(BQ) Part 1 book MGH cardiology broad review presents the following contents: History and physical examination, acute coronary syndrome, chronic coronary artery disease, hypertension, lipoprotein disorders, diabetes mellitus and the metabolic syndrome, nuclear cardiology and exercise stress testing, diseases of the aorta,...
Hanna K Gaggin James L Januzzi, Jr Editors MGH cardiology Board Review 123 MGH Cardiology Board Review MGH Cardiology Board Review Editors Hanna K Gaggin Cardiology Division Department of Medicine Massachusetts General Hospital Boston Massachusetts USA James L Januzzi, Jr Cardiology Division Department of Medicine Massachusetts General Hospital Boston Massachusetts USA ISBN 978-1-4471-4482-3 ISBN 978-1-4471-4483-0 DOI 10.1007/978-1-4471-4483-0 Springer London Heidelberg New York Dordrecht (eBook) Library of Congress Control Number: 2013939842 © Springer-Verlag London 2014 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer Permissions for use may be obtained through RightsLink at the Copyright Clearance Center Violations are liable to prosecution under the respective Copyright Law The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied, with respect to the material contained herein Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword When I was asked to write a foreword for this remarkable cardiology board review book, I could not help but hark back to the time when I finished my cardiology training half a century ago Our knowledge base and our ability to treat patients with cardiovascular diseases were so limited then Our board exams consisted of a written part with only multiple choice questions and a clinical exam in which we worked up and—with considerable trepidation— presented patients to some of the most distinguished clinicians in American cardiology Computers and high tech were still years away The avalanche of amazing advances in the diagnosis and treatment of heart disease was just beginning Fast forward to today Current cardiology board examinations are administered using a computer terminal with complex multiple choice questions, often accompanied by high resolution images of not only electrocardiograms and x-rays that were the mainstays of diagnosis 50 years ago, but also dynamic images of coronary arteriograms, echocardiograms and other techniques currently used in the diagnosis of cardiovascular diseases Therapy has also become ever more complex—from pharmacology to interventions to medical devices to guidelines The increased emphasis on board examinations for initial certification coupled with the need for periodic recertification poses a big challenge for the test-taker, given the incredible breadth of knowledge that is now required to pass the board examinations Compounding the problem is the further subspecialization within the specialty of cardiovascular diseases itself Indeed, while in the course of a busy day, a cardiologist may encounter a broad range of important problems represented on the examination, there are many topics in cardiology which he or she may not frequently face As examples, the general cardiologist may not easily decipher the intracardiac electrograms that are second nature to the electrophysiologist Pediatric cardiologists adept in complex congenital heart disease (a topic that instills fear in the hearts of many board-takers) may not have much experience in the management of acute coronary syndromes Yet wherever one finds his or her niche in cardiology there is a level of knowledge encompassing the whole breath of cardiovascular diseases that one is expected to possess That is what the board examinations are all about Getting ready for the board examinations requires the diligent use of available board preparation resources It is in this context that I am so enthusiastic about the publication of the Massachusetts General Hospital (MGH) Cardiology Board Review Book by Drs Gaggin and Januzzi, Jr of our Division of Cardiology Representing contributions by a broad array of the best and brightest from our Division, this comprehensive review book has a concise, easy-to-read, visually appealing layout that will assist both those who are taking the boards initially as well as those seeking recertification after many years of practice The authors and editors are careful not to overwhelm the reader with irrelevant information so commonly found in board review books, some of which are as long as a standard cardiology textbook Indeed the contents of this book are designed to contain the most important, most pertinent and most often tested topics in each subject—essentially, what the authors and editors believe the reader needs to know in order to pass the board examinations Furthermore, the inclusion of a multi-media format—easily accessed from the publisher’s website—that displays video V VI F O R EWO R D loops of coronary arteriograms, ventriculograms and echocardiograms corresponding to still images in the textbook simulate the actual experience of taking the boards, and adds an extra dimension that is lacking from most board review books And importantly, the added value of multiple choice questions designed by people who recently sat for the exams further enhances the value of this book for board takers It gives me great pride to see the name of the MGH Cardiac Division on this book Since the Division was founded by Dr Paul Dudley White in 1917, the MGH has enjoyed a rich tradition of excellence in the practice and the teaching of clinical cardiology Dr White’s single-authored textbook—Heart Disease—first published in 1931 was the definitive reference text in cardiology for many years Subsequently the MGH Cardiac Division published a highly acclaimed textbook—The Practice of Cardiology Numerous members of the MGH Cardiac Division have either published or contributed to textbooks in cardiovascular diseases This Board Review Book edited by Drs Gaggin and Januzzi, Jr is an important new educational resource, and adds further luster to the long tradition of the MGH for excellence in clinical teaching Roman W DeSanctis, M.D James and Evelyn Jenks, Professor of Medicine, Harvard Medical School Physician and Director of Clinical Cardiology Emeritus, Massachusetts General Hospital, Boston, MA, USA Preface It has been quite a journey—from the inception of this book’s concept while a fellow at the University of Pittsburgh Medical Center years ago to working with the fearless authors at Mass General who took on this challenge, and now the submission of the completed book All I can think of are the people who made this possible Dr James Januzzi, Jr my super mentor and co-editor, and Dr G William Dec, for bringing me into Mass General and supporting my ambitious concept with all their resources All the authors of this book who worked tirelessly, sometimes edits after edits, to make it of quality and of substance It was my pleasure to have gotten to know them and their dedication to education through this book Drs Doug Drachman, Eric Isselbacher, Randy Zusman, Igor Palacios, Ik-Kyung Jang, Quynh Truong, Rory Weiner and Aaron Baggish for their advice and for being the first brave ones to sign up for the book I can’t thank enough Drs Barry London and Mike Mathier from UPMC who entrusted me with the Board Review Conference Dr John Gorcsan for opening my eyes to the art of research and presentation whose teachings on organization of material for learning I have used again and again Drs Fred Crock, Mark Schmidhofer, Prem Soman, Jenifer Lee, Bill Katz and the great late Jim Shaver for always being available Too numerous to name, all the fellows and faculty members at the University of Pittsburgh Medical Center who contributed to the Board Review Conference Everything I learned, I learned from Drs Robert Vorona and J Catesby Ware at the Eastern Virginia Medical School I always strive to emulate their work ethic, character and compassion On a personal note, I have to credit my mom, Hee Jung Kim, for making sure that I pursue what I love and for being the wisest, strongest woman I know My sisters, Han Holmberg and Dr Amy Pollak for always giving me the brutal truth My very special angels, Ruth and Jim Clark—their sense of curiosity, adventure and philanthropy are inspirational My best friends, Drs Ranjith Shetty and Mattie Campbell for making sure that I appreciate life outside of work But above all, I would like to thank my ultimate partner-in-crime and love, Robert T Gaggin I didn’t know such a wonderful, amazing person existed I will work hard to make you proud Boston, MA, USA Hanna K Gaggin, MD, MPH It is a marvelous thing to teach An effective teacher leaves an indelible mark on the student, and can result in a profound effect on a person’s career I remember exact lessons taught to me by my first mentor and physician/teacher—my father—even before I went to medical school, while some of the most powerful bedside physical diagnosis lessons taught to me by Dr Jack Chadbourne in medical school, Dr Eugene Braunwald in residency, or Drs Roman DeSanctis and Dolph Hutter during fellowship similarly remain with me years later These powerful forces inspired me to teach—something that remains a major focus for my career In parallel, I have also realized the importance of preparing for assessment exams such as the Cardiology Boards, thus it is in this context that I am so very proud to have worked with my VII VIII P R E FAC E colleague Dr Hanna Gaggin together with members from the MGH Division of Cardiology to write this important textbook I am grateful to all my colleagues that supported this effort—there is nothing more satisfying than coming to work every day surrounded by a group of peers that inspire me to work harder, learn more, and help patients on a daily basis I would also like to recognize my Chief of Cardiology, Dr G William Dec, who enthusiastically supported this textbook In addition, it goes without saying that I would like to thank my mentor, Dr Roman W DeSanctis, from whom I learned more clinical cardiology than most textbooks could ever teach Finally, to my daughters Caterina and Julianne, and especially my wife Roberta: thank you for endlessly supporting my dreams and my efforts—without you and your love and support, I would never be able to what I Boston, MA, USA James L Januzzi, Jr., MD, FACC, FESC How to Ace the Boards The cardiovascular board exam is expensive, often stressful and time-consuming A well thought out preparation is especially important as you want to pass it the first time you take it! This is also a great opportunity to consolidate your experience and knowledge, brush up on rare disorders, while familiarizing yourself with the latest clinical practice guidelines In this book, we have pooled the talents, expertise and teaching experience of the best and brightest at Mass General to help you all of the above This book is not meant to be all-inclusive—there are several excellent text books for that—but rather, it is meant to be a primer for the highlights of the cardiology topics (including board-style questions, electrocardiograms [ECG] and imaging studies) covered in the Cardiovascular Disease Board exam for the busy clinicians and fellows The inspiration for this book came from the board review course run by Dr Gaggin while at the University of Pittsburgh Medical Center and the feedback from the fellows and faculty members who recently took the exam Dr Januzzi, Jr is a frequent faculty member of board review courses and multiple clinical practice guideline committees, and has won many teaching awards for his role in the education of fellows and residents at Mass General Importantly, Dr Gaggin herself recently sat for the initial board exam in cardiology, while Dr Januzzi, Jr recently re-certified Here are our thoughts on how to ace the boards Basic exam information What’s new in 2012–2013 Exam tips The Plan when you have a year before your certification The Plan when you have a month before your certification When you are re-certifying—the basics The Plan for your maintenance of certification BASIC EXAMINATION INFORMATION ■ You MUST visit the official American Board of Internal Medicine (ABIM) website first and obtain exact dates and requirements as they often change: (http://www.abim.org), get information by specialty, Cardiovascular Disease ■ Key dates, initial certification – Register early—as soon as registration opens up (typically March 1)—in order to get your first choice in testing center ■ Registration deadline: typically May – The examination is at the end of October/early November after completing clinical cardiology fellowship – If you must cancel, make sure to it within the designated time (typically September 1) IX 256 G SAYE R AN D M.J S E M I G R AN RHC RRR RV RVEF SCD TPG TTE VO2 WU Right heart catheterization Relative risk reduction Right ventricular Right ventricular ejection fraction Sudden cardiac death Transpulmonary gradient Transthoracic echocardiogram Peak oxygen consumption Woods Units INTRODUCTION Chronic heart failure (HF) is a common manifestation of cardiovascular (CV) disease, affecting more than six million adults in the United States [1] Despite overall improvements in cardiovascular health, the incidence of HF has remained stable due to the aging of the population as well as improved survival following myocardial infarction (MI) Among patients over the age of 65, the incidence of HF is approximately % annually [1] Major advances have occurred in the understanding of HF pathophysiology and treatment, leading to significant declines in HF-related mortality [2] However, it remains a cause of significant morbidity and mortality, resulting in more than one million hospitalizations and 50,000 deaths annually [1] For more, see Chaps 14 and 17 DEFI NITION OF HF ■ Inability of heart to pump enough blood to meet metabolic needs of tissues ■ Can be caused by inability of ventricle to fill, inability to pump or systemic process causing excess metabolic demand ■ Symptoms: poor exercise tolerance (fatigue or dyspnea) ■ Signs: evidence of fluid retention or poor perfusion ■ American Heart Association (AHA) Classification – based on disease progression and therapeutic strategy [3] − Stage A – patients at high risk for development of HF without evidence of structural heart disease or symptoms of HF − Stage B – patients with structural heart disease but without symptoms or signs of HF − Stage C – patients with structural heart disease and current or prior symptoms of HF − Stage D – patients with refractory HF requiring advanced therapies ■ New York Heart Association (NYHA) classification – based on symptoms − − − − Class I – No limitation of ordinary physical activity Class II – mild symptoms with ordinary physical activity Class III – marked limitation of physical activity Class IV – symptoms of HF at rest or with minimal physical activity CAUSES OF CHRONIC HF ■ Ischemic cardiomyopathy – coronary artery disease (CAD) most common cause of left ventricular (LV) systolic dysfunction in developed countries − MI → regional scar and loss of contractility → adverse remodeling of remaining segments → LV dilatation and dysfunction − If hibernating myocardium present, revascularization may improve LV function ■ Nonischemic dilated cardiomyopathy (NIDCM) − Idiopathic – up to 50 % of NIDCM [4] − Toxins – HF potentially reversible with removal of offending agent C HAPTE R 15 • C H R O N I C AN D E N D- STAG E H EART FAI LU R E ■ Alcohol – direct toxic effect on cardiomyocytes ■ Cocaine – unclear pathophysiology, may include coronary vasospasm, direct myocardial toxicity ■ Medications (Anthracyclines, Trastuzumab, Cyclophosphamide) − Hypertension (HTN) ■ Initially causes concentric LV hypertrophy (LVH) but can eventually progress to dilated cardiomyopathy − Viral myocarditis ■ Myocardial injury caused by virus or autoimmune response to viral remnants ■ Initial infection may present acutely or may be silent − Other infectious causes ■ HIV – associated with high viral titers ■ Chagas Disease – prevalent in Central and South America ■ Lyme Disease – typically associated with conduction disturbances − Genetic ■ Familial dilated cardiomyopathy ■ LV non-compaction ■ Arrhythmogenic right ventricular cardiomyopathy − Tachycardia-induced cardiomyopathy ■ Can be due to atrial arrhythmias, ventricular arrhythmias (VAs) or premature ventricular contractions ■ Resolves with control of heart rate or elimination of arrhythmia − Peripartum Cardiomyopathy ■ Occurs in last month of pregnancy or within months of delivery ■ LV function usually improves but high rate of recurrent LV dysfunction with subsequent pregnancies − Hypothyroidism − Obstructive sleep apnea − Uremia ■ HF with preserved Ejection Fraction (HFpEF) − LV ejection fraction (LVEF) >50 % in approximately half of all HF patients [5] − Compared to patients with LV systolic dysfunction, HFpEF patients are more likely to be older, female, hypertensive, and have atrial fibrillation (AF) [6] − Similar survival to HF with reduced ejection fraction (HFrEF) – median survival of 2.1 years from diagnosis [5, 6] − Presence of diastolic dysfunction (by echo or invasive hemodynamics) required for diagnosis but pathophysiology complex − No treatments proven to prolong survival or decrease HF hospitalizations in HFpEF patients ■ Valvular heart disease − Any valvular lesion can cause HF symptoms in presence or absence of LV systolic dysfunction ■ Hypertrophic cardiomyopathy (HCM) − Inherited disorder associated with mutation of sarcomere genes − Present in 1/500 people with varying degrees of expression [7] − Results in marked ventricular hypertrophy, often asymmetric with predominant interventricular septal thickening ■ May also have mid-ventricular and apical hypertrophy variants − HF symptoms result from dynamic outflow tract obstruction, mitral regurgitation, diastolic dysfunction − First-line therapy are beta-blockers or calcium-channel blockers to reduce contractility and obstruction − Refractory symptoms may respond to surgical septal myectomy or alcohol septal ablation 257 258 G SAYE R AN D M.J S E M I G R AN ■ Restrictive cardiomyopathy − Idiopathic restrictive cardiomyopathy − Infiltrative diseases ■ Sarcoidosis – usually presents with arrhythmias or sudden death ■ Amyloidosis – senile, familial, or associated with abnormal light chain production (AL amyloidosis) − Initially normal LV systolic function, with subsequent deterioration of LVEF − Storage diseases ■ Fabry’s Disease − − − − X-linked genetic disorder Deficiency of a-galactosidase A → lysosomal storage disease Characterized by marked LVH – may be confused for HCM Can be treated with enzyme replacement ■ Hemochromatosis − Inherited genetic order or secondary to large volume of blood transfusions − Characterized by myocardial deposition of iron − Endomyocardial fibrosis ■ Diffuse fibrosis of ventricular endocardium of unclear etiology ■ Most common worldwide cause of restrictive cardiomyopathy ■ Mostly found in Africa, Asia and South America − Radiation Therapy ■ Damages blood vessels → inflammation → myocardial fibrosis → decreased ventricular compliance ■ Right ventricular (RV) failure − Almost always associated with pulmonary hypertension (PH) − Final consequence of many congenital heart lesions, particularly in context of Eisenmenger syndrome (irreversible PH) ■ Constrictive Pericarditis − May be caused by: ■ Prior cardiac surgery ■ Radiation ■ Infections (Tuberculosis, bacterial, parasitic) − Resolves with surgical pericardiectomy PATHOPHYSIOLOGY OF CHRONIC HF (FIG 15-1) ■ Acute injury to myocardium causes decreased cardiac output (CO) and end-organ perfusion ■ Neurohormonal activation − Upregulation of renin-angiotensin-aldosterone system ■ Increased angiotensin II → systemic and renal arterial vasoconstriction ■ Increased aldosterone → renal sodium retention − Sympathetic nervous system activation ■ Release of catecholamines (e.g norepinephrine) ■ Results in enhanced myocardial contractility and systemic vasoconstriction ■ Decreases distal water delivery in kidney due to reduction in glomerular filtration rate (GFR) → decreased excretion of water C HAPTE R 15 • C H R O N I C AN D E N D- STAG E H EART FAI LU R E 259 Myocardial injury ↓ Cardiac output Short-term adaptive processes Renal Na retention Renal H2O retention Vasoconstriction ↑ Contractility Angiotensin II Aldosterone Catecholamines ↑ RAAS ↑ Endothelin Myocardial toxicity ↑ SNS ↑ ADH Long-term maladaptive consequences ↑ Myocardial O2 demand ↑ Myocardial wall stress ↑ Myocardial stiffness Ventricular remodeling (–) Counterregulatory systems BNP/ANP NO/cGMP ? HF symptoms Morbidity and mortality FIGURE 15-1 A schematic representation of the pathophysiology of chronic heart failure due to impaired LV systolic function The initiating event is an injury that leads to myocardial dysfunction The body compensates for decreased cardiac output by activating multiple neurohormonal systems In the acute phase, these mechanisms act to maintain adequate perfusion of systemic organs, but may also result in congestion and HF symptoms Over time, these compensatory systems have adverse effects on the LV, stimulating further neurohormonal activation, worsening HF symptoms and ultimately leading to HF mortality Counter-regulatory systems, including the natriuretic peptides, are upregulated to prevent the adverse effects of neurohormonal activation Abbreviations: RAAS renin-angiotensin-aldosterone system, SNS sympathetic nervous system, ADH antidiuretic hormone, BNP B-type natriuretic peptide, ANP atrial natriuretic peptide, NO nitric oxide, cGMP cyclic guanosine monophosphate, HF heart failure − Release of anti-diuretic hormone ■ Enhances reabsorption of water by renal collecting tubules − Ventricular remodeling ■ Type of remodeling depends on type of stress placed on ventricle ■ Pressure overload (e.g aortic stenosis) − Concentric remodeling → LVH − Reduced wall stress via LaPlace’s Law (stress inversely proportional to wall thickness) ■ Volume overload (e.g mitral regurgitation) − Eccentric remodeling → ventricular dilatation − Increased preload maintains cardiac output via Frank-Starling mechanism 260 G SAYE R AN D M.J S E M I G R AN ■ Myocardial injury (e.g MI) − Stretching of scarred tissue → mixed pressure and volume load on non-infarcted tissue − Ventricular dilatation → maintenance of cardiac output ■ Acute compensatory responses become deleterious over time − Progressive ventricular dilatation → increased wall stress (LaPlace: stress proportional to chamber radius) − Ongoing ventricular remodeling causes progressive HF EVALUATION OF CHRONIC HF ■ Comprehensive history with focus on potential etiologies of cardiomyopathy − − − − Detailed alcohol, drug, toxin exposure Atherosclerotic risk factors, history of MI Systemic systems indicative of extracardiac disease Family history of HF, CAD or sudden cardiac death ■ Symptom assessment − − − − Dyspnea most common symptom NYHA Classification Congestion (orthopnea, paroxysmal nocturnal dyspnea) Low CO (fatigue, impaired cognition) ■ Physical Examination − Signs of congestion ■ Rales and/or pleural effusions on pulmonary exam – can be absent in long-standing HF despite elevated left-sided pressures ■ Elevated jugular venous pressure (JVP) ■ Positive hepatojugular reflex – sustained rise in JVP with compression of right upper quadrant of abdomen ■ Ascites ■ Lower extremity edema − Signs of low CO ■ ■ ■ ■ ■ Hypotension Sinus tachycardia Narrow pulse pressure Cool extremities Diminished pulses − Other findings ■ ■ ■ ■ ■ Displaced and enlarged point of maximal impulse Third heart sound (S3) RV heave Prominent pulmonic component of second heart sound (P2) Murmurs of functional mitral and tricuspid regurgitation ■ Diagnostic testing − Laboratory analyses ■ Basic metabolic panel, complete blood count, liver function tests, thyroid-stimulating hormone, urinalysis, hemoglobin A1C or fasting glucose ■ HIV test, iron studies (to screen for hemochromatosis) and sleep study should be considered in most patients ■ Further testing in selected patients depending on risk factors for specific etiologies of HF − ECG – arrhythmias, conduction disturbances, voltage (high or low), ectopy − Chest X-ray – cardiac chamber enlargement, pleural effusions, interstitial or pulmonary edema − Transthoracic echocardiogram (TTE) C HAPTE R 15 • C H R O N I C AN D E N D- STAG E H EART FAI LU R E ■ ■ ■ ■ ■ ■ LV and RV systolic function Presence of scar or wall motion abnormalities – suggestive of CAD Diastolic function of LV Quantification of chamber dilation and ventricular hypertrophy Identification of valvular abnormalities Presence of pericardial effusion − Assessment for obstructive CAD with coronary angiography or noninvasive imaging in patients with CAD risk factors − Cardiopulmonary exercise testing (CPET) – measurement of peak oxygen uptake (VO2) provides assessment of relative contributions of cardiac disease and pulmonary disease to dyspnea as well as prognostic information − Endomyocardial biopsy not helpful in most cases unless specific diagnosis suspected that would alter management − Signal-averaged electrocardiogram not recommended in routine assessment PROGNOSIS OF CHRONIC HF ■ Factors associated with worse prognosis in chronic HF include: − − − − − − LVEF – 39 % increase in mortality for each 10 % drop in LVEF [8] RV ejection fraction (RVEF) 120 ms [11] VO2 70 Cutoff for age is center-dependent Limited data on outcomes in older age group Malignancy Can be listed after malignancy successfully treated – length of time post-treatment depends on malignancy Obesity BMI >30 kg/m2 associated with worse outcomes [44] Fixed PH (PVR > WU or TPG > 15 mmHg) Can be listed if TPG or PVR can be lowered with medical therapy or mechanical therapy (IABP, LVAD) Diabetes Can be transplanted in absence of end-organ complications if diabetes can be controlled with diet and medication Smoking and substance abuse Most centers require >6 months abstinence prior to listing Abbreviations: PH pulmonary hypertension, PVR pulmonary vascular resistance, WU Woods Units, TPG transpulmonary gradient, BMI body mass index, IABP intra-aortic balloon pump, LVAD left ventricular assist device − Testing ■ Right heart catheterization (RHC) − Assessment of filling pressures and CO − Determine need for inotropic therapy or mechanical circulatory support (MCS) − Assess PH ■ Increased risk of death if PA systolic pressure >60 and PVR >5 Woods Units (WU) or transpulmonary gradient (TPG) >15 [43] ■ If transpulmonary gradient (TPG) > 15 or PVR > WU, evaluate response to systemic or selective pulmonary vasodilator ■ Patients with reversibility of PH may benefit from inpatient tailored therapy to lower filling pressures or from MCS (intra-aortic balloon pump or LVAD) to unload LV ■ Utility of type phosphodiesterase inhibitors as selective pulmonary vasodilators in patients with HFrEF and secondary PH is currently under investigation (PITCH HF study) ■ RHC should be repeated serially to assess for changes in hemodynamics and urgency of transplantation ■ CPET – can be used to assess functional status, prognosis and guide listing for transplant but should not be sole criteria used to assess patient eligibility − Reasonable to consider transplant if: ■ Peak VO2 < 14 ml/kg/min in absence of beta-blocker ■ Peak VO2 < 12 ml/kg/min in presence of beta-blocker ■ Peak VO2 < 50 % predicted peak VO2 C HAPTE R 15 • C H R O N I C AN D E N D- STAG E H EART FAI LU R E 267 − Complications of cardiac transplantation ■ Acute cellular rejection – T-cell mediated inflammatory infiltration of allograft − Managed with enhanced immunosuppression ■ Humoral rejection – Antibody-mediated graft dysfunction − Managed with enhanced immunosuppression − May require antibody-depleting therapies ■ Cardiac allograft vasculopathy − Progressive concentric intimal thickening of epicardial and subepicardial coronary arteries − Leads to chronic graft dysfunction and sudden cardiac death − May require repeat cardiac transplantation ■ Infections − Susceptible to opportunistic infections (pneumocystis, toxoplasmosis) − Increased rate of viral infections (e.g cytomegalovirus) ■ Malignancy − Post-transplant lymphoproliferative disorder ■ B-cell lymphoma induced by infection with Epstein-Barr Virus ■ Treated by reduction of immunosuppression and antiviral therapies ■ Drug Toxicities − Calcineurin Inhibitors (tacrolimus, cyclosporine) – renal dysfunction, tremor − Antimetabolites (mycophenolate mofetil, azathioprine) – bone marrow suppression − Corticosteroids – hyperglycemia, osteoporosis, HTN, weight gain REVIEW QUESTIONS A 65 year old woman with a history of a myocardial infarction and LV systolic dysfunction with an LVEF of 28 % comes to clinic for follow-up She has a mild limitation of her exercise capacity due to dyspnea She has been treated for HF for the past months and is currently taking lisinopril 20 mg daily, carvedilol 6.25 mg twice a day, furosemide 40 mg daily, warfarin and potassium chloride She continues to have dyspnea with moderate exertion She reports compliance with her medications and adherence to a low sodium diet An ICD was placed months ago, and she has not had any shocks Her blood pressure is 115/70 mmHg and heart rate is 90 bpm The examination is notable for an irregular rhythm, a mitral regurgitation murmur and bibasilar crackles Jugular venous pressure is mildly elevated and there is trace pitting edema in her lower extremities The electrocardiogram shows atrial fibrillation with a QRS width of 110 ms The serum sodium is 132 mmol/L, potassium 4.3 meq/L, BUN 45 mg/dL and creatinine 2.1 mg/dL Liver function tests are normal What is the best change to her current therapy to improve her long-term survival? (a) Add losartan 25 mg daily (b) Add spironolactone 25 mg daily (c) Increase carvedilol to 12.5 mg twice a day (d) Implant a cardiac resynchronization device (e) Add digoxin 125 mg daily Which of the following statements is true with regard to her atrial fibrillation? (a) Addition of digoxin would be useful to better control her ventricular response (b) Either amiodarone or sotalol would be a good choice for a rhythm control strategy (c) Sinus rhythm is preferable in patients with atrial fibrillation because it reduces mortality (d) Diltiazem is the best choice for an additional rate-control agent An 81 year old woman with a history of hypertension is seen due to shortness of breath while climbing stairs and inability to lie flat at night A recent echocardiogram shows normal LV size and function with an LVEF of 65 % She has mild mitral regurgitation, a dilated left atrium and her right ventricular systolic pressure is estimated at 48 mmHg She is currently taking hydrochlorothiazide 25 mg daily and amlodipine mg daily Her blood pressure is 160/95 mmHg and heart rate is 85 bpm On examination, her JVP is about 12 cm H2O and there is a positive hepatojugular reflex The heart rate is irregular with a prominent S4 There are bibasilar crackles and 2+ pitting lower extremity edema Electrocardiogram shows atrial fibrillation Which of the following statements is NOT true? 268 G SAYE R AN D M.J S E M I G R AN and heart rate is 98 bpm Examination shows a jugular venous pressure of 10 cm H20, clear lung fields, a regular rate with a third heart sound, and a tricuspid regurgitation murmur His abdomen is distended and he has cool extremities with 1+ lower extremity edema Right heart catheterization shows a pulmonary capillary wedge pressure of 25 mmHg, with a mean pulmonary arterial pressure of 40 mmHg The CO is 3.0 L/min His PVR is Woods Units, and there is no change with administration of sodium nitroprusside or inhaled nitric oxide At this time, all of the following are appropriate EXCEPT: (a) Palliative care consultation (b) Initiation of intravenous inotrope (c) Consideration of LVAD placement (d) Cardiac transplantation (a) Discontinuation of hydrochlorothiazide and initiation of furosemide is reasonable to relieve her congestion (b) Cardioversion to sinus rhythm should be considered to reduce her HF symptoms (c) Addition of lisinopril and titration to reduce her blood pressure into the normal range will provide long-term symptomatic benefit (d) A beta-blocker should be added to reduce the incidence of sudden cardiac death A 62 year old man with a chronic non-ischemic cardiomyopathy is admitted for a HF exacerbation This is his fourth admission in the last year He has dyspnea with minimal activity and is unable to leave his home His blood pressure is 95/40 mmHg ANSWERS (c) Beta-blockers and ACE-inhibitors have a Class I indication in the treatment of chronic HF due to LV systolic dysfunction These medications should be titrated to maximally tolerated levels to achieve their full benefit on symptoms and mortality The addition of an angiotensin-receptor blocker to therapy with an ACEinhibitor has been shown to reduce hospitalizations but not to improve survival This combinations should be used with caution when there is significant renal failure Spironolactone also has a Class I indication for treatment of HF in the presence of NYHA Class III-IV symptoms The patient in this scenario has NYHA Class II symptoms Furthermore, spironolactone should not be used in women with a serum creatinine >2.0 mg/dL A cardiac resynchronization device is only indicated in patients on optimal medical therapy who have a QRS width >120 ms Digoxin is approved for the treatment of symptoms in chronic HF but has no effect on mortality (a) Digoxin is a useful agent for the management of atrial fibrillation in patients with LV systolic dysfunction It works at the atrioventricular node to slow conduction and reduce the ventricular response to atrial fibrillation Digoxin has also been shown to reduce symptoms and hospitalizations in patients with chronic HF Amiodarone is also a useful agent for the management of atrial fibrillation in chronic HF; however sotalol is relatively contraindicated in patients with a low LVEF due to its negative inotropic properties No studies have demonstrated a mortality benefit to the maintenance of sinus rhythm in heart failure, although it may provide symptom relief Calcium-channel blockers should not be used in LV systolic dysfunction due to their negative inotropy (d) No medical therapies have been shown to produce a survival benefit in the management of HFpEF Goals of therapy include reduction of congestion and control of blood pressure Due to stiff ventricles, HFpEF patients tend to have more symptoms in atrial fibrillation and often benefit from maintenance of sinus rhythm (d) This patient has advanced HF (AHA Stage D) with low cardiac output and recurrent hospitalizations He should be considered for advanced therapies Cardiac transplantation would be a consideration if his PVR was lower However, a PVR > 4.0 Woods Units is an absolute contraindication to transplantation If an elevated PVR can be lowered with medications, these patients may be considered for transplant In this case, the patient did not respond to an attempt at vasodilator therapies during his right heart catheterization In some cases, PVR may come down following LVAD implantation It is not possible to know if that will be the case with this patient Palliative care, continuous inotropic infusions and LVADs are all potential options for the treatment of advanced HF REFERENCES Roger VL, Go AS, Lloyd Jones DM, Benjamin EJ, Berry JD, Borden WB, et al Heart disease and stroke statistic – 2012 update: a report from the American Heart Association Circulation 2012;125:e2–220 Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al Trends in heart failure incidence and survival in a community-based population JAMA 2004;292:344–50 Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult – summary article Circulation 2005;112:1825–52 Felker GM, Thompson RE, 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Januzzi, Jr Cardiology Division Department of Medicine Massachusetts General Hospital Boston Massachusetts USA ISBN 978 -1- 44 71- 4482-3 ISBN 978 -1- 44 71- 4483-0 DOI 10 .10 07/978 -1- 44 71- 4483-0 Springer.. .MGH Cardiology Board Review MGH Cardiology Board Review Editors Hanna K Gaggin Cardiology Division Department of Medicine Massachusetts General Hospital... diseases Pharmacology Heart failure Physiology/biochemistry Miscellaneous 13 .0 12 .5 12 .0 12 .0 5.0 4.0 9.0 7.0 5.0 13 .0 6.0 1. 5 H OW TO AC E TH E B OAR D S ■ Know where your weaknesses are, and expect