BibTex format

author = {Simoes, Monteiro de Marvao A and McGurk, K and Zheng, S and Thanaj, M and Bai, W and Duan, J and Biffi, C and Mazzarotto, F and Statton, B and Dawes, T and Savioli, N and Halliday, B and Xu, X and Buchan, R and Baksi, A and Quinlan, M and Tokarczuk, P and Tayal, U and Francis, C and Whiffin, N and Theotokis, A and Zhang, X and Jang, M and Berry, A and Pantazis, A and Barton, P and Rueckert, D and Prasad, S and Walsh, R and Ho, C and Cook, S and Ware, J and O'Regan, D},
doi = {10.1016/j.jacc.2021.07.017},
journal = {Journal of the American College of Cardiology},
pages = {1097--1110},
title = {Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy},
url = {},
volume = {78},
year = {2021}

RIS format (EndNote, RefMan)

AB - Background: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomereencoding genes, but little is known about the clinical significance of these variants in thegeneral population.Objectives: To compare lifetime outcomes and cardiovascular phenotypes according to thepresence of rare variants in sarcomere-encoding genes amongst middle-aged adults.Methods: We analysed whole exome sequencing and cardiac magnetic resonance (CMR)imaging in UK Biobank participants stratified by sarcomere-encoding variant status.Results: The prevalence of rare variants (allele frequency <0.00004) in HCM-associatedsarcomere-encoding genes in 200,584 participants was 2.9% (n=5,712; 1 in 35), and theprevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was0.25% (n=493, 1 in 407). SARC-HCM-P/LP variants were associated with increased risk ofdeath or major adverse cardiac events compared to controls (HR 1.69, 95% CI 1.38 to 2.07,p<0.001), mainly due to heart failure endpoints (HR 4.23, 95% CI 3.07 to 5.83, p<0.001). In21,322 participants with CMR, SARC-HCM-P/LP were associated with asymmetric increasein left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) buthypertrophy (≥13mm) was only present in 18.4% (n=9/49, 95% CI 9 to 32%). SARC-HCMP/LP were still associated with heart failure after adjustment for wall thickness (HR 6.74,95% CI 2.43 to 18.7, p<0.001).Conclusions: In this population of middle-aged adults, SARC-HCM-P/LP variants have lowaggregate penetrance for overt HCM but are associated with increased risk of adversecardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absoluteevent rates are low, identification of these variants may enhance risk stratification beyondfamilial disease.
AU - Simoes,Monteiro de Marvao A
AU - McGurk,K
AU - Zheng,S
AU - Thanaj,M
AU - Bai,W
AU - Duan,J
AU - Biffi,C
AU - Mazzarotto,F
AU - Statton,B
AU - Dawes,T
AU - Savioli,N
AU - Halliday,B
AU - Xu,X
AU - Buchan,R
AU - Baksi,A
AU - Quinlan,M
AU - Tokarczuk,P
AU - Tayal,U
AU - Francis,C
AU - Whiffin,N
AU - Theotokis,A
AU - Zhang,X
AU - Jang,M
AU - Berry,A
AU - Pantazis,A
AU - Barton,P
AU - Rueckert,D
AU - Prasad,S
AU - Walsh,R
AU - Ho,C
AU - Cook,S
AU - Ware,J
AU - O'Regan,D
DO - 10.1016/j.jacc.2021.07.017
EP - 1110
PY - 2021///
SN - 0735-1097
SP - 1097
TI - Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy
T2 - Journal of the American College of Cardiology
UR -
UR -
UR -
VL - 78
ER -