Cardionerds: A Cardiology Podcast – Détails, épisodes et analyse

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.

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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

• Salah HM, Savarese G, Rosano GMC, et al. Intravenous iron infusion in patients with heart failure: a systematic review and study-level meta-analysis. ESC Heart Fail. 2023;10(2):1473-1480. doi:10.1002/ehf2.14310. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053151/

• Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020;396(10266):1895-1904. doi:10.1016/S0140-6736(20)32339-4. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32339-4/abstract

• Kalra PR, Cleland JGF, Petrie MC, et al; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022;400(10369):2199-2209. doi:10.1016/S0140-6736(22)02083
  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02083-9/fulltext
• Mentz RJ, Garg J, Rockhold FW, et al; HEART-FID Investigators. Ferric Carboxymaltose in Heart Failure with Iron Deficiency. N Engl J Med. 2023;389(11):975-986. doi:10.1056/NEJMoa2304968. https://www.nejm.org/doi/full/10.1056/NEJMoa2304968

• 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

• Anker SD, Comin Colet J, Filippatos G, et al. Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency. N Engl J Med. 2009;361(25):2436-2448. doi:10.1056/NEJMoa0908355. https://www.nejm.org/doi/full/10.1056/NEJMoa0908355

• 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/

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

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

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 intern, Pace 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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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 Intern, Dr. 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

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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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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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

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 intern, Pace 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

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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