Open AccessPoor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy
Author(s) -
Merlo Marco,
Sinagra Gianfranco,
Carniel Elisa,
Slavov Dobromir,
Zhu Xiao,
Barbati Giulia,
Spezzacatene Anita,
Ramani Federica,
Salcedo Ernesto,
Di Lenarda Andrea,
Mestroni Luisa,
Taylor Matthew R. G.
Publication year - 2013
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12116
Subject(s) - myh7 , medicine , heart failure , dilated cardiomyopathy , cardiology , heart transplantation , sudden cardiac death , hypertrophic cardiomyopathy , genetics , gene , biology , gene isoform
Background In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry. Methods DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3 , TNNT2 , and TTN were identified. Genotype–phenotype association analysis was performed, and long‐term survival‐free from death or heart transplant was compared between carriers and noncarriers. Results We found 24 rare variants (3 in MYH6 , 3 in MYH7 , 3 in MYBPC3 , 2 in TNNT2 , and 13 in TTN) affecting 52 subjects in 25 families. The phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure deaths, 8 heart transplants, 2 ventricular fibrillations). There was no difference in the overall long‐term survival between carriers and the 33 noncarriers ( p = 0.322). However after 50 years of age, the combined endpoint of death or transplant was decreased in carriers as compared to noncarriers ( p = 0.026). Conclusions Patients with DCM carrying rare variants in sarcomeric genes manifest a poorer prognosis as compared to noncarriers after the age of 50 years. These data further support the role of genetic testing in DCM for risk stratification.