BACKGROUND The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. METHODS Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. RESULTS From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3-2.8]). The incidence of new HCM-LVSD was ≈7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively). CONCLUSIONS HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).

中文翻译：

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肥厚型心肌病伴左心室收缩功能障碍：来自 SHaRe 登记处的见解。


背景术语“末期”已用于描述伴有左心室收缩功能障碍(LVSD)的肥厚性心肌病(HCM)，定义为当左心室射血分数为<50%时发生。据报道，HCM-LVSD 的预后很差，但由于其相对罕见，自然史的特征仍然不完全。方法 来自 11 个大容量 HCM 专科中心（组成国际 SHaRe 登记处（肌节人类心肌病登记处））的数据被用来描述 HCM-LVSD 患者的自然史。 Cox 比例风险模型用于确定预后和事件发展的预测因素。结果 在 6793 名 HCM 患者队列中，553 名 (8%) 符合 HCM-LVSD 标准。总体而言，75% 的 HCM-LVSD 患者经历了临床相关事件，35% 的患者达到了复合结局（全因死亡 [n=128]、心脏移植 [n=55] 或左心室辅助装置植入 [n= 9]）。识别 HCM-LVSD 后，达到复合结果的中位时间为 8.4 年。然而，自然历史中存在很大的个体差异。复合结果的重要预测因子包括存在多种致病性/可能致病性肌节变异（风险比 [HR]，5.6 [95% CI，2.3-13.5]）、心房颤动（HR，2.6 [95% CI，1.7-3.5]） ]）和左心室射血分数<35%（HR，2.0 [95% CI，1.3-2.8]）。 15 年来新发 HCM-LVSD 的发生率约为 7.5%。发生 HCM-LVSD 的重要预测因素包括左心室腔尺寸增大（HR，1.1 [95% CI，1.0-1.3]）和室壁厚度（HR，1.3 [95% CI，1.1-1.4]）、左心室射血分数50% 至 60%（HR，1.8 [95% CI，1.2，2.8]-2.8 [95% CI，1.8-4。2]）在基线评估时，心脏磁共振成像上存在晚期钆增强（HR，2.3 [95％CI，1.0-4.9]），以及存在致病性/可能致病性的肌节变异，特别是在细丝基因中（HR，分别为 1.5 [95% CI，1.0-2.1] 和 2.5 [95% CI，1.2-5.1]）。结论 HCM-LVSD 影响约 8% 的 HCM 患者。尽管 HCM-LVSD 的自然病程各不相同，但 75% 的患者经历了不良事件，其中 35% 的患者经历了相当于出现收缩功能障碍后中位时间 8.4 年的死亡。除了临床特征外，遗传底物似乎在预后（多种肌节变异）和 HCM-LVSD（细丝变异）事件发生的风险中发挥着作用。