Cardionerds: A Cardiology Podcast

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. Jump to: Case media – Case teaching – References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media – immune checkpoint inhibitor myocarditis Episode Schematics & Teaching CardioNerds Myocarditis, updated 1.20.21 Pearls – immune checkpoint inhibitor myocarditis 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. 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. Endomyocardial biopsy should be considered in patients with a high clinical suspicion but negative or ambiguous non-invasive imaging. Early initiation of corticosteroids within 24 hours of presentation is associated with better outcomes. ICIs should be discontinued indefinitely in those with Grade 3 or 4 disease. Notes – immune checkpoint inhibitor myocarditis 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. References 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 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 Ganatra S, Neilan TG. Immune checkpoint inhibitor-associated myocarditis. Oncologist. 2018;23(8):879–86. https://doi.org/10. 1634/theoncologist.2018-0130 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 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 CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

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 Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Cardiovascular Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – Omega-3 Fatty Acids & The Battle Of The Oils Coming soon! Show notes – Omega-3 Fatty Acids & The Battle Of The Oils Coming soon! References – Omega-3 Fatty Acids & The Battle Of The Oils 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]. 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. 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. 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. 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. 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. Guest Profiles Dr. Pam Taub 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 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. CardioNerds Lipids Production Team Tommy Das, MD Dr. Rick Ferraro Amit Goyal, MD Daniel Ambinder, MD

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. Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Cardiac Critical Care PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes – Cardiogenic Shock and Valvular Heart Disease 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. 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. 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. Echocardiography is critical to understand the etiology and severity of valvular shock, and invasive hemodynamics are often needed to guide medical and mechanical interventions. 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. Show notes – Cardiogenic Shock and Valvular Heart Disease 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.  References – Cardiogenic Shock and Valvular Heart Disease 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. Guest Profiles Dr. Paul Cremer 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 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. CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Dr. Yoav Karpenshif Amit Goyal, MD Daniel Ambinder, MD

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. Question #6 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 glipizideB. Start saxagliptinC. Start empagliflozinD. No changes Answer #6 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. CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

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. Question #5 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. TrueB. False Answer #5 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. CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Dr. Roger Blumenthal, Director of the Ciccarone Center for the Prevention of Cardiovascular Disease at Johns Hopkins, discusses guidelines for cardiovascular prevention. They cover the management of hypertension in a 40-year-old woman, emphasizing lifestyle interventions and combination therapy. They also discuss the assessment of risk and antiplatelet therapy for blood pressure management, highlighting the importance of lifestyle changes and a two-drug combination approach.

Dr. Kim Williams, Chief of the Division of Cardiology, discusses the 2021 ESC Cardiovascular Prevention Guidelines. Topics include dietary recommendations for reducing cardiovascular disease risk, ASCVD modifications, sodium restriction and fiber intake, and controversies surrounding saturated fat and vitamin supplementation.

Dr. Allison Bailey, an advanced heart failure and transplant cardiologist, answers a question about cardiovascular prevention guidelines. The podcast covers the use of coronary artery calcium scoring for risk reclassification, guidelines for cardiovascular prevention and risk classification, and promoting healthy lifestyle and risk stratification using CAC score.

This question refers to Sections 3.2 and 3.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern, student Dr. Hirsh Elhence, answered first by Ohio State University Cardiology Fellow Dr. Alli Bigeh, and then by expert faculty Dr. Eugene Yang. Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #1 A 48-year-old Pakistani woman with rheumatoid arthritis comes to your clinic asking how she can reduce her risk of ASCVD. Her mother died of an MI at age 45, her father is healthy at age 79. Her calculated 10-year risk based on SCORE2 is 3%. SBP is 120 mmHg, LDL is 120 mg/dL. What is the next best step?  A. Order an echocardiogram B. Schedule a follow-up appointment in 1 year C. Discuss initiating a statin D. Repeat lipid panel in 3-5 years  Answer #1 Answer: C. Discuss Initiating a statin  The absolute benefit derived from risk factor modification depends on the absolute risk of CVD and the absolute improvements in each risk factor category. Risk factor treatment recommendations are based on categories of CVD risk (“low-to-moderate”, “high”, and “very high”). The cut-off risk levels for these categories are numerically different for various age groups to avoid undertreatment in the young and to avoid overtreatment in the elderly. As age is a major driver of CVD risk, but lifelong risk factor treatment benefit is higher in younger people, the risk thresholds for considering treatment are lower for younger people as per the ESC guidelines. Treatment decisions should be made with shared decision-making valuing patient preference.   Option A is INCORRECT- there is a lack of convincing evidence that echocardiography improves CVD risk reclassification, and it is NOT recommended to improve CV risk prediction. (Class III, LOE B)  Option B is INCORRECT- simply doing nothing is not appropriate for this patient with elevated CVD risk.   Option C is CORRECT- This patient has a seemingly low 10-year CVD risk based on SCORE 2 of 3% and her SBP is controlled; however, given her age she is considered as having high CVD risk, therefore treatment should be considered. Stepwise approach involves targeting LDL <100 (class IIa) so initiating a statin would be appropriate. This patient also carries several risk enhancing modifiers including Pakistani ethnicity, family history of premature CVD, and inflammatory comorbidity. All patients should be counseled on smoking cessation, lifestyle modifications, and target SBP <160 mmHg.  Option D is INCORRECT- repeating a lipid panel without risk factor modification will not change treatment recommendations for this patient with elevated CVD risk.   Main Takeaway  In summary, when a patient <50 years old without established ASCVD has an estimated 10-year risk 2.5 to <7.5% they are considered high CVD risk and risk factor treatment should be considered. Risk modifiers should also be taken into consideration.  *Of note- ACC/AHA guidelines recommend the ASCVD risk calculator to estimate 10-year risk and do not restructure CVD risk groups according to age groups. High risk in the ACC/AHA guidelines is considered to be >20%.  Guideline Location Table 5 and Figure 5, Page 3251 3.2.3.4, Page 3253 3.2.3, Figure 6 page 3252 3.3, Pages 3258-3259  CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!