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Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy
Author(s) -
Mathew J.,
Zahavich L.,
LafreniereRoula M.,
Wilson J.,
George K.,
Benson L.,
Bowdin S.,
Mital S.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13157
Subject(s) - hypertrophic cardiomyopathy , myh7 , medicine , sudden cardiac death , hazard ratio , cardiology , mace , cardiomyopathy , heart failure , genetics , biology , gene , confidence interval , gene isoform , myocardial infarction , conventional pci
Children with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death (SCD) and other life‐threatening events. We assessed if affected gene and variant burden predict outcomes. Patients <18 years old with primary HCM with a pathogenic variant or variant of uncertain significance in cardiomyopathy genes were included. Association of gene and variant number and type with freedom from major adverse cardiac events (MACE), that is, ICD insertion, myectomy, aborted SCD, transplantation or death, was assessed by Cox regression. A total of 98 of 155 gene‐tested patients carried a non‐benign variant. The primary affected gene was MYH7 in 35% ( MYH7 +) and MYBPC3 in 49% ( MYBPC3 +). MYH7+ patients had earlier disease onset and higher risk of MACE (hazard ratio 2.7, 95% CI 1.3‐5.7). Risk of MACE was also higher in patients with multiple variants (n = 16) (HR 2.5, CI: 1.1‐5.9) compared to a propensity score‐matched single variant subset, after adjustment for primary gene, and in patients with de novo ( n = 18) vs inherited variants (HR 5.7, CI: 2.6‐12.7). Affected gene (eg, MYH7 ), higher variant burden and de novo variant status are independently associated with earlier onset and higher frequency of adverse outcomes in pediatric HCM, highlighting the importance of genetic risk stratification in HCM.