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Genotype and Family History as Risk Markers of Sudden Cardiac Death in Hypertrophic Cardiomyopathy
Ali Sakhnini1, Mahdi Montazeri1, Cindy Chow1
1Division of Cardiology, Peter Munk Cardiac Centre, University Health Network and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Insights
Family history of sudden cardiac death (SCD) is an independent risk marker in hypertrophic cardiomyopathy (HCM). Genotype-positive patients with a family history of SCD face a higher risk, suggesting targeted ICD interventions.
Area of Science:
- Cardiology
- Genetics
- Sudden Cardiac Death Research
Background:
- Limited data exist on genetic markers for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM).
- The independent risk conferred by family history of SCD (FHxSCD) in HCM, irrespective of genotype, remains unclear.
Purpose of the Study:
- To evaluate the association between genotype, FHxSCD, and SCD outcomes in HCM patients.
- To explore integrating genetic information into SCD risk stratification models for HCM.
Main Methods:
- A historical cohort study involving 3,258 patients from two HCM referral centers.
- Multivariable hazard regression analysis was employed to assess the association of FHxSCD and genotype with SCD.
Main Results:
- Both FHxSCD (HR: 1.83) and being genotype-positive (HR: 1.52) were independently associated with increased SCD risk.
- Among patients with FHxSCD and no other risk factors, genotype-positive individuals had a 6.4% risk of SCD at 5 years, versus 2.6% for genotype-negative individuals.
Conclusions:
- FHxSCD is an independent risk marker for SCD in adult HCM patients, even when accounting for genotype.
- Genotype-positive patients with FHxSCD and no other risk markers are at high risk for SCD.
- Most genotype-negative patients with FHxSCD may not require ICD insertion unless other risk factors are present.
Background:
There are limited data on genotype as a risk marker of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). It remains unknown whether family history of SCD (FHxSCD) is a risk marker of SCD independently of genotype.
Objectives:
The goal of this study was to assess the association of genotype and FHxSCD with SCD outcomes in HCM and investigate methods for incorporation of genotype into SCD risk stratification models.
Methods:
This historical cohort study used registries of 2 HCM referral centers. Association of FHxSCD and genotype with SCD was assessed by multivariable hazard regression analysis.
Results:
Of 3,258 patients, 896 (27.5%) were genotype-positive, and 332 (10.2%) had FHxSCD. During 4.9 years' median follow-up, 114 patients reached the SCD outcome. On multivariable analysis, the hazard ratios for SCD were 1.83 (95% CI: 1.161-2.9; P = 0.01) for FHxSCD and 1.52 (95% CI: 1.01-2.31; P = 0.047) for being genotype-positive. Among patients with FHxSCD but no other risk markers, the risk of SCD events was 6.4% at 5 years (95% CI: 2.7%-14.9%) in genotype-positive patients and 2.6% (95% CI: 0.6%-10.0%) in genotype-negative patients.
Conclusions:
FHxSCD remained independently associated with SCD in adult patients with HCM even after adjusting for genotype. Among patients with FHxSCD but no other risk markers, genotype-positive patients were at high risk of SCD but genotype-negative patients were not. These data suggest that ICD insertion is not indicated for most genotype-negative patients with FHxSCD unless other risk markers are present.
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