The Paradigm of Sudden Death Prevention in Hypertrophic Cardiomyopathy
2024; Elsevier BV; Volume: 212; Linguagem: Inglês
10.1016/j.amjcard.2023.10.076
ISSN1879-1913
AutoresMartin S. Maron, Ethan J. Rowin, Barry J. Maron,
Tópico(s)Viral Infections and Immunology Research
ResumoHypertrophic cardiomyopathy (HCM) is a relatively common and, often, inherited cardiac disease, once regarded as largely untreatable with ominous prognosis and, perhaps, most visibly as a common cause of sudden cardiac death (SCD) in the young. However, HCM is now more accurately considered a treatable disease with management options that significantly alter its clinical course. This is particularly true for SCD because the penetration of implantable cardioverter-defibrillators into HCM practice enables primary prevention device therapy that reliably terminates potentially lethal ventricular tachyarrhythmias (3% to 4%/year). This therapeutic advance is largely responsible for >10-fold decrease in the overall disease-related mortality to 0.5%/year, independent of patient age. A guideline-based clinical risk stratification algorithm has evolved, which included variables identifiable with cardiac magnetic resonance: ≥1 risk markers judged major within the clinical profile of an individual patient, associated with a measure of physician judgment and shared decision-making, can be sufficient to consider the recommendation of a prophylactic defibrillator implant. Implantable cardioverter-defibrillator decisions using the American College of Cardiology and the American Heart Association traditional major risk marker strategy are associated with a 95% sensitivity for identifying those patients who subsequently experience appropriate therapy, albeit often 5 to 10+ years after implant but without heart failure deterioration or death after a device intervention. A mathematical SCD risk score proposed by European Society of Cardiology is associated with a relatively low sensitivity (33%) for predicting and preventing SCD events but with potential for less device overtreatment. Hypertrophic cardiomyopathy (HCM) is a relatively common and, often, inherited cardiac disease, once regarded as largely untreatable with ominous prognosis and, perhaps, most visibly as a common cause of sudden cardiac death (SCD) in the young. However, HCM is now more accurately considered a treatable disease with management options that significantly alter its clinical course. This is particularly true for SCD because the penetration of implantable cardioverter-defibrillators into HCM practice enables primary prevention device therapy that reliably terminates potentially lethal ventricular tachyarrhythmias (3% to 4%/year). This therapeutic advance is largely responsible for >10-fold decrease in the overall disease-related mortality to 0.5%/year, independent of patient age. A guideline-based clinical risk stratification algorithm has evolved, which included variables identifiable with cardiac magnetic resonance: ≥1 risk markers judged major within the clinical profile of an individual patient, associated with a measure of physician judgment and shared decision-making, can be sufficient to consider the recommendation of a prophylactic defibrillator implant. Implantable cardioverter-defibrillator decisions using the American College of Cardiology and the American Heart Association traditional major risk marker strategy are associated with a 95% sensitivity for identifying those patients who subsequently experience appropriate therapy, albeit often 5 to 10+ years after implant but without heart failure deterioration or death after a device intervention. A mathematical SCD risk score proposed by European Society of Cardiology is associated with a relatively low sensitivity (33%) for predicting and preventing SCD events but with potential for less device overtreatment. Substantial progress has been made over the last several decades toward a mature risk stratification strategy with the potential to identify nearly all at-risk patients with hypertrophic cardiomyopathy (HCM). This advance, along with the introduction of implantable cardioverter-defibrillators (ICDs) to HCM some 20 years ago, has significantly altered the clinical course and landscape of this disease for many patients. Sudden cardiac death (SCD) prevention has reduced HCM mortality, making the preservation of life and the potential for normal or extended longevity a reality for most patients with this heterogeneous disease. In series published over decades, HCM has been 1 of the most common causes of SCD in young patients, many of whom are asymptomatic.1Maron BJ Clinical course and management of hypertrophic cardiomyopathy.N Engl J Med. 2018; 379: 655-668Crossref PubMed Scopus (460) Google Scholar, 2Aro AL Nair SG Reinier K Jayaraman R Stecker EC Uy-Evanado A Rusinaru C Jui J Chugh SS Population burden of sudden death associated with hypertrophic cardiomyopathy.Circulation. 2017; 136: 1665-1667Crossref PubMed Scopus (23) Google Scholar, 3Weissler-Snir A Allan K Cunningham K Connelly KA Lee DS Spears DA Rakowski H Dorian P Hypertrophic cardiomyopathy-related sudden cardiac death in young people in Ontario.Circulation. 2019; 140: 1706-1716Crossref PubMed Scopus (68) Google Scholar, 4Maron BJ Mackey-Bojack S Facile E Duncanson E Rowin EJ Maron MS Hypertrophic cardiomyopathy and sudden death initially identified at autopsy.Am J Cardiol. 2020; 127: 139-141Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 5Cannan CR Reeder GS Bailey KR Melton 3rd, LJ Gersh BJ Natural history of hypertrophic cardiomyopathy. A population-based study, 1976 through 1990.Circulation. 1995; 92: 2488-2495Crossref PubMed Google Scholar, 6Maron BJ Doerer JJ Haas TS Tierney DM Mueller FO Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, Analysis of 1866 deaths in the United States, 1980–2006.Circulation. 2009; 119: 1085-1092Crossref PubMed Scopus (1590) Google Scholar The annual SCD rate is now 60 years ago, at autopsy in 8 young people who died suddenly,22Teare D Asymmetrical hypertrophy of the heart in young adults.Br Heart J. 1958; 20: 1-8Crossref PubMed Google Scholar it came to be regarded as a common cause of nontraumatic SCD, particularly, in the young.9Maron BJ Rowin EJ Casey SA Maron MS How hypertrophic cardiomyopathy became a contemporary treatable genetic disease with low mortality: shaped by 50 years of clinical research and practice.JAMA Cardiol. 2016; 1: 98-105Crossref PubMed Scopus (178) Google Scholar Despite this visibility, HCM remains, to this day, a statistically low–event rate condition,2Aro AL Nair SG Reinier K Jayaraman R Stecker EC Uy-Evanado A Rusinaru C Jui J Chugh SS Population burden of sudden death associated with hypertrophic cardiomyopathy.Circulation. 2017; 136: 1665-1667Crossref PubMed Scopus (23) Google Scholar, 3Weissler-Snir A Allan K Cunningham K Connelly KA Lee DS Spears DA Rakowski H Dorian P Hypertrophic cardiomyopathy-related sudden cardiac death in young people in Ontario.Circulation. 2019; 140: 1706-1716Crossref PubMed Scopus (68) Google Scholar, 4Maron BJ Mackey-Bojack S Facile E Duncanson E Rowin EJ Maron MS Hypertrophic cardiomyopathy and sudden death initially identified at autopsy.Am J Cardiol. 2020; 127: 139-141Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 5Cannan CR Reeder GS Bailey KR Melton 3rd, LJ Gersh BJ Natural history of hypertrophic cardiomyopathy. A population-based study, 1976 through 1990.Circulation. 1995; 92: 2488-2495Crossref PubMed Google Scholar,13Maron BJ Rowin EJ Maron MS Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator.Heart Rhythm. 2021; 18: 1012-1023Abstract Full Text Full Text PDF PubMed Google Scholar in which SCDs are uncommon in both clinically undiagnosed patients2Aro AL Nair SG Reinier K Jayaraman R Stecker EC Uy-Evanado A Rusinaru C Jui J Chugh SS Population burden of sudden death associated with hypertrophic cardiomyopathy.Circulation. 2017; 136: 1665-1667Crossref PubMed Scopus (23) Google Scholar, 3Weissler-Snir A Allan K Cunningham K Connelly KA Lee DS Spears DA Rakowski H Dorian P Hypertrophic cardiomyopathy-related sudden cardiac death in young people in Ontario.Circulation. 2019; 140: 1706-1716Crossref PubMed Scopus (68) Google Scholar, 4Maron BJ Mackey-Bojack S Facile E Duncanson E Rowin EJ Maron MS Hypertrophic cardiomyopathy and sudden death initially identified at autopsy.Am J Cardiol. 2020; 127: 139-141Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 5Cannan CR Reeder GS Bailey KR Melton 3rd, LJ Gersh BJ Natural history of hypertrophic cardiomyopathy. A population-based study, 1976 through 1990.Circulation. 1995; 92: 2488-2495Crossref PubMed Google Scholar and in hospital-based cohorts.7Maron MS Rowin EJ Wessler BS Mooney PJ Fatima A Patel P Koethe BC Romashko M Link MS Maron BJ Enhanced American College of Cardiology/American Heart Association strategy for prevention of sudden cardiac death in high risk patients With Hypertrophic Cardiomyopathy.JAMA Cardiol. 2019; 4: 644-657Crossref PubMed Scopus (206) Google Scholar11Maron BJ Estes NAM Rowin EJ Maron MS Reynolds MR Development of the implantable cardioverter-defibrillator: JACC historical breakthroughs in perspective.J Am Coll Cardiol. 2023; 82: 353-373Crossref PubMed Google Scholar,23Rowin EJ Maron MS Chan RH Hausvater A Wang W Rastegar H Maron BJ Interaction of adverse disease related pathways in hypertrophic cardiomyopathy.Am J Cardiol. 2017; 120: 2256-2264Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar In cohort surveys, at-risk patients with HCM are characterized as young with no or only mild symptoms.11Maron BJ Estes NAM Rowin EJ Maron MS Reynolds MR Development of the implantable cardioverter-defibrillator: JACC historical breakthroughs in perspective.J Am Coll Cardiol. 2023; 82: 353-373Crossref PubMed Google Scholar13Maron BJ Rowin EJ Maron MS Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator.Heart Rhythm. 2021; 18: 1012-1023Abstract Full Text Full Text PDF PubMed Google Scholar This profile is supported by the recognition that HCM is a frequent cause of SCD in young competitive athletes.6Maron BJ Doerer JJ Haas TS Tierney DM Mueller FO Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, Analysis of 1866 deaths in the United States, 1980–2006.Circulation. 2009; 119: 1085-1092Crossref PubMed Scopus (1590) Google Scholar Studies in patients with ICDs, however, demonstrate that lethal arrhythmic events are most commonly terminated by appropriate device therapy in midlife, with the average age in the mid-40s.9Maron BJ Rowin EJ Casey SA Maron MS How hypertrophic cardiomyopathy became a contemporary treatable genetic disease with low mortality: shaped by 50 years of clinical research and practice.JAMA Cardiol. 2016; 1: 98-105Crossref PubMed Scopus (178) Google Scholar,13Maron BJ Rowin EJ Maron MS Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator.Heart Rhythm. 2021; 18: 1012-1023Abstract Full Text Full Text PDF PubMed Google Scholar,23Rowin EJ Maron MS Chan RH Hausvater A Wang W Rastegar H Maron BJ Interaction of adverse disease related pathways in hypertrophic cardiomyopathy.Am J Cardiol. 2017; 120: 2256-2264Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar,24Maron BJ Rowin EJ Casey SA Haas TS Chan RH Udelson JE Garberich RF Lesser JR Appelbaum E Manning WJ Maron MS Risk stratification and outcome of patients with hypertrophic cardiomyopathy >= 60 years of age.Circulation. 2013; 127: 585-593Crossref PubMed Scopus (183) Google Scholar The events are infrequent in patients aged 60 years and older.24Maron BJ Rowin EJ Casey SA Haas TS Chan RH Udelson JE Garberich RF Lesser JR Appelbaum E Manning WJ Maron MS Risk stratification and outcome of patients with hypertrophic cardiomyopathy >= 60 years of age.Circulation. 2013; 127: 585-593Crossref PubMed Scopus (183) Google Scholar,25Maron BJ Rowin EJ Casey SA Garberich RF Maron MS What do patients with hypertrophic cardiomyopathy die from?.Am J Cardiol. 2016; 117: 434-435Abstract Full Text Full Text PDF PubMed Google Scholar The SCD risk does not appear to differ according to gender or race.26Rowin EJ Maron MS Wells S Patel PP Koethe BC Maron BJ Impact of sex on clinical course and survival in the contemporary treatment era for hypertrophic cardiomyopathy.J Am Heart Assoc. 2019; 8e012041Crossref PubMed Scopus (54) Google Scholar,27Wells S Rowin EJ Bhatt V Maron MS Maron BJ Association between race and clinical profile of patients referred for hypertrophic cardiomyopathy.Circulation. 2018; 137: 1973-1975Crossref PubMed Scopus (29) Google Scholar Although identifying patients with HCM at the highest risk for SCD is now possible, predicting the precise timing of these isolated events has proved daunting. For example, there is no demonstrable circadian periodicity for ICD interventions,28Maron BJ Semsarian C Shen WK Link MS Epstein AE Estes 3rd, NA Almquist A Giudici MC Haas TS Hodges JS Spirito P Circadian patterns in the occurrence of malignant ventricular tachyarrhythmias triggering defibrillator interventions in patients with hypertrophic cardiomyopathy.Heart Rhythm. 2009; 6: 599-602Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar and substantial time delays frequently elapse between the recognition of high-risk status and the first ventricular tachycardia (VT)/ventricular fibrillation (VF) episode. A total of 1/3 of patients do not experience a shockable arrhythmia for 10 or more years after ICD implant,10Rowin EJ Burrows A Madias C Estes 3rd, NAM Link MS Maron MS Maron BJ Long-term outcome in high-risk patients with hypertrophic cardiomyopathy after primary prevention defibrillator implants.Circ Arrhythm Electrophysiol. 2020; 13e008123Crossref PubMed Scopus (17) Google Scholar and some patients are known to have survived for extended periods after cardiac arrest (up to >30 years), without subsequent arrhythmic events. The often-unpredictable arrhythmic substrate in HCM is morphologically diverse, with disorganized architecture and characteristically bizarre arrangement of myocytes, microvascular abnormalities, and interstitial/replacement fibrosis13Maron BJ Rowin EJ Maron MS Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator.Heart Rhythm. 2021; 18: 1012-1023Abstract Full Text Full Text PDF PubMed Google Scholar,29Maron BJ Rowin EJ Maron MS Paradigm of sudden death prevention in hypertrophic cardiomyopathy.Circ Res. 2019; 125: 370-378Crossref PubMed Scopus (46) Google Scholar (Figure 1). Mechanisms leading to ventricular arrhythmogenicity are likely multifactorial but importantly include re-entry circuits29Maron BJ Rowin EJ Maron MS Paradigm of sudden death prevention in hypertrophic cardiomyopathy.Circ Res. 2019; 125: 370-378Crossref PubMed Scopus (46) Google Scholar in close proximity to myocardial fibrosis/scar that can be identified by cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE).30Chan RH Maron BJ Olivotto I Pencina MJ Assenza GE Haas T Lesser JR Gruner C Crean AM Rakowski H Udelson JE Rowin E Lombardi M Cecchi F Tomberli B Spirito P Formisano F Biagini E Rapezzi C De Cecco CN Autore C Cook EF Hong SN Gibson CM Manning WJ Appelbaum E Maron MS Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.Circulation. 2014; 130: 484-495Crossref PubMed Scopus (719) Google Scholar, 31Weissler-Snir A Hindieh W Spears DA Adler A Rakowski H Chan RH The relationship between the quantitative extent of late gadolinium enhancement and burden of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy: A delayed contrast-enhanced magnetic resonance study.J Cardiovasc Electrophysiol. 2019; 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A family history of SCD based on the recognition of individual pedigrees with the clustering of malignant events, was later added. Ultimately, distinctive findings on CMR and other markers were added to the algorithm.13Maron BJ Rowin EJ Maron MS Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator.Heart Rhythm. 2021; 18: 1012-1023Abstract Full Text Full Text PDF PubMed Google Scholar,30Chan RH Maron BJ Olivotto I Pencina MJ Assenza GE Haas T Lesser JR Gruner C Crean AM Rakowski H Udelson JE Rowin E Lombardi M Cecchi F Tomberli B Spirito P Formisano F Biagini E Rapezzi C De Cecco CN Autore C Cook EF Hong SN Gibson CM Manning WJ Appelbaum E
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