Cardionerds: A Cardiology Podcast

CardioNerds Tommy Das (Program Director of the CardioNerds Academy and cardiology fellow at Cleveland Clinic), Rick Ferraro (Director of CardioNerds Journal Club and cardiology fellow at the Johns Hopkins Hospital), and CardioNerds Healy Honor Roll Ambassador Dr. Justice Oranefo (UConn cardiology fellow) discuss omega-3 fatty acids acid with Dr. Ty Gluckman, preventive cardiologist and medical director of the Center for Cardiovascular Analytics, Research, and Data Science (CARDS) at the Providence St. Joseph Heart Institute in Portland, Oregon. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen. In the recent years, purified omega 3 fatty acids and its esters have emerged as a potential new tool in our arsenal for management of hypertriglyceridemia and atherosclerotic coronary artery disease. In this episode we review the sources and basic structure of these compounds, as well as their metabolic effects as it pertains to cardiovascular disease. Using hypothetical patient cases, we also discuss scenarios in which these therapies can be useful. 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 Lipid Series 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 (n-3) fatty acids are a class of polyunsaturated fatty acids [PUFA]. The most studied n-3 fatty acids include eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and alpha linoleic acid [ALA]. ALA is found in certain vegetable oils while EPA and DHA are abundant in fish sources. Cardiovascular benefits of n-3 fatty acids include blood pressure reduction, enhanced diastolic function, triglyceride reduction, and immunomodulatory properties. Inflammation plays a major role in the atherogenic process and plaque rupture. Inflammatory marker hs-CRP is a risk enhancing factor for predicting future ASCVD risk. Ongoing trials are investigating therapy that target the inflammatory process in treatment of atherosclerotic heart disease. Prevention and management of ASCVD require aggressive lifestyle modifications and medical therapy addressing risk factors and underlying inflammatory conditions. Purified forms of n-3 fatty acids are approved for the treatment of severe hypertriglyceridemia and as an adjunct therapy to statins for reduction of coronary events in high-risk individuals. Show notes 1. What are omega 3 (n-3) fatty acids? What are the natural sources of n-3 fatty acids? n-3 fatty acids are class of polyunsaturated fatty acids [PUFA]. PUFA are types of unsaturated fats that have more than one double bond in their backbone. PUFAs are important constituents of the phospholipids of all cell membranes. The most studied n-3 fatty acids include eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and alpha linoleic acid [ALA]. ALA is found in certain vegetable oils including walnuts, flaxseeds, chia seeds. EPA and DHA are abundant in cold water fish oils such as salmon, mackerel, tuna sardines. Interestingly, farm raised fish usually have higher levels of EPA and DHA than wild caught fish; however, this depends on what the fish are fed. Another important class of PUFAs are omega 6 (n-6) fatty acids, found in vegetable oils (1,2).  2. What are the metabolic effects of omega 3 fatty acids? Multiple early studies have demonstrated the anti-inflammatory properties of n-3 fatty acids. The typical Western diet with a high arachidonic acid (an n-6 fatty acid) content promotes atherogenesis leading to the high incidence of CAD in this population. Supplementation with diets rich in DHA and EPA has been associated with reduced arachidonic acid content as well as reduced markers of inflammation. The relative dietary ratios of n-6:n-3 fatty acids have major implications for cardiovascular health. Anti-inflammatory mechanism of n-3 fatty acids include cell membrane stabilization, anti-oxidant properties, reduced leukocyte chemotaxis. (1-3). Other studied cardiovascular benefits of n-3 fatty acids include triglyceride lowering properties (11, 12), blood pressure and heart rate reduction (13, 14), improved endothelial function and antithrombotic properties (15, 16). Importantly, EPA and DHA are distinct molecules (different hydrocarbon length and number of double bonds) with different biologic effects. EPA assumes an extended conformation in cellular membranes, allowing it to neutralize reactive oxygen species, facilitate membrane stabilization, and limit oxidation of LDL cholesterol more easily. In contrast, DHA has a longer carbon chain and has one additional double bond, resulting in less membrane stabilization. DHA also inhibits formation of Dihomo-γ-linolenic acid (DGLA), which is important for production of anti-inflammatory eicosanoids and thus can also increase levels of LDL cholesterol. 3. What role does inflammation play in coronary artery disease? The impact of inflammation in the pathogenesis of atherosclerosis and plaque rupture has been well studied. Inflammatory mediators such CRP, IL-6, and myeloperoxidase have been found to be associated with increased cardiovascular risk. The JUPITER trial demonstrated the benefit of statin therapy in patients with elevated hsCRP. Subsequent trials targeting inflammation in the management of CAD have shown promise. Examples include the LoDoCo which investigated colchicine therapy and the CANTOS trial with investigated the IL-1 beta inhibitor canakinumab. The pathogenic role of inflammation and potential therapeutic role of anti-inflammatory therapy remain key areas of interest and multiple pharmacologic agents are undergoing investigation. (6, 7, 8, 17, 18). Check out the #CardsJC on the LoDoCo 2 trial for more on Colchicine in the management of CAD. Table 1 below summarizes notable trials of anti-inflammatory therapies for ASCVD. 4. What is the role for n-3 fatty acids in management of coronary artery disease? While a diet rich in n-3 fatty acids is associated with a lower risk of cardiovascular events, supplementation with over-the-counter fish oil containing supplements have not demonstrated significant cardiovascular benefits. Purified forms of high dose n-3 fatty acid esters consisting of EPA and/or DHA have shown mixed results as therapies for ASCVD. In the JELIS trial, patients with hypercholesterolemia treated with high dose icosapent ethyl (an EPA ester) in addition to pravastatin 10mg/day or simvastatin 5mg/day experienced reduced incidence of cardiac events and reduced LDL with greater benefit seen in patients with impaired glucose metabolism. The REDUCE-IT trial showed similar results in patients with atherosclerotic disease and high risk patients with elevated fasting triglycerides. Interestingly, the STRENGTH trial, in which patients were treated with combination EPA+DHA, did not show a benefit in the treatment arm. Icosapent ethyl is currently indicated as an adjunct therapy in addition to maximally tolerated statin therapy in patients with triglyceride levels ≥150 mg/dL and either established cardiovascular disease or type 2 diabetes mellitus plus ≥2 risk factors for cardiovascular disease to reduce incidence of cardiac events. (19 – 21). Check out the #CardsJC on the STRENGTH trial for an overview of relevant trial data. Table 2 below summarizes notable trials of omega-3 fatty acids for ASCVD. 5. What is the role of n-3 fatty acids in management of hypertriglyceridemia? In the approach to hypertriglyceridemia, be sure to identify and treat secondary causes (alcoholism, hypothyroidism, uncontrolled diabetes, etc) before instituting pharmacotherapy. Enjoy the CardioNerds “Causes of Hypertriglyceridemia” infographic developed by Dr. Teodora Donisan. The 2021 ACC expert consensus decision pathway on the management of ASCVD in patients with hypertriglyceridemia provides guidelines and algorithmic strategies to management of hypertriglyceridemia in several patient populations (22). The triglyceride reducing properties of n-3 fatty acids have been demonstrated on several trials including the EVOLVE trial (11). One should note that while several therapies reduce triglycerides, the potential benefits from n-3 fatty acids likely extend beyond triglyceride reduction. Table 1. Previous randomized controlled trials investigating colchicine and other anti-inflammatory therapies in the treatment of atherosclerotic ischemic heart disease Table 2. Review of relevant randomized control trials on Omega-3 fatty acids. CAD, coronary artery disease; CV, cardiovascular; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; MACE, major adverse cardiovascular events. Infographic. Causes of Hypertriglyceridemia by Dr. Teodora Donisan. References – Triglycerides MOZAFFARIAN, D. & WU, J.H.Y., 2011. Omega-3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors, Molecular Pathways, and Clinical Events. Journal of the American College of Cardiology, 58(20), pp.2047–2067. Calder, Philip C, 2010. Omega-3 fatty acids and inflammatory processes. Nutrients, 2(3), pp.355–374. Raphael, William & Sordillo, Lorraine M, 2013. Dietary polyunsaturated fatty acids and inflammation: The role of phospholipid biosynthesis. International journal of molecular sciences, 14(10), pp.21167–21188. Schwalfenberg, G., 2006. Omega-3 fatty acids: their beneficial role in cardiovascular health. Canadian family physician, 52(6), pp.734–740. Hansson, Göran K, 2005. Mechanisms of disease: Inflammation, atherosclerosis, and coronary artery disease. The New England journal of medicine, 352(16), pp.1626–1695. Ridker, Paul M et al., 2008. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. The New England journal of medicine, 359(21), pp.2195–2207. Ridker, Paul M et al., 2017. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. The New England journal of medicine, 377(12), pp.1119–1131. Tardif, Jean-Claude et al., 2019. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. The New England journal of medicine, 381(26), pp.2497–2505. Xin, Wei, Wei, Wei & Li, Xiaoying, 2012. Effects of fish oil supplementation on inflammatory markers in chronic heart failure: a meta-analysis of randomized controlled trials. BMC cardiovascular disorders, 12(1), p.77. Li, Kelei et al., 2014. Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: A meta-analysis. PloS one, 9(2), p.e88103. Skulas-Ray, Ann C et al., 2019. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation (New York, N.Y.), 140(12), pp.CIR0000000000000709–e691. Bhatt, Deepak L et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22. Geleijnse, J.M. et al., 2002. Blood pressure response to fish oil supplementation : metaregression analysis of randomized trials. Journal of hypertension, 20(8), pp.1493–1499. Mozaffarian, D. et al., 2005. Effect of fish oil on heart rate in humans. A meta-analysis of randomized controlled trials. Circulation (New York, N.Y.), 112(13), pp.1945–1952. Dangardt, F. et al., 2010. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis, 212(2), pp.580–585. Goodfellow, J. et al., 2000. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. Journal of the American College of Cardiology, 35(2), pp.265–270. Nidorf, S.M. et al., 2020. Colchicine in Patients with Chronic Coronary Disease. The New England journal of medicine, 383(19), pp.1838–1847. Nidorf, Stefan M., MD, MBBS et al., 2013. Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease. Journal of the American College of Cardiology, 61(4), pp.404–410. Yokoyama, Mitsuhiro, Dr et al., 2007. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet (British edition), 369(9567), pp.1090–1098. Bhatt, D.L. et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22. Nicholls, S.J. et al., 2020. 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 : the journal of the American Medical Association, 324(22), pp.2268–2280. Virani, S.S. et al., 2021. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia. Journal of the American College of Cardiology, 78(9), pp.960–993. Guest Profiles Dr. Ty Gluckman Dr. Ty Gluckman is the medical director of the Center for Cardiovascular Analytics, Research, and Data Science (CARDS) at the Providence St. Joseph Heart Institute in Portland, Oregon and an adjunct faculty member of the Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins Hospital. He has previously served as National Clinical Quality Expert for the ACC Patient Navigator Program and currently serves as National Chair of the ACC Patient Navigator Program-Focus MI. Additionally, Dr. Gluckman is a leader not only in the field of cardiovascular prevention, but also care coordination, quality improvement, and even App development as the lead developer of the ACC/AHA ASCVD risk calculator app Dr. Justice Oranefo Dr. Justice Oranefo is a cardiology fellow at University of Connecticut. Following his undergraduate degree in Biomedical Science in the United Kingdom, he completed medical school at St George’s University Grenada followed by Internal Medicine residency at University of Massachusetts. He is passionate about medical education and diversity in medicine. CardioNerds Lipids Production Team Tommy Das, MD Dr. Rick Ferraro Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Loie Farina (Northwestern University CardioNerds Ambassador), Dr. Josh Cheema, and Dr. Graham Peigh from Northwestern University for drinks along the shores of Lake Michigan at North Avenue Beach. They discuss a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presents with progressive symptoms of heart failure and is found to have a severe, non-ischemic cardiomyopathy. The etiology of her cardiomyopathy is not clear until her untimely death. She is ultimately diagnosed with cardiac AL amyloidosis with isolated vascular involvement a real occam’s razor or hickam’s dictum conundrum. We discuss the work-up and management of her condition including a detailed discussion of the differential diagnosis, the underlying features of systemic sclerosis with cardiac involvement as well as cardiac amyloidosis, the role of a shock team in managing cardiogenic shock, and how to identify those with advanced or stage D heart failure. Advanced heart failure expert Dr. Yasmin Raza (Northwestern University) provides the ECPR segment. Episode introduction by CardioNerds Clinical Trialist Dr. Liane Arcinas. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen. Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls – Notes – 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 Summary – Occam’s Razor or Hickam’s Dictum? This is a case of a 52-year-old woman with limited cutaneous systemic sclerosis who presented with progressive dyspnea on exertion and weight loss over the course of 1 year. Her initial work-up was notable for abnormal PFTs and finding of interstitial pneumonia on high-resolution CT, an ECG with frequent PVCs and normal voltage, a transthoracic echocardiogram with a mildly reduced ejection fraction of 40%, and a right/left heart catheterization with normal coronary arteries, filling pressures, and cardiac output. Scleroderma-related cardiac involvement is suspected. She is placed on GDMT, but her condition worsens over the next several months, and repeat echocardiogram shows severely reduced biventricular function, reduced LV global longitudinal strain (GLS) with apical preservation of strain, severely reduced mitral annular tissue Doppler velocities, and a normal left ventricular wall thickness. Scleroderma-related cardiac involvement remains highest on the differential, but because of some findings on the echo that are concerning for cardiac amyloidosis, an endomyocardial biopsy was obtained. It showed vascular amyloid deposition without interstitial involvement. The diagnosis of cardiac amyloid was discussed but deemed unlikely due to lack of interstitial involvement. However, a serologic work-up soon revealed a monoclonal serum lambda light chain and a follow-up bone marrow biopsy showed 20% plasma cells. She was discharged with very near-term follow-up in oncology clinic with a presumptive diagnosis of AL amyloidosis, but she unfortunately returned in shock and suffered a cardiac arrest. She initially survived and underwent emergent veno-arterial extracorporeal membrane oxygenation (VA ECMO) cannulation with subsequent left ventricular assist device placement (LVAD). However, she passed away due to post-operative hemorrhage. Autopsy was consistent with a final diagnosis of cardiac AL amyloidosis with isolated vascular involvement.  Case Media – Occam’s Razor or Hickam’s Dictum? EKG CXR TTE Pathology CMR Episode Teaching -Occam’s Razor or Hickam’s Dictum? Pearls Scleroderma causes repeated focal ischemia-reperfusion injuries which result in patchy myocardial fibrosis. Cardiac involvement in scleroderma is frequent but often not clinically evident; when symptomatic, it is associated with a poor prognosis.  Myocardial dysfunction in cardiac AL amyloidosis can result from myocardial infiltration, vascular deposition causing microvascular dysfunction and ischemia, and direct cardiotoxicity from circulating light chains.  While isolated vascular amyloid is very rare, it can occur and can be seen without key characteristics of interstitial amyloid deposition, namely left ventricular hypertrophy and low voltage on an ECG.   Cardiogenic shock outcomes are improved by multi-disciplinary discussions, commonly referred to as a “shock team call.”   Heart failure is a progressive, morbid, and potentially fatal condition. LVADs and heart transplantation improve life expectancy and decrease morbidity among patients with stage D heart failure. Identification of patients with advanced heart failure can be challenging – a helpful mnemonic is “I NEED HELP  Notes – Occam’s Razor or Hickam’s Dictum? 1. How does scleroderma affect the heart?  Scleroderma is a connective tissue disorder characterized by extracellular matrix deposition, with widespread fibrosis of the skin and visceral organs, microvascular injury, and evidence of immune system activation.   Cardiac involvement is common, although likely underestimated as it is often subclinical, and the estimated prevalence varies widely. Myocardial involvement is identified in up to 80% of patients in histological studies and clinical myocardial dysfunction is recognized in 15-25%. When clinically evident, cardiac involvement portends a poor prognosis, with up to a 70% mortality at 5 years. Approximately 25% of scleroderma-related deaths are due to cardiac causes.  Primary involvement is thought to be mediated by repeated focal ischemic-reperfusion injury, impaired microcirculation, inflammation, and eventual focal irreversible fibrosis leading to heart failure and arrhythmias.  Cardiac involvement can also occur secondary to lung or renal disease, pulmonary arterial hypertension, or other cardiovascular risk factors.   Cardiac manifestations:  Myocardial failure: diastolic dysfunction is frequently reported but less commonly associated with diastolic heart failure. Systolic dysfunction can also occur, but severe systolic dysfunction is rare.   Electrical failure: arrhythmias and conduction disorders  Pericardial failure: pericarditis and pericardial effusion  Coronary failure: coronary microvascular dysfunction  Valvular failure: valvular involvement (uncommon)   2. What is cardiac amyloidosis (CA) and what is the pathophysiology?   For an in-depth review of Cardiac Amyloidosis, enjoy the CardioNerds Cardiac Amyloid Series!  Amyloidosis is a process in which proteins misfold, aggregate, and form amyloid fibrils that deposit in various organs, thereby causing tissue injury and organ malfunction. The most common types of cardiac amyloidosis are AL (light chain) and TTR (transthyretin).   AL amyloidosis is a hematologic disorder of clonal plasma cells that overproduce light chains, which may deposit in any organ sparing the central nervous system, and commonly deposit in the heart and kidneys.   Delayed diagnoses are common, with an estimated one-third of patients visiting five or more physicians before receiving the diagnosis. Cardiac involvement with heart failure portends a particularly poor prognosis, with a median survival from onset of heart failure of less than six months without treatment. Stem cell transplantation has been shown to improve survival if performed prior to the diagnosis of advanced heart failure. Unfortunately, about 80% of patients are not candidates for aggressive therapy due to advanced stage of disease.  In CA, amyloid deposits infiltrate and expand the extracellular space which results in increased ventricular wall thickness and classically manifests as a restrictive cardiomyopathy with relatively preserved EF; however, a subset of patients may present with reduced LVEF and minimal or no ventricular wall thickening.   Patients with AL cardiac amyloidosis tend to have greater severity of heart failure than TTR despite less morphological involvement (in terms of LV wall thickness), felt due to the toxic effect of light chain amyloid fibrils on the tissue resulting in a toxic-infiltrative cardiomyopathy.   Additional mechanisms thought to play a major contributing role in cardiac AL amyloidosis:  Circulating light chains cause direct cardiotoxicity through cardiomyocyte oxidant stress and abnormal vascular reactivity, impairing vasodilation   Vascular amyloid deposition in the small intramural coronary vessels results in microvascular dysfunction and global myocardial ischemia. Vascular involvement is common in AL cardiac amyloidosis (much more common than in TTR cardiac amyloid). A pathology study demonstrated obstructive intramural coronary amyloidosis in 63 of 96 patients (66%) and 86% of these patients had microscopic evidence of myocardial ischemia. Isolated vascular involvement, however, is rare – 97% of patients in this study had interstitial involvement.   Coronary microvascular dysfunction occurs via 3 major mechanisms:   Structural – with amyloid deposition in the vessel wall causing wall thickening and luminal stenosis  Extravascular – through extrinsic compression of the microvasculature from perivascular and interstitial amyloid deposits and decreased diastolic perfusion  Functional – through autonomic and endothelial dysfunction  3. What are common cardiac MRI (CMR) findings in scleroderma heart disease and cardiac amyloidosis?  First, a review of a few key concepts in CMR (also, enjoy Episode #33. Cardiac MRI with Dr. Deborah Kwon):  Native T1 signals are increased by edema (e.g. acute infarction) and an increase in interstitial space (e.g. fibrosis, amyloidosis). T1 signals are decreased by lipid and iron overload.   Gadolinium contrast agents are distributed throughout the extracellular space and shorten the T1 relaxation times of myocardium in proportion to local concentrations of gadolinium – areas of fibrosis/scar will exhibit shorter T1 relaxation times (due to higher gadolinium proportion).  Extracellular volume fraction is calculated using myocardial and blood T1 before and after contrast is administered. It serves as a marker of myocardial tissue remodeling; ECV is increased in amyloid and excessive collagen deposition and serves as a robust marker of myocardial fibrosis.  Late gadolinium enhancement (LGE) – depicts relative difference in the T1 recovery times between enhancing areas of fibrosis or scar (T1 shortened due to accumulation of extracellular gadolinium contrast agent) and normal nulled myocardium (longer T1 as gadolinium contrast agent is more rapidly washed out).  T2 weighted imaging – sensitive to regional or global increases in myocardial water content (i.e. edema).  Scleroderma CMR findings:   Perfusion defects – predominantly stress perfusion abnormalities, less common at rest  Increased signal intensity on T2-weighted sequences  Increase in ECV  Delayed enhancement – mainly linear and typically mid-wall (spares the endocardium)   Accurate assessment of RV function, which is particularly important given risk of PAH in these patients  Amyloid CMR findings:  T1 signal abnormalities  Increase in ECV  Classically, causes global subendocardial LGE in a noncoronary distribution; however, LGE can also be diffuse and transmural or more localized and patchy  Difficulty nulling the myocardium (the myocardium appears similar to the blood pool)  Myocardial nulling” refers to an inversion recovery pulse sequence that is used to null the signal from a desired tissue to accentuate surrounding pathology.   Normally, the blood pool nulls before the myocardium but in amyloid myocardium nulls simultaneously or before the blood pool  4. How do we identify if someone has Stage D or advanced heart failure?  A topic of critical importance is identifying which patients have advanced or Stage D heart failure, those that are so sick that GDMT alone or interventions including cardiac resynchronization therapy, implantable pulmonary artery pressure monitor, or percutaneous mitral valve repair are unlikely to prolong life and prevent suffering. These patients benefit from timely evaluation for advanced heart failure therapies: left ventricular assist device (LVAD) or orthotopic heart transplant (OHT).   Heart failure is a progressive condition. A study in JACC HF in 2017 with Dr. Javed Butler as the senior author showed that in a cohort of outpatients with Stage C HF, 25% progressed to Stage D or died within a 3-year span. They estimated that 100,000 patients a year progress from Stage C to Stage D.   Unfortunately, it is not always clear who has made this transition until it is too late. This was reinforced by a study published in 2021 in the Journal of Cardiac Failure. This was a multi-center retrospective analysis of referral patterns for LVAD/transplant, and they showed that 40% of the 515 patients studied were deemed to be too sick to qualify for an advanced therapy, and 60% of the referrals coming from the inpatient setting, clearly too late in the disease course.  So how do we identify patients with advanced HF? In addition to the guideline document mentioned, there is a popular mnemonic that can help you remember red flags.  The mnemonic is “I NEED HELP.”  I Inotropes N NYHA class III or IV  E End organ damage  E Very low EF, <20%  D Defibrillator shocks  H Hospitalization, >1 in last 12 months  E Edema with escalating diuretic doses  L Low blood pressure   P Progressive intolerance of GDMT   This identification schema is not perfect, and neither are our definitions for staging patients with heart failure. This is an area in need of active research.   5. What is a “shock team” and what is its role in the management of cardiogenic shock?   In cardiogenic shock, diminished cardiac output leads to systemic hypoperfusion and resultant ischemia, inflammation, vasoconstriction, and salt/fluid retention with volume overload. The short-term mortality in CS is >40%.  A multidisciplinary shock team, composed of advanced heart failure, cardiac surgery, interventional cardiology, and critical care facilitates timely consultation and decision making. Observational studies suggest that a shock team approach may improve CS outcomes. A 2019 study published in JACC evaluated the impact of a standardized team-based approach in 204 consecutive patients with CS. 204 consecutive patients with CS were enrolled. They found that 30-day survival in 2017 and 2018 was 57.9% and 76.6%, respectively compared with a 30-day survival of 47% in 2016 (P<0.01).   For more on this, enjoy Episode #168. Cardiogenic Shock – Initial Assessment and The Shock Team Call with Dr. Anu Lala as part of the CardioNerds Cardiac Critical Care Series.  References Bissell LA, Anderson M, Burgess M, et al. Consensus best practice pathway of the UK Systemic Sclerosis Study group: management of cardiac disease in systemic sclerosis. Rheumatology (Oxford). 2017;56(6):912-921. https://pubmed.ncbi.nlm.nih.gov/28160468/  Bissell LA, Md Yusof MY, Buch MH. Primary myocardial disease in scleroderma-a comprehensive review of the literature to inform the UK Systemic Sclerosis Study Group cardiac working group. Rheumatology (Oxford). 2017;56(6):882-895. https://pubmed.ncbi.nlm.nih.gov/27940590/  Tehrani BN, Truesdell AG, Sherwood MW, et al. Standardized Team-Based Care for Cardiogenic Shock. Journal of the American College of Cardiology. 2019;73(13):1659-1669. https://pubmed.ncbi.nlm.nih.gov/30947919/  Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S. Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review. Journal of Cardiovascular Magnetic Resonance. 2016;18(1):89. https://pubmed.ncbi.nlm.nih.gov/27899132/  Hachulla A-L, Launay D, Gaxotte V, et al. Cardiac magnetic resonance imaging in systemic sclerosis: a cross-sectional observational study of 52 patients. Annals of the Rheumatic Diseases. 2009;68(12):1878-1884. https://pubmed.ncbi.nlm.nih.gov/19054830/  Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis. Circulation. 2017;135(14):1357-1377. https://pubmed.ncbi.nlm.nih.gov/28373528/  Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol. 2016;68(12):1323-1341. https://pubmed.ncbi.nlm.nih.gov/27634125/  Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-1212. https://pubmed.ncbi.nlm.nih.gov/19752327/  Kalogeropoulos AP, Samman-Tahhan A, Hedley JS, et al. Progression to Stage D Heart Failure Among Outpatients With Stage C Heart Failure and Reduced Ejection Fraction. JACC Heart Fail. 2017;5(7):528-537. https://pubmed.ncbi.nlm.nih.gov/28624484/  Fang JC, Ewald GA, Allen LA, et al. Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee. J Card Fail. 2015;21(6):519-534. https://pubmed.ncbi.nlm.nih.gov/25953697/  Herr JJ, Ravichandran A, Sheikh FH, et al. Practices of Referring Patients to Advanced Heart Failure Centers. J Card Fail. https://pubmed.ncbi.nlm.nih.gov/34146684/  Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435-1443. https://pubmed.ncbi.nlm.nih.gov/11794191/  Alanna A. MorrisMD, MSc, FAHA, Chair, Prateeti Khazanie, MD, MPH, Vice Chair, Mark H. Drazner, MD, MSc, Vice Chair, Nancy M. Albert, PhD, Khadijah Breathett, MD, MS, FAHA, Lauren B. Cooper, MD, MHS, Howard J. Eisen, MD, Patrick O’Gara, MD, Stuart D. Russell, MD, on behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Hypertension. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001016  CardioNerds Case Report Production Team Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

Approximately 350,000 adults per year in the US experienced out-of-hospital cardiac arrest (OHCA). Only about 10% of such patients survive their initial hospitalization. The key drivers of successful resuscitation from OHCA are bystander cardiopulmonary resuscitation (CPR) and public use of an automated external defibrillator (AED). Survival rates from OHCA vary dramatically between US regions. For instance, the extracorporeal CPR (eCPR) program at the University of Minnesota has over a 40% survival rate in patients with OHCA and refractory ventricular fibrillation (VF) based on data published in the ARREST trial. In this episode, we are joined by experts from the University of Minnesota, including Dr. Jason Bartos (Interventional and Critical Care Faculty) and Dr. Julie Power (Chief Fellow at University of Minnesota and CardioNerds Academy Fellow), along with Dr. Yoav Karpenshif (Co-Chair Critical Care Series, University of Pennsylvania) and CardioNerds Co-Founders (Amit Goyal and Dan Ambinder) to discuss cardiac arrest, E-CPR, & post-arrest care. This includes targeted temperature management, coronary angiography and revascularization, as well as the growing field of eCPR and VA ECMO.  Episode introduction by CardioNerds Clinical Trialist Dr. Jason Feinman. Audio editing by CardioNerds Academy Intern, Shivani Reddy. 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. Claim free CME for enjoying this episode! Disclosures: None 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! Abbreviations – Cardiac Arrest, E-CPR, & Post-Arrest Care eCPR- extracorporeal cardiopulmonary resuscitation VA ECMO- veno-arterial extracorporeal membrane oxygenation VT/VF- ventricular tachycardia/ventricular fibrillation ACLS- advanced cardiovascular life support ROSC- return of spontaneous circulation- OHCA- out-of-hospital cardiac arrest IHCA- in-hospital cardiac arrest TTM- targeted temperature management Pearls and Quotes – Cardiac Arrest, E-CPR, & Post-Arrest Care The ARREST trial showed early VA ECMO-facilitated resuscitation for patients with OHCA and refractory VF significantly improved survival to hospital discharge when compared to standard ACLS treatment. Coronary artery disease is common in the setting of cardiac arrest, with up to 96% of patients with STEMI on post resuscitation EKG and up to 85% of refractory out-of-hospital VT/VF arrests. Guidelines recommend emergent coronary angiography for patients with ST-segment elevation on the post-ROSC ECG. The role of timing of revascularization after ROSC in patients without STEMI or shock is unknown. The role of coronary angiography in cardiac arrest with nonshockable rhythms is also unclear. The current AHA guidelines recommend initiation of targeted temperature management between 32°C and 36°C for at least 24 hours for all patients who do not follow commands after ROSC in both OHCA and IHCA. Show notes – Cardiac Arrest, E-CPR, & Post-Arrest Care 1. What are early post arrest management considerations? The key drivers of successful resuscitations from OHCA: CPR and public use of AEDs in the field. After initial stabilization, care of the critically ill post-arrest patient hinges on hemodynamic support, mechanical ventilation, temperature management, attending to adverse sequelae of arrest, and diagnosis and treatment of underlying causes of arrest. Coronary artery disease is common in the setting of VT/VF cardiac arrest, with up to 96% of patients with STEMI on post resuscitation EKG and up to 85% of refractory out-of-hospital VT/VF arrests. In the early post-arrest state, it is also important to diagnose and treat infections and any neurologic injury. Neurologic compromise is a common cause of mortality in patients who achieve ROSC. Over 50%, and in some cohorts around 75%, of patients with death after resuscitated OHCA die of neurologic injury. 2. What is the current evidence for targeted temperature management (TTM)? “[This is] the most hotly debated topic right now in the field of cardiac arrest.” – Dr. Jason Bartos Current AHA guidelines recommend initiation of targeted temperature management between 32°C and 36°C for at least 24 hours for all patients who do not follow commands after ROSC in both OHCA and IHCA. TTM is a relatively safe and effective strategy that can improve neurological outcomes in patients who remain comatose after achieving ROSC from cardiac arrest. Current evidence supports a broad range of TTM from 33°C to 36°C and should be maintained for 24 hours. Although TTM should be initiated as early as possible, prehospital initiation of cooling has not been shown to improve survival outcomes. The TTM2 trial showed that in patient with coma following OHCA, targeted hypothermia versus normothermia (i.e., fever control) was not associated with improved survival or functional outcomes compared to normothermia. It should be noted that patients on VA ECMO were not included in this trial. 3. What are some possible complications from TTM? Arrhythmias: Hypothermia slows cardiac conduction leading to bradycardia and QT prolongation which can exacerbate underlying arrhythmias such as VT/VF. Consideration can be given to actively rewarming the patient in the setting of VT/VF. Clotting: Core temperatures below 35°C impede the clotting cascade and platelet function. Because of this, if a patient develops significant non-compressible bleeding while undergoing TTM, consideration should be given to actively rewarm the patient. Shivering is a natural response to hypothermia. Suppression of this is crucial for TTM. First line strategies include propofol, fentanyl, or midazolam. Dexmedetomidine is effective, but side effects of bradycardia can limit its use. Buspirone (a 5-HT agonist), when used in conjunction with opiate analgesia or dexmedetomidine, has been shown to lower the shivering threshold. Neuromuscular blocking agents are highly effective at preventing shivering but confound the neurologic examination and may mask seizures. Patients need to be deeply sedated (typically RASS –4 or lower) and be followed with train-of-four assessments. Diuresis increases with hypothermia potentially leading to electrolyte loss of potassium, magnesium and phosphorous. Therefore, electrolytes need to be frequently monitored. Interestingly, total body potassium may not actually be low due to cellular shifts; thus, conservative replacement is recommended. Insulin resistance can develop as well. 4. How do we select appropriate patients to pursue revascularization and consider the timing of revascularization in patients with recent cardiac arrest? Guidelines recommend emergent coronary angiography for patients with ST-segment elevation on the post-ROSC ECG. However, the role and timing of revascularization after ROSC in patients without STEMI or shock is unknown. The role of coronary angiography in cardiac arrest with non-shockable rhythms is also unknown. 5. What is the physiologic basis for eCPR? The biggest predictor of post-arrest outcome is time. In the ALPS trial (2016), patients who underwent zero to nine minutes of CPR with ROSC had a survival of 65%. Survival dropped by 17% for every extra 10 minutes of CPR, such that there were no survivors in the amiodarone arm of the trial after 40 minutes. The results of this study were replicated at the University of Minnesota: OHCA brought to University of Minnesota Cath lab within 30 minutes of their cardiac arrest had a >90% survival rate. Survival rate drops over elapsed time: for every additional 10 minutes of ACLS, there is 25% additional mortality. If VA ECMO is initiated >90 minutes after arrest, survival is poor (10-15%). The study showed eCPR was associated with improved neurologically favorable survival at all CPR durations <60 minutes, despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival. 6. What is the evidence base for eCPR? The ARREST trial (the 1st RCT of eCPR) showed that early VA ECMO-facilitated resuscitation for patients with OHCA and refractory VF significantly improved survival to hospital discharge when compared to standard ACLS treatment. The trial comprised of 30 OHCA patients in refractory VT/VF (failed 3 shocks in the field) and ongoing CPR randomized to usual ACLS vs VA ECMO placement in the cath lab with subsequent coronary angiogram. The plan was to enroll 77 patients in the trial; however, after the 1st analysis, the trial was stopped early due to reaching pre-specified benefit endpoint. There was a large improvement in the primary outcome of survival to hospital discharge (43% versus 7%). Survival to 3 and 6 months was also better in the VA ECMO CPR group (43% vs 0%, p=0.006). The ARREST trial showed that early VA ECMO-facilitated resuscitation for patients with OHCA and refractory VF significantly improved survival to hospital discharge when compared to standard ACLS treatment. Based on this evidence, we know the likelihood of ROSC in the field drops significantly after 20-25 minutes. Thus, if the patient receives >3 shocks or >15-20 min of ongoing CPR without recovery of a perfusing rhythm, VA ECMO should be considered. References – Cardiac Arrest, E-CPR, & Post-Arrest Care Bartos JA, Grunau B, Carlson C, et al. Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation. Circulation. 2020 Mar 17;141(11):877-886. Garcia S, Drexel T, Bekwelem W, et al.. Early access to the cardiac catheterization laboratory for patients resuscitated from cardiac arrest due to a shockable rhythm: the Minnesota Resuscitation Consortium Twin Cities Unified Protocol. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556. doi:10.1056/NEJMoa012689 Inoue A, Hifumi T, Sakamoto T, Kuroda Y. Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest in Adult Patients. J Am Heart Assoc. 2020;9(7):e015291. Kudenchuk PJ, Leroux BG, Daya M, et al. Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation. 2017 Nov 28;136(22):2119-2131. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2019;380(15):1397-1407. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(16 2):S366-S468. Sonnier, M, Rittenberger, JC. State-of-the-art considerations in post-arrest care. JACEP Open 2020; 1: 107-116. Yannopoulos D, Bartos J, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020;396(10265):1807-1816. Yannopoulos D, Bartos JA, Aufderheide TP, et al. American Heart Association Emergency Cardiovascular Care Committee. The Evolving Role of the Cardiac Catheterization Laboratory in the Management of Patients With Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.Circulation. 2019; 139:e530–e552. Guest Profiles Dr. Jason Bartos Dr. Jason Bartos was born and raised in Maple Plain, MN. He completed his undergraduate work in Chemistry and Psychology at St. John’s University and went on to earn his PhD in Pharmacology from the University of Iowa. He then moved to Stanford University School of Medicine where he earned his MD and completed Internal Medicine residency. He moved to the University of Minnesota in 2012 where he completed fellowships in Cardiovascular Medicine, Critical Care Cardiology, and Interventional Cardiology. Dr. Bartos is board-certified in internal medicine, cardiology, critical care medicine, and interventional cardiology. His clinical interests include cardiac critical care, resuscitation, advanced hemodynamic support, pulmonary embolus, and coronary artery disease and intervention. He is the Medical Director of the Cardiovascular Intensive Care Unit. Dr. Bartos’s research interests include resuscitation, advanced hemodynamic support, and recovery from cardiac arrest. He has performed research in the field of ischemia and reperfusion injury for 20 years describing the molecular pathways of injury in models of cerebral ischemia and investigating potential therapies to mitigate the effects of reperfusion injury in heart transplantation, myocardial infarction, and refractory cardiac arrest. Dr. Bartos is the Associate Medical Director of the Center for Resuscitation Medicine at the University of Minnesota and the President of the Minnesota Mobile Resuscitation Consortium where he works to improve survival for patients suffering cardiac arrest. This work has resulted in the development of protocols utilizing rapid transport from the field, peripherally placed veno-arterial ECMO, coronary reperfusion, and subsequent cardiac intensive care to improve outcomes for patients with refractory VT/VF cardiac arrest. Dr. Juliette Power Dr. Julie Power @JuliettePower44 is a cheif cardiology fellow at the University of Minnesota. She completed medical school at Drexel University in Philadelphia followed by residency training at Allegheny General Hospital in Pittsburgh where she also served a Chief Resident. In addition to a continued involvement in medical education, Julie plans to pursue additional training in interventional cardiology after her general cardiology fellowship. In her free time, she enjoys spending time with family and friends, including exploring Minnesota with her boyfriend, Steve. CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Amit Goyal, MD Daniel Ambinder, MD

CardioNerd (Amit Goyal), Dr. Zarina Sharalaya (Interventional cardiology fellow at the Cleveland Clinic), Dr. Ashley Mohadjer (Interventional cardiology fellow, Vanderbuilt Heart and Vascular Institute), and Dr. Laurie Mbuntum (Cardiology fellow, UTSW) join Dr. Ki Park (Associate professor of medicine and an interventional cardiologist at the University of Florida and Malcom Randall VA Medical Center in Gainesville, FL.) for a a well-rounded discussion on all things ‘Women-in-Cardiology’ #WIC . Dr. Ki Park discusses how she nurtured her interest in interventional cardiology, and further shares her thoughts and passion for cardio-obsetrics. She shares her advice for trainees thinking about interventional or cardioobetrics and anecdotes from her training as a successful woman in the field. We discuss the need for education on pregnancy outcomes and long-term cardiovascular risk, ideas to lower maternal mortality, how to start a women’s cardiovascular clinic, and her thoughts on how the field may look in the future. Special message by Florida ACC State Chapter Governor, Dr. David Perloff. Episode introduction and audio editing by CardioNerds Academy Intern, Shivani Reddy. 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. Video Version • Notes • Production Team Claim free CME just for enjoying this episode! There are no relevant disclosures for this episode. The PA-ACC & CardioNerds Narratives in Cardiology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Video version – Interventional Cardiology, Cardioobstetrics, & Work Life Integration with Dr. Ki Park https://youtu.be/_oYUc-_sdfU Tweetorial – Interventional Cardiology, Cardioobstetrics, & Work Life Integration with Dr. Ki Park https://twitter.com/gurleen_kaur96/status/1495921275545563136?s=21 Quotables – Interventional Cardiology, Cardioobstetrics, & Work Life Integration with Dr. Ki Park “I like the work life integration as opposed to work life balance. Balance just implies that you always have everything aligned perfectly at all times and that is just not doable.” Dr. Ki Park Show notes – Interventional Cardiology, Cardioobstetrics, & Work Life Integration with Dr. Ki Park Why is screening for OB-GYN history for cardiovascular risk is important, and who should be responsible? Pregnancy is nature’s stress test and in some women can unmask someone’s predisposition to cardiac disease Yearly screening for diabetes, hypertension, dyslipidemia Big interdisciplinary effort in attempt to try to capture all women at risk, as many will not present with manifestation of disease initially How did you nurture your interest in cardioobsetrics? In interventional cardiology? Meetings and societies Connect with those who work in the field, social media Regarding interventional cardiology – having interest in procedures, do as many cases “hands on” as possible, learning from mistakes What advise do you have to achieve work and life balance? It’s important to understand the various occupational hazards of radiation exposure which include but are not limited to brain tumors, cataracts, thyroid disease, cardiovascular diseases, musculosketal problems and reproductive side effects. Have grace, one can’t be 100% at every single thing all the time Its more work life integration as opposed to a balance Prioritize different things on different days, be honest with children and explain why you do what you do in age appropriate terms Maternal mortality is high in this country with cardiovascular disease as a leading cause. What are important factors to improve maternal mortality? Education Improving access to care in the peripartum stage for mothers, particularly since the focus in that period is on baby Legislature to improve insurance coverage         Where do you see cardioobsetrics field going in the next few years? Make the knowledge more mainstream Education of subspecialty fellows within cardiovascular education Collaboration with ACOG and maternal fetal medicine societies More registries of patients to continue to learn more about these women What was involved to create the women’s heart clinic in your institution? Start small – there are plenty of women who want to seek specialized care Having an MFM and congenital faculty at the same institution was helpful Seek advice from those at expert centers           What advise do you have for trainees looking to pursue a career in interventional cardiology who are worried about work-life integration? Understand what you’re getting into, particularly for that year    Don’t be afraid to ask for help from friends or family at home to allow for more quality time with significant others, kids, friends, etc — this isn’t a sign of weakness You don’t have to be perfect Physicians have been found to delay childbearing compared to peers in other professions. What are your thoughts on this? Progress has been made and overall there is increased awareness and support Leave for trainees should be more flexible          More societal and institutional support Production Team Dr. Gurleen Kaur Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), ACHD series co-chair Dr. Daniel Clark (Vanderbilt University), and ACHD FIT lead Dr. Danielle Massarella (Toronto University Health Network) join ACHD expert Dr. Yuli Kim (Associated Professor of Medicine & Pediatrics at the University of Pennsylvania), to discuss single ventricular heart disease and Fontan palliation. They cover the varied anatomical conditions that can require 3-step surgical palliation culminating in the Fontan circulation, which is characterized by passive pulmonary blood flow, high venous pressures, and low cardiac output. Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship and CardioNerds Academy Fellow).  The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark. The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more Claim free CME for enjoying this episode! Disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Adult Congenital Heart Disease PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls There are various forms of unpalliated ‘single ventricle’ congenital heart disease. The three main hemodynamic issues that need to be addressed in any form are unbalanced flow, pulmonary over-circulation, and blood mixing.  The Fontan palliation is a series of operations for congenital heart disease patients in whom biventricular repair is not feasible.  In the completed Fontan circulation, systemic venous blood is surgically routed directly to the lungs, effectively bypassing the heart, and creating passive pulmonary blood flow.  The hallmarks of the Fontan circulation (and Fontan failure) are elevated central venous pressure and low cardiac output.  Patients with Fontan circulation may experience significant morbidity in the long term from both cardiac and non-cardiac sequelae, and require lifelong specialist care.  Show notes 1. Why do some patients require Fontan palliation?  Many different types of anatomies may ultimately require single ventricular palliation via the Fontan procedure due to inadequate biventricular function to support both pulmonary and systemic circulations. Some examples include Tricuspid Atresia (hypoplastic RV), Double Inlet Left Ventricle (DILV; hypoplastic RV), Hypoplastic Left Heart Syndrome (HLHS; hypoplastic LV), and atrioventricular septal defects (AVSD; either RV or LV may be inadequate based on “commitment” of the common AV valve).  The Fontan procedure was first described in 1971; at this time, mortality of single ventricular patients exceeded 90% in the first year of life.  2. What are the stages of Fontan palliation?  Effective pulmonary blood flow/balancing flow to the pulmonary and systemic circulations: for many conditions, this involves retrograde pulmonary blood flow from a systemic -> PA shunt (i.e. Blalock-Taussig-Thomas “BTT” shunt in which the subclavian artery is turned down and anastomosed to the pulmonary artery). In infants, the pulmonary vascular resistance (PVR) is high perinatally and gradually lowers over the first 3 months of life to adult levels with exposure to the atmosphere’s natural pulmonary vasodilator: oxygen. Thus, in the first 3 months of life babies have an intrinsic PVR that is too high to directly connect the venous system to the lung arteries and thereby require staged surgeries.  Protect the pulmonary vasculature from overcirculation: ultimately, the goal of single ventricular palliation is rerouting systemic venous drainage directly to the pulmonary vasculature passively, without a cardiac pumping chamber. This volume unloads the common ventricle and allows it a better chance to function over the lifespan by pumping only to a single circuit: the systemic vascular bed. Thus, steps 2 and 3 of Fontan palliation are passive head/neck venous connection to the pulmonary arteries (now typically accomplished with the modified bidirectional Glenn operation that anastomoses the SVC to the RPA typically) and finally total cavopulmonary connection by the Fontan conduit connecting the lower body’s venous return from the IVC to the Fontan tunnel and up to the RPA.  3. What is the ultimate “plumbing” of Fontan circulation? Venous blood from the head/neck is connected directly from the SVC to the right pulmonary artery (RPA; typically, via a Glenn operation). Venous blood from the legs, abdomen/pelvis and lower body is connected directly to the RPA via the Fontan tunnel. In sum, the pulmonary blood flow enters passively, without a pump to send venous blood to the lungs. http://pted.org/?id=fontan3 4. What are the types of Fontan? The classic Fontan operation involved a direct venous connection to the right atrium with an atriopulmonary connection to the RPA. Contemporary era Fontan operations typically involve the lateral tunnel (LT) or extracardiac conduit. The LT incorporates pericardium in the creation of the Fontan conduit along the surface of the heart, while the extracardiac conduit is entirely prosthetic material (typically GoreTex). https://www.ahajournals.org/doi/epub/10.1161/CIR.0000000000000696 5. What are the common complications of Fontan circulation? Cardiac Arrhythmias: both atrial and ventricular arrhythmias can be common, especially owing to surgical scar lines, residual valvular disease, and hemodynamic sequelae of the Fontan palliation Ventricular dysfunction: this may take the form of both systolic and/or diastolic dysfunction Valvular disease: atrioventricular valvular insufficiency, etc. Thromboembolic complications: venous stasis, endothelial damage, and exposure of von Willebrand factor contribute to a risk of thrombosis and risk of paradoxical emboli into the systemic circulation for patients with residual venous-arterial system connections (such as Fontan fenestration/baffle leak) Extracardiac Neurocognitive: mental health disorders (including PTSD, depression, and anxiety) are common, as are executive function limitations that can be identified as early as childhood Fontan-associated liver disease (FALD): including risk of developing hepatocellular carcinoma Renal disease: chronic kidney disease/renal venous hypertension Lymphatic: protein-losing enteropathy (PLE) and plastic bronchitis 6. When is it time to refer a patient with Fontan palliation for heart transplantation evaluation? This is a very challenging, multidisciplinary decision that must weigh operative risk, HT candidacy, allosensitization, need for multi-organ transplantation (heart-liver, heart-lung, etc.), and patient-centered discussion about their goals of care. The team must way high near-term per-transplantation risk with improved long-term outcomes. References 1. Cetta F, Dearani J, O’Leary P and Driscoll D.Tricuspid Valve Disorders: Atresia, Dysplasia and Ebstein Anomaly. In: H. Allen, R. Shaddy, D. Penny, T. Feltes and F. Cetta, eds. Moss and Adams’ Heart Disease in Infants, Children and Adolescents Philadelphia: Wolters Kluwer; 2016. 2. Book WM, Gerardin J, Saraf A, Valente AM, Rodriquez III F. Clinical phenotypes of fontan failure: implications for management. Congenit Heart Dis. 2016;11:296–308. https://pubmed.ncbi.nlm.nih.gov/27226033/ 3. Rychlik J, Atz AM, Celermajer DS, Deal BJ, Gatzoulis MA, Gewillig MH et al. American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing. Evaluation and Management of the Child and Adult With Fontan  Circulation: A Scientific Statement From the American Heart Association. Circulation. 2019 Jul 1. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000696 Meet Our Collaborators! Adult Congenital Heart AssociationFounded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers CHiP Network The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information. Heart UniversityHeart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/ Guest Profiles Dr. Yuli Kim Yuli Y. Kim, MD, is a board-certified cardiologist in the Cardiac Center and Medical Director of the Philadelphia Adult Congenital Heart Center at Children’s Hospital of Philadelphia. She completed medical school at University of Virginia School of Medicine, Internal Medicine residency at Johns Hopkins Hospital, fellowships in Cardiovascular medicine at the Cleveland Clinic, ACHD/Advanced Congenital Imaging at Children’s Hospital in Boston, and completed a post-doctoral fellowship at the NIH. Dr. Danielle Massarella Dr. Danielle Massarella received her Hons. BSc. in Biology & Psychology from York University. She excelled and was the recipient of the Dean of Clinical Medicine Award at her graduation.  Her experience in gross anatomy class was particularly inspirational, and led her to pursue a specialty in cardiology. Danielle went on to pursue a 3-year residency in pediatrics and fellowship in pediatric cardiology at Case Western Reserve University and at Rainbow Babies and Children’s Hospital in Cleveland.  From there, Danielle went on to pursue advanced subspecialty training in adult congenital heart disease at Toronto’s University Health Network Adult Congenital Cardiac Clinic CardioNerds Adult Congenital Heart Disease Production Team Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal), Dr. Natalie Stokes (Cardiology Fellow at UPMC and Co-Chair of the Cardionerds Cardio-Ob series), fellow lead Dr. Victoria Thomas (Cardionerds Ambassador, Vanderbilt University Medical Center), join Dr. Rachel Bond (Women’s Heart Health Systems Director at Dignity Health, Arizona) for a cardio-obstetrics discussion about Black maternal health. Episode introduction by CardioNerds Clinical Trialist Dr. Chistabel Nyange. Audio editing by CardioNerds Academy Intern, Christian Faaborg-Andersen. This episode was developed in collaboration with the Association of Black Cardiologists. ABC is a 501(c)3 nonprofit organization whose mission is to promote the prevention and treatment of cardiovascular disease, including stroke, in Black persons and other minority populations, and to achieve health equity for all through the elimination of disparities. Learn more at https://abcardio.org/. Notes • References • Guest Profiles • Production Team CardioNerds Cardio-Obstetrics Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes 1. Why does Black Maternal Health need to be deliberately highlighted episode on CardioNerds? Black women are three-four times more likely to die during their pregnancy. The deaths are primarily tied to cardiomyopathy and cardiovascular conditions such as coronary artery disease, pulmonary hypertension, chronic hypertension, preeclampsia, and eclampsia. 63-68% of this cardiovascular mortality is preventable depending on one’s racial identity.  As CardioNerds, we must educate ourselves on why this occurs and identifying diseases that may place patients at increased risk. Studies have shown the Black maternal mortality crisis exist irrespective of one’s education or socioeconomic status. We must recognize and admit that some patients are being treated differently because of their race and ethnicity alone. 2.     When we consider or acknowledge a patient’s race, what should CardioNerds think about? Race is an important factor to think about, but we must remember that it is an imperfect variable. We should not focus on biology or genetic make-up. We should think about social determinants of health. 60% of the time social and personal aspects dictate one’s health. Unconscious biases and structural racism are likely playing a major role in race-based health inequities. 3.     What are other vulnerable groups that have increased mortality rates related to cardioobstetric care? Native American women have similar maternal mortality rates to Black populations. Women who are veterans, live in rural communities, and/or are currently incarcerated have increased risk of mortality 4.     What are some of the social determinants of health that should be considered for these patients? Food deserts or having poor access to nutrient rich/quality foods make these vulnerable patients have increased risk factors for high cholesterol, high blood pressure, obesity, and diabetes which increase the risk for pregnancy complications and infertility. The above vulnerable populations can have less access to higher levels of care for high-risk pregnancies. 5.     What are some of the preventable causes of maternal mortality? Clinicians should actively listen to their patients’ concerns. There have been several media stories in the news and on CardioNerds episodes where women’s concerns were not acknowledged or taken seriously. Preconception counseling is important to provide to all patients. 50% of women have one risk factor for cardiovascular disease when entering pregnancy. We should have discussions with patients regarding their lifestyles, with an emphasis on exercise and diet. 6.     What are some of the psychosocial or health related differences we see in black mothers when compared to other races? The effect of stress is affecting not just black mothers but black women in general by predisposing them to increased cardiovascular disease and cognitive impairment. The stress effects on black women are being called superwoman schema. Superwoman schema is a combination/phenomenon of gender and racial oppression’s effect on the allostatic load (cumulative biological stress).  Studies have shown that black women’s chronic stress levels affect their sympathetic nervous system with an inability to fight off or perhaps produce too much inflammatory response. This increases the risk of a variety worsening chronic morbidities in particular worsening cardiovascular health. One in eight women will struggle with infertility. Black women are two times more likely to suffer from infertility compared to their White counterparts. This is largely due to increased uterine fibroids. Black women are also less likely to be referred to a reproductive endocrinology specialist. 7.     What pre-counseling assessments or work-up should be considered for women trying to conceive? Consider getting a baseline ECG as that would give a nice idea of structurally of what is going on within the heart. If there are several risk factors, there can be consideration for a baseline echocardiogram. There should be a specific focus on lifestyle. As cardiologists, we should try to have our patients monitor their weight and follow a well-balanced diet with exercise. They should monitor their   blood pressure. Also try to have a birthing plan with OBGYN team as there is data to support that a birthing plan can lead to better outcomes for high-risk pregnancy. 8.     What are some of the tools that have been recently used to help reduce black maternal mortality? Patients that are likely to have higher pregnancy complications should be considered to follow not only with a maternal fetal medicine doctor, but there should be consideration for extra help with a doula or a midwife if possible. We should promote home blood pressure monitoring during pregnancy and post-partum as there have been trials supporting the fact that blood pressure control was more successful using texting/ambulatory monitoring strategies vs office visits alone. Digital platforms such as MAHMEE are closing gaps in care to connect patients in their pregnancy and postpartum care to help with all patients but especially underserved populations. References 1.     Bond RM, Gaither K, Nasser SA, et al. Working Agenda for Black Mothers: A Position Paper from the Association of Black Cardiologists on Solutions to Improving Black Maternal Health. Circ Cardiovasc Qual Outcomes. 2021;14(2):e007643. doi:10.1161/CIRCOUTCOMES.120.007643 2.     Havranek EP, Mujahid MS, Barr DA, et al. Social Determinants of Risk and Outcomes for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2015;132(9):873-898. doi:10.1161/CIR.0000000000000228 3.     Chandra A, Copen CE, Stephen EH. Infertility and impaired fecundity in the United States, 1982-2010: data from the National Survey of Family Growth. Natl Health Stat Report. 2013;(67):1-19. 4.     Woods-Giscombé CL. Superwoman schema: African American women’s views on stress, strength, and health. Qual Health Res. 2010;20(5):668-683. doi:10.1177/1049732310361892 5.     Allen AM, Wang Y, Chae DH, et al. Racial discrimination, the superwoman schema, and allostatic load: exploring an integrative stress-coping model among African American women. Ann N Y Acad Sci. 2019;1457(1):104-127. doi:10.1111/nyas.14188 6.     Ofili EO, Schanberg LE, Hutchinson B, et al. The Association of Black Cardiologists (ABC) Cardiovascular Implementation Study (CVIS): A Research Registry Integrating Social Determinants to Support Care for Underserved Patients. Int J Environ Res Public Health. 2019;16(9):1631. Published 2019 May 10. doi:10.3390/ijerph16091631 7.     Lantz PM, Low LK, Varkey S, Watson RL. Doulas as childbirth paraprofessionals: results from a national survey. Womens Health Issues. 2005;15(3):109-116. doi:10.1016/j.whi.2005.01.002 8.     Pregnancy mortality surveillance system. Centers for Disease Control and Prevention. https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm. Published November 25, 2020. Accessed December 18, 2021. 9.     Cairns AE, Tucker KL, Leeson P, et al. Self-Management of Postnatal Hypertension: The SNAP-HT Trial. Hypertension. 2018;72(2):425-432. doi:10.1161/HYPERTENSIONAHA.118.10911 10.  Hirshberg A, Sammel MD, Srinivas SK. Text message remote monitoring reduced racial disparities in postpartum blood pressure ascertainment. Am J Obstet Gynecol. 2019;221(3):283-285. doi:10.1016/j.ajog.2019.05.011 11.  Vedam S, Stoll K, MacDorman M, et al. Mapping integration of midwives across the United States: Impact on access, equity, and outcomes. PLoS One. 2018;13(2):e0192523. Published 2018 Feb 21. doi:10.1371/journal.pone.0192523 Guest Profiles Dr. Rachel Bond Rachel M Bond, MD, FACC, Women’s Heart Health & Prevention Specialist is devoted to expert diagnosis and treatment for improved patient outcomes. Her expertise is in cardiovascular disease with special interest in women’s heart health, prevention, lipid disorders, pregnancy-related heart disease, cardio-oncology and autoimmune-related heart disease.Dr. Bond is a board-certified attending cardiologist and the System Director of the Women’s Heart Health Program at Dignity Health in Arizona. She is affiliated with Chandler Regional Medical Center & Mercy Gilbert Medical Center. She is board certificated in cardiovascular disease, internal medicine, echocardiography and nuclear cardiology and is a registered physician in vascular interpretation. Dr. Bond is a well-known spokesperson for the American Heart Association, Go Red for Women Campaign. Dr. Victoria Thomas Dr. Victoria Thomas @Drvic_thomas is a cardiology fellow at Vanderbilt University. She completed medical school at University of Chicago-Pritzker School of Medicine followed by residency training at Indiana University. Victoria is fervent about medical and patient education along with promoting health equity and decreasing health disparities. She is currently deciding between a Master of Education or Science in Clinical Investigation. Her research interest are curriculum development, cardiac ATTR, and coronary artery disease. CardioNerds Cardioobstetrics Production Team

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Jaya Kanduri, Dr. Dan Lu, and Dr. Joe Wang from Weill Cornell Cardiology for Levain cookies in Central Park. The ECPR is provided by Dr. Harsimran Singh (Cardiology Program Director and Interventional Cardiologist with expertise in ACHD). Episode introduction by CardioNerds Clinical Trialist Dr. Jeremy Brooksbank. We discuss a case of a 24-year-old female with a history of unicuspid aortic valve with associated aortopathy status post mechanical aortic valve replacement and Bentall procedure at age 16 presents with acute onset substernal chest pain and shortness of breath. She was found to have mechanical aortic valve obstruction and severe aortic regurgitation resulting in cardiogenic shock. Unfortunately, the shock quickly progressed to refractory cardiac arrest requiring mechanical support with VA-ECMO before valve debridement was performed in the operating room. The differential for mechanical prosthetic valve stenosis includes pannus, thrombus, or vegetation. She was eventually found to have thrombus obstructing the outflow tract and holding the mechanical leaflets open leading to torrential regurgitation. She underwent successful surgical debridement. We discuss unicuspid aortic valve and associated aortopathy, surgical considerations regarding AVR, diagnosis and management of prosthetic valve dysfunction, approach to cardiogenic shock and considerations around activating and managing VA-ECMO. With this episode, the CardioNerds family warmly welcomes Weill Cornell Cardiology to the CardioNerds Healy Honor Roll. The CardioNerds Healy Honor Roll programs support and foster the the CardioNerds spirit and mission of democratizing cardiovascular education. Healy Honor Roll programs nominate fellows from their program who are highly motivated and are passionate about medical education. The Weill Cornell fellowship program director, Dr. Harsimran Singh has nominated Dr. Jaya Kanduri for this position. Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls – Notes – 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 ECG CXR Echo RHC PSL AP3 Color LHC – LCA LHC – LCA RCA Aortogram TEE TEE 2 Episode Teaching Pearls – Mechanical Valve Thrombosis (1) Unicuspid aortic valves present with aortic stenosis earlier in life. There can be concurrent aortic regurgitation and, like bicuspid aortic valves, unicuspids can be associated with aortopathy as well as other congenital anomalies. (2) Prosthetic valve stenosis is assessed with different echocardiographic parameters than what we use for native valves. The differential for mechanical valve stenosis includes pannus, thrombus, or vegetation. Patient prosthesis mismatch may also lead to elevated gradients. (3) VA-ECMO provides robust flow in the setting of cardiogenic shock as well as gas exchange. While this flow may improve end-organ perfusion, it also increases left ventricular afterload, thereby potentially worsening LV ischemia and impeding LV recovery. Elevated afterload may also decrease innate contractility and prevent aortic valve leaflets from opening. Therefore, if a patient with a mechanical valve is on VA-ECMO, ensuring valve opening to prevent valve (or ventricular) thrombosis is paramount. (4) Venting is sometimes necessary to decrease the left ventricular end diastolic pressure from the high afterload imposed by VA-ECMO. A microaxial temporary LVAD (example – Impella device) directly unloads the left ventricle, but cannot be used in the setting of a mechanical aortic valve. TandemHeart is also a consideration (inflow cannula placed across the interatrial septum in the left atrium) to unload the LV, but does not improve flow across the aortic valve so can lead to thrombus if a mechanical valve is present. Intra-aortic balloon counterpulsation using an IABP can be used to decrease afterload on the native heart and increase coronary perfusion, but does not directly unload the left ventricle. (5) Acute mechanical valve thrombosis can be managed with emergency surgery or with low dose fibrinolytic therapy. Surgery is preferable when operative risk is low and if there are contraindications to fibrinolytic therapy such as prior intracranial hemorrhage or active bleeding. (6) VA-ECMO can be weaned by slowly decreasing flow rates and assessing native cardiac function, hemodynamic response, and end-organ perfusion with assessments including echocardiography and pulmonary artery catheterization. Notes – Mechanical Valve Thrombosis 1. What is a unicuspid aortic valve? Unicuspid aortic valves (UAVs) are rare with an incidence of only 0.02%. There are two types of UAVs. Acommisural UAVs have a single cusp with a stenotic central orifice and rudimentary commissures that do not divide the valve (pin-hole shaped), and are usually complicated by severe stenosis in early childhood. Unicommisural UAVs are composed of a single cusp with a single commissural attachment to the aortic wall and an elongated orifice (slit-like orifice), which has a less aggressive course and is generally discovered in adulthood. Aortic stenosis is almost universal among UAVs, present with or without aortic regurgitation in 92% of cases. Some series have shown 14% of cases with concurrent aortopathy. UAVs may be associated with congenital abnormalities likes anomalous coronaries, PDA, VSD and coarctation. 2. How do we assess for aortic prosthetic valve stenosis? Assessment for mechanical valve stenosis involves different echocardiographic parameters than when evaluating a native valve. Doppler velocity index (DVI) is the dimensionless index with LVOT VTI/AV VTI, with severe stenosis suggested by a ratio of <0.25. Acceleration time (AT) is the time from onset to peak velocity of the continuous wave Doppler jet with severe stenosis suggested by >100msec (it takes longer to gush through a more stenotic valve). Effective orifice area (EOA) <0.8 suggests severe stenosis. A rounded symmetrical contour of the prosthetic valve VTI is more suggestive of severe stenosis, versus a triangular and early peaking jet. Acceptable ranges for prosthetic valve gradients are different from native valves due to intrinsically higher gradients, with mechanical being higher than bioprosthetic. In evaluating for prosthetic valve stenosis, we need to compare expected gradients for a given valve against those being measured. Evaluating trends over time is invaluable. 3. What are the percutaneous mechanical circulatory support options for cardiogenic shock? MCS options include counterpulsation using an IABP, microaxial temporary LVAD (like the Impella devie), TandemHeart, and VA-ECMO. The IABP improves diastolic coronary perfusion and systolic afterload reduction. However, there is only 0-1 L/min of flow provided, and no direct LV decompression. Microaxial temporary LVADs directly unload the LV with the flow pump placed across the aortic valve. These devices can provide 2-5L/min of flow depending on which device is used. The TandemHeart directly unloads the LV as well with an inflow cannula placed in the LA and outflow cannula placed in the femoral artery (requiring a transseptal puncture), and provides 2.5-5L/min of flow. VA-ECMO can provide up to 3-7L/min of flow. 4. What are unique considerations of mechanical support and VA-ECMO in the setting of a mechanical aortic valve? With a mechanical aortic valve, it is important for the valve leaflets open to prevent leaflet thrombosis. High afterload from the VA-ECMO circuit due to retrograde flow can prevent the aortic valve from opening, especially if myocardial contractility is already compromised. Therefore, special consideration needs to be given to the flow rate of the circuit and maintaining native LV output. Venting options are limited with a mechanical aortic valve. A device cannot be placed across the valve and so microaxial flow pumps are contraindicated. TandemHeart effectively decompresses the LV by sucking blood from the LA, but does not promote flow across the aortic valve and predisposes to thrombus formation. IABP is the ideal device in the setting of a mechanical aortic valve as flow through the aortic valve is promoted, however there is no direct decompression of the LV and efficacy may be limited. 5. What is the acute management of mechanical valve thrombosis? Mechanical valve thrombosis is managed acutely with emergent surgery or use of low dose fibrinolytic therapy. Surgery is preferable when surgical expertise is readily available, operative risk is low, and there are contraindications to fibrinolysis. Other reasons to prefer surgery include recurrent valve thrombosis, severe heart failure symptoms, large clot size (>0.8cm2), presence of LA thrombus or concomitant CAD in need of revascularization, presence of other valve disease, and presence of possible pannus (which would not respond to fibrinolysis).  6. What is the approach to weaning VA-ECMO? Assessment of echocardiographic features, hemodynamics, and end-organ perfusion is essential for a successful VA-ECMO wean. First a turndown of the circuit is performed where the ECMO flow is decreased in a protocolized fashion. This should reduce afterload and therefore increase LV contractile reserve, as well as increase preload with return of flow through the ventricles. With these changes, successful hemodynamic parameters to look for are stable cardiac index, central venous pressure, pulmonary arterial pressures, and systemic blood pressures. Successful echocardiographic parameters include an increase in LVEF >20-25%, aortic VTI ≥10 cm, lateral mitral annulus peak systolic velocity ≥6 cm/s, and a normal appearing RV with midline septum. Of note the risk of thrombosis increases with lower circuit flows, so particular attention must be given to anticoagulation during weaning. As antegrade flow through the native LV increases and retrograde through the VA-ECMO circuit decreases, beware of the north-south syndrome. This is caused by a mixing cloud of oxygenated blood from ECMO and potentially deoxygenated blood from the LV (if pulmonary gas exchange is compromised). As this mixing cloud progressively travels distally from the aortic root, it may predispose to coronary and then neurologic ischemia. We can monitor for this using ABGs obtained from the right arm. Stay tuned for more on this as part of the biventricular shock discussion as part of the CardioNerds Critical Care Cardiology Series. https://www.onlinejase.com/article/S0894-7317(09)00676-2/fulltext References Abbas, A. (n.d.). Echocardiographic Evaluation of Aortic Valve Prosthesis. Retrieved from https://asecho.org/wp-content/uploads/2016/04/4.16-Abbas-Aortic-Valve-Prosthesis.pdf Eckman, P. M., Katz, J. N., El Banayosy, A., Bohula, E. A., Sun, B., & Van Diepen, S. (2019). Veno-Arterial extracorporeal Membrane Oxygenation For cardiogenic shock. Circulation,140(24), 2019-2037. doi:10.1161/circulationaha.119.034512 Klein, L., & Dorobanţu, L. (2016). Mechanical circulatory support. Current Approach to Heart Failure,311-333. doi:10.1007/978-3-319-45237-1_15 Li, Y., Yan, S., Gao, S., Liu, M., Lou, S., Liu, G., . . . Gao, B. (2018). Effect of an intra-aortic balloon pump with venoarterial extracorporeal membrane oxygenation on mortality of patients with cardiogenic shock: A systematic review and meta-analysis†. European Journal of Cardio-Thoracic Surgery,55(3), 395-404. doi:10.1093/ejcts/ezy304 Malekan, R., Spielvogel, D., Saunders, P. C., Lansman, S. L., & Griepp, R. B. (2011). The completion bentall procedure. The Annals of Thoracic Surgery,92(1), 362-363. doi:10.1016/j.athoracsur.2011.02.078 Otto, C. M., Nishimura, R. A., Bonow, R. O., Carabello, B. A., Erwin, J. P., Gentile, F., . . . Toly, C. (2021). 2020 ACC/AHA guideline for the management of patients with Valvular heart disease: A report of the American College OF CARDIOLOGY/AMERICAN Heart ASSOCIATION Joint Committee on clinical practice guidelines. Circulation,143(5). doi:10.1161/cir.0000000000000923 Patel, S. M., Lipinski, J., Al-Kindi, S. G., Patel, T., Saric, P., Li, J., . . . Bezerra, H. G. (2019). Simultaneous Venoarterial extracorporeal Membrane oxygenation AND Percutaneous left Ventricular Decompression therapy WITH IMPELLA is associated with improved outcomes in REFRACTORY cardiogenic shock. ASAIO Journal,65(1), 21-28. doi:10.1097/mat.0000000000000767 Rao, P., Khalpey, Z., Smith, R., Burkhoff, D., & Kociol, R. D. (2018). Venoarterial extracorporeal Membrane Oxygenation For cardiogenic shock and cardiac arrest. Circulation: Heart Failure,11(9). doi:10.1161/circheartfailure.118.004905 Salazar, M. (n.d.). Echocardiographic Evaluation of Prosthetic Valves. Retrieved from https://www.asefoundation.org/wp-content/uploads/2016/10/Evaluation-of-Prosthetic-Valves-Supe.pdf Thota, V., & Mookadam, F. (2011). Unicuspid aortic valve. Aortic Valve. doi:10.5772/24280 CardioNerds Case Report Production Team Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

The hemodynamic evaluation of cardiogenic shock obtained via a Swan-Ganz catheter plays an essential role in the characterization of cardiogenic shock patients. Join Dr. Nosheen Reza, (Assistant Professor of Medicine and Advanced Heart Failure and Transplant cardiologist at the Hospital of the University of Pennsylvania), episode fellow lead Dr. Brian McCauley (Interventional and Critical Care Fellow at the Hospital of the University of Pennsylvania), Dr. Mark Belkin (Cardiac Critical Care Series Co-Chair and AHFT fellow at University of Chicago), and CardioNerds Co-Founders, Amit Goyal and Dan Ambinder, for this tour through the heart aboard the Swan-Ganz catheter. In this episode, we evaluate three separate admissions for a single patient to highlight pearls regarding waveform assessment, evaluating cardiac output, phenotyping hemodynamic profiles, targeted therapies based on hemodynamics and so much more. Episode introduction and audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship). Claim free CME for enjoying this episode! Disclosures: None 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 – Hemodynamic Evaluation of Cardiogenic Shock Swan-Ganz catheters are not dead #ReviveTheSwan!  They remain a useful tool to characterize cardiac patients & to help direct therapy, especially in Cardiogenic Shock. When looking at Swan-Ganz catheter data, it is important to always interpret your own tracings, to know what values are acquired directly, and which values are derived. It is important to understand the strengths and weakness of hemodynamic characterization by Swan-Ganz catheters Advanced metrics such as cardiac power output, pulmonary artery pulsatility index, and aortic pulsatility index are extremely useful in further phenotyping patients as well as guiding mechanical support platforms “The data will be wrong if the preparation is not right” Show notes – Hemodynamic Evaluation of Cardiogenic Shock 1. Swan-Ganz catheters are a useful tool to characterize cardiac patients and to direct therapy.  With the ESCAPE trial in 2004, Swan-Ganz catheter utilization dropped drastically outside transplant centers across the United States (2).  While the ESCAPE trial did demonstrate the possibility of harm when using a Swan-Ganz catheter, many of the truly ill cardiac patients we care for would have been excluded from the trial. For instance, patients on dobutamine at doses above 3 µg/kg/min or any dose of milrinone during the hospitalization were excluded from the trial. This is a classic example of “throwing the baby out with the bath water.” In a recent large, multicenter cardiogenic shock registry, complete hemodynamic assessment using pulmonary artery catheters prior to MCS is associated with lower in-hospital mortality compared with incomplete or no assessment (3). 2. When looking at Swan-Ganz catheter data, it is important to always interpret your own tracings, to know what values are acquired directly, and which values are derived. Incomplete or incorrect data can lead to mischaracterization of our patients.  Therefore, it is essential to review all of the tracings, calculations, and data acquired for each individual patient before any clinical adjustments are made (1).  An incomplete pulmonary capillary wedge tracing is an example from clinical practice (causing the PCWP, and therefore the left-sided filling pressures to be overestimated).  It is equally important to know the limitations of cardiac output equations, and that no one measurement is perfect. Foibles of the Fick equation include assumed rather than measured oxygen consumption and variations in hemoglobin concentration.  Traditionally, thermodilution has been thought to be likely less accurate in presence of tricuspid regurgitation, which could lead to blending of the cold dilutant, but recent data suggests even in these circumstances it remains the preferred method for estimating cardiac output over indirect Fick. 3. What are some tips of measuring a PCWP correctly? To ensure that we get the wedge pressure correctly, we must first make sure we understand the wedge pressure in relation to the respiratory cycle. For the majority of patients, the end expiratory intrathoracic pressure will be close to 0, and it will have the least influence on our readings. Thus, for most patients, that is why we measure the wedge pressure at end expiration. However, in patients with severe lung disease or significant obesity, the intrathoracic pressure may not be close to 0 at end expiration or there may be wide swings in intrathoracic pressure. For these patients, it is a reminder to look at the tracings yourself, and we may need to average the PCWP over the respiratory cycle. When we are measuring the PCWP, we have to remember that we are using it as a surrogate of the LV end-diastolic pressure. The point of the cardiac cycle when the pressure in the pulmonary veins, left atrium and LV are closest to equal is end-diastole. Thus, we typically want to measure the PCWP in end-diastole, which would specifically be measuring the mean of the A-wave. Now, for patients with severe mitral regurgitation and/or significant atrial myopathy leading to large V-waves, the wedge pressure estimated at end-diastole will not necessarily reflect the mean wedge (averaged throughout the cardiac cycle) that the pulmonary circulation “sees” throughout the cardiac cycle. As has been a theme in this episode, we have to make sure our inputs are accurate to appropriately help our patients. In this circumstance of large V-waves, if we were calculating the pulmonary vascular resistance (Mean PA Pressure – PCWP / CO), but used the end-diastolic PCWP instead of the PCWP averaged through the cardiac cycle we may end up with an inaccurate estimation of PVR. 4.Advanced metrics such as cardiac power output, pulmonary artery pulsatility index, and aortic pulsatility index are extremely useful in further characterizing hemodynamics. Over the past several years individual indices of ventricular performance have been developed and studied, these include CPO, PAPi, API, and LVSWI (4,5,10-12). These values can further flesh out our hemodynamic profiles, and help guide decision-making for choosing the proper mechanical circulatory support platform (7,8,9). See the infographic developed by CardioNerds Academy Fellow Ahmed Ghoneem for more information on different thresholds for these parameters. The API is a novel hemodynamic parameter that was recently applied to ESCAPE trial patients by series Co-Chair, Mark Belkin. 5. “The data will be wrong if the preparation is not right.” Dr. Reza’s point on the episode is apt and high-yield. Incorrect data acquisition and/or interpretation will not benefit our patients. We need to know what values are measured directly (chamber pressures, SvO2) and which are derived (cardiac output/index, SVR/PVR, CPO/PAPi/API, and so forth).  As cardiologists and intensivists, we need to be critical of the tracings themselves, avoid anchoring to a single value, and be observant of the overall hemodynamic trajectory our patient is taking.  Only through thoughtful intervention in coordination with careful and consistent monitoring will we bring to bear the benefits bestowed by Swan-Ganz catheter supplemented-care (1). Schematics and Graphics – Hemodynamic Evaluation of Cardiogenic Shock RHC Tracings Discussed in the Episode References – Hemodynamic Evaluation of Cardiogenic Shock 1.Ragosta M. Textbook of Clinical Hemodynamics. Elsevier; 2017. 2.Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294(13):1625-33. https://jamanetwork.com/journals/jama/fullarticle/201634 3. Garan AR, Kanwar M, Thayer KL, et al. Complete hemodynamic profiling with pulmonary artery catheters in cardiogenic shock is associated with lower in-hospital mortality. JACC Heart Fail. 2020;8(11):903-913.  https://pubmed.ncbi.nlm.nih.gov/33121702/ 4.Korabathina R., Heffernan K.S., Paruchuri V., Patel A.R., Mudd J.O., Prutkin J.M., et al: The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction. Catheter Cardiovasc Interv 2012; 80: pp. 593-600.  https://pubmed.ncbi.nlm.nih.gov/21954053/ 5.Fincke R, Hochman JS, Lowe AM, et al. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol. 2004;44(2):340-8.  https://pubmed.ncbi.nlm.nih.gov/15261929/ 6.Kochav SM, Flores RJ, Truby LK, Topkara VK. Prognostic impact of pulmonary artery pulsatility index (Papi) in patients with advanced heart failure: insights from the escape trial. J Card Fail. 2018;24(7):453-459. https://pubmed.ncbi.nlm.nih.gov/29597051/ 7.Feldman D, Naidu SS.  Percutaneous Mechanical Circulatory Support Devices. Cardiac Interventions Today. 2016; 10 (1): 26-33.  https://citoday.com/articles/2016-jan-feb/cover-stories 8.Briceno N, Kapur NK, Perera D. Percutaneous mechanical circulatory support: current concepts and future directions. Heart. 2016;102(18):1494-507.  https://pubmed.ncbi.nlm.nih.gov/27503999/ 9.Baran DA, Grines CL, Bailey S, et al. Scai clinical expert consensus statement on the classification of cardiogenic shock: this document was endorsed by the american college of cardiology (Acc), the american heart association (Aha), the society of critical care medicine (Sccm), and the society of thoracic surgeons (Sts) in april 2019. Catheter Cardiovasc Interv. Published online May 19, 2019:ccd.28329.  https://pubmed.ncbi.nlm.nih.gov/31104355/ 10.Drazner MH, Velez-Martinez M, Ayers CR, et al. Relationship of right- to left-sided ventricular filling pressures in advanced heart failure: insights from the ESCAPE trial. Circ Heart Fail. 2013;6(2):264-270.  https://pubmed.ncbi.nlm.nih.gov/23392790/ 11.Belkin MN, Alenghat FJ, Besser SA, et al. Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial. ESC Heart Fail. 2021;8(2):1522-1530.  https://pubmed.ncbi.nlm.nih.gov/33595923/ 12. Belkin MN, Kalantari SA, Kanelidis AJ, et al. Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure. J Card Fail. 2021;27(10):1045-1052. https://pubmed.ncbi.nlm.nih.gov/34048919/ 13. Araj FG, Mammen PPA. Alternans of the Pulse Is Rarely an Alternans of Prognosis. J Card Fail. 2021 Nov;27(11):1302-1303. doi: 10.1016/j.cardfail.2021.06.023. Epub 2021 Jul 26. PMID: 34324926. Guest Profiles Dr. Nosheen Reza Dr. Nosheen Reza is a cardiologist and translational researcher at the University of Pennsylvania focusing on advanced heart failure and transplant cardiology and cardiovascular genetics, genomics, and phenomics. She obtained her medical degree from the University of Virginia School of Medicine in 2012 and completed her internal medicine residency training at the Massachusetts General Hospital in 2015. She then completed her Cardiovascular Disease fellowship at the University of Pennsylvania in 2018 and served as 2017-2018 Chief Fellow. At Penn, Dr. Reza pursued additional scholarship in genomic medicine as an NIH T32-funded postdoctoral fellow and in healthcare quality as a Penn Benjamin & Mary Siddons Measey Fellow in Quality Improvement and Patient Safety. She completed her final year of clinical training at Penn in Advanced Heart Failure and Transplant Cardiology and joined the faculty at the University of Pennsylvania in July 2020. Dr. Reza is passionate about medical education and has won many distinctions in the field throughout her training. She serves as an editorial board member for JACC: Case Reports, JACC: CardioOncology, and Current Cardiovascular Risk Reports. Dr. Reza is an active leader in the Heart Failure Society of America, American Heart Association, and American College of Cardiology at the local and national levels and volunteers on multiple leadership councils and steering committees within these organizations. Dr. Brian McCauley Dr. Brian McCauley is an interventional cardiology fellow at the University of Pennsylvania where he also completed his general cardiology fellowship. Received his medical degree from Cooper Medical School of Rowan University, and internal medicine residency at Brown University. CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), Dr. Zarina Sharalaya (Interventional Cardiology Fellow at the Cleveland Clinic), and Dr. Simrat Kaur (General Cardiology Fellow at the Cleveland Clinic) join Dr. Samir Kapadia, the Chair of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. They discuss future advancements in the field of structural interventional cardiology. Dr. Kapadia sheds light on his journey starting as an international medical graduate from India and speaks about his mentors that helped shape his career and his life. We later delve into several advancements in the field of structural and interventional cardiology, along with the amalgamation of different sub-specialities with intervention such as heart failure and critical care cardiology. We also discuss the measures being taken to reduce the occupational hazards associated with interventional cardiology and how to make this field more appealing to women in cardiology. Special message by Ohio ACC State Chapter Governor, Dr. Kanny Grewal. 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. Video Version • Notes • References • Production Team Claim free CME just for enjoying this episode! There are no relevant disclosures for this episode. The PA-ACC & CardioNerds Narratives in Cardiology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Tweetorial on Innovation, Excellence and Leadership in Interventional Cardiology with by Dr. Gurleen Kaur https://twitter.com/gurleen_kaur96/status/1484205728663576590?s=21 Video version – Innovation, Excellence and Leadership in Interventional Cardiology with Dr. Samir Kapadia https://youtu.be/BfqnRkaVGkk Quotables – Innovation, Excellence and Leadership in Interventional Cardiology with Dr. Samir Kapadia “A very important thing for all international medical graduates and for everybody, for that matter – it is important to recognize that the opportunities are what you perceive and not what others perceive.” Dr. Samir Kapadia Show notes – Innovation, Excellence and Leadership in Interventional Cardiology with Dr. Samir Kapadia How do international medical graduates contribute to the work force in medicine across the United States of America? International medical graduates account for 25% of the physician work force, with over 85% being involved in direct patient care. IMGs are usually accomplished, consummate and highly motivated physicians who often have to overcome challenges such as language proficiency, acculturation and difficulties with obtaining a visa status in the United States. IMGs also help fill gaps in health care by working in geographical areas that are otherwise not desirable by US or Canadian medical graduates. IMGs contribute to diversity of the field which provides a richer training environment, improved access to health care for underrepresented minorities, as well as better patient outcomes. What are key qualities of a good mentor? A good mentor is responsible for enhancing the education of his or her mentees along with motivating them to challenge their limits. Qualities of a good mentor extend beyond mere mentorship to sponsorship, where the mentor opens up his or her network for the mentee allowing them to pursue a path of success. A mentor serves as an advisor and a counselor, helping his or her mentees navigate difficult paths teaching them to become resilient physicians. A mentor also serves as a confidante for the trainee with whom mentees can share their dreams, aspirations and vulnerabilities knowing not only will this be kept in confidence but will also provide a catalyst for their growth. What are the recent advancements in minimizing radiation exposures for structural cardiologists? It’s important to understand the various occupational hazards of radiation exposure which include but are not limited to brain tumors, cataracts, thyroid disease, cardiovascular diseases, musculosketal problems and reproductive side effects. When dealing with possible occupational radiation exposure, we should strive for the ALARA (as low as reasonably achievable) principle of radioprotection. The RADPAD (RADPAD 5100A-O; Worldwide Innovations & Technologies, Inc, Lenexa, KS) is a new development that is a lead field shield that is placed between the patient and the operator to reduce scatter radiation and significantly reduce operator radiation exposure. The use of Zero gravity lead is a novel suspension shield which has also been shown to significantly reduce the operator radiation exposure and potentially decrease orthopedic injuries particularly spinal injuries secondary to the protective lead garments. What are the future directions for structural interventions and how is the field of structural cardiology going to evolve in the next few years? The future of structural cardiology provides great promise. After the success of transcatheter aortic valve replacement (TAVR) and transcatheter mitral valve edge to edge repair (TEER), there has been increasing development in tricuspid interventions as well as interventions for severe mitral stenosis due to mitral annular calcification. The amalgamation of structural interventional cardiology and heart failure as well as with critical care are also exciting fields that is still developing. Advancements in left ventricular restoration devices such as the Revivant TC system may help several patients with end stage congestive heart failure due to ischemic heart disease. References Steward DE. The internal medicine workforce, international medical graduates, and medical school  departments of medicine. Am J Med 2003;115(1):80–4. Doi: 10.1016/s0002-9343(03)00307-3. Kostis JB., Ahmad B. International medical graduates and the cardiology workforce. J Am Coll Cardiol 2004;44(6):1172–4. Doi: 10.1016/j.jacc.2004.05.081. Al Hussein Al Awamlh B. Alien J-1 Physicians in a Pandemic. JAMA Intern Med 2021;181(6):743–4. Doi: 10.1001/jamainternmed.2021.0730. David YN., Issaka RB. Advancing diversity: the role of international medical graduates. Lancet Gastroenterol Hepatol 2021;6(12):980–1. Doi: 10.1016/S2468-1253(21)00376-9. Shikhar A. Mentorship During Fellowship. J Am Coll Cardiol 2014;64(15):1637–8. Doi: 10.1016/j.jacc.2014.08.017. Tobin MJ. Mentoring: seven roles and some specifics. Am J Respir Crit Care Med 2004;170(2):114–7. Doi: 10.1164/rccm.2405004. Picano E., Vano E. The Radiation Issue in Cardiology: the time for action is now. Cardiovasc Ultrasound 2011;9(1):35. Doi: 10.1186/1476-7120-9-35. Vlastra W., Delewi R., Sjauw KD., et al. Efficacy of the RADPAD Protection Drape in Reducing Operators’ Radiation Exposure in  the Catheterization Laboratory: A Sham-Controlled Randomized Trial. Circ Cardiovasc Interv 2017;10(11). Doi: 10.1161/CIRCINTERVENTIONS.117.006058. Zanca F., Dabin J., Collard C., et al. Evaluation of a suspended radiation protection system to reduce operator exposure in  cardiology interventional procedures. Catheter Cardiovasc Interv  Off J Soc  Card Angiogr Interv 2021;98(5):E687–94. Doi: 10.1002/ccd.29894. GP., Y.S. C. Continuing Advances and Challenges of Structural Heart Imaging. JACC Cardiovasc Imaging 2021;14(1):128–30. Doi: 10.1016/j.jcmg.2020.12.002. Klein P., Anker SD., Wechsler A., et al. Less invasive ventricular reconstruction for ischaemic heart failure. Eur J Heart Fail 2019;21(12):1638–50. Doi: 10.1002/ejhf.1669. Production Team Dr. Gurleen Kaur Amit Goyal, MD Daniel Ambinder, MD

In this episode, CardioNerds (Amit Goyal), ACHD series co-chair,  Dr. Josh Saef (ACHD fellow at University of Pennsylvania) and episode lead fellow, Dr. Brynn Connor (Pediatric Cardiology fellow at Lucile Packard Children’s Hospital at Stanford) are joined by Dr. Maan Jokhadar (Advanced heart failure and adult congenital heart disease specialist at Emory University) to discuss transposition of the great arteries. Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian. For a brief review of the basic anatomy and physiology of D-TGA, check-out this great video by Dr. Maan Jokhadar! The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark. The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more Claim free CME for enjoying this episode! Disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Adult Congenital Heart Disease PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! https://www.youtube.com/watch?v=Ifu8nVtXT_c Pearls (1) In D-TGA following an atrial switch operation, the right ventricle IS the systemic ventricle! (2) Evaluation of systemic right ventricular function often requires use of both transthoracic echocardiography and cardiac MRI. (3) Use of medical heart failure therapies should be individualized, without any proven long-term mortality benefit and potential unique complications in this patient population (i.e. SA node dysfunction).  Show notes D-transposition of the great arteries (D-TGA) is one of the most common forms of cyanotic congenital heart disease presenting in the newborn period. Anatomically, d-transposition of the great arteries is characterized by atrioventricular concordance and ventriculoarterial discordance, such that the aorta arises from the morphologic right ventricle and pulmonary artery arises from the morphologic left ventricle. The resultant physiology is that of a parallel circulation, with deoxygenated blood recirculating in the systemic circulation (via the RA-RV) and oxygenated blood recirculating in the pulmonary circulation (via the LA-LV). At birth, this invariably results in cyanosis, with survival dependent upon adequate mixing of the two circulations via an atrial or ventricular level defect. Prior to surgical advances in the late 1950s, this lesion was uniformly fatal, with most infants dying before their first birthday. The subsequent development of the Senning and Mustard atrial-level repairs led to good immediate outcomes and improved long-term survival. However, following these “physiologic” types of repair, patients are far from cured, with several long-term established complications, including (1) dysfunction of the systemic right ventricle, (2) tricuspid regurgitation (the systemic atrioventricular valve), (3) atrial and ventricular arrhythmias, and (4) systemic and pulmonary venous baffles leaks and obstruction. These complications ultimately lead to substantial morbidity and premature mortality, with ACHD providers facing unique challenges in the medical and surgical management of this heterogenous patient population. 1. What are the basic anatomic features of d-transposition of the great arteries (d-TGA)? D-transposition of the great arteries is defined by the origin of the arterial trunks from the morphologically inappropriate ventricle, specifically with the aorta arising from the morphologic right ventricle (now the systemic ventricle) and the pulmonary trunk arising from the morphologic left ventricle. This is termed “ventriculoarterial discordance”, and importantly, does not define the spatial relationship of the great arteries. Rather, the “d” terminology refers to the looping of the ventricles and distinguishes d-TGA from l-TGA (or congenitally corrected transposition), where there is additional atrioventricular discordance.  The resultant physiology is that of a parallel circulation, with deoxygenated blood recirculating in the systemic circulation and oxygenated blood recirculating in the pulmonary circulation. At birth, this invariably results in cyanosis, with survival dependent upon adequate mixing of the two circulations via an atrial or ventricular level defect. There are three major anatomic variations in dTGA, including dTGA with an intact ventricular septum (most common), dTGA with a ventricular septal defect, and dTGA with LVOT obstruction. These anatomic subtypes can lead to variable presentations in the neonatal period, as well as pose unique challenges to surgical repair, and are therefore important diagnostic considerations. The arrangement of the coronary arteries and their spatial course can additionally be highly variable, posing added complications when performing the arterial switch operation (which requires reimplantation of the coronary arteries into the neo-aortic root). The most common, “usual,” arrangement is the left coronary artery originating off the anterior facing sinus, and the right coronary artery originating off the posterior facing sinus. 2. What surgical approaches have been utilized in the management of D-TGA?What are the key features of aortic coarctation anatomy? Prior to surgical advances in the late 1950s, this lesion was uniformly fatal, with most infants dying before the age of 1 year. Infants were initially palliated with an atrial septostomy, which allowed for mixing at the atrial level and improved survival in the immediate newborn period. However, these infants were still left with profound cyanosis, with inevitable mortality in the first year of life. In the mid-1950s, the Senning (1958) and Mustard (1964) atrial-level repairs were first performed, with good short-term outcomes and improved long-term survival. In the Senning procedure, a baffle is created within the atria that redirects the deoxygenated caval blood to the mitral valve and the oxygenated pulmonary venous blood to the tricuspid valve with use of native atrial tissue. Mustard subsequently described a simpler technique with creation of an atrial baffle using synthetic patch material. By the late 1980s, late complications of these repairs became well recognized, with the ultimate adoption of the neonatal arterial switch operation, which remains the gold standard for surgical management of transposition. 3. What are the long-term complications of the Mustard and Senning procedures? Systemic Right Ventricular Dysfunction: Clinical Features – Systemic RV dysfunction is an evitable consequence of the atrial switch operation, with 50% of patients developing right ventricular systolic dysfunction by 30 years of age. While right ventricular dysfunction is often mild and clinically asymptomatic for several years, patients ultimately develop related symptomatology over the subsequent 10-20 years. Most commonly, patients present to care with diminished exercise tolerance, with symptomatic arrhythmias being an additional common reason for patients to seek care. Diagnosis Accurate assessment of RV size and function in this population is critical for adequate surveillance and management planning. However, quantitative right ventricular assessment remains challenging, with no model for comparison and no clear criteria for abnormalities. Volumetric assessments are the gold standard, although made difficult by the complex geometry of the right ventricle. Cardiac MRI is most commonly utilized to assess RV size and systolic function, and additionally permits simultaneous evaluation of the systemic and pulmonary venous baffles and quantitative assessment of the degree of tricuspid regurgitation (the systemic AV valve). Transthoracic echocardiography is still routinely employed for serial evaluation of systemic right ventricular function. However, providers should have a low threshold to obtain further advanced imaging with any significant change in symptomatology or qualitative decrement in right ventricular systolic function on serial echocardiographic assessment. Management Medical Therapy: In contrast to ischemic cardiomyopathy, there are no long-term, randomized, placebo-controlled drug trials evaluating the efficacy of ACEI/ARB/ARNI or beta-blockers on systemic RV function. Small studies performed to date have not shown any appreciable benefit of ACEI/ARB on improving right ventricular ejection fraction or exercise capacity, which may reflect minimal baseline activation of the renin-angiotensin-aldosterone system in this form of heart failure. Use of beta-blocker therapy pathophysiologically makes sense, specifically reducing myocardial oxygen demand and allowing for improved ventricular filling; however, prior studies have produced mixed results, with evidence of improved right ventricular remodelingalthough no appreciable improvement in right ventricular ejection fraction, functional class, or long-term survival. Use of beta-blockers should also be cautioned in patients with established SA node dysfunction. Left Ventricular Re-Training: Conversion to an arterial switch operation often requires a staged approach to ensure that the left ventricle is adequately “trained” to handle systemic pressures. The left ventricle becomes rapidly deconditioned with time when continually exposed to the low-resistant pulmonary circuit, losing its ability to generate systemic pressure. Therefore, initial pulmonary artery banding is often required for left ventricle re-training, although this strategy has had variable success rates. Historically, age has been deemed an important factor in predicting the success of pulmonary artery banding, although this has not been consistently shown. The criteria for successful conversion post-banding are often extrapolated from l-TGA literature, and include generation of near systemic or systemic left ventricular pressures, presence of normal left ventricular systolic function, absent left ventricular diastolic dysfunction (LVEDP <12), an adequate LV mass (65 g/m2), and absent significant AV valve regurgitation. Cardiac transplantation has been successfully performed in this patient population, and should remain a consideration in medically refractory heart failure. Arrhythmias & Sudden Cardiac Death Arrhythmias are the most frequently observed adverse event following the atrial switch operation, with normal sinus rhythm being maintained in only 40-50% of patients at 15-20 years. In the initial post-operative period (first ~15 years), bradyarrhythmias predominate, with development of SA node dysfunction attributable to ischemic injury incurred at the time of surgery or fibrosis related to surgical suture/scar lines. Resultant chronotropic incompetence is commonly observed, with up to 20% of patients requiring pacemaker placement. Atrial arrhythmias are initially observed in the immediate post-operative period and have been shown to progress across the lifespan (affecting up to 50% of patients). These are typically re-entrant in nature, with IART and atrial flutter/fibrillation frequently observed. The underlying risk factors for their development are likely multifactorial, including atrial enlargement related to tricuspid regurgitation, suture line related fibrosis, and chronic hemodynamic stress from systemic RV failure. Given challenges imposed with use of anti-arrhythmic therapies (specifically with the high prevalence of SA and AV node dysfunction in this patient population), catheter ablation is typically employed for management of atrial arrhythmias (with a success rate upwards of 80%). Sudden cardiac death is known to occur in 2-15% of patients following the atrial switch operation and is predominantly felt to be arrhythmic in nature. Unlike in other forms of congenital heart disease (i.e. tetralogy of Fallot) and ischemic heart disease, there are no well-established risk factors for sudden cardiac death. Prior studies have found an association with surgical risk factors (initial surgery performed at an early age, earlier era of surgical repair, presence of VSD), and prior documented atrial arrhythmias, although there does not appear to be any consistent correlation with other traditional risk variables, including the presence of right ventricular systolic dysfunction, a prolonged QRS duration, history of ventricular arrhythmias on event monitor, or inducible ventricular arrhythmias on EP study. As a result, indications for ICD implantation are not well established and should be individualized, especially given the potential risks for development of baffle obstruction and “inappropriate” shocks in this patient population. Historic indications for ICD implantation have included a prior history of syncope with documented ventricular arrhythmias. Systemic/Pulmonary Venous Baffle Obstruction: Occurs in up to 30% of patients, with the systemic venous baffle most commonly involved. Diagnosis can often be made on cardiac MRI or with cardiac catheterization. Management typically involves systemic anticoagulation and transcatheter stenting and/or balloon dilation. 4. What are the long-term outcomes of d-TGA following an atrial switch operation? When compared with prior largely palliative procedures, the atrial switch operation substantially improved long-term survival in d-TGA, with an 80% survival rate at 25 years and 70% survival at 40 years post-repair. Early mortality is typically incurred in the setting of post-operative arrhythmias, with late mortality being predominantly related to systemic right ventricular dysfunction and fatal arrhythmias. As highlighted above, substantial morbidity is still incurred, with only a 19% event free survival at 40 years. Reintervention is predominantly required for (1) baffle related complications (stenosis and/or obstruction), (2) arrhythmias (requiring pacemaker and/or ICD implantation), and tricuspid regurgitation For a great discussion on dTGA following the atrial switch operation, check-out this great ACHA webinar by Dr. Lui: https://www.achaheart.org/your-heart/webinars/archive/living-life-fully-post-mustard-or-senning-in-the-adult-tga-patient/ References Cuypers JA, Eindhoven JA, Slager MA, Opić P, Utens EM, Helbing WA, Witsenburg M, van den Bosch AE, Ouhlous M, van Domburg RT, Rizopoulos D, Meijboom FJ, Bogers AJ, Roos-Hesselink JW. The natural and unnatural history of the Mustard procedure: long-term outcome up to 40 years. Eur Heart J. 2014 Jul 1;35(25):1666-74. doi: 10.1093/eurheartj/ehu102. Epub 2014 Mar 18. PMID: 24644309. Bottega NA, Silversides CK, Oechslin EN, Dissanayake K, Harrison JL, Provost Y, Harris L. Stenosis of the superior limb of the systemic venous baffle following a Mustard procedure: an under-recognized problem. Int J Cardiol. 2012 Jan 12;154(1):32-7. doi: 10.1016/j.ijcard.2010.08.064. Epub 2010 Oct 8. PMID: 20934761. Chow PC, Liang XC, Lam WW, Cheung EW, Wong KT, Cheung YF. Mechanical right ventricular dyssynchrony in patients after atrial switch operation for transposition of the great arteries. Am J Cardiol. 2008 Mar 15;101(6):874-81. doi: 10.1016/j.amjcard.2007.11.033. Epub 2008 Feb 21. PMID: 18328857. Cohen MS, Eidem BW, Cetta F, Fogel MA, Frommelt PC, Ganame J, Han BK, Kimball TR, Johnson RK, Mertens L, Paridon SM, Powell AJ, Lopez L. Multimodality Imaging Guidelines of Patients with Transposition of the Great Arteries: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. 2016 Jul;29(7):571-621. doi: 10.1016/j.echo.2016.04.002. PMID: 27372954. Couperus LE, Vliegen HW, Zandstra TE, Kiès P, Jongbloed MRM, Holman ER, Zeppenfeld K, Hazekamp MG, Schalij MJ, Scherptong RWC. Long-term outcome after atrial correction for transposition of the great arteries. Heart. 2019 May;105(10):790-796. doi: 10.1136/heartjnl-2018-313647. Epub 2018 Nov 10. PMID: 30415204. Dore A, Houde C, Chan KL, Ducharme A, Khairy P, Juneau M, Marcotte F, Mercier LA. Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial. Circulation. 2005 Oct 18;112(16):2411-6. doi: 10.1161/CIRCULATIONAHA.105.543470. Epub 2005 Oct 10. PMID: 16216961. Doughan AR, McConnell ME, Book WM. Effect of beta blockers (carvedilol or metoprolol XL) in patients with transposition of great arteries and dysfunction of the systemic right ventricle. Am J Cardiol. 2007 Mar 1;99(5):704-6. doi: 10.1016/j.amjcard.2006.10.025. Epub 2007 Jan 8. PMID: 17317376. Fricke TA, Konstantinov IE. Arterial Switch Operation: Operative Approach and Outcomes. Ann Thorac Surg. 2019 Jan;107(1):302-310. doi: 10.1016/j.athoracsur.2018.06.002. PMID: 30009809. Graham TP Jr, Bernard YD, Mellen BG, Celermajer D, Baumgartner H, Cetta F, Connolly HM, Davidson WR, Dellborg M, Foster E, Gersony WM, Gessner IH, Hurwitz RA, Kaemmerer H, Kugler JD, Murphy DJ, Noonan JA, Morris C, Perloff JK, Sanders SP, Sutherland JL. Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study. J Am Coll Cardiol. 2000 Jul;36(1):255-61. doi: 10.1016/s0735-1097(00)00682-3. PMID: 10898443. Giardini A, Lovato L, Donti A, Formigari R, Gargiulo G, Picchio FM, Fattori R. A pilot study on the effects of carvedilol on right ventricular remodelling and exercise tolerance in patients with systemic right ventricle. Int J Cardiol. 2007 Jan 8;114(2):241-6. doi: 10.1016/j.ijcard.2006.01.048. PMID: 21882492. Jimenez-Juan L, Joshi SB, Wintersperger BJ, Yan AT, Ley S, Crean AM, Nguyen ET, Deva DP, Paul NS, Wald RM. Assessment of right ventricular volumes and function using cardiovascular magnetic resonance cine imaging after atrial redirection surgery for complete transposition of the great arteries. Int J Cardiovasc Imaging. 2013 Feb;29(2):335-42. doi: 10.1007/s10554-012-0083-8. Epub 2012 Jul 12. PMID: 22790330. Kammeraad JA, van Deurzen CH, Sreeram N, Bink-Boelkens MT, Ottenkamp J, Helbing WA, Lam J, Sobotka-Plojhar MA, Daniels O, Balaji S. Predictors of sudden cardiac death after Mustard or Senning repair for transposition of the great arteries. J Am Coll Cardiol. 2004 Sep 1;44(5):1095-102. doi: 10.1016/j.jacc.2004.05.073. PMID: 15337224. Khairy P. Sudden cardiac death in transposition of the great arteries with a Mustard or Senning baffle: the myocardial ischemia hypothesis. Curr Opin Cardiol. 2017 Jan;32(1):101-107. doi: 10.1097/HCO.0000000000000353. PMID: 27801691. Khairy P, Clair M, Fernandes SM, Blume ED, Powell AJ, Newburger JW, Landzberg MJ, Mayer JE Jr. Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries. Circulation. 2013 Jan 22;127(3):331-9. doi: 10.1161/CIRCULATIONAHA.112.135046. Epub 2012 Dec 12. PMID: 23239839. Khairy P, Harris L, Landzberg MJ, Fernandes SM, Barlow A, Mercier LA, Viswanathan S, Chetaille P, Gordon E, Dore A, Cecchin F. Sudden death and defibrillators in transposition of the great arteries with intra-atrial baffles: a multicenter study. Circ Arrhythm Electrophysiol. 2008 Oct;1(4):250-7. doi: 10.1161/CIRCEP.108.776120. Epub 2008 Sep 12. PMID: 19808416. Kiesewetter C, Michael K, Morgan J, Veldtman GR. Left ventricular dysfunction after cardiac resynchronization therapy in congenital heart disease patients with a failing systemic right ventricle. Pacing Clin Electrophysiol. 2008 Feb;31(2):159-62. doi: 10.1111/j.1540-8159.2007.00963.x. PMID: 18233967. Love BA, Mehta D, Fuster VF. Evaluation and management of the adult patient with transposition of the great arteries following atrial-level (Senning or Mustard) repair. Nat Clin Pract Cardiovasc Med. 2008 Aug;5(8):454-67. doi: 10.1038/ncpcardio1252. Epub 2008 Jul 1. PMID: 18594551. Robinson B, Heise CT, Moore JW, Anella J, Sokoloski M, Eshaghpour E. Afterload reduction therapy in patients following intraatrial baffle operation for transposition of the great arteries. Pediatr Cardiol. 2002 Nov-Dec;23(6):618-23. doi: 10.1007/s00246-002-0046-2. PMID: 12530495. Roos-Hesselink JW, Meijboom FJ, Spitaels SE, van Domburg R, van Rijen EH, Utens EM, McGhie J, Bos E, Bogers AJ, Simoons ML. Decline in ventricular function and clinical condition after Mustard repair for transposition of the great arteries (a prospective study of 22-29 years). Eur Heart J. 2004 Jul;25(14):1264-70. doi: 10.1016/j.ehj.2004.03.009. PMID: 15246646. Scherptong RW, Vliegen HW, Winter MM, Holman ER, Mulder BJ, van der Wall EE, Hazekamp MG. Tricuspid valve surgery in adults with a dysfunctional systemic right ventricle: repair or replace? Circulation. 2009 Mar 24;119(11):1467-72. doi: 10.1161/CIRCULATIONAHA.108.805135. Epub 2009 Mar 9. PMID: 19273722. Mainwaring RD, Patrick WL, Ibrahimiye AN, Watanabe N, Lui GK, Hanley FL. An Analysis of Left Ventricular Retraining in Patients With Dextro- and Levo-Transposition of the Great Arteries. Ann Thorac Surg. 2018 Mar;105(3):823-829. doi: 10.1016/j.athoracsur.2017.11.047. Epub 2017 Dec 20. PMID: 29274314 Watanabe N, Mainwaring RD, Carrillo SA, Lui GK, Reddy VM, Hanley FL. Left Ventricular Retraining and Late Arterial Switch for D-Transposition of the Great Arteries. Ann Thorac Surg. 2015 May;99(5):1655-61; discussion 1661-3. doi: 10.1016/j.athoracsur.2014.12.084. Epub 2015 Mar 24. PMID: 25817887. Wheeler M, Grigg L, Zentner D. Can we predict sudden cardiac death in long-term survivors of atrial switch surgery for transposition of the great arteries? Congenit Heart Dis. 2014 Jul-Aug;9(4):326-32. doi: 10.1111/chd.12145. Epub 2013 Oct 23. PMID: 24151816. Meet Our Collaborators! Adult Congenital Heart AssociationFounded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers CHiP Network The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information. Heart UniversityHeart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/ Guest Profiles Dr. Maan Jokhadar Dr. Maan Jokhadar is associate professor of medicine with specialization in heart failure/transplant and in adult congenital heart disease at Emory University in Atlanta. He is the fellowship director for the Emory Adult Congenital Heart Disease training program and is board certified in internal medicine, cardiovascular disease, advanced heart failure/transplantation, adult congenital heart disease, and echocardiography. Dr. Jokhadar graduated from the University of Damascus School of Medicine in Syria and then went to Mayo Clinic in Rochester, Minnesota for internal medicine residency. He then completed cardiology and subspecialty training at Emory University, where he is currently on faculty. Dr. Jokhadar is the recipient of numerous teaching awards. Dr. Brynn Connor Dr. Brynn Connor is currently a Pediatric Cardiology fellow at Lucile Packard Children’s Hospital at Stanford. She completed her combined Internal Medicine and Pediatrics Residency at George University Hospital, and will ultimately be pursuing a career in Adult Congenital Heart Disease. CardioNerds Adult Congenital Heart Disease Production Team Amit Goyal, MD Daniel Ambinder, MD