Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)

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art_HO_Genotype_and_Lifetime_Burden_of_Disease_in_Hypertrophic_2018.PDF (1.19 MB)
Citações na Scopus
434
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Autores
HO, Carolyn Y.
DAY, Sharlene M.
ASHLEY, Euan A.
MICHELS, Michelle
JACOBY, Daniel
CIRINO, Allison L.
FOX, Jonathan C.
LAKDAWALA, Neal K.
WARE, James S.
Citação
CIRCULATION, v.138, n.14, p.1387-1398, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The SHaRe registry (Sarcomeric Human Cardiomyopathy Registry) was established to provide the scale of data required to address these issues, aggregating longitudinal data sets curated by 8 international HCM specialty centers. Methods: Data on 4591 patients with HCM (2763 genotyped) followed up for a mean of 5.46.9 years (24791 patient-years; median, 2.9 years; interquartile range, 0.3-7.9 years) were analyzed for cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association functional class III/IV symptoms (all making up the overall composite end point), and left ventricular ejection fraction <35%. Outcomes were analyzed individually and as composite end points. Results: Median age at diagnosis was 45.8 (interquartile range, 30.9-58.1) years, and 37% of patients were female. Age at diagnosis and sarcomere mutation status were predictive of outcomes. Patients <40 years old at diagnosis had a 77% (95% CI, 72-80) cumulative incidence of the overall composite outcome by 60 years of age compared with 32% (95% CI, 29-36) by 70 years of age for patients diagnosed at >60 years old. Young patients with HCM (age, 20-29 years) had 4-fold higher mortality than the general US population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had a 2-fold greater risk for adverse outcomes compared with patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% (95% CI, 23-40) of patients <40 years of age at diagnosis but in 1% (95% CI, 1-2) of those >60 years old at diagnosis. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years after diagnosis. Young age at diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life and the need to develop disease-modifying therapies.
Palavras-chave
cardiomyopathy, hypertrophic, genetics, natural history, registries, risk
URI
https://observatorio.fm.usp.br/handle/OPI/29764
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - ODS/03