Medical Treatment Strategies for Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart disease inherited in an autosomal dominant pattern with an estimated prevalence of 0.6% in the general population. Clinical manifestations of HCM vary considerably, with symptoms ranging from none or mild exercise intolerance to severe lifestyle-limiting symptoms, advanced heart failure, and sudden cardiac death. Current management options for HCM include lifestyle modifications, familial screening with genetic counseling, pharmacotherapy for symptom control, sudden cardiac death risk stratification with or without defibrillator implantation, septal reduction therapy, and, in some cases, heart transplantation. Only recently have strongly targeted medical therapies for HCM, such as myosin inhibitors, been studied in multicenter randomized controlled trials. In this report, we review the currently available medical treatments for HCM and the future directions of HCM pharmacotherapy, and we highlight important unmet needs in this population. Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart disease inherited in an autosomal dominant pattern with an estimated prevalence of 0.6% in the general population. Clinical manifestations of HCM vary considerably, with symptoms ranging from none or mild exercise intolerance to severe lifestyle-limiting symptoms, advanced heart failure, and sudden cardiac death. Current management options for HCM include lifestyle modifications, familial screening with genetic counseling, pharmacotherapy for symptom control, sudden cardiac death risk stratification with or without defibrillator implantation, septal reduction therapy, and, in some cases, heart transplantation. Only recently have strongly targeted medical therapies for HCM, such as myosin inhibitors, been studied in multicenter randomized controlled trials. In this report, we review the currently available medical treatments for HCM and the future directions of HCM pharmacotherapy, and we highlight important unmet needs in this population. Hypertrophic cardiomyopathy (HCM) is a genetic heart disease inherited in an autosomal dominant pattern and is the leading cause of sudden cardiac death (SCD) in young athletes. Early epidemiologic studies reported a prevalence of 0.2%1Maron BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Coronary Artery Risk Development in (Young) Adults.Circulation. 1995; 92: 785-789Crossref PubMed Google Scholar in the general population, but it is now recognized that this is underestimated and that up to 0.6% of the population may carry HCM-causing sarcomere mutations.2Semsarian C Ingles J Maron MS Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy.J Am Coll Cardiol. 2015; 65: 1249-1254Crossref PubMed Scopus (805) Google Scholar Currently, variants in 1 of 8 genes that encode cardiac sarcomere proteins have been implicated in the development of HCM, but the 2 most common pathogenic gene variants are ꞵ myosin heavy chain 7 (MYH7) and myosin-binding protein C3.3Ho CY Day SM Ashley EA Michels M Pereira AC Jacoby D Cirino AL Fox JC Lakdawala NK Ware JS Caleshu CA Helms AS Colan SD Girolami F Cecchi F Seidman CE Sajeev G Signorovitch J Green EM Olivotto I. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the sarcomeric Human cardiomyopathy Registry (SHaRe).Circulation. 2018; 138: 1387-1398Crossref PubMed Scopus (409) Google Scholar HCM is characterized by left ventricular (LV) hypertrophy in the absence of other cardiac, systemic, or metabolic diseases capable of explaining the degree of LV hypertrophy. Clinical manifestations of HCM vary considerably, with symptoms ranging from none or mild exercise intolerance to severe lifestyle-limiting symptoms such as chest pain secondary to microvascular ischemia, syncope, or dyspnea on exertion secondary to LV outflow tract (LVOT) obstruction, atrial and/or ventricular arrhythmias, diastolic dysfunction, advanced heart failure, and SCD.4Hutt E Nissen SE Desai MY. Unmet needs in the treatment of hypertrophic cardiomyopathy.Future Cardiol. 2021; 17: 1261-1267Google Scholar Obstructive HCM (oHCM) is characterized by LVOT obstruction and is present in approximately 75% of patients with HCM.3Ho CY Day SM Ashley EA Michels M Pereira AC Jacoby D Cirino AL Fox JC Lakdawala NK Ware JS Caleshu CA Helms AS Colan SD Girolami F Cecchi F Seidman CE Sajeev G Signorovitch J Green EM Olivotto I. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the sarcomeric Human cardiomyopathy Registry (SHaRe).Circulation. 2018; 138: 1387-1398Crossref PubMed Scopus (409) Google Scholar LVOT obstruction is due to a combination of septal hypertrophy and abnormal blood flow kinetics causing systolic anterior motion of the mitral valve leaflets. This is often associated with anatomic abnormalities of the mitral valve such as long leaflets and abnormalities of the subvalvular apparatus such as presence of multiheaded, hypertrophied, and anteriorly displaced papillary muscles, all of which cause a narrow LVOT.5Patel P Dhillon A Popovic ZB Smedira NG Rizzo J Thamilarasan M Agler D Lytle BW Lever HM Desai MY. Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients without severe septal hypertrophy: implications of mitral valve and papillary muscle abnormalities assessed using cardiac magnetic resonance and echocardiography.Circ Cardiovasc Imaging. 2015; 8e003132Crossref Scopus (139) Google Scholar Patients with HCM without LVOT obstruction or non-oHCM (nHCM) comprise 1/3 of cases and pose a diagnostic and therapeutic challenge. Symptoms such as dyspnea and chest discomfort are common and are a result of increased LV filling pressures due to diastolic dysfunction, increased myocardial oxygen demand, and microvascular dysfunction.6Ommen SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76: e159-e240Crossref PubMed Scopus (320) Google Scholar Recent studies have recognized that patients with nHCM may have a larger scar burden and higher rates of microvascular ischemia than do those with oHCM, and that long-term mortality risk is not low as previously believed.7Lu DY Pozios I Haileselassie B Ventoulis I Liu H Sorensen LL Canepa M Phillip S Abraham MR Abraham TP. Clinical outcomes in patients with nonobstructive, labile, and obstructive hypertrophic cardiomyopathy.J Am Heart Assoc. 2018; 7e006657Crossref Scopus (41) Google Scholar,8Pelliccia F Pasceri V Limongelli G Autore C Basso C Corrado D Imazio M Rapezzi C Sinagra G Mercuro G Working Group on Cardiomyopathies and Pericardial Diseases of the Italian Society of CardiologyLong-term outcome of nonobstructive versus obstructive hypertrophic cardiomyopathy: a systematic review and meta-analysis.Int J Cardiol. 2017; 243: 379-384Abstract Full Text Full Text PDF PubMed Google Scholar Until recently, this patient population had no proved medical treatment options, and heart transplantation was the only definitive therapy, which in many cases is a challenge owing to unfavorable organ allocation for this condition. Current management options for HCM include lifestyle modification, familial screening with genetic counseling, pharmacotherapy for symptom control, SCD risk stratification with or without defibrillator implantation, septal reduction therapy (SRT), and, in some cases, heart transplantation.4Hutt E Nissen SE Desai MY. Unmet needs in the treatment of hypertrophic cardiomyopathy.Future Cardiol. 2021; 17: 1261-1267Google Scholar Until recently, pharmacotherapy in HCM was limited to β blockers, calcium channel blockers, and disopyramide and diuretics in refractory cases, but cardiac myosin inhibitors (CMIs) are rapidly becoming the preferred medical therapy in HCM, with mavacamten being the first-in-class Food and Drug Administration-approved agent to specifically target symptomatic oHCM. Medical management of HCM was first studied in 1967 by Dr. Eugene Braunwald, who described amelioration of angina pectoris and improvement in exercise tolerance in patients with “idiopathic hypertrophic subaortic stenosis” with the use of propranolol in a single-blind, placebo-controlled study.9Cohen LS Braunwald E. Amelioration of angina pectoris in idiopathic hypertrophic subaortic stenosis with beta-adrenergic blockade.Circulation. 1967; 35: 847-851Crossref PubMed Scopus (125) Google Scholar This study included 7 patients with angina and an established diagnosis of HCM, 5 of whom had and 2 with propranolol improvement in exercise tolerance in of 7 patients on the of treatment with the on by which β are to symptoms and LVOT in HCM is a combination of in heart and causing increased increased and myocardial oxygen all of which may systolic anterior motion and LVOT obstruction, LV In may and ventricular SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76: e159-e240Crossref PubMed Scopus (320) Google Scholar first described use of β in HCM, β have been studied in this patient population and have been the therapy for LVOT obstruction in patients with on the of clinical and clinical SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76: e159-e240Crossref PubMed Scopus (320) Google B of propranolol and in hypertrophic Heart 35: PubMed Google Scholar was not recently that the first randomized controlled β in HCM was of in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. 2021; PubMed Scopus Google left ventricular and exercise in obstructive hypertrophic cardiomyopathy.J Am Full Text Full Text PDF PubMed Scopus Google Scholar This was a randomized in patients with symptomatic the and clinical of of treatment LVOT than exercise LVOT and LVOT In New Heart Association of by the and LV treatment than with but exercise oxygen and not the study of in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. 2021; PubMed Scopus Google left ventricular and exercise in obstructive hypertrophic cardiomyopathy.J Am Full Text Full Text PDF PubMed Scopus Google Scholar This study not long-term of but it a on to LVOT reduction with β and low in this patient population. Dr. of use in HCM, Maron BJ a to the treatment of hypertrophic on exercise and symptomatic PubMed Google Scholar described the use of therapy for improvement in exercise and symptom in patients with HCM with and 2 with in a randomized study. This study exercise of patients on on and of and on and of improvement of exercise by on with and by on propranolol with without the of the 2 it of for symptom management in HCM, with This was by a study that a of and for exercise tolerance in patients with H H of and in the treatment of hypertrophic Heart PubMed Google Scholar to using β blockers, the of calcium channel is to symptoms by LV diastolic pressures and LV filling with a heart In of calcium have been in the myocardial of patients with HCM who or and have been associated with diastolic due to SE M in hypertrophic on PubMed Scopus Google Scholar calcium been to an important in the treatment of diastolic in this patient Hypertrophic obstructive of and treatment on left ventricular systolic and diastolic Heart PubMed Scopus Google Scholar This been to the with and but therapy not improvement in diastolic β and calcium channel have symptom in patients with HCM, the combination of not been studied but may have a in the management of and atrial E G V F B therapy in hypertrophic J Cardiol. Full Text Full Text PDF PubMed Google Scholar is a channel that is a In it is to owing to and it is of this with no that disopyramide in the LVOT of patients with A D A of of disopyramide for obstructive hypertrophic cardiomyopathy Am Heart Assoc. 2017; Scholar is limited by that include and and by with the risk for was first in in by subaortic and clinical improvement J PubMed Scopus Google Scholar who reported of disopyramide in and LVOT in the was in a multicenter of patients with symptomatic oHCM, amelioration of symptoms and a reduction in LVOT without This study that of patients without the for and that mortality was in patients with this not I Elliott S S Maron BJ. study of the and of disopyramide in obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. PubMed Scopus Google Scholar many of patients not on β or calcium therapy, disopyramide the pharmacotherapy in oHCM. use in patients with HCM may for atrial Current using disopyramide or β and/or calcium channel or have been or not in patients with this agent is a for patients with who have severe symptoms to LVOT obstruction and therapy, those who are not for or have no to an capable of SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76: e159-e240Crossref PubMed Scopus (320) Google Scholar disopyramide the it only in combination with β or to of atrial SR Mital S Burke MA Day SM Deswal A Elliott P Evanovich LL Hung J Joglar JA Kantor P Kimmelstiel C Kittleson M Link MS Maron MS Martinez MW Miyake CY Schaff HV Semsarian C Sorajja P. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76: e159-e240Crossref PubMed Scopus (320) Google Scholar all therapies described are 1 by the the of is is from or This the unmet that patients with HCM recently available is a that the of myosin to Jacoby D A A D J J M treatment for obstructive hypertrophic cardiomyopathy: A Clinical PubMed Scopus Google Scholar was first studied in a of and reduction in and in LVOT obstruction in an JA S Green EM A of sarcomere left ventricular outflow tract obstruction in hypertrophic Scholar a 1 clinical study in subjects and patients with HCM a which to the of in with Hypertrophic and Left a study in patients with Jacoby D A A D J J M treatment for obstructive hypertrophic cardiomyopathy: A Clinical PubMed Scopus Google Scholar This study that for LVOT obstruction and exercise and symptoms in patients with oHCM. the study to in with Obstructive Hypertrophic a placebo-controlled in patients with that mavacamten with an improvement in with improvement or by without of in of the mavacamten with in the to In secondary have an improvement in LVOT and in exercise and with JA Elliott P CY Olivotto I S C M Jacoby for treatment of symptomatic obstructive hypertrophic cardiomyopathy analysis of a 2021; Full Text Full Text PDF PubMed Scopus Google I A Abraham A P S Lakdawala NK A M J J SM SD D M JM A CY Jacoby D study for treatment of symptomatic obstructive hypertrophic cardiomyopathy a 2020; Full Text Full Text PDF PubMed Scopus Google Olivotto I Elliott S MS A JM V A A of mavacamten on of exercise oxygen a secondary analysis of the randomized Cardiol. Scholar long-term of this study is an study with patients from a of in LVOT of in LVOT and in of to reduction in LV was was a in with and the of patients in from to F S D Abraham A P D G G Olivotto I of mavacamten in patients with obstructive hypertrophic cardiomyopathy: of the Am Coll Cardiol. 2021; Scholar recently, to in Obstructive HCM for a in patients with medical therapy, combination therapy in the studied patients who for for mavacamten for In was a with to mavacamten and a up to only of patients in the mavacamten the of versus in the in LVOT to and reduction by in to A SS Smedira NG Schaff H E C JM Nissen in patients with obstructive hypertrophic cardiomyopathy for septal reduction Am Coll Cardiol. PubMed Scopus Google Scholar patients in the mavacamten no with in LVOT and S A SS Smedira Schaff HV E C A Nissen myosin in patients with obstructive HCM for septal reduction outcomes PubMed Scopus Google Scholar In and have a improvement in LV left atrial of diastolic and myocardial A S A M SS Schaff H Smedira NG Nissen SE Desai MY. and left ventricular diastolic in patients with obstructive hypertrophic cardiomyopathy for septal reduction insights from the Cardiovasc Imaging. Scopus Google S M J V M A A Lakdawala NK M A F B Jacoby cardiac in obstructive hypertrophic cardiomyopathy: cardiac magnetic resonance 2021; PubMed Scopus Google Scholar been to symptoms and long-term of patients with to an to that of the general SR Maron BJ Olivotto I Maron MS Cecchi F S BJ JA Schaff HV of septal on in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. PubMed Scopus Google A Smedira NG Popovic ZB Thamilarasan M P Lever HM Desai MY. in I versus for in hypertrophic obstructive cardiomyopathy.J Am Heart Assoc. 2021; Scopus Google A Smedira NG P Thamilarasan M Lytle BW Lever of long-term outcomes in symptomatic hypertrophic obstructive cardiomyopathy patients of left ventricular outflow tract PubMed Scopus Google Scholar only a are to and and A Smedira NG A S Thamilarasan M Popovic ZB B SR Desai MY. septal reduction in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. PubMed Scopus Google Scholar a for the management of such as mavacamten an important but the of is on use of are Society of of the of Patients in the study who had been with mavacamten for on patients who had been randomized to to the patients with symptomatic for the that of patients in the mavacamten and of patients in the the In the mavacamten 1 was and 1 was not In the and not of patients mavacamten long A S A M Lakdawala NK A D SS Smedira NG Schaff H E C Nissen SE in patients with hypertrophic cardiomyopathy for septal from the randomized clinical Cardiol. PubMed Scopus Google Scholar that for patients with symptomatic oHCM, is and improvement with the for and a therapeutic for mavacamten is the first therapy, other are clinical trials. This which the 2 and is to A Olivotto I. myosin inhibitors as a treatment for obstructive hypertrophic cardiomyopathy: the of the Am Heart Assoc. Scopus Google Scholar is a of cardiac myosin that by to cardiac myosin a MS A Olivotto I S A P Lakdawala NK F A C MA A SD H S A Abraham and 2 study of in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. PubMed Scopus Google Scholar 1 in that myocardial in a and was a that 2 a of of and of C S M J P J J J E of a cardiac myosin for the treatment of hypertrophic cardiomyopathy.J 2021; PubMed Scopus Google Scholar 2 that and LVOT with and a in MS A Olivotto I S A P Lakdawala NK F A C MA A SD H S A Abraham and 2 study of in patients with obstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. PubMed Scopus Google Scholar was improvement in of the of that in of the and was associated with improvement in of the most important with use is a reduction in to this been reported to with mavacamten in to of patients with I A Abraham A P S Lakdawala NK A M J J SM SD D M JM A CY Jacoby D study for treatment of symptomatic obstructive hypertrophic cardiomyopathy a 2020; Full Text Full Text PDF PubMed Scopus Google A SS Smedira NG Schaff H E C JM Nissen in patients with obstructive hypertrophic cardiomyopathy for septal reduction Am Coll Cardiol. PubMed Scopus Google S A SS Smedira Schaff HV E C A Nissen myosin in patients with obstructive HCM for septal reduction outcomes PubMed Scopus Google Scholar the a reduction in of to the of this mavacamten is only the Risk and to and of the Drug for on Scholar management of nHCM a therapeutic the limited of currently available the use of β and calcium channel a 1 in HCM this been on the described which not specifically patients without LVOT In patients with nHCM have symptom burden by diastolic dysfunction, and therapies are on and LV filling pressures with β blockers, and Jacoby D A A D J J M treatment for obstructive hypertrophic cardiomyopathy: A Clinical PubMed Scopus Google Scholar first of mavacamten in nHCM was of in Patients Hypertrophic (nHCM) and Left a placebo-controlled study. included with symptomatic nHCM and that treatment was associated with a reduction in and cardiac improvement in myocardial CY M JM SM Jacoby D Lakdawala NK A F S SD A of mavacamten in symptomatic patients with nonobstructive hypertrophic cardiomyopathy.J Am Coll Cardiol. 2020; PubMed Scopus Google Scholar In an mavacamten was and reduction in in patients with from studies of and in patients with symptomatic obstructive hypertrophic cardiomyopathy on Scholar A of mavacamten use in patients was reported Society of with now available to of the patients who was 5 and to of patients mavacamten treatment was associated with in from to in LVOT left atrial and of the patients had a LVOT of in from studies of and in patients with symptomatic obstructive hypertrophic cardiomyopathy on Scholar the clinical of this in nHCM is and to in of in the medical management of patients with HCM is the Society of cardiomyopathy management to the E A E Basso C E Elliott M P Ingles J S Limongelli G B J Olivotto I A S Ware JS for the management of Heart PubMed Scopus Google myosin to with of in to a β to symptoms in with or LVOT myosin to with of as in with symptomatic or LVOT obstruction who are or have to β blockers, or disopyramide the of the available mavacamten for patients with who have symptoms and LVOT obstruction of β or calcium channel to In in patients who have an for but to or or have no to an HCM to therapies in is to disopyramide from and a to of therapy, only for patients with or intolerance to the use of in are limited to include use in this patient population in but this in the 5 1 and 1 the of study and of the available medical treatment for patients with medical treatment for patients with HCM with study and of of angina and exercise tolerance to and LVOT obstruction and of to controlled randomized channel exercise to a with exercise tolerance to symptoms and LVOT by myosin 2 and exercise LVOT obstruction, and in to the of patients guideline for and in exercise LVOT controlled left ventricular outflow nHCM hypertrophic New Heart obstructive hypertrophic septal reduction in a LVOT left ventricular outflow nHCM hypertrophic New Heart obstructive hypertrophic septal reduction limited in the medical treatment of HCM and in the the a development with the of mavacamten to the is to the of the have on practice long-term on outcomes to the and on symptoms and of are of with may to medical management of HCM to which is and to in patients with oHCM, with low associated mortality and low risk low as but a risk of heart atrial and LVOT obstruction cardiac A Smedira NG P Thamilarasan M Lytle BW Lever of long-term outcomes in symptomatic hypertrophic obstructive cardiomyopathy patients of left ventricular outflow tract PubMed Scopus Google Scholar In future of medical management in patients with studies the of in patients with the of in ventricular and SCD not but of the development of may the of for defibrillator therapy, and ventricular studies to on is we as an to management of symptomatic patients with treatment for patients with diastolic MR mitral of randomized controlled is in patients with and to who are not on disopyramide or therapy with or calcium channel the of it is to a I a of diastolic MR mitral of randomized controlled is in patients with and to who are not on disopyramide or therapy with or calcium channel the of it is to a I a of important and in the management of HCM is the development of gene therapies that include gene and gene A A C F Liu JC M Ashley E of disease in 2020; PubMed Scopus Google D H M JM A S Liu Seidman Seidman in hypertrophic cardiomyopathy in PubMed Scopus Google Scholar In gene using and been studied in gene been in and in using with pathogenic myosin-binding protein or using with or to AC M F H A Liu of hypertrophic cardiomyopathy in and PubMed Scopus Google therapies for hypertrophic PubMed Scopus Google Scholar studies have of pathogenic in up to of ventricular with reduction in hypertrophy and but have been associated with to which pathogenic to of to the pathogenic This was to but the narrow therapeutic of D H M JM A S Liu Seidman Seidman in hypertrophic cardiomyopathy in PubMed Scopus Google Scholar therapies have been studied in and the to or cardiomyopathy not In the of or cardiac and the and of which may long-term are to therapies for hypertrophic PubMed Scopus Google Scholar are many and to to it is that unmet needs in the medical management of symptoms, for the management of atrial and ventricular in this population. is that therapies the of by and but studies are to in this population. Until recently, medical treatment of HCM was limited to β blockers, calcium channel blockers, and diuretics in cases, all of which have for symptom of and This the for therapies such as and heart transplantation. and heart transplantation in this patient population, are with to in to the limited of organ for for patients with symptomatic development of therapies studied in randomized controlled such as mavacamten and a for patients with HCM to of and long-term

Topics & Concepts