Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies

Aug 11, 2023
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Authors:
Jansen M, de Brouwer R, Hassanzada F, et al.
Citation:
Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study. JACC Heart Fail 2023;Aug 9:[Epub ahead of print].
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • Early penetrance and major cardiomyopathy-related events (MCEs) were common among NCCMvariant and DCMvariant carriers of MYH7.
  • Furthermore, associated phenotype, variant localization in the MHC-β converter region, and a family history of early MCEs were identified as prognostic factors for penetrance.
  • Screening at younger ages may be warranted for relatives of MYH7 carriers, particularly in those with NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.

Study Questions:

What is the penetrance and prognosis of MYH7 variant-associated cardiomyopathies?

Methods:

The investigators assessed penetrance and major cardiomyopathy-related events (MCEs) in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests using a multicenter cohort study. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results:

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [interquartile range, 19.5-50.2 years]) were included. Hypertrophic cardiomyopathy (HCM) was diagnosed in 226 subjects, noncompaction cardiomyopathy (NCCM) in 70, and dilated cardiomyopathy (DCM) in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted hazard ratio [aHR], 1.87; 95% confidence interval [CI], 1.15-3.04; p = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR, 21.17; 95% CI, 4.81-93.20; p < 0.001) and subjects with a family history of early MCEs (adjusted HR, 2.45; 95% CI, 1.09-5.50; p = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR, 1.82; 95% CI, 1.15-2.87; p = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR, 38.82; 95% CI, 5.16-291.88; p < 0.001).

Conclusions:

The authors report that MYH7 variants can cause cardiomyopathies and MCEs at a young age.

Perspective:

This retrospective cohort study reports that early penetrance and MCEs were common among NCCMvariant and DCMvariant carriers of MYH7. Furthermore, associated phenotype, variant localization in the MHC-β converter region, and a family history of early MCEs were identified as prognostic factors for penetrance. These data suggest that screening at younger ages may be warranted for relatives of MYH7 carriers, particularly in those with NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years. Overall, these data may help individualize risk stratification in MYH7 variant carriers.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Acute Heart Failure

Keywords: Cardiomyopathies, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Diagnostic Tests, Routine, Genetic Variation, Heart Defects, Congenital, Heart Failure, Penetrance, Prognosis, Secondary Prevention, Young Adult


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