Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCxrhyR6McsFKRMqZn75dVKjcS0066-782X201800060053210.5935/abc.20180101Short EditorialPrevention of Sudden Death in Hypertrophic CardiomyopathyArteaga-FernándezEdmundoAntunesMurillo de OliveiraUniversidade de São PauloFaculdade de MedicinaInstituto do Coração do Hospital das ClínicasSão PauloSPBrazilInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (INCOR HC FMUSP), São Paulo, SP - BrazilMailing address: Edmundo Arteaga-Fernández. Rua Arruda Alvim, 49/111. Postal Code 05410-020, São Paulo, SP - Brazil. E-mail: Edmundo.arteaga@incor.usp.br0620181106532533This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.KeywordsCardiomyopathy, HypertrophicDeath, Sudden, Cardiac / prevention & controlHeart Defects, Congenital
Hypertrophic cardiomyopathy (HCM) is the most common congenital disease, and sudden death (SD), its most feared complication, was already mentioned by Donald Teare1 in the first description of the disease, being observed in 7 out of 8 patients. SD occurs during daily activities, after exercises and even during sleep; it may affect young athletes, which has a great impact on the media. This has required considerable effort by researchers in defining clinical factors and complementary tests that could be used in the screening of individuals at higher risk that could benefit from implantable cardioverter defibrillator (ICD) and also to prevent SD, since it is caused by tachycardia and ventricular fibrillation.2 HCM favors the occurrence of ventricular arrythmias - hypertrophy causes repolarization dispersion; myocyte disarray and increased fibrosis create areas of conduction block and predispose to reentry arrhythmias; and abnormalities in ion fluxes, such as calcium, during repolarization may also trigger arrhythmias. In addition, this complex arrhythmogenic substrate may be modulated by impaired autonomic response, myocardial ischemia and left ventricular outflow tract obstruction.2-4 If we consider deaths from cardiovascular causes, in patients with HCM, they account for 0.5%-1.5% deaths a year, which is near to that of the general population.2 In HCM patients considered as high risk, SD may reach 2.5% of deaths a year.5 However, the accurate identification of these patients for preventive therapy with ICD may be challenging.
Before the guidelines were published,3 it was known that manifestations of HCM in children younger than 10 years old with diastolic or systolic dysfunction, SD in first-degree relatives younger than 50 years, nonsustained ventricular tachycardia, syncope and myocardial hypertrophy > 30 mm were factors associated with SD, and the last four fully considered as indications for ICD in the first guideline (2011).2
Today, we know that the positive predictive value of each of these factors is low, and there is little evidence suggesting a higher predictive value of any of these factors. However, some authors have considered only one risk factor for indication of ICD.6
The two largest multicentric studies grounded in the American guidelines2 - one of adults (n = 506, mean age of 42; mean follow-up period of 3.7 years) showed that for primary prevention ICD indication, in 75% of cases, the devices were used in 4%/year, whereas for the secondary prevention, intervention rates were 12%/year in 25% of cases. Therapies were found in 20% of patients and inappropriate shocks in 27%, with 7% of complications.7 The other study involved 224 children and adolescents (mean age of 14 years; mean follow-up of 4.3 years). Primary prevention was indicated in 84% of cases and secondary prevention indicated for 16% of cases. Intervention rates were similar to those in adults, with therapies and inappropriate shocks in 19% and 41% of cases, respectively.8
The 2014 European Guidelines (ESC) recommended a new sudden-death risk model based on a longitudinal, retrospective, multicenter study risk calculation model (n = 3,675) and seven variables - age, history of SD, syncope, wall thickness, left atrial diameter, left ventricular outflow gradient and nonsustained ventricular tachycardia. In primary prevention, the risk calculation encompasses three SD risk levels at five years - low, moderate and high - for patients older than 16 years.3,9 This risk prediction model, validated in Europe10 (n = 706) and in South America11 (n = 502), was shown to better predict individual risks as compared with that used in North America and Canada societies. However, a study12 using the ESC risk calculation model (n = 1,629, age > 16 years) showed that most patients with HCM or with previous ICD were classified as low risk and therefore would remain unprotected from SD. The authors concluded that the primary risk stratification using this model is unreliable for prediction of future SD events.13
In this issue of Arquivos Brasileiros de Cardiologia, in a cohort study (n = 105), Reis et al.14 compared the American and the European guidelines in stratifying SD risk, and concluded that the European model reduces the proportion of patients with indication for ICD.
We can affirm that, despite continuous advances in knowledge,10,15 the assessment of SD risk in HCM is limited to a small number of patients (5%) and is still a great challenge. The guidelines have so far included increasing number of risk factors15 with low predictive value, and validated for a frequent, but still underdiagnosed disease, characterized by patients with a normal life cycle and free from SD.
Short Editorial regarding the article: Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: What has Changed in The Guidelines?
Acknowledgements
We thank the colleagues Adriana Paula Tirone, Afonso Akio Shiozaki, Afonso Yoshikiro Matsumoto, Aloir Queiroz de Araujo, Julia Daher Carneiro Marsiglia, Paula de Cássia Buck and Paulo de Tarso Jorge Medeiros, for their contribution to the study of hypertrophic cardiomyopathy.
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Circulation. 2011;124(24):2761-796.GershBJMaronBJBonowRODearaniJAFiferMALinkMSAmerican College of Cardiology Foundation/American Heart Association Task Force on Practice GuidelinesAmerican Association for Thoracic SurgeryAmerican Society of EchocardiographyAmerican Society of Nuclear CardiologyHeart Failure Society of AmericaHeart Rhythm SocietySociety for Cardiovascular Angiography and InterventionsSociety of Thoracic Surgeons2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice GuidelinesCirculation201112424276127963 Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733-79.ElliottPMAnastasakisABorgerMABorggrefeMCecchiFCharronP2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC)Eur Heart J20143539273327794 Arteaga E, Ianni BM, Fernandes F, Mady C. Benign outcome in a long-term follow-up of patients with hypertrophic cardiomyopathy in Brazil. Am Heart J. 2005;149(6):1099-105.ArteagaEIanniBMFernandesFMadyCBenign outcome in a long-term follow-up of patients with hypertrophic cardiomyopathy in BrazilAm Heart J20051496109911055 Maron BJ, Casey SA, Poliac LC, Gohman TE, Almquist AK, Aeppli DM. Clinical course of hypertrophic cardiomyopathy in regional United States cohort. JAMA. 1999;281(7):650-5. Erratum in: JAMA. 1999;281(24):2288.MaronBJCaseySAPoliacLCGohmanTEAlmquistAKAeppliDMClinical course of hypertrophic cardiomyopathy in regional United States cohortErratum in JAMA. 1999;281(24):2288JAMA199928176506556 Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014;64(1):83-99. Erratum in: J Am Coll Cardiol. 2014;64(11):1188.MaronBJOmmenSRSemsarianCSpiritoPOlivottoIMaronMSHypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicineErratum in J Am Coll Cardiol. 2014;64(11):1188J Am Coll Cardiol201464183997 Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA. 2007;298(4):405-12. Erratum in: JAMA. 2007;298(13):1516.MaronBJSpiritoPShenWKHaasTSFormisanoFLinkMSImplantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathyErratum in JAMA. 2007;298(13):1516JAMA200729844054128 Maron BJ, Spirito P, Ackerman MJ, Casey SA, Semsarian C, Estes NA 3rd, et al. Prevention of sudden cardiac death with the implantable cardioverter-defibrillators in children and adolescent with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;61(14):1527-35.MaronBJSpiritoPAckermanMJCaseySASemsarianCEstesNA3rdPrevention of sudden cardiac death with the implantable cardioverter-defibrillators in children and adolescent with hypertrophic cardiomyopathyJ Am Coll Cardiol20136114152715359 O'Mahony C, Jichi F, Pavlou M, Monserrat L, Anastasakis A, Rapezzi C, et al; Hypertrophic Cardiomyopathy Outcomes Investigators. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD). Eur Heart J. 2014;35(30):2010-20.O'MahonyCJichiFPavlouMMonserratLAnastasakisARapezziCHypertrophic Cardiomyopathy Outcomes InvestigatorsA novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD)Eur Heart J201435302010202010 Vriesendorp PA, Schinkel AF, Liebregts M, Theuns DA, van Cleemput J, Ten Cate FJ, et al. Validation of the 2014 European Society of Cardiology Guidelines risk prediction mode for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrhythm Eletrophysiol. 2015;8(4):829-35.VriesendorpPASchinkelAFLiebregtsMTheunsDAvan CleemputJTen CateFJValidation of the 2014 European Society of Cardiology Guidelines risk prediction mode for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathyCirc Arrhythm Eletrophysiol20158482983511 Fernandez A, Quiroga A, Ochoa JP, Mysuta M, Casabé JH, Biagetti M, et al. Validation of the 2014 European Society of Cardiology sudden cardiac death risk prediction model in hypertrophic cardiomyopathy in a reference center in south America. Am J Cardiol. 2016;118(1):121-6.FernandezAQuirogaAOchoaJPMysutaMCasabéJHBiagettiMValidation of the 2014 European Society of Cardiology sudden cardiac death risk prediction model in hypertrophic cardiomyopathy in a reference center in south AmericaAm J Cardiol2016118112112612 Maron BJ, Casey SA, Chan RH, Garberich RF, Rowin EJ, Maron MS. Independent assessment of the European Society of Cardiology sudden death risk model for hypertrophic cardiomyopathy. Am J Cardiol. 2015;116(5):757-64.MaronBJCaseySAChanRHGarberichRFRowinEJMaronMSIndependent assessment of the European Society of Cardiology sudden death risk model for hypertrophic cardiomyopathyAm J Cardiol2015116575776413 Maron BJ, Maron BS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm. 2016;13(5):1155-65.MaronBJMaronBSContemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathyHeart Rhythm20161351155116514 Reis L, Teixeira R, Fernandes A, et al. Prevenção de morte súbita cardíaca em doentes com miocardiopatia hipertrófica: o que mudou nas guidelines? Arq Bras Cardiol. 2018; 110(6):524-531.ReisLTeixeiraRFernandesAPrevenção de morte súbita cardíaca em doentes com miocardiopatia hipertrófica: o que mudou nas guidelines?Arq Bras Cardiol2018110652453115 de Oliveira Antunes M, Samesima N, Pereira Filho HG, Matsumoto AY, Verrier RL, et al. Exercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathy. J Electrocardiol. 2017;50(2):184-90.de Oliveira AntunesMSamesimaNPereiraHGFilhoMatsumotoAYVerrierRLExercise-induced quantitative microvolt T-wave alternans in hypertrophic cardiomyopathyJ Electrocardiol2017502184190MinieditorialPrevenção da Morte Súbita na Cardiomiopatia HipertróficaArteaga-FernándezEdmundoAntunesMurillo de OliveiraInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (INCOR HC FMUSP), São Paulo, SP - BrasilCorrespondência: Edmundo Arteaga-Fernández. Rua Arruda Alvim, 49/111. CEP 05410-020, São Paulo, SP - Brasil. E-mail: Edmundo.arteaga@incor.usp.brPalavras-chaveCardiomiopatia HipertróficaMorte Súbita Cardíaca / prevenção & controleCardiopatias Congênitas
A cardiomiopatia hipertrófica (CH) é a doença cardíaca congênita mais frequente, e a morte inesperada (MI) sua complicação mais temida, foi destacada na descrição inicial da doença feita por Donald Teare,1 na qual relatava a ocorrência desse evento em 7 de 8 pacientes. MI ocorre durante as atividades cotidianas, ou após atividades físicas e mesmo durante sono, podendo se manifestar em jovens atletas, causando grande impacto na mídia. Isso tem requerido empenho dos pesquisadores na procura de fatores clínicos e de exames complementares que auxiliem na identificação daqueles de maior risco para indicação do cardiodesfibrilador implantável (CDI) e prevenção dessa fatalidade, uma vez que a causa é a taquicardia ou fibrilação ventricular.2 Na CH, há substrato que favorece o aparecimento de arritmias ventriculares. A hipertrofia causa dispersão da repolarização; o desarranjo dos miócitos e o aumento da fibrose criam áreas de bloqueio de condução que predispõem às arritmias por reentrada; e as do fluxo de íons como o cálcio durante a repolarização podem desencadear arritmias. Ainda, esse complexo substrato arritmogênico pode ser modulado por distúrbios de resposta autonômica, isquemia miocárdica e obstrução da via de saída do VE. Porém, não podemos esquecer que disfunção diastólica, sistólica e eventos tromboembólicos também são causas de morte.2-4 Se falarmos de morte de origem cardiovascular, em pacientes com CH ocorre em 0,5% a 1,5%/ano, próxima à mortalidade da população geral.2 Em pacientes com CH considerados de alto risco, a MI pode chegar a 2,5%.5 Entretanto, a questão é identificar com grande poder de acerto quais são esses pacientes para, assim, indicar o tratamento preventivo com o CDI.
Antes das publicações das diretrizes3 já sabíamos que a manifestação da CH em crianças < 10 anos com disfunção diastólica ou sistólica, MI em parentes de 1º grau e idade < 50 anos, taquicardia ventricular não sustentada, síncope e hipertrofia do miocárdio > 30 mm eram fatores de MI, sendo que os 4 últimos foram considerados universalmente na indicação de CDI na primeira Diretriz de 2011 (EUA).2
Hoje sabemos que o valor preditivo positivo de cada fator de risco é baixo e poucas evidências sugerem maior poder preditivo de algum deles. Porém, há autores que consideram apenas um fator de risco para a indicação do CDI.6
Os dois maiores estudos multicêntricos com base na diretriz americana2 - um com adultos (n=506, idade média = 42 anos, seguimento médio = 3,7 anos) mostrou que na indicação da prevenção primária, 75% casos utilizaram os aparelhos em 4%/ano e na secundária, 25% casos em 12%/ano. As terapias foram observadas em 20% e os choques inapropriados em 27%, com 7% de complicações .7 No estudo com 224 crianças e adolescentes (média = 14 anos e seguimento médio = 4,3 anos) houve indicação de prevenção primária em 84% casos e secundária em 16% casos e a proporção de utilização por ano foi semelhante à dos adultos, com terapias em 19% e choques inapropriados em 41%.8
A diretriz europeia de 2014 (ESC) recomendou um novo modelo de cálculo de risco de MI baseado em estudo longitudinal, retrospectivo e multicêntrico (n = 3675), utilizando sete variáveis: idade, história familiar de MI, síncope, espessura da parede, diâmetro do átrio esquerdo, gradiente de via de saída do ventrículo esquerdo e presença de taquicardia ventricular não sustentada. Na prevenção primária, o cálculo de risco contempla uma pontuação com três níveis de risco de MI (baixo, médio e elevado) em cinco anos para pacientes > 16 anos.3,9 Este cálculo, validado por estudos realizados na Europa10 (n = 706) e America do Sul11 (n = 502) mostrou-se superior na avaliação do risco individual quando comparado ao utilizado pelas sociedades da América do Norte e Canadá. Entretanto, outro estudo12 aplicando o cálculo de risco da ESC (n = 1629, idade > 16 anos) mostrou que a maioria dos pacientes com MI ou que tiveram terapias do CDI, eram classificados como de baixo risco e, assim, estariam desprotegidos de MI. Concluíram que a estratificação de risco primário por este modelo não é confiável como preditor de futuros eventos de MI.13
Reis et al.,14 publica nesta edição estudo de coorte (n = 105) comparando a estratificação de risco de MI entre as diretrizes americana e europeia concluindo que o modelo de risco europeu diminui a proporção de pacientes com indicação de CDI.
Podemos afirmar que a avaliação do risco de MI na CH está restrita a um pequeno subgrupo de pacientes (5%) e continua sendo um grande desafio, apesar dos avanços constantes no conhecimento.10,15 As diretrizes foram baseadas em fatores de risco cada vez mais numerosos,15 com baixo valor preditivo e validados por fórmulas matemáticas para uma doença frequente, porém pouco diagnosticada em que a maioria dos pacientes tem seu ciclo vital normal e livre da MI.
Minieditorial referente ao artigo: Prevenção de Morte Súbita Cardíaca em Doentes com Miocardiopatia Hipertrófica: O Que Mudou nas Guidelines?
Agradecimentos
Aos colegas Adriana Paula Tirone, Afonso Akio Shiozaki, Afonso Yoshikiro Matsumoto, Aloir Queiroz de Araujo, Julia Daher Carneiro Marsiglia, Paula de Cássia Buck e Paulo de Tarso Jorge Medeiros, pela colaboração no estudo da cardiomiopatia hipertrófica.