Abstract 17764: Multiple Gene Mutations Predicted Poor Prognosis in Patients with Hypertrophic Cardiomyopathy
BACKGROUND The clinical outcomes of hypertrophic cardiomyopathy (HCM) are largely unpredictable. The presence of multiple mutations in HCM patients was revealed recently and suggested to be associated with malignant manifestations, mostly in case reports. However, the long-term clinical implication of multiple mutations has not been well determined. In this study we assessed the prognostic value of multiple mutations in a prospectively collected and comprehensively genotyped Chinese HCM cohort.
METHODS Twenty-five reported pathogenic genes were screened in 169 unrelated HCM patients and 176 health controls with multiplexing targeted resequencing. Patients were grouped based on mutation dosage: no mutation was detected (no mutation), single mutation and multiple mutations (≥2 mutations). The incidence of cardiovascular death and other adverse outcomes were recorded through a follow-up of 6.1±3.6 years. The correlation of multiple mutations with clinical outcomes was assessed.
RESULTS Total 111 mutations were identified in 108 (63.9%) patients of which 76 were classified as novel. Multiple mutations were found in 29 (17.2%) patients, including 25 double and 4 triple. During follow-up, cardiovascular death occurred in 19 (11.3%) patients and 52.6% of them had multiple mutations. Multivariate analysis showed that multiple mutations significantly increased the risk of cardiovascular death compared with no mutation (HR, 5.15; 95% CI, 1.74 to 15.22; P=0.001) and single mutation (HR, 12.11; 95% CI, 3.63 to 40.38; P<0.001). The age at cardiovascular death was much younger in patients with multiple mutations (37.0±13.9 years) than those with no mutation (59.0±11.0 years; P=0.008) and with single mutation (56.0±13.5 years; P=0.03). Multiple mutations also predicted increased risk for other adverse outcomes, including heart failure, stroke, atrial fibrillation and septal reduction therapy (vs. no mutation: HR, 2.21; 95% CI, 1.14 to 4.30; P=0.01 and vs. single mutation: HR, 1.93; 95% CI, 1.05 to 3.53; P=0.02).
CONCLUSIONS Our study demonstrated that the prevalence of multiple mutations in HCM patients is considerable high. Multiple mutations predict malignant prognosis and can be added to the prediction algorithm for risk stratification of HCM.
- © 2012 by American Heart Association, Inc.