Cardionerds: A Cardiology Podcast

The following question refers to Section 7.4 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by New York Medical College medical student and CardioNerds Intern Akiva Rosenzveig, answered first by Cornell cardiology fellow and CardioNerds Ambassador Dr. Jaya Kanduri, and then by expert faculty Dr. Randall Starling. Dr. Starling is Professor of Medicine and an advanced heart failure and transplant cardiologist at the Cleveland Clinic where he was formerly the Section Head of Heart Failure, Vice Chairman of Cardiovascular Medicine, and member of the Cleveland Clinic Board of Governors. Dr. Starling is also Past President of the Heart Failure Society of America in 2018-2019. Dr. Staring was among the earliest CardioNerds faculty guests and has since been a valuable source of mentorship and inspiration. Dr. Starling’s sponsorship and support was instrumental in the origins of the CardioNerds Clinical Trials Program. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #6 Mr. D is a 50-year-old man who presented two months ago with palpations and new onset bilateral lower extremity swelling. Review of systems was negative for prior syncope. On transthoracic echocardiogram, he had an LVEF of 40% with moderate RV dilation and dysfunction. EKG showed inverted T-waves and low-amplitude signals just after the QRS in leads V1-V3. Ambulatory monitor revealed several episodes non-sustained ventricular tachycardia with a LBBB morphology. He was initiated on GDMT and underwent genetic testing that revealed 2 desmosomal gene variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). Is the following statement true or false? “ICD implantation is inappropriate at this time because his LVEF is >35%” True   False   Answer #6 Explanation This statement is False. ICD implantation is reasonable to decrease sudden death in patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death who have an LVEF ≤45% (Class 2a, LOE B-NR). While the HF guidelines do not define high-risk features of sudden death, the 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy identify major and minor risk factors for ventricular arrhythmias as follows: Major criteria: NSVT, inducibility of VT during EPS, LVEF ≤ 49%. Minor criteria: male sex, >1000 premature ventricular contractions (PVCs)/24 hours, RV dysfunction, proband status, 2 or more desmosomal variants. According to the HRS statement, high risk is defined as having either three major, two major and two minor, or one major and four minor risk factors for a class 2a recommendation for primary prevention ICD in this population (LOE B-NR). Based on these criteria, our patient has 2 major risk factors (NSVT & LVEF ≤ 49%), and 3 minor risk factors (male sex, RV dysfunction, and 2 desmosomal variants) for ventricular arrhythmias. Therefore, ICD implantation for primary prevention of sudden cardiac death is reasonable. Decisions around ICD implantation for primary prevention remain challenging and depend on estimated risk for SCD, co-morbidities, and patient preferences, and so should be guided by shared decision making weighing the possible benefits against the risks, especially in younger patients. Main Takeaway In patients with genetic arrhythmogenic cardiomyopathy with high-risk features of sudden death with LVEF ≤ 45%, implantation of ICD is reasonable. Guideline Loc. Section 7.4 Also: Section 3.10 from “Towbin, J. A., McKenna, W. J., Abrams, D. J., Ackerman, M. J., Calkins, H., Darrieux, F. C. C., Daubert, J. P., de Chillou, C., DePasquale, E. C., Desai, M. Y., Estes, N. A. M., Hua, W., Indik, J. H., Ingles, J., James, C. A., John, R. M., Judge, D. P., Keegan, R., Krahn, A. D., … Zareba, W. (2019). 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm, 16(11), e301–e372. https://doi.org/10.1016/j.hrthm.2019.05.007”   Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 7.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by New York Medical College medical student and CardioNerds Intern Akiva Rosenzveig, answered first by Cornell cardiology fellow and CardioNerds Ambassador Dr. Jaya Kanduri, and then by expert faculty Dr. Clyde Yancy. Dr. Yancy is Professor of Medicine and Medical Social Sciences, Chief of Cardiology, and Vice Dean for Diversity and Inclusion at Northwestern University, and a member of the AHA/ACC/HFSA Heart Failure Guideline Writing Committee. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #5 Ms. L is a 65-year-old woman with nonischemic cardiomyopathy with a left ventricular ejection fraction (LVEF) of 35%, hypertension, and type 2 diabetes mellitus. She has been admitted to the hospital with decompensated heart failure (HF) twice in the last six months and admits that she struggles to understand how to take her medications and adjust her sodium intake to prevent this.  Which of the following interventions has the potential to decrease the risk of rehospitalization and/or improve mortality? A Access to a multidisciplinary team (physicians, nurses, pharmacists, social workers, care managers, etc) to assist with management of her HF   B Engaging in a mobile app aimed at improving HF self-care   C Vaccination against respiratory illnesses   D A & C   Answer #5   The correct answer is D – both A (access to a multidisciplinary team) and C (vaccination against respiratory illness).   Choice A is correct. Multidisciplinary teams involving physicians, nurses, pharmacists, social workers, care managers, dieticians, and others, have been shown in multiple RCTs, metanalyses, and Cochrane reviews to both reduce hospital admissions and all-cause mortality. As such, it is a class I recommendation (LOE A) that patients with HF should receive care from multidisciplinary teams to facilitate the implementation of GDMT, address potential barriers to self-care, reduce the risk of subsequent rehospitalization for HF, and improve survival. Choice B is incorrect.  Self-care in HF comprises treatment adherence and health maintenance behaviors. Patients with HF should learn to take medications as prescribed, restrict sodium intake, stay physically active, and get vaccinations. They also should understand how to monitor for signs and symptoms of worsening HF, and what to do in response to symptoms when they occur. Interventions focused on improving the self-care of HF patients significantly reduce hospitalizations and all-cause mortality as well as improve quality of life. Therefore, patients with HF should receive specific education and support to facilitate HF self-care in a multidisciplinary manner (Class I, LOE B-R). However, the method of delivery and education matters. Reinforcement with structured telephone support has been shown to be effective. In contrast the efficacy of mobile health-delivered educational interventions in improve self-care in patients with HF remains uncertain. Choice C is correct. In patients with HF, vaccinating against respiratory illnesses is reasonable to reduce mortality (Class 2a, LOE B-NR). For example, administration of the influenza vaccine in HF patients has been shown to reduce all-cause mortality and hospitalizations. Main Takeaway Implementation of multidisciplinary care teams has been proven to reduce rehospitalization and mortality in HF patients. While education on self-care of HF patients is important, not all delivery methods have been shown to be effective. Guideline Loc. Section 7.1 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 4.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Texas Tech University medical student and CardioNerds Academy Intern Dr. Adriana Mares, answered first by Baylor University cardiology fellow and CardioNerds FIT Trialist Dr. Shiva Patlolla, and then by expert faculty Dr. Eldrin Lewis. Dr. Lewis is an Advanced Heart Failure and Transplant Cardiologist, Professor of Medicine and Chief of the Division of Cardiovascular Medicine at Stanford University. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #4 Mr. Stevens is a 55-year-old man who presents with progressively worsening dyspnea on exertion for the past 2 weeks. He has associated paroxysmal nocturnal dyspnea, intermittent exertional chest pressure, and bilateral lower extremity edema. Otherwise, Mr. Stevens does not have any medical history and does not take any medications.  Which of the following will be helpful for diagnosis at this time? A  Detailed history and physical examination B  Chest x-ray C  Blood workup including CBC, CMP, NT proBNP D  12-lead ECG E All of the above   Answer #4   The correct answer is E – All of the above.  Mr. Stevens presents with signs and symptoms of volume overload concerning for new onset heart failure. The history and physical exam remain the cornerstone in the assessment of patients with HF. Not only is the H&P valuable for identifying the presence of heart failure but also may provide hints about the degree of congestion, underlying etiology, and alternative diagnoses. As such H&P earns a Class 1 indication for a variety of reasons in patients with heart failure: 1.       Vital signs and evidence of clinical congestion should be assessed at each encounter to guide overall management, including adjustment of diuretics and other medications (Class 1, LOE B-NR) 2.       Clinical factors indicating the presence of advanced HF should be sought via the history and physical examination (Class 1, LOE B-NR) 3.       A 3-generation family history should be obtained or updated when assessing the cause of the cardiomyopathy to identify possible inherited disease (Class 1, LOE B-NR) 4.       A thorough history and physical examination should direct diagnostic strategies to uncover specific causes that may warrant disease-specific management (Class 1, LOE B-NR) 5.       A thorough history and physical examination should be obtained and performed to identify cardiac and noncardiac disorders, lifestyle and behavioral factors, and social determinants of health that might cause or accelerate the development or progression of HF (Class 1, LOE C-EO) Building on the H&P, laboratory evaluation provides important information about comorbidities, suitability for and adverse effects of treatments, potential causes or confounders of HF, severity and prognosis of HF, and more. As such, for patients who are diagnosed with HF, laboratory evaluation should include complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone to optimize management (Class 1, LOE C-EO). In addition, the specific cause of HF should be explored using additional laboratory testing for appropriate management (LOE 1, LOE B-NR). In patients presenting with dyspnea such as Mr. Stevens, measurement of B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is useful to support a diagnosis or exclusion of HF (Class 1, LOE A); and in those with chronic HF, measurements of BNP or NT-proBNP levels are recommended for risk stratification (Class 1, LOE A). In addition to bloodwork, electrocardiography is part of the routine evaluation of a patient with HF and provides important information on rhythm, heart rate, QRS morphology and duration, cause, and prognosis of HF. So for all patients with HF, a 12-lead ECG should be performed at the initial encounter to optimize management (Class 1, LOE C-EO). Imaging is essential in the diagnosis and management of heart failure. In patients with suspected or new-onset HF, or those presenting with acute decompensated HF, a chest x-ray should be performed to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient’s symptoms (Class 1, LOE C-LD). Additionally, in those with suspected or newly diagnosed HF, transthoracic echocardiography (TTE) should be performed during the initial evaluation to assess cardiac structure and function (Class 1, LOE C-LD); and when echocardiography is inadequate, alternative imaging (e.g.,  cardiac magnetic resonance [CMR], cardiac computed tomography [CT], radionuclide imaging) is recommended for assessment of LVEF (Class 1, LOE C-LD). Main Takeaway  In patients who present with signs and symptoms of volume overload concerning for new-onset heart failure, it is essential to rule out non-cardiac causes and assess for specific underlying causes of heart failure by using detailed history and physical examination. Once heart failure diagnosis is established, further workup with laboratory testing, ECG, and non-invasive cardiac imaging is warranted to investigate the etiology of heart failure and guide further management. Special attention should be given to detection of signs and symptoms suggesting an advanced stage of disease. Guideline Loc.  Section 4.1 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 3.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Texas Tech University medical student and CardioNerds Academy Intern Dr. Adriana Mares, answered first by Rochester General Hospital cardiology fellow and Director of CardioNerds Journal Club Dr. Devesh Rai, and then by expert faculty Dr. Shelley Zieroth. Dr. Zieroth is an advanced heart failure and transplant cardiologist, Head of the Medical Heart Failure Program, the Winnipeg Regional Health Authority Cardiac Sciences Program, and an Associate Professor in the Section of Cardiology at the University of Manitoba. Dr. Zieroth is a past president of the Canadian Heart Failure Society. She is a steering committee member for PARAGLIE-HF and a PI Mentor for the CardioNerds Clinical Trials Program. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #3 Which of the following is/are true about heart failure epidemiology? A Although the absolute number of patients with HF has partly grown, the incidence of HF has decreased B Non-Hispanic Black patients have the highest death rate per capita resulting from HF C In patients with established HF, non-Hispanic Black patients have a higher HF hospitalization rate compared with non-Hispanic White patients D In patients with established HF, non-Hispanic Black patients have a lower death rate compared with non-Hispanic White patients E All of the above Answer #3 Explanation    The correct answer is “E – all of the above.”   Although the absolute number of patients with HF has partly grown as a result of the increasing number of older adults, the incidence of HF has decreased. There is decreasing incidence of HFrEF and increasing incidence of HFpEF. The health and socioeconomic burden of HF is growing. Beginning in 2012, the age-adjusted death-rate per capita for HF increased for the first time in the US. HF hospitalizations have also been increasing in the US. In 2017, there were 1.2 million HF hospitalizations in the US among 924,000 patients with HF, a 26% increase compared with 2013.   Non-Hispanic Black patients have the highest death rate per capita. A report examining the US population found the age-adjusted mortality rate for HF to be 92 per 100,000 individuals for non-Hispanic Black patients, 87 per 100,000 for non-Hispanic White patients, and 53 per 100,000 for Hispanic patients.   Among patients with established HF, non-Hispanic Black patients experienced a higher rate of HF hospitalization and a lower rate of death than non-Hispanic White patients with HF.Hispanic patients with HF have been found to have similar or higher HF hospitalization rates and similar or lower mortality rates compared with non-Hispanic White patients. Asian/Pacific Islander patients with HF have had a similar rate of hospitalization as non-Hispanic White patients but a lower death rate.   These racial and ethnic disparities warrant studies and health policy changes to address health inequity. Main Takeaway Racial and ethnic disparities in death resulting from HF persist, with non-Hispanic Black patients having the highest death rate per capita, and a higher rate of HF hospitalization. Further clinical studies and health policy changes are needed to address these inequalities. Guideline Loc. Section 3.1 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 6.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Mount Sinai Hospital cardiology fellow and CardioNerds FIT Trialist Dr. Jason Feinman, and then by expert faculty Dr. Mark Drazner. Dr. Drazner is an advanced heart failure and transplant cardiologist, Professor of Medicine, and Clinical Chief of Cardiology at UT Southwestern. He is the President of the Heart Failure Society of America. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #2 A 67-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, and active tobacco smoking presents to the emergency room with substernal chest pain for the past 5 hours. An electrocardiogram reveals ST segment elevations in the anterior precordial leads and he is transferred emergently to the catheterization laboratory. Coronary angiography reveals 100% occlusion of the proximal left anterior descending artery, and he is successfully treated with a drug eluting stent resulting in TIMI 3 coronary flow. Following his procedure, a transthoracic echocardiogram is performed which reveals a left ventricular ejection fraction of 35% with a hypokinetic anterior wall. Which of the following medications would be the best choice to prevent the incidence of heart failure and reduce mortality? A Lisinopril B Diltiazem C Carvedilol D Sacubitril-valsartan E Both A and C Answer #2 The correct answer is E – both lisinopril and carvedilol are appropriate to reduce the incidence of heart failure and mortality. Evidence-based beta-blockers and ACE inhibitors both have Class 1 recommendations in patients with a recent myocardial infarction and left ventricular ejection fraction ≤ 40% to reduce the incidence of heart failure and to reduce mortality. Multiple randomized controlled trials have investigated both medications in the post myocardial infarction setting and demonstrated improved ventricular remodeling as well as benefits for mortality and development of incident heart failure. At this time, there is not sufficient evidence to recommend ARNi over ACEi for patients with reduced LVEF following acute MI. The PARADISE-MI trial randomized a total of 5,661 patients with myocardial infarction complicated by a reduced LVEF, pulmonary congestion, or both to receive either sacubitril-valsartan (97-103mg twice daily) or ramipril (5mg twice daily). After a median follow up time of 22 months, there was no statistically significant difference in the primary outcome of cardiovascular death or incident heart failure. At this time, ARNi have not been included in the guidelines for this specific population. Diltiazem is a non-dihydropyridine calcium channel blocker, a family of drugs with negative inotropic effects and which may be harmful in patients with depressed LVEF (Class 3: Harm, LOE C-LD). Main Takeaway:  For patients with recent myocardial infarction and reduced left ventricular function both beta blockers and ACEi have Class 1 recommendations to reduce the incidence of heart failure and decrease mortality. Guideline Location: Section 6.1 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 2.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Mount Sinai Hospital cardiology fellow and CardioNerds FIT Trialist Dr. Jason Feinman, and then by expert faculty Dr. Biykem Bozkurt. Dr. Bozkurt is the Mary and Gordon Cain Chair, Professor of Medicine, Director of the Winters Center for Heart Failure Research, and an advanced heart failure and transplant cardiologist at Baylor College of Medicine in Houston, TX. She is former President of HFSA, former senior associate editor for Circulation, current Editor-In-Chief of JACC Heart Failure. Dr. Bozkurt was the Vice Chair of the writing committee for the 2022 Heart Failure Guidelines. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #1 A 23-year-old man presents to his primary care physician for an annual visit. His father was diagnosed with idiopathic cardiomyopathy at 40 years of age. His blood pressure in clinic is 146/90 mmHg. He is a personal trainer and exercises daily, including both weightlifting and cardio. He denies any anabolic steroid use. He is an active tobacco smoker, approximately ½ pack per day. Review of systems is negative for symptoms. What stage of heart failure most appropriately describes his current status? A Stage A B Stage B C Stage C D Stage D E None of the above Answer #1 The correct answer is A – Stage A of heart failure. Overall, the ACC/AHA stages of HF were designed to emphasize the development and progression of disease. More advanced stages and progression are associated with reduced survival. Stage A HF is where patients are “at risk for HF”, but without current or previous symptoms or signs of HF, and without structural/functional heart disease or abnormal biomarkers. At-risk patients include those with hypertension, cardiovascular disease, diabetes, obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or family history of cardiomyopathy. Stage B HF is the “pre-heart failure” stage where patients are without current or previous symptoms or signs of HF but do have at least one of the following: Structural heart disease (i.e., reduced left or right ventricular systolic function, ventricular hypertrophy, chamber enlargement, wall motion abnormalities, and valvular heart disease) Evidence of increased filling pressures Risk factors and increased natriuretic peptide levels or persistently elevated cardiac troponin in the absence of an alternate diagnosis Stage C HF indicates symptomatic heart failure where patients have current or previous symptoms or signs of HF. Stage D HF indicates advanced heart failure with marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize guideline-directed medical therapy. Therapeutic interventions in each stage aim to modify risk factors (Stage A), treat risk and structural heart disease to prevent HF (stage B), and reduce symptoms, morbidity, and mortality (stages C and D). Given this patient’s family and social histories, along with the clinical finding of elevated blood pressure, he is best classified as having Stage A, or at risk for HF. Were he to have signs of cardiac abnormalities on chest X-ray, ECG, biomarkers, or other testing, he would then be classified as having Stage B, or pre-heart failure. Main Takeaway: It is important to identify patients who are at risk for heart failure (Stage A HF) early to modify risk factors and prevent disease progression. Guideline location: Section 2.1, Figure 1, Table 3 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Join CardioNerds (Dr. Mark Belkin and Dr. Natalie Tapaskar) as they discuss the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure with Writing Committee Chair Dr. Paul Heidenreich. They discuss how one gets involved with a guideline writing committee, the nuts and bolts of the guideline writing process, pitfalls and utility of the term “GDMT,” background behind inclusion of “Value Statements,” potential omissions from the document, clinical uptake of recommendations, and anticipated changes for the next iteration. Audio editing by CardioNerds academy intern, Pace Wetstein. This discussion is a prelude to the CardioNerds Decipher The Guidelines Series designed to enhance understanding and uptake of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. We will be using high-impact, board-style, clinical vignette-based questions to highlight core concepts relevant to your practice. We will do so by releasing several short bite-sized Pods with one question per episode. Note that the cases used are hypothetical and created solely to illustrate core concepts. This series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The importance of recognition and diagnosis of cardiac amyloidosis is at an all-time high due to its high prevalence and improved therapeutic strategies. Here we discuss what CardioNerds need to know about the manifestations, diagnosis, and management of transthyretin (ATTR) and light chain (AL) cardiac amyloidosis. Join Dr. Dan Ambinder (CardioNerds Cofounder), Dr. Dinu-Valentin Balanescu (Series Cochair, Chief Resident at Beaumont Health, and soon FIT at Mayo Clinic), and Dr. Dan Davies (Episode FIT Lead and FIT at Mayo Clinic) as they discuss cardiac amyloidosis with Dr. Omar Siddiqi, cardiologist at the Boston University Amyloidosis Center and program director for the general cardiovascular fellowship program at Boston University, a CardioNerds Healy Honor Roll Program. Episode notes were drafted by Dr. Dan Davies. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. Access the CardioNerds Cardiac Amyloidosis Series for a deep dive into this important topic. This episode is supported by a grant from Pfizer Inc. This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan.  Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Pearls • Notes • References • Production Team CardioNerds Cardio-Oncology 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 Cardiac amyloidosis is no longer considered a rare disease, especially transthyretin amyloidosis in older male patients with HFpEF and aortic stenosis. Echocardiogram is the “gate keeper” of cardiac imaging and provides initial evidence of amyloid infiltration, while cardiac MRI can help refine the presence of an infiltrative cardiomyopathy versus other causes of increased wall thickness. The most clinically important types of amyloid heart disease are transthyretin (ATTR) and light chain (AL) amyloidosis. The workup to differentiate these disorders includes a gammopathy panel to screen for the presence of potentially amyloidogenic light chains (serum and urine electrophoresis WITH immunofixation and serum free light chains), and cardiac scintigraphy with Technetium-99m-labeled bone-seeking tracers (PYP, DPD, etc.) to identify cardiac aTTR infiltration if the gammopathy panel is unrevealing. There is still a role for endomyocardial biopsy in the diagnosis of cardiac amyloidosis! All patients in whom there is concern for cardiac amyloidosis and gammopathy panel indicates the presence of monoclonal light chains should have a biopsy to obtain a tissue diagnosis of likely AL amyloidosis. Alternatively, an endocardial biopsy may prove valuable in patients who have confusing phenotypic features between amyloid types, such as a patient with abnormal monoclonal protein and positive PYP imaging. Be suspicious of heart failure patients that do not tolerate typical medications that lower heart rate. In the restrictive cardiomyopathy of cardiac amyloidosis, patients are reliant on higher heart rates to compensate for the inability to augment stroke volume. Be suspicious of amyloidosis in patients with recurrent left atrial thrombi despite anticoagulation. Show notes CardioNerds Cardiac Amyloid, updated 1.20.21 1. What is cardiac amyloidosis and how common is it? Cardiac amyloidosis is adisorder caused by misfolding of proteins into insoluble forms which are deposited into extracellular spaces of the heart, commonly causing a stiff and thick heart with progressive diastolic dysfunction with restrictive hemodynamics and ensuing heart failure. The two most common types of amyloid protein that affect the heart are transthyretin (ATTR) and light chain (AL). Transthyretin amyloidosis is caused by a misfolded transporter protein produced by the liver, while light chain amyloidosis is caused by a misfolded light chain immunoglobulin produced by clonal plasma cells. ATTR cardiac amyloidosis may be present in 6-17% of older patients with HFpEF and increased wall thickness, as well as in 4-16% of patients undergoing intervention for severe aortic stenosis. AL amyloidosis is much rarer, with a prevalence of about 12 cases per million persons per year. 2. What are some non-cardiac clues to the presence of cardiac amyloidosis? Non-cardiac clinical clues for transthyretin amyloidosis (ATTR) include spinal stenosis, biceps tendon rupture, carpal tunnel syndrome (particularly when bilateral), and peripheral neuropathy. Bilateral carpal tunnel syndrome may be present in up to 60% of ATTR-CA patients with over 40% having a history of biceps tendon rupture. Non-cardiac clinical clues for light chain amyloidosis (AL) include renal disease (esp. nephrotic syndrome), macroglossia, autonomic and peripheral neuropathy, and periorbital purpura (racoon eyes). 3. What are common multimodality imaging features used for the diagnosis of cardiac amyloidosis? For an in-depth discussion about the use of multimodality imaging in the diagnosis of cardiac amyloidosis, enjoy CardioNerds Episode #109 – Nuclear & Multimodality Imaging: Cardiac Amyloidosis. Echocardiography (echo) is among the first test performed in patients for the diagnosis of cardiovascular symptoms and may provide initial clues to the diagnosis. Features of cardiac amyloidosis on echocardiogram include increased left ventricular wall thickness (>12 mm, classically concentric) with abnormal diastolic function, increased right ventricular free wall and interatrial septal thickness, as well as increased valve thickness. There may be a small pericardial effusion. Left ventricular strain is usually abnormal with a characteristic apical sparing pattern. A granular, or sparkling, appearance of the myocardium has been classically described but is poorly predictive. Cardiac magnetic resonance (CMR) imaging is often used for differentiation of increased left ventricular wall thickness (infiltrative cardiomyopathies, hypertrophic cardiomyopathies, etc.) and in patients at increased risk of AL cardiac amyloidosis. Common features specific to CMR include abnormal myocardial nulling (blood pool nulls before the myocardium on inversion recovery sequences), elevated native T1 value, increased extracellular volume (ECV), and late gadolinium enhancement (classically in a diffuse, non-ischemic pattern). Bone scintigraphy (technetium pyrophosphate [PYP] or DPD) is a nuclear imaging study used for the diagnosis of transthyretin amyloidosis. In the absence of an abnormal monoclonal protein, the sensitivity and specificity approach 100%, allowing for the “non-biopsy” diagnosis of ATTR-CA (specifically in the context of a negative gammopathy panel). The 2019 multi-society diagnostic guidelines recommend SPECT imaging be used in combination planar imaging for all cases to improve predictive characteristics. 4. How are heart failure and arrhythmias managed in patients with cardiac amyloidosis? The mainstay of heart failure therapy in cardiac amyloidosis is loop diuretics with or without aldosterone antagonists. Spironolactone was shown to be effective in patients with a phenotype suggesting cardiac amyloidosis in a subgroup analysis of TOPCAT. Patients often have poor tolerance of guideline directed medical therapies for heart failure, including beta blockers and calcium channel blockers, with ACEI/ARB/ARNI frequently limited by hypotension. The SGLT2 inhibitors appear to be tolerated in patients with cardiac amyloidosis but more research is needed to determine impact on cardiovascular outcomes. Rate and rhythm control strategies for atrial arrhythmias can both be successful, but patients may be intolerant of medications. The risk of cardioembolic events in amyloid patients with atrial fibrillations is elevated, independent of CHA2DS2 -VASc score, and therefore all patients should be offered anticoagulation. Be suspicious of amyloidosis in patients with recurrent left atrial appendage thrombi despite anticoagulation. 5. What specific therapies can be used for transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis? Tafamidis is a transthyretin stabilizer that inhibits tetramer dissociation and reduces amyloid deposition in extracellular tissue. It is the only FDA approved medication for transthyretin cardiac amyloidosis and was shown to be associated with reduced mortality and heart failure hospitalization compared to control in the ATTR-ACT trial. Patisiran is a small interfering RNA that works as a gene silencer for ATTR protein production and is FDA approved for patients with polyneuropathy secondary to hereditary ATTR. Analysis of cardiac outcomes in the APOLLO trial suggest early stabilization of left ventricular wall thickness and reduction in natriuretic peptides in patients with features of concomitant cardiac involvement. Specific therapies for AL amyloidosis are managed by hematologists with the goal of complete hematologic response to prevent further immunoglobulin production and amyloid deposition. These therapies typically include chemotherapy regimens (e.g. cyclophosphamide, bortezomib, dexamethasone [CyBorD]), daratumumab (an anti-CD38 antibody), with or without autologous stem cell transplantation. There are many ongoing trials with novel therapies, with specific interest in treatments targeting removal of systemically deposited amyloid fibrils. References Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2—evidence base and standardized methods of imaging. J. Nucl. Cardiol. 26, 2065–2123 (2019). Link Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization. J. Nucl. Cardiol. 27, 659–673 (2020). Link Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, Grogan M, Cheng RK. ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2021;3(4):488-505. Link Witteles RM, Liedtke M. AL Amyloidosis for the Cardiologist and Oncologist: Epidemiology, Diagnosis, and Management. JACC CardioOncol. 2019;1(1):117-130. Link Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. Link Gertz, M. A., & Dispenzieri, A. (2020). Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. Jama, 324(1), 79-89. https://jamanetwork.com/journals/jama/fullarticle/2767867 Cappelli, F., Zampieri, M., Fumagalli, C., Nardi, G., Del Monaco, G., Matucci Cerinic, M., Allinovi, M., Taborchi, G., Martone, R., Gabriele, M., Ungar, A., Moggi Pignone, A., Marchionni, N., Di Mario, C., Olivotto, I., & Perfetto, F. (2021). Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype. J Intern Med, 289(6), 831-839. https://pubmed.ncbi.nlm.nih.gov/33615623/ Sperry, B. W., Hanna, M., Shah, S. J., Jaber, W. A., & Spertus, J. A. (2021). Spironolactone in Patients With an Echocardiographic HFpEF Phenotype Suggestive of Cardiac Amyloidosis: Results From TOPCAT. JACC Heart Fail, 9(11), 795-802. https://www.sciencedirect.com/science/article/pii/S2213177921003206?via%3Dihub Dobner, S., Bernhard, B., Asatryan, B., Windecker, S., Stortecky, S., Pilgrim, T., Gräni, C., & Hunziker, L. (2022). SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin. ESC Heart Fail. https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14188 Meet Our Collaborators International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

This episode is focused on Palliative Care and Shared Decision-Making in the CICU. In this episode, we learn about how the principles of palliative care and shared decision-making apply to our patients across the spectrum of cardiovascular care, especially in the cardiac intensive care unit. We discuss pivotal trials of specialty palliative care and decision aids in cardiology and how they might inform our practice to enhance patient quality of life and improve goal-concordant care. Finally, we discuss practical tips and communication strategies for how to engage patients about end-of-life decisions and topics that can be utilized from outpatient to inpatient to critical care settings. “We need to help patients hope for the best and plan for the worst as time goes on.” Dr. Larry Allen Series co-chairs Dr. Eunice Dugan and Dr. Karan Desai, along with CardioNerds Co-founder Amit Goyal are joined by FIT lead, Dr. Sarah Chuzi. Dr. Chuzi is a Chicagoan and completed her internal medicine residency, cardiology fellowship, AHFTC fellowship and is now Assistant Professor at Northwestern University. Our episode expert is a true national leader in shared decision-making and palliative care in heart failure – Dr. Larry Allen, Medical Director of Advanced Heart Failure and the Co-Director of the Colorado Program for Patient-Centered Decisions at the University of Colorado School of Medicine. Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen. The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark Belkin, Dr. Eunice Dugan, Dr. Karan Desai, and Dr. Yoav Karpenshif. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Pearls • Notes • References • Production Team 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 – Palliative Care and Shared Decision-Making in the CICU 1. “Much of what we do in cardiology is thinking about how to make people feel better (not just improving cardiac function or length of life). So, on a day-to-day basis we are really providing primary palliative care.” – Dr. Larry Allen 2. “Risk models in cardiology can only be so accurate… While risk models can give us some grounding, we also need to embrace the concept of uncertainty, and help patients understand that there are a variety of things that might happen to them, suggest some things they might plan for, and continue to iteratively come back to the patient and reevaluate what their options are.” – Dr. Larry Allen 3. “Our goal is to help people live happy, healthy, full lives. But, everyone dies. So understanding that death is a part of life and understanding how to help them make those transitions is critical” – Dr. Larry Allen 4. “Having good deaths is a part of good healthcare. We can’t ignore that. We can’t fight against it. We should embrace it. And we have the opportunity to do that.” – Dr. Larry Allen 5. We should still keep in mind the concept of medical futility and determining what options are reasonable for patients. Part of shared decision-making includes discussing what interventions would not be feasible or helpful with patients and families Show notes – Palliative Care and Shared Decision-Making in the CICU Notes drafted by Dr. Sarah Chuzi. 1. How are the basic principles of palliative care relevant to cardiology, and can you define the key concepts of shared decision-making, primary palliative care, specialty (or secondary) palliative care, and hospice care? Throughout medicine, we confront the concepts of symptom control, difficult medical decision-making, and end-of-life. These are the principles of palliative care and they apply very easily across the spectrum of cardiology. Shared decision-making is a meeting between two experts – the patient and the clinician. The patient is the expert in what’s important to them and their hopes, fears, values, goals, and preferences. The clinician is the expert in the medical aspects of care, including care that is not possible, care that might be high value, and the potential trade-offs and range of outcomes involved in a medical decision. Palliative care is defined by the WHO – as care that deals with patient symptoms and quality of life. Increasingly, the terms primary and secondary palliative care are used. Primary palliative care is care provided by a general clinician (or cardiologist), while secondary palliative care is provided by a board-certified palliative care clinician. Hospice care is really a health insurance benefit that provides a certain group of services (e.g. nurses, equipment) for patients who have terminal illness and less than 6 months to live. 2. What have we learned from existing trials looking at specialty palliative care in heart failure? A few large trials (CASA, ENABLE, SWAP-HF, PAL-HF) of specialty palliative care interventions in heart failure have shown mixed results. One of the reasons for this is the heterogeneity in patient and caregiver adjustment/symptoms at baseline. Future trials will need to determine which patients and caregivers are really in need of interventions or assistance surrounding some of these issues.  3. What are some strategies trainees can use to help elucidate a patient’s goals and values and engage in shared decision-making in high intensity, critical care situations? Trying to determine (from the patient or family) whether the patient is a medical maximizer or minimizer can be helpful; i.e., what is his preference for aggressiveness of care. Obtaining collateral from a patient’s power of attorney/next of kin/proxy about prior discussions regarding goals and values is valuable. We should still keep in mind the concept of medical futility and determining what options are reasonable for patients. Part of shared decision-making includes discussing what interventions would not feasible or helpful with patients and families. 4. What is the role of decision aids in the process of deciding whether to pursue LVAD implantation? Decision aids are unique from educational materials in that decision aids discuss alternative treatment options, including what life might be like if a certain treatment option is not pursued. Decision aids encourage patients to reflect on their values and then try to map the decisions in the context of their values. The research group at the University of Colorado developed a decision aid to help patients and their families determine whether an LVAD would be an appropriate medical intervention for them. The decision aid is available online (patientdecisionaid.org) and includes a 26-minute video and an 8-page pamphlet. Currently, they are being disseminated nationally in a large implementation trial. The DECIDE-LVAD trial demonstrated that this decision aid improved values-choice concordance for patients considering LVAD therapy. 5. What are the benefits of hospice for patients with cardiac disease and how does hospice fall short? It’s important to understand what hospice will and will not cover. The hospice benefit is a fixed payment per day. So, it’s important to consider what treatments might be covered and to discuss this with patients and families.  For patients with advanced cardiac disease, coverage of inotropes is a common issue that we encounter. It’s important to prepare patients for the fact that inotropes may not be accepted in a given hospice program. Additionally, sometimes clinicians struggle with how to continue to provide care for patients who enter hospice as we try to navigate how to stay involved in their care while respecting their wishes to be at home and not necessarily come to clinic. References – Palliative Care and Shared Decision-Making in the CICU Rogers JG, Patel CB, Mentz RJ, et al. The palliative care in heart failure (PAL-HF) randomized, controlled clinical trial. 2017. J Am Coll Cardiol, 70(3): 331-341. Allen LA, Mcilvennan CK, Thompson JS, et al. Effectiveness of an intervention supporting shared decision making for destination therapy left ventricular assist device: the DECIDE-LVAD randomized clinical trial. 2018. JAMA Intern Med, 178(4): 520-529. Warraich HJ, Patel CB, Kochar A, Rogers JG, Patel MR. Incorporating shared decision making and palliative care into cardiogenic shock pathways. 2010. J Am Coll Cardiol, 74(4): 501-502. Chuzi S, Khan SS, Pak ES. Primary palliative care education in advanced heart failure and transplant cardiology fellowships. 2021. J Am Coll Cardiol, 77(4): 501-505.  

Partial anomalous pulmonary venous return refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. This causes left to right shunting which may have hemodynamic and therefore clinical significance, warranting repair in some patients. Join CardioNerds to learn about partial anomalous pulmonary venous return! Dr. Dan Ambinder (CardioNerds co-founder), Dr. Josh Saef (ACHD FIT at the University of Pennsylvania and ACHD Series co-chair), and Dr. Tripti Gupta (ACHD FIT at Vanderbilt University and episode lead) learn from Dr. Ian Harris (Director of the Adult Congenital Heart Disease program at University of California, San Francisco). Audio editing by CardioNerds Academy Intern, student doctor Shivani Reddy. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh 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 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 – Partial Anomalous Pulmonary Venous Return (PAPVR) What is partial anomalous pulmonary venous return (PAPVR)? PAPVR refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. Often, this means one or more pulmonary veins empty into the right atrium or a systemic vein such as the superior vena cava or inferior vena cava. Physiologically, this produces a left-to-right shunt, allowing for already-oxygenated blood to recirculate into the lungs and result in excessive pulmonary blood flow.  What are the clinical features of PAPVR? Diagnosis is usually incidental on a cross sectional imaging such as CTA or CMR. The most common associated lesion is an atrial-level defect. It is unusual for a single anomalous pulmonary venous connection of only 1 pulmonary lobe to result in significant shunting. Patients with a significant degree of left to right shunting may have right heart dilatation or symptoms of dyspnea on exertion. When are some strategies for managing patients with PAPVR? A surgical correction is recommended for patients with PAPVR when functional capacity is impaired and RV enlargement is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (aka: ratio of pulmonary flow (Qp) to systemic flow (Qs) is > 1.5:1), PA systolic pressure is less than 50% systemic pressure and pulmonary venous resistance is less than one third of systemic venous resistance. Surgical repair involves intracaval baffling of the left atrium (Warden procedure) or direct reimplantation of the anomalous pulmonary vein into the left atrium. Pregnancy is well tolerated in patients with repaired PAPVR. In patients with unrepaired lesion who may have right sided heart dilatation and/or pulmonary hypertension, preconception evaluation and counseling should address how pregnancy may affect mother’s and fetus’s health. Antibiotic prophylaxis for infective endocarditis is typically not needed unless patients are less than 6 months from recent surgery, have residual defect at the patch margin or prior history of infective endocarditis. Show notes – Partial Anomalous Pulmonary Venous Return (PAPVR) Notes (drafted by Dr. Tripti Gupta): 1. What is partial anomalous pulmonary venous return? Anatomically, partial anomalous pulmonary venous return refers to anomalies in which one or more (but not all) of the pulmonary veins connects to a location other than the left atrium. Often, this means one or more pulmonary veins empty into the right atrium or a systemic vein such as the superior vena cava (SVC) or inferior vena cava (IVC). Physiologically, this produces a left-to-right shunt, allowing for already-oxygenated blood to recirculate into the lungs and result in excessive pulmonary blood flow.  If all pulmonary veins from both lungs drain to an anomalous site or in an abnormal fashion, then it is identified as a total anomalous pulmonary venous return (TAPVR). Patients with TAPVR often require surgical intervention in childhood. A bit of a nuance in terminology – partial anomalous pulmonary venous return (PAPVR) vs. partial anomalous pulmonary venous connection (PAPVC), requires some explanation. The suffix “return” refers to vessels returning to a chamber (ex: pulmonary vein returns to morphological left atrium after blood functionally mixes with systemic venous return or is redirected via an atrial septal defect) vs. “connection” implies abnormal anatomic attachments.  2. How does this happen? What is the embryological explanation for PAPVR? We know that the pulmonary veins originate from the posterior aspect of the left atrium. Meanwhile, the lung buds that arise from the lung parenchyma canalize as a vessel and gradually connect to the developing pulmonary veins. Some theories say that the lung buds are initially enmeshed in the splanchnic plexus which drains into the cardinal and umbilical vitelline veins (systemic venous system). By week 4 of gestation, the pulmonary veins from the left atrium connects with the superior portion of the splanchnic plexus to form the pulmonary plexus and ultimately loses its connection with the splanchnic plexus. The pulmonary vein is then supposed to divide into 4 branches, 2 on right and 2 on left, each with an orifice at the left atrium. Failure of one or more of the pulmonary veins to separate from the systemic venous systemic results in PAPVC/TAPVC. 3. What are some major clinical findings in PAPVR? PAPVR is typically an incidental diagnosis on CT or MRI in asymptomatic patients when these scans are done for another reason. Many patients with PAPVR may remain asymptomatic throughout childhood and adult life. Physiological changes may depend on degree of left to right shunt, number of veins involved, their sites of connection and associated lesions. 80% of anomalous connections are of the right sided pulmonary veins and 20% affect the left sided pulmonary veins. The most common variants include: Right upper pulmonary vein or right middle pulmonary vein to SVC, azygos vein, or right atrium. This variant is the most common and can be often associated with a sinus venosus defect. Right pulmonary veins to IVC, usually via a single trunk draining caudally and connecting to the IVC near the diaphragm. This variant is sometimes known as Scimitar syndrome. When you look at the descending trunk connecting the right venous return to the right atrium on x-ray or fluoroscopy, it has a crescent-like shape, like a Turkish sword from the Ottoman Empire or a scimitar, hence the name Scimitar syndrome. Left pulmonary vein(s) to the innominate vein via a vertical vein. Left pulmonary veins to the coronary sinus. If more that 50% of a person’s pulmonary venous return drains anomalously to the right side of the heart, there may be right heart enlargement and presentation of symptoms such as dyspnea on exertion earlier in life. Physical exam findings may include prominent right ventricular impulse, a systolic ejection murmur at the left upper sternal border, split S2, and possibly a mid-diastolic rumble. In the absence of an ASD, these findings may not be obvious. On ECG, a RBBB morphology, RAD or first-degree heart block is associated with right ventricular volume enlargement. On echocardiogram, RV enlargement without left heart dysfunction should raise suspicion for anomalous pulmonary venous connection. Other hints can include the presence of a sinus venosus ASD, secundum ASD or RV enlargement that is significantly large for a small ASD/PFO. While left sided pulmonary veins can be visualized on the suprasternal view of transthoracic echocardiogram, right sided veins are more challenging on TTE. A TEE can be used to identify the site and drainage of pulmonary veins. A right heart catheterization is useful to identify the presence and etiology of pulmonary hypertension and quantify flows in pulmonary and systemic system and presence of a shunt. Selective angiography of the right and left pulmonary arteries can confirm the presence and course of pulmonary veins on levophase. A gated cardiac CTA or CMR is helpful and recommended for definitive diagnosis. A CTA offers higher spatial resolution than a CMR at the cost of radiation and iodinated contrast exposure. A CMR offers high resolution for defining vascular anatomy, quantifying chamber dimensions, estimate shunt burden and degree of stenoses using flow quantification techniques. In addition, respiratory-gated 3D whole heart imaging or MRA can be used for multiplanar reconstruction and aid in perioperative planning. Patients with TAPVR present with cyanosis at birth and need urgent surgical correction. 4. What conditions are associated with PAPVR? 80% of patients with PAPVR lesion may have an associated atrial level defect. In particular, a superior sinus venosus defect is frequently associated with right sided anomalous pulmonary venous connections. Other associated cardiac lesions include conotruncal abnormalities such as Tetralogy of Fallot or double outlet right ventricle, ventricular septal defects, and valvular abnormalities such as pulmonary stenosis, mitral or aortic stenosis or atresia and aortic arch anomalies. Anomalous pulmonary venous connections can also be seen in patients with heterotaxy syndrome, where mispositioned organs such as the heart, lungs, stomach, intestines, and liver may be in nonstandard locations within the chest and abdomen. 5. What are some main considerations for surgical repair for PAPVR? Cross sectional imaging such as CTA or CMR may be helpful to identify pulmonary venous connections and other extracardiac vascular anatomy. It is unusual for a single anomalous pulmonary venous connection of only 1 pulmonary lobe to result in a sufficient volume load to justify surgical repair. However, if a patient has symptoms referable to the shunt, there is >1 anomalous vein, and a moderate or large left-to-right shunt, then surgical repair is associated with a reduction in RV size and PA pressure. Pulmonary hypertension is a risk for adverse outcomes with surgery. A hemodynamic assessment with may help identify pressures, saturations, and degree of shunting. A surgical correction is recommended for patients with PAPVR when functional capacity is impaired and RV enlargement is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (aka: ratio of pulmonary flow (Qp) to systemic flow (Qs) is > 1.5:1), PA systolic pressure is less than 50% systemic pressure and pulmonary venous resistance is less than one third of systemic venous resistance. Surgery can involve intracaval baffling of the left atrium (warden procedure) or direct reimplantation of the anomalous pulmonary vein directly into the left atrium. Repair of PAPVR may be considered at the time of closure of sinus venosus or other ASD. Transcatheter therapies are an area of ongoing innovation. References – Partial Anomalous Pulmonary Venous Return (PAPVR) Gatzoullis MA, Webb GD, Daubeney PEF. Chapter 37: Partial Anomalous Pulmonary Venous Connections and Scimitar Syndrome In: Diagnosis and Management of Adult Congenital Heart Disease. 3rd ed. Elsevier Health Sciences; 2017: 354-361 Kao CC, Hsieh CC, Cheng PJ et al. Total Anomalous Pulmonary Venous Connection: From Embryology to a Prenatal Ultrasound Diagnostic Update. J Med Ultrasound. Sep 2017; 25 (3): 130-137 Pendela VS, Tan BEX, Chowdhury M, Chow M. Partial Anomalous Pulmonary Venous Return Presenting in Adults: A Case Series with Review of Literature. Cureus. 2020 Jun 1; 12 (6): e8388 Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. Apr 2 2019;139(14):e698-e800. Meet Our Collaborators! Adult Congenital Heart 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/ CardioNerds Adult Congenital Heart Disease Production Team Amit Goyal, MD Daniel Ambinder, MD