of which the most common are hypertension, ischemic heart disease, diabetes, anemia, chronic kidney disease, morbid obesity, frailty, and malnutrition. These conditions can markedly impact patients’ tolerance to GDMT and can inform prognosis.

Not only was Mrs. F found with HFrEF (most likely due to ischemic cardiomyopathy), but she also suffers from severe multi-vessel coronary artery disease, hypertension, and non-insulin dependent type 2 diabetes mellitus.

In addition to starting optimized GDMT for HF, specific comorbidities in the heart failure patient warrant specific treatment strategies. Mrs. Framingham would benefit from a change in her diabetic regimen, namely switching from linagliptin to an SGLT2 inhibitor (e.g., empagliflozin, dapagliflozin). In patients with HF and type 2 diabetes, the

use of SGLT2i is recommended for the management of hyperglycemia and to reduce HF related morbidity and mortality (Class 1, LOE A).

Furthermore, as she has diabetes, symptomatic severe multi-vessel CAD, and LVEF≤35%, surgical revascularization with coronary artery bypass grafting is warranted to improve symptoms, cardiovascular hospitalizations, and long-term all-cause mortality (Class 1, LOE B-R). Given the severity of her coronary disease, presence of diabetes mellitus, and coronary anatomy suitable for bypass, percutaneous (i.e., PCI) or medical treatment alone are inappropriate (options B, D).

 

Although she does not have anemia, she may benefit from IV iron. IV iron supplementation has been shown in the FAIR-HF, IRONOUT HF, and AFFIRM-AHF trials to significantly improve NYHA functional class, 6-minute walk test, quality of life, and decrease hospitalizations for HF, independently of anemia. These effects were not seen with iron given orally (options B, D). Iron deficiency is usually defined as ferritin level <100 μg /L or 100 to 300 μg/L, if the transferrin saturation is <20%.  Therefore, in patients with HFrEF and iron deficiency with or without anemia, intravenous iron replacement is reasonable to improve functional status and QOL (Class 2a, LOE B-R).

 

Although HF is a pro-thrombotic state, anticoagulation is not warranted empirically in Mrs. F, who has no evidence of thrombus or high-risk features suggesting impending thrombus (options A, E).

Main Takeaway

In summary, multimorbidity is frequent in heart failure patients and treatment targeted to specific morbidities is warranted. In patients with heart failure and diabetes, an SGLT2 inhibitor should be part of the medication regimen. Intravenous iron supplementation should be considered in iron-deficient patients independent of anemia. In patients with heart failure with LVEF≤35% and severe coronary artery disease with suitable anatomy, coronary artery bypass grafting is recommended. 

Guideline Loc.

Section 10.1, Figure 14

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284. Atrial Fibrillation: Mechanical Stroke Prevention in Atrial Fibrillation with Dr. Christopher Ellis10 Apr 202301:03:10

CardioNerds Amit Goyal, Dr. Colin Blumenthal, Dr. Kelly Arps and Dr. Justice Oranefo discuss mechanical stroke prevention in atrial fibrillation with Dr. Christopher Ellis, cardiac electrophysiology lab director and director of the left atrial appendage closure program at Vanderbilt University. There has been a significant increase in the number of patients undergoing left atrial appendage occlusion (LAAO). This trend is expected to continue with current and upcoming clinical data on this topic. In this episode we dive into the rationale behind LAAO and explore several historical facts. We then proceed to the current state of practice including currently available options, appropriate indications, post op care, and potential complications. Notes were drafted by Dr. Justice Oranefo. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal.

This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.

We have collaborated with VCU Health to provide CME. Claim free CME here!

Disclosures: Dr. Ellis discloses grant or research support from Boston Scientific, Abbott-St Jude, advisor for Atricure and Medtronic.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls and Quotes – Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation
  1. Surgical or catheter based left atrial appendage occlusion results in mechanical exclusion of the left atrial appendage, which is the most common source of thrombus leading to embolic events in patients with non-rheumatic atrial fibrillation.
  2. Surgical LAAO should be considered in patients with atrial fibrillation and CHA2DS2VASC score ≥ 2 undergoing cardiac surgery for other indications.
  3. Endocardial LAAO devices such as WATCHMAN FLX and AMULET are approved for stroke prevention in patients with atrial fibrillation with a CHA2DS2VASC score ≥ 2 and have an appropriate reason to seek a non-drug alternative to anticoagulation therapy.
  4. Appropriate patient selection and post-operative anticoagulation and imaging strategy are crucial for prevention and management of complications related to LAAO.
Notes – Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation

What are the types of LAAO device?

Left atrial appendage occlusion devices can be divided into epicardial closure and endocardial closure.

Epicardial techniques/devices include surgical ligation, Atriclip, and Lariat. These techniques require pericardial access (either by open thoracotomy or thoracoscopic access). The goals are complete exclusion and ischemic necrosis of the LAA.

LARIAT device

Atriclip device

Endocardial techniques include WATCHMAN FLX and AMULET devices. These techniques require the use of nitinol-based devices which are delivered into the LAA via a transeptal approach. These devices become endothelialized over time resulting in occlusion of the LAA.

AMULET device

WATCHMAN FLX

Who is the ideal candidate for surgical LAAO?

Several studies have evaluated the efficacy of surgical LAA occlusion. The most prominent being the LAOS III trial which randomized 4770 patients with atrial fibrillation and CHA2DS2VASC ≥ 2 undergoing cardiac surgery for other reasons to surgical LAAO vs no LAAO (3,4). The primary outcome of ischemic stroke or systemic embolization occurred in 4.8% of patients in the LAAO group vs 7% of patients in control group over an average follow-up of 3.8 years. Though patients were randomized to LAAO, there was no requirement to stop anticoagulation and this difference was seen despite 75% of patients continuing anticoagulation. Additionally, there was no significant difference in operation time and bleeding complications.

Based on these findings, LAAO should be considered in patients with atrial fibrillation undergoing cardiac surgery for other reasons regardless of the anticipated anticoagulation strategy.

This ability to perform surgical LAAO requires safe access to the pericardial space. For this reason, conditions that create pericardial adhesions (e.g., prior cardiac surgery, chest radiation or trauma, multiple prior ablations) can limit the ability to perform surgical LAAO.

Who is the ideal candidate for endocardial LAAO?

Several  randomized controlled trials and cohort studies have evaluated the utility of both the AMULET and WATCHMAN devices in stroke prevention with the most notable being the PREVAIL, PROTECT AF, and AMULET IDE trials (5,6,7,8,9,10).

Based on the available data, these devices are indicated for stroke prevention in patients with non-valvular atrial fibrillation, a CHA2DS2VASC score ≥ 2 and an appropriate reason to seek a non-drug alternative to anticoagulation therapy. A classic example is a patient with recurrent GI bleeding despite multiple attempts to tolerate anticoagulation. These devices can also be considered in patients with high-risk professions suck as police officers or fire fighters.

Several individual factors also affect the feasibly of endocardial LAAO. A suitable LAA anatomy is necessary for safe device implant (13). Other important considerations are nickel allergy (consider formal allergy testing in patients with suspected nickel allergy), surgical repair of the atrial septum, and severe kyphoscolisis (making adequate transeptal access difficult).

There is no strong data comparing LAAO to DOAC in patients without high bleeding risk, however this question is being studied in 2 ongoing trials, CHAMPION AF (WATCHMAN FLX) and CATALYST (AMULET).

What are the complications of LAAO?

Surgical LAAO is safe and effective when there is complete occlusion of the LAA, however, historically ~ 20-30% are unsuccessful due to incomplete occlusion. More modern surgical techniques including confirmation with intra-operative transesophageal echocardiogram and the Atriclip have demonstrates a higher rate of success. Though the addition of a LAAO has not been shown to add significant time or risk to an already planned cardiac surgery, this requires a patient to already have an indication for surgery and carries the associated risks of that procedure.

Endocardial LAAO has the advantage of being minimally invasive, but procedural complications such as cardiac tamponade, bleeding, and stroke can occur. More recent data has shown a < 1% procedural risk with the WATCHMAN FLX device. Other post procedural complications of endocardial LAAO devices include peridevice leak (~ 10% incidence; leaks ≥ 3mm are associated with an increased risk of stroke) and device related thrombus (DRT; 2-3% incidence). Device embolism is rare but carries potentially devastating consequences (12).

What is the anticipated post operative care following LAAO?

Post operative care with surgical LAAO is predominently dictated by the primary indication for surgery. Due to the high incidence incomplete exclusion, an intra or post-operative TEE is necessary to document complete LAA occlusion. As for anticoagulation, there is no current randomized control trial data that supports using surgical LAAO as an alternative to AC. As previously discussed, a lower incidence of stroke was seen in the LAOS III trial, but this trial specifically studied using surgical LAAO as an adjunct to OAC, not as a replacement.

With endocardial LAAO, appropriate patient and device selection as well as adequate post-operative care is crucial to maximize safety and efficacy. Patients must be able to tolerate some degree of short-term anticoagulation with the goal to safely transition to single anti-platelet therapy while minimizing the risk of stroke and bleeding. This involves OAC for at least 45 days followed by aspirin monotherapy if no DRT or peridevice leak is seen on post-op imaging. DAPT (aspirin and clopidogrel) can be used instead of OAC in the early phase however there is not strong data for this strategy (11). Post-op imaging (TEE or CTA) is required approximately ~45 days, 6 months, and 1 year after the procedure.

In patients who have undergone LAAO, LAA imaging is recommended prior to cardioversion, however, in the absence of DRT or device leaks anticoagulation is not necessary post cardioversion (14,15).

References
  1. Belcher, J.R. & Somerville, W., 1955. Systemic Embolism and Left Auricular Thrombosis in Relation to Mitral Valvotomy. British Medical Journal, 2(4946), pp.1000–1003.
  2. Blackshear, J.L. & Odell, J.A., 1996. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. The Annals of thoracic surgery, 61(2), pp.755–759.
  3. Friedman, D.J. et al., 2018. Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery. JAMA : the journal of the American Medical Association, 319(4), pp.365–374.
  4. Whitlock, R.P. et al., 2021. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. The New England journal of medicine, 384(22), pp.2081–2091.
  5. Reddy, V.Y. et al., 2014. Percutaneous Left Atrial Appendage Closure vs Warfarin for Atrial Fibrillation: A Randomized Clinical Trial. JAMA : the journal of the American Medical Association, 312(19), pp.1988–1998.
  6. Belgaid, D.R. et al., 2016. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. International journal of cardiology, 219, pp.177–179.
  7. Freeman, J.V. et al., 2020. The NCDR Left Atrial Appendage Occlusion Registry. Journal of the American College of Cardiology, 75(13), pp.1503–1518.
  8. REDDY, V.Y. et al., 2013. Left Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral Anticoagulation: The ASAP Study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). Journal of the American College of Cardiology, 61(25), pp.2551–2556.
  9. Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial [published correction appears in J Am Coll Cardiol. 2014 Sep 16;64(11):1186]. J Am Coll Cardiol. 2014;64(1):1-12. doi:10.1016/j.jacc.2014.04.029 
  10. Lakkireddy D, Thaler D, Ellis CR, et al. Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized, Controlled Trial. Circulation. 2021;144(19):1543-1552. doi:10.1161/CIRCULATIONAHA.121.057063
  11. Magdi M, Renjithal SLM, Mubasher M, et al. The WATCHMAN device and post-implantation anticoagulation management. A review of key studies and the risk of device-related thrombosis. Am J Cardiovasc Dis. 2021;11(6):714-722. Published 2021 Dec 15.
  12. Della Rocca DG, Magnocavallo M, Gianni C, et al. Procedural and short-term follow-up outcomes of Amplatzer Amulet occluder versus Watchman FLX device: A meta-analysis. Heart Rhythm. 2022;19(6):1017-1018. doi:10.1016/j.hrthm.2022.02.007
  13. Maan A, Heist EK. Left Atrial Appendage Anatomy: Implications for Endocardial Catheter-based Device Closure. J Innov Card Rhythm Manag. 2020;11(7):4179-4186. Published 2020 Jul 15. doi:10.19102/icrm.2020.110704
  14. Maarse M, Wintgens LIS, Ponomarenko A, et al. Impact of anticoagulation strategy after left atrial appendage occlusion in patients requiring direct current cardioversion. J Cardiovasc Electrophysiol. 2021;32(3):737-744. doi:10.1111/jce.14889
  15. Sharma SP, Turagam MK, Gopinathannair R, et al. Direct Current Cardioversion of Atrial Fibrillation in Patients With Left Atrial Appendage Occlusion Devices. J Am Coll Cardiol. 2019;74(18):2267-2274. doi:10.1016/j.jacc.2019.08.1045
283. CardioNerds Rounds: Challenging Cases – Cardio-Obstetrics and Heart Failure with Dr. Mary Norine (Minnow) Walsh 05 Apr 202300:35:48

It’s another session of CardioNerds Rounds! In these rounds, Dr. Jenna Skowronski (Chief FIT at University of Pittsburgh) and Dr. Natalie Stokes (Formerly FIT at University of Pittsburgh and now General Cardiology Faculty at University of Pittsburgh) join transformational leader, educator and researcher, Dr. Mary Norine Walsh (Director of Heart Failure and Transplantation at Ascension St. Vincent Heart Center and Program Director of AHFT at St. Vincent) to discuss cardio-obstetrics and heart failure cases. Amongst her many accomplishments, Dr. Walsh is past president of the American College of Cardiology, Deputy Editor of JACC Case Reports, and a preeminent voice and thought leader in women’s cardiovascular health. Audio editing by CardioNerds academy internPace Wetstein.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes

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Show notes – Cardio-Obstetrics and Heart Failure

Case 1 Synopsis:

A woman in her earlier 30s, G1P1, with a history significant for peripartum cardiomyopathy presents to clinic for pre-conception counseling.  Her prior pregnancy was in her late 20s with an uneventful pre-natal course and a spontaneous vaginal delivery at 37w2d.  Two weeks after delivery, she experienced symptoms of heart failure and was found to have a new diagnosis of HFrEF. At that time TTE showed LVEF 30-35%, LVIDd 5.1cm (top normal size), diffuse hypokinesis. At that time, she was diuresed and discharged on metoprolol succinate 25mg po daily and furosemide 20mg po daily.  She had one follow up visit 6 months postpartum and the furosemide was discontinued.  Today in your office, she has NYHA Class I symptoms with no signs of symptoms of congestion. She walks daily and does vigorous exercise 1-2 times per week, while remaining on metoprolol.  Repeat TTE with LVEF 45-50% and similar LV size. She would like to have another child and was referred to you for counseling.

Case 1 Rounding Pearls:

  1. Dr. Walsh discussed extensively the importance of full GDMT in this patient who was initially undertreated with only a beta blocker.  If patients are breastfeeding, clinicians should consider the addition of ACE-Inhibitor and Spironolactone. Otherwise, if not breastfeeding, they should receive maximally tolerated doses of full GDMT. For more details on medical therapy for Heart Failure during pregnancy and after, refer to this previous CardioNerds Episode with Dr. Julie Damp.
  2. Patients with peripartum cardiomyopathy are at highest risk of worsening LV systolic function when they have persistent LV systolic dysfunction from their initial diagnosis. In this circumstance, shared decision making is paramount.  These patients should receive counseling on contraception and risk of pregnancy on worsening LV function, death, & fetal demise. In addition, counseling includes discussing with patients limited options in some states for complete, comprehensive reproductive care, including pregnancy termination.
  3. If patients with prior peripartum cardiomyopathy do become pregnant, a team-based approach including cardiologists, maternal fetal medicine, and obstetrics (amongst other team members) is essential to determine care & delivery timing/method.  These patients should also be examined for signs of decompensation throughout the pregnancy, including rales, S3 or a reported history of PND. For more about pregnancy physiology and signs of Heart Failure in pregnancy, refer to this previous episode with Dr. Garima Sharma.

Case 2 Synopsis:

A woman in her early 30s, G4P2022, with a history significant for polysubstance use disorder is transferred to your hospital POD #0 from an emergent C-section at 37w in cardiogenic shock.  She presented to the local hospital with cough, dyspnea, and abdominal pain and urine toxicology was positive for methamphetamines.  During evaluation she went into an SVT that was treated with metoprolol and was complicated by fetal decelerations. TTE showed LVEF 15%, LV dilation, and RV dysfunction. Given the fetal decelerations she had an emergent C-Section. We discussed her management as she progressed into SCAI Stage E Cardiogenic Shock.

Case 2 Rounding Pearls:

  1. The etiology of cardiomyopathy in this patient could be tachycardia induced, peripartum, toxic, or familial. A full evaluation is essential to determine if anything is reversible.  SVT ablation could be considered if this was felt to be a driver.
  2. Approaches to durable mechanical circulatory support (MCS) such as a durable LVAD in patients with polysubstance use disorders are institution specific.  Multidisciplinary input should be sought, including cardiology, cardiothoracic surgery, social work, nursing, nutrition, palliative care, and pharmacy.
  3. Consideration of temporary MCS as a bridge to transplant vs durable MCS should be considered again on a case-by-case basis, keeping in mind the current transplant allocation system that has made those patients with durable LVAD less likely to receive a transplant.
  4. We have previously discussed cases on the CardioNerds podcast that reflect this nuance. Consider listening again to these episodes from the CardioNerds team at Medical College Wisconsin and the University of Pennsylvania.
Infographic by CardioNerds Academy Chief of House Jones (2023) Dr. Alaa Diab References – Cardio-Obstetrics and Heart Failure
  1. Bauersachs J, Arrigo M, Hilfiker-Kleiner D, et al. Current management of patients with severe acute peripartum cardiomyopathy: practical guidance from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 2016;18(9):1096-1105. doi:10.1002/ejhf.586
  2. Bauersachs J, König T, van der Meer P, et al. Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 2019;21(7):827-843. doi:10.1002/ejhf.1493
  3. Davis MB, Arany Z, McNamara DM, Goland S, Elkayam U. Peripartum Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(2):207-221. doi:10.1016/j.jacc.2019.11.014
  4. Writing Committee Members; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Card Fail. 2022;28(5):e1-e167. doi:10.1016/j.cardfail.2022.02.010
Production Team https://www.cardionerds.com/wp-content/uploads/2020/08/FullSizeRender.jpegKaran Desai, MD https://www.cardionerds.com/wp-content/uploads/2021/03/Natalie-Stokes-MD.jpgNatalie Stokes, MD https://www.cardionerds.com/wp-content/uploads/2020/07/Amit-Goyal-MD.pngAmit Goyal, MD https://www.cardionerds.com/wp-content/uploads/2020/07/Dan-copy.jpegDaniel Ambinder, MD
282. Guidelines: 2021 ESC Cardiovascular Prevention – Question #20 with Dr. Michael Wesley Milks05 Apr 202300:13:33

The following question refers to Section 3.4 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Adriana Mares, answered first by Brigham & Women’s medicine intern & Director of CardioNerds Internship Dr. Gurleen Kaur, and then by expert faculty Dr. Michael Wesley Milks.

Dr. Milks is a staff cardiologist and assistant professor of clinical medicine at the Ohio State University Wexner Medical Center where he serves as the Director of Cardiac Rehabilitation and an associate program director of the cardiovascular fellowship. He specializes in preventive cardiology and is a member of the American College of Cardiology’s Cardiovascular Disease Prevention Leadership Council.

The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association.



Question #20

Ms. Ruma Toid is a 65-year-old African American woman who presents to your clinic in Ohio for routine follow up. She has a history of rheumatoid arthritis, hypertension, obesity, and sleep apnea. Her medications include methotrexate and atenolol. Her blood pressure in the office is 120/80 mmHg, heart rate 68 bpm, and oxygen saturation 99% on room air. Recent lipid testing revealed total cholesterol 165 mg/dL, HDL 42 mg/dL, and LDL 118 mg/dL. She was recently advised to talk to her doctor about taking a statin due to her risk factors but in the past has heard negative things about those medications and would like your advice on next steps. Her calculated ASCVD risk score based on the Pooled Cohort Equation is 7%. Which of the following choices would be the next step?

A

She is at borderline risk for ASCVD events. A statin is not indicated at this time.

B

Due to her history of rheumatoid arthritis, her calculated ASCVD risk should be multiplied by 1.5, yielding an ASCVD risk of 10.5% placing her in the intermediate risk category. Moderate intensity statin would be indicated.

C

When other risk factors are present, rheumatoid arthritis is no longer an enhancing risk factor.

D

Statins are contraindicated when taking methotrexate.



Answer #20

Explanation

The correct answer is B. Due to her history of rheumatoid arthritis, her calculated ASCVD risk should be multiplied by 1.5, yielding an ASCVD risk of 10.5% placing her in the intermediate risk category. Moderate intensity statin would be indicated.

 

Due to her history of rheumatoid arthritis, her calculated ASCVD risk should be multiplied by 1.5, yielding an ASCVD risk of 10.5% placing her in the intermediate risk category. Moderate intensity statin would be indicated. The ESC gives a Class IIa (LOE B) indication to multiply the calculated total CVD risk by a factor of 1.5 in adults with rheumatoid arthritis due to the observed 50% increased CVD risk in patients with rheumatoid arthritis.

 

This 50% increase in CVD risk attributed to RA is present beyond traditional risk factors, making answer choice C wrong.

 

Answer A is incorrect because when borderline risk is calculated, one should still look for risk enhancers that could potentially increase ASCVD risk before final determination of statin indication.

 

Answer choice D is false as there is no contraindication to take both methotrexate and statins together.

 

Note that it is appropriate to use the pool cohort equations and American risk thresholds for this patient since she is in America where the PCE was validated (versus using SCORE2 risk model which would be more appropriate for European populations).

Main Takeaway

Inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease increase a person’s risk for ASCVD events. Specifically for rheumatoid arthritis, there is a Class IIa indication to multiply the calculated risk score by 1.5 to account for rheumatoid arthritis as a risk enhancer.

Guideline Loc.

Section 3.4.6

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281. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #14 with Dr. Javed Butler04 Apr 202300:13:28

The following question refers to Section 9.5 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Duke University cardiology fellow and CardioNerds FIT Ambassador Dr. Aman Kansal, and then by expert faculty Dr. Javed Butler.

Dr. Butler is an advanced heart failure and transplant cardiologist, President of the Baylor Scott and White Research Institute, Senior Vice President for the Baylor Scott and White Health, and Distinguished Professor of Medicine at the University of Mississippi.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.



Question #14

Mrs. Hart is a 70-year-old woman hospitalized for a 2-week course of progressive exertional dyspnea, increasing peripheral edema, and mental status changes. She has a history of coronary artery disease, hypertension, and heart failure for which she takes aspirin, furosemide, carvedilol, lisinopril, and spironolactone. On physical exam, the patient is afebrile, BP is 80/60 mmHg, heart rate is 120 bpm, and respiratory rate is 28 breaths/min with O2 saturation of 92% breathing room air. She is sitting upright and is confused. Jugular venous pulsations are elevated. Cardiac exam reveals an S3 gallop. There is ascites and significant flank edema on abdominal exam. Her lower extremities have 2+ pitting edema to her knees and are cool to touch. Her labs are significant for an elevated serum Creatinine of 3.0 from a baseline of 1.0 mg/dL, lactate of 3.0 mmol/L, and liver enzyme elevation in the 300s U/L.

Which of the following is the most appropriate initial treatment?

A Increase carvedilol B Start dobutamine C Increase lisinopril D Start nitroprusside



Answer #14

Explanation The Correct answer is B – start dobutamine.

This patient with progressive congestive symptoms, mental status changes, and signs of hypoperfusion and end-organ dysfunction meets the clinical criteria of cardiogenic shock. The Class 1 recommendation is that in patients with cardiogenic shock, intravenous inotropic support should be used to maintain systemic perfusion and maintain end-organ performance (LOE B-NR). Their broad availability, ease of administration, and clinician familiarity favor such agents as first line when signs of hypoperfusion persist. Interestingly, despite their ubiquitous use for management of cardiogenic shock, there is a lack of robust evidence to suggest the clear benefit of one agent over another.  Therefore, the choice of a specific agent is guided by additional factors including vital signs, concurrent arrhythmias, and availability. For this patient, dobutamine is the only inotrope listed. Although she is tachycardic, her lack of arrhythmia makes dobutamine relatively lower risk and does not outweigh the potential benefits.

Choice A – Increase carvedilol – is not correct. Beta-blockers should be continued in HF hospitalization whenever possible; however, in a patient with low cardiac output and signs of shock, beta-blockers should be discontinued due to their negative inotropic effects.

Choice C – Increase lisinopril – is not correct. Afterload reduction is reasonable to decrease myocardial oxygen demand. However, given the hypotension and renal dysfunction, increasing lisinopril could be potentially dangerous by further exacerbating hypotension and renal dysfunction. Furthermore, given her tenuous hemodynamic status, it would be more beneficial to start an IV medication that is easier to monitor and rapidly titrate.

Choice D – Start nitroprusside – is not correct. Intravenous Vasodilators are helpful for improving cardiac output in high SVR states when the patient is normotensive or even hypertensive. However, this patient is HYPOtensive and so vasodilators should be held.

Main Takeaway In patients with cardiogenic shock, intravenous inotropic support should be used to maintain systemic perfusion and preserve end-organ performance. Guideline Loc. Section 9.5

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280. CCC: Sedation in the Cardiac ICU with Dr. Christopher Domenico02 Apr 202300:54:38

The practice of critical care cardiology relies on the use of invasive hemodynamics, mechanical ventilation, mechanical circulatory support, and other advanced techniques to help our patients recover from critical cardiac illnesses. To facilitate these interventions, it is essential to have a broad understanding of how sedation and analgesia keep our patients comfortable and safe throughout their time in the CICU. In this episode, series co-chair, Dr. Yoav Karpenshif, and CardioNerds co-founder, Dr. Daniel Ambinder, are joined by Dr. Natalie Tapaskar, cardiology fellow and CardioNerds FIT Ambassador from Stanford, and faculty expert, Dr. Chris Domenico, to discuss sedation in the cardiac ICU. Notes were drafted by Dr. Natalie Tapaskar. Audio editing by CardioNerds academy intern, Anusha Gandhi.

We discuss the use of analgesics and sedative medications in the cardiac ICU. We dissect three cases of VT storm, heart failure associated cardiogenic shock, and cardiac arrest. We assess the hemodynamic, arrhythmic, and metabolic effects of opioids and sedatives and delve into the altered pharmacokinetics of these drugs during targeted temperature management. Most importantly, we highlight the use of structured pain and sedation scoring systems and discuss the recognition and management of ICU delirium both from a pharmacologic and non-pharmacologic standpoint.

The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark BelkinDr. Eunice DuganDr. Karan Desai, and Dr. Yoav Karpenshif.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes – Sedation in the Cardiac ICU with Dr. Christopher Domenico
  1. Think about analgesia and sedation as separate entities with management of analgesia first and sedation second. Frequent re-assessment of needs should be performed to reduce ICU delirium and improve long-term outcomes.
  2. Fentanyl is generally a good starting point for analgesia in the ICU since it is fast on/fast off, but can stick around for a long time the longer it is used. The choice of bolus or continuous infusion opioids depends on the clinical scenario and personal/institutional preference. Remember to administer bolus doses that are 50-100% of the hourly continuous infusion dose to reach steady state faster.
  3. When managing refractory VT storm with sedative agents (propofol, benzodiazepines and/or dexmedetomidine), you should target the deepest level of sedation necessary to suppress sympathetic drive.
  4. For cardiogenic shock patients, the choice of sedative agent is a nuanced decision. Think about etomidate first for intubation as it has the least cardiovascular and hemodynamic impact. And remember the propofol trifecta: negative inotropy, direct vasodilation, and bradycardia!
  5. Pharmacokinetics are disrupted during targeted temperature management, thus be weary of overly sedating patients due to reduced drug clearance.
Show notes – Sedation in the Cardiac ICU with Dr. Christopher Domenico
  • How do we initiate analgesics and sedatives?
    • Analgesia first and sedation second!
  • Analgesia: think about how to reduce a patient’s pain
    • Everyone has a different pain tolerance and critically ill patients can have moderate to severe pain at baseline.
    • Metrics to assess pain include self-reported scales, behavioral scales, facial expressions, extremity movement, compliance with the ventilator, tachycardia, tachypnea, and hypertension.
  • Sedation: think about how to reduce a patient’s agitation or anxiety
    • The target depth of sedation depends on the clinical scenario.
      • For example, a patient with a femoral balloon pump may need more sedation if agitation is causing excessive lower extremity movement and thus a higher risk of device dislodgement.
    • Use the Richmond Agitation and Sedation Scale (RASS) for titrating sedation leve.
      • -5 – Unarousable. No response to voice or physical stimuli
      • -4 – Deep sedation. No response to voice, but movement or eye opening to physical stimulation
      • -3 – Moderate sedation. Movement or eye-opening to voice
      • -2 – Light sedation. Briefly awakens to voice
      • -1 – Drowsy. Not fully alert, but has sustained awakening to voice
      • 0 – Alert and calm
      • +1 – Restless. Anxious, apprehensive, but not aggressive
      • +2 – Agitated. Frequent non-purposeful movement, fights vent
      • +3 – Very agitated. Pulls or removes tubes/catheters
      • +4 – Combative. Violent, immediate danger to staff
  • What are the different opioid options and when should we use them?
    • Break down opioids into 3 groups (as per Dr. Domenico):
      • Group 1 (morphine, hydromorphone, fentanyl) for pain management in the ICU.
        • Onset of action: Fentanyl is the quickest on/off (30 seconds-2 minutes), but is highly lipophilic, redistributing in fatty tissues after ~30 minutes. The longer you use fentanyl, the longer it will stick around – i.e. “context-sensitive half-time.” Morphine and Hydromorphone have an onset from 5-15 minutes.
        • Half-life: All 3 are similar at 2-4 hours. (Fentanyl can be even higher the longer it is used).
        • Metabolism: Morphine is metabolized by the liver, but has active metabolites that are renally cleared; thus, be cautious with high doses in renal impairment. Fentanyl is metabolized by the CYP system thus it accumulates in hepatic dysfunction.
      • Group 2 (remifentanil and sufentanil) generally for use in the operating room.
        • Onset of action: Both are very quick on/off ranging from 1-3 minutes.
        • Half-life: Remifentanil’s is 3-10 minutes, whereas sufentanil’s is 2-3 hours.
        • Metabolism: Remifentanil demonstrates no accumulation in hepatic or renal impairment, thus is a good choice in these scenarios. Beware of the rare possibility of serotonin syndrome with both these agents.
      • Group 3 (methadone) as a bridge to wean off from long term infusions of other opioids.
        • Onset of action: 1-20 minutes when given intravenously, but 3-5 days when given orally.
        • Half-life: Ranges from 8-60 hours.
        • Metabolism: Hepatic, exercise caution with dysfunction. Also monitor for QT prolongation.
  • Should we administer opioids as boluses or continuous infusions?
    • There is no strong data to guide bolus versus continuous infusion dosing of opioids and the choice is often left up to personal/institutional preference. Small studies in emergency department patients suggest there is less ICU delirium post-intubation with bolus dosing over continuous infusions of opioids.
    • Generally, think about starting with bolus dosing to assess a patient’s true needs, but patients may require continuous infusions if they are receiving frequent boluses.
    • When increasing the rate of a continuous infusion, one can reach steady state faster by administering bolus doses at 50-100% of the hourly dose of the infusion.
  • How should we use analgesics and sedatives for management of arrhythmias, specifically VT storm?
    • The main goal in refractory VT storm is to sedate the patient as deeply as necessary to suppress their sympathetic drive. Generally, the choice of sedative agent is less important than the level of sedation achieved.
      • Propofol, benzodiazepines, and dexmedetomidine can all decrease sympathetic drive.
      • Propofol has some anti-arrhythmic effects via autonomic nervous system modulation.
      • Dexmedetomidine may increase the arrhythmogenic threshold.
      • Benzodiazepines have no direct effect on the conduction system.
    • Opioids have GABA agonist properties and thus have some anti-arrhythmic properties. However, opioids alone are rarely effective in managing malignant arrhythmias unless pain is the main trigger for the arrhythmia. 
    • In some animal studies, fentanyl and morphine are thought to increase the ventricular fibrillation threshold, but this is not validated with hard outcomes in clinical trials.
  • What sedatives are safe to use for intubation in cardiogenic shock?
    • Induction: Etomidate, ketamine, and propofol are common agents used for induction of sedation peri-intubation.
      • Etomidate – has minimal cardiovascular/hemodynamic effects and should be considered first for induction in cardiogenic shock. Can lead to adrenal insufficiency. 
      • Ketamine – is a direct vasoconstrictor (including coronary arteries) and results in hypertension and tachycardia. It should be avoided in patients with ACS. It may have a direct myocardial depressant effect, so its use is avoided in prolonged shock states.
      • Propofol – has a plethora of properties-sedative, hypnotic, amnestic, antiemetic, and anticonvulsant, but importantly has NO ANALGESIC properties. Remember its hemodynamic trifecta: negative inotropy, direct vasodilation, and bradycardia. It is also highly lipophilic, with a long half-life with extended infusions- i.e. “context-sensitive half-time”. Don’t forget to check triglyceride levels at baseline and at regular intervals while on a continuous infusion.
    • Maintenance: Propofol, benzodiazepines, and dexmedetomidine can be used for maintenance of sedation post-intubation.
      • Benzodiazepines
        • Also have a plethora of properties- sedative, amnestic, anticonvulsant, anxiolytic, and hypnotic but NO ANALGESIC properties.
        • Midazolam is quicker on/off (2-5 minutes) compared to lorazepam. Midazolam can accumulate in renal dysfunction. Think about polyethylene toxicity when patients on lorazepam at high doses for extended periods of time develop metabolic acidosis.
        • In general, benzodiazepines use is associated with increased ventilator time, ICU delirium, and ICU length of stay.
      • Dexmedetomidine
        • Is an alpha 2 agonist and thus monitor for hypotension and bradycardia with ongoing use. It does not cause respiratory depression. It generally does not result in deep sedation (less than -2) and is not very effective for acute management of agitation. Consider its use for patients that require mild sedation during extubation.
  • What are general principles of analgesia and sedation during targeted temperature management?
    • Always assess baseline pain and RASS prior to medication initiation. Once the need for analgesia and sedation is established, these medications should be started prior to initiating cooling protocols.
    • Consider using the lowest effective doses of medications to increase the ability to perform accurate neuro-prognostication.
    • Pharmacokinetics are disrupted during TTM, including absorption, distribution, metabolism, and excretion. These properties may vary among drugs of the same class.
      • In hypothermia, there is a general decrease in global drug perfusion as there is shunting of blood away from non-vital organs and intra-vascular volume of distribution is reduced. Drug clearance may be reduced, thus be cautious of over-sedation.
      • Serum creatinine may not be a reliable indicator of renal function during TTM as there is a decrease in creatinine synthesis and secretion.
    • Remember that hypothermia can cause hypomagnesemia, check and replete often!
  • How should we manage shivering?
    • Shivering increases baseline metabolic activity and is associated with decreased brain tissue oxygenation and can lead to worsening hypoxic brain injury.
    • Assess shivering using the bedside shivering assessment scale (BSAS).
    • Use the Columbia anti-shivering protocol to achieve shiver control with the least sedating regimen.
    • There is limited data on opioids versus neuromuscular blockade for shivering, both strategies may be effective. Generally, neuromuscular blockade is considered after other strategies have failed.
  • How do we assess and treat ICU delirium?
    • Delirium should be assessed frequently using metrics such as the Confusion Assessment Method (CAM-ICU) or the Intensive Care Delirium Screening checklist (ICDSC).
      • CAM-ICU assesses for acute changes or fluctuation in mental status, inattention, altered level of consciousness, and disorganized thinking.
    • There is not a lot of data on the use of antipsychotics to treat ICU delirium.
      • Haloperidol is most often used even though data is limited.
      • Quetiapine has some positive data in small studies. Try to start with 15 mg q12 hours and titrate up to reach a target dose of 200 mg q12 hours as needed. Be cautious of hypertension and QT prolongation.
      • Very few patients will require antipsychotics once they leave the hospital, unless they have a pre-existing indication.
    • Non-pharmacologic methods should always be used such as sleep hygiene, freedom from lines/catheters, early mobilization, avoidance of constipation, and providing glasses/hearing aids as needed.
  • What strategies can be used to limit analgesia and sedation and why is that important?
    • Constant re-evaluation of the need for analgesia and sedation is paramount to reducing ventilator time, ICU delirium, and ICU and hospital length of stay.
    • Ask yourself if the RASS goal is the same today as it was yesterday. Re-evaluate often.
    • Take sedation vacations! Spontaneous breathing and spontaneous awakening trials should be performed at least daily if it is safe for the patient.
    • Consider re-introduction of home medications when appropriate, such as gabapentin for neuropathic pain or prior psychiatric medications.
References
  1. Riker RR, Gagnon DJ, May T, Seder DB, Fraser GL. Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest. Best Practice & Research Clinical Anaesthesiology. 2015;29(4):435-450. doi:10.1016/j.bpa.2015.09.006
  2. Zakaria S, Kwong HJ, Sevransky JE, Williams MS, Chandra-Strobos N. Editor’s Choice-The cardiovascular implications of sedatives in the cardiac intensive care unit. European Heart Journal: Acute Cardiovascular Care. 2018;7(7):671-683. doi:10.1177/2048872617695231
  3. Schenone A, Chen K, Andress K, Militello M, Cho L. Editor’s Choice- Sedation in the coronary intensive care unit: An adapted algorithm for critically ill cardiovascular patient. European Heart Journal: Acute Cardiovascular Care. 2019;8(2):167-175. doi:10.1177/2048872617753797
  4. Van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement from the American Heart Association. Circulation. 2017;136(16):e232-e268. doi:10.1161/CIR.0000000000000525
279. Guidelines: 2021 ESC Cardiovascular Prevention – Question #19 with Dr. Eugene Yang29 Mar 202300:06:43

The following question refers to Section 3.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern, student Dr. Hirsh Elhence, answered first by Ohio State University Cardiology Fellow Dr. Alli Bigeh, and then by expert faculty Dr. Eugene Yang.

Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section. 

The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association.

Question #19

True or False: A 70-year-old male has an estimated 10-year ASCVD risk (using SCORE2-OP) of 7.5% which confers a very high CVD risk and necessitates treatment with a statin.  TRUE  FALSE 

Answer #19

Explanation   FALSE – CVD risk thresholds for risk factor treatment are higher in apparently healthy people 70 years and older in order to prevent overtreatment in the elderly. A 10-year CVD risk ≥15% is considered “very high risk” for individuals ≥70 years of age (compared to a ≥7.5% cut-off for “very high risk” in younger patients <50 years old). For these patients, treatment of ASCVD risk factors, including lipid-lowering medications, is recommended (class IIb).  Lifetime benefit of treatment in terms of time gained free of CVD is lower in older people. The SCORE2-OP algorithm estimates 5-year and 10-year fatal and non-fatal CVD events adjusted for competing risks of non-CVD mortality. Treatment and risk stratification should (as with all patients) be individualized.  

For patient >70 years of age, a 10-year CVD risk of 7.5 to <15% is considered “high risk”, and treatment of risk factors should be considered taking CVD risk modifiers, frailty, lifetime treatment benefit, comorbidities, polypharmacy, and patient preference into account.  

For patient >70 years of age, a 10-year CVD risk of <7.5 is considered “low-to-moderate risk” and would generally not qualify for risk factor treatment unless one or several risk modifiers are present.  

Smoking cessation, lifestyle recommendations and a SBP <160 mmHg are recommended for all. 

Main Takeaway 
  • CVD risk assessment for patients 70-years and older is estimated using the SCORE2-OP algorithm. A predicted 10-year CVD risk score of ≥15% confers a very high CVD risk, however, this it is a class IIb indication to initiate/intensify lipid lowering therapies in these patients. Decision should be individualized and based on benefits vs risk assessment. 
Guideline Loc. 
  • 3.2.3.5 

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377. CardioOncology:  Multi-modality Imaging in Cardio-Oncology with Dr. Nausheen Akhter24 Jun 202400:15:19

CardioNerds Co-Founder Dr. Daniel Ambinder, Series Co-Chair Dr. Giselle Suero Abreu (FIT at MGH), and Episode Lead Dr. Iva Minga (FIT at the University of Chicago) discuss the use of multi-modality cardiovascular imaging in cardio-oncology with expert faculty Dr. Nausheen Akhter (Northwestern University). Show notes were drafted by Dr. Sukriti Banthiya and episode audio was edited by CardioNerds Intern and student Dr. Diane Masket.

They use illustrative cases to discuss:

  1. Recommendations on the use of multimodality imaging, including advanced echocardiographic techniques and cardiac MRI, in patients receiving cardiotoxic therapies and long-term surveillance.
  2. Role of nuclear imaging (MUGA scan) in monitoring left ventricular ejection fraction.
  3. Use of computed tomography to identify and/or monitor coronary disease.
  4. Imaging diagnosis of cardiac amyloidosis.

This episode is supported by a grant from Pfizer Inc.

This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero AbreuDr. Dinu Balanescu, and Dr. Teodora Donisan

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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References –  Multi-modality Imaging in Cardio-Oncology
  1. Baldassarre L, Ganatra S, Lopez-Mattei J, et al. Advances in Multimodality Imaging in Cardio-Oncology. J Am Coll Cardiol. 2022 Oct, 80 (16) 1560–1578.
Meet Our Collaborators

International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

278. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #13 with Dr. Anu Lala29 Mar 202300:21:02

The following question refers to Section 9.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Duke University cardiology fellow and CardioNerds FIT Ambassador Dr. Aman Kansal, and then by expert faculty Dr. Anu Lala.

Dr. Lala is an advanced heart failure and transplant cardiologist, associate professor of medicine and population health science and policy, Director of Heart Failure Research, and Program Director for the Advanced Heart Failure and Transplant fellowship training program at Mount Sinai. Dr. Lala is deputy editor for the Journal of Cardiac Failure. Dr. Lala has been a champion and role model for CardioNerds. She has been a PI mentor for the CardioNerds Clinical Trials Network and continues to serve in the program’s leadership. She is also a faculty mentor for this very 2022 heart failure decipher the guidelines series.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #13

Mrs. Hart is a 63-year-old woman with a history of non-ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 20-25%) presenting with 5 days of worsening dyspnea and orthopnea. She takes carvedilol 12.5mg BID, sacubitril-valsartan 24-46mg BID, empagliflozin 10mg daily, and furosemide 40mg daily and reports that she has been able to take all her medications. What is the initial management for Mrs. H? A Assess her degree of congestion and hypoperfusion B Search for precipitating factors C Evaluate her overall trajectory D All of the above E None of the above

Answer #13

Explanation The correct answer is D – all of the above.

 

Choice A is correct because in patients hospitalized with heart failure, the severity of congestion and adequacy of perfusion should be assessed to guide triage and initial therapy (Class 1, LOE C-LD). Congestion can be assessed by using the clinical exam to gauge right and left-sided filling pressures (e.g., elevated JVP, S3, edema) which are usually proportional in decompensation of chronic HF with low EF; however, up to 1 in 4 patients have a mismatch between right- and left-sided filling pressures. Hypoperfusion can be suspected from narrow pulse pressure and cool extremities, intolerance to neurohormonal antagonists, worsening renal function, altered mental status, and/or an elevated serum lactate. For more on the bedside evaluation of heart failure, enjoy Episode #142 – The Role of the Clinical Examination in Patients With Heart Failure – with Dr. Mark Drazner.

Choice B, searching for precipitating factors is also correct. In patients hospitalized with HF, the common precipitating factors and the overall patient trajectory should be assessed to guide appropriate therapy (Class 1, LOE C-LD). Common precipitating factors include ischemic and nonischemic causes, such as acute coronary syndromes, atrial fibrillation and other arrhythmias, uncontrolled HTN, other cardiac disease (e.g., endocarditis), acute infections, anemia, thyroid dysfunction, non-adherence to medications or new medications. When initial clinical assessment does not suggest congestion or hypoperfusion, symptoms of HF may be a result of transient ischemia, arrhythmias, or noncardiac disease such as chronic pulmonary disease or pneumonia, and more focused assessments may be warranted.

Lastly, Choice C, evaluation of a patient’s trajectory is correct as hospitalization for HF is a sentinel event that signals worse prognosis and provides key opportunities to redirect the disease trajectory – including establishment of optimal volume status before and after discharge. During the HF hospitalization, the approach to management should include and address precipitating factors, comorbidities, and previous limitations to ongoing disease management related to social determinants of health. The disease trajectory for patients hospitalized with reduced EF is markedly improved by optimization of recommended medical therapies, which should be initiated or increased toward target doses once the efficacy of diuresis has been shown.

Main Takeaway In summary, when a patient is admitted for acute decompensated heart failure, initial management involves assessing the patient’s degree of congestion and hypoperfusion, identifying and addressing precipitating factors, and evaluating overall patient trajectory to guide appropriate triage and therapy. Guideline Loc. Section 9.1, Table 21

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277. Case Report: When Infarction Brings the Walls Down – Brigham and Women’s Hospital28 Mar 202301:05:22

CardioNerds (Amit and Dan) join Dr. Maria Pabon (cardiology fellow), Dr. Kevin Bersell (cardiology fellow), Dr. Saad Sultan Ghumman (interventional cardiology fellow), and Dr. Rhanderson Cardoso (cardiovascular imaging fellow) from Brigham and Women’s Hospital. Together, they explore a complex case of STEMI that was further complicated by ventricular free wall rupture. Additionally, Dr. Ajar Kochar, Program Director for Interventional Cardiology at Brigham and Women’s Hospital, provides an insightful “ECPR” segment, adding a unique perspective to the case. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

This is the case of a patient who presented with STEMI and was found to have a moderate pericardial effusion with echogenic material within the pericardial space concerning for thrombus. Urgent CTA/CT surgery was engaged due to concern for dissection, but no evidence of dissection, rupture or intramural hematoma was found. The patient underwent an urgent pericardiocentesis which yielded 350cc of hemorrhagic fluid, leading to an improvement in hemodynamic status. A coronary angiogram was performed which showed a 100% thrombotic occlusion of OM 1, the culprit lesion for the STEMI. Due to the possibility of a delayed STEMI and high suspicion for mechanical complication of MI, aspirin and IV cangrelor were chosen as the preferred antiplatelet strategy. However, cangrelor was held and cardiac surgery was consulted, as LV free wall rupture was suspected. The patient underwent urgent repair of the LV free wall rupture, with an uneventful post-op recovery and discharge on day 8 to cardiac rehab.

CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Case Media Pearls – When Infarction Brings the Walls Down – Brigham and Women’s Hospital
  1. In the era of primary PCI, mechanical complications of MI are relatively rare.
  2. Timely recognition using multi-modality imaging and prompt surgical intervention can result in favorable outcomes.
  3. An approach that involves a Heart Team can be advantageous in optimizing outcomes in such complex cases.
Show Notes – When Infarction Brings the Walls Down – Brigham and Women’s Hospital
  1. Incidence of post AMI LV free wall rupture:
    • 0.1-1%
  2. Risk factors for LV Free wall Rupture:
    • Older age
    • Female sex
    • Prior HTN
    • 1st lateral or Anterior Wall MI
  3. Protective factors towards free wall rupture:
    • LV hypertrophy
    • CHF
    • Hx of prior infarcts
    • Chronic ischemic heart disease
    • Early use of beta blockers post MI
    • Timely intervention
  4. Incidence of Mortality associated with mechanical rupture related to AMI:
    • 8-10%
  5. When to suspect a mechanical complication of AMI:
    • AMI with shock/hypotension
    • New murmur
    • New pericardial effusion > 10mm on bedside echo
  6. Other etiologies that can cause free wall rupture:
    • Trauma
    • Cardiac infection
    • Aortic dissection
    • Cardiac tumors
    • Infiltrative diseases
    • Iatrogenic from PCI or surgical procedures
References – When Infarction Brings the Walls Down – Brigham and Women’s Hospital
  1. Varghese S, Ohlow MA. Left ventricular free wall rupture in myocardial infarction: A retrospective analysis from a single tertiary center. JRSM Cardiovasc Dis. 2019 Jan-Dec;8:2048004019896692. doi: 10.1177/2048004019896692. PMID: 31970072.
  2. Pineda-De Paz, D.O., Hernández-del Rio, J.E., González-Padilla, C. et al. Left ventricular free-wall rupture, a potentially lethal mechanical complication of acute myocardial infarction: an unusual and illustrative case report. BMC Cardiovasc Disord 19, 80 (2019). https://doi.org/10.1186/s12872-019-1063-x
  3. Yip HK, Wu CJ, Chang HW, Wang CP, Cheng CI, Chua S, Chen MC. Cardiac rupture complicating acute myocardial infarction in the direct percutaneous coronary intervention reperfusion era. Chest 2003;124:565–71. doi: 10.1378/chest.124.2.565. PMID: 12907558.
  4. Sutherland FW, Guell FJ, Pathi VL, Naik SK. Postinfarction ventricular free wall rupture: strategies for diagnosis and treatment. Ann Thorac Surg 1996;61:1281–5. doi: 10.1016/0003-4975(95)00953-6. PMID: 8627055.
  5. Meta-analysis of corticosteroid treatment in acute myocardial infarction. Am J Cardiol 2003;91:1055–9. doi: 10.1016/S0002-9149(03)00216-4. PMID: 12745097.

 

276. Left Ventricular Assist Devices and Renal Dysfunction with Dr. Brian Houston and Dr. Nisha Bansal22 Mar 202300:57:24

CardioNerds (Dr. Amit Goyal), Dr. Sonu Abraham (CardioNerds Ambassador from Lahey Hospital and Medical Center, Burlington, MA) discuss left ventricular assist devices (LVAD) and the implications of renal dysfunction with Dr. Brian Houston and Dr. Nisha Bansal. This episode will focus on the intersection of left ventricular assist devices and renal dysfunction. Patients with a combination of heart failure and renal dysfunction overall have a guarded prognosis and their management poses unique challenges to the clinician. We initially discuss the basics of an LVAD and general approach to LVAD candidacy evaluation. We then discuss specific implications of acute kidney injury, presence of preexisting CKD, and end stage renal disease in patients with/being considered for an LVAD. Risk factor identification and prognostication allows for appropriate selection of the right candidates for an LVAD in the context of renal disease. Dr. Brian Houston is the Director of the Mechanical Circulatory Support program at Medical University of South Carolina. Dr. Nisha Bansal is an Associate Professor and the Arthur Stach Family Endowed Professor in the Division of Nephrology, an investigator at the Kidney Research Institute, the Director of Nephrology Clinical and Research Education, and the Director of the Kidney-Heart Service at the University of Washington. Notes were drafted by Dr. Sonu Abraham and episode audio was edited by student Dr. Chelsea Amo-Tweneboah.

Check out the CardioNerds Failure Heart Success Series Page for more heart success episodes and content!

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls – Left Ventricular Assist Devices and Renal Dysfunction
  1. End stage renal disease (CKD on dialysis) is considered an absolute contraindication for LVAD implantation. Select young patients who are being considered for heart-kidney transplantation in the near future may be candidates for an LVAD as a bridge to heart-kidney transplantation.
  2. LVAD implantation can improve kidney function in the short term in patients with AKI primarily caused by cardio-renal syndrome.
  3. Patients with pre-existing CKD (not dialysis dependent) have a greater risk of developing AKI after LVAD implantation.  
  4. Several dialysis modalities including in-center hemodialysis, home hemodialysis, and peritoneal dialysis are available for LVAD patients. However, there are several challenges associated with each modality.
  5. An AV graft is a useful vascular access option in LVAD patients undergoing hemodialysis due to a lower risk of infection and ease of immediate use.
  6. Causes for anemia in patients with an LVAD and renal dysfunction include anemia of chronic disease, gastrointestinal bleeding, and pump thrombosis leading to hemolysis.
Show notes – Left Ventricular Assist Devices and Renal Dysfunction

Notes: (drafted by Dr. Sonu Abraham)

What is a left ventricular assist device (LVAD) and what are its components?

An LVAD supports circulation by unloading the left ventricle and providing increased cardiac output to help support organ perfusion. Use in properly selected patients is associated with improved quality of life and increased survival. The current iteration of LVADs offer continuous flow, as opposed to the older versions which employed pulsatile flow.

Components of the LVAD:

  • Inflow cannula (sucks blood from the LV)
  • Pump
  • Outflow cannula (dumps blood into the aorta)
  • Percutaneous driveline
  • Electrical controller

How is a patient evaluated for LVAD candidacy?

The 2 main questions to be answered during the evaluation of a patient for an LVAD are:

            1. Are they sick enough? Do they have end stage heart failure?

            2. Do we expect the benefits of an LVAD to outweigh the risks?

  • Presence/absence of right ventricular failure
  • Other life limiting organ failure: Kidney failure/lung disease/liver failure/vascular disease
  • Anatomic concerns (ex. LV size)
  • Surgical risk (ex. Prior sternotomies, calcified aorta, etc)
  • Psychosocial aspects
  • Shared decision making (Does the patient want the device?)

What are the outcomes of patients with end stage renal disease (chronic kidney disease on dialysis) after LVAD implantation?

  • Patients with ESRD have a high burden of comorbidities. 40% of dialysis patients have heart failure.
  • The combination of heart failure and ESRD propounds a poor prognosis. Patients with ESRD without heart failure have a 40% survival in 5 years. Conversely, those with ESRD and heart failure have a < 20% survival in 5 years.
  • A retrospective analysis of the United States Renal Data System revealed that 50% patients on dialysis who received an LVAD died during the index hospitalization, compared to those not on dialysis whose in hospital mortality was <10%. The median survival was ~3 weeks. By 6 months after LVAD implantation, ~70% of patients on dialysis had died.
  • Based on INTERMACS data, kidney function is one of the strongest predictors of outcomes in patients with an LVAD.

What are the specific situations in which an LVAD might be offered to a patient with ESRD?

  • We may consider LVAD implantation in ESRD patients under specific circumstances.
  • Young patients with good functional status and good end organ function otherwise, who may be a candidate for heart-kidney transplantation in the near future, may be considered for LVAD implantation as a bridge to heart-kidney transplantation.
  • If it is felt that the patient’s renal dysfunction can be improved by augmenting cardiac output and the hemodynamics suggest cardio-renal syndrome, in very select patients on recently initiated dialysis LVAD implantation may be considered. Renal imaging showing absence of scarring and the absence of proteinuria suggest a better prognostic sign and may suggest cardio-renal syndrome.

In patients with acute kidney injury (with no prior history of CKD) being evaluated for LVAD implantation, what is the effect of an LVAD on kidney function?

  • Effect of an LVAD on kidney function: There is typically an initial improvement in kidney function, particularly in the first month post-implantation, due to restoration of normal hemodynamics with improvement in cardiac output and relieving renal venous congestion. Long term data, however, suggests gradual deterioration of kidney function in the long term. This is possibly due to kidney insults from the LVAD itself. The continuous flow of the LVAD can lead to periarteritis, hyperplasia of the renal arterial smooth muscle cells, and neurohormonal activation of the RAAS system leading to kidney injury over time.
  • Creatinine may not be the best marker of kidney function in these patients. Cystatin C and tubular kidney injury markers, soon to be commercially available, may be better markers of kidney function.

Does having chronic kidney disease (not dialysis dependent) increase the risk of worsening kidney function after LVAD implantation?

The occurrence of AKI after LVAD worsens outcomes. The presence of CKD prior to LVAD implantation increases this risk of AKI after LVAD implantation. Patients with CKD stage 3 or more have a 1-year mortality of >30% after LVAD implantation. In patients who have AKI after LVAD implantation, 30-day mortality is 18% and 1 year mortality is 40% with increased risk of infection, multisystem organ failure, and longer length of stay.

Common causes of AKI after LVAD implantation include:

  1. Right ventricular failure
  1. Bleeding requiring blood products and crystalloids, contributing to congestion.
  1. Longer cardio-pulmonary bypass

Hemolysis

Based on a 10-year case series from the Mayo clinic, 15% of patients with LVAD require renal replacement therapy. If GFR<45 and there is proteinuria, the risk increased to 40%.

The 4 risk factors to predict AKI and RRT requirement after LVAD:

  • Presence of a low GFR
  • Proteinuria
  • Increased RA pressure
  • Longer cardio-pulmonary bypass time
  • The HEARTMATE III Risk Score provides individual survival prediction at 1- and 2-years post LVAD implantation – includes BUN and sodium levels

What are the options available to patients in terms of long-term dialysis once LVAD patients are dialysis dependent?

  • There are 3 main options for long term RRT:
    • In-center hemodialysis
    • Home hemodialysis
    • Peritoneal dialysis
  • Considerations:
    • In center Hemodialysis:
      • Challenges: large ultrafiltration rates can lead to lower MAPs, anticoagulation considerations (bleeding complications), high risk of infection (central venous catheter), pragmatic challenges (technical expertise of the dialysis staff, comfort of the attending nephrologist, transportation issues).
    • Peritoneal dialysis:
      • Benefits: decreased risk of infection (however anatomical considerations with respect to proximity to the driveline should be taken into account), more physiological and less hemodynamic instability, no need for anticoagulation.
      • Challenge: home based therapy (burden on the patient and family members)

What are the options in terms of vascular access in patients with an LVAD who are started on hemodialysis?

  • Central venous HD catheters – high risk of infection and therefore, not preferred.
  • AV fistula – low rates of infection, however, it takes 2-3 months for fistula maturation.
  • AV graft – preferred due to lower risk of infection, ability to use immediately.

What are the causes for anemia in patients with an LVAD and renal dysfunction?

  • Anemia of chronic disease
  • Increased risk of gastrointestinal bleed
    • Anticoagulation requirement
    • Acquired Von Willebrand deficiency
    • Higher burden of arterio-venous malformations
  • Pump thrombosis can lead to hemolysis

What are the implications of blood transfusions and use of erythropoietin stimulating agents (ESAs) in these patients?

  • Judicious use of blood transfusions is advised particularly in patients waiting for a heart transplantation due to increased risk of antigen sensitization which can limit their potential donor pool.
  • Those who receive ESAs have a dose-dependent increased risk of pump thrombosis and all-cause mortality. This was however, studied in patients with a HEARTMATE II (axial flow device) as opposed to the currently most commonly used pump which is the HEARTMATE III (centrifugal flow device) known to have an overall lower risk of pump thrombosis.
References
  1. Peritoneal Dialysis Following Left Ventricular Assist Device Placement and Kidney Recovery: A Case Report Kidney Med. 2021;3(3):438-441. Published 2021 Feb 17. doi:10.1016/j.xkme.2020.12.009
  2. Bansal N, Hailpern SM, Katz R, et al. Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease. JAMA Intern Med. 2018;178(2):204-209. doi:10.1001/jamainternmed.2017.4831
  3. Butler J, Geisberg C, Howser R, et al. Relationship between renal function and left ventricular assist device use. Ann Thorac Surg. 2006;81(5):1745-1751. doi:10.1016/j.athoracsur.2005.11.061
  4. Haglund NA, Feurer ID, Dwyer JP, et al. Does renal dysfunction and method of bridging support influence heart transplant graft survival?. Ann Thorac Surg. 2014;98(3):835-841. doi:10.1016/j.athoracsur.2014.05.059
  5. Jawaid O, Gaddy A, Omar HR, Guglin M. Ventricular Assist Devices and Chronic Kidney Replacement Therapy: Technology and Outcomes. Adv Chronic Kidney Dis. 2021;28(1):37-46. doi:10.1053/j.ackd.2021.01.002
  6. Ootaki C, Yamashita M, Ootaki Y, et al. Reduced pulsatility induces periarteritis in kidney: role of the local renin-angiotensin system. J Thorac Cardiovasc Surg. 2008;136(1):150-158. doi:10.1016/j.jtcvs.2007.12.023
  7. Patel AM, Eduardo Rame J, Rudnick MR. How does the nephrologist manage an LVAD patient on chronic maintenance dialysis?. Semin Dial. 2014;27(3):284-288. doi:10.1111/sdi.12229
  8. Roehm B, Vest AR, Weiner DE. Left Ventricular Assist Devices, Kidney Disease, and Dialysis. Am J Kidney Dis. 2018;71(2):257-266. doi:10.1053/j.ajkd.2017.09.019
  9. Sandner SE, Zimpfer D, Zrunek P, et al. Renal function and outcome after continuous flow left ventricular assist device implantation. Ann Thorac Surg. 2009;87(4):1072-1078. doi:10.1016/j.athoracsur.2009.01.022
  10. Wettersten N, Estrella M, Brambatti M, et al. Kidney Function Following Left Ventricular Assist Device Implantation: An Observational Cohort Study. Kidney Med. 2021;3(3):378-385.e1. Published 2021 Apr 2. doi:10.1016/j.xkme.2021.01.009
  11. Yalcin YC, Muslem R, Veen KM, et al. Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study. J Card Fail. 2020;26(4):333-341. doi:10.1016/j.cardfail.2020.01.010
  12. Yoshioka D, Sakaguchi T, Saito S, et al. Predictor of early mortality for severe heart failure patients with left ventricular assist device implantation: significance of INTERMACS level and renal function. Circ J. 2012;76(7):1631-1638. doi:10.1253/circj.cj-11-1452
275. Case Report: A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital20 Mar 202300:42:29

CardioNerds (Amit and Dan) join Dr. Khaled Abdelrahman, Dr. Gurleen Kaur, and Dr. Danny Pipilas from the Brigham and Women’s Hospital Residency Program for Italian food and cannolis at the North End in Boston as they discuss the case of an elderly man with primary cardiac lymphoma. They review an approach to intracardiac masses, discuss advantages and disadvantages of various imaging modalities for the evaluation of intracardiac masses, and also delve into anthracycline toxicity. The E-CPR segment is provided by Dr. Ron Blankstein, Associate Director of the Cardiovascular Imaging Program and Director of Cardiac Computed Tomography at Brigham and Women’s Hospital. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

A 76-year-old man with a history of hyperlipidemia presented with one month of progressively worsening fatigue, weight loss, and dyspnea on exertion. Physical exam was notable for a 3/6 systolic murmur at the left upper sternal border, a flopping sound along the sternum heard throughout the cardiac cycle, and JVP elevated to the level of the mandible. TTE revealed a large heterogeneous echodensity in the right ventricular (RV) free wall that extended into the pericardium and into the RV myocardium with mobile components in the RV cavity and obstruction of the RV outflow tract. Nongated CT chest showed a solid nodule in the periphery of the left lower lung lobe. Gated cardiac CTA revealed a large heterogenous mass in the right atrioventricular groove that encased the proximal thoracic aorta and pulmonary artery and invaded the RV myocardium and RV outflow tract along with a large pericardial effusion. On cardiac MRI, the mass was isointense to the myocardium on T1-weighted images, hyperintense on T2-weighted images, and had heterogenous enhancement on late gadolinium enhancement images. Overall, the imaging findings were highly suspicious for cardiac lymphoma which was confirmed with biopsy of the lung nodule; pathology showed a large B cell lymphoma. The patient was treated with R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and TTE after 6 cycles of chemotherapy demonstrated resolution of the RV mass.

CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Case Media 1.  There is a large homogeneous mass in the right atrioventricular groove that extends anterior to the right ventricular outflow tract, pulmonary artery, and ascending aorta, measuring up to 9.4 x 7.1 cm (axial) x 13 cm (craniocaudal). The mass encases the proximal thoracic aorta and pulmonary artery. The mass invades the right ventricular myocardium, the right ventricular outflow tract, the pulmonary artery, and proximal main pulmonary artery. There is severe stenosis of the right ventricular outflow tract due to obstruction by the mass. The mass encases the right coronary artery, without compression of the artery. There is enhancement of this mass on delayed contrast imaging. Collectively, these findings suggest cardiac lymphoma. 
2.  There is a large pericardial effusion, circumferential, measuring up to 2.2 cm adjacent to the right atrium and up to 2.3 cm anterior to the intraventricular septum. There is pericardial enhancement, indicative of pericardial inflammation. 
3.  This study was not optimized for the assessment of the coronary arteries. However, there are severe coronary artery calcifications. There is possible severe stenosis of the mid LAD. 
4.  Aneurysmal dilatation of the thoracic aorta, with measurements as reported in the narrative.  1. Normal left ventricular size and function.
 
2. There is a large homogenous, soft-tissue intensity mass in the right atrioventricular groove infiltrating the right ventricle free wall and cranially extending anterior to the aorta and main pulmonary artery. The mass encases the main pulmonary artery, the aortic root, the right coronary artery, and the left main coronary artery. The mass invades the right ventricular outflow tract and proximal main pulmonary artery, resulting in severe luminal narrowing at the level of the RVOT/pulmonary artery valve. For the dimensions of the mass, please refer to cardiac CT from 12/1/2021. The mass is isointense to myocardium on T1-weighted images and hyperintense on T2-weighted images. The mass avidly enhances on first-pass perfusion images. There is heterogeneous enhancement of the mass on late gadolinium enhancement images.
 
3. There is a large circumferential pericardial effusion, measuring up to 2.3 cm. The left ventricular cavity size and wall thickness are normal. Left ventricular systolic function is normal. There are no segmental left ventricular wall motion abnormalities noted. The estimated ejection fraction is 60%. The right ventricular size is normal. Right ventricular systolic function is mildly decreased. Mildly dilated ascending aorta. Mild AI. Mild MR. There is large heterogenous echodensity in the RV free wall that extends into the parietal pericardium and also into the RV myocardium with mobile components in the RV cavity apical to the tricuspid valve and immediately adjacent to the pulmonic valve. There is obstruction of flow out of the RVOT with a peak and mean gradient of 27 and 16 mmHg respectively. There appears to be some vascularity to this structure (seen best on clips 17 and 18) and overall findings are highly suspicious for tumor.  There is a small to moderate pericardial effusion. Anterior to the RV there is a larger collection that is probably pleural in etiology. Recommend cross-sectional imaging for further evaluation. There is no RV chamber collapse to suggest tamponade physiology. 1.  Intensely FDG avid infiltrative mediastinal most likely high-grade lymphoma..
2.  Additional discrete mediastinal and hilar nodes, and left lower lobe nodule, most likely additional areas of lymphomatous involvement. Moderate uptake along right adrenal nodule may represent additional site of lymphomatous involvement
3.  Small bilateral pleural effusions and small to moderate pericardial effusion. Pearls – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital
  1. In the diagnostic approach for cardiac masses, consider: 1) age of patient at time of presentation, 2) epidemiologic likelihood and clinical probability, 3) location of tumor, and 4) tissue characterization of the mass on CMR.
  2. CMR allows for better characterization of soft tissues and can assess mass morphology, dimensions, homogeneity, and infiltration into surrounding tissues.
  3. On CMR, cardiac lymphoma typically shows isointensity on T1 imaging and hyperintensity on T2 images.
  4. Cardiac CT allows for high spatial and temporal resolution, and can be useful to define cardiac masses that involve the coronary arteries; compared to CMR, cardiac CT has a greater ability to assess calcifications within a mass itself.
  5. Cardiac lymphomas have a predilection of right heart chambers, especially right atrium and can affect the AV groove, encasing the right coronary artery.
  6. Global systolic longitudinal myocardial strain on TTE is an indicator of early anthracycline-induced cardiomyopathy before overt reduction in ejection fraction.
Show Notes – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital
  1. What is the approach to an enlarged cardiac silhouette noted on chest x-ray?
    1. Cardiothoracic ratio of greater than 50%.
    1. Two possible “buckets” of diagnoses to consider are enlargement of heart related to cardiomegaly as opposed to a pericardial process like a pericardial effusion.
    1. For cardiomegaly, it can be from dilated or hypertrophic cardiomyopathy with most common causes including coronary artery disease, hypertension, valvular heart disease, and arrythmia-induced cardiomyopathy. Other buckets to consider are inflammatory causes, either infectious or autoimmune, as well as infiltrative diseases like amyloid or sarcoid, toxins (alcohol, cocaine, medications), endocrine, and nutritional causes (like a B1 or selenium deficiency).
    1. The most sensitive sign of a pericardial effusion on chest x-ray is enlargement of cardiac silhouette with a sensitivity of around 71%, but low specificity (1).
    1. With pericardial effusion, symmetric expansion of the heart contour leads to a globular appearance which is commonly referred to as flask-shaped or the water bottle sign (1).
  • What is the approach to intracardiac masses?
    • First, consider the age of the patient at the time of presentation since certain clinical entities like rhabdomyomas and fibromas are more common in the pediatric population (2).
    • Second, consider the epidemiologic likelihood and clinical probability. In a patient with a recent anterior wall MI and akinetic ventricular apex, a cardiac mass on echo would raise concern for an intracardiac thrombus (2).
    • Third, consider the location of the tumor. If the mass is on the valves, consider thrombus or a vegetation. While masses in the chambers can still represent thrombus, would also consider myxomas, lymphomas, and metastases (2).
    • Fourth, consider the tissue characterization of the mass on further diagnostic imaging such as CMR (2).
  • What is the role of multimodality imaging in the evaluation of intracardiac masses?
  • TTE is the first modality utilized in evaluation of a cardiac mass. TEE is useful specifically when valvular lesions are suspected or in patients with atrial masses or with mobile valvular lesions. It can help to characterize size, morphology, attachment site, extension, and hemodynamic effects.
  • CMR allows for better characterization of soft tissue and can assess mass morphology, dimensions, homogeneity, infiltration in surrounding tissues. These can all help differentiate different types of masses and whether a mass is benign or malignant. Signal characteristics gathered from T1, T2, early gadolinium enhancement, and late gadolinium enhancement sequences can further assess fatty infiltration, necrosis, hemorrhage, and vascularity within a mass (3, 4).
  • Cardiac CT is another option and offers high spatial and temporal resolution, multiplanar image reconstruction capabilities, and fast acquisition times. The large field of view also allows for assessment of chest and lung tissue, vascular structures, and assessment for other masses in the chest. CT may also be more helpful in defining surgical approaches and assessing how masses may involve the coronary arteries and assess for coronary artery calcifications or obstructive coronary disease (4).
  • FDG-PET is also another valuable imaging option which offers evaluation of metabolic activity of tumors. PET imaging can also help guide biopsy location, staging, and planning for cancer therapy.
  • What are key features of Primary Cardiac Lymphoma?
    • Diffuse large B-cell lymphoma is the most common subtype, though others like Burkitt lymphoma, low grade B –cell lymphoma, and T-cell lymphoma have also been described.
    • They occur more commonly in immunocompromised individuals and in immunocompetent patients, only account for 1.3% of primary cardiac tumors
    • Presenting symptoms are usually nonspecific. They may manifest as dysrhythmias like heart block, syncopal episodes, or even restrictive cardiomyopathy.
    • Approximately 20% of patients may develop acute heart failure before other symptoms.
    • On echocardiogram, these tumors appear homogeneous, with predilection of right heart chambers, especially right atrium. The AV groove can be affected, potentially encasing the right coronary artery (5).
    • On CMR, tissue appears isointense on T1-weighted imaging. On T2-weighted imaging, lesions are mildly hyperintense due to diffuse edema (5).
  • What are risk factors associated with anthracycline toxicity and what are strategies for preventing and monitoring for cardiotoxicity when anthracycline therapy is planned?
    • Up to 35% of patients receiving anthracycline therapy develop some form of cardiotoxicity (6).
    • The risk of developing anthracycline induced cardiotoxicity is directly proportional to the dose of anthracycline received, and after studies demonstrated HF incidence of 26% with doxorubicin dose of 550mg/m2 as compared to 5% with dose of 400mg/m2, efforts have been made to limit cumulative anthracycline doses to 400 to 450mg/m2. In addition, hypertension, DM, and obesity are all associated with increased risk (6).
    • There are two primary prevention strategies: using cardioprotective agents, and aiming to reduce potency of the anthracyclines. For cardioprotection, dexrazoxane is an FDA-approved cardioprotective agent for anthracycline induced cardiotoxicity (7).
    • TTE is the most common modality used for detection and monitoring of anthracycline toxicity on the heart. While LV dysfunction is most commonly detected, recent investigations suggest that RV function is also significantly affected by anthracycline toxicity (8).
    • Global systolic longitudinal myocardial strain on TTE has also emerged as a reproducible indicator of early anthracycline-related myocardial dysfunction and future reduction in LVEF (9).
References – A Rare Cause Of Fatigue, Dyspnea, And Weight Loss In An Elderly Man – Brigham and Women’s Hospital
  1. https://www.acc.org/latest-in-cardiology/articles/2019/09/09/10/46/chest-radiograph-signs-suggestive-of-pericardial-disease
  2. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, Westwood M, Ghosh AK, Guha A. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC CardioOncol. 2020 Jun 16;2(2):293-
  3. Motwani M, Kidambi A, Herzog BA, Uddin A, Greenwood JP, Plein S. MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology. 2013 Jul;268(1):26-43.
  4. Lopez-Mattei JC, Lu Y. Multimodality Imaging in Cardiac Masses: To Standardize Recommendations, The Time Is Now! JACC Cardiovasc Imaging. 2020 Nov;13(11):2412-2414.
  5. Jeudy J, Kirsch J, Tavora F, Burke AP, Franks TJ, Mohammed TL, Frazier AA, Galvin JR. From the radiologic pathology archives: cardiac lymphoma: radiologic-pathologic correlation. Radiographics. 2012 Sep-Oct;32(5):1369-80.
  6. Henriksen PA. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart. 2018 Jun;104(12):971-977.
  7. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014 Sep 2;64(9):938-45
  8. Liu JE. Anthracycline-Induced Cardiotoxicity: Remembering the Forgotten Ventricle. JACC CardioOncol. 2020;2(1):23-25.
  9. Potter E, Marwick TH. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):260-274.

 

274. Cardio-Oncology: Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Cardiologist Perspective with Dr. Joerg Hermann16 Mar 202300:55:00

CardioNerds co-founder Amit Goyal, Dr. Dinu Balanescu, Dr. Teodora Donisan, and Dr. Anjali Agarwalla get the cardiologist perspective of Cancer Therapy-Related Cardiac Dysfunction (CTRCD) from Dr. Joerg Hermann. We previously learned from the oncologist perspective with Dr. Susan Dent in Episode #261! In this episode, we discuss the history of cancer therapies and our developing understanding of how these life-saving medications can cause cardiac toxicities. As we manage patients in the CardioNerds CardioOncology clinic, we ask Dr. Hermann how the general cardiologist should approach patients with a cancer diagnosis, when should a patient be referred to a cardiooncology specialist, and what are the common cardiotoxicities to look out for. We’ll also place a quick consult to our guest expert’s goldendoodle! Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

This episode is supported by a grant from Pfizer Inc.

This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero AbreuDr. Dinu Balanescu, and Dr. Teodora Donisan

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes – Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Cardiologist Perspective with Dr. Joerg Hermann
  1. Patients with malignancy will incur several “hits” in addition to their malignancy and its subsequent treatment — these include their genetics, environment, and comorbidities. The role of the cardiologist is to identify how the combination of these “hits” can bring cardiovascular disease to the forefront and where we can intervene upon it.
  2. The sooner we recognize cardiotoxicity, the better the outcome for our patients. Patients should receive baseline risk assessment with TTE and biomarkers with routine surveillance.
  3. You cannot assign a percentage to cardiac risk in cancer. Patients require a multidisciplinary approach with constant monitoring and surveillance.
  4. Consider exercise testing when conducting pre-treatment risk assessment and during monitoring. Peak VO2 abnormalities is often the first marker of cardiotoxicity — though note that it correlates well with global longitudinal strain (GLS).
  5. If someone develops a cardiovascular complication of chemotherapy, this should prompt referral to cardiooncology.
Show notes – Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Cardiologist Perspective with Dr. Joerg Hermann

What types of cardiovascular pathology occur in the setting of cancer and its treatment?

We conventionally thought of cardiotoxicities as being of two types:

  • Type 1: irreversible cardiac injury that does not improve despite withdrawal of offending chemotherapeutic (protype = classic anthracycline cardiotoxicity)
  • Type 2: reversible cardiac dysfunction that improves with discontinuation of chemotherapeutic (prototype = classic traztuzumab cardiotoxicity)

However, we have begun moving away from this thought process as it has become more evident that injuries historically thought of as “type 1” may not be as relentless as previously understood, and that patients with type 2 dysfunction may not actually be returning to completely normal after the offending agent is withdrawn. As such, this episode proposes two other ways to frame our understanding of cardiotoxicities: a clinical/practical approach, based on symptoms (symptomatic vs asymptomatic — this is the approach used by the ESC guidelines), and a mechanistic approach: direct effect on cardiac myocytes, indirect effects (e.g., effect on coronaries), and inflammatory effects.

The 2021 International Cardiooncology Society (ICOS) consensus statement defines five major forms of cancer therapy related cardiac dysfunction (CTRCD):

  • Cardiac dysfunction/heart failure:
    • Asymptomatic: defined by changes in ejection fraction. This may be mild (LVEF >50% AND either new decline in GLS by >15% from baseline or new rise in troponin or NTproBNP), moderate (new LVEF reduction by ≥10 percentage points to 40 – 49% AND either new decline in GLS by >15% from baseline or new rise in troponin or NTproBNP), or severe (new LVEF reduction to < 40%).
    • Symptomatic: defined by severity of symptoms and intensity of treatment required. This may be mild (mild HF symptoms, no intensification of therapy required), moderate (need for outpatient intensification of diuretic and HF therapy), severe (HF hospitalization), or very severe (requiring inotropic or mechanical circulatory support, consideration for transplant).
  • Vascular toxicity: namely, myocardial infarction or stroke. Three primary forms:
    • Vasospasm
    • Thrombosis
    • Atherosclerosis
  • Arrhythmia/QTc prolongation
  • Hypertension
  • Myocarditis: made especially prominent by immune checkpoint inhibitors

Note that the definitions for these toxicities require a baseline assessment of LVEF, global longitudinal strain, and cardiac biomarkers. As such, these should be considered part of pre-treatment risk assessment for any patient planned to undergo therapy known to be cardiotoxic.

Who are the “usual suspects” in CTRCD?

The “five pillars” of cancer therapy can each cause a form of cardiotoxicity. These pillars are:

  • Conventional chemotherapeutics: designed to stop highly proliferative cells from proliferating by inhibiting DNA synthesis.
    • Anthracyclines, such as doxorubicin, etoposide. Mechanism: intercalates into DNA, disrupting topoisomerase-mediated DNA repair and replication. Primary form of cardiotoxicity: cardiomyopathy (can also cause arrhythmia).
    • Alkylating agents, such as cyclophosphamide. Mechanism: cross-links DNA. Primary form of cardiotoxicity: high doses can cause hemorrhagic pericarditis; we also see arrhythmia, cardiomyopathy, and arterial vascular disease.
    • Antimetabolites, such as 5-fluorouracil, gemcitabine. Mechanism: replaces base pairs, preventing synthesis. Primary form of cardiotoxicity: cardiomyopathy, arterial vascular disease.
  • Targeted therapies: monoclonal antibodies that inhibit cell signaling pathways that are pivotal in tumor cells.
    • HER2 inhibitors
    • Tyrosine kinase inhibitors
    • VEGF inhibitors, such as bevacizumab. Mechanism: inhibits angiogenesis via VEGF inhibition. Primary form of cardiotoxicity: hypertension, thrombosis, and occasionally cardiomyopathy.
  • Immune therapies: immunologic therapies that are “targeted” at receptors identified on specific tumor receptors
    • CAR-T cell therapy
    • Immune checkpoint inhibitors
  • Radiation therapy
  • Surgery

The first three of these — conventional chemotherapeutics, targeted therapies, and immune therapies — are the three classes we think about as causing CTRCD.

Pearls from the ESC 2022 guidelines

  • Cardiovascular risk in patients with cancer is a dynamic variable that requires a multidisciplinary team approach.
  • All patients with cancer who are scheduled to receive a potentially cardiotoxic anticancer therapy should receive a baseline cardiovascular risk assessment that includes transthoracic echocardiography with measurement of global longitudinal strain as well as baseline cardiac biomarkers.
  • In patients who are at high risk or very high risk of CTRCD as based on the risk stratification provided in the guidelines, efforts should be made to minimize the use of cardiotoxic agents (including the consideration of dexrazoxane and liposomal anthracyclines) and to initiate cardioprotective agents (like ACE-i/ARB, beta blockers, and statins).
  • In patients who develop asymptomatic, mild decreases in LVEF, especially in the setting of HER2 inhibitors, chemotherapy should be continued with the addition of cardioprotective therapy.
  • After the completion of chemotherapeutics, cardioprotective medications should be de-escalated in patients at low risk of future cardiovascular events.

Pearl from the ACC.23 meeting (March 4-6, 2023, New Orleans, LA) The STOP-CA trial is a multicenter, randomized, double-blind, placebo-controlled study presented at ACC.23. The study analyzed 286 patients with lymphoma undergoing treatment with anthracyclines. Baseline left ventricular ejection fraction (LVEF) was 63%. Patients were randomized into a group receiving atorvastatin 40 mg daily and a group receiving placebo. The primary endpoint of LVEF decline ≥10% at 12 months was seen in 9% of patients in the atorvastatin group and 22% of patients in the placebo group, with no difference in rates of adverse events. In conclusion, statins may have an important role in the prevention of anthracycline-associated cardiac dysfunction in lymphoma patients. For more on the STOP-CA trial, check out the ACC Fits-On-The-Go coverage by CardioNerds CardioOncology series co-chair Dr. Teodora Donisan, with lead authors Dr. Tomas Neilan and Dr. Marielle Scherrer-Crosbie. The STOP-CA trial was presented after the recording of this episode and is thus not addressed in the episode.

References – Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Cardiologist Perspective with Dr. Joerg Hermann

Herrmann J, McCullough KB, Habermann TM. How I treat cardiovascular complications in patients with lymphoid malignancies. Blood. 2022;139(10):1501-1516. doi:10.1182/blood.2019003893

Herrmann J, Lenihan D, Armenian S, et al. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J. 2022;43(4):280-299. doi:10.1093/eurheartj/ehab674

Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244

Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol. 2010;7(10):564-575. doi:10.1038/nrcardio.2010.121

 Yu AF, Flynn JR, Moskowitz CS, et al. Long-term Cardiopulmonary Consequences of Treatment-Induced Cardiotoxicity in Survivors of ERBB2-Positive Breast Cancer. JAMA Cardiol. 2020;5(3):309-317. doi:10.1001/jamacardio.2019.5586

Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17(8):474-502. doi:10.1038/s41569-020-0348-1

Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1 [published correction appears in J Am Coll Cardiol. 2018 Feb 6;71(5):587]. J Am Coll Cardiol. 2017;70(20):2536-2551. doi:10.1016/j.jacc.2017.09.1096

Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2. J Am Coll Cardiol. 2017;70(20):2552-2565. doi:10.1016/j.jacc.2017.09.1095

Meet Our Collaborators

International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

273. Digital Health: The Digital Transformation of Cardiovascular Medicine with Dr. Dipti Itchhaporia14 Mar 202300:29:34

Join CardioNerds Co-Founder Dr. Dan Ambinder, Dr. Nino Isakadze (EP Fellow at Johns Hopkins Hospital), Dr. Karan Desai (Cardiology Faculty at Johns Hopkins Hospital and Johns Hopkins Bayview) and student Dr. Shivani Reddy (Medical Student at Western Michigan University Homer Stryker SOM), as they discuss how digital health in changing the landscape of CV Disease Management with Dr. Dipti Itchhaporia (Past President of the ACC). The overall goal of this episode is to broadly describe the current landscape of digital health for cardiovascular disease, define “digital health tools” and describe their role in cardiovascular disease management. Episode audio was edited by student Dr. Shivani Reddy and show notes were developed by Dr. Nino Isakadze.

In this series, supported by an ACC Chapter Grant and in collaboration with Corrie Health, we hope to provide all CardioNerds out there a primer on the role of digital heath in cardiovascular medicine. Use of versatile hardware and software devices is skyrocketing in everyday life. This provides unique platforms to support healthcare management outside the walls of the hospital for patients with or at risk for cardiovascular disease. In addition, evolution of artificial intelligence, machine learning, and telemedicine is augmenting clinical decision making at a new level fueling a revolution in cardiovascular disease care delivery. Digital health has the potential to bridge the gap in healthcare access, lower costs of healthcare and promote equitable delivery of evidence-based care to patients.

This CardioNerds Digital Health series is made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Nino Isakadze and Dr. Karan Desai.  

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls and Quotes
  1. COVID 19 pandemic accelerated the digital transformation of healthcare.
  2. Digital health tools exist for disease prediction, diagnosis and management.
  3. Digital health can increase access to care and lower overall cost expenditure.
  4. Clinicians, policy makers, and insurance providers should be involved to facilitate rapid and effective adoption of digital health interventions to better patient and population health.
Notes

1. How did the COVID-19 pandemic accelerate the process of adopting digital health tools in healthcare including cardiovascular disease management?

  • Although technological advances and technological transformation have been implemented in many aspects of our lives, their adoption in healthcare, including cardiovascular disease management has lagged behind.
  • The COVID-19 pandemic was a force that led to the Tech-celeration as we adopted telemedicine and remote patient monitoring platforms in a short time to preserve access to healthcare.
  • Technology became essential not to replace but to support face to face interactions.
  • Reimbursement models were rapidly created that fit digital healthcare delivery; however it remains unclear whether these models will continue to be in effect in the post pandemic era.

2.  Can you discuss broadly the current landscape of evidence-based digital health tools available for cardiovascular disease management?

  • Three components of digital health landscape can be broken down as follows:
    • Virtual care/telehealth platforms
    • Remote patient monitoring systems including implanted devices, patches, wearables, smartphone applications and more
    • Artificial intelligence to allow meaningful use of the big data obtained from remote patient monitoring systems in therapeutic and disease management pathways

   3. How can we balance benefits and burden of digital health tools? 

  • The pure definition of digital transformation is using digital tools to make lives of patients and clinicians better.
  • The data we derive from digital health technologies is only useful insofar that it can be used to affect change. We need analytical tools like AI to create actionable information and summary sheets to summarize data in meaningful ways.
  • While developing digital health tools, companies should engage in co-designing processes with end users. In the case, clinicians should receive iterative feedback so that tools that are developed meet user needs.

   4. What are the ways to ensure inclusiveness in design and delivery of digital health tools for disease management to every patient, including those from underrepresented racial and ethnic groups?

  • We need to improve access to infrastructure needed to operate digital health tools. This requires engagement with institutions, organizations and legislators.
  • Digital health tools need to be co-designed with a diverse set of users including those with low tech literacy as well as multiple stakeholders.
  • We need to communicate with community members when translating science to make sure that the process is transparent to address any trust issues or skepticism.

5. How do we ensure data privacy, especially when health data is stored on different servers? 

  • There are gaps in federal legislation that need to be addressed.
  • IT health standards for handling data collected outside hospital settings with digital health tools should be developed in an iterative manner. When health IT standards are developed, we need to enforce them and ensure that they are working well with feedback systems.
  • Individuals need to control how their data is health systems and other entities use and store their data.
  • Clinicians need to trust that data is stored in a secure manner when appropriate channels are utilized.
  • Data management should be a transparent process.
  • Confidentiality is going to be fundamental and all entities involved should be subject to HIPPA rules.

6. How can big organizations help advocate for updated reimbursement models and policy changes to allow for greater adoption of digital health tools?

  • Big professional organizations have pivotal roles in promoting the digital transformation, and implementing digital re-design.
  • Big professional organizations can act as conduits between different stakeholders, promote digital literacy in public as well as among professionals.
  • They can create standards and guidelines on proper use of digital health technology, facilitate robust studies to test clinical impact, and advocate for reimbursement and policy changes.

 7. What are the near future and long-term opportunities of digital health tools in cardiovascular disease management?

  • Digital transformation is in progress, and we need clinicians to be at the center of innovation to drive development of care pathways and care delivery models.
  • Digital solutions should promote health equity, add value to healthcare systems, and promote wellbeing of clinicians
References
  1. Bayoumy K, Gaber M, Elshafeey A, et al. Smart wearable devices in cardiovascular care: where we are and how to move forward. Nat Rev Cardiol. 2021 Aug;18(8):581-599. doi: 10.1038/s41569-021-00522-7. Epub 2021 Mar 4. PMID: 33664502.
  2. Cowie MR, Lam CSP. Remote monitoring and digital health tools in CVD management. Nat Rev Cardiol. 2021 Jul;18(7):457-458. doi: 10.1038/s41569-021-00548-x. PMID: 33824486; PMCID: PMC8023506.
  3. Itchhaporia D. Navigating the Path to Digital Transformation. J Am Coll Cardiol. 2021 Jul 27;78(4):412-414. doi: 10.1016/j.jacc.2021.06.018. PMID: 34294274.
272. CardioNerds Rounds: Challenging Cases – Hemodynamics and Mechanical Circulatory Support with Dr. Daniel Burkhoff12 Mar 202300:32:05

It’s another session of CardioNerds Rounds! In these rounds, Dr. Karan Desai (Formerly FIT at University of Maryland Medical Center and currently faculty at Johns Hopkins School of Medicine) joins Dr. Dan Burkhoff (Director of Heart Failure, Hemodynamics and MCS Research at the Cardiovascular Research Foundation) to discuss mechanical circulatory support options through the lens of pressure-volume loops! Dr. Burkhoff is the author of Harvi, an interactive simulation-based application for teaching and researching many aspects of ventricular hemodynamics. Don’t miss this wonderfully nerdy episode with a world-renowned expert in hemodynamics and MCS! Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes

Challenging Cases – Atrial Fibrillation with Dr. Hugh Calkins

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Show notes – Hemodynamics and Mechanical Circulatory Support

Case Synopsis:

Case Synopsis
We focused on one case during these rounds. A man in his mid-50s presented to his local community hospital with 3 days of chest pain, nausea, and vomiting. He appeared ill in the emergency room with HR in the 150s, BP 90/70s and ECG demonstrating inferior ST elevations. He was taken emergently to the catheterization lab and received overlapping stents to his right coronary artery. Over the next 24 hours, he developed a new harsh systolic murmur heard throughout his precordium and progressed to cardiogenic shock. Echocardiogram demonstrated a large basal inferoseptum ventricular septal rupture. From this point, we discussed the hemodynamics of VSR and MCS options.

Case Takeaways

  1. Dr. Burkhoff took us through the hemodynamics of VSR with pressure-volume loops to better understand the pathology and impact of various MCS options. Of note, there are no MCS devices specifically approved to treat acute ventricular septal rupture.
  2. In regards to the acute hemodynamic effects of a VSR (an abrupt left to right shunt), there are several aspects to note. First, the effective LV afterload is reduced; however, there is less “forward flow” as well and as a consequence, decreased left-sided cardiac output (“Qs”) and blood pressure. At the same time, flow through the pulmonary artery increases (the “Qp”). Additionally, due to the abrupt shunt flow, there is increased RV “loading” with increasing central venous pressure and pulmonary artery pressure.
  3. The hemodynamic priorities in treating patients with cardiogenic shock and VSR are to normalize blood pressure, cardiac output, and oxygen delivery, while attempting to minimize shunt flow to allow healing. However, medications and MCS are unlikely to completely normalize hemodynamics. For instance, if the patient was placed on peripheral VA ECMO, while total CO and BP may increase, flow across the VSR could also increase at high ECMO flows (e.g., by introducing more LV afterload).
  4. In patients with persistent cardiogenic shock and VSR, short-term MCS to divert flow away from the shunt can be an effective strategy. LV-to-aorta or LA-to-arterial MCS may provide the best single-device hemodynamic profiles by decreasing shunt flow, reducing pulmonary capillary wedge pressure, and improving blood pressure.
  5. Surgical and percutaneous VSD repair are the definitive treatment options. If able to stabilize patients and pursue delayed repair, it may lead to better outcomes by allowing for better tissue substrate for a more effective repair.

Enjoy this ACC.org Expert Analysis by Goyal and Menon to learn more about post-myocardial infarction ventricular septal rupture.

References
  1. Pahuja M, Schrage B, Westermann D et al. Hemodynamic Effects of Mechanical Circulatory Support Devices in Ventricular Septal Defect. Circ Heart Fail. 2019 Jul;12(7):e005981. doi: 10.1161/CIRCHEARTFAILURE.119.005981.
  2. TEACH Videos via Harvi.Org: https://harvi.org/book/data/00%20-%20TeachVideos/TeachVideos.html
Production Team https://www.cardionerds.com/wp-content/uploads/2020/08/FullSizeRender.jpegKaran Desai, MD https://www.cardionerds.com/wp-content/uploads/2021/03/Natalie-Stokes-MD.jpgNatalie Stokes, MD https://www.cardionerds.com/wp-content/uploads/2020/07/Amit-Goyal-MD.pngAmit Goyal, MD https://www.cardionerds.com/wp-content/uploads/2020/07/Dan-copy.jpegDaniel Ambinder, MD
271. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #12 with Dr. Shashank Sinha08 Mar 202300:16:58

The following question refers to Section 9.5 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Western Michigan University medical student & CardioNerds Intern Shivani Reddy, answered first by Brigham & Women’s medicine resident and Director of CardioNerds Internship Dr. Gurleen Kaur, and then by expert faculty Dr. Shashank Sinha.

Dr. Sinha is an Assistant Professor of Medical Education at the University of Virginia School of Medicine and an advanced heart failure, MCS, and transplant cardiologist at Inova Fairfax Medical Campus. He currently serves as both the Director of the Cardiac Intensive Care Unit and Cardiovascular Critical Care Research Program at Inova Fairfax. He is also a Steering Committee member for the multicenter Cardiogenic Shock Working Group and Critical Care Cardiology Trials Network and an Associate Editor for the Journal of Cardiac Failure, the official Journal of the Heart Failure Society of America.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #12

Mr. Shock is a 65-year-old man with a history of hypertension and non-ischemic cardiomyopathy (LVEF 25%) who is admitted with acute decompensated heart failure. He is currently being diuresed with a bumetanide drip, but is only making 20 cc/hour of urine. On exam, blood pressure is 85/68 mmHg and heart rate is 110 bpm. His JVP is at 12 cm and extremities are cool with thready pulses. Bloodwork is notable for a lactate of 3.5 mmol/L and creatinine of 2.5 mg/dL (baseline Cr 1.2 mg/dL). What is the most appropriate next step?

A

Augment diuresis with metolazone

B

Start sodium nitroprusside

C

Start dobutamine

D

Start oral metoprolol

E

None of the above

Answer #12

Explanation

The correct answer is C – start dobutamine.

 

In this scenario, the patient is in cardiogenic shock given hypotension and evidence of end-organ hypoperfusion on exam and labs. The patient’s cool extremities, low urine output, elevated lactate, and elevated creatinine all point towards hypoperfusion.

 

In patients with cardiogenic shock, intravenous inotropic support should be used to maintain systemic perfusion and preserve end-organ function (Class 1, LOE B-NR). Further, in patients with cardiogenic shock whose end-organ function cannot be maintained by pharmacologic means, temporary MCS is reasonable to support cardiac function (Class 2a, LOE B-NR).

 

The SCAI Cardiogenic Shock Criteria can be used to divide patients into stages. Stage A is a patient at risk for cardiogenic shock but currently not with any signs or symptoms, for example, a patient presenting with a myocardial infarction without present evidence of shock. Stage B is “pre-shock” – this may be a patient who has volume overload, tachycardia, and hypotension but does not have hypoperfusion based on exam and lab evaluation. Stage C is classic cardiogenic shock – the cold and wet profile. Bedside findings for Stage C shock include cool extremities, weak pulses, altered mental status, decreased urine output, and/or respiratory distress. Lab findings include impaired renal function, increased lactate, increased hepatic enzymes, and/or acidosis. Stage D is deteriorating with worsening hypotension and hypoperfusion with escalating use of pressors or mechanical circulatory support. Finally, stage E is extremis with refractory hypotension and hypoperfusion, with circulatory collapse. Our patient in the question stem is in SCAI stage C, or classic cardiogenic shock.

 

Choice A is incorrect. Augmenting diuresis with metolazone can be useful in a patient with diuretic resistance and decompensated heart failure. However, this patient is hypotensive and fits the wet and cool profile and will benefit from inotropic support to increase end organ perfusion.

 

Choice B is incorrect. Sodium nitroprusside can be used to increase cardiac output in cardiogenic shock and is particularly useful in patients with high systemic vascular resistance. Indeed, intravenous nitroglycerin and nitroprusside have a Class 2a indication (LOE B-NR) in patients who are admitted with decompensated HF without systemic hypotension as an adjuvant to diuretic therapy for relief of dyspnea. However, our patient is hypotensive and so vasodilators would not be appropriate at this time.

 

Choice C is incorrect. Metoprolol, a negative inotropic agent, should not be used in this patient with cardiogenic shock.

 

Relevant to this question is the use of invasive hemodynamic monitoring to guide therapy. The use a PA line has a Class 2b indication (LOE B-NR) in patients presenting with cardiogenic shock to define hemodynamic subsets and appropriate management strategies. Obtaining hemodynamic data via a PA line can also be particularly useful when escalating to mechanical circulatory support, when there is diagnostic uncertainty, or when a patient in shock is not responding to empiric initial shock measures. While the use of PA catheters has been controversial since the ESCAPE trial which showed no benefit in decompensated HF, the trial did not actually enroll patients with cardiogenic shock. Several observational studies have shown association between PA catheter use and improved outcomes in cardiogenic shock, particularly in conjunction with short-term MCS. PA catheters are a diagnostic tool and are best utilized when hemodynamic information can be translated into appropriate interventions, such as determining response to medical and MCS therapy, weaning off of MCS support, or uncovering right ventricular failure to guide appropriate therapy.

 

In the case of cardiogenic shock, studies have shown benefit with multidisciplinary teams of HF and critical care specialists, interventional cardiologists, and cardiac surgeons. Such teams should also be capable of providing appropriate palliative care. There is a Class 2a (LOE B-NR) recommendation for management of patients with cardiogenic shock by an experienced multidisciplinary team.

Main Takeaway

In summary, it is important to recognize cardiogenic shock early based on clinical criteria of hypotension and hypoperfusion and begin prompt initiation of IV inotropic agents such as dobutamine and/or MCS to optimize end-organ perfusion. When there is insufficient clinical improvement with initial measures, invasive hemodynamic assessment is recommended.

Guideline Loc.

Section 9.5

Tables 22-24


Decipher the Guidelines: 2022 Heart Failure Guidelines Page
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270. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #11 with Dr. Prateeti Khazanie07 Mar 202300:18:19

The following question refers to Section 8.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Western Michigan University medical student & CardioNerds Intern Shivani Reddy, answered first by Brigham & Women’s medicine resident and Director of CardioNerds Internship Dr. Gurleen Kaur, and then by expert faculty Dr. Prateeti Khazanie.

Dr. Khazanie is an Associate Professor and Advanced Heart Failure and Transplant Cardiologist at the University of Colorado. She was an undergraduate at Duke University as a B.N. Duke Scholar. She spent two years at the NIH in the lab of Dr. Anthony Fauci and completed a dual MD-MPH program at Duke Medical School. When she started residency, she thought she was going to be an ID doctor, but she fell in love with cardiology at Stanford where she was an intern, resident, and then chief resident. She went back to Duke for her general cardiology and advanced heart failure/transplant fellowships as well as research training at the DCRI. Dr. Khazanie joined the University of Colorado in 2015 as a health services clinician researcher with a focus on improving health equity and bioethics in advanced heart failure care. She mentors medical students, residents, and fellows and is a faculty mentor for the University of Colorado Cardiology Fellows “House of Cards” mentoring group. She has research funding from the NIH/NHLBI K23, NIH Ethics Grant, and Ludeman Center for Women’s Health Research. Dr. Khazanie is an author on the 2022 ACC/AHA/HFSA HF Guidelines, the 2021 HFSA Universal Definition of Heart Failure, and multiple scientific statements.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #11

A 64-year-old woman with a history of chronic systolic heart failure secondary to NICM (LVEF 15-20%) s/p dual chamber ICD presents for routine follow-up. She reports several months of progressive fatigue, dyspnea, and peripheral edema. She has been hospitalized twice in the past year with acute decompensated heart failure. Efforts to optimize guideline directed medical therapy have been tempered by episodes of lightheadedness and hypotension. Her exam is notable for an elevated JVP, an S3 heart sound, and a III/VI holosystolic murmur best heard at the apex with radiation to the axilla. Labs show Na 130 mmol/L, Cr 1.8 mg/dL (from 1.1 mg/dL 6 months prior), and NT-proBNP 1,200 pg/mL. ECG in clinic shows sinus rhythm and a nonspecific IVCD with QRS 116 ms. Her most recent TTE shows biventricular dilation with LVEF 15-20%, moderate functional MR, moderate functional TR and estimated RVSP of 40mmHg. What is the most appropriate next step in management? A Refer to electrophysiology for upgrade to CRT-D B Increase sacubitril-valsartan dose C Refer for advanced therapies evaluation D Start treatment with milrinone infusion

Answer #11

Explanation The correct answer is C – refer for advanced therapies evaluation.

Our patient has multiple signs and symptoms of advanced heart failure including NYHA Class III-IV functional status, persistently elevated natriuretic peptides, severely reduced LVEF, evidence of end organ dysfunction, multiple hospitalizations for ADHF, edema despite escalating doses of diuretics, and progressive intolerance to GDMT. Importantly, the 2018 European Society of Cardiology revised definition of advanced HF focuses on refractory symptoms rather than cardiac function and more clearly acknowledges that advanced HF can occur in patients without severely reduced LVEF, such as in those with isolated RV dysfunction, uncorrectable valvular or congenital heart disease, and in patients with preserved and mildly reduced LVEF.

In such patients with advanced heart failure, when consistent with the patient’s goals of care, timely referral for HF specialty care is recommended to review HF management and assess suitability for advanced HF therapies (eg, LVAD, cardiac transplantation, palliative care, and palliative inotropes) (Class I, LOE C-LD).

Clinical indicators of advanced heart failure should prompt a possible referral to an advanced HF specialist and can be remembered by the INEEDHELP acronym:

·       I – IV inotropes

·       N – NYHA IIIb-VI or persistently elevated natriuretic peptides

·       E – End-organ dysfunction

·       E – EF ≤ 35%

·       D – Defibrillator shocks

·       H – Hospitalizations > 1 in past year

·       E – Edema despite escalating diuretics

·       L – Low systolic blood pressure (≤90) or high heart rate

·       P – Prognostic medication; progressive intolerance or down-titration of GDMT

It would not be appropriate to refer to EP for CRT-D upgrade as this is a Class 3 recommendation (LOE B-R) in patients with QRS duration <120 ms for no benefit.

Increasing the dose of sacubitril-valsartan would not be appropriate in this setting as the patient would be likely unable to tolerate a higher dose given her complaints of lightheadedness and episodes of hypotension.

Initiating treatment with IV inotropes would not be appropriate in this setting. Although the use of IV inotropes is given a Class 1 recommendation (LOE B-NR) for the treatment of cardiogenic shock, the patient described in the question stem does not meet clinical criteria for cardiogenic shock.

Main Takeaway Clinical indicators for advanced heart failure can be remembered by the I-Need-Help acronym, and there is a Class 1, LOE C recommendation for these patients to be referred to HF specialists for further management and assessment for advanced therapies, when consistent with the patient’s goals of care. Guideline Loc. Section 8.1

Tables 16-18




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269. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #10 with Dr. Michelle Kittleson28 Feb 202300:11:35

The following question refers to Section 7.7 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by St. George’s University medical student and CardioNerds Intern Chelsea Tweneboah, answered first by Baylor College of Medicine Cardiology Fellow and CardioNerds Ambassador Dr. Jamal Mahar, and then by expert faculty Dr. Michelle Kittleson.

Dr. Kittleson is Director of Education in Heart Failure and Transplantation, Director of Heart Failure Research, and Professor of Medicine at the Smidt Heart Institute, Cedars-Sinai. She is Deputy Editor of the Journal of Heart and Lung Transplantation, on Guideline Writing Committees for the American College of Cardiology (ACC)/American Heart Association, is the Co Editor-in-Chief for the ACC Heart Failure Self-Assessment Program, and on the Board of Directors for the Heart Failure Society of America. Her Clinician’s Guide to the 2022 Heart Failure guidelines, published in the Journal of Cardiac Failure, are a must-read for everyone!

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #10

Ms. Heffpefner is a 54-year-old woman who comes to your office for a routine visit. She does report increased fatigue and dyspnea on exertion without new orthopnea or extremity edema. She was previously diagnosed with type 2 diabetes, morbid obesity, obstructive sleep apnea, and TIA. She is currently prescribed metformin 1000mg twice daily, aspirin 81mg daily, rosuvastatin 40mg nightly, and furosemide 40mg daily. In clinic, her BP is 140/85 mmHg, HR is 110/min (rhythm irregularly irregular, found to be atrial fibrillation on ECG), and BMI is 43 kg/m2. Transthoracic echo shows an LVEF of 60%, moderate LV hypertrophy, moderate LA enlargement, and grade 2 diastolic dysfunction with no significant valvulopathy. What is the best next step?

A

Provide reassurance

B

Refer for gastric bypass

C

Refer for atrial fibrillation ablation

D

Start metoprolol and apixaban

Answer #10

Explanation

The correct answer is D – start metoprolol and apixaban.

Ms. Hefpeffner has a new diagnosis of atrial fibrillation (AF) and has a significantly elevated risk for embolic stroke based on her CHA2DS2-VASc score of 6 (hypertension, diabetes, heart failure, prior TIA, and female sex). The relationship between AF and HF is complex and the presence of either worsens the status of the other. Managing AF in patients with HFpEF can lead to symptom improvement (Class 2a, LOR C-EO). However, large, randomized trial data are unavailable to specifically guide therapy in patients with AF and HFpEF.

 

Generally, management of AF involves stroke prevention, rate and/or rhythm control, and lifestyle / risk-factor modification. With regards to stroke prevention, patients with chronic HF with permanent-persistent-paroxysmal AF and a CHA2DS2-VASc score of ≥2 (for men) and ≥3 (for women) should receive chronic anticoagulant therapy (Class 1, LOE A). When anticoagulation is used in chronic HF patients with AF, a DOAC is recommended over warfarin in eligible patients (Class 1, LOE A).

The decision for rate versus rhythm control should be individualized and reflects both patient symptoms and the likelihood of better ventricular function with sinus rhythm. For patients with HF and symptoms caused by AF, AF ablation is reasonable to improve symptoms and QOL (Class 2a, LOE B-R). However, referring for catheter ablation would be premature before first attempting rate control and instituting anticoagulation therapy.

 

Traditionally, beta-blockers and nondihydropyridine calcium channel blockers are used as first-line agents for rate control in AF. Interestingly, a small open-label trial, RATE-AF in elderly patients with AF and symptoms of HF (mostly with preserved LVEF), compared bisoprolol to digoxin. Although the primary endpoint of quality of life at 6 months was similar between the 2 groups, several secondary QOL endpoints, functional capacity, and reduction in NT-proBNP favored digoxin at 12 months, with similar rate reductions in both groups. More side effects (such as dizziness, lethargy, and hypotension) were seen with bisoprolol than with digoxin. However, digoxin has a narrow therapeutic window and needs to be monitored more closely.

Option A (provide reassurance) is inappropriate as this patient has heart failure with preserved EF, defined by signs and symptoms of HF in patients with an LVEF of 50% or more. Echocardiogram hints in this case include LV hypertrophy and diastolic dysfunction. Our patient also has comorbidities frequently associated with HFpEF such as hypertension, diabetes, OSA, and obesity. Other common comorbidities include CAD, CKD, and atrial arrhythmias. When diagnosing HFpEF, care must be taken to rule out mimicking conditions such as pulmonary hypertension or amyloidosis. A large portion of the management of HFpEF includes managing comorbid conditions such as hypertension, OSA, and atrial fibrillation. At this time, she is symptomatic with atrial fibrillation and rapid ventricular response, and warrants both rate control and stroke prophylaxis.

 

Although gastric bypass should be considered for patients with a BMI >35 kg/m2 with comorbidities (such as HTN or diabetes) and patients with a BMI > 40 kg/m2 independent of comorbid conditions, this is not the best next step at this time. First, she should receive anticoagulation to reduce the risk of stroke and achieve better control of her HR and BP.

 

Patients with HFpEF and hypertension should have medication titrated to attain blood pressure targets in accordance with published clinical practice guidelines to prevent morbidity (Class 1, LOE C-LD). Although the optimal BP goal and antihypertensive regimen in patient with HFpEF is not known, HFpEF trials so far have shown that RAAS antagonists including ACEi, ARB, MRA and possibly ARNi could be first-line agents to treat HTN in patients with HFpEF. Beta blockers may be used to treat hypertension in patients with a history of

MI, symptomatic CAD, or AF with rapid ventricular response. These effects need to be balanced with the potential contribution of chronotropic incompetence to exercise intolerance in some patients.

Main Takeaway

In patients with HFpEF, the diagnosis and management of comorbidities are very important, especially the treatment of HTN (Class 1, LOE C-LD) and AF (Class 2a, LOE C-EO).

Guideline Loc.

Section 7.7.1, Figure 12

Section 10.2


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376. Case Report: Tamponade or Cardiovascular Support? A case of Pericardial Decompression Syndrome – University of Michigan21 Jun 202400:17:25

CardioNerds cofounders, Dan Ambinder joins Drs. Aishwarya Pastapur, Oyinkansola Osobamiro, and Rafik Issa from the University of Michigan for drinks in Ann Arbor. They discuss the following case of pericardial decompression syndrome. Expert commentary is provided by Dr. Brett Wanamaker. Notes were drafted by Dr. Aishwarya Pastapur and Dr. Rafik Issa. The episode audio was engineered by CardioNerds Intern student Dr. Atefeh Ghorbanzadeh.

A woman in her 50s with a past medical history of stage IV lung cancer (with metastatic involvement of the liver, bone, and brain), previous saddle pulmonary emboli, pericardial effusion, and malignant pleural effusions presents with dyspnea. She was found to have a pericardial effusion with tamponade physiology relieved by pericardiocentesis. We discuss the management of cardiac tamponade, indications for pericardiocentesis, how to monitor for post-pericardiocentesis complications, and what to keep on your differential diagnosis for decompensation after pericardiocentesis. We discuss the epidemiology, pathophysiology, diagnosis, and management of pericardial decompression syndrome.

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Case Media – Pericardial Decompression Syndrome Pearls – Pericardial Decompression Syndrome
  • Diminished heart sounds, a low-voltage EKG with electrical alternans, elevated jugular venous pressure/pulsations (JVP), and the presence of pulses paradoxes are important findings that could suggest tamponade.
  • McConnell sign is strongly concerning for right ventricular failure and pulmonary hypertension, potentially due to acute pulmonary embolism.
  • Mechanical thrombectomy for pulmonary embolism is not feasible if the emboli are diffusely scattered without a central lesion to target.
  • For patients who experience decompensation following pericardiocentesis, consider perforation, tamponade re-accumulation, or pericardial decompression syndrome (PDS).
  • When possible, avoid draining more than 1L of pericardial fluid at once to minimize the risk of PDS.
Notes – Pericardial Decompression Syndrome

What is Pericardial Decompression Syndrome (PDS), and how does it present?

  • Pericardial decompression syndrome is a rare, life-threatening syndrome occurring in about 5-10% of cases with paradoxical worsening of hemodynamics after pericardial drainage.
    • The clinical presentation ranges from pulmonary edema to cardiogenic shock to death, occurring a few hours to days after a successful pericardiocentesis.

What is the underlying mechanism for PDS?

The pathophysiology behind PDS is debated, but there are three proposed mechanisms:

  1. Paradoxical Hemodynamic Derangement: After pericardiocentesis, venous return to the RV rapidly increases, resulting in RV expansion and potentially septal deviation towards the LV. Subsequently, the LV experiences decreased preload while still facing increased afterload as a compensatory response to obstructive shock, leading to decompensation.
    1. Myocardial Ischemia: Increased intrapericardial pressure may impair coronary perfusion, leading to myocardial ischemia. Upon pericardiocentesis, there is myocardial stunning with increased demand due to increased venous return and cardiac output
    1. Sympathetic Withdrawal: Withdrawal of sympathetic activation after drainage of pericardial fluid can trigger cardiovascular collapse

What are the risk factors for developing PDS, and how can we mitigate those risks for prevention?

  • Generally, patients with long-standing pericardial effusion with chronic compression of the heart, such as those with malignant pericardial effusions, are more vulnerable to developing PDS after pericardiocentesis.
    • Additionally, rapid fluid removal increases the risk. In terms of prevention, removing fluid to normalize CVP and MAP and letting the rest of the fluid drain slowly may mitigate the risk.

How do we manage a patient with PDS?

  • The management of PDS is supportive, focusing on addressing hemodynamic and respiratory derangements.
    • The underlying pathophysiology should resolve in 24-48 hours.

What is the prevalence and prognosis of PDS?

  • PDS affects 5-10% of pericardiocentesis procedures, although the exact frequency is difficult to ascertain.
    • It is a self-resolving process as the heart re-adapts to the new hemodynamics.
    • However, during the episode of PDS, mortality can be as high as 30% per some studies.
References – Pericardial Decompression Syndrome
  1. Schnur M. Understanding Pulsus Paradoxus. Accessed February 27, 2024. https://nursingcenter.com/ncblog/august-2021/understanding-pulsus-paradoxus
  2. Carlini’ ’Caterina Chiara De, Maggiolini’ ’Stefano. Pericardiocentesis in cardiac tamponade: indications and practical aspects. Accessed February 27, 2024. https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-15/Pericardiocentesis-in-cardiac-tamponade-indications-and-practical-aspects
  3. Angouras DC, Dosios T. Pericardial Decompression Syndrome: A Term for a Well-Defined but Rather Underreported Complication of Pericardial Drainage. The Annals of Thoracic Surgery. 2010;89(5):1702-1703. doi:10.1016/j.athoracsur.2009.11.073
  4. Imazio M. Pericardial decompression syndrome: A rare but potentially fatal complication of pericardial drainage to be recognized and prevented. European Heart Journal Acute Cardiovascular Care. 2015;4(2):121-123. doi:10.1177/2048872614557771
  5. Prabhakar Y, Goyal A, Khalid N, et al. Pericardial decompression syndrome: A comprehensive review. World Journal of Cardiology. 2019;11(12):282-291. doi:10.4330/wjc.v11.i12.282
  6. Sobieski C, Herner M, Goyal N, et al. Pericardial Decompression Syndrome After Drainage of Chronic Pericardial Effusions. JACC: Case Reports. 2022;4(22):1515-1521. doi:10.1016/j.jaccas.2022.08.023
  7. Chhabra L. Pericardial Decompression Syndrome. American College of Cardiology. Accessed February 27, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2020/04/13/09/05/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2020%2f04%2f13%2f09%2f05%2fPericardial-Decompression-Syndrome
  8. Pradhan R, Okabe T, Yoshida K, Angouras DC, DeCaro MV, Marhefka GD. Patient characteristics and predictors of mortality associated with pericardial decompression syndrome: a comprehensive analysis of published cases. European Heart Journal Acute Cardiovascular Care. 2015;4(2):113-120. doi:10.1177/2048872614547975
  9. Amro A, Mansoor K, Amro M, et al. A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome. Current Cardiology Reviews. 17(1):101-110.
268. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #9 with Dr. Nancy Sweitzer22 Feb 202300:12:31

The following question refers to Section 7.6 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by premedical student and CardioNerds Intern Pacey Wetstein, answered first by Baylor College of Medicine Cardiology Fellow and CardioNerds Ambassador Dr. Jamal Mahar, and then by expert faculty Dr. Nancy Sweitzer.

Dr. Sweitzer is Professor of Medicine, Vice Chair of Clinical Research for the Department of Medicine, and Director of Clinical Research for the Division of Cardiology at Washington University School of Medicine. She is the editor-in-chief of Circulation: Heart Failure. Dr. Sweitzer is a faculty mentor for this Decipher the HF Guidelines series.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #9

Mr. Flo Zin is a 64-year-old man who comes to discuss persistent lower extremity edema and dyspnea with mild exertion. He takes amlodipine for hypertension but has no other known comorbidities. In the clinic, his heart rate is 52 bpm and blood pressure is 120/70 mmHg. Physical exam reveals mildly elevated jugular venous pulsations and 1+ bilateral lower extremity edema. Labs show an unremarkable CBC, normal renal function and electrolytes, a Hb A1c of 6.1%, and an NT-proBNP of 750 (no prior baseline available). On echocardiogram, his LVEF is 44% and nuclear stress testing was negative for inducible ischemia. What is the best next step in management? A Add furosemide BID and daily metolazone B Start empagliflozin and furosemide as needed C Start metoprolol succinate D No change to medical therapy

Answer #9

Explanation The correct answer is B – start empagliflozin and furosemide as needed.

The patient described here has heart failure with mildly reduced EF (HFmrEF), given LVEF in the range of 41-49%.

In patients with HF who have fluid retention, diuretics are recommended to relieve congestion, improve symptoms, and prevent worsening HF (Class 1, LOE B-NR). For patients with HF and congestive symptoms, addition of a thiazide (eg, metolazone) to treatment with a loop diuretic should be reserved for patients who do not respond to moderate or high-dose loop diuretics to minimize electrolyte abnormalities (Class 1, LOE B-NR). Therefore, option A is not correct as he is only mildly congested on examination, and likely would not require such aggressive decongestive therapy, particularly with normal renal function. Adding a thiazide diuretic without first optimizing loop diuretic dosing would be premature.

The EMPEROR-Preserved trial showed a significant benefit of the SGLT2i, empagliflozin, in patients with symptomatic HF, with LVEF >40% and elevated natriuretic peptides. The 21% reduction in the primary composite endpoint of time to HF hospitalization or cardiovascular death was driven mostly by a significant 29% reduction in time to HF hospitalization, with no benefit on all-cause mortality. Empagliflozin also resulted in a significant reduction in total HF hospitalizations, decrease in the slope of the eGFR decline, and a modest improvement in QOL at 52 weeks. Of note, the benefit was similar irrespective of the presence or absence of diabetes at baseline. In a subgroup of 1983 patients with LVEF 41% to 49% in EMPEROR-Preserved, empagliflozin, an SGLT2i, reduced the risk of the primary composite endpoint of cardiovascular death or hospitalization for HF. Therefore, in patients with HFmrEF, SGLT2i can be beneficial in decreasing HF hospitalizations and cardiovascular mortality (Class 2a, LOE B-R). Furthermore, by inhibiting glucose reabsorption in the kidney, they have a diuretic effect which may help ease congestion and limit loop diuretic dosing. SGLT2i are beneficial to the vast majority of cardiovascular patients but are contraindicated in patients with type 1 diabetes or prior episodes of diabetic ketoacidosis as they may cause euglycemic DKA.

Option C is incorrect. Among patients with current or previous symptomatic HFmrEF (LVEF, 41%–49%), use of evidence-based beta blockers for HFrEF, ARNi, ACEi, or ARB, and MRAs may be considered to reduce the risk of HF hospitalization and cardiovascular mortality, particularly among patients with LVEF on the lower end of this spectrum (Class 2b, LOE B-NR). However, the patient’s heart rate is already low and so initiating a beta blocker would be inappropriate. Switching his calcium channel blocker to ARNi may be considered.

Option D is not correct as we can help counsel him on lifestyle and medication changes which can relieve his symptoms and reduce his risk of HF hospitalizations and mortality.

Main Takeaway In patients with HFmrEF, diuretics are useful for decongestion and symptomatic improvement (Class 1) and there is a role for GDMT including SGLT2i (Class 2a) and BB, ARNI, ACEi/ARB, MRA (Class 2b). Guideline Loc. Section 7.6.1, Figure 11


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267. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #8 with Dr. Gregg Fonarow21 Feb 202300:10:43

The following question refers to Section 7.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Palisades Medical Center medicine resident & CardioNerds Intern Dr. Maryam Barkhordarian, answered first by MedStar Washington Hospital Center cardiology hospitalist & CardioNerds Academy Graduate Dr. Luis Calderon, and then by expert faculty Dr. Gregg Fonarow.

Dr. Fonarow is the Professor of Medicine and Interim Chief of UCLA’s Division of Cardiology, Director of the Ahmanson-UCLA Cardiomyopathy Center, and Co-director of UCLA’s Preventative Cardiology Program.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #8

Ms. Flo Zinn is a 60-year-old woman seen in cardiology clinic for follow up of her chronic HFrEF management. She has a history of stable coronary artery disease, hypertension, hypothyroidism, and recurrent urinary tract infections. She does not have a history of diabetes and recent hemoglobin A1c is 5.0%. Her current medications include carvedilol, sacubitril-valsartan, eplerenone, and atorvastatin. Her friend was recently placed on an SGLT2 inhibitor and asks if she should be considered for one as well. Which of the following is the most important consideration when deciding to start this patient on an SGLT2 inhibitor?

A

The patient does not have a history of type 2 diabetes and so does not qualify for SGLT2 inhibitor therapy

B

While SGLT2 inhibitors improve hospitalization rates for HFrEF, there is no evidence that they improve cardiovascular mortality

C

Patients taking SGLT2 inhibitors tend to suffer a more rapid decline in renal function than patients not taking SGLT2 inhibitor therapy

D

Patients may be at a higher risk for genitourinary infections if an SGLT2 inhibitor is started

Answer #8

Explanation

 

The correct answer is D – SGLT2 inhibitors have been associated with increased risk of genitourinary infections.

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have gathered a lot of press recently as the new kid on the block with respect to heart failure management. While they were initially developed as antihyperglycemic medications for treating diabetes, early cardiovascular outcomes trials showed reduced rates of heart failure hospitalization amongst study participants independent of glucose-lowering effects and irrespective of baseline heart failure status – only 10-14% of patients carried a heart failure diagnosis at baseline. This prompted trials to study the effects of SGLT2 inhibitors in patients with symptomatic chronic HFrEF who were already on guideline directed medical therapy irrespective of the presence of type 2 diabetes mellitus. The DAPA-HF and EMPEROR-Reduced trials showed that dapagliflozin and empagliflozin, respectively, both conferred statistically significant improvements in a composite of heart failure hospitalizations and cardiovascular death (Option B). Most interestingly, these effects were seen irrespective of diabetes history. In light of these findings, the 2022 HF guidelines recommend SGLT2 inhibitors in patients with chronic, symptomatic HFrEF with or without diabetes to reduce hospitalization for HF and cardiovascular mortality (Class I, LOE A).

The benefits of SGLT2 inhibitors extend beyond cardiovascular health. Analyses of the DAPA-HF and EMPEROR-Reduced trials showed that patients receiving SGLT2 inhibitor therapy had fewer serious renal outcomes and slower rates of decline in eGFR than patients in the control groups.

As with all medications, though, SGLT2 inhibitors must be used with an awareness of some potentially serious side effects. SGLT2 inhibitors have been associated with higher rates of genitourinary infections, potentially related to the increased glycosuria associated with sodium-glucose co-transporter 2 inhibition. Trials have shown a 2 to 4-fold increased risk of vulvovaginal candidiasis for patients on SGLT2is compared to placebo. SGLT2 inhibitor use has also been associated with bacterial urinary tract infections, Fournier’s gangrene, and euglycemic ketoacidosis.

Main Takeaway

SGLT2 inhibitors are now a class I recommendation for patients with chronic symptomatic HFrEF regardless of whether or not they have diabetes. Although SGLT2i increased risk for genital infections, they were otherwise well tolerated in the trials.

Guideline Loc.

Section 7.3.4


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266. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #7 with Dr. Robert Mentz15 Feb 202300:12:20

The following question refers to Section 7.3.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

The question is asked by Palisades Medical Center medicine resident & CardioNerds Intern Dr. Maryam Barkhordarian, answered first by MedStar Washington Hospital Center cardiology hospitalist & CardioNerds Academy Graduate Dr. Luis Calderon, and then by expert faculty Dr. Robert Mentz

Dr. Mentz is associate professor of medicine and section chief for Heart Failure at Duke University, a clinical researcher at the Duke Clinical Research Institute, and editor-in-chief of the Journal of Cardiac Failure. Dr. Mentz is a mentor for the CardioNerds Clinical Trials Network as lead principal investigator for PARAGLIDE-HF and is a series mentor for this very 2022 heart failure Decipher the Guidelines Series. For these reasons and many more, he was awarded the Master CardioNerd Award during ACC22. Welcome Dr. Mentz! 

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #7

Ms. Valarie Sartan is a 55-year-old woman with a history of HFrEF (EF 35%) and well controlled, non-insulin dependent diabetes mellitus who presents to heart failure clinic for routine follow up. She is currently being treated with metoprolol succinate 200mg daily, lisinopril 10mg daily, empagliflozin 10mg daily, and spironolactone 50mg daily. She notes stable dyspnea with moderate exertion, making it difficult to do her yardwork. On exam she is well appearing, and blood pressure is 115/70 mmHg with normal jugular venous pulsations and trace bilateral lower extremity edema. On labs, her potassium is 4.0 mmol/L and creatinine is 0.7 mg/dL with an eGFR > 60 mL/min/1.73m2. Which of the following options would be the most appropriate next step in heart failure therapy?  A  Increase lisinopril to 40mg daily  B  Increase spironolactone to 100mg daily  C  Add sacubitril-valsartan to her regimen  D  Discontinue lisinopril and start sacubitril-valsartan in 36 hours  E  No change 

Answer #7

Explanation   The correct answer is D – transitioning from an ACEi to an ARNi is the most appropriate next step in management.  

The renin-angiotensin aldosterone system (RAAS) is upregulated in patients with chronic heart failure with reduced ejection fraction (HFrEF). Blockade of the RAAS system with ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), or angiotensin receptor neprilysin inhibitors (ARNi) have proven mortality benefit in these patients.  

The PARADIGM-HF trial compared sacubitril-valsartan (an ARNi) with enalapril in symptomatic patients with HFrEF. Patients receiving ARNi incurred a 20% relative risk reduction in the composite primary endpoint of cardiovascular death or heart failure hospitalization. Based on these results, the 2022 heart failure guidelines recommend replacing an ACEi or ARB for an ARNi in patients with chronic symptomatic HFrEF with NYHA class II or III symptoms to further reduce morbidity and mortality (Option D). This is a class I recommendation with level of evidence of B-R and is also of high economic value. Making no changes at this time would be inappropriate (Option E). 

While it would be reasonable to increase the dose of lisinopril to 40mg (Option A), this should be pursued only if ARNi therapy is not tolerated.  

Mineralocorticoid receptor antagonists (MRAs) have a class I (LOE A) recommendation in patients with HFrEF and NYHA class II to IV to reduce morbidity and mortality, provided that eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L, and there is careful monitoring of potassium, renal function, and diuretic dosing. However, the starting dose of spironolactone (or eplerenone) is 25 mg orally daily, increased to 50 mg daily orally after a month. Higher doses may be appropriate for other indications but are not advocated for HFrEF as the sole indication and so option B is incorrect.  

Guidance on starting an ARNi 

While switching from an ACEi to an ARNi, note that ARNi should not be administered concomitantly with ACEi or within 36 hours of the last dose of an ACEi (Class 3 for Harm, LOE B-R). This recommendation comes largely from studies of omapatrilat—a combination ACEi/neprilysin inhibitor. Patients receiving omapatrilat suffered significantly increased risk of angioedema thought secondary to dual suppression of both ACE and neprilysin leading to high concentrations of bradykinin. The current guidelines therefore recommend a washout period of at least 36 hours between the last ACEi dose and the first ARNi dose. If this patient were being transitioned from an ARB such as valsartan, then the first dose of ARNi could simply be given in lieu of the next anticipated dose of ARB.  

When initiating sacubitril-valsartan, it is important to monitor for signs of hypotension. With this patient’s blood pressure of 115/70 mmHg in clinic, she should have enough blood pressure room to tolerate the new medication; both PARADIGM-HF (ARNi vs ACEi in stable chronic HFrEF) and PIONEER-HF (ARNi vs ACEi in hospitalized patients with ADHF) excluded patients with SBP < 100 mmHg. That said, every patient responds differently, and anticipatory guidance should be given to anybody starting a new drug. In particular, Ms. H.F. should be counseled on symptoms that could reflect low blood pressure, such as lightheadedness or orthostatic syncope, asked to call her provider should she experience anything concerning. Laboratory follow-up should include renal function and potassium levels. ARNis should not be initiated on any patient with a history of angioedema (Class III for Harm, LOE C-LD). While this patient likely does not have this history since she is tolerating and ACEi, it is an important part of any CardioNerd’s checklist when reaching for RAAS inhibitors.  

Main Takeaway  Patients with symptomatic HFrEF who are tolerating ACEi or ARB therapy should be transitioned to ARNi therapy to further reduce morbidity and mortality.  Expert Suggestions 
  • Offer tips & tricks for initiating and monitoring ARNis in the outpatient setting.  
  • Discuss PIONEER-HF & initiation in the inpatient setting.  
  • Discuss ACEi & ARB combination therapy. 
Guideline Loc.  Section 7.3.1  


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265. Case Report: An Unusual Case of Non-ischemic Cardiomyopathy – Cleveland Clinic15 Feb 202300:53:33

CardioNerds co-founder Daniel Ambinder joins Cleveland Clinic cardiology fellows, Dr. Essa Hariri, Dr. Anna Scandinaro, and Dr. Beka Bekhdatze, Clinical pharmacist at Cleveland Clinic, Dr. Ashley Kasper, and Dr. Craig Parris from Ohio State University Medical Center for a walk at Edgewater Park in Cleveland, Ohio. Dr. Andrew Higgins (Crtitical Care Cardiology and Advanced HF / Transplant Cardiology at Cleveland Clinic) provides the ECPR for this episode. They discuss the following case involving a rare cause of non-ischemic cardiomyopathy. A young African American male was admitted for cardiogenic shock following an admission a month earlier for treatment resistant psychosis. He was diagnosed with medication-induced non-ischemic cardiomyopathy, which resolved with a remarkable recovery of his systolic function after discontinuation of the culprit medication, Clozapine. Episode notes were drafted by Dr. Essa Hariri. Audio editing by CardioNerds Academy Intern, student doctor Shivani Reddy.

Enjoy this case report co-published in US Cardiology Review: Clozapine-induced Cardiomyopathy: A Case Report

CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls – An Unusual Case of Non-ischemic Cardiomyopathy
  1. The diagnosis of drug-induced non-ischemic cardiomyopathy is usually one of exclusion. High clinical suspicion is needed to diagnose drug-induced cardiomyopathy.
  2. Missing the culprit medication causing drug-induced cardiomyopathy could be detrimental as there is a high probability of reversing a systolic dysfunction after stopping the offending medication.
  3. Clozapine is an effective medication for the treatment-resistant schizophrenia and is associated with reduced suicide risk.
  4. Clozapine is reported to cause drug-induced cardiomyopathy and is more common with rapid drug titration. Clozapine is more commonly associated with myocarditis.
  5. Close monitoring and vigilance are critical to preventing cardiac complications associated with initiating clozapine.
  6. The management of clozapine-associated cardiomyopathy includes clozapine cessation and heart failure guideline-directed medical therapy.
Show Notes – An Unusual Case of Non-ischemic Cardiomyopathy

We treated a case of clozapine-associated cardiomyopathy presenting in cardiogenic shock. Drug-induced cardiomyopathy is a common yet under-recognized etiology of non-ischemic cardiomyopathy. Clozapine is an FDA-approved atypical antipsychotic medication frequently prescribed for treatment-resistant schizophrenia and the only antipsychotic agent that has been proven to significantly reduce suicide among this patient population.

However, Clozapine is reported to be associated with several forms of cardiotoxicity, including myocarditis (most common), subclinical clozapine associated cardiotoxicity, and least commonly, drug-induced cardiomyopathy. Clozapine-associated cardiomyopathy should be considered as a differential diagnosis in schizophrenic patients presenting with signs of acute heart failure. 

Rapid titration of clozapine is a risk factor for clozapine-associated cardiomyopathy and clozapine-associated myocarditis. To date, there is no evidence or consensus supporting preemptive screening. According to the American Psychiatric Association, whenever clozapine-induced myocarditis or cardiomyopathy is suspected, a cardiology consult is warranted. Experts recommend, when initiating clozapine, to obtain baseline troponin, CRP, and echocardiography upon drug initiation. This is followed by daily symptom assessment and a hemodynamic assessment on every other day. A biochemical assessment of CRP and troponin levels is warranted every 7 days. The authors recommend clozapine caseation if troponin rises above twice the upper normal limit or if CRP levels exceeds 100 mg/L. Because clozapine is a highly effective medication in treating schizophrenia, close monitoring and vigilance is critical to prevent deleterious complications associated with drug cardiotoxicity. Several mechanisms have been proposed to explain the cardiotoxicities reported with clozapine. Most patients with clozapine-associated cardiotoxicity remain asymptomatic, while others may present with typical acute congestive heart failure. The most common presenting symptom was shortness of breath (60%) followed by palpitations (36%), and the main echocardiographic finding in all patients with this disease is systolic dysfunction with reduced ejection fraction.

The management of clozapine-associated cardiomyopathy includes clozapine cessation and heart failure guideline-directed medical therapy. Clozapine suspension along with conventional heart failure management have led to a significant improvement in left ventricular function. Decisions regarding resuming clozapine therapy are highly individualized and should consider weighing in the risks and benefits of treatment. Whenever clozapine is rechallenged, very close monitoring and frequent echocardiography may be warranted to prevent subsequent cardiotoxicity.

References – An Unusual Case of Non-ischemic Cardiomyopathy

1.        Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report from the American Heart Association. Circulation. 2022;145(8). doi:10.1161/CIR.0000000000001052

2.        Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the united states a policy statement from the american heart association. Circ Heart Fail. 2013;6(3). doi:10.1161/HHF.0b013e318291329a

3.        VanDyck TJ, Pinsky MR. Hemodynamic monitoring in cardiogenic shock. Curr Opin Crit Care. 2021;27(4). doi:10.1097/MCC.0000000000000838

4.        Keepers GA, Fochtmann LJ, Anzia JM, et al. The American psychiatric association practice guideline for the treatment of patients with schizophrenia. American Journal of Psychiatry. 2020;177(9). doi:10.1176/appi.ajp.2020.177901

5.        Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: A meta-analysis. Schizophr Res. 2005;73(2-3). doi:10.1016/j.schres.2004.05.015

6.        Taipale H, Tanskanen A, Mehtälä J, Vattulainen P, Correll CU, Tiihonen J. 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry. 2020;19(1):61-68. doi:10.1002/wps.20699

7.        Citrome L, McEvoy JP, Saklad SR. A guide to the management of clozapine-related tolerability and safety concerns. Clin Schizophr Relat Psychoses. 2016;10(3). doi:10.3371/1935-1232.10.3.163

8.        Knoph KN, Morgan RJ, Palmer BA, et al. Clozapine-induced cardiomyopathy and myocarditis monitoring: A systematic review. Schizophr Res. 2018;199. doi:10.1016/j.schres.2018.03.006

9.        Kanniah G, Kumar S. Clozapine associated cardiotoxicity: Issues, challenges and way forward. Asian J Psychiatr. 2020;50. doi:10.1016/j.ajp.2020.101950

10.      Curto M, Girardi N, Lionetto L, Ciavarella GM, Ferracuti S, Baldessarini RJ. Systematic Review of Clozapine Cardiotoxicity. Curr Psychiatry Rep. 2016;18(7). doi:10.1007/s11920-016-0704-3

11.      Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheterization and Cardiovascular Interventions. 2019;94(1). doi:10.1002/ccd.28329

12.      Alawami M, Wasywich C, Cicovic A, Kenedi C. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol. 2014;176(2). doi:10.1016/j.ijcard.2014.07.103

13.      Arzuk E, Karakuş F, Orhan H. Bioactivation of clozapine by mitochondria of the murine heart: Possible cause of cardiotoxicity. Toxicology. 2021;447. doi:10.1016/j.tox.2020.152628

14.      Vaddadi KS, Soosai E, Vaddadi G. Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003;55(3). doi:10.1046/j.1365-2125.2003.01773.x

15.      Yost BL, Gleich GJ, Fryer AD. Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein. J Appl Physiol. 1999;87(4). doi:10.1152/jappl.1999.87.4.1272

16.      Yuen JWY, Kim DD, Procyshyn RM, White RF, Honer WG, Barr AM. Clozapine-induced cardiovascular side effects and autonomic dysfunction: A systematic review. Front Neurosci. 2018;12(APR). doi:10.3389/fnins.2018.00203

17.      Ronaldson KJ, Taylor AJ, Fitzgerald PB, Topliss DJ, Elsik M, McNeil JJ. Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls. Journal of Clinical Psychiatry. 2010;71(8). doi:10.4088/JCP.09m05024yel

18.      de Leon J, Tang YL, Baptista T, Cohen D, Schulte PFJ. Titrating clozapine amidst recommendations proposing high myocarditis risk and rapid titrations. Acta Psychiatr Scand. 2015;132(4). doi:10.1111/acps.12421

19.      Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, Wolfe R, McNeil JJ. Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: A case-control study. Schizophr Res. 2012;141(2-3). doi:10.1016/j.schres.2012.08.018

20.      Ronaldson KJ, Fitzgerald PB, Taylor AJ, Topliss DJ, McNeil JJ. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Australian and New Zealand Journal of Psychiatry. 2011;45(6). doi:10.3109/00048674.2011.572852

21.      Patel RK, Moore AM, Piper S, et al. Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists. Psychiatry Res. 2019;282. doi:10.1016/j.psychres.2019.112491

22.      Cook SC, Ferguson BA, Cotes RO, Heinrich TW, Schwartz AC. Clozapine-Induced Myocarditis: Prevention and Considerations in Rechallenge. Psychosomatics. 2015;56(6). doi:10.1016/j.psym.2015.07.002

23.      de Leon J, Schoretsanitis G, Smith RL, et al. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels [published correction appears in Pharmacopsychiatry. 2022 Jan 20;:]. Pharmacopsychiatry. 2022;55(2):73-86. doi:10.1055/a-1625-6388

 

264. CCC:  Approach to Renal Replacement Therapy in the CICU with Dr. Joel Topf12 Feb 202300:47:42

Renal replacement therapy (RRT) is routinely utilized in the CICU. Series co-chairs Dr. Eunice Dugan and Dr Karan Desai along with CardioNerds Co-founder Dr. Daniel Ambinder were joined by FIT lead and CardioNerds Ambassador from University of Washington, Dr. Tomio Tran. Our episode expert is world-renowned nephrologist Dr. Joel Topf. Dr. Topf is Medical Director of Research at St. Clair Nephrology, and editor of the Handbook of Critical Care Nephrology. In this episode, we describe a case of cardiogenic shock due to acute myocardial infarction resulting in renal failure, ultimately requiring continuous RRT (CRRT). We discuss the most common causes of AKI within the cardiac ICU, indications for initiating RRT, evidence on the timing of RRT, different modes of RRT, basic management of the RRT circuit, and how to transition patients off of RRT during renal recovery. Episode notes were drafted by Dr. Tomio Tran. Audio editing by CardioNerds Academy InternDr. Maryam Barkhordarian.

The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark BelkinDr. Eunice DuganDr. Karan Desai, and Dr. Yoav Karpenshif.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is made possible with support from Glass.Health – The first digital notebook designed for doctors. Follow @GlassHealthHQ for the latest product updates!

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Pearls • Notes • References • Production Team

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Pearls and Quotes – Approach to Renal Replacement Therapy in the CICU
  1. Do not commit “Renalism” – withholding lifesaving treatments from patients with renal impairment due to fear of causing renal injury. Shared decision making is key.
  2. In the ICU, most of the time, AKI is caused by ATN due to adverse hemodynamics. Nephrologists can help determine the cause if the patient has an atypical presentation.
  3. Late dialysis initiation is non-inferior to early dialysis initiation. Early initiation may lead to higher rates of prolonged time on dialysis.
  4. Slow low efficiency daily diafiltration (SLEDD) vs CRRT are equivalent in terms of outcomes and are the preferred methods among patients with hypotension. Intermittent Hemodialysis (iHD) can be used once patients are hemodynamically stable.
  5. A “Furosemide Stress Test” can be used to test intact renal function or renal recovery by challenging the nephron to make urine.
Show notes – Approach to Renal Replacement Therapy in the CICU

What are the risk factors and differential for AKI in the CICU?

  • Start by using the pre-renal vs intrinsic renal vs post-renal framework. Additional considerations in cardiac patients include contrast induced nephropathy, pigment nephropathy, cardiorenal syndrome. Enjoy Episode 262. Management of Cardiorenal Syndrome in the CICU.
  • In the ICU setting, intrinsic renal injury due to ATN is among the most common etiology of AKI.
  • Many risk factors for AKI are not modifiable in the ICU. Optimize renal function by avoiding nephrotoxins, minimizing contrast usage, and keeping the MAP >65-75 mmHg.
  • Contrast nephropathy as an etiology is questionable and may be a marker of a sicker patient population. Avoid “Renalism” – providing substandard care to patients with renal disease due to fear of worsening renal function.
  • Most etiologies are treated with supportive care.

What is the approach to timing of renal replacement therapy initiation?

  • Definitions for early vs late vs very late initiation of RRT:
    • Early – Worsening AKI without indications for RRT
    • Late – Worsening AKI with relative indications for RRT
    • Very late – Worsening AKI with strict indications for RRT
  • Late initiation is noninferior in terms of mortality; early initiation is associated with higher rates of prolonged/permanent RRT.1,2,3
  • Very late initiation associated with worse outcomes.4 In general, start RRT if there are absolute indications (“AEIOU) or the patient is anuric with a high BUN (~140) as delaying RRT much further is associated with worse outcomes.
  • “Furosemide Stress Test” (FST) can be used to predict RRT need.5
    • 1 mg/kg IV for diuretic naive, 1.5 mg/kg IV if on diuretic
    • Goal = 200 cc urine over 1-2 hours

For the non-nephrologists, what are options for RRT acutely and how do they work?

  • There are two principles of RRT:
    • Convection – movement of solutes through semipermeable membrane using pressure
      • Ultrafiltration – volume removal using convection; fluid is then replaced to prevent hypovolemia
        • Fluid removed has the same composition of the plasma
        • Negative fluid balance is the difference between volume removed and replacement fluid; goal usually 25-250 cc/hour
    • Diffusion – movement of solutes from high to low concentration
      • Dialysate runs countercurrent through semipermeable membrane
      • Typical dialysate composition – normal sodium, magnesium, low potassium, no creatinine, no BUN, high bicarbonate
      • Does not remove fluid
  • There are 3 types of RRT: iHD (intermittent hemodialysis), CRRT (continuous renal replacement therapy), SLEDD (slow low efficiency daily diafiltration)
    • None have been shown to be superior in normotensive patients
    • iHD can remove potassium and toxins more quickly
    • SLEDD and CRRT are equivalent and preferred for hypotensive patients.6
      • SLEDD is less labor intensive
      • Institutions usually have a preference of one modality over another
    • Peritoneal dialysis has been used in the ICU in some specialized centers, but is not common.
  • There are 3 methods of CRRT:
    • Continuous hemodialysis
      • Removes fluid by diffusion
      • Uses dialysate, no replacement fluid
      • Removes small-medium sized molecules
    • Continuous hemofiltration
      • Removes fluid by convection
      • No dialysate, needs replacement fluid
      • Removes large sized molecules
    • Continuous hemodiafiltration
      • Removes fluid by diffusion and convection
      • Uses dialysate and replacement fluid

What should non-nephrologists understand about daily management of patients on CVVH?

  • CICU clinicians should frequently communicate fluid balance and hemodialysis goals with nephrology and nurses
  • The circuit has 2 pumps: 1 to pull fluid, another to push fluid back
    • Monitor daily pressure trends as deviations may implicate issues with the access
    • Look at I/Os on the circuit to determine fluid balance
  • Ask RN if filter is clotting off because this can cause blood loss anemia due to the amount of blood lost when the circuit needs to be changed
  • Electrolyte management:
    • After 1-2 days of normalizing hyperkalemia, try to keep potassium steady using a 4 K bath
    • CRRT can drop phosphorous precipitously, which may cause cardiac myocyte dysfunction; add Na-Phos if necessary.
  • Very important: frequent line checks to identify infections. If the line is in for several days and begin considering a switch to a tunneled dialysis catheter, especially if longer-term RRT is expected.

How does the CICU team monitor for native renal recovery and initiate cardiovascular GDMT?

  • The CICU team should assess daily trends in urine output. Patients may spontaneously make more urine especially as critical illness resolves. Consider trialing diuretics (FST) to assess recovery. Once hemodynamics improves, transition to iHD if there is still a persistent indication for RRT. Temporary dialysis lines are infection prone; consider exchanging for a tunneled iHD line if in place >1 week.
  • Many GDMT medications, often crucial for CV optimization, are considered nephrotoxic and may increase serum potassium. Therefore, it is important to be thoughtful about timing of initiation.
  • Consider initiating GDMT when the Cr is trending towards baseline. Cr is “cosmetic”, and the team should tolerate some Cr increases with life-saving GDMT. Please note that trends in potassium levels is more important than Cr with “nephrotoxic” CV meds.
  • There may be a role for gastrointestinal potassium binders to facilitate GDMT optimization, but the clinical safety and efficacy remains unanswered (trials are underway). 
  • It is crucial for patients to get back on GDMT for improved long term cardiac outcomes.
References
  1. Gaudry S, Hajage D, Schortgen F, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. New England Journal of Medicine. 2016;375(2):122-133.
  2. STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med. 2020;383(3):240-251.
  3. Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the elain randomized clinical trial. JAMA. 2016;315(20):2190.
  4. Gaudry S, Hajage D, Martin-Lefevre L, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. The Lancet. 2021;397(10281):1293-1300.
  5. Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17(5):R207.
  6. Rabindranath K, Adams J, Macleod AM, Muirhead N. Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev. 2007;(3):CD003773.
263. ACHD: Patent Ductus Arteriosus & Eisenmenger Syndrome with Dr. Candice Silversides10 Feb 202300:27:24

Join CardioNerds to learn about patent ducts arteriosus and Eisenmenger syndrome! Dr. Dan Ambinder (CardioNerds co-founder), ACHD series co-chair Dr. Dan Clark,  Dr. Tony Pastor (ACHD fellow, Harvard Medical School), and Dr. Kate Wilcox, Medicine/Pediatrics Resident, Medical College of Wisconsin join Dr. Candice Silversides (Editor-in-chief #JACCAdvances) for this terrific discussion. Notes were drafted by Dr. Kate Wilcox. .Audio editing by CardioNerds Academy InternDr. Maryam Barkhordarian.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh SaefDr. Agnes Koczo, and Dr. Dan Clark.

The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more

Disclosures: None

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Pearls – Patent Ductus Arteriosus & Eisenmenger Syndrome
  1. The ductus arteriosus, which is formed from the distal portion of the left sixth arch, is key to fetal circulation because it allows blood to bypass the high resistance pulmonary circuit present in utero.
  2. After birth there is a significant drop in pulmonary vascular resistance (PVR) which generally leads to functional ductal closure within 48 hours (permanent seal takes 2-3 weeks to form).
  3. Risk factors for having a PDA include birth before 37 weeks of gestation, trisomy 21, and congenital rubella.
  4. A PDA results in a left to right shunt (qP:qS >1) which over time overloads the left side of the heart and causes pulmonary vascular remodeling. The extra workload on the left side of the heart causes left atrial (can cause atrial arrhythmias) and left ventricular dilation.
  5. If left untreated you can eventually have shunt reversal due to very high PVR (Eisenmenger physiology). There are some treatment options at this point (pulmonary vasodilators, etc) but it’s definitely better to close the PDA before this point.
  6. One interesting physical exam finding that can stem from shunt reversal in a hemodynamically significant PDA is differential cyanosis (upper body or pre-ductal saturations will be higher than lower body/post-ductal saturations). You can also see clubbing in the toes but not the hands for the same reason.
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Adult Congenital Heart Association
Founded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers

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262. CCC: Management of Cardiorenal Syndrome in the CICU with Dr. Nayan Arora and Dr. Elliott Miller06 Feb 202300:41:18

The Cardiorenal Syndrome is commonly encountered, and frequently misunderstood. Join the CardioNerds team as we discuss the complex interplay between the heart and kidneys with Dr. Elliott Miller (Assistant Professor of Medicine at Yale University School of Medicine and Associate Medical Director of the Cardiac Intensive Care Unit of Yale New Haven Hospital), and Dr. Nayan Arora (Clinical Assistant Professor of Medicine and Nephrologist at the University of Washington Medical Center). We are hosted by FIT lead Dr. Matthew Delfiner (Cardiology Fellow at Temple University), Cardiac Critical Care Series Co-Chairs Dr. Mark Belkin (AHFTC faculty at University of Chicago) and Dr. Karan Desai (Cardiologist at Johns Hopkins Hospital), and CardioNerds Co-Found Dr. Dan Ambinder. In this episode we discuss the definition and pathophysiology of the cardiorenal syndrome, explore strategies for initial diuresis and diuretic resistance, and management of the common heart failure medications in this setting. Show notes were developed by Dr. Matthew Delfiner. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark BelkinDr. Eunice DuganDr. Karan Desai, and Dr. Yoav Karpenshif.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes – Management of Cardiorenal Syndrome in the CICU
  1. Cardiorenal syndrome (CRS) represents a range of clinical entities in which there is both heart and kidney dysfunction, and can be driven by one, or both, of the organs.
  2. CRS is caused by reduced renal perfusion, elevated renal congestion, or a combination of the two. Treatment therefore focuses on increasing perfusion, by optimizing cardiac output and mean arterial pressure, and reducing congestion through diuresis.
  3. Patients should be monitored for an adequate response to the initial diuretic dose within 2 hours of administration. If the response is inadequate, the loop diuretic dose should be doubled.
  4. Diuretic resistance can be managed via sequential nephron blockade, most commonly with thiazide diuretics, but also with amiloride, high-dose spironolactone, or acetazolamide, as these target different regions of the nephron.
  5. In cases of refractory diuretic resistance, hypertonic saline can be considered with the help of an experienced clinician.
  6. Continuation or cessation of renin-angiotensin-aldosterone system (RAAS) inhibitors in the setting of CRS should be made on a case-by-case basis.
Show notes – Management of Cardiorenal Syndrome in the CICU

1. Cardiorenal syndrome (CRS) is a collection of signs/symptoms that indicate injury to both the heart and kidneys. Organ dysfunction in one can drive dysfunction in the other. Cardiorenal syndrome can be categorized as:

  • Type 1 – Acute heart failure causing acute kidney injury
  • Type 2 – Chronic heart failure causing chronic kidney injury
  • Type 3 – Acute kidney injury causing acute heart failure
  • Type 4 – Chronic kidney injury causing chronic heart failure
  • Type 5 – Co-development of heart and kidney injury by another systemic process.

These categories can be helpful for education, discussion, and research purposes, but they do not usually enter clinical practice on a regular basis since different categories of cardiorenal syndrome are not necessarily treated differently.

2. CRS is caused by either reduced renal perfusion, elevated renal congestion, or a combination of the two. When dealing with CRS, note that:

  • CRS can be caused by poor kidney perfusion, though is mostly driven by low renal perfusion pressure.
  • Renal perfusion pressure is the gradient between renal arteries and renal veins, which can be approximated by mean arterial pressure (MAP) minus central venous pressure (CVP)
  • CRS can therefore be treated by reducing CVP (i.e. with diuresis) or increasing MAP or cardiac output

3. Renal decongestion is achieved primarily through diuresis.

  • For diuretic “naïve” patients, furosemide 40 mg IV is a reasonable starting dose
  • For patients already on diuretics prior to admission, increasing their home dose by 2.5x (administered intravenously) usually achieves an adequate initial response
  • Patients should be reassessed 1-2 hours after their initial diuretics dose. If the patient has not made 200 mL of urine, the loop diuretic dose should be doubled.
  • Diuretic dose and urine output have a logarithmic relationship, meaning doubling the dose does not double the urine output. Once you reach a certain dose threshold, you won’t necessarily increase the quantity of diuresis, but rather you will increase the duration of diuresis.

4. It is okay if creatinine rises with diuresis, to a degree.

  • Creatinine elevation with decongestion is more a sign of hemoconcentration and is paradoxically associated with better outcomes.
  • However, if the creatinine rises by more than 30-50% and you are not seeing clinical evidence of decongestion, then that is likely a poor prognostic sign.

5. There are multiple ways to manage diuretic resistance.

  • Diuretic resistance is often due to a variety of mechanisms including increased sodium reabsorption and hypertrophy of the distal convoluted tubule. Sequential nephron blockade can be considered, most commonly with a thiazide diuretic in addition to a loop diuretic, after the loop diuretic dose is sufficiently optimized.
  • Patients with diuretic resistance may also have increased sodium reabsorption in the proximal tubule, so acetazolamide may be helpful in certain cases. Check out the CardioNerds Journal Club on the ADVOR trial!
  • Amiloride and high doses of spironolactone can be used to target the collecting ducts.
  • Finally, hypertonic saline has been used to address persistent diuretic resistance in certain cases, though should be done with an experienced clinician.

6. Decisions regarding cessation versus continuation of renin-angiotensin-aldosterone system (RAAS) inhibitors in the setting of CRS should be made on a case-by-case basis.

  • RAAS inhibitors may not specifically cause harm, but they may make it difficult to discern whether a change in creatinine related to their use versus worsening renal function.
  • On the other hand, there is an increased likelihood that RAAS inhibitors are not resumed when they are held in CRS, which is associated with worse outcomes. Therefore, it is imperative that there is a plan made to resume these medications if they are held.
References
261. Cardio-Oncology: Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Oncologist Perspective with Dr. Susan Dent31 Jan 202300:45:40

Dr. Filip Ionescu (hematology-oncology fellow at Moffitt Cancer Center in Tampa, FL), Dr. Teodora Donisan (cardiology fellow at the Mayo Clinic in Rochester, MN and CardioNerds House Thomas chief), Dr. Sarah Waliany (internal medicine chief resident at Stanford University in Palo Alto, CA), Dr. Dinu Balanescu (internal medicine chief resident at Beaumont Hospital in Royal Oak, MI) and Dr. Amit Goyal (structural interventional cardiology fellow at the Cleveland Clinic, in Cleveland, OH and CardioNerds Co-Founder), discuss the cardiotoxicities of common cancer treatments with Dr. Susan Dent, a medical oncologist and one of the founders of the field of Cardio-Oncology. Using the recently published ESC Guidelines on cardio-oncology, they cover cardiovascular risk stratification in oncology patients, pretreatment testing, as well as prevention and management of established cardiotoxicity resulting from anthracyclines, trastuzumab, and fluoropyrimidines. They touch on the unique aspects of cardio-oncology encountered in patients with breast cancer, rectal cancer, and lung cancer, who are frequently the recipients of multiple cardiotoxic treatments. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

Access the CardioNerds Cardiac Amyloidosis Series for a deep dive into this important topic.

This episode is supported by a grant from Pfizer Inc.

This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero AbreuDr. Dinu Balanescu, and Dr. Teodora Donisan

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls and Quotes – Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Oncologist Perspective with Dr. Susan Dent
  1. Formal cardiovascular risk stratification must be performed prior to initiating a potentially cardiotoxic anticancer treatment regimen. Considering both drug toxicity and patient-related factors (e.g., age, smoking, hypertension etc) is important. 
  2. Anthracyclines affect the cardiomyocyte in complex ways which lead to a largely irreversible cardiomyopathy. All patients should have a pretreatment echocardiogram and ECG. 
  3. Trastuzumab cardiotoxicity, by contrast, is more like stunning the myocardium, which manifests as a reversible decrease in left ventricular ejection fraction which generally normalizes upon discontinuation of the drug. 
  4. The treatment of chemotherapy-induced cardiomyopathy should involve interdisciplinary discussions and shared decision making with the patient. Beyond guideline-directed medical therapy of heart failure with reduced ejection fraction, management can include temporarily holding or permanently discontinuing the offending agent. 
  5. Fluoropyrimidine-associated cardiotoxicity manifests as cardiac ischemia from coronary vasospasm. A 5FU infusion is essentially a stress test as it tends to unmask clinically silent atherosclerosis. 
Show notes
  1. What is the basic pretreatment assessment of any oncology patient who is to receive a potentially cardiotoxic regimen? 

Awareness and management of the cardiovascular toxicity of oncology treatments are of paramount importance to be able to deliver treatment safely and to achieve maximal efficacy guided by an expert multidisciplinary team. Thanks to Dr. Dent and her colleagues’ work, this year we have seen the publication of the first Cardio-Oncology guideline (1). Perhaps the most important recommendation is that cancer patients about to start a cardiotoxic regimen should undergo formal cardiovascular risk stratification by considering both the adverse profile of the planned treatment and patient-related factors (e.g., preexisting heart disease, hypertension, smoking). High-risk patients may be referred early to a cardio-oncologist who can anticipate and mitigate toxicities. In addition to risk stratification, specific treatment modalities may require additional imaging and biochemical testing as outlined next. 

  1. How does anthracycline-induced cardiotoxicity present and what are the risk factors to consider? 

Anthracycline-induced cardiotoxicity generally manifests as a permanent decrease in left ventricular ejection fraction (LVEF) caused by direct toxic effect of the cytotoxic chemotherapy on the cardiomyocytes. The risk factors for developing anthracycline-induced cardiotoxicity are cumulative anthracycline dose, advanced age, pretreatment low-normal LVEF, prior cardiovascular disease, as well as other established cardiovascular risk factors (e.g., hypertension, diabetes, obesity, smoking).  

  1. What is included in the work-up of a patient about to begin an anthracycline-containing regimen? 

All patients who are about to received anthracyclines require a baseline echocardiogram, ideally with global longitudinal strain, and an electrocardiogram. For patients who are at moderate-to-high risk of developing cardiomyopathy, B-type natriuretic peptide and Troponin can also be helpful for monitoring.  

  1. How is established anthracycline-induced cardiotoxicity typically managed? 

When a decrease in LVEF below 50% is detected, management usually involves holding the anthracycline and repeating imaging. At this point, discussion with a cardio-oncologist about the initiation of ACC/AHA guideline-directed medical therapy (GDMT) is warranted. If there is improvement in the LVEF with this approach, the decision to rechallenge is nuanced and often part of a multidisciplinary and shared decision-making process with the patient.  

  1. What are some proven strategies to prevent or mitigate anthracycline-induced cardiotoxicity? 

In the case of a rechallenge, two ways to mitigate the risk of cardiac damage are using liposomal doxorubicin, which is a less cardiotoxic anthracycline formulation, and co-administration of dexrazoxane, which is the only FDA-approved cardioprotectant for use in this setting. 

  1. What is trastuzumab and how does the cardiotoxicity associated with its use differ from that caused by anthracyclines? 

Trastuzumab is a monoclonal antibody directed against the HER2 receptor molecule expressed on breast cancer cells. The actual mechanism of trastuzumab-associated cardiotoxicity is not clear, but it appears to be more akin to myocardial stunning and is generally reversible. If it occurs, a decrease in LVEF appears early and for most patients withholding the drug is effective in reversing the effect.  

  1. How is trastuzumab-associated cardiotoxicity managed? 

For those patients with a nadir LVEF < 50%, there is evidence to support the efficacy of GDMT. For those with an LVEF decrease in the 40-49% range, trastuzumab can be continued concomitantly with GDMT and close monitoring of LVEF. In cases with severe LVEF decrease <40%, the decision to continue or rechallenge becomes more complicated and always should involve a multidisciplinary discussion of the risks and benefits of either approach. Depending on the goal of treatment (curative in the adjuvant setting or palliative in the metastatic setting), the actual predicted benefit and whether the cardiac function recovers with GDMT, trastuzumab could potentially be restarted.  

  1. How do novel antibody drug conjugates that contain trastuzumab differ in their cardiotoxicity profile from the naked antibody? 

In recent years we have seen the advent of antibody drug conjugates (T-DM1, T-DXd) which in addition the antibody directed against HER2 (trastuzumab) also carry a cytotoxic payload (2). While the experience with these newer agents is still limited, early data suggest these are no more cardiotoxic than trastuzumab. However, the impact of long-term, sequential exposure to these agents on cardiovascular outcomes is unknown. 

  1. What are fluoropyrimidines and how does fluoropyrimidine-associated cardiotoxicity manifest clinically? 

Fluoropyrimidines are analogs of nucleic acid bases which inhibit synthesis of DNA and RNA. These are some of the most widely use anticancer drugs and examples include 5-fluorouracil (5FU) and capecitabine (an oral prodrug of 5FU). Fluoropyrimidine-associated cardiotoxicity presents primarily with cardiac ischemia caused by coronary vasospasm or endothelial damage, although these are not the only mechanisms by which these drugs can damage the cardiovascular system (3). This is a phenomenon which typically occurs early in therapy after 1-2 cycles and its incidence varies greatly with the mode of administration, occurring in >10% of patients treated with a 5FU infusion (or continuous capecitabine) versus in 3-5% of those who receive the 5FU as a bolus.  

  1. What is the management of fluoropyrimidine-associated cardiotoxicity? 

Rechallenge is possible in select patients who take active part in the decision-making process and who are deemed to derive substantially larger benefits than risks from continuing. When done, rechallenges usually take place in an inpatient setting with close monitoring and co-administration of calcium channel blockers and nitrates. 

  1. Is it possible to rechallenge patients with ischemic symptoms induced by fluoropyrimidine treatment? 

Generally, presentations are clinically apparent with symptoms of ischemia and management necessarily includes holding the drug and performing an ischemic work-up which may require invasive testing such as coronary angiography. If there is a clear temporal association with fluoropyrimidine use and ischemic symptoms, a multidisciplinary discussion on whether treatment should be continued is warranted.  

  1. What is unique about the cardiotoxicity of oncology therapy in lung cancer patients? 

Lung cancer patients are the perfect storm for cardiotoxicity. The prevalence of smoking is very high in this particular cohort which correlates with preexisting cardiovascular disease. Furthermore, radiation to the chest, tyrosine kinase inhibitors (TKIs) targeting EGFR or ALK, and immune checkpoint inhibitors are frequently part of the treatment schema and have defined cardiovascular toxicities (4). As such, these patients are very likely to benefit from cardiology consultation and optimization of cardiovascular risk factors prior to initiating cancer therapy. 

  1. What is the cardiovascular toxicity of TKIs? 

These systemic treatments were initially developed for metastatic disease but are now making their way into the adjuvant setting. These drugs can maintain efficacy for a long time which translates into prolonged exposure and cardiovascular side effects such as hypertension and QT prolongation.  

  1. What is the cardiovascular toxicity of immune checkpoint inhibitors? 

Immune checkpoint inhibitors can cause hyperactivation of the immune system resulting in immune attack of normal structures, such as the myocardium. While immune-mediated myocarditis is uncommon (1-2%), it can be very severe with mortality rates approaching 50%, underlining the importance of early recognition and treatment. 

References – Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Oncologist Perspective with Dr. Susan Dent

1. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC). European Heart Journal. Published online August 26, 2022:ehac244. doi:10.1093/eurheartj/ehac244 

2. Dent SF, Morse A, Burnette S, Guha A, Moore H. Cardiovascular Toxicity of Novel HER2-Targeted Therapies in the Treatment of Breast Cancer. Current Oncology Reports. 2021;23(11). doi:10.1007/s11912-021-01114-x 

3. Sara JD, Kaur J, Khodadadi R, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018;10:1758835918780140. doi:10.1177/1758835918780140 

4. Kunimasa K, Kamada R, Oka T, et al. Cardiac Adverse Events in EGFR-Mutated Non-Small Cell Lung Cancer Treated With Osimertinib. JACC: CardioOncology. 2020;2(1):1-10. doi:10.1016/j.jaccao.2020.02.003 

Meet Our Collaborators

International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

260. Case Report: Cardioembolic Stroke from an Unusual Valve Pathology from The University of Alabama at Birmingham22 Jan 202300:35:42

CardioNerds Cofounder Dr. Amit Goyal join Dr. Usman Hasnie and Dr. Will Morgan from University of Alabama at Birmingham for a hike up Red Mountain. They discuss the following case: A 75-year-old woman with prior mitral valve ring annuloplasty presented with subacute, intermittent, self-limiting neurologic deficits. Brain MRI revealed multiple subacute embolic events consistent with cardioembolic phenomena. Transesophageal echochardiogram discovered a mobile mass on the mitral valve as the likely cause for cardioembolic stroke. She was taken for surgical repair of the mitral valve. Tissue biopsy confirmed that the mass was an IgG4-related pseudotumor. Expert commentary is provided by Dr. Neal Miller (Assistant Professor of Cardiology, University of Alabama at Birmingham). Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares

Check out this published case report here: IgG4-Related Disease Masquerading as Culture-Negative Endocarditis!

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is made possible with support from Glass.Health – The first digital notebook designed for doctors. Follow @GlassHealthHQ for the latest product updates!

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Pearls – Cardioembolic Stroke due to an IgG4-related pseudotumor
  1. Surgical indications for endocarditis include severe heart failure, valvular dysfunction with severe hemodynamic compromise, prosthetic valve infection, invasion beyond the valve leaflets, recurrent systemic embolization, large mobile vegetations, or persistent sepsis (in infective endocarditis) despite adequate antibiotic therapy.
  2. IgG4 related disease is rare, and likely underrecognized due to the lack of reliable biomarkers. Biopsy and histologic confirmation are imperative to clinch the diagnosis.
  3. Cardiac manifestations of IgG4-related disease are rare but are often related to aortopathies. Valvular disease is extremely rare as a manifestation of the disease.
  4. Treatment of IgG4 related disease includes steroids as the first line treatment.
  5. IgG4 related disease requires a multi-disciplinary approach to both diagnose and treat.
Show Notes – Cardioembolic Stroke due to an IgG4-related pseudotumor

Notes were drafted by Dr. Hasnie and Dr. Morgan

  1. IgG4-related disease has a very diverse presentation including mimicry of infection, malignancy and other autoimmune conditions. It is a fibroinflammatory condition that results in deposition of IgG4 positive plasma cells. It has been described in multiple organ systems including the pancreas, kidneys, lungs and salivary glands. 
  2. Cardiac manifestations are extremely rare and valvular disease even more so. There are thirteen cases of IgG4 related valvular disease, and of these only two had mitral valve involvement such as this case. The most commonly reported cardiovascular manifestations are related to aortopathies. 
  3. This disease remains poorly understood at this point. There are no true biomarkers that can be used to risk stratify the diagnosis for clinicians. Biopsy is imperative to the diagnosis. Even serum IgG4 levels are normal in 30% of cases despite meeting histologic criteria on biopsy making the diagnosis incredibly difficult to make. 
  4. While guidelines have not been developed to guide treatment of IgG4-related disease, steroids are considered the first line treatment option for patients. Often times dosing is 2-4 weeks with a prolonged taper. When looking for glucocorticoid sparing agents, azathioprine, mycophenolate mofetil, and methotrexate are considered alternatives. 
References – Cardioembolic Stroke due to an IgG4-related pseudotumor

1. Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4- related autoimmune disease. J Gastroenterol 2003;38:982-4.

 
2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181-1192. doi:10.1038/modpathol.2012.72

 
3. Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res (Hoboken) 2010;62:1312-8.

 
4. Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM, Stone JR. IgG4 related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 2009;60:313945.

 
5. Saeki T, Saito A, Hiura T, et al. Lymphoplasmacytic infiltration of multiple organs with immunoreactivity for IgG4: IgG4-related systemic disease. Intern Med 2006;45:163-7.

 
6. Kamisawa T, Takuma K, Egawa N, Tsuruta K, Sasaki T. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol 2010;7:401-9.

 
7. Shakir A, Wheeler Y, Krishnaswamy G. The enigmatic immunoglobulin G4-related disease and its varied cardiovascular manifestations. Heart. 2021;107(10):790-798. doi:10.1136/heartjnl-2020-318041

 
8. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, et al. Cardiac tumors: JACC cardio oncology state-of-the-art review. J Am Coll Cardiol CardioOnc. 2020;2:293–311

 
9. Selkane C, Amahzoune B, Chavanis N, et al. Changing management of cardiac myxoma based on a series of 40 cases with long-term follow-up. Ann Thorac Surg. 2003;76(6):1935-1938. doi:10.1016/s0003-4975(03)01245-1

 
10. Sun JP, Asher CR, Yang XS, et al. Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients. Circulation. 2001;103(22):2687-2693. doi:10.1161/01.cir.103.22.

11. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539-551. doi:10.1056/NEJMra1104650

12. Hasnie UA, Herrera LN, Morgan WS, Rodriguez JM, Litovsky S, Chatham WW, Winokur T, Muzny CA. IgG4-Related Disease Masquerading As Culture-Negative Endocarditis. AIM Clinical Cases. 2022;1. doi: 10.7326/aimcc.2022.0075

13. 2016 ASE Guideline: https://www.asecho.org/wp-content/uploads/2016/01/2016_Cardiac-Source-of-Embolism.pdf

14.  Shakir A, Wheeler Y, Krishnaswamy G. The enigmatic immunoglobulin G4-related disease and its varied cardiovascular manifestations Heart 2021;107:790-798.

15. Karadeniz H, Vaglio A. IgG4-related disease: a contemporary review. Turk J Med Sci. 2020 Nov 3;50(SI-2):1616-1631. doi: 10.3906/sag-2006-375. PMID: 32777900; PMCID: PMC7672352.

259. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #6 with Dr. Randall Starling20 Jan 202300:09:31

The following question refers to Section 7.4 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by New York Medical College medical student and CardioNerds Intern Akiva Rosenzveig, answered first by Cornell cardiology fellow and CardioNerds Ambassador Dr. Jaya Kanduri, and then by expert faculty Dr. Randall Starling.

Dr. Starling is Professor of Medicine and an advanced heart failure and transplant cardiologist at the Cleveland Clinic where he was formerly the Section Head of Heart Failure, Vice Chairman of Cardiovascular Medicine, and member of the Cleveland Clinic Board of Governors. Dr. Starling is also Past President of the Heart Failure Society of America in 2018-2019. Dr. Staring was among the earliest CardioNerds faculty guests and has since been a valuable source of mentorship and inspiration. Dr. Starling’s sponsorship and support was instrumental in the origins of the CardioNerds Clinical Trials Program.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #6

Mr. D is a 50-year-old man who presented two months ago with palpations and new onset bilateral lower extremity swelling. Review of systems was negative for prior syncope. On transthoracic echocardiogram, he had an LVEF of 40% with moderate RV dilation and dysfunction. EKG showed inverted T-waves and low-amplitude signals just after the QRS in leads V1-V3. Ambulatory monitor revealed several episodes non-sustained ventricular tachycardia with a LBBB morphology.

He was initiated on GDMT and underwent genetic testing that revealed 2 desmosomal gene variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC).

Is the following statement true or false?

“ICD implantation is inappropriate at this time because his LVEF is >35%”

True

 

False

 

Answer #6

Explanation

This statement is False. ICD implantation is reasonable to decrease sudden death in patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death who have an LVEF ≤45% (Class 2a, LOE B-NR).

While the HF guidelines do not define high-risk features of sudden death, the 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy identify major and minor risk factors for ventricular arrhythmias as follows:

  • Major criteria: NSVT, inducibility of VT during EPS, LVEF ≤ 49%.
  • Minor criteria: male sex, >1000 premature ventricular contractions (PVCs)/24 hours, RV dysfunction, proband status, 2 or more desmosomal variants.

According to the HRS statement, high risk is defined as having either three major, two major and two minor, or one major and four minor risk factors for a class 2a recommendation for primary prevention ICD in this population (LOE B-NR).

Based on these criteria, our patient has 2 major risk factors (NSVT & LVEF ≤ 49%), and 3 minor risk factors (male sex, RV dysfunction, and 2 desmosomal variants) for ventricular arrhythmias. Therefore, ICD implantation for primary prevention of sudden cardiac death is reasonable.

Decisions around ICD implantation for primary prevention remain challenging and depend on estimated risk for SCD, co-morbidities, and patient preferences, and so should be guided by shared decision making weighing the possible benefits against the risks, especially in younger patients.

Main Takeaway

In patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death with LVEF ≤ 45%, implantation of ICD is reasonable.

Guideline Loc.

Section 7.4

Also: Section 3.10 from “Towbin, J. A., McKenna, W. J., Abrams, D. J., Ackerman, M. J., Calkins, H., Darrieux, F. C. C., Daubert, J. P., de Chillou, C., DePasquale, E. C., Desai, M. Y., Estes, N. A. M., Hua, W., Indik, J. H., Ingles, J., James, C. A., John, R. M., Judge, D. P., Keegan, R., Krahn, A. D., … Zareba, W. (2019). 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm, 16(11), e301–e372. https://doi.org/10.1016/j.hrthm.2019.05.007”

 


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375. Beyond the Boards: Foundations of Cardiovascular Prevention with Dr. Stephen Kopecky06 Jun 202400:15:53

CardioNerds (Amit Goyal and Dan Ambinder), Dr. Jaya Kanduri, and Dr. Jason Feinman discuss foundations of cardiovascular prevention with Dr. Stephen Kopecky. In this episode, the CardioNerds and topic expert Dr. Stephen Kopecky tackle cardiovascular prevention. They focus on how to identify patients at risk for cardiovascular disease by using the pooled cohort equation and discuss how to incorporate additional risk-enhancing factors in risk estimation. Later, they discuss the role of non-invasive imaging and testing for further patient risk stratification. Last, they discuss the appropriate pharmacologic interventions for patient care, how to determine what LDL-c to target for each patient, and how to modify your treatment modalities in response to side effects or the need for further lipid-lowering therapies.

Notes were drafted by Dr. Jason Feinman. Audio was engineered by CardioNerds Intern Christiana Dangas.

The CardioNerds Beyond the Boards Series was inspired by the Mayo Clinic Cardiovascular Board Review Course and designed in collaboration with the course directors Dr. Amy Pollak, Dr. Jeffrey Geske, and Dr. Michael Cullen.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Pearls and Quotes – Foundations of Cardiovascular Prevention
  1. The 2018 cardiovascular prevention guidelines indicate that a single equation, like the pooled risk equation, does not fit everyone. There are additional risk enhancers that are not factored into the pooled risk equation that can impact an individual’s risk
  2. These factors are often conditions that increase inflammation but can also include family history, ethnicity, chronic kidney disease, metabolic syndrome, premature menopause or gestational diabetes, and rheumatologic conditions
  3. Data from Get With The Guidelines demonstrates that the average LDL at the time of the first myocardial infarction is 105 mg/dL.
  4. Coronary artery calcium scores or a carotid ultrasound can be used to further risk stratify patients. However, CAC is likely to be negative in young women. A CAC of zero can be used to “de-risk” some patients but should not be used to guide therapy in the setting of tobacco usage, diabetes mellitus, or familial hypercholesterolemia.
  5. Strategies to mitigate risk include healthy lifestyle habits and selectively targeting key risk factors including LDL, hypertriglyceridemia, inflammation, and the GLP1-pathway. Upcoming medications may address elevated Lp(a).
Notes – Foundations of Cardiovascular Prevention

Notes: Notes drafted by Dr. Jason Feinman.

How do you assess an individual’s risk for cardiovascular disease?

  • The paramount role of primary prevention is the assessment and mitigation of an individual’s risk for ASCVD event.1
  • The 10-year ASCVD risk calculator is a commonly used tool to assess an individual’s risk and to guide shared decision-making conversations and recommendations.2
  • Individuals can be characterized as having low (less than 5%), borderline (5%-7.5%), intermediate (7.5%-20%), or high (greater than 20%) risk.2
  • The 10-year ASCVD risk calculator has varying validation in ethnic minorities, and other risk calculators, such as the Framingham CVD risk score, may be considered in those groups.3-5
  • Additional risk enhancers may be used to guide recommendations for individuals at borderline or intermediate risk.1

What additional imaging testing may be beneficial in the assessment of an individual’s risk?

  • Individuals with intermediate or borderline risk may benefit from further non-invasive imaging to help guide therapeutic recommendations.2
  • Coronary artery calcification is a marker of underlying atherosclerosis, which can help to reclassify patients to be at higher risk for ASCVD events and support interventions to help lower this risk.6
  • Conversely, a score of zero can help to reclassify individuals into lower-risk groups
  • A score of zero should be used with caution in young women who are more likely to have non-calcified plaque and should not be used as a marker of low risk in individuals with other risk factors, including diabetes mellitus and tobacco usage.1

What non-pharmacological interventions may be considered to lower an individual’s ASCVD risk?

  • The 2019 guidelines give a class I recommendation for a diet of vegetables, fruits, nuts, whole grains, and fish to lower ASCVD risk factors.1
  • Increased intake of sugar has been demonstrated to correlate with increased rates of type 2 diabetes mellitus and subsequent increased risk for cardiovascular events.7
  • At least 150 minutes per week of moderate-intensity or 75 minutes of vigorous intensive is recommended to reduce the risk of ASCVD events.1

What pharmacological interventions can be considered for individuals with prior ASCVD events or at high risk for ASCVD?

  • A moderate-intensity statin is recommended for individuals at intermediate risk of ASCVD events with risk enhancers with a goal reduction in LDL-c of 30% or more.1
  • For individuals at a high 10-year risk for ASCVD events, a 50% reduction in LDL-C is recommended.1
  • A doubling of a statin dose can be predicted to lead to a 6% further reduction in LDL-C
  • Ezetimibe can be considered as adjunct therapy for individuals receiving statin therapy who do not reach their target LDL-C.2

How do you determine the goal LDL-c?

  • LDL goal is based on a history of prior ASCVD events and the risk of future ASCVD events.
  • For secondary prevention, especially for individuals at high risk for ASCVD events, an LDL goal of at least less than 70 mg/dL is recommended2
References – Foundations of Cardiovascular Prevention
  1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Sep 10;140(11):e649-e650] [published correction appears in Circulation. 2020 Jan 28;141(4):e60] [published correction appears in Circulation. 2020 Apr 21;141(16):e774]. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
  2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Jun 18;139(25):e1182-e1186] [published correction appears in Circulation. 2023 Aug 15;148(7):e5]. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625
  3. Yang X, Li J, Hu D, et al. Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China). Circulation. 2016;134(19):1430-1440. doi:10.1161/CIRCULATIONAHA.116.022367
  4. Jung KJ, Jang Y, Oh DJ, et al. The ACC/AHA 2013 pooled cohort equations compared to a Korean Risk Prediction Model for atherosclerotic cardiovascular disease. Atherosclerosis. 2015;242(1):367-375. doi:10.1016/j.atherosclerosis.2015.07.033
  5. D’Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753. doi:10.1161/CIRCULATIONAHA.107.699579
  6. DeFilippis AP, Young R, Carrubba CJ, et al. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Ann Intern Med. 2015;162(4):266-275. doi:10.7326/M14-1281
  7. Löfvenborg JE, Andersson T, Carlsson PO, et al. Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Eur J Endocrinol. 2016;175(6):605-614. doi:10.1530/EJE-16-0376
258. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #5 with Dr. Clyde Yancy20 Jan 202300:12:02

The following question refers to Section 7.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by New York Medical College medical student and CardioNerds Intern Akiva Rosenzveig, answered first by Cornell cardiology fellow and CardioNerds Ambassador Dr. Jaya Kanduri, and then by expert faculty Dr. Clyde Yancy.

Dr. Yancy is Professor of Medicine and Medical Social Sciences, Chief of Cardiology, and Vice Dean for Diversity and Inclusion at Northwestern University, and a member of the AHA/ACC/HFSA Heart Failure Guideline Writing Committee.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #5

Ms. L is a 65-year-old woman with nonischemic cardiomyopathy with a left ventricular ejection fraction (LVEF) of 35%, hypertension, and type 2 diabetes mellitus. She has been admitted to the hospital with decompensated heart failure (HF) twice in the last six months and admits that she struggles to understand how to take her medications and adjust her sodium intake to prevent this.  Which of the following interventions has the potential to decrease the risk of rehospitalization and/or improve mortality?

A

Access to a multidisciplinary team (physicians, nurses, pharmacists, social workers, care managers, etc) to assist with management of her HF

 

B

Engaging in a mobile app aimed at improving HF self-care

 

C

Vaccination against respiratory illnesses

 

D

A & C

 

Answer #5

 

The correct answer is D – both A (access to a multidisciplinary team) and C (vaccination against respiratory illness).

 

Choice A is correct. Multidisciplinary teams involving physicians, nurses, pharmacists, social workers, care managers, dieticians, and others, have been shown in multiple RCTs, metanalyses, and Cochrane reviews to both reduce hospital admissions and all-cause mortality. As such, it is a class I recommendation (LOE A) that patients with HF should receive care from multidisciplinary teams to facilitate the implementation of GDMT, address potential barriers to self-care, reduce the risk of subsequent rehospitalization for HF, and improve survival.

Choice B is incorrect.  Self-care in HF comprises treatment adherence and health maintenance behaviors. Patients with HF should learn to take medications as prescribed, restrict sodium intake, stay physically active, and get vaccinations. They also should understand how to monitor for signs and symptoms of worsening HF, and what to do in response to symptoms when they occur. Interventions focused on improving the self-care of HF patients significantly reduce hospitalizations and all-cause mortality as well as improve quality of life. Therefore, patients with HF should receive specific education and support to facilitate HF self-care in a multidisciplinary manner (Class I, LOE B-R). However, the method of delivery and education matters. Reinforcement with structured telephone support has been shown to be effective. In contrast the efficacy of mobile health-delivered educational interventions in improve self-care in patients with HF remains uncertain.

Choice C is correct. In patients with HF, vaccinating against respiratory illnesses is reasonable to reduce mortality (Class 2a, LOE B-NR). For example, administration of the influenza vaccine in HF patients has been shown to reduce all-cause mortality and hospitalizations.

Main Takeaway

Implementation of multidisciplinary care teams has been proven to reduce rehospitalization and mortality in HF patients. While education on self-care of HF patients is important, not all delivery methods have been shown to be effective.

Guideline Loc.

Section 7.1


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257. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #4 with Dr. Eldrin Lewis15 Jan 202300:23:42

The following question refers to Section 4.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Texas Tech University medical student and CardioNerds Academy Intern Dr. Adriana Mares, answered first by Baylor University cardiology fellow and CardioNerds FIT Trialist Dr. Shiva Patlolla, and then by expert faculty Dr. Eldrin Lewis.

Dr. Lewis is an Advanced Heart Failure and Transplant Cardiologist, Professor of Medicine and Chief of the Division of Cardiovascular Medicine at Stanford University.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #4

Mr. Stevens is a 55-year-old man who presents with progressively worsening dyspnea on exertion for the past 2 weeks. He has associated paroxysmal nocturnal dyspnea, intermittent exertional chest pressure, and bilateral lower extremity edema. Otherwise, Mr. Stevens does not have any medical history and does not take any medications. 

Which of the following will be helpful for diagnosis at this time?

A

 Detailed history and physical examination

B

 Chest x-ray

C

 Blood workup including CBC, CMP, NT proBNP

D

 12-lead ECG

E

All of the above

 

Answer #4

 

The correct answer is E – All of the above. 

Mr. Stevens presents with signs and symptoms of volume overload concerning for new onset heart failure. The history and physical exam remain the cornerstone in the assessment of patients with HF. Not only is the H&P valuable for identifying the presence of heart failure but also may provide hints about the degree of congestion, underlying etiology, and alternative diagnoses. As such H&P earns a Class 1 indication for a variety of reasons in patients with heart failure:

1.       Vital signs and evidence of clinical congestion should be assessed at each encounter to guide overall management, including adjustment of diuretics and other medications (Class 1, LOE B-NR)

2.       Clinical factors indicating the presence of advanced HF should be sought via the history and physical examination (Class 1, LOE B-NR)

3.       A 3-generation family history should be obtained or updated when assessing the cause of the cardiomyopathy to identify possible inherited disease (Class 1, LOE B-NR)

4.       A thorough history and physical examination should direct diagnostic strategies to uncover specific causes that may warrant disease-specific management (Class 1, LOE B-NR)

5.       A thorough history and physical examination should be obtained and performed to identify cardiac and noncardiac disorders, lifestyle and behavioral factors, and social determinants of health that might cause or accelerate the development or progression of HF (Class 1, LOE C-EO)

Building on the H&P, laboratory evaluation provides important information about comorbidities, suitability for and adverse effects of treatments, potential causes or confounders of HF, severity and prognosis of HF, and more. As such, for patients who are diagnosed with HF, laboratory evaluation should include complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone to optimize management (Class 1, LOE C-EO). In addition, the specific cause of HF should be explored using additional laboratory testing for appropriate management (LOE 1, LOE B-NR). In patients presenting with dyspnea such as Mr. Stevens, measurement of B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is useful to support a diagnosis or exclusion of HF (Class 1, LOE A); and in those with chronic HF, measurements of BNP or NT-proBNP levels are recommended for risk stratification (Class 1, LOE A).

In addition to bloodwork, electrocardiography is part of the routine evaluation of a patient with HF and provides important information on rhythm, heart rate, QRS morphology and duration, cause, and prognosis of HF. So for all patients with HF, a 12-lead ECG should be performed at the initial encounter to optimize management (Class 1, LOE C-EO).

Imaging is essential in the diagnosis and management of heart failure. In patients with suspected or new-onset HF, or those presenting with acute decompensated

HF, a chest x-ray should be performed to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient’s symptoms (Class 1, LOE C-LD). Additionally, in those with suspected or newly diagnosed HF, transthoracic echocardiography (TTE) should be performed during the initial evaluation to assess cardiac structure and function (Class 1, LOE C-LD); and when echocardiography is inadequate, alternative imaging (e.g.,  cardiac

magnetic resonance [CMR], cardiac computed tomography [CT], radionuclide imaging) is recommended for assessment of LVEF (Class 1, LOE C-LD).

Main Takeaway 

In patients who present with signs and symptoms of volume overload concerning for new-onset heart failure, it is essential to rule out non-cardiac causes and assess for specific underlying causes of heart failure by using detailed history and physical examination. Once heart failure diagnosis is established, further workup with laboratory testing, ECG, and non-invasive cardiac imaging is warranted to investigate the etiology of heart failure and guide further management. Special attention should be given to detection of signs and symptoms suggesting an advanced stage of disease.

Guideline Loc. 

Section 4.1


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256. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #3 with Dr. Shelley Zieroth13 Jan 202300:08:11

The following question refers to Section 3.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Texas Tech University medical student and CardioNerds Academy Intern Dr. Adriana Mares, answered first by Rochester General Hospital cardiology fellow and Director of CardioNerds Journal Club Dr. Devesh Rai, and then by expert faculty Dr. Shelley Zieroth.

Dr. Zieroth is an advanced heart failure and transplant cardiologist, Head of the Medical Heart Failure Program, the Winnipeg Regional Health Authority Cardiac Sciences Program, and an Associate Professor in the Section of Cardiology at the University of Manitoba. Dr. Zieroth is a past president of the Canadian Heart Failure Society. She is a steering committee member for PARAGLIE-HF and a PI Mentor for the CardioNerds Clinical Trials Program.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #3

Which of the following is/are true about heart failure epidemiology?

A

Although the absolute number of patients with HF has partly grown, the incidence of HF has decreased

B

Non-Hispanic Black patients have the highest death rate per capita resulting from HF

C

In patients with established HF, non-Hispanic Black patients have a higher HF hospitalization rate compared with non-Hispanic White patients

D

In patients with established HF, non-Hispanic Black patients have a lower death rate compared with non-Hispanic White patients

E

All of the above

Answer #3

Explanation 

 

The correct answer is “E – all of the above.”

 

Although the absolute number of patients with HF has partly grown as a result of the increasing number of older adults, the incidence of HF has decreased. There is decreasing incidence of HFrEF and increasing incidence of HFpEF. The health and socioeconomic burden of HF is growing. Beginning in 2012, the age-adjusted death-rate per capita for HF increased for the first time in the US. HF hospitalizations have also been increasing in the US. In 2017, there were 1.2 million HF hospitalizations in the US among 924,000 patients with HF, a 26% increase compared with 2013.

 

Non-Hispanic Black patients have the highest death rate per capita. A report examining the US population found the age-adjusted mortality rate for HF to be 92 per 100,000 individuals for non-Hispanic Black patients, 87 per 100,000 for non-Hispanic White patients, and 53 per 100,000 for Hispanic patients.

 

Among patients with established HF, non-Hispanic Black patients experienced a higher rate of HF hospitalization and a lower rate of death than non-Hispanic White patients with HF.Hispanic patients with HF have been found to have similar or higher HF hospitalization rates and similar or lower mortality rates compared with non-Hispanic White patients.

Asian/Pacific Islander patients with HF have had a similar rate of hospitalization as non-Hispanic White patients but a lower death rate.

 

These racial and ethnic disparities warrant studies and health policy changes to address health inequity.

Main Takeaway

Racial and ethnic disparities in death resulting from HF persist, with non-Hispanic Black patients having the highest death rate per capita, and a higher rate of HF hospitalization. Further clinical studies and health policy changes are needed to address these inequalities.

Guideline Loc.

Section 3.1


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255. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #2 with Dr. Mark Drazner10 Jan 202300:08:08

The following question refers to Section 6.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Mount Sinai Hospital cardiology fellow and CardioNerds FIT Trialist Dr. Jason Feinman, and then by expert faculty Dr. Mark Drazner.

Dr. Drazner is an advanced heart failure and transplant cardiologist, Professor of Medicine, and Clinical Chief of Cardiology at UT Southwestern. He is the President of the Heart Failure Society of America.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #2

A 67-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, and active tobacco smoking presents to the emergency room with substernal chest pain for the past 5 hours. An electrocardiogram reveals ST segment elevations in the anterior precordial leads and he is transferred emergently to the catheterization laboratory. Coronary angiography reveals 100% occlusion of the proximal left anterior descending artery, and he is successfully treated with a drug eluting stent resulting in TIMI 3 coronary flow. Following his procedure, a transthoracic echocardiogram is performed which reveals a left ventricular ejection fraction of 35% with a hypokinetic anterior wall. Which of the following medications would be the best choice to prevent the incidence of heart failure and reduce mortality?

A

Lisinopril

B

Diltiazem

C

Carvedilol

D

Sacubitril-valsartan

E

Both A and C

Answer #2

The correct answer is E – both lisinopril and carvedilol are appropriate to reduce the incidence of heart failure and mortality.

Evidence-based beta-blockers and ACE inhibitors both have Class 1 recommendations in patients with a recent myocardial infarction and left ventricular ejection fraction ≤ 40% to reduce the incidence of heart failure and to reduce mortality. Multiple randomized controlled trials have investigated both medications in the post myocardial infarction setting and demonstrated improved ventricular remodeling as well as benefits for mortality and development of incident heart failure.

At this time, there is not sufficient evidence to recommend ARNi over ACEi for patients with reduced LVEF following acute MI. The PARADISE-MI trial randomized a total of 5,661 patients with myocardial infarction complicated by a reduced LVEF, pulmonary congestion, or both to receive either sacubitril-valsartan (97-103mg twice daily) or ramipril (5mg twice daily). After a median follow up time of 22 months, there was no statistically significant difference in the primary outcome of cardiovascular death or incident heart failure. At this time, ARNi have not been included in the guidelines for this specific population.

Diltiazem is a non-dihydropyridine calcium channel blocker, a family of drugs with negative inotropic effects and which may be harmful in patients with depressed LVEF (Class 3: Harm, LOE C-LD).

Main Takeaway: 

For patients with recent myocardial infarction and reduced left ventricular function both beta blockers and ACEi have Class 1 recommendations to reduce the incidence of heart failure and decrease mortality.

Guideline Location:

Section 6.1


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254. Guidelines: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Question #1 with Dr. Biykem Bozkurt09 Jan 202300:12:44

The following question refers to Section 2.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Mount Sinai Hospital cardiology fellow and CardioNerds FIT Trialist Dr. Jason Feinman, and then by expert faculty Dr. Biykem Bozkurt.

Dr. Bozkurt is the Mary and Gordon Cain Chair, Professor of Medicine, Director of the Winters Center for Heart Failure Research, and an advanced heart failure and transplant cardiologist at Baylor College of Medicine in Houston, TX. She is former President of HFSA, former senior associate editor for Circulation, current Editor-In-Chief of JACC Heart Failure. Dr. Bozkurt was the Vice Chair of the writing committee for the 2022 Heart Failure Guidelines.

The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Question #1

A 23-year-old man presents to his primary care physician for an annual visit. His father was diagnosed with idiopathic cardiomyopathy at 40 years of age. His blood pressure in clinic is 146/90 mmHg. He is a personal trainer and exercises daily, including both weightlifting and cardio. He denies any anabolic steroid use. He is an active tobacco smoker, approximately ½ pack per day. Review of systems is negative for symptoms. What stage of heart failure most appropriately describes his current status?

A

Stage A

B

Stage B

C

Stage C

D

Stage D

E

None of the above

Answer #1

The correct answer is A – Stage A of heart failure.

Overall, the ACC/AHA stages of HF were designed to emphasize the development and progression of disease. More advanced stages and progression are associated with reduced survival.

Stage A HF is where patients are “at risk for HF”, but without current or previous symptoms or signs of HF, and without structural/functional heart disease or abnormal biomarkers. At-risk patients include those with hypertension, cardiovascular disease, diabetes, obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or family history of cardiomyopathy.

Stage B HF is the “pre-heart failure” stage where patients are without current or previous symptoms or signs of HF but do have at least one of the following:

Structural heart disease (i.e., reduced left or right ventricular systolic function, ventricular hypertrophy, chamber enlargement, wall motion abnormalities, and valvular heart disease)

  • Evidence of increased filling pressures
  • Risk factors and increased natriuretic peptide levels or persistently elevated cardiac troponin in the absence of an alternate diagnosis

Stage C HF indicates symptomatic heart failure where patients have current or previous symptoms or signs of HF.

Stage D HF indicates advanced heart failure with marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize guideline-directed medical therapy.

Therapeutic interventions in each stage aim to modify risk factors (Stage A), treat risk and structural heart disease to prevent HF (stage B), and reduce symptoms, morbidity, and mortality (stages C and D).

Given this patient’s family and social histories, along with the clinical finding of elevated blood pressure, he is best classified as having Stage A, or at risk for HF. Were he to have signs of cardiac abnormalities on chest X-ray, ECG, biomarkers, or other testing, he would then be classified as having Stage B, or pre-heart failure.

Main Takeaway:

It is important to identify patients who are at risk for heart failure (Stage A HF) early to modify risk factors and prevent disease progression.

Guideline location:

Section 2.1, Figure 1, Table 3


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253. The 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure – Perspectives from Writing Committee Chair Dr. Paul Heidenreich08 Jan 202300:38:47

Join CardioNerds (Dr. Mark Belkin and Dr. Natalie Tapaskar) as they discuss the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure with Writing Committee Chair Dr. Paul Heidenreich. They discuss how one gets involved with a guideline writing committee, the nuts and bolts of the guideline writing process, pitfalls and utility of the term “GDMT,” background behind inclusion of “Value Statements,” potential omissions from the document, clinical uptake of recommendations, and anticipated changes for the next iteration. Audio editing by CardioNerds academy internPace Wetstein.

This discussion is a prelude to the CardioNerds Decipher The Guidelines Series designed to enhance understanding and uptake of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. We will be using high-impact, board-style, clinical vignette-based questions to highlight core concepts relevant to your practice. We will do so by releasing several short bite-sized Pods with one question per episode. Note that the cases used are hypothetical and created solely to illustrate core concepts.

This series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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252. Cardio-Oncology: Cardiac Amyloidosis with Dr. Omar Siddiqi06 Jan 202300:56:23

The importance of recognition and diagnosis of cardiac amyloidosis is at an all-time high due to its high prevalence and improved therapeutic strategies. Here we discuss what CardioNerds need to know about the manifestations, diagnosis, and management of transthyretin (ATTR) and light chain (AL) cardiac amyloidosis. Join Dr. Dan Ambinder (CardioNerds Cofounder), Dr. Dinu-Valentin Balanescu (Series Cochair, Chief Resident at Beaumont Health, and soon FIT at Mayo Clinic), and Dr. Dan Davies (Episode FIT Lead and FIT at Mayo Clinic) as they discuss cardiac amyloidosis with Dr. Omar Siddiqi, cardiologist at the Boston University Amyloidosis Center and program director for the general cardiovascular fellowship program at Boston University, a CardioNerds Healy Honor Roll Program. Episode notes were drafted by Dr. Dan Davies. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

Access the CardioNerds Cardiac Amyloidosis Series for a deep dive into this important topic.

This episode is supported by a grant from Pfizer Inc.

This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero AbreuDr. Dinu Balanescu, and Dr. Teodora Donisan

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes
  1. Cardiac amyloidosis is no longer considered a rare disease, especially transthyretin amyloidosis in older male patients with HFpEF and aortic stenosis.
  2. Echocardiogram is the “gate keeper” of cardiac imaging and provides initial evidence of amyloid infiltration, while cardiac MRI can help refine the presence of an infiltrative cardiomyopathy versus other causes of increased wall thickness.
  3. The most clinically important types of amyloid heart disease are transthyretin (ATTR) and light chain (AL) amyloidosis. The workup to differentiate these disorders includes a gammopathy panel to screen for the presence of potentially amyloidogenic light chains (serum and urine electrophoresis WITH immunofixation and serum free light chains), and cardiac scintigraphy with Technetium-99m-labeled bone-seeking tracers (PYP, DPD, etc.) to identify cardiac aTTR infiltration if the gammopathy panel is unrevealing.
  4. There is still a role for endomyocardial biopsy in the diagnosis of cardiac amyloidosis! All patients in whom there is concern for cardiac amyloidosis and gammopathy panel indicates the presence of monoclonal light chains should have a biopsy to obtain a tissue diagnosis of likely AL amyloidosis. Alternatively, an endocardial biopsy may prove valuable in patients who have confusing phenotypic features between amyloid types, such as a patient with abnormal monoclonal protein and positive PYP imaging.
  5. Be suspicious of heart failure patients that do not tolerate typical medications that lower heart rate. In the restrictive cardiomyopathy of cardiac amyloidosis, patients are reliant on higher heart rates to compensate for the inability to augment stroke volume.
  6. Be suspicious of amyloidosis in patients with recurrent left atrial thrombi despite anticoagulation.
Show notes CardioNerds Cardiac Amyloid, updated 1.20.21

1. What is cardiac amyloidosis and how common is it?

  • Cardiac amyloidosis is adisorder caused by misfolding of proteins into insoluble forms which are deposited into extracellular spaces of the heart, commonly causing a stiff and thick heart with progressive diastolic dysfunction with restrictive hemodynamics and ensuing heart failure.
  • The two most common types of amyloid protein that affect the heart are transthyretin (ATTR) and light chain (AL). Transthyretin amyloidosis is caused by a misfolded transporter protein produced by the liver, while light chain amyloidosis is caused by a misfolded light chain immunoglobulin produced by clonal plasma cells.
  • ATTR cardiac amyloidosis may be present in 6-17% of older patients with HFpEF and increased wall thickness, as well as in 4-16% of patients undergoing intervention for severe aortic stenosis. AL amyloidosis is much rarer, with a prevalence of about 12 cases per million persons per year.

2. What are some non-cardiac clues to the presence of cardiac amyloidosis?

  • Non-cardiac clinical clues for transthyretin amyloidosis (ATTR) include spinal stenosis, biceps tendon rupture, carpal tunnel syndrome (particularly when bilateral), and peripheral neuropathy.
    • Bilateral carpal tunnel syndrome may be present in up to 60% of ATTR-CA patients with over 40% having a history of biceps tendon rupture.
  • Non-cardiac clinical clues for light chain amyloidosis (AL) include renal disease (esp. nephrotic syndrome), macroglossia, autonomic and peripheral neuropathy, and periorbital purpura (racoon eyes).

3. What are common multimodality imaging features used for the diagnosis of cardiac amyloidosis?

  • For an in-depth discussion about the use of multimodality imaging in the diagnosis of cardiac amyloidosis, enjoy CardioNerds Episode #109 – Nuclear & Multimodality Imaging: Cardiac Amyloidosis.
  • Echocardiography (echo) is among the first test performed in patients for the diagnosis of cardiovascular symptoms and may provide initial clues to the diagnosis. Features of cardiac amyloidosis on echocardiogram include increased left ventricular wall thickness (>12 mm, classically concentric) with abnormal diastolic function, increased right ventricular free wall and interatrial septal thickness, as well as increased valve thickness. There may be a small pericardial effusion. Left ventricular strain is usually abnormal with a characteristic apical sparing pattern. A granular, or sparkling, appearance of the myocardium has been classically described but is poorly predictive.
  • Cardiac magnetic resonance (CMR) imaging is often used for differentiation of increased left ventricular wall thickness (infiltrative cardiomyopathies, hypertrophic cardiomyopathies, etc.) and in patients at increased risk of AL cardiac amyloidosis. Common features specific to CMR include abnormal myocardial nulling (blood pool nulls before the myocardium on inversion recovery sequences), elevated native T1 value, increased extracellular volume (ECV), and late gadolinium enhancement (classically in a diffuse, non-ischemic pattern).
  • Bone scintigraphy (technetium pyrophosphate [PYP] or DPD) is a nuclear imaging study used for the diagnosis of transthyretin amyloidosis. In the absence of an abnormal monoclonal protein, the sensitivity and specificity approach 100%, allowing for the “non-biopsy” diagnosis of ATTR-CA (specifically in the context of a negative gammopathy panel). The 2019 multi-society diagnostic guidelines recommend SPECT imaging be used in combination planar imaging for all cases to improve predictive characteristics.

4. How are heart failure and arrhythmias managed in patients with cardiac amyloidosis?

  • The mainstay of heart failure therapy in cardiac amyloidosis is loop diuretics with or without aldosterone antagonists. Spironolactone was shown to be effective in patients with a phenotype suggesting cardiac amyloidosis in a subgroup analysis of TOPCAT.
  • Patients often have poor tolerance of guideline directed medical therapies for heart failure, including beta blockers and calcium channel blockers, with ACEI/ARB/ARNI frequently limited by hypotension. The SGLT2 inhibitors appear to be tolerated in patients with cardiac amyloidosis but more research is needed to determine impact on cardiovascular outcomes.
  • Rate and rhythm control strategies for atrial arrhythmias can both be successful, but patients may be intolerant of medications. The risk of cardioembolic events in amyloid patients with atrial fibrillations is elevated, independent of CHA2DS2 -VASc score, and therefore all patients should be offered anticoagulation. Be suspicious of amyloidosis in patients with recurrent left atrial appendage thrombi despite anticoagulation.

5. What specific therapies can be used for transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis?

  • Tafamidis is a transthyretin stabilizer that inhibits tetramer dissociation and reduces amyloid deposition in extracellular tissue. It is the only FDA approved medication for transthyretin cardiac amyloidosis and was shown to be associated with reduced mortality and heart failure hospitalization compared to control in the ATTR-ACT trial.
  • Patisiran is a small interfering RNA that works as a gene silencer for ATTR protein production and is FDA approved for patients with polyneuropathy secondary to hereditary ATTR. Analysis of cardiac outcomes in the APOLLO trial suggest early stabilization of left ventricular wall thickness and reduction in natriuretic peptides in patients with features of concomitant cardiac involvement.
  • Specific therapies for AL amyloidosis are managed by hematologists with the goal of complete hematologic response to prevent further immunoglobulin production and amyloid deposition. These therapies typically include chemotherapy regimens (e.g. cyclophosphamide, bortezomib, dexamethasone [CyBorD]), daratumumab (an anti-CD38 antibody), with or without autologous stem cell transplantation.
  • There are many ongoing trials with novel therapies, with specific interest in treatments targeting removal of systemically deposited amyloid fibrils.
References
  1. Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2—evidence base and standardized methods of imaging. J. Nucl. Cardiol. 26, 2065–2123 (2019). Link
  2. Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization. J. Nucl. Cardiol. 27, 659–673 (2020). Link
  3. Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, Grogan M, Cheng RK. ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2021;3(4):488-505. Link
  4. Witteles RM, Liedtke M. AL Amyloidosis for the Cardiologist and Oncologist: Epidemiology, Diagnosis, and Management. JACC CardioOncol. 2019;1(1):117-130. Link
  5. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. Link
  6. Gertz, M. A., & Dispenzieri, A. (2020). Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. Jama, 324(1), 79-89. https://jamanetwork.com/journals/jama/fullarticle/2767867
  7. Cappelli, F., Zampieri, M., Fumagalli, C., Nardi, G., Del Monaco, G., Matucci Cerinic, M., Allinovi, M., Taborchi, G., Martone, R., Gabriele, M., Ungar, A., Moggi Pignone, A., Marchionni, N., Di Mario, C., Olivotto, I., & Perfetto, F. (2021). Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype. J Intern Med, 289(6), 831-839. https://pubmed.ncbi.nlm.nih.gov/33615623/
  8. Sperry, B. W., Hanna, M., Shah, S. J., Jaber, W. A., & Spertus, J. A. (2021). Spironolactone in Patients With an Echocardiographic HFpEF Phenotype Suggestive of Cardiac Amyloidosis: Results From TOPCAT. JACC Heart Fail, 9(11), 795-802. https://www.sciencedirect.com/science/article/pii/S2213177921003206?via%3Dihub
  9. Dobner, S., Bernhard, B., Asatryan, B., Windecker, S., Stortecky, S., Pilgrim, T., Gräni, C., & Hunziker, L. (2022). SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin. ESC Heart Fail. https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14188
Meet Our Collaborators

International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

251. CCC: Palliative Care and Shared Decision-Making in the CICU with Dr. Larry Allen01 Jan 202300:58:50

This episode is focused on Palliative Care and Shared Decision-Making in the CICU. In this episode, we learn about how the principles of palliative care and shared decision-making apply to our patients across the spectrum of cardiovascular care, especially in the cardiac intensive care unit. We discuss pivotal trials of specialty palliative care and decision aids in cardiology and how they might inform our practice to enhance patient quality of life and improve goal-concordant care. Finally, we discuss practical tips and communication strategies for how to engage patients about end-of-life decisions and topics that can be utilized from outpatient to inpatient to critical care settings.

“We need to help patients hope for the best and plan for the worst as time goes on.”

Dr. Larry Allen

Series co-chairs Dr. Eunice Dugan and Dr. Karan Desai, along with CardioNerds Co-founder Amit Goyal are joined by FIT lead, Dr. Sarah Chuzi. Dr. Chuzi is a Chicagoan and completed her internal medicine residency, cardiology fellowship, AHFTC fellowship and is now Assistant Professor at Northwestern University. Our episode expert is a true national leader in shared decision-making and palliative care in heart failure – Dr. Larry Allen, Medical Director of Advanced Heart Failure and the Co-Director of the Colorado Program for Patient-Centered Decisions at the University of Colorado School of Medicine. Audio editing by CardioNerds Academy InternDr. Christian Faaborg-Andersen.

The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark BelkinDr. Eunice DuganDr. Karan Desai, and Dr. Yoav Karpenshif.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes – Palliative Care and Shared Decision-Making in the CICU

1. “Much of what we do in cardiology is thinking about how to make people feel better (not just improving cardiac function or length of life). So, on a day-to-day basis we are really providing primary palliative care.” – Dr. Larry Allen

2. “Risk models in cardiology can only be so accurate… While risk models can give us some grounding, we also need to embrace the concept of uncertainty, and help patients understand that there are a variety of things that might happen to them, suggest some things they might plan for, and continue to iteratively come back to the patient and reevaluate what their options are.” – Dr. Larry Allen

3. “Our goal is to help people live happy, healthy, full lives. But, everyone dies. So understanding that death is a part of life and understanding how to help them make those transitions is critical” – Dr. Larry Allen

4. “Having good deaths is a part of good healthcare. We can’t ignore that. We can’t fight against it. We should embrace it. And we have the opportunity to do that.” – Dr. Larry Allen

5. We should still keep in mind the concept of medical futility and determining what options are reasonable for patients. Part of shared decision-making includes discussing what interventions would not be feasible or helpful with patients and families

Show notes – Palliative Care and Shared Decision-Making in the CICU

Notes drafted by Dr. Sarah Chuzi.

1. How are the basic principles of palliative care relevant to cardiology, and can you define the key concepts of shared decision-making, primary palliative care, specialty (or secondary) palliative care, and hospice care?

  • Throughout medicine, we confront the concepts of symptom control, difficult medical decision-making, and end-of-life. These are the principles of palliative care and they apply very easily across the spectrum of cardiology.
  • Shared decision-making is a meeting between two experts – the patient and the clinician. The patient is the expert in what’s important to them and their hopes, fears, values, goals, and preferences. The clinician is the expert in the medical aspects of care, including care that is not possible, care that might be high value, and the potential trade-offs and range of outcomes involved in a medical decision.
  • Palliative care is defined by the WHO – as care that deals with patient symptoms and quality of life. Increasingly, the terms primary and secondary palliative care are used. Primary palliative care is care provided by a general clinician (or cardiologist), while secondary palliative care is provided by a board-certified palliative care clinician.
  • Hospice care is really a health insurance benefit that provides a certain group of services (e.g. nurses, equipment) for patients who have terminal illness and less than 6 months to live.

2. What have we learned from existing trials looking at specialty palliative care in heart failure?

  • A few large trials (CASA, ENABLE, SWAP-HF, PAL-HF) of specialty palliative care interventions in heart failure have shown mixed results.
  • One of the reasons for this is the heterogeneity in patient and caregiver adjustment/symptoms at baseline.
  • Future trials will need to determine which patients and caregivers are really in need of interventions or assistance surrounding some of these issues. 

3. What are some strategies trainees can use to help elucidate a patient’s goals and values and engage in shared decision-making in high intensity, critical care situations?

  • Trying to determine (from the patient or family) whether the patient is a medical maximizer or minimizer can be helpful; i.e., what is his preference for aggressiveness of care.
  • Obtaining collateral from a patient’s power of attorney/next of kin/proxy about prior discussions regarding goals and values is valuable.
  • We should still keep in mind the concept of medical futility and determining what options are reasonable for patients. Part of shared decision-making includes discussing what interventions would not feasible or helpful with patients and families.

4. What is the role of decision aids in the process of deciding whether to pursue LVAD implantation?

  • Decision aids are unique from educational materials in that decision aids discuss alternative treatment options, including what life might be like if a certain treatment option is not pursued. Decision aids encourage patients to reflect on their values and then try to map the decisions in the context of their values.
  • The research group at the University of Colorado developed a decision aid to help patients and their families determine whether an LVAD would be an appropriate medical intervention for them. The decision aid is available online (patientdecisionaid.org) and includes a 26-minute video and an 8-page pamphlet. Currently, they are being disseminated nationally in a large implementation trial. The DECIDE-LVAD trial demonstrated that this decision aid improved values-choice concordance for patients considering LVAD therapy.

5. What are the benefits of hospice for patients with cardiac disease and how does hospice fall short?

  • It’s important to understand what hospice will and will not cover. The hospice benefit is a fixed payment per day. So, it’s important to consider what treatments might be covered and to discuss this with patients and families. 
  • For patients with advanced cardiac disease, coverage of inotropes is a common issue that we encounter. It’s important to prepare patients for the fact that inotropes may not be accepted in a given hospice program.
  • Additionally, sometimes clinicians struggle with how to continue to provide care for patients who enter hospice as we try to navigate how to stay involved in their care while respecting their wishes to be at home and not necessarily come to clinic.
References – Palliative Care and Shared Decision-Making in the CICU

Rogers JG, Patel CB, Mentz RJ, et al. The palliative care in heart failure (PAL-HF) randomized, controlled clinical trial. 2017. J Am Coll Cardiol, 70(3): 331-341.

Allen LA, Mcilvennan CK, Thompson JS, et al. Effectiveness of an intervention supporting shared decision making for destination therapy left ventricular assist device: the DECIDE-LVAD randomized clinical trial. 2018. JAMA Intern Med, 178(4): 520-529.

Warraich HJ, Patel CB, Kochar A, Rogers JG, Patel MR. Incorporating shared decision making and palliative care into cardiogenic shock pathways. 2010. J Am Coll Cardiol, 74(4): 501-502.

Chuzi S, Khan SS, Pak ES. Primary palliative care education in advanced heart failure and transplant cardiology fellowships. 2021. J Am Coll Cardiol, 77(4): 501-505.  

250. ACHD: Partial Anomalous Pulmonary Venous Return (PAPVR) with Dr. Ian Harris26 Dec 202200:43:28

Partial anomalous pulmonary venous return refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. This causes left to right shunting which may have hemodynamic and therefore clinical significance, warranting repair in some patients.

Join CardioNerds to learn about partial anomalous pulmonary venous return! Dr. Dan Ambinder (CardioNerds co-founder), Dr. Josh Saef (ACHD FIT at the University of Pennsylvania and ACHD Series co-chair), and Dr. Tripti Gupta (ACHD FIT at Vanderbilt University and episode lead) learn from Dr. Ian Harris (Director of the Adult Congenital Heart Disease program at University of California, San Francisco). Audio editing by CardioNerds Academy Intern, student doctor Shivani Reddy.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh SaefDr. Agnes Koczo, and Dr. Dan Clark.

The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more

Disclosures: None

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Pearls – Partial Anomalous Pulmonary Venous Return (PAPVR)
  1. What is partial anomalous pulmonary venous return (PAPVR)?
    • PAPVR refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. Often, this means one or more pulmonary veins empty into the right atrium or a systemic vein such as the superior vena cava or inferior vena cava. Physiologically, this produces a left-to-right shunt, allowing for already-oxygenated blood to recirculate into the lungs and result in excessive pulmonary blood flow. 
  2. What are the clinical features of PAPVR?
    • Diagnosis is usually incidental on a cross sectional imaging such as CTA or CMR.
    • The most common associated lesion is an atrial-level defect.
    • It is unusual for a single anomalous pulmonary venous connection of only 1 pulmonary lobe to result in significant shunting.
    • Patients with a significant degree of left to right shunting may have right heart dilatation or symptoms of dyspnea on exertion.
  3. When are some strategies for managing patients with PAPVR?
    • A surgical correction is recommended for patients with PAPVR when functional capacity is impaired and RV enlargement is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (aka: ratio of pulmonary flow (Qp) to systemic flow (Qs) is > 1.5:1), PA systolic pressure is less than 50% systemic pressure and pulmonary venous resistance is less than one third of systemic venous resistance.
    • Surgical repair involves intracaval baffling of the left atrium (Warden procedure) or direct reimplantation of the anomalous pulmonary vein into the left atrium.
    • Pregnancy is well tolerated in patients with repaired PAPVR. In patients with unrepaired lesion who may have right sided heart dilatation and/or pulmonary hypertension, preconception evaluation and counseling should address how pregnancy may affect mother’s and fetus’s health.
    • Antibiotic prophylaxis for infective endocarditis is typically not needed unless patients are less than 6 months from recent surgery, have residual defect at the patch margin or prior history of infective endocarditis.
Show notes – Partial Anomalous Pulmonary Venous Return (PAPVR)

Notes (drafted by Dr. Tripti Gupta):

1. What is partial anomalous pulmonary venous return?

  • Anatomically, partial anomalous pulmonary venous return refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. Often, this means one or more pulmonary veins empty into the right atrium or a systemic vein such as the superior vena cava (SVC) or inferior vena cava (IVC).
    • Physiologically, this produces a left-to-right shunt, allowing for already-oxygenated blood to recirculate into the lungs and result in excessive pulmonary blood flow. 
    • If all pulmonary veins from both lungs drain to an anomalous site or in an abnormal fashion, then it is identified as a total anomalous pulmonary venous return (TAPVR). Patients with TAPVR often require surgical intervention in childhood.
    • A bit of a nuance in terminology – partial anomalous pulmonary venous return (PAPVR) vs. partial anomalous pulmonary venous connection (PAPVC), requires some explanation. The suffix “return” refers to vessels returning to a chamber (ex: pulmonary vein returns to morphological left atrium after blood functionally mixes with systemic venous return or is redirected via an atrial septal defect) vs. “connection” implies abnormal anatomic attachments. 

2. How does this happen? What is the embryological explanation for PAPVR?

  • We know that the pulmonary veins originate from the posterior aspect of the left atrium. Meanwhile, the lung buds that arise from the lung parenchyma canalize as a vessel and gradually connect to the developing pulmonary veins.
  • Some theories say that the lung buds are initially enmeshed in the splanchnic plexus which drains into the cardinal and umbilical vitelline veins (systemic venous system). By week 4 of gestation, the pulmonary veins from the left atrium connects with the superior portion of the splanchnic plexus to form the pulmonary plexus and ultimately loses its connection with the splanchnic plexus.
  • The pulmonary vein is then supposed to divide into 4 branches, 2 on right and 2 on left, each with an orifice at the left atrium. Failure of one or more of the pulmonary veins to separate from the systemic venous systemic results in PAPVC/TAPVC.

3. What are some major clinical findings in PAPVR?

  • PAPVR is typically an incidental diagnosis on CT or MRI in asymptomatic patients when these scans are done for another reason. Many patients with PAPVR may remain asymptomatic throughout childhood and adult life.
  • Physiological changes may depend on degree of left to right shunt, number of veins involved, their sites of connection and associated lesions.
  • 80% of anomalous connections are of the right sided pulmonary veins and 20% affect the left sided pulmonary veins. The most common variants include:
    • Right upper pulmonary vein or right middle pulmonary vein to SVC, azygos vein, or right atrium. This variant is the most common and can be often associated with a sinus venosus defect.
    • Right pulmonary veins to IVC, usually via a single trunk draining caudally and connecting to the IVC near the diaphragm. This variant is sometimes known as Scimitar syndrome. When you look at the descending trunk connecting the right venous return to the right atrium on x-ray or fluoroscopy, it has a crescent-like shape, like a Turkish sword from the Ottoman Empire or a scimitar, hence the name Scimitar syndrome.
    • Left pulmonary vein(s) to the innominate vein via a vertical vein.
    • Left pulmonary veins to the coronary sinus.
  • If more that 50% of a person’s pulmonary venous return drains anomalously to the right side of the heart, there may be right heart enlargement and presentation of symptoms such as dyspnea on exertion earlier in life.
  • Physical exam findings may include prominent right ventricular impulse, a systolic ejection murmur at the left upper sternal border, split S2, and possibly a mid-diastolic rumble. In the absence of an ASD, these findings may not be obvious.
  • On ECG, a RBBB morphology, RAD or first-degree heart block is associated with right ventricular volume enlargement.
  • On echocardiogram, RV enlargement without left heart dysfunction should raise suspicion for anomalous pulmonary venous connection. Other hints can include the presence of a sinus venosus ASD, secundum ASD or RV enlargement that is significantly large for a small ASD/PFO. While left sided pulmonary veins can be visualized on the suprasternal view of transthoracic echocardiogram, right sided veins are more challenging on TTE. A TEE can be used to identify the site and drainage of pulmonary veins.
  • A right heart catheterization is useful to identify the presence and etiology of pulmonary hypertension and quantify flows in pulmonary and systemic system and presence of a shunt. Selective angiography of the right and left pulmonary arteries can confirm the presence and course of pulmonary veins on levophase.
  • A gated cardiac CTA or CMR is helpful and recommended for definitive diagnosis. A CTA offers higher spatial resolution than a CMR at the cost of radiation and iodinated contrast exposure. A CMR offers high resolution for defining vascular anatomy, quantifying chamber dimensions, estimate shunt burden and degree of stenoses using flow quantification techniques. In addition, respiratory-gated 3D whole heart imaging or MRA can be used for multiplanar reconstruction and aid in perioperative planning.
  • Patients with TAPVR present with cyanosis at birth and need urgent surgical correction.

4. What conditions are associated with PAPVR?

  • 80% of patients with PAPVR lesion may have an associated atrial level defect. In particular, a superior sinus venosus defect is frequently associated with right sided anomalous pulmonary venous connections.
  • Other associated cardiac lesions include conotruncal abnormalities such as Tetralogy of Fallot or double outlet right ventricle, ventricular septal defects, and valvular abnormalities such as pulmonary stenosis, mitral or aortic stenosis or atresia and aortic arch anomalies.
  • Anomalous pulmonary venous connections can also be seen in patients with heterotaxy syndrome, where mispositioned organs such as the heart, lungs, stomach, intestines, and liver may be in nonstandard locations within the chest and abdomen.

5. What are some main considerations for surgical repair for PAPVR?

  • Cross sectional imaging such as CTA or CMR may be helpful to identify pulmonary venous connections and other extracardiac vascular anatomy.
  • It is unusual for a single anomalous pulmonary venous connection of only 1 pulmonary lobe to result in a sufficient volume load to justify surgical repair. However, if a patient has symptoms referable to the shunt, there is >1 anomalous vein, and a moderate or large left-to-right shunt, then surgical repair is associated with a reduction in RV size and PA pressure. Pulmonary hypertension is a risk for adverse outcomes with surgery.
  • A hemodynamic assessment with may help identify pressures, saturations, and degree of shunting.
  • A surgical correction is recommended for patients with PAPVR when functional capacity is impaired and RV enlargement is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (aka: ratio of pulmonary flow (Qp) to systemic flow (Qs) is > 1.5:1), PA systolic pressure is less than 50% systemic pressure and pulmonary venous resistance is less than one third of systemic venous resistance.
  • Surgery can involve intracaval baffling of the left atrium (warden procedure) or direct reimplantation of the anomalous pulmonary vein directly into the left atrium.
  • Repair of PAPVR may be considered at the time of closure of sinus venosus or other ASD.
  • Transcatheter therapies are an area of ongoing innovation.
References – Partial Anomalous Pulmonary Venous Return (PAPVR)
  1. Gatzoullis MA, Webb GD, Daubeney PEF. Chapter 37: Partial Anomalous Pulmonary Venous Connections and Scimitar Syndrome In: Diagnosis and Management of Adult Congenital Heart Disease. 3rd ed. Elsevier Health Sciences; 2017: 354-361
  2. Kao CC, Hsieh CC, Cheng PJ et al. Total Anomalous Pulmonary Venous Connection: From Embryology to a Prenatal Ultrasound Diagnostic Update. J Med Ultrasound. Sep 2017; 25 (3): 130-137
  3. Pendela VS, Tan BEX, Chowdhury M, Chow M. Partial Anomalous Pulmonary Venous Return Presenting in Adults: A Case Series with Review of Literature. Cureus. 2020 Jun 1; 12 (6): e8388
  4. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. Apr 2 2019;139(14):e698-e800.
Meet Our Collaborators!

Adult Congenital Heart Association
Founded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers

https://www.achaheart.org/

CHiP Network

The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information.

https://thechipnetwork.org/

Heart University
Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/

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249. CardioNerds Rounds: Challenging Cases – HFpEF Diagnosis and Management with Dr. Jane Wilcox18 Dec 202200:39:22

It’s another session of CardioNerds Rounds! In these rounds, Dr. Loie Farina (Advanced Heart Failure and Transplant Fellow at Northwestern University) joins Dr. Jane Wilcox (Chief of the Section of Heart Failure Treatment and Recovery at Northwestern University) to discuss the nuances of HFpEF diagnosis and management. Dr. Wilcox is also the Associate Director of the T1 Center for Cardiovascular Therapeutics in the Bluhm Cardiovascular Institute and Director of the Myocardial Recovery Clinic at Northwestern University. Dr. Wilcox is a prolific researcher, clinician, and thought leader in Heart Failure and we are honored to have her on CardioNerds Rounds! Notes were drafted by Dr. Karan Desai. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes

Speaker disclosures: None

Challenging Cases – Atrial Fibrillation with Dr. Hugh Calkins

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Show notes – HFpEF Diagnosis and Management

Case #1 Synopsis:

A woman in her 80s with a history of HFpEF presented with worsening dyspnea on exertion over the course of a year but significantly worsening over the past two months. Her other history includes prior breast cancer with chemotherapy and radiation therapy, permanent atrial fibrillation with AV node ablation and CRT-P, and CKD Stage III. She presented for an outpatient RHC with exercise to further characterize her HFpEF. Her echo showed normal LV size, no LVH, LVEF of 50%, decreased RV systolic function, severe left atrial enlargement, significantly elevated E/e’ and mild MR. Right heart catheterization showed moderately elevated bi-ventricular filling pressures at rest but with passive leg raise and Stage 1 exercise the wedge pressure rose significantly. We were asked to comment on management.

Case #1 Takeaways

  1. Amongst the things that were discussed were the role of specific therapies in symptomatic patients with HFpEF. In patients with HFpEF and documented congestion, they will require diuretic therapy for symptomatic relief. But in addition to diuretic therapy, we discussed starting HFpEF-specific therapies. Amongst, those specific therapies mineralocorticoid receptor antagonist (MRA) and sodium-glucose co-transporter 2 (SGLT2) inhibitor.
  2. In multiple trials that have included patients with HFPEF, SGLT2i have reduced the risk of hospitalization. This includes the EMPEROR-PRESERVED Trial (see the CardioNerds Journal Club discussion on the trial) in which nearly 6000 patients with NYHA Class II-IV symptoms, EF > 40% and elevated NT-proBNP with a prior HF hospitalization within the past 12 months were randomized to Empagliflozin or placebo. The primary outcome – death from CV causes or hospitalization for Heart Failure – was significantly lower in the SGLT2i arm (13.8% vs 17.1%, 95% CI 0.69-0.90, P <0.001).
  3. In regards to MRA, an important trial was the TOPCAT trial which randomized patients with symptomatic HF and LVEF > 45% to receive either spironolactone or placebo. The primary endpoint (death from CV cause, aborted cardiac arrest, or hospitalization for HF) was not statistically different between treatment arms. Of note, however, there were concerns for regional differences which is outlined well in this NEJM Evidence piece.

Case #2 Synopsis:

A woman in her 70s with history of hypertension, obesity, and COPD presented to the office for an evaluation of dyspnea. She had noted two years of dyspnea with moderate exercise and had developed lower extremity swelling. She had an echocardiogram that showed normal LV size and function, no LVH, global longitudinal strain at -21% (normal), grade 1 diastolic dysfunction and mild left atrial enlargement. Amongst the initial questions we were asked was how would we approach the diagnostic evaluation of her dyspnea?

Case #2 Takeaways

  1. There were several things we covered with Dr. Wilcox regarding this patient. One of the things we discussed was whether the patient has HFpEF and then concomitantly, if we suspect and confirm HFpEF, attempting to elucidate an etiology for the patient’s HFpEF.
  2. There are diagnostic scores, such as the H2FPEF score that can estimate the probability of HFpEF versus a non-cardiac cause of a patient’s symptoms. There are limitations to the scoring systems – including echocardiographic parameters that may not be available at point of care or prone to error – but it can refine a clinician’s pre-test probability for HFpEF.
  3. Amongst other testing, an important note is that coronary artery disease is common in patients with HFpEF and may be a potentially treatable and reversible cause of HFpEF. Thus, evaluation for ischemia is recommended and given a Class IIa recommendation in the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure.
References – HFpEF Diagnosis and Management
  1. Anker SD, Butler J, Filippatos G et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. doi: 10.1056/NEJMoa2107038. Epub 2021 Aug 27. PMID: 34449189.
  2. Heidenreich P, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022 May, 79 (17) e263–e421.
  3. Pfeffer MA, Claggett B, Assmann SF et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Circulation2015; 131:34-42.25406305
  4. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med2014; 370:1383-1392. 10.1056/NEJMoa1313731 24716680.
  5. Reddy YNV, Carter RE, Obokata M et al. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646. PMID: 29792299; PMCID: PMC6202181.
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374. Case Report: Unraveling the Mystery – When Childhood Chest Pain Holds the Key to a Genetic Heart Condition – Wayne State University31 May 202400:28:27

This case report explores the intricacies of familial hypercholesterolemia (FH), delving into its genetic basis, atherosclerotic cascade, and early-onset cardiovascular complications. It examines established diagnostic criteria and emphasizes personalized management, including statins, novel therapies, and lifestyle modifications.

CardioNerds cofounders (Drs. Amit Goyal and Danial Ambinder) join Dr. Irfan Shafi, Dr. Preeya Prakash, and Dr. Rebecca Theisen from the Wayne State University/DMC and Central Michigan University at Campus Martius in Downtown Detroit for some holiday ice-skating! They discuss an interesting pediatric case (see case synopsis below). Dr. Luis C Afonso provides the Expert CardioNerd Perspectives & Review segment for this episode. Audio editing by CardioNerds academy internPace Wetstein.

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Case Synopsis

FH, a 9-year-old female with no previous medical history, recently moved back to the US from Iraq. She presented to establish care and discuss new-onset chest pain and dyspnea. A systolic ejection murmur was noted during her initial visit to the pediatrician, prompting cholesterol testing and a cardiology referral. Testing revealed, alarming cholesterol levels (Total Cholesterol: 802 mg/dL, LDL: 731 mg/dL, Triglycerides: 123 mg/dL) prompted concern for cardiac involvement.

Due to persistent symptoms, FH was transferred to Children’s Hospital of Michigan. Despite normal findings on EKG and chest x-ray, a 2/6 systolic murmur was noted. She was discharged with a cardiology clinic follow-up.

However, two days later, FH experienced severe chest pain at rest, sweating, and difficulty breathing. She was transported to Children’s Hospital again, and her troponin level measured 3000, and her total cholesterol was 695 mg/dL. An echocardiogram revealed valvar and supravalvar aortic stenosis, necessitating collaboration between Pediatric and Adult cardiology teams.

CTA thorax revealed severe supravalvular stenosis, a hypoplastic right coronary artery, and significant coronary artery obstructions. Diagnostic cardiac catheterization confirmed severe aortic stenosis and coronary artery disease, leading to the decision for surgical intervention.

FH underwent the Ross operation, left main coronary artery augmentation, and right coronary artery reimplantation. Intraoperatively, atherosclerotic plaques were observed in multiple cardiac structures.

FH’s recovery was uneventful, discharged on a regimen including Atorvastatin, Ezetimibe, evolocumab, and antiplatelet therapy. Persistent high LDL levels required regular plasmapheresis. Plans for evaluations in Genetics, Lipid Clinic, Endocrine, and Gastroenterology were made, potentially leading to a liver transplant assessment. Given the severity of her condition, a heart/liver transplant might be considered in the future.

Conclusion:

This case of FH highlights the complex presentation of severe aortic stenosis and coronary artery disease in a pediatric patient. Urgent diagnosis, interdisciplinary collaboration, and aggressive management were crucial. The case underscores the importance of comprehensive care for pediatric patients with rare cardiac conditions, emphasizing collaboration between specialties for optimal outcomes and long-term well-being.

Case Media Pearls – Familial Hypercholesterolemia
  • Mutations in LDLR, ApoB, or PCSK9 genes disrupt LDL-C clearance, leading to a cascade of events culminating in accelerated atherosclerosis and early-onset cardiovascular complications (e.g., CAD, aortic stenosis, PAD, stroke).
  • Diagnosis of familial hypercholesterolemia relies on a combination of clinical features (xanthomas, corneal arcus, high LDL-C), family history, and genetic testing guided by established criteria like DCLN or NLA recommendations.
  • Supravalvular aortic stenosis, while common in many congenital cases, should raise suspicion of homozygous familial hypercholesterolemia in the setting of extensively elevated LDL and unexpected coronary artery disease.
  • A multidisciplinary approach, including involvement of pediatric and adult cardiology teams, lipid specialists and cardiothoracic surgeons, should be involved in the overall evaluation and management of these patients, both at initiation of diagnosis, and in an outpatient setting.
  • In patients with FH, it is important to delineate between homozygous and heterozygous manifestations, as this can have extensive implications on treatment, management and the overall clinical prognosis and further disease sequelae that the patient may experience.
References – Familial Hypercholesterolemia
  1. Shah, N. (2020). Familial hypercholesterolemia: Early diagnosis and treatment is key for cardiovascular prevention.Cleveland Clinic Journal of Medicine, 87(5), 109-120. https://pubmed.ncbi.nlm.nih.gov/23469913/
  2. Turgeon, R. D., Barry, A. R., & Pearson, G. J. (2023). Familial hypercholesterolemia: Review of diagnosis,screening, and treatment. American Journal of Health-System Pharmacy, 80(11), 917-929.https://pubmed.ncbi.nlm.nih.gov/26796832/
  3. Collins, R. T. (2018). Cardiovascular disease in Williams syndrome. Current Opinion in Pediatrics, 30(5), 609-615. https://www.ncbi.nlm.nih.gov/books/NBK544278/
  4. Collins, R. T., Kaplan, P., Somes, G. W., & Rome, J. J. (2010). Long-term outcomes of patients with cardiovascular abnormalities and Williams syndrome. American Journal of Cardiology, 105(6), 874-878.https://pubmed.ncbi.nlm.nih.gov/30045083/
  5. Honjo, R. S., Monteleone, V. F., Aiello, V. D., Wagenfuhr, J., Issa, V. S., Pomerantzeff, P. M. A., Furusawa, E. A.,Zanardo, E. A., Kulikowski, L. D., Bertola, D. R., & Kim, C. A. (2022). Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases. American Journal of Medical Genetics. Part A,188(3), 676-682. https://www.ncbi.nlm.nih.gov/books/NBK544278/
  6. Pham, P. P., Moller, J. H., Hills, C., Larson, V., & Pyles, L. (2009). Cardiac catheterization and operative outcomes from a multicenter consortium for children with Williams syndrome. Pediatric Cardiology, 30(1), 9-14.https://pubmed.ncbi.nlm.nih.gov/19052807/
  7. Olsen, M., Fahy, C. J., Costi, D. A., Kelly, A. J., & Burgoyne, L. L. (2014). Anaesthesia-related haemodynamic complications in Williams syndrome patients: A review of one institution’s experience. Anaesthesia and Intensive Care, 42(6), 619-624. https://pubmed.ncbi.nlm.nih.gov/25233176/
  8. Harada-Shiba, M., Arai, H., Ishigaki, Y., Ishibashi, S., Okamura, T., Ogura, M., Dobashi, K., Nohara, A., Bujo, H.,Miyauchi, K., Yamashita, S., & Yokote, K. (2018). Guidelines for diagnosis and treatment of familial hypercholesterolemia 2017. Journal of Atherosclerosis and Thrombosis, 25(8), 751-770.https://pubmed.ncbi.nlm.nih.gov/29877295/
  9. Alnouri, F., & Santos, R. D. (2022). New trends and therapies for familial hypercholesterolemia. Journal of Clinical Medicine, 11(22), 6638. https://pubmed.ncbi.nlm.nih.gov/36431115/
248. Cardiovascular Genomics: Frontiers in Clinical Genetics in Cardiovascular Prevention with Dr. Pradeep Natarajan08 Dec 202200:59:50

As the burden of cardiovascular disease increases in the United States, the importance of enhanced screening tools, early risk prediction, and prevention strategies grows. Novel risk scoring methods, including polygenic risk scores (PRS), may help identify patients that benefit from early intervention and risk modification. In this episode, we discuss how a PRS is calculated, how to incorporate a PRS into clinical practice, and current barriers to the equitable implementation of risk scores. In terms of frontiers in clinical genetics we also discuss the burgeoning field of pharmacogenetics and how pharmacogenetics may be used to identify responders and non-responders to certain therapies.

Join CardioNerds Dr. Jessie Holtzman (CardioNerds Academy Chief and Chief Resident and soon FIT at UCSF), Dr. Alaa Diab (CardioNerds Academy Fellow and Medicine Resident at GBMC), and student doctor Hirsh Elhence (CardioNerds Academy Intern and medical student at USC Keck School of Medicine) as they discuss frontiers in clinical genetics with Dr. Pradeep Natarajan (Director of Preventive Cardiology, Massachusetts General Hospital). Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.

This episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.

This CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References

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Pearls – Frontiers in Clinical Genetics in Cardiovascular Prevention
  1. For common diseases like coronary artery disease, rare mutations may confer a several-fold increased risk of disease – for instance, in familial hypercholesterolemia, a single rare mutation may confer as much as a three-fold increase in risk of coronary artery disease. However, for most common diseases, the overall cumulative impact of several common genetic variants may be greater than that of a monogenetic trait.
  2. Family history is a particularly coarse predictor of CV risk, highlighting the need for polygenic risk scores. In particular, younger patients with borderline cardiovascular risk may benefit from the use of a polygenic risk score in the determination of their overall cardiovascular risk profile.
  3. A polygenic risk score (PRS) is a weighted sum of several risk-conferring alleles. The weight assigned to an allele is determined by the strength of the association between the allele and CV disease, as determined by genome-wide association studies (GWAS).
  4. The data used for genome-wide associated studies in cardiovascular disease have historically included populations primarily of European ancestry. However, more data is being collected from diverse patient cohorts to increase the external validity and broader applicability of such studies.
  5. Pharmacogenetic polygenic risk scores may be used to predict drug efficacy and toxicity, as well as to identify biologically plausible drug targets for clinical trial design.
Show notes – Frontiers in Clinical Genetics in Cardiovascular Prevention

What is a polygenic risk score (PRS)?

  • Monogenic conditions are those in which a variant in a single gene causes a pathological phenotype. For example, familial hypercholesterolemia is often the result of a mutated allele in the LDL receptor gene.
  • In contrast, polygenic risk suggests that there are variants in multiple genes that all confer risk independently, each with a small individual effect size. By aggregating many variants, a risk score may be able to provide an estimate as to the degree of one’s risk of cardiovascular disease.
  • By comparing the allele frequencies of genes between patients with and without cardiovascular disease, risk-conferring alleles may be identified. These studies are called genome-wide association studies (GWAS). From GWAS, PRS can then be calculated by aggregating several risk-conferring alleles.

What is the clinical utility of PRS?

  • Current uses of PRS
    • Family history is a coarse predictor of CV disease. The addition of a PRS to a risk assessment may improve the clinician’s ability to risk stratify patients.
    • Calculating PRS can help identify patients who need early intervention, even in the absence of traditional risk factors (such as hypercholesterolemia or diabetes mellitus). For example, imagine a patient in the top 20th percentile for polygenic risk with a relatively normal LDL. Despite the lack of hyperlipidemia, some evidence may suggest that a statin or aggressive lifestyle modification would lower CV risk in this patient.
    • In particular, for younger patients with borderline CV risk (as measured by traditional risk factors such as blood pressure, age, etc.), a high PRS might promote aggressive lifestyle modification or pharmacotherapy.
  • Potential future uses
    • Pharmacogenomics – Understanding a patient’s genotype may help identify responders and non-responders to certain medications. For example, CYP2C19 is an enzyme that aids in the activation of Clopidogrel. Therefore, patients with a mutation in CYP2C19 may not respond as robustly to Clopidogrel and therefore alternate pharmacotherapy would be recommended.
  • What are the barriers to equity?
    • Historically, GWAS studies largely enrolled patients of European ancestry. As such, the external validity of PRS outside of populations of European descent has been questioned. The NIH has prioritized capturing data from more diverse cohorts, associated with an increase in databases including patients of more varied ancestry.
    • The availability of direct-to-consumer genome sequencing kits may make calculating PRS more feasible for the broader population. However, such tests remain limited in their utility without interpretation by genetic counselors or cardiovascular geneticists.
References – Frontiers in Clinical Genetics in Cardiovascular Prevention
  1. Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, Kathiresan S. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018 Sep;50(9):1219-1224. doi: 10.1038/s41588-018-0183-z. Epub 2018 Aug 13. PMID: 30104762; PMCID: PMC6128408.
  2. O’Sullivan JW, Raghavan S, Marquez-Luna C, Luzum JA, Damrauer SM, Ashley EA, O’Donnell CJ, Willer CJ, Natarajan P; American Heart Association Council on Genomic and Precision Medicine; Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease. Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2022 Aug 23;146(8):e93-e118. doi: 10.1161/CIR.0000000000001077. Epub 2022 Jul 18. PMID: 35862132.
247. CCC: Biventricular Failure and the Use of VA-ECMO with Dr. Ann Gage05 Dec 202200:54:56

In this episode, we discuss the utility of veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) for the temporary management of biventricular failure and cardiogenic shock requiring full cardiopulmonary support. Here, we define the types of ECMO and describe the unique physiology of this mechanical circulatory support platform, as well as review the potential complications and management strategies. Most notably, we highlight indications for and contraindications to the use of VA-ECMO and review the importance of patient selection.  Lastly, we discuss de-escalation and de-cannulation strategies for patients on VA-ECMO as a bridge to recovery.

Join Dr. Amit Goyal (CardioNerds Cofounder and FIT at Cleveland Clinic), Dr. Yoav Karpenshif (Series Co-chair and FIT at University of Pennsylvania), and Dr. Megan Burke (Episode FIT Lead and FIT at University of Pennsylvania) as they learn about how to care for some of our sickest patients from Dr. Ann Gage, interventional and critical care cardiologist at Centennial Heart. At the beginning of the episode, enjoy a message from the very first CardioNerds Scholar, Dr. Katie Vaughan (Chief Resident and soon Cardiology Fellow at BIDMC). Episode notes were developed by Dr. Megan Burke. Audio editing by CardioNerds Academy Intern, Hirsh Elhence.

The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark BelkinDr. Eunice DuganDr. Karan Desai, and Dr. Yoav Karpenshif.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

Pearls • Notes • References • Production Team

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Pearls and Quotes – Biventricular Failure and the Use of VA-ECMO
  1. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a form of temporary mechanical circulatory support that can do the work of both the heart and lungs.
  2. The ECMO circuit is a narcissist, i.e. cannulas are named in reference to the circuit and not the patient (“inflow” vs “outflow”).
  3. The decision to utilize ECMO should be made by a multidisciplinary shock team and patient selection is KEY!
  4. ECMO physiology rule #1: VA-ECMO increases LV afterload
  5. Patients on VA-ECMO should be monitored with a PA catheter and an arterial line in the right arm
Show notes – Biventricular Failure and the Use of VA-ECMO

Notes drafted by Dr. Megan Burke.

1. What is ECMO and what are the different types?

  • Extracorporeal membrane oxygenation (ECMO) is a temporary form of mechanical life support that comes in two flavors: veno-arterial, or “VA” and veno-venous, or “VV.” 
  • VV-ECMO supports extracorporeal gas exchange in the setting of acute respiratory failure
  • VA-ECMO provides full circulatory support in addition to gas exchange, doing the work of both the heart and lungs. 

2. What are the components and “anatomy” of the VA-ECMO circuit?

  • The circuit is made up of the following major components:
    • Venous (inflow) cannula
    • Centrifugal Pump
    • Oxygenator (also responsible for CO2 removal)
    • Arterial (outflow) cannula
  • The cannulas are named in reference to the ECMO circuit, not the patient. Dr. Gage suggests that we think of the ECMO circuit (and mechanical circulatory support in general) as narcissistic, i.e. flow is always in reference to the device.
  • Gas exchange happens in the oxygenator. In the oxygenator blood flows through thin filaments that allow for diffusion of oxygen and carbon dioxide. Gas flows in the opposite direction of blood flow to maximize diffusion through the countercurrent effect. Oxygenation is determined by rate of blood flow through the oxygenator and FiO2 delivered. Carbon dioxide removal is determined by rate of countercurrent gas flow, referred to as the sweep speed.

3. What are the indications for VA-ECMO?

  • VA-ECMO is utilized in the setting of severe refractory cardiogenic shock (in the setting of left, right, or biventricular failure) and cardiac arrest. It is a temporary mechanical circulatory support platform, and should be used as a bridge to recovery or a more durable therapy (i.e. durable mechanical support or transplant). Due to lack of randomized data, there are no consensus guidelines for the use of VA-ECMO, and the decision to implement it should be made as part of a multidisciplinary cardiogenic shock team. Common indications include cardiogenic shock, refractory ventricular arrhythmias, massive pulmonary embolism, cardiac arrest, and failure to wean from cardiopulmonary bypass during surgery. The absolute and relative contra-indications to ECMO vary by institution.
  • Given the high mortality rates for patients on VA-ECMO (hospital mortality is approximately 50%, and 6-month survival is as low as 30%), patient selection is key. There are multiple pre VA-ECMO risk factors independently associated with poor outcomes. These include older age, female sex, higher body mass index, and markers of increased severity of illness including laboratory evidence of end-organ dysfunction and longer duration of mechanical ventilation.

4. What are the pathophysiological consequences of VA-ECMO and how do we monitor and treat them?

  • The goal of VA-ECMO is to provide perfusion, however unlike other forms of mechanical circulatory support, it is NOT supporting the heart’s ability to pump blood. In fact, VA-ECMO increases left ventricular afterload, because blood enters the aorta from the outflow cannula somewhere between the aortic root and the diaphragm (depending on cannulation strategy). This creates increased aortic pressure and increased left ventricular volume and afterload, which can lead to pulmonary edema and worsened myocardial demand. In the most extreme cases, the aortic pressure can exceed the left ventricular systolic pressure, thereby preventing blood from ejecting from the LV. This can lead to stasis, thrombus formation, and strokes. For this reason, echocardiography is used frequently to monitor LV ejection. One key marker is the opening of the aortic valve with every beat.
  • Furthermore, hemodynamic monitoring with a pulmonary artery catheter and a RIGHT radial arterial line is essential for management of patient’s on ECMO.
    • The PA catheter allows for an estimation of the filling pressures. Of note, the mixed venous O2 cannot be used to estimate cardiac output when a patient is on VA-ECMO, but low levels still do correlate with poor tissue perfusion and worse outcomes.
    • In general, it is essential to have an arterial catheter in a patient on VA-ECMO to monitor for arterial pulsatility, which is a surrogate for the contribution of the patient’s heart to perfusion.
    • Specifically, a RIGHT radial arterial line is key in these patients because blood from it originates the brachiocephalic artery, which is the closest branch in the aortic arch to the coronary arteries and great vessels of the aortic arch and therefore best estimates the oxygen content in the coronaries and brain. This is key because when a patient is on peripheral VA-ECMO, oxygenated blood arrives to the heart retrograde from the femoral artery. If the left ventricle retains or regains contractility, the poorly oxygenated blood from the lungs (in patients with concurrent significant respiratory failure) is ejected into the proximal aorta. This can lead to the so called “North-south” or “Harlequin” syndrome, where the head and right upper extremity are relatively hypoxic compared to the rest of the body. Arterial blood gases from a right radial arterial line can forewarn of possible coronary and cerebral hypoxia during LV recovery as this syndrome develops and the “mixing” cloud develops.
  • For patients with poor ejection, there are various strategies to decompress, or “vent,” the left ventricle. Strategies include use of medicines to reduce afterload and/or improve inotropy, creation of an atrial septal defect to offload the left heart, and use of temporary mechanical circulatory support devices (IABP or percutaneous LVAD) to allow blood to more easily leave the LV.
  • Treatment of the North-South Syndrome focuses on increasing the oxygenation of blood ejecting from the left ventricle through vent management or adding another venous catheter to pre-oxygenate blood before entering the lungs (VAV-ECMO). Increasing VA-ECMO flow can also shift the mixing zone towards the aortic arch and improve oxygenation, but this will also increase the LV afterload.
  • Other complications of the ECMO circuit include infection, bleeding, and limb ischemia (due to the large bore vascular access), as well as stroke, hemolysis, and thrombus formation (due to the extracorporeal circuitry).

5. How is VA-ECMO weaned?

  • If a patient is on VA-ECMO support as a bridge to recovery, the ability to wean a patient off the circuit relies on invasive hemodynamics, echocardiography, and an assessment of improving end-organ function.
  • The flow of blood out of the circuit can be gradually weaned down to allow for the patient’s native heart to do more of the work of perfusion. Once the patient is thought to be ready for decannulation it is common to perform a turndown study under echocardiographic guidance, where serial evaluations of biventricular function are done at different flow speeds.
  • VA-ECMO is usually decannulated in the operating room to allow for surgical repair of the vasculature in the setting of large bore access.
References – Biventricular Failure and the Use of VA-ECMO
  1. Papolos AI, Kenigsberg BB, Berg DD, Alviar CL, Bohula E, Burke JA, Carnicelli AP, Chaudhry SP, Drakos S, Gerber DA, Guo J, Horowitz JM, Katz JN, Keeley EC, Metkus TS, Nativi-Nicolau J, Snell JR, Sinha SS, Tymchak WJ, Van Diepen S, Morrow DA, Barnett CF; Critical Care Cardiology Trials Network Investigators. Management and Outcomes of Cardiogenic Shock in Cardiac ICUs With Versus Without Shock Teams. J Am Coll Cardiol. 2021 Sep 28;78(13):1309-1317. doi: 10.1016/j.jacc.2021.07.044. PMID: 34556316.
  2. Burkhoff D, Sayer G, Doshi D, Uriel N. Hemodynamics of Mechanical Circulatory Support. J Am Coll Cardiol. 2015;66(23):2663-2674. doi:10.1016/j.jacc.2015.10.017
  3. Guglin M, Zucker MJ, Bazan VM, et al. Venoarterial ECMO for Adults: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019;73(6):698-716. doi:10.1016/j.jacc.2018.11.038
  4. Keebler ME, Haddad EV, Choi CW, et al. Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock. JACC Heart Fail. 2018;6(6):503-516. doi:10.1016/j.jchf.2017.11.017
  5. Rao P, Khalpey Z, Smith R, Burkhoff D, Kociol RD. Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock and Cardiac Arrest. Circ Heart Fail. 2018;11(9):e004905. doi:10.1161/CIRCHEARTFAILURE.118.004905
  6. Tehrani BN, Truesdell AG, Psotka MA, et al. A Standardized and Comprehensive Approach to the Management of Cardiogenic Shock. JACC Hear Fail. 2020;8(11):879-891. doi:10.1016/j.jchf.2020.09.005
  7. Grant C, Richards JB, Frakes M, Cohen J, Wilcox SR. ECMO and Right Ventricular Failure: Review of the Literature. J Intensive Care Med. 2021;36(3):352-360. doi:10.1177/0885066619900503
  8.  Debaty G, Babaz V, Durand M, et al. Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis. Resuscitation. 2017;112:1-10. doi:10.1016/j.resuscitation.2016.12.011
  9. Russo JJ, Aleksova N, Pitcher I, et al. Left Ventricular Unloading During Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock. J Am Coll Cardiol. 2019;73(6):654-662. doi:10.1016/j.jacc.2018.10.085
  10. ELSO General Guidelines Extracorporeal Life Support Organization (ELSO) General Guidelines for All ECLS Cases.; 2017. www.elso.org. Accessed April 10, 2021.
  11. Su Y, Liu K, Zheng JL, Li X, Zhu DM, Zhang Y, Zhang YJ, Wang CS, Shi TT, Luo Z, Tu GW. Hemodynamic monitoring in patients with venoarterial extracorporeal membrane oxygenation. Ann Transl Med. 2020 Jun;8(12):792. doi: 10.21037/atm.2020.03.186. PMID: 32647717; PMCID: PMC7333156.
CardioNerds Cardiac Critical Care Production Team
      246. Cardiovascular Genomics: Genetic Counseling & Family Screening in Arrhythmogenic Cardiomyopathies with Dr. Allison Hays and Dr. Cindy James30 Nov 202200:45:25

      The CardioNerds Cardiovascular Genomics Series continues! In this episode Dr. Dan Ambinder (CardioNerds Cofounder and Interventional Cardiologist), Dr. Anjali Wagle (FIT Ambassador at Johns Hopkins) and Dr. James Sampognaro (medicine resident at Johns Hopkins Osler Medicine Residency) learn from Dr. Allison Hays (Associate Professor of Medicine, Division of Cardiology, Johns Hopkins CMR researcher and Medical Director of Echocardiography) and Dr. Cindy James (Associate Professor of Medicine and certified genetic counselor at Johns Hopkins with research focusing on cardiovascular genetic counseling and arrhythmogenic cardiomyopathies). They discuss arrhythmogenic RV cardiomyopathy as the context to learn about genetic counseling and family screening.  Episode script and notes were developed by Dr. Anjali Wagle. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah.

      This episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.

      This CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs.

      Check out this REVIEW describing the “Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy” by Nitin Malik, Allison Hays, and colleagues.  

      For related episodes, please enjoy these case-based discussions: 

      Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

      Pearls • Notes • References

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      Show notes – Genetic Counseling & Family Screening in Arrhythmogenic Cardiomyopathies

      Notes (developed by Dr. Anjali Wagle)  

      1. What is the underlying pathophysiology of arrhythmogenic RV cardiomyopathy (ARVC)? 
      • Fibrofatty replacement cardiac myocytes 
      • Associated with genetically mediated disruption of desmosomal proteins  
      • This leads to thinning and weakness of the heart that can lead to aneurysms and progressive dilatation and failure of the right ventricle (RV) 
      1. How is ARVC diagnosed? 
      • 2010 taskforce criteria (Marcus et al, 2010):   
        • RV structural abnormalities including findings seen on echocardiogram, MRI, and RV angiography 
        • Pathological criteria 
        • Repolarization abnormalities  
        • Depolarization/conduction abnormalities  
        • Ventricular arrhythmias  
        • Genetics and/or family history  
      1. How does ARVC present?  
      • Young, healthy individual will have symptoms of arrhythmias (syncope, pre-syncope, SCD) or heart failure 
      • Family screening  
      1. What are the inheritance and genetic factors of ARVC? 
      • Autosomal dominant pattern 
      • Low penetrance and variable expressivity  
      • Half of patients who are index cases will be found to have a mutation in the desmosomal gene.  
      1. What are the most common mutations associated with ARVC? 
      • Most commonly the genes involved are plakophilin-2 (PKP-2) and desmoplakin.  
      • For PKP-2 the most common mutations are truncating mutations.  
      • In patients who have inherited two truncating mutations, this will result in neonatal lethality.  
      1. Is there a difference in the genetic factors of left and right arrhythmogenic cardiomyopathy?  
      • ACM is disproportionally a right dominated cardiomyopathy. Left dominated cardiomyopathy has a different genetic profile.  
      • Pathogenic variants in desmoplakin disproportionally cause biventricular forms of ACM or left dominated forms.  
      1. What are the echocardiographic findings in ACM? 
      • Wall thinning and aneurysmal dilation in the sub-tricuspid region, RV outflow tract, or base also known as the “triangle of dysplasia.” 
      • Progression of disease tends to be from the base to the apex. 
      1. Why is cardiac MRI the preferred imaging modality in ACM? 
      • Higher spatial resolution and improved visualization of the right ventricle 
      1. Can imaging help define prognosis in ACM? 
      • Top two strongest measures of prognostic value in ACM are: 
        • RV fractional change area < 33% 
        • Tricuspid annular plane systolic exertion < 1.7cm  
      References – Genetic Counseling & Family Screening in Arrhythmogenic Cardiomyopathies

      Malik, N., Mukherjee, M., Wu, K. C., Zimmerman, S. L., Zhan, J., Calkins, H., James, C. A., Gilotra, N. A., Sheikh, F. H., Tandri, H., Kutty, S., & Hays, A. G. (2022). Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. Cardiovascular Imaging, 15(2), e013725. https://doi.org/10.1161/CIRCIMAGING.121.013725 

      Marcus FI, McKenna WJ, Duane S, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MGPJ, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DMY, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. Circulation. 2010;121:1533–1541.  

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