abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC São Paulo, SP, Brazil TQB9f8vNycsvdKcsmbv7kMJ S0066-782X2013000500009 S0066-782X(13)10000500009 10.5935/abc.20130078 Artigos Originais Arritmias ventriculares e hipertrofia ventricular esquerda na cardiomiopatia hipertrófica Mattos Beatriz Piva e Torres Marco Antonio Rodrigues Freitas Valéria Centeno de Scolari Fernando Luís Loreto Melina Silva de Rio Grande do Sul Universidade Federal do Rio Grande do Sul Serviço de Cardiologia Brazil Porto Alegre Rio Grande do Sul Universidade Federal do Rio Grande do Sul Faculdade de Medicina Brazil 05 2013 100 5 452 459 26 06 2012 19 11 2012 31 10 2012 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

FUNDAMENTO: Na Cardiomiopatia Hipertrófica (CMH), o grau de Hipertrofia Ventricular Esquerda (HVE) poderia influenciar o desenvolvimento de arritmias ventriculares. OBJETIVO: Analisar, na CMH, a associação entre a ocorrência de arritmias ventriculares no eletrocardiograma-Holter (ECG-Holter) e o grau de HVE determinado ao ecocardiograma pela espessura parietal máxima (EPM) e Índice de Massa (IM). MÉTODOS: Cinquenta e quatro pacientes consecutivos com CMH realizaram ECG-Holter de 24 horas e ecocardiograma para avaliação do grau de HVE através da EPM e IM. Foram estabelecidos dois níveis para a ocorrência de arritmias ventriculares: I - extrassístoles isoladas ou pareadas e II - Taquicardia Ventricular Não Sustentada (TVNS). RESULTADOS: Nos 13 pacientes (24%) com TVNS (nível II), houve maior frequência de EPM do ventrículo esquerdo (VE) > 21 mm (n = 10, 77%; 25 ± 4 mm) e IMVE > 144 g/m² (n = 10, 77%; 200 ± 30 g/m²), em relação àqueles que apresentavam apenas arritmia extrassistólica (nível I) (n = 41, 76%), em que essas medidas foram identificadas em, respectivamente, 37% (n = 15, 23 ± 1 mm), p = 0,023, e 39% (n = 16, 192 ± 53 g/m²) dos casos, p = 0,026. Os citados valores de corte foram determinados por curva ROC com intervalo de confiança de 95%. O registro de TVNS foi mais comum em pacientes com EPMVE > 21 mm e IMVE > 144 g/m² (8 de 13; 62%), do que naqueles com uma (4 de 13; 31%) ou nenhuma (1 de 13; 8%) variável ecocardiográfica acima dos valores de corte, p = 0,04. CONCLUSÃO: A ocorrência de arritmias ventriculares no Holter associou-se, na CMH, ao grau de HVE, avaliado pelo ecocardiograma através da respectiva EPM e IM.

 Arritmias Cardíacas Hipertrofia Ventricular Esquerda Cardiomiopatia Hipertrófica 12 04 2013

Arritmias ventriculares e hipertrofia ventricular esquerda na cardiomiopatia hipertrófica

Beatriz Piva e MattosI,II; Marco Antonio Rodrigues TorresI,II; Valéria Centeno de FreitasI, Fernando Luís ScolariII, Melina Silva de LoretoII

IServiço de Cardiologia do Hospital de Clínicas de Porto Alegre

IIFaculdade de Medicina - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil

Correspondência

RESUMO

FUNDAMENTO: Na Cardiomiopatia Hipertrófica (CMH), o grau de Hipertrofia Ventricular Esquerda (HVE) poderia influenciar o desenvolvimento de arritmias ventriculares.

OBJETIVO: Analisar, na CMH, a associação entre a ocorrência de arritmias ventriculares no eletrocardiograma-Holter (ECG-Holter) e o grau de HVE determinado ao ecocardiograma pela espessura parietal máxima (EPM) e Índice de Massa (IM).

MÉTODOS: Cinquenta e quatro pacientes consecutivos com CMH realizaram ECG-Holter de 24 horas e ecocardiograma para avaliação do grau de HVE através da EPM e IM. Foram estabelecidos dois níveis para a ocorrência de arritmias ventriculares: I - extrassístoles isoladas ou pareadas e II - Taquicardia Ventricular Não Sustentada (TVNS).

RESULTADOS: Nos 13 pacientes (24%) com TVNS (nível II), houve maior frequência de EPM do ventrículo esquerdo (VE) > 21 mm (n = 10, 77%; 25 ± 4 mm) e IMVE > 144 g/m2 (n = 10, 77%; 200 ± 30 g/m2), em relação àqueles que apresentavam apenas arritmia extrassistólica (nível I) (n = 41, 76%), em que essas medidas foram identificadas em, respectivamente, 37% (n = 15, 23 ± 1 mm), p = 0,023, e 39% (n = 16, 192 ± 53 g/m2) dos casos, p = 0,026. Os citados valores de corte foram determinados por curva ROC com intervalo de confiança de 95%. O registro de TVNS foi mais comum em pacientes com EPMVE > 21 mm e IMVE > 144 g/m2 (8 de 13; 62%), do que naqueles com uma (4 de 13; 31%) ou nenhuma (1 de 13; 8%) variável ecocardiográfica acima dos valores de corte, p = 0,04.

CONCLUSÃO: A ocorrência de arritmias ventriculares no Holter associou-se, na CMH, ao grau de HVE, avaliado pelo ecocardiograma através da respectiva EPM e IM.

Palavras-chave: Arritmias Cardíacas, Hipertrofia Ventricular Esquerda, Cardiomiopatia Hipertrófica.

Introdução

A Cardiomiopatia Hipertrófica (CMH) é uma doença genética complexa cujo diagnóstico fundamenta-se na identificação de Hipertrofia Ventricular Esquerda (HVE) evidenciada na ausência de dilatação da câmara e de qualquer outra condição capaz de causar anomalia em grau semelhante1. Em jovens com menos de 25 anos e atletas, é causa principal de morte súbita, produzida por fibrilação ventricular precedida ou não por taquicardia ventricular2-4. O padrão histopatológico característico representado por hipertrofia e desorganização celular, aliadas a fibrose, predispõe ao surgimento de arritmias ventriculares, as quais expressam a condução eletrofisiológica anômala e a instabilidade elétrica do miocárdio5-7.

O registro de taquicardia ventricular não sustentada no eletrocardiograma-Holter (ECG-Holter) e HVE maciça com espessura parietal máxima > 30 mm são considerados preditores de morte súbita nessa doença4,8-11. Estudos baseados em necropsia ou em corações explantados com CMH identificam relação direta entre o grau de fibrose e a espessura parietal máxima do ventrículo esquerdo (VE)12,13. Áreas de fibrose, detectadas na forma de realce tardio por meio de ressonância magnética com gadolíneo, relacionam-se ao registro de arritmias ventriculares e, provavelmente, a morte súbita14-19. Todavia, não foi ainda claramente demonstrado se o aumento das espessuras parietais do VE favorece a ocorrência de arritmias ventriculares14,20-22. O objetivo deste estudo é analisar a associação entre o grau de HVE, determinado ao ecocardiograma, e a ocorrência de arritmias ventriculares registradas no ECG-Holter de 24 horas numa coorte ambulatorial não referenciada com CMH.

Métodos

Seleção de pacientes

Foram estudados 54 pacientes consecutivos de uma coorte não referenciada registrada no Ambulatório de CMH do Serviço de Cardiologia do Hospital de Clínicas de Porto Alegre, UFRGS, entre março de 2007 e dezembro de 2011. O diagnóstico de CMH foi estabelecido com base no quadro clínico e na identificação por meio do ecocardiograma de HVE assimétrica com espessura parietal máxima > 15 mm em qualquer segmento e razão septo/parede posterior > 1,3, na ausência de dilatação da câmara e de outra causa. Foram considerados critérios de exclusão: hipertrofia concêntrica do VE, outras formas de cardiomiopatia, doença arterial coronariana, valvopatias e cardiopatias congênitas. Os pacientes foram submetidos preliminarmente a avaliação clínica e eletrocardiográfica, seguida de ecocardiograma em repouso e ECG-Holter de 24 horas, realizados de forma contemporânea. O ecocardiograma foi registrado por um único examinador. Os resultados do ECG-Holter foram avaliados sem o conhecimento prévio do diagnóstico. Foi valorizada a utilização ou não de medicação cardioativa. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa local. Todos os pacientes assinaram termo de consentimento livre e esclarecido.

Ecocardiograma

O ecocardiograma transtorácico uni e bidimensional com Doppler pulsado e contínuo a cores foi realizado em repouso para avaliação da estrutura e função das câmaras cardíacas, incluindo a análise espectral dos fluxos de acordo com recomendações atuais23. As avaliações foram realizadas com equipamento Vivid 7, General Eletric (GE Healthcare, Milwaukee, WI, USA). As imagens foram obtidas nos cortes paraesternal longitudinal, paraesternal transversal e apical de duas, três, quatro e cinco câmaras, com transdutores multifrequenciais de 2,5 a 3,5 mHz, posicionados de forma padronizada com o paciente em decúbito lateral esquerdo. Foram valorizadas as seguintes medidas: diâmetro do átrio esquerdo, diâmetro diastólico final do VE, diâmetro sistólico final do VE, espessura diastólica final do septo interventricular, espessura diastólica final da parede posterior do VE, massa do VE indexada para área de superfície corporal e fração de ejeção. A espessura parietal máxima foi considerada como aquela correspondente ao segmento do VE que exibia maior grau de espessamento. O grau de HVE foi avaliado mediante a respectiva espessura parietal máxima e índice de massa. O gradiente máximo no trato-de-saída do VE foi medido em repouso e sob manobra de Valsalva em corte apical de cinco câmaras com Doppler contínuo dirigido paralelamente à via-de-saída dessa câmara, de acordo com a equação de Bernoulli modificada. A presença de obstrução foi definida como impedância mecânica ao fluxo na via-de-saída do VE, resultante do contato ou aproximação da válvula mitral com o septo interventricular na mesossístole. O registro de gradiente sistólico máximo > 30 mmHg em repouso foi considerado compatível com formas obstrutivas. Obstrução latente foi definida por gradiente < 30 mmHg em repouso, e > 30 mmHg com manobra de Valsalva. Formas não obstrutivas corresponderam àquelas com gradiente em repouso e sob Valsalva < 30 mmHg.

Eletrocardiograma-Holter

O ECG-Holter ambulatorial de 24 horas constou do registro de três derivações, DII, V1 e V5 modificadas, com analisador GE Mars 8000 e gravador GE Seer Light (GE Medical Systems, Milwaukee, WI, USA). Extrassístoles ventriculares pareadas foram caracterizadas como correspondentes a duas extrassístoles consecutivas e taquicardia ventricular não sustentada pela presença de três ou mais extrassístoles consecutivas com frequência cardíaca > 100 batimentos/minuto. Nos pacientes com mais de um ECG-Holter, contemporâneo ao ecocardiograma, foi selecionado aquele com maior frequência de arritmias ventriculares. Foram estabelecidos dois níveis para arritmias ventriculares: I - extrassístoles isoladas ou pareadas, e II - taquicardia ventricular não sustentada.

Análise Estatística

Os dados quantitativos foram descritos pela média e desvio padrão ou por meio de medianas (Md) e intervalos interquartílicos (percentis 25 e 75). As variáveis categóricas foram expressas por frequência absoluta e relativa. As diferenças entre dois grupos, com base na comparação de variáveis contínuas com distribuição simétrica e assimétrica foram analisadas, respectivamente, pelo teste t de Student para amostras independentes e teste de Mann-Whitney. As variáveis categóricas foram comparadas pelo teste qui-quadrado para heterogeneidade e qui-quadrado para tendência linear. A partir da curva ROC, com Intervalo de Confiança (IC) de 95%, foram determinados os valores de corte das medidas ecocardiográficas referentes à espessura parietal máxima do VE e índice de massa do VE, capazes de discriminar os pacientes com maior e menor frequência de arritmias ventriculares. Os dados foram processados no software SPSS versão 18.0 (SPSS Inc., Chicago, Illinois,USA). O nível de significância adotado foi de p < 0,05.

Resultados

Características dos pacientes

A média de idade foi de 54 ± 13 anos, sendo 48 (89%) > 40 anos e 33 (61%) do sexo feminino. Houve predomínio de casos com leve ou moderado comprometimento da capacidade funcional (Classe Funcional New York Heart Association - CFNYHA I/II, n = 40; 74%) em relação àqueles com grave limitação (CFNYHA III/IV, n = 14; 26%). Todos os pacientes estavam sob uso de medicação: 41 (76%) betabloqueadores, 17 (31%) bloqueadores dos canais de cálcio, verapamil ou diltiazem, e 5 (9%) amiodarona (Tabela 1).

Eletrocardiograma-Holter

Arritmias ventriculares no ECG-Holter foram identificadas em todos os casos. Extrassístoles ventriculares isoladas manifestaram-se em 46 (85%) pacientes, com variação de 1 a 1461, média 130 ± 277. Vinte (37%) exibiam extrassístoles ventriculares pareadas em número de 1 a 15 e 12 (22%) e 13 (24%) taquicardia ventricular não sustentada, com 1 a 7 salvas, de 3 a 24 batimentos. Os pacientes com taquicardia ventricular não sustentada apresentaram em relação aos sem essa arritmia (n = 41, 76%) maior número de extrassístoles ventriculares isoladas (Md 131, p25 = 6,25 e p75 = 316 versus Md 9, p25 = 1 e p75 = 91, p = 0,027) e pareadas (Md 2, p25 = 0, p75 = 5 versus Md 0 p25 = 0, p75 = 1, p = 0,013). Os dados demográficos e clínicos não diferiram entre os pacientes com nível I e II de arritmias ventriculares (Tabala 1).

Ecocardiograma

A média da espessura parietal máxima do VE observada foi de 20 ± 4 mm com variação de 15 a 34 mm. Houve predomínio de hipertrofia leve ou moderada do VE: 26 (48%) apresentavam medidas entre 15 e 19 mm, 21 (39%) entre 20 e 24 mm, 6 (11%) entre 25 e 29 mm e apenas 1 (2%) > 30 mm. O índice de massa do VE evidenciou variação de 97 a 248 g / m2, média de 158 ± 18 g/m2. Formas obstrutivas incidiram em 21 (39%) pacientes, obstrutivas latentes em 6 (11%) e não obstrutivas em 27 (50%) (Tabela 2).

Arritmias ventriculares e hipertrofia ventricular esquerda

A espessura parietal máxima do VE foi significativamente mais elevada nos pacientes com taquicardia ventricular não sustentada (nível II) em relação àqueles que evidenciavam apenas arritmia extrassistólica (nível I) (23 ± 5 mm versus 19 ± 4 mm; p = 0,001). O índice de massa do VE foi significativamente maior no nível II (182 ± 45 g/m2versus 151 ± 48 g/m2; p = 0,049). As demais variáveis ecocardiográficas não diferiram entre os grupos (Tabela 2).

Através de curva ROC com IC de 95%, foi demonstrado que espessura parietal máxima do VE > 21 mm e índice de massa do VE > 144 g/m2 representaram os valores de corte capazes de identificar pacientes com maior prevalência de taquicardia ventricular não sustentada no ECG-Holter. Nos 13 pacientes (24%) com taquicardia ventricular não sustentada, houve maior frequência de espessura parietal máxima do ventrículo esquerdo > 21 mm (n = 10, 77%; 25 ± 4 mm) e índice de massa do VE > 144 g/m2 (n = 10, 77%; 200 ± 30 g/m2), em relação aqueles que exibiam apenas arritmia extrassistólica (n = 41, 77%), em que essas medidas foram identificadas em respectivamente 37% (n = 15, 23 ± 1 mm), p = 0,023, e 39% (n = 16, 192 ± 53 g/m2) dos casos, p = 0,026 (Figura 1).

O registro de taquicardia ventricular não sustentada foi mais comum em pacientes com espessura parietal máxima do VE > 21 mm e índice de massa do VE > 144 g / m2 (8 de 13; 62%), do que naqueles com uma (4 de 13; 31%) ou nenhuma (1 de 13; 8%) variável ecocardiográfica acima dos valores de corte, p = 0,04. A prevalência de taquicardia ventricular não sustentada no ECG-Holter elevou-se de forma direta e progressiva com o número de descritores ecocardiográficos de HVE considerados para análise (qui-quadrado para tendência linear p = 0,04) (Figura 2). A curva ROC evidenciou que espessura parietal máxima do VE > 21 mm apresentou sensibilidade de 77% e especificidade de 64%, com valor preditivo positivo e negativo de respectivamente 40% e 90%, para detecção de taquicardia ventricular não sustentada no ECG-Holter (área sob a curva ROC 0,767; IC95% 0,614 - 0,920). Índice de massa do VE > 144 g/m2 evidenciou sensibilidade de 77% e especificidade de 61%, com valor preditivo positivo de 39% e negativo de 89% (área sob a curva ROC 0,713; IC95% 0,530 - 0,900) (Figura 3).

Discussão

Este estudo demonstrou que a HVE, quanto mais acentuada, mais favorece a arritmogênese na CMH. A ocorrência de taquicardia ventricular não sustentada associou-se a maior grau de comprometimento do VE, quando avaliado pela espessura parietal máxima e índice de massa. O registro de taquicardia ventricular não sustentada mostrou-se mais frequente em situações em que ambos os descritores ecocardiográficos de HVE se apresentavam mais elevados. O caráter assimétrico da hipertrofia e sua distribuição heterogênea tornam menos fidedigna a aferição do índice de massa do VE por meio do ecocardiograma na CMH24. Ainda que frequentemente elevado, exibe fraca correlação com a espessura parietal máxima do VE, quando da avaliação por meio de ressonância magnética25. Todavia, na presente análise, evidenciou-se que o registro de taquicardia ventricular não sustentada, além de associar-se a maior índice de massa, foi mais frequente nos casos em que tanto este como a espessura parietal máxima encontravam-se elevados.

As arritmias ventriculares constituem manifestação característica da CMH, uma doença que, pelo seu componente arritmogênico, é considerada de evolução imprevisível, com taxas anuais de morte súbita estimadas em 1%26. Estudos fundamentados na análise do ECG-Holter de 24-48h em populações baseadas na comunidade20 e em centros de referência27-29 identificaram extrassístoles ventriculares em 80%-95% dos casos, em número variável de 1 a 5.000. Batimentos extrassistólicos ventriculares pareados foram registrados em 30%-40% dos traçados e taquicardia ventricular não sustentada em 20%-30%, em salvas breves e pouco frequentes de 3 a 26 batimentos. No presente estudo, extrassístoles ventriculares pareadas foram evidenciadas em 37% dos pacientes e taquicardia ventricular não sustentada em 24%, com salvas de 3 a 24 batimentos. Em relação a estudos prévios, observou-se prevalência semelhante de arritmias ventriculares, embora o menor grau de seleção da amostra e o predomínio de pacientes em faixa etária > 40 anos com leve ou moderado grau de HVE.

O registro de taquicardia ventricular não sustentada no ECG-Holter elevaria a suscetibilidade à morte súbita, ainda que com reduzido valor preditivo positivo27-30. As arritmias ventriculares na CMH são originadas por reentrada e emergem de um substrato eletrofisiológico caracterizado por vias de condução lenta e ativação ventricular retardada4,7. Em eletrogramas, o registro de potenciais de pequena amplitude e inscrição tardia, denominados fracionamentos, refletiriam a ativação ventricular anômala e predisporiam à morte súbita7. A maior parte dos episódios de taquicardia ventricular aqui observados eram monomórficos, precedidos por extrassístoles e seriam possivelmente abolidos por paceamento antitaquicardia31.

A hipótese de o grau de HVE influenciar a arritmogênese na CMH é considerada10,11, embora sem a devida comprovação. Investigação inicial demonstrou relação entre a extensão da HVE e o registro de taquicardia ventricular no ECG-Holter32. Os estudos subsequentes que avaliaram a relação entre a espessura parietal máxima do VE e a ocorrência de taquicardia ventricular não sustentada evidenciaram resultados discordantes14,20,21, incluindo aqueles gerados numa mesma instituição, com algum grau presumível de superposição de amostras14,20. Em uma dessas análises, foi demonstrado que o registro de taquicardia ventricular não sustentada incidia de forma proporcional ao grau de HVE, acometendo 50% daqueles com espessura parietal máxima > 30 mm20. Conclusões divergentes poderiam ser atribuídas ao grau de seleção da amostra, à metodologia utilizada e ao caráter heterogêneo da doença. Ao contrário do nosso estudo, em nenhum dos mencionados foram incluídos batimentos extrassistólicos isolados ou pareados. No entanto, predomínio de extrassístoles ventriculares multifocais ou pareadas e de taquicardia ventricular não sustentada foi descrito previamente em pacientes com HVE extensa, septal ou de parede livre anterolateral, em relação a casos com acometimento restrito ao septo22. Em modelos com mutações humanas da CMH, foi demonstrada associação do grau de hipertrofia e arritmias ventriculares induzidas33. Em mutação do gene da α-tropomiosina, arritmias ventriculares foram induzidas em um terço dos casos e evidenciaram correlação com a espessura parietal máxima do VE e o número de fatores de risco para morte súbita34.

Pacientes com espessura parietal máxima do VE > 30 mm, particularmente jovens e idosos, apresentam maior mortalidade cardiovascular e risco de morte súbita10,11,35. A HVE, ao aumentar o estresse parietal e o consumo de oxigênio, condicionaria à isquemia miocárdica, importante estímulo para o desenvolvimento de arritmias1. O papel da hipertrofia miocárdica na arritmogênese da CMH poderia ser questionado, ante a descrição de morte súbita em carreadores de mutações do gene da troponina T com espessuras parietais do VE normais ou levemente aumentadas6. Fibrilação ventricular é igualmente relatada nas mutações da cadeia pesada da β-miosina cardíaca com HVE ausente ou de expressão tardia36.

A arquitetura anômala do miocárdio, representada por desorganização celular e fibrose, interfere com a condução do estímulo, produz bloqueio unidirecional e favorece o mecanismo de reentrada4,7,11. Fibrose reparativa desenvolve-se, provavelmente, induzida por isquemia miocárdica silenciosa e morte celular consequentes à hipertrofia do miócito e a doença da microcirculação12,15. Estado pré-fibrótico indicativo do aumento da síntese de colágeno antecederia o desenvolvimento de HVE na CMH37. A deposição de colágeno na forma de fibrose reparativa é identificada em faixa etária precoce e tende a expandir-se com o avançar da idade5. Em portadores de CMH acometidos por morte súbita, com doença causada por outros genes que não o da troponina T, a presença de extensas áreas de fibrose evidencia potencial relação entre o substrato histopatológico e o desenvolvimento de arritmias ventriculares fatais6. Mais recentemente, a análise de biopsias endomiocárdicas de CMH demonstrou que a elevação da fração de volume de colágeno se associava a maior mortalidade38.

O aumento da massa miocárdica e das espessuras parietais do VE na CMH não é somente determinado pela hipertrofia do miócito, mas decorre em grande parte da expansão da matriz extracelular, na forma de fibrose reparativa12,15. Estudos com ressonância magnética com gadolíneo demonstraram correlação da fibrose detectada por realce tardio com a espessura do septo interventricular, determinada tanto por esse método quanto pelo ecocardiograma16,39, o mesmo não sucedendo em relação à massa global do VE39. O realce tardio identifica a presença de fibrose intramiocárdica, de caráter reparativo em 40% a 80% dos casos de CMH, ocupando de 0,4% a 65% do miocárdio ventricular16-18. Em análise multivariada18 e em meta-análise recente19, a fibrose detectada por ressonância magnética mostrou-se preditor independente de mortalidade, mas para que essa seja considerada marcador de prognóstico e morte súbita, é necessária comprovação adicional1. A associação de fibrose identificada por ressonância magnética14-17 ou tomografia computadorizada com múltiplos detectores40 e taquiarritmias ventriculares, de caráter fatal ou não, sugere a existência de um elo fisiopatológico entre arritmogênese e fibrose na CMH. Tal fato justificaria a constatada associação entre a maior frequência de arritmias ventriculares e o espessamento parietal do VE, do qual a fibrose é um dos fatores determinantes. Entretanto, não está esclarecido se o aumento das espessuras parietais do VE dependente de fibrose reflete as consequências de um processo de isquemia miocárdica crônica influenciado pela hipertrofia celular e doença da microcirculação ou resulta da ativação de fatores genéticos ainda não bem conhecidos.

A aqui demonstrada associação entre a ocorrência de arritmias ventriculares e o grau de HVE contribuiria para individualização de fatores que predispõem a arritmogênese na CMH. O presente estudo evidenciou que espessura parietal máxima do VE > 21 mm e índice de massa > 144 g/m2 constituíram características capazes de conferir maior instabilidade elétrica ao miocárdio em portadores dessa doença.

Limitações do estudo

A possibilidade de nossos resultados refletirem em algum grau as características próprias da amostra não pode ser afastada. A inclusão predominante de indivíduos em faixa etária mais avançada com menor grau de seleção, provavelmente de menor risco, poderia limitar as conclusões a populações com esse perfil. No entanto, admite-se que a população estudada possa ser também representativa da doença, tanto quanto aqueles atendidos em centros de referência.

Conclusões

Neste estudo baseado em uma coorte de pacientes ambulatoriais com CMH não referenciados, em faixa etária predominante acima de 40 anos, verificou-se associação entre a ocorrência de arritmias ventriculares no ECG-Holter e o grau de HVE avaliado ao ecocardiograma pela espessura parietal máxima e índice de massa. Maior prevalência de taquicardia ventricular não sustentada foi evidenciada nos casos em que ambos os descritores ecocardiográficos de HVE eram mais elevados.

Referências

1. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):e783-831.

2. Mattos BP, Torres MA, Freitas VC. Avaliação diagnóstica da cardiomiopatia hipertrófica em fase clínica e pré-clínica. Arq Bras Cardiol. 2008;91(1):51-62.

3. Elliot PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, et al. Sudden death in hypertrophic cardiomyopathy: identification of high-risk patients. J Am Coll Cardiol. 2000;36(7):2212-8.

4. Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010;121(3):445-56. Erratum in: Circulation. 2010 Jul 6;122(1):e7.

5. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36-44.

6. Varnava AM, Elliot PM, Baboonian C, Davison F, Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease. Circulation. 2001;104(12):1380-4.

7. Saumarez RC, Pytkowski M, Sterlinski M, Bourke JP, Clague JR, Cobbe SM, et al. Paced ventricular electrogram fractionation predicts sudden death in hypertrophic cardiomyopathy. Eur Heart J. 2008:29(13):1653-61.

8. Piva e Mattos B. Estratificação de risco para morte súbita na cardiomiopatia hipertrófica: bases genéticas e clínicas. Arq Bras Cardiol. 2006;87(3):391-9.

9. Medeiros Pde T, Martinelli Filho M, Arteaga E, Costa R, Siqueira S, Mady C, et al. Cardiomiopatia hipertrófica: importância dos eventos arrítmicos em pacientes com risco de morte súbita. Arq Bras Cardiol. 2006:87(5):649-57.

10. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342(24):1778-85.

11. Elliot PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet. 2001;357(9254):420-4.

12. Basso CD, Thiene G, Corrado D, Buja G, Melacini P, Nava A. Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia. Hum Pathol. 2000;31(8):988-98.

13. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476-82.

14. Adabag AS, Maron BJ, Appelbaum E, Harrigan CJ, Buros JL, Gibson CM, et al. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. J Am Coll Cardiol. 2008;51(14):1369-74.

15. Kwon DH, Setser RM, Popovic ZB, Thamilarasan M, Sola S, Schoenhagen P, et al. Association of myocardial fibrosis, electrocardiography and ventricular tachyarrhythmia in hypertrophic cardiomyopathy: a delayed contrast enhanced MRI study. Int J Cardiovasc Imaging. 2008;24(6):617-25.

16. Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, et al. Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail. 2010;3(1):51-8.

17. O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, et al. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56(11):867-74.

18. Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, et al. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56(11):875-87.

19. Green JJ, Berger JS, Kramer CM, Salermo M. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging. 2012;5(4):370-7.

20. Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;45(5):697-704.

21. Olivotto I, Gistri R, Petrone P, Pedemonte E, Vargiu D, Cecchi F. Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41(2):315-21.

22. Cheng X, Kusachi S, Urabe N, Nogami K, Takemoto M, Morishita N, et al. Association between high grade ventricular arrhythmia and extent of left ventricular hypertrophy in hypertrophic cardiomyopathy. Acta Med Okayama. 1991;45(3):155-9.

23. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-63.

24. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum of left ventricular hypertrophic in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol. 1995;26(7):1699-708.

25. Olivotto I, Maron MS, Autore C, Lesser JR, Rega L, Casolo G, et al. Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2008;52(7):559-66.

26. Sen-Chowdhry S, McKenna WJ. Sudden death from genetic and acquired cardiomyopathies. Circulation. 2012;125(12):1563-76.

27. Maron BJ, Savage DD, Wolfson JK, Epstein SE. Prognostic significance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study. Am J Cardiol. 1981;48(2):252-7.

28. McKenna WJ, England D, Doi YL, Oakley C, Goodwin JF. Arrhythmia in hypertrophic cardiomyopathy. I: Influence and prognosis. Br Heart J. 1981;46(2):168-72

29. Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol. 2003;42(5):873-9.

30. Elliott PM, Gimeno JR, Tomé MT, Shah J, Ward D, Thaman R, et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J. 2006;27(16):1933-41.

31. O'Mahony C, Lambiase PD, Rahman SM, Cardona M, Calcagnino M, Quarta G, et al. The relation of ventricular arrhythmia electrophysiological characteristics to cardiac phenotype and circadian patterns in hypertrophic cardiomyopathy. Europace. 2012;14(5):724-33.

32. Spirito P, Watson RM, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60(14):1137-42.

33. Wang L, Seidman JG, Seidman CE. Narrative review: harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy. Ann Intern Med. 2010;152(8):513-20.

34. Hedman A, Hartikainen, Vanninen E, Laitinen T, Jääskeläinen P, Laakso M, et al. Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the α-tropomyosin gene. J Moll Cell Cardiol. 2004;36(1):91-9. Erratum in J Moll Cell Cardiol. 2004;36(4):607-8.

35. Sorajja P, Nishimura RA, Ommen SR, Ackerman MJ, Tajik AJ, Gersh BJ. Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy. J Am Soc Echocardiogr. 2006;19(6):788-95.

36. Cristiaans I, Lekanne dit Deprez RH, van Langen IM, Wilde AA. Ventricular fibrillation in MYH7-related hypertrophic cardiomyopathy before onset of ventricular hypertrophy. Heart Rhythm. 2009;6(9):1366-9.

37. Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010;363(6):552-63.

38. Arteaga E, de Araújo AQ, Bernstein M, Ramires FJ, Ianni BM, Fernandes F, et al. Valor prognóstico da fração de volume de colágeno na cardiomiopatia hipertrófica. Arq Bras Cardiol. 2009;92(3):210-4, 216-20.

39. Prinz C, Hering D, Bitter T, Horstkotte D, Faber L. Left atrial size and left ventricular hypertrophy correlate with myocardial fibrosis in patients with hypertrophic cardiomyopathy. Acta Cardiol. 2011;66(2):153-7.

40. Shiozaki AA, Senra T, Arteaga E, Pita CG, Martinelli Filho M, Ávila LF, et al. Fibrose miocárdica em pacientes com cardiomiopatia hipertrófica com alto risco para morte súbita cardíaca. Arq Bras Cardiol. 2010;94(4):535-40.

Beatriz Piva e Mattos

Rua Luciana de Abreu, 233 Apto 801, Moinhos de Vento

CEP 90570-060, Porto Alegre, RS - Brasil

E-mail:

bpmattos@cardiol.br

Artigo recebido em 26/06/12, revisado em 31/10/12, aceito em 19/11/12.

1. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):e783-831. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Circulation 2011 e783 831 24 124 Gersh BJ Maron BJ Bonow RO Dearani JA Fifer MA Link MS 2. Mattos BP, Torres MA, Freitas VC. Avaliação diagnóstica da cardiomiopatia hipertrófica em fase clínica e pré-clínica. Arq Bras Cardiol. 2008;91(1):51-62. Avaliação diagnóstica da cardiomiopatia hipertrófica em fase clínica e pré-clínica Arq Bras Cardiol 2008 51 62 1 91 Mattos BP Torres MA Freitas VC 3. Elliot PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, et al. Sudden death in hypertrophic cardiomyopathy: identification of high-risk patients. J Am Coll Cardiol. 2000;36(7):2212-8. Sudden death in hypertrophic cardiomyopathy: identification of high-risk patients J Am Coll Cardiol 2000 2212 8 7 36 Elliot PM Poloniecki J Dickie S Sharma S Monserrat L Varnava A 4. Maron BJ. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010;121(3):445-56. Erratum in: Circulation. 2010 Jul 6;122(1):e7. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy Circulation 2010 445 56 3 121 Maron BJ 5. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000;35(1):36-44. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death J Am Coll Cardiol 2000 36 44 1 35 Shirani J Pick R Roberts WC Maron BJ 6. Varnava AM, Elliot PM, Baboonian C, Davison F, Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease. Circulation. 2001;104(12):1380-4. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease Circulation 2001 1380 4 12 104 Varnava AM Elliot PM Baboonian C Davison F Davies MJ McKenna WJ 7. Saumarez RC, Pytkowski M, Sterlinski M, Bourke JP, Clague JR, Cobbe SM, et al. Paced ventricular electrogram fractionation predicts sudden death in hypertrophic cardiomyopathy. Eur Heart J. 2008:29(13):1653-61. Paced ventricular electrogram fractionation predicts sudden death in hypertrophic cardiomyopathy Eur Heart J 2008 1653 61 13 29 Saumarez RC Pytkowski M Sterlinski M Bourke JP Clague JR Cobbe SM 8. Piva e Mattos B. Estratificação de risco para morte súbita na cardiomiopatia hipertrófica: bases genéticas e clínicas. Arq Bras Cardiol. 2006;87(3):391-9. Estratificação de risco para morte súbita na cardiomiopatia hipertrófica: bases genéticas e clínicas Arq Bras Cardiol 2006 391 9 3 87 Piva e Mattos B 9. Medeiros Pde T, Martinelli Filho M, Arteaga E, Costa R, Siqueira S, Mady C, et al. Cardiomiopatia hipertrófica: importância dos eventos arrítmicos em pacientes com risco de morte súbita. Arq Bras Cardiol. 2006:87(5):649-57. Cardiomiopatia hipertrófica: importância dos eventos arrítmicos em pacientes com risco de morte súbita Arq Bras Cardiol 2006 649 57 5 87 Medeiros Pde T Martinelli Filho M Arteaga E Costa R Siqueira S Mady C 10. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342(24):1778-85. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy N Engl J Med 2000 1778 85 24 342 Spirito P Bellone P Harris KM Bernabo P Bruzzi P Maron BJ 11. Elliot PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet. 2001;357(9254):420-4. Relation between severity of left ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy Lancet 2001 420 4 9254 357 Elliot PM Gimeno Blanes JR Mahon NG Poloniecki JD McKenna WJ 12. Basso CD, Thiene G, Corrado D, Buja G, Melacini P, Nava A. Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia. Hum Pathol. 2000;31(8):988-98. Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia Hum Pathol 2000 988 98 8 31 Basso CD Thiene G Corrado D Buja G Melacini P Nava A 13. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476-82. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease Heart 2000 476 82 5 84 Varnava AM Elliott PM Sharma S McKenna WJ Davies MJ 14. Adabag AS, Maron BJ, Appelbaum E, Harrigan CJ, Buros JL, Gibson CM, et al. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. J Am Coll Cardiol. 2008;51(14):1369-74. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance J Am Coll Cardiol 2008 1369 74 14 51 Adabag AS Maron BJ Appelbaum E Harrigan CJ Buros JL Gibson CM 15. Kwon DH, Setser RM, Popovic ZB, Thamilarasan M, Sola S, Schoenhagen P, et al. Association of myocardial fibrosis, electrocardiography and ventricular tachyarrhythmia in hypertrophic cardiomyopathy: a delayed contrast enhanced MRI study. Int J Cardiovasc Imaging. 2008;24(6):617-25. Association of myocardial fibrosis, electrocardiography and ventricular tachyarrhythmia in hypertrophic cardiomyopathy: a delayed contrast enhanced MRI study Int J Cardiovasc Imaging 2008 617 25 6 24 Kwon DH Setser RM Popovic ZB Thamilarasan M Sola S Schoenhagen P 16. Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, et al. Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail. 2010;3(1):51-8. Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy Circ Heart Fail 2010 51 8 1 3 Rubinshtein R Glockner JF Ommen SR Araoz PA Ackerman MJ Sorajja P 17. O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, et al. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56(11):867-74. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy J Am Coll Cardiol 2010 867 74 11 56 O'Hanlon R Grasso A Roughton M Moon JC Clark S Wage R 18. Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, et al. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56(11):875-87. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy J Am Coll Cardiol 2010 875 87 11 56 Bruder O Wagner A Jensen CJ Schneider S Ong P Kispert EM 19. Green JJ, Berger JS, Kramer CM, Salermo M. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging. 2012;5(4):370-7. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy JACC Cardiovasc Imaging 2012 370 7 4 5 Green JJ Berger JS Kramer CM Salermo M 20. Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;45(5):697-704. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy J Am Coll Cardiol 2005 697 704 5 45 Adabag AS Casey SA Kuskowski MA Zenovich AG Maron BJ 21. Olivotto I, Gistri R, Petrone P, Pedemonte E, Vargiu D, Cecchi F. Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41(2):315-21. Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy J Am Coll Cardiol 2003 315 21 2 41 Olivotto I Gistri R Petrone P Pedemonte E Vargiu D Cecchi F 22. Cheng X, Kusachi S, Urabe N, Nogami K, Takemoto M, Morishita N, et al. Association between high grade ventricular arrhythmia and extent of left ventricular hypertrophy in hypertrophic cardiomyopathy. Acta Med Okayama. 1991;45(3):155-9. Association between high grade ventricular arrhythmia and extent of left ventricular hypertrophy in hypertrophic cardiomyopathy Acta Med Okayama 1991 155 9 3 45 Cheng X Kusachi S Urabe N Nogami K Takemoto M Morishita N 23. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-63. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology J Am Soc Echocardiogr 2005 1440 63 12 18 Lang RM Bierig M Devereux RB Flachskampf FA Foster E Pellikka PA 24. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum of left ventricular hypertrophic in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol. 1995;26(7):1699-708. Phenotypic spectrum of left ventricular hypertrophic in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients J Am Coll Cardiol 1995 1699 708 7 26 Klues HG Schiffers A Maron BJ 25. Olivotto I, Maron MS, Autore C, Lesser JR, Rega L, Casolo G, et al. Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2008;52(7):559-66. Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy J Am Coll Cardiol 2008 559 66 7 52 Olivotto I Maron MS Autore C Lesser JR Rega L Casolo G 26. Sen-Chowdhry S, McKenna WJ. Sudden death from genetic and acquired cardiomyopathies. Circulation. 2012;125(12):1563-76. Sudden death from genetic and acquired cardiomyopathies Circulation 2012 1563 76 12 125 Sen-Chowdhry S McKenna WJ 27. Maron BJ, Savage DD, Wolfson JK, Epstein SE. Prognostic significance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study. Am J Cardiol. 1981;48(2):252-7. Prognostic significance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study Am J Cardiol 1981 252 7 2 48 Maron BJ Savage DD Wolfson JK Epstein SE 28. McKenna WJ, England D, Doi YL, Oakley C, Goodwin JF. Arrhythmia in hypertrophic cardiomyopathy. I: Influence and prognosis. Br Heart J. 1981;46(2):168-72 Arrhythmia in hypertrophic cardiomyopathy: I: Influence and prognosis Br Heart J 1981 168 72 2 46 McKenna WJ England D Doi YL Oakley C Goodwin JF 29. Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol. 2003;42(5):873-9. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients J Am Coll Cardiol 2003 873 9 5 42 Monserrat L Elliott PM Gimeno JR Sharma S Penas-Lado M McKenna WJ 30. Elliott PM, Gimeno JR, Tomé MT, Shah J, Ward D, Thaman R, et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J. 2006;27(16):1933-41. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy Eur Heart J 2006 1933 41 16 27 Elliott PM Gimeno JR Tomé MT Shah J Ward D Thaman R 31. O'Mahony C, Lambiase PD, Rahman SM, Cardona M, Calcagnino M, Quarta G, et al. The relation of ventricular arrhythmia electrophysiological characteristics to cardiac phenotype and circadian patterns in hypertrophic cardiomyopathy. Europace. 2012;14(5):724-33. The relation of ventricular arrhythmia electrophysiological characteristics to cardiac phenotype and circadian patterns in hypertrophic cardiomyopathy Europace 2012 724 33 5 14 O'Mahony C Lambiase PD Rahman SM Cardona M Calcagnino M Quarta G 32. Spirito P, Watson RM, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60(14):1137-42. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy Am J Cardiol 1987 1137 42 14 60 Spirito P Watson RM Maron BJ 33. Wang L, Seidman JG, Seidman CE. Narrative review: harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy. Ann Intern Med. 2010;152(8):513-20. Narrative review: harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy Ann Intern Med 2010 513 20 8 152 Wang L Seidman JG Seidman CE Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the a-tropomyosin gene J Moll Cell Cardiol 2004 91 9 1 36 Hedman A Hartikainen Vanninen E Laitinen T Jääskeläinen P Laakso M 35. Sorajja P, Nishimura RA, Ommen SR, Ackerman MJ, Tajik AJ, Gersh BJ. Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy. J Am Soc Echocardiogr. 2006;19(6):788-95. Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy J Am Soc Echocardiogr 2006 788 95 6 19 Sorajja P Nishimura RA Ommen SR Ackerman MJ Tajik AJ Gersh BJ 36. Cristiaans I, Lekanne dit Deprez RH, van Langen IM, Wilde AA. Ventricular fibrillation in MYH7-related hypertrophic cardiomyopathy before onset of ventricular hypertrophy. Heart Rhythm. 2009;6(9):1366-9. Ventricular fibrillation in MYH7-related hypertrophic cardiomyopathy before onset of ventricular hypertrophy Heart Rhythm 2009 1366 9 9 6 Cristiaans I Lekanne dit Deprez RH van Langen IM Wilde AA 37. Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010;363(6):552-63. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy N Engl J Med 2010 552 63 6 363 Ho CY López B Coelho-Filho OR Lakdawala NK Cirino AL Jarolim P 38. Arteaga E, de Araújo AQ, Bernstein M, Ramires FJ, Ianni BM, Fernandes F, et al. Valor prognóstico da fração de volume de colágeno na cardiomiopatia hipertrófica. Arq Bras Cardiol. 2009;92(3):210-4, 216-20. Valor prognóstico da fração de volume de colágeno na cardiomiopatia hipertrófica Arq Bras Cardiol 2009 210 4 92 Arteaga E de Araújo AQ Bernstein M Ramires FJ Ianni BM Fernandes F 39. Prinz C, Hering D, Bitter T, Horstkotte D, Faber L. Left atrial size and left ventricular hypertrophy correlate with myocardial fibrosis in patients with hypertrophic cardiomyopathy. Acta Cardiol. 2011;66(2):153-7. Left atrial size and left ventricular hypertrophy correlate with myocardial fibrosis in patients with hypertrophic cardiomyopathy Acta Cardiol 2011 153 7 2 66 Prinz C Hering D Bitter T Horstkotte D Faber L 40. Shiozaki AA, Senra T, Arteaga E, Pita CG, Martinelli Filho M, Ávila LF, et al. Fibrose miocárdica em pacientes com cardiomiopatia hipertrófica com alto risco para morte súbita cardíaca. Arq Bras Cardiol. 2010;94(4):535-40. Fibrose miocárdica em pacientes com cardiomiopatia hipertrófica com alto risco para morte súbita cardíaca Arq Bras Cardiol 2010 535 40 4 94 Shiozaki AA Senra T Arteaga E Pita CG Martinelli Filho M Ávila LF Original Articles Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy

BACKGROUND: In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. OBJECTIVE: In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). METHODS: Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). RESULTS: In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). CONCLUSION: In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

 Arrhythmias, Cardiac Hypertrophy, Left Ventricular Cardiomyopathy, Hypertrophic

Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy

Beatriz Piva e MattosI,II; Marco Antonio Rodrigues TorresI,II; Valéria Centeno de FreitasI; Fernando Luís ScolariII; Melina Silva de LoretoII

IServiço de Cardiologia do Hospital de Clínicas de Porto Alegre

IIFaculdade de Medicina - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil

Mailing Address

ABSTRACT

BACKGROUND: In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias.

OBJECTIVE: In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI).

METHODS: Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT).

RESULTS: In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m2 (n = 10, 77%, 200 ± 30 g/m2), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m2) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m2 (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04).

CONCLUSION: In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

Keywords: Arrhythmias, Cardiac; Hypertrophy, Left Ventricular; Cardiomyopathy, Hypertrophic.

Introduction

Hypertrophic Cardiomyopathy (HCM) is a complex genetic disease, the diagnosis of which is based on the identification of left ventricular hypertrophy (LVH) demonstrated by absence of dilatation of the chamber and any other condition that can cause an abnormality of a similar degree1. In young people under 25 years of age and athletes, it is the main cause of sudden death, produced by ventricular fibrillation that may or may not be preceded by ventricular tachycardia2-4. characteristic histopathological pattern represented by hypertrophy and cellular disorganization, coupled with fibrosis, predisposes victims to the onset of ventricular arrhythmias, which express the abnormal electrophysiological conduction and the electric instability of the myocardium5-7.

Records of non-sustained ventricular tachycardia on Holter electrocardiogram-(ECG-Holter) and massive LVH with a maximum parietal thickness > 30 mm are considered predictors of sudden death in this disease4,8-11. Studies based on necropsy or in transplanted HCM hearts identify a direct relationship between the degree of fibrosis and the maximum parietal thickness of the left ventricle (LV)12,13. Areas of fibrosis, detected in the form of late highlight by means of magnetic resonance imaging with gadolinium, relate to the risk of ventricular arrhythmias and, probably, to sudden death14-19. However, it has not yet been clearly shown if the increase in the parietal thickness of the LV favors the occurrence of ventricular arrhythmias14,20-22. The objective of this study is to analyze the association between the level of LVH, determined by echocardiogram, and the occurrence of ventricular arrhythmias captured by 24-hour ECG-Holter monitoring in an outpatient cohort unreferenced with HCM.

Methods

Patient selection

Fifty-four consecutive patients were chosen from an unreferenced cohort registered at the HCM Outpatient Clinic of the Cardiology Service of the Hospital de Clinicas de Porto Alegre, UFRGS, between March 2007 and December 2011. The HCM diagnosis was established based on the clinical condition and on identification by means of asymmetrical LVH echocardiogram with maximum parietal thickness > 15 mm in any segment and septum/posterior wall ratio of > 1.3 in the absence of dilatation of the chamber and another cause. Exclusion criteria included the following: LV concentric hypertrophy, other forms of cardiomyopathy, coronary artery disease, and/or congenital valvular heart disease. Patients underwent a preliminary clinical and electrocardiographic evaluation, followed by resting echocardiography and 24-hour ECG-Holter performed in the traditional way. The echocardiogram was recorded by a single examiner. The results of the ECG-Holter were evaluated blindly, without prior knowledge of the diagnosis. The use of cardioactive medication was not a consideration for either inclusion or exclusion from the study. This study was approved by the local Research Ethics Committee. All patients signed an informed consent form.

Echocardiogram

Mono and two-dimensional transthoracic echocardiography with pulsed and continuous color Doppler was performed at rest to evaluate the structure and function of the heart chambers, including spectral flow analysis according to current recommendations23. The evaluations were performed with Vivid 7 General Electric equipment (GE Healthcare, Milwaukee, WI, USA). The images obtained included parasternal longitudinal cuts and cross-parasternal and apical views of two, three, four and five chambers with multifrequency transducers of 2.5 to 3.5 MHz, performed in a standardized manner with the patient in the left decubitus position. The following measures were considered: left atrial diameter, final diastolic diameter of LV, end systolic diameter of LV, end diastolic thickness of the interventricular septum, end diastolic thickness of the posterior wall of the LV, LV mass indexed with body surface area and ejection fraction. The maximum parietal thickness was regarded as the one corresponding to the LV segment, which exhibited the greatest degree of thickening. The degree of LVH was evaluated by the maximum wall thickness and body mass index. The maximum gradient in the left ventricular outflow tract was measured at rest and during the Valsalva maneuver with the apical cut-off of five chambers, with continuous Doppler directed parallel to the outflow tract of this chamber according to Bernoulli's modified equation. The presence of occlusion was defined as the mechanical impedance of the left ventricular outflow tract, resulting from contact or approximation of the mitral valve with the interventricular septum in mesosystole. The record of a maximum systolic gradient > 30 mmHg at rest was considered compatible with obstructive forms. Latent obstruction was defined by a gradient <30 mm Hg at rest and > 30 mmHg with Valsalva maneuver. Non-obstructive forms corresponded to a gradient at rest and with Valsalva < 30 mmHg.

Holter electrocardiogram

The outpatient 24-hour ECG-Holter monitor recorded three leads: VII modified V1 and V5. Recordings were analyzed using the GE Mars 8000 and the recorder was the GE Seer Light (GE Medical Systems, Milwaukee, WI, USA). Paired ventricular extrasystoles were characterized as two consecutive extrasystoles, and non-sustained ventricular tachycardia was characterized by the presence of three or more consecutive extrasystoles with a rate of > 100 beats / minute. In patients with more than one Holter ECG, concurrent to the echocardiography, the one with the greatest frequency of ventricular arrhythmia was selected. Two levels were established for ventricular arrhythmias: level I - alone or paired extrasystoles and level II - non-sustained ventricular tachycardia.

Statistical Analysis

Quantitative data were described by mean and standard deviation, or by median (Md) and interquartile intervals (25th and 75th percentiles). The category variables were expressed by absolute and relative frequency. The differences between two groups, based on the comparison of continuous variables with symmetric and asymmetric distribution, were analyzed, respectively, using the Student t test for independent samples and the Mann-Whitney test. Category variables were compared using the chi-square test for heterogeneity and chi-square for linear trend. From the ROC curve with a confidence interval (CI) of 95%, cutoff values for echocardiographic measurements regarding the maximum parietal thickness of LV and mass index of LV were determined, in order to discriminate between patients with higher and lower frequency of ventricular arrhythmias. The data were processed using SPSS software, version 18.0 (SPSS Inc., Chicago, Illinois, USA). The level of statistical significance adopted was p < 0.05.

Results

Characteristics of the patients

Mean age was 54 ± 13 years, with 48 (89%) > 40 years; 33 (61%) were female. There was a predominance of cases with light or moderate impairment of functional capacity (New York Heart Association Functional Class - CFNYHA I/II, n = 40, 74%) compared with those with severe limitation (CFNYHA III/IV, n = 14, 26%). All patients were taking prescribed medication: 41 (76%) used beta-blockers, 17 (31%) used calcium channel blockers such as verapamil or diltiazem, and 5 (9%) used amiodarone (Table 1).

Holter electrocardiogram

Ventricular arrhythmias on ECG-Holter exam were identified in all cases. Isolated ventricular extrasystoles were seen in 46 (85%) patients, ranging from 1 to 1461, with an average of 130 ± 277. Twenty (37%) had paired ventricular extrasystoles numbering 1 to 15, and 12 (22%) and 13 (24%) experienced non-sustained ventricular tachycardia (NSVT), with 1 to 7 saved, ranging from 3 to 24 beats. Patients with NSVT presented, relative to those without this arrhythmia (n = 41, 76%), a higher number of isolated ventricular extrasystoles (Md 131, p25 = 6.25 and p75 = 316 versus Md 9, p25 and p75 = 1 and p75 = 91, p = 0.27) and paired extrasystoles (Md 2, p25 = 0, p75 = 5 versus Md 0 p25 = 0, p75 = 1, p = 0.013). Demographic and clinical data did not differ between patients with level I and II ventricular arrhythmias (Table 1).

Echocardiogram

The mean maximum LV parietal thickness observed was 20 ± 4 mm, with a variation of 15 to 34 mm. There was a predominance of light or moderate hypertrophy of the left ventricle: 26 (48%) had measurements between 15 and 19 mm, 21 (39%) measured between 20 and 24 mm, six (11%) measured between 25 and 29 mm and only one (2%) measured > 30 mm. The LV mass index showed a variation from 97 to 248 g/m2, with a mean of 158 ± 18 g / m2. Obstructive forms of hypertrophy occurred in 21 (39%) patients, obstructive latent form in 6 (11%) and non-obstructive form in 27 (50%) (Table 2).

Ventricular Arrhythmias and left ventricular hypertrophy

The maximum LV wall thickness was significantly higher in patients with non-sustained ventricular tachycardia (level II) compared with those who only experienced extrasystoles (level I) (23 ± 5 mm versus 19 ± 4 mm, p = 0.001). The mass index of the LV was significantly higher in level II patients (182 ± 45 g /m2versus 151 ± 48 g/m2; p = 0.049). The other echocardiographic variables did not differ among the groups (Table 2).

Through the ROC curve with a CI of 95%, it was demonstrated that maximum parietal thickness of the LV of > 21 mm and a mass LV index of > 144 g/m2 represented cutoff values capable of identifying patients with a higher prevalence of non-sustained ventricular tachycardia on ECG-Holter. In the 13 patients (24%) with non-sustained ventricular tachycardia, there was a higher frequency of maximum wall thickness of the left ventricle > 21 mm (n = 10, 77%, 25 ± 4 mm) and an LV mass index > 144 g / m2 (n = 10, 77%; 200 ± 30 g/m2), in relation to those with extrasystole arrhythmia only (n = 41, 77%), where these measures were identified, respectively, in 37% (n = 15, 23 ± 1 mm), p = 0.023 and 39% (n = 16.192 ± 53 g/m2) of the cases, p = 0.026 (Figure 1).

The record of non-sustained ventricular tachycardia was more common in patients with a maximum wall thickness of the LV > 21 mm and an LV mass index > 144 g/m2 (8 of 13, 62%) than in those with one (4 of 13; 31%) or no (1 of 13; 8%) echocardiographic variable above the cutoff values (p = 0.04). The predominance of non-sustained ventricular tachycardia on ECG-Holter rose directly and progressively with the number of echocardiographic descriptors of LVH considered for analysis (chi-square for linear tendency, p = 0.04) (Figure 2). The ROC curve showed that maximum wall thickness of the LV > 21 mm had a sensitivity of 77% and a specificity of 64%, with positive and negative predictive values of 40% and 90%, respectively, for detection of non-sustained ventricular tachycardia on Holter ECG (area under the ROC curve 0.767; CI95% 0.614 - 0.920). Mass index of the LV > 144 g/m2 showed a sensitivity of 77% and a specificity of 61%, with a positive predictive value of 39% and a negative predictive value of 89% (area under the ROC curve 0.713; CI95% 0.530 - 0.900) (Figure 3).

Discussion

This study demonstrated that the more severe the LVH, the more conducive it is to arrhythmogenesis in HCM. The occurrence of non-sustained ventricular tachycardia was associated with greater impairment of the LV, when assessed by maximal wall thickness and body mass index. The record of non-sustained ventricular tachycardia was more frequent in patients where both echocardiographic descriptors of LVH were higher. The asymmetrical character of the hypertrophy and its heterogeneous distribution, shown by echocardiography, were the measurements of LV mass index that were less reliable in HCM24. Even though LV mass index is frequently high, it shows a weak correlation with the maximum parietal thickness of the LV when evaluated by means of magnetic resonance imaging25. However, in this analysis, it is noted that the record of non-sustained ventricular tachycardia, in addition to its association with a higher mass index, was more frequent in the cases where the maximum parietal thickness was high.

Ventricular arrhythmias are the characteristic manifestation of HCM, a disease that is considered unpredictable in its development due to its arrhythmogenic potential, with annual rates of sudden death estimated at 1%26. Studies based on 24- to 48-hour ECG-Holter analysis in populations based in the community20 and in reference centers 27-29 identified ventricular extrasystoles in 80% to95% of the cases, with numbers of extrasystoles varying from 1 to 5,000. Paired ventricular extrasystolic beats were found in 30% to 40% of the recordings, and non-sustained ventricular tachycardia was found in 20% to 30%, in brief savings with a frequency ranging from 3 to 36 beats. In this study, paired ventricular extrasystoles were observed in 37% of the patients and non-sustained ventricular tachycardia in 24%, with savings of 3-24 beats. Compared with previous studies, we observed a similar prevalence of ventricular arrhythmias, despite the lowest degree of sample selection and the prevalence of patients aged > 40 years with light or moderate degree of LVH.

The record of non-sustained ventricular tachycardia on Holter ECG would seem to increase the susceptibility to sudden death, but has a low positive predictive value27-30. Ventricular arrhythmias in HCM originate from re-entry and arise from an electrophysiological substrate characterized by slow conduction routes and late ventricular activation4,7. In electrograms, the registration of small amplitude and late inscription potentials, called subdivisions, would reflect abnormal ventricular activation and would predispose to sudden death7. Most of the ventricular tachycardia episodes observed here were monomorphic, preceded by extrasystoles, and would possibly be abolished by antitachycardia pacing31.

Support for the hypothesis that the degree of LVH would influence arrhythmogenesis in HCM is considerable10,11, although it has not been properly confirmed. Early investigation showed the extent of the relationship between LVH and registration of ventricular tachycardia on ECG-Holter32. Subsequent studies that assessed the relationship between the maximum parietal thickness of the LV and the occurrence of non-sustained ventricular tachycardia showed conflicting results14,20,21, even when carried out in the same institution, with some presumable degree of sample superposition14,20. In one of these analyses, it was shown that the registration of non-sustained ventricular tachycardia would proportionately influence the level of LVH, afflicting 50% of those with a maximum parietal thickness > 30 mm20. Divergent conclusions could be attributed to the level of sample selection, to the methodology used and to the heterogeneous character of the disease. Unlike our study, none of the mentioned studies included isolated or paired extrasystolic beats. However, the prevalence of multifocal or paired ventricular extrasystoles and of non-sustained ventricular tachycardia was previously described in patients with extensive septal or free anterolateral wall LVH, in comparison with cases with involvement restricted to the septum22. In models with human mutations of HCM, an association between the level of hypertrophy and induced ventricular arrhythmias was seen33. In the presence of mutation of the α-tropmyosin gene, ventricular arrhythmias were induced in one-third of the cases; a correlation was also observed with the maximum parietal thickness of the LV and the number of risk factors for sudden death34.

Patients with a maximum wall thickness of the LV > 30 mm, particularly the young and elderly, are at increased risk of cardiovascular mortality and sudden death10,11,35. LVH, when increasing parietal stress and oxygen consumption, would lead to myocardial infarction, an important stimulus for the development of arrhythmias1. The role of myocardial hypertrophy in arrhythmogenesis in HCM was questioned before the description of sudden death in carriers of troponin T gene mutations with normal or slightly increased LV parietal thicknesses6. Ventricular fibrillation is also reported in patients with mutations of the cardiac β-myosin heavy chain with absent or late LVH36.

The anomalous architecture of the myocardium, represented by cellular disorganization and fibrosis, interferes with the conduction of the stimulus, producing unidirectional block and favoring a reentry mechanism.4,7,11. Reparative fibrosis probably develops, induced by silent myocardial ischemia and cellular death as a consequence of myocyte hypertrophy and microcirculatory disease12,15. Prefibrotic conditions indicative of the increase in collagen synthesis would precede LVH development in HCM37. The deposition of collagen in the form of reparative fibrosis is identified at an early age and tends to worsen with age5. In carriers of HCM who are victims of sudden death, when the disease is caused by other genes than the troponin T gene the presence of extensive areas of fibrosis shows the potential relationship between the histopathological substrate and the development of fatal ventricular arrhythmias6. More recently, the analysis of endomyocardial biopsies in HCM showed that the increase in the fraction of collagen volume was associated with higher mortality38.

The increase in myocardial mass and LV wall thickness in HCM is determined not only by myocyte hypertrophy, but is also largely due to the expansion of the extracellular matrix resulting from reparative fibrosis12,15. Studies with magnetic resonance imaging using gadolinium showed correlation of fibrosis detected by late enhancement with the thickness of the interventricular septum, determined both by this method and by echocardiogram16,39, the same not occurring in relation to the global LV mass39. Late enhancement identifies the presence of intra-myocardial fibrosis of a reparative nature in 40% to 80% of HCM cases, occupying from 0.4% to 65% of the ventricular myocardium16-18. In a multivariate analysis18 and in a recent meta-analysis19, the fibrosis detected by magnetic resonance proved to be an independent predictor of mortality. However, for this to be considered a marker of prognosis and sudden death, additional confirmation is required1. The association of fibrosis identified by magnetic resonance imaging14-17 or computer tomography with multiple detectors40 and fatal or non-fatal ventricular arrhythmias suggests the existence of a physiopathological link between arrhythmogenesis and fibrosis in HCM. This fact justifies the association observed between the higher frequency of ventricular arrhythmias and LV wall thickening, of which fibrosis is one of the determining factors. However, it is unclear whether the increase in LV wall thickness is dependent on fibrosis, reflecting the consequences of a process of chronic myocardial ischemia influenced by cellular hypertrophy and disease of the microcirculation, or whether it results from activation or genetic factors not yet understood or discovered.

The association demonstrated here between the occurrence of ventricular arrhythmias and the degree of LVH could contribute to individualization of factors that predispose to arrhythmogenesis in HCM. The present study showed that the maximum wall thickness of LV > 21 mm and the mass index > 144 g/m2 are characteristics that may lead to greater myocardial electrical instability in these patients.

Limitations of the study

The possibility that our results reflect, to some degree, the very characteristics of the sample cannot be ruled out. The predominant inclusion of individuals in an older age group with the lowest degree of selection, although probably less risky, could limit the inferences to populations with this profile. However, it must also be noted that the study population may also be representative of the disease, as well as those treated at referral centers.

Conclusions

In this study based on a cohort of unreferenced ambulatory patients with HCM, of a predominant age group above 40 years, there was an association between the occurrence of ventricular arrhythmias found on ECG-Holter exam and the degree of LVH evaluated by echocardiography and determined by maximal wall thickness index and mass index. A higher prevalence of non-sustained ventricular tachycardia was evidenced when both echocardiographic descriptors of LVH were higher.

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Manuscript received July 26, 2012; manuscript revised October 31, 2012; accepted November 11, 2012.