Value of Genetic Testing for the Prediction of Long-Term Outcome in Patients With Hypertrophic Cardiomyopathy

Pathogenic gene mutations are found in about 50% of patients with hypertrophic cardiomyopathy (HC). Previous studies have shown an association between sarcomere mutations and medium-term outcome. The association with long-term outcome has not been described. The aim of this cohort study was to assess the long-term outcomes of patients with genotype positive (G+) and genotype negative (G−) HC. The study population consisted of 626 patients with HC (512 probands and 114 relatives) who underwent phenotyping and genetic testing from 1985 to 2014. End points were all-cause mortality, cardiovascular (CV) mortality, heart failure (HF)–related mortality, and sudden cardiac death/aborted sudden cardiac death (SCD/aborted SCD). Kaplan–Meier and multivariate Cox regression analyses were performed. A pathogenic mutation was detected in 327 patients (52%). G+ probands were younger than G− probands (46 ± 15 vs 55 ± 15 years, p <0.001), had more non sustained ventricular tachycardia (34% vs 13%; p <0.001), more often a history of syncope (14% vs 7%; p = 0.016), and more extreme hypertrophy (maximal wall thickness ≥30 mm, 7% vs 1%; p <0.001). G− probands were more symptomatic (New York Heart Association ≥II, 73% vs 53%, p <0.001) and had higher left ventricular outflow tract gradients (42 ± 39 vs 29 ± 33 mm Hg, p = 0.001). During 12 ± 9 years of follow-up, G+ status was an independent risk factor for all-cause mortality (hazard ratio [HR] 1.90, 95% CI 1.14 to 3.15; p = 0.014), CV mortality (HR 2.82, 95% CI 1.49 to 5.36; p = 0.002), HF-related mortality (HR 6.33, 95% CI 1.79 to 22.41; p = 0.004), and SCD/aborted SCD (HR 2.88, 95% CI 1.23 to 6.71; p = 0.015). In conclusion, during long-term follow-up, patients with G+ HC are at increased risk of all-cause death, CV death, HF-related death, and SCD/aborted SCD.