Lorenzini, M;
Norrish, G;
Field, E;
Ochoa, JP;
Cicerchia, M;
Akhtar, MM;
Syrris, P;
... Elliott, PM; + view all
(2020)
Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers.
Journal of the American College of Cardiology
, 76
(5)
pp. 550-559.
10.1016/j.jacc.2020.06.011.
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Abstract
BACKGROUND: Predictive genetic screening of relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM. OBJECTIVES: The aim of this study was to determine the incidence of new HCM diagnosis in SP mutation carriers. METHODS: This was a retrospective analysis of adult and pediatric SP mutation carriers identified during family screening who did not fulfill diagnostic criteria for HCM at first evaluation. RESULTS: The authors evaluated 285 individuals from 156 families (median age 14.2 years [interquartile range: 6.8 to 31.6 years], 141 [49.5%] male individuals); 145 (50.9%) underwent cardiac magnetic resonance (CMR). Frequency of causal genes was as follows: MYBPC3 n ¼ 123 (43.2%), MYH7 n ¼ 69 (24.2%), TNNI3 n ¼ 39 (13.7%), TNNT2 n ¼ 34 (11.9%), TPM1 n ¼ 9 (3.2%), MYL2 n ¼ 6 (2.1%), ACTC1 n ¼ 1 (0.4%), multiple mutations n ¼ 4 (1.4%). Median follow-up was 8.0 years (interquartile range: 4.0 to 13.3 years) and 86 (30.2%) patients developed HCM; 16 of 50 (32.0%) fulfilled diagnostic criteria on CMR but not echocardiography. Estimated HCM penetrance at 15 years of follow-up was 46% (95% confidence interval [CI]: 38% to 54%). In a multivariable model adjusted for age and stratified for CMR, independent predictors of HCM development were male sex (hazard ratio [HR]: 2.91; 95% CI: 1.82 to 4.65) and abnormal electrocardiogram (ECG) (HR: 4.02; 95% CI: 2.51 to 6.44); TNNI3 variants had the lowest risk (HR: 0.19; 95% CI: 0.07 to 0.55, compared to MYBPC3). CONCLUSIONS: Following a first negative screening, approximately 50% of SP mutation carriers develop HCM over 15 years of follow-up. Male sex and an abnormal ECG are associated with a higher risk of developing HCM. Regular CMR should be considered in long-term screening.
| Type: | Article |
|---|---|
| Title: | Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jacc.2020.06.011 |
| Publisher version: | https://doi.org/10.1016/j.jacc.2020.06.011 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10106549 |
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