Episodes Archives - Cardionerds

CardioNerds (Amit Goyal and Daniel Ambinder), join Dr. Kara Denby (Interventional cardiology fellow, Cleveland Clinic), Dr. Tony Pastor (ACHD fellow, Harvard Medical School), Dr. Katie Berlacher (Cardiology program director, UPMC), and Dr. Stephen Cook (ACHD cardiologist, Indiana University) to discuss empowering the LGBTQIA+ community of cardiovascular patients & professionals and more in this installment of the Narratives in Cardiology Series. This episode features the Indiana ACC Chapter. Episode introduction and audio editing by CardioNerds Academy Intern, Pace Wetstein.

This discussion was inspired by this perspective piece on ACC.org titled: Finding Our Voices: Building an LGBTQIA+ Community Within Cardiology. To learn more about diversity and equity among the LGBTQIA+ population, check out this webinar organized by the ACC.

The PA-ACC & CardioNerds Narratives in Cardiology is a multimedia educational series jointly developed by the Pennsylvania Chapter ACC, the ACC Fellows in Training Section, and the CardioNerds Platform with the goal to promote diversity, equity, and inclusion in cardiology. In this series, we host inspiring faculty and fellows from various ACC chapters to discuss their areas of expertise and their individual narratives. Join us for these captivating conversations as we celebrate our differences and share our joy for practicing cardiovascular medicine. We thank our project mentors Dr. Katie Berlacher and Dr. Nosheen Reza.

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1/ Episode 197, @PaChapterACC & @CardioNerds Narratives in Cardiology episode featured a discussion w/ @KaraDenbyMD, @DrTonyPastor, @KBerlacher, @stephencookmd

Follow this #CardsNarratives🧵on the discussion about Empowering the LGBTQIA+ Community of CV Patients & Professionals pic.twitter.com/CiYZYFcWA9

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CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Sonu Abraham (Cardiology fellow, Lahey Hospital and Medical Center), Dr. Amitoj Singh (Internal Medicine Resident, Lahey Hospital and Medical Center), Dr. Ahmed Ghoneem (Internal Medicine Resident, Lahey Hospital and Medical Center, CardioNerds Academy Chief) and Dr. Aanika Balaji (Internal Medicine Resident, Johns Hopkins) for a scrumptious meal on the Boston Harbor as they discuss a case of a young woman with metastatic melanoma on immune checkpoint inhibitors presenting with dyspnea. The presentation, risk factors, work up and management of patients with immune checkpoint inhibitor induced myocarditis are described. The E-CPR segment is provided by Dr. Sarju Ganatra, the founding director of the cardio-oncology program at Lahey Clinic.  CardioNerds Clinical Trialist Dr. Carrie Mahurin (University of Vermont Medical Center) is introduced at the beginning of the episode.

A 41-year-old woman presented with mild dyspnea on exertion and non-productive cough. She had a history of Hashimoto thyroiditis, nodular thyroid s/p resection on levothyroxine, and metastatic melanoma on immune checkpoint inhibitor therapy with ipilimumab and nivolumab. She also had a history of obesity and underwent gastric bypass surgery several years prior. Though she lost weight after the surgery, she regained a significant amount and was 244 lbs with a BMI of 42. Her exam findings were remarkable for tachycardia, bilateral pulmonary rales, elevated JVP, and symmetric pedal edema. Investigations revealed a mild troponin elevation, non-specific EKG changes, and TTE with severely reduced left ventricular function (EF 15%) and a low GLS. Cardiac MRI showed patchy delayed myocardial enhancement in a non-ischemic distribution with marked global hypokinesis and EF of 11%. Endomyocardial biopsy confirmed the diagnosis of immune checkpoint inhibitor (ICI) associated myocarditis. The ICI therapy was discontinued and she was treated with high dose intravenous corticosteroids followed by a prolonged oral steroid taper with clinical improvement and complete recovery of left ventricular function.

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1. ICI-associated myocarditis has a high mortality rate necessitating a high degree of clinical suspicion. When in doubt, check it out! The initial 4 diagnostic pillars include EKG, troponin, BNP and TTE. Cardiac MRI and endomyocardial biopsy help to confirm the diagnosis.
2. Left ventricular function is normal in 50% of these patients with ICI-associated myocarditis, so the ejection fraction is not a sensitive test for ruling this out.
3. Endomyocardial biopsy should be considered in patients with a high clinical suspicion but negative or ambiguous non-invasive imaging.
4. Early initiation of corticosteroids within 24 hours of presentation is associated with better outcomes.
5. ICIs should be discontinued indefinitely in those with Grade 3 or 4 disease.

1. Immune checkpoint inhibitors – What are they and why should we as cardiologists know about them?

• Immune checkpoint inhibitors (ICI) boost the host immune response against tumor cells by inhibiting the intrinsic brakes of the immune response.
• There are currently 7 FDA approved drugs in this group: one CTLA-4-blocking antibody called ipilimumab; three PD-1-blocking antibodies [nivolumab, pembrolizumab, and cemiplimab]; and three PD-L1-blocking antibodies [atezolizumab, avelumab, and durvalumab].
• Like a car, T-cells have an ignition switch, gas pedals, and brakes.
• T-cells become activated when receptors on the surface of the T-cell bind to an antigen on the surface of the invading cells like cancer cells.
• Think of the T-cell receptor as the ignition switch and the antigen as the key.
• Antigen presenting cells patrol the body and pick up evidence of foreign antigens like cancer which they present to T-cells in the lymph nodes via the T-cell receptor.
• Like gas pedals, there are co-stimulatory signals like CD 28 which interact with proteins on the antigen presenting cells. With these “gas pedal” stimuli, T-cells get activated, multiply, and hunt for the cancer and finally kill the cancer cells.
• The T-cells also have “breaks” or “checkpoints” to down-regulate the immune response.
• The Cytotoxic T-lymphocyte antigen 4, also called the CTLA-4, acts to slow down the activation of T-cells.
• Further down the line, there is another checkpoint called the Programmed cell death 1 or PD-1. PD-1 is a molecule on the surface of T-cells which acts as another set of brakes.
• When a T cell with PD-1 on its surface interacts with another cell which has a PD-1 ligand (PD-L1), the T-cell activity is down-regulated.
• Many cancer cells overexpress PD-L1 to fight back against the T cells, by putting a “brake” on their immune response.
• By removing these brakes, we can augment the T-cells’ immune response against cancer cells.
• But if the T-cells mount an exaggerated response against normal host cells, then an autoimmune process ensues leading to “immune-related adverse events” (irAEs) like ICI-associated myocarditis.

2. Who are at risk of developing ICI-associated myocarditis?

• Anti-CTLA 4 therapy is associated with a higher prevalence of cardiotoxicity than the PD-1 and PD-L1 inhibitors.
• Combination therapy (i.e., when 2 or more ICIs are given together) increase the risk of irAEs.
• Preexisting diabetes, obesity, and autoimmune disease have been found to be independent risk factors.
• An association of preexisting cardiovascular risk factors like hypertension and smoking with the development of ICI-induced myocarditis has been suggested.

3. What are the prevalence and prognosis of ICI-associated myocarditis?

• Immune checkpoint inhibitors have various forms of cardiotoxicities, but ICI-associated myocarditis is the most feared complication.
• The overall prevalence is 1.2% to 2.4% when using combination ICI therapy. However, the estimated rate of mortality in ICI associated myocarditis is 38 to 46%.
• Approximately 50% of these patients with myocarditis may develop heart failure, cardiogenic shock, complete heart block, cardiac arrest, and ventricular arrhythmias.

4. What is the differential diagnose for ICI-associated myocarditis?

• The differential diagnoses are acute coronary syndrome, stress cardiomyopathy, other forms of myocarditis, pericarditis, pneumonitis, viral myocarditis, endocrinopathies, cardiac sarcoidosis and other causes of cardiomyopathy and heart failure including prior cardiotoxic therapy.

5. What are the initial investigations to be done for ICI-associated myocarditis?

• EKG, troponin, BNP, and TTE (as needed) are the basic 4 pillars of testing in patients with suspected ICI induced myocarditis.
• Nearly all patients with myocarditis have an abnormal EKG. These are however non-specific findings like sinus tachycardia, QRS or QT prolongation, conduction abnormalities, diffuse T-wave inversion, abnormal Q waves, atrial or ventricular arrhythmias, local or diffuse ST elevation.
• Troponins are elevated in most cases, up to 94% in one study. The implications of the level of troponin elevation are not completely clear but there is data that suggests that higher levels of troponin elevation are associated with worse cardiovascular outcomes.
• BNP can be elevated if the patient is in heart failure or volume overloaded. However, it lacks sensitivity and specificity for ICI associated myocarditis and is not always helpful.
• Even patients with fulminant myocarditis can present with a normal left ventricular function. Around 50% of patients with ICI induced myocarditis have been found to have a normal LV function. Also, among those who had major adverse cardiac events, 38% had a normal EF.

6. How do you grade severity?

The American Society of Clinical Oncology broadly categorized the intensity of disease into 4 groups:

• G1 – Mildly abnormal screening tests and no symptoms
• G2 – Abnormal screening tests with mild symptoms
• G3 – Moderately abnormal screening tests (arrhythmia, cardiac biomarker > upper limits of normal and significant echocardiographic findings) and symptoms with mild activity.
• G4 – Moderate to severe decompensation, hemodynamic instability, cardiac biomarker > 3 upper limit of normal, requiring intravenous medications or interventions.

To summarize, G1 and G2 are considered stable and minimally symptomatic and G3 and G4 are very symptomatic or unstable patients and will need to be admitted.                    

7. What are the treatment options?

• Prompt initiation of immunosuppressive therapy is critical for these patients.
• The first line agents are corticosteroids.
• Start with high dose corticosteroids within 24 hours of presentation. Typically, we start with intravenous methylprednisolone 1000 mg daily for 3 days, followed by oral prednisone 1 mg/kg/day.
• The steroids should then be tapered slowly over at least 4–6 weeks only after resolution of symptoms, normalization of LVEF or stabilization of arrhythmias.
• If unresponsive to steroids, tacrolimus, mycophenolate mofetil, anti-thymocyte globulin, iv gamma globulin and plasmapheresis are alternative therapies.

8. Is it safe to restart ICIs after treatment?

• The current recommendation is a definite discontinuation of ICI in case of grade 3 (severe) or life threatening (grade 4) immune related adverse events.
• May consider re-challenge in those with milder disease and complete cardiac recovery – individualized and multidisciplinary team approach.

1. Patel RP, Parikh R, Gunturu KS, et al. Cardiotoxicity of Immune Checkpoint Inhibitors. Curr Oncol Rep. 2021;23(7):79. Published 2021 May 3. doi:10.1007/s11912-021-01070-6
2. Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018;71(16):1755-1764. doi:10.1016/j.jacc.2018.02.037
3. Ganatra S, Neilan TG. Immune checkpoint inhibitor-associated myocarditis. Oncologist. 2018;23(8):879–86. https://doi.org/10. 1634/theoncologist.2018-0130
4. Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, et al. Major adverse cardiovascular events and the timing and dose of corticosteroids in immune checkpoint inhibitorassociated myocarditis. Circulation. 2020;141(24):2031–4. https:// doi.org/10.1161/CIRCULATIONAHA.119.044703
5. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714-1768. doi:10.1200/JCO.2017.77.6385

The CardioNerds Academy Class of 2021 graduation ceremony kicked off the inaugural Sanjay V Desai Lecture: Growth Mindset, Power of Yet, & Pursuit of Mastery. Join us as Dr. Tommy Das (CardioNerds Academy Program Director), and Dr. Saman Nematollahi (CardioNerds Academy Director of Research) discuss Growth Mindset with Dr. Keri Shafer and Dr. David Hirsh. Terrific acting by Dr. Patrick Zakka, Dr. Teodora Donisan, Dr. Ahmed Ghoneem, and Dr. Jessie Holtzman.

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. Keri Shafer is an adult congenital heart disease specialist at Boston Children’s Hospital, and an assistant professor of pediatrics within Harvard Medical School. She completed internal medicine residency at Beth Israel Deaconess Medical Center, before completing cardiology fellowship at UT Southwestern and Adult Congenital and Pulmonary Hypertension subspecialty training at Boston Children’s and BWH.   

Dr. David Hirsh is an associate professor of Medicine within Harvard Medical School, as well as the director of the HMS Academy fellowship in medical education and the associate dean of undergraduate medical education.

Relevant disclosures: None

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CardioNerds, Amit Goyal, Dr. Tommy Das (Program Director of the CardioNerds Academy and Cardiology fellow at Cleveland Clinic), Dr. Rick Ferraro (Director of CardioNerds Journal Club and Cardiology fellow at the Johns Hopkins Hospital), Dr. Patrick Zakka (CardioNerds Academy Chief fellow of House Jones and Cardiology fellow at UCLA) discuss omega-3 fatty acids & the battle of the oils with Dr. Pam Taub, Director of Step Family Foundation Cardiovascular Rehabilitation and Wellness Center and Professor of Medicine at UC San Diego. Learn all about the different types of omega-3 fatty acids and the differences between prescription omega-3 fatty acids and dietary supplement fish oils. Audio editing by CardioNerds Academy Intern, Shivani Reddy.

This episode is part of the CardioNerds Lipids Series which is a comprehensive series lead by co-chairs Dr. Rick Ferraro and Dr. Tommy Das and is developed in collaboration with the American Society For Preventive Cardiology (ASPC).

Relevant disclosures: None

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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].
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]. Circulation. 2019;139(25):e1082-e1143.
3. Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk [published correction appears in Atherosclerosis. 2020 Jan;292:160-162] [published correction appears in Atherosclerosis. 2020 Feb;294:80-82]. Atherosclerosis. 2019;290:140-205.
4. Bhatt D, Steg P, Miller M et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22.
5. Budoff M, Bhatt D, Kinninger A et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J. 2020;41(40):3925-3932.
6. Nicholls S, Lincoff A, Garcia M et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268-2280.

Dr. Pam Taub, Professor of Medicine, is the founding director of the StepFamily Foundation Cardiac Rehabilitation and Wellness Center at the University of California, San Diego. Dr. Taub is a leader in preventive cardiology and has authored over one hundred publications, abstracts and book chapters. Dr. Taub is a leader in multiple professional societies, including board membership for the American Society of Preventive Cardiology.

Dr. Patrick Zakka completed his medical school at the American University of Beirut in Lebanon, followed by internal medicine residency and a chief resident year at Emory University. He is currently a first year cardiology fellow at UCLA and graduated as a CardioNerds fellow in House Taussig and is now the Chief Fellow of House Jones.

In this episode we discuss cardiogenic shock due to valvular heart disease. Join Dr. Pranoti Hiremath (Interventional cardiology fellow, Johns Hopkins), Dr. Karan Desai (CN Critical Care Series Co-Chair, Cardiology fellow, University of Maryland), Dr. Yoav Karpenshif (CN Critical Care Series Co-Chair, Chief cardiology fellow, University of Pennsylvania), and Amit Goyal (CardioNerds Co-Founder) as they interview Dr. Paul Cremer (Associate Director of the Cardiac Intensive Care Unit and Associate Director of the Cardiovascular Fellowship at the Cleveland Clinic) in this broad overview of valvular shock. We discuss the nuances in diagnosis, differing presentations and how physical exam, multi-modality imaging, and invasive hemodynamics can inform management. Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship and CardioNerds Academy Fellow).

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 Belkin, Dr. Eunice Dugan, Dr. Karan Desai, and Dr. Yoav Karpenshif.

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1. Shock due to valve disease is the result of a structural abnormality that may be temporized with medical therapy and circulatory support devices. However, it is ultimately best treated with a structural solution in the form of either percutaneous valvular therapies or cardiac surgery.
2. When treating a patient with cardiogenic shock with normal or hyperdynamic ventricular function, we should keep a high index of suspicion for valvular disease. The cardiac output may be reduced due to a stenotic lesion “blocking” forward flow or regurgitant lesion causing backward flow.
3. Acute mitral and aortic regurgitation will typically not manifest as a loud murmur on physical exam. The combination of hypotension and rapid flow of regurgitant blood on an “unprepared” cardiac chamber results in rapid equalization of chamber pressures, shortening the intensity and duration of the murmur. On transthoracic echocardiogram, for instance with acute MR, color Doppler may not show a large turbulent jet, and thus the MR may be underestimated or not appreciated at all.
4. Echocardiography is critical to understand the etiology and severity of valvular shock, and invasive hemodynamics are often needed to guide medical and mechanical interventions.
5. In multi-valve disease with severe aortic stenosis and functional mitral regurgitation, we typically treat the aortic stenosis first, since the mitral regurgitation may improve from the reduction in afterload associated with treating aortic stenosis.

1. Shock due to valve disease arises due to a structural problem that may be temporized with medical therapy and circulatory support devices, but is ultimately best treated with a structural solution in the form of either percutaneous valvular therapies or cardiac surgery.

• Stabilizing therapies for acute mitral regurgitation include afterload reduction with vasodilators, diuresis as needed to reduce pulmonary edema, and mechanical circulatory support including intra-aortic balloon pumps.
• Therapies for acute aortic regurgitation are typically more limited and include vasopressors such as epinephrine.  Bradycardia should be avoided with agents such as dobutamine or temporary pacing to reduce time in diastole. Temporary mechanical circulatory support options are limited in the setting of acute AR, though case reports of techniques such as LAVA ECMO (left atrial venoarterial extracorpeal membrane oxygenation) as a bridge to definitive therapy have been reported.
• There are several factors to consider in patients with aortic stenosis and cardiogenic shock.
  • In some patients with aortic stenosis and LV dysfunction, the shock is a result of LV pressure overload potentially leading to congestion, the high afterload introduced on the LV by the stenotic aortic valve, and increased systemic vascular resistance (compensatory for the failing LV). In these patients, acute vasodilators (specifically nitroprusside) can relieve the additive afterload on the LV imposed by increased SVR as a bridge to definitive therapy.
  • In other patients with severe AS, the LV faces high afterload at the level of the aortic valve but the SVR is relatively low (as well as the pressures in the aortic root which can reduce coronary perfusion), and thus these patients may require a pure alpha agonist (e.g., phenylephrine) to reduce the afterload mismatch and reduce myocardial ischemia.
  • Furthermore, when patients have high LV filling pressures, they are reliant on longer diastole times and an atrial kick to promote LV filling and thus rapid atrial fibrillation can be highly detrimental. In both phenotypes, mechanical circulatory support may be needed as a bridge to valve surgery or TAVR.
  • Percutaneous balloon valvuloplasty of the aortic valve may be utilized as a bridge to definitive therapy in select patients
• In scenarios of valvular disease and cardiogenic shock, right heart catheterization can be helpful to guide and titrate medical therapy and inform decisions to escalate to mechanical circulatory support.
• Percutaneous therapies (e.g., TAVR or Transcatheter Edge to Edge Repair with MitraClip) are increasingly being utilized as a “primary” therapy on a case by case basis for patients in cardiogenic shock with valvular disease. More data is needed to inform patient phenotypes who would benefit from such a strategy without futility.

2. What is the differential diagnosis for cardiogenic shock with normal or hyperdynamic left ventricular function?

• One framework to approach cardiogenic shock with normal or hyperdynamic left systolic function is to consider (1) pericardial failure with constriction or tamponade; (2) myocardial failure with severe restrictive disease (3) electrical failure with new arrhythmia, or (4) valvular failure.
• In this scenario, we should have a high index of suspicion for valvular disease.  The cardiac output may be reduced due to a stenotic lesion blocking forward flow or regurgitant lesion causing backward flow.

3. If I don’t hear a significant murmur on examination, does that rule out an acute regurgitant valvular disease as a cause of shock?

• Acute mitral and aortic regurgitation may not manifest as a loud murmur on physical exam. In severe, acute AR, a murmur may not be audible if the diastolic pressure in the LV and aorta equilibrate quickly. Similarly, in acute, severe MR, there can be a rapid rise in LA Pressure reducing the driving pressure across the mitral valve.
• On transthoracic echocardiogram, the same pathophysiology can explain why acute regurgitant lesions may not be readily apparent. For instance, with acute MR, color Doppler may not show a large turbulent jet, and thus the MR may be underestimated or not appreciated at all. In patients with sudden hemodynamic instability after myocardial infarction with hyperdynamic LV function by TTE, for instance, and no other cause for deterioration, TEE can be helpful in evaluating for Acute MR due to papillary muscle or chordal rupture. 

4. Echocardiography and guidance with right heart catheterization is helpful to understand the etiology and severity of valvular shock.

• Echocardiography can help determine whether valve dysfunction is primary (e.g. leaflet perforation due to endocarditis) versus secondary (e.g. dilated left ventricle leading to functional mitral regurgitation), as well as provide clues to the chronicity of valve disease.
• A right heart catheterization can help inform whether valvular disease is the primary insult or if other factors are contributing, inform an initial management strategy (e.g., medical therapies alone vs. mechanical circulatory support), and assess response to therapy.

5. In multi-valve disease, what is the best way to differentiate which lesion is the culprit?

• These scenarios are not uncommon and require clinicians to use a multi-modal approach, from patient history, exam, echocardiography, other imaging modalities, and invasive hemodynamics. Identifying the “primary” lesion can still be difficult even after multiple data points.
• Empiric therapy and assessment of subsequent hemodynamic response may be one way to practically approach multi-valve disease.
• One scenario covered on the episode was patients with severe aortic stenosis and severe mitral regurgitation. The MR in this scenario may be partly functional due to high LV systolic pressures and may improve with intervention on the aortic valve. Thus, one approach would be to treat AS and evaluate if the MR improves. 

Erlebach M, Lange R. Multivalvular Disease: Percutaneous Management in 2019 and Beyond. Interv Cardiol. 2019;14(3):142-146. Published 2019 Nov 18. doi:10.15420/icr.2019.13.R1

Khot UN, Novaro GM, Popović ZB, Mills RM, Thomas JD, Tuzcu EM, Hammer D, Nissen SE, Francis GS. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med. 2003 May 1;348(18):1756-63. doi: 10.1056/NEJMoa022021. PMID: 12724481.

Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2021 Feb 2;143(5):e228] [published correction appears in Circulation. 2021 Mar 9;143(10):e784]. Circulation. 2021;143(5):e35-e71. doi:10.1161/CIR.0000000000000932.

Unger P, Clavel MA, Lindman BR, Mathieu P, Pibarot P. Pathophysiology and management of multivalvular disease. Nat Rev Cardiol. 2016;13(7):429-440. doi:10.1038/nrcardio.2016.57.

Dr. Paul Cremer earned a Bachelor’s degree in molecular biology from Princeton University, Princeton, NJ, and his medical degree from Harvard Medical School, Boston, MA. Following completion of his internal medicine residency at Massachusetts General Hospital, he worked as a physician for two years at the Navajo IHS Chinle Comprehensive Health Care Facility in Chinle, Ariz. He then continued his postdoctoral training with a three-year fellowship in cardiovascular medicine and a subsequent two-year fellowship in advanced cardiovascular imaging, both at Cleveland Clinic. He joined the Cleveland Clinic staff in 2017. He is the director of the Cleveland Clinic CCU.  He enjoys swimming and reading fantasy books with his daughters. He joins the cardionerds cardiology podcast to shed insight on cardiac amyloid imaging.

Dr. Pranoti Hiremath is an interventional cardiology fellow at Johns Hopkins. She completed her MD at HMS, did her residency in Internal Medicine at University of Washington, and her Cardiology fellowship of Hopkins.

The following question refers to Section 4.8 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSF resident Dr. Jessie Holtzman, and then by expert faculty Dr. Melissa Tracy.

Dr. Tracy is a preventive cardiologist, echocardiographer, Director of Cardiac Rehabilitation, and solid organ transplant cardiologist at Rush University.

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.

A 62-year-old man with a history of non-obstructive coronary artery disease, heart failure with reduced ejection fraction (EF 30-35%), stage III chronic kidney disease, and type II diabetes mellitus presents to your clinic to establish care. His only medications are aspirin 81 mg daily and metformin 1000 mg BID, which he has taken since being diagnosed with diabetes mellitus 5 years ago. His hemoglobin A1c is 6.8%. What changes would you recommend to his medications at this time?

A. Start glipizide
B. Start saxagliptin
C. Start empagliflozin
D. No changes

The correct answer is C – start empagliflozin.

The Trials involving SGLT-2 inhibitors and GLP-1R agonists have shown cardiovascular benefits independent of glycemic control and metformin use.

The ADA recommends metformin as a first-line therapy for all patients with type 2 DM. The ESC also recommends metformin as first-line therapy but only in patients without ASCVD, CKD, or HF (Class I, LOE B). If a patient has ASCVD, metformin can be considered (Class IIa, LOE B). Rather, for those patients with type 2 DM and ASCVD, the ESC recommends the use of GLP-1R agonist or SGLT-2 inhibitors with proven outcome benefits to reduce CV and/or cardiorenal outcomes (Class I, LOE A). Additionally, for those with type 2 DM and either CKD or HFrEF, the ESC recommends the use of SGLT-2 inhibitor to improve outcomes (Class I, LOE A).

In contrast to the ADA, the view of the ESC is that metformin should be considered but is not mandatory first-line treatment in patients with diabetes and ASCVD or evidence of target organ damage. The initiation of metformin in such patients should not forego or delay the initiation of evidence-based SGLT2 inhibitors or GLP-1RAs.

Therefore, the next best step for our patient is to start an SGLT-2 inhibitor given his history of CAD, HF, and CKD. While this patient’s A1c goal is within the range recommended for patients with Type 2 DM and ASCVD (<7%), given his CAD, HF, and CKD an SGLT-2 inhibitor should still be added.

Saxagliptin is a DPP-4 inhibitor, a class of drugs that showed no effect of MACE but increased risk of HF hospitalization in patients with DM and existing.

Lifestyle management is a top priority for ASCVD prevention and management of DM. Lifestyle intervention lowers future microvascular and macrovascular risks as well as mortality in the longer term. Intensive lifestyle changes with low-calorie diets and mean weight losses in the region of 10 kg leads to remission of type 2 DM in around 46% of cases at 1 year and 36% by 2 years. Smoking cessation, a diet low in saturated fat and high in fiber, aerobic physical activity, strength training, and reduction in energy intake for weight optimization are all recommended for patient with diabetes mellitus (Class I).

Main Takeaway

In patients with Type 2 DM and ASCVD or end organ dysfunction, SGLT-2 inhibitors or GLP-1R agonists should be recommended regardless of background therapy or glycemic control. For patients with type 2 diabetes mellitus and CKD or HFrEF, SGLT-2 inhibitor is recommended.

Guideline Location

Section 4.8.1, Pages 3289-90.

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The following question refers to Section 4.10 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSD fellow Dr. Patrick Azcarate, and then by expert faculty Dr. Laurence Sperling.

Dr. Laurence Sperling is the Katz Professor in Preventive Cardiology at the Emory University School of Medicine and Founder of Preventive Cardiology at the Emory Clinic. Dr. Sperling was a member of the writing group for the 2018 Cholesterol Guidelines, serves as Co-Chair for the ACC’s Cardiometabolic and Diabetes working group, and is Co-Chair of the WHF Roadmap for Cardiovascular Prevention in Diabetes.

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.

The European Society of Cardiology Prevention guidelines currently recommend that low-dose colchicine (0.5mg/day) may be considered for the primary prevention of cardiovascular disease.

A. True
B. False

The correct answer is False. 

The correct answer is False.

The European Society of Cardiology recommends that low-dose colchicine may be considered as an adjunctive therapy for secondary rather than primary prevention of cardiovascular disease in individuals whose risk factors are otherwise insufficiently controlled (Class IIb, LOE A). A broad evidence base currently supports that inflammation has pro-atherosclerotic effects and that reducing inflammation may reduce atherogenesis in high-risk patients.

The initial LoDoCo trial in 2013 first demonstrated a 10.7% absolute risk reduction in acute coronary syndrome, out of hospital cardiac arrest, and non-cardioembolic ischemic stroke with daily low-dose colchicine; however, results were clouded by small sample size. Subsequently, the CANTOS trial in 2017 demonstrated a 15% relative reduction in non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death with Canakinumab, an anti-inflammatory monoclonal antibody inhibitor of interleukin-1. More recently, the COLCOT trial in 2019 studying patients with recent AMI and LoDoCo2 trial in 2021 studying patients with stable chronic CAD both demonstrated reductions in myocardial infarction, cardiovascular mortality, CVA, and ischemia-driven revascularization with colchicine 0.5mg/day. In the LoDoCo2 trial, stable CAD was defined either angiographically, by coronary CT, CAC >400, or history of CABG >10 years prior with evidence of failed grafts or angioplasty since that time.

In high-risk individuals with stable ischemic heart disease, the most recent evidence suggests that once daily low dose colchicine may reduce myocardial infarction and other ischemic events. Future studies may assess the biochemical markers including the trend of lipids and inflammatory markers to identify subpopulations that may benefit most from this therapy.

Main Takeaway:

Based upon the 2021 ESC Prevention Guidelines, clinicians may consider initiating low-dose colchicine (0.5mg/day) for secondary prevention of cardiovascular disease, particularly if other risk factors are insufficiently controlled or if recurrent CVD events occur despite optimal therapy.

Guideline Location: 

Section 4.10, page 3291.

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The following question refers to Section 4.7 and figure 16 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Student Dr. Shivani Reddy, answered first by Fellow at Johns Hopkins Dr. Rick Ferraro, and then by expert faculty Dr. Roger Blumenthal.

Dr. Roger Blumenthal is professor of medicine at Johns Hopkins where he is Director of the Ciccarone Center for the Prevention of Cardiovascular Disease. He was instrumental in developing the 2018 ACC/AHA CV Prevention Guidelines. Dr. Blumenthal has also been an incredible mentor to CardioNerds from our earliest days.

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.

Ms. K.M. is a 40-year-old woman presenting to the outpatient clinic for a routine physical exam required for her employment as an airline stewardess. She states she has been in her usual good health but does experience occasional headaches and lightheadedness while in flight. On exam her BP was noted to be 170/90. The diagnosis of hypertension is confirmed during a subsequent clinic visit. What would be the most appropriate initial therapy recommendation(s) for Ms. K.M.?

A. Initiate single drug therapy with a beta-blocker.
B. Discuss and initiate lifestyle interventions
C. Initiate two-drug combination therapy with a thiazide-like diuretic, BB, CCB, or an ARB.
D. Both B and C 

The correct answer is D.

Both B (lifestyle interventions) and C (initial combination therapy) are appropriate at this time.

Lifestyle interventions are indicated for all patients with high-normal BP or hypertension because they can delay the need for drug treatment or complement the BP-lowering effect of drug treatment (Class 1). Moreover, most lifestyle interventions have health benefits beyond their effect on BP.

Single-drug therapy will rarely achieve optimal BP control. Therefore, initial antihypertensive therapy with a combination of two drugs, preferably as a single-pill combination, is recommended for the management of HTN (Class 1). The only exceptions would be patients with a baseline BP close to the recommended target, who might achieve that target with a single drug, or very old (>80 years) or frail patients who may better tolerate a gentler reduction of BP.

Five major classes of BP-lowering drug therapy have shown benefit in reducing CV events; angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics.

A combination of an ACE inhibitor or ARB with a CCB or thiazide/thiazide-like diuretic is the preferred initial therapy for most patients with hypertension (Class 1). For those in whom treatment requires escalation to three drugs, a combination of an ACE inhibitor or ARB with a CCB and a thiazide/thiazide-like diuretic should be used (Class 1).

Resistant hypertension is defined as BP being uncontrolled despite treatment with optimal or best-tolerated doses of three or more drugs including a diuretic, and confirmed by ABPM or HBPM. Spironolactone is the most effective drug for lowering BP in resistant hypertension when added to existing treatment; however, the risk of hyperkalaemia is increased in patients with CKD. When spironolactone is not tolerated, amiloride, alpha-blockers, beta-blockers, or centrally acting drugs, such as clonidine, have evidence supporting their use. Renal denervation and device-based therapy may be considered for specific cases.

Beta-blockers should be used when there is a specific indication (e.g. angina, post myocardial infarction, arrythmia, HFrEF, or as an alternative to an ACE inhibitor or ARB in women of child-bearing potential). Combinations of an ACE inhibitor and an ARB are not recommended because of no added benefit on outcomes and increased risk of harm (Class III).

The diagnosis and treatment of hypertension in women is similar to that in men, except for women of child-bearing potential or during pregnancy, because of potential adverse effects of some drugs on the fetus, especially in the first trimester. In addition, the effect of oral contraceptive pills on the risk of developing or worsening hypertension should be considered.

Main Takeaway:

Combination drug therapies are more effective in lowering BP than monotherapy. BP management in women is similar to men with the exception of child-bearing potential given potential teratogenicity of some agents.

Guideline Location:

4.7.5.1-4, Page 3288

Figure 16, pg. 3287

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The following question refers to Section 4.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Dr. Maryam Barkhordarian, answered first by medicine resident CardioNerds Academy House Chief Dr. Ahmed Ghoneem, and then by expert faculty Dr. Kim Williams.

Dr. Williams is Chief of the Division of Cardiology and is Professor of Medicine and Cardiology at Rush University Medical Center. He has served as President of ASNC, Chairman of the Board of the Association of Black Cardiologists (ABC, 2008-2010), and President of the American College of Cardiology (ACC, 2015-2016).

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.

Mrs. B is a 56-year-old African American woman with a past medical history significant for type 2 diabetes (HbA1C 7.6) and hypercholesterolemia. Her calculated ASCVD risk score today is 12.5% and her BMI is 24kg/m2. She is concerned about her high cholesterol levels despite being on a statin and feels that her diet is “not healthy enough.” She is interested in making dietary changes to help reduce her ASCVD risk. Which of the following recommendations is appropriate?

A. Sodium restriction to <3g /day will be of no benefit because she is not hypertensive.
B. Isocaloric substitution of saturated fat with polyunsaturated fat is associated with reduction of CHD risk.
C. Dietary fiber intake is associated with GI benefits but has no CV risk reduction benefit.
D. Supplementing diet with vitamins A, B, C and E helps reduce ASCVD risk.

The correct answer is B.

Risk of CHD is reduced when dietary saturated fats are replaced with other foods having similar caloric values. The greatest reduction was observed when saturated fats were isocalorically replaced with polyunsaturated fats (↓25%), followed by monounsaturated fats (↓15%) and carbohydrates from whole grains (↓9%). This is a class 1a recommendation in the ESC guidelines and a class IIa recommendation in the 2019 ACC/AHA guidelines. Conversely, increased trans fatty acid intake is associated with increased CHD risk. A regulation of the European Union (EU) Commission has set the upper limit of trans fats to 2 g per 100 g of fat. The ACC/AHA guidelines recommend that the intake of trans fats should be avoided (a class III: harm).

Choice A is incorrect because dietary sodium restriction is recommended not only for control of blood pressure, but also for reduction of ASCVD risk. In a meta-analysis, salt reduction of 2.5 g/day resulted in a 20% reduction of ASCVD events (RR 0.80). Reduction of salt intake is a class 1 recommendation in the ESC guidelines compared to a class IIa recommendation in the 2019 ACC/AHA guidelines.

Choice C is incorrect because a 10 g/day higher fiber intake was associated with a 16% lower risk of stroke (RR 0.84) and a 6% lower risk of type 2 DM (RR 0.94). A high fiber intake may reduce postprandial glucose responses after carbohydrate-rich meals and also lower triglyceride levels. The Mediterranean diet is rich in fiber (it includes high intakes of fruits, vegetables, pulses and wholegrain products) and is a class I recommendation.

Choice D is incorrect because while vitamin supplementation has been associated with reduction in ASCVD risk in observational studies, intervention trials have failed to show any benefit. 

Main Takeaway:

A healthy diet is recommended as a cornerstone of CVD prevention in all individuals, independent of their underlying co-morbidities. Replacing saturated with unsaturated fats, reducing salt intake, and choosing a more plant-based diet that is rich in fiber can lower risk of CVD.

Guideline Location
Section 4.3.2, Page 3270

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The following question refers to Section 3.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern 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. Allison Bailey.

Dr. Bailey is an advanced heart failure and transplant cardiologist at Centennial Heart. She is the editor-in-chief of the American College of Cardiology’s Extended Learning (ACCEL) editorial board and was a member of the writing group for the 2018 American Lipid Guidelines. 

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.

Mr. Early M. Eye is a 55-year-old man with a history of GERD who is seeing you in clinic as he is concerned about his family history of early myocardial infarction and would like to discuss if he should be taking a statin for cardiovascular prevention. He has never smoked tobacco. His 10-year CVD risk is estimated to be 8%. Which imaging modality is recommended by the ESC guidelines to reclassify his CVD risk?

A. Coronary Artery Calcium (CAC) scoring
B. Echocardiography
C. Ankle brachial index
D. Contrast enhanced computed tomography coronary angiography (CCTA)
E. None of the above

The correct answer is A.

Coronary artery calcium (CAC) scoring can reclassify CVD risk upwards and downwards and should specifically be considered in patients with calculated risk scores that are around decision thresholds. CAC scores which are high-than-expected for age and sex increase estimated future CVD risk. Notably, CAC scoring may also be used to “de-risk” if CAC is absent or lower-than-expected. The 2021 ESC Prevention Guidelines give a Class IIb (LOE B) recommendation to consider CAC scoring to improve risk classification around treatment decision thresholds. However, one limitation of CAC is that it does not provide direct information on total plaque burden or stenosis severity. In addition, there is also a Class IIb (LOE B) recommendation to use plaque detection by carotid ultrasound as an alternative when CAC scoring is unavailable or not feasible. Plaque assessed through carotid ultrasound is defined as presence of wall thickening that is >50% greater than the surrounding vessel wall or a focal region with intima-media thickness measurement >1.5mm that protrudes into the lumen.

Similar to the ESC Prevention Guidelines, the 2019 ACC/AHA guidelines on primary prevention of CVD also have a Class IIa recommendation for using CAC score, and explicitly mention its use for adults at intermediate risk (>7.5% to <20% 10-year ASCVD risk) with cut-offs including >100 Agatson units to reclassify risk upwards and CAC of 0 to reclassify risk downwards. However, the guidelines also mention that clinicians should not down-classify risk in patients who have CAC of 0 if they are current smokers, have diabetes, have a family history of ASCVD, or have chronic inflammatory conditions. Furthermore, the 2018 ACC/AHA Cholesterol guidelines have a Class IIa recommendation that if CAC is 0, it is reasonable to withhold statin therapy and reassess risk in 5 to 10 years, as long as higher risk conditions that we just discussed are absent. If CAC is 1-99, it is reasonable to initiate statin therapy for patients ≥ 55 years of age.

Choice B is incorrect. Echocardiography is not recommended to improve CV risk prediction due to lack of convincing evidence that it improves CVD risk reclassification.

Choice C is incorrect. While the 2013 ESC guidelines mentioned that ABI may be considered as a risk modifier in CVD risk estimation, the newer 2021 guidelines state that ankle brachial index has limited potential in terms of reclassification risk, though an individual patient data meta-analysis showed there may be utility for women at intermediate risk. 12-27% of middle-aged individuals can have an abnormal ankle brachial index, defined as less than 0.9, of which 50-89% may not have typical claudication symptoms. Conversely, the 2019 ACC/AHA guidelines include ABI <0.9 as a risk-enhancing factor.

Choice D is incorrect. Coronary computed tomographic angiography (CCTA) has been shown in studies such as SCOT-HEART to have utility in predicting cardiac events in patients with stable chest pain and can identify coronary stenosis. It is not currently recommended by ESC guidelines for prognostic value or risk classification in asymptomatic patients.

According to the ESC guidelines, routine vascular testing or imaging other than CAC scoring or carotid ultrasound for plaque determination are not recommended (Class III, LOE B).

In terms of this patient’s family history of premature CVD, the ESC guidelines describe that even though family history is significantly associated with CVD in studies, it only marginally improves the prediction of CVD risk beyond conventional ASCVD risk factors. However, family history should still be obtained regularly when seeing patients, and if there is a positive family history of ASCVD, a comprehensive CVD risk assessment is warranted. Importantly, family history is not binary and those with a greater “dose” of family history (more relatives affected at earlier ages) may be at greater risk.

Main Takeaway

When a patient without established ASCVD has an estimated 10-year risk around treatment decision thresholds, CAC scoring is the best-established imaging modality to improve CVD risk stratification.

Guideline Location

Section 3.3.3, page 3259

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