Improving sudden cardiac death risk stratification in hypertrophic cardiomyopathy using established clinical variables and genetic information.

Background And Aims: The cardiac societies of Europe and the United States have established different risk models for preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). The aim of this study is to validate current SCD risk prediction methods in a German HCM cohort and to improve them by the addition of genotype information.

Methods: HCM patients without prior SCD or equivalent arrhythmic events ≥ 18 years of age were enrolled in an expert cardiomyopathy center in Germany. The primary endpoint was defined as SCD/-equivalent within 5 years of baseline evaluation. 5-year SCD-risk estimates and recommendations for ICD implantations, as defined by the ESC and AHA/ACC guidelines, were analyzed. Multivariate cox proportional hazards analyses were integrated with genetic findings as additive SCD risk.

Results: 283 patients were included and followed for in median 5.77 years (2.92; 8.85). A disease-causing variant was found in 138 (49%) patients. 14 (5%) patients reached the SCD endpoint (5-year incidence 4.9%). Kaplan-Meier survival analysis shows significantly lower overall SCD event-free survival for patients with an identified disease-causing variant (p < 0.05). The ESC HCM Risk-SCD model showed an area-under-the-curve (AUC) of 0.74 (95% CI 0.68-0.79; p < 0.0001) with a sensitivity of 0.29 (95% CI 0.08-0.58) and specificity of 0.83 (95% CI 0.78-0.88) for a risk estimate ≥ 6%/5-years. By comparison, the AHA/ACC HCM SCD risk stratification model showed an AUC of 0.70 (95% CI 0.65-0.76; p = 0.003) with a sensitivity of 0.93 (95% CI, 0.66-0.998) and specificity of 0.28 (95% CI 0.23-0.34) at the respective cut-off. The modified SCD Risk Score with genetic information yielded an AUC of 0.76 (95% CI 0.71-0.81; p < 0.0001) with a sensitivity of 0.86 (95% CI 0.57-0.98) and specificity of 0.69 (95% CI 0.63-0.74). The number-needed-to-treat (NNT) to prevent 1 SCD event by prophylactic ICD-implantation is 13 for the ESC model, 28 for AHA/ACC and 9 for the modified Genotype-model.

Conclusion: This study confirms the performance of current risk models in clinical decision making. The integration of genetic findings into current SCD risk stratification methods seem feasible and can add in decision making, especially in borderline risk-groups. A subgroup of patients with high SCD risk remains unidentified by current risk scores.