Institute for Cardiomyopathies & Center for Cardiogenetics, Department of Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), Standort Heidelberg/Mannheim, 69120, Heidelberg, Germany.
Clin Res Cardiol. 2024 May;113(5):728-736. doi: 10.1007/s00392-023-02310-4. Epub 2023 Oct 4.
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.
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.
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.
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.
欧洲和美国的心脏协会已经为肥厚型心肌病（HCM）制定了不同的预防心源性猝死（SCD）风险模型。本研究的目的是在德国的 HCM 队列中验证当前的 SCD 风险预测方法，并通过添加基因型信息来改进这些方法。
在德国的一家专家心肌病中心，招募了无 SCD 或等效心律失常事件史≥18 岁的 HCM 患者。主要终点定义为基线评估后 5 年内 SCD/-等效事件。分析了 ESC 和 AHA/ACC 指南定义的 5 年 SCD 风险估计值和 ICD 植入建议。多变量 Cox 比例风险分析与遗传发现相结合，作为附加的 SCD 风险。
共纳入 283 例患者，中位随访时间为 5.77 年（2.92；8.85）。在 138 例（49%）患者中发现了致病变异。14 例（5%）患者达到 SCD 终点（5 年发生率 4.9%）。Kaplan-Meier 生存分析显示，携带致病变异的患者整体 SCD 无事件生存率显著降低（p<0.05）。ESC HCM Risk-SCD 模型的曲线下面积（AUC）为 0.74（95%CI 0.68-0.79；p<0.0001），敏感性为 0.29（95%CI 0.08-0.58），特异性为 0.83（95%CI 0.78-0.88），风险估计值≥6%/5 年。相比之下，AHA/ACC HCM SCD 风险分层模型的 AUC 为 0.70（95%CI 0.65-0.76；p=0.003），敏感性为 0.93（95%CI，0.66-0.998），特异性为 0.28（95%CI 0.23-0.34）。基于遗传信息的改良 SCD 风险评分的 AUC 为 0.76（95%CI 0.71-0.81；p<0.0001），敏感性为 0.86（95%CI 0.57-0.98），特异性为 0.69（95%CI 0.63-0.74）。预防 ICD 植入的 SCD 事件的 NNT 为 13 例 ESC 模型，28 例 AHA/ACC 模型，9 例改良基因型模型。
本研究证实了当前风险模型在临床决策中的性能。将遗传发现纳入当前的 SCD 风险分层方法似乎是可行的，可以在决策中提供帮助，尤其是在风险边缘群体中。目前的风险评分仍无法识别某些高 SCD 风险的患者亚组。
