Background Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. Objectives The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. Methods In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. Results Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/− groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). Conclusions In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis.

中文翻译：

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Titin 心肌病的表型和临床结果

背景 对由于肌动蛋白截断 (TTNtv) 引起的扩张型心肌病 (DCM) 的理解提高可能有助于指导患者分层。目的 本研究的目的是建立 TTNtv 基因型、心脏表型和 DCM 结局之间的关系。方法 在这项前瞻性、观察性队列研究中，DCM 患者接受了临床评估、晚期钆增强心血管磁共振、TTN 测序以及对心血管死亡、主要心律失常和主要心力衰竭事件的主要复合终点基因型不知情的裁定随访. 结果 在招募的 716 名受试者中（平均年龄 53.5 ± 14.3 岁；469 名男性 [65.5%]；577 名 [80.6%] 纽约心脏协会功能等级 I/II），83 名（11.6%）患有 TTNtv。TTNtv 患者在入组时更年轻（49.0 岁对 54.1 岁；p = 0。002）并且与没有 TTNtv 的患者相比，左心室质量指数较低（减少 5.1 g/m2；padjusted = 0.03）。TTNtv+/- 组之间的双心室射血分数没有差异。总体而言，604 名患者中有 78 名（12.9%）达到了主要终点（中位随访 3.9 年；四分位距：2.0 至 5.8 年），包括 71 名 TTNtv 患者中的 9 名（12.7%）和 533 名患者中的 69 名（12.9%）没有。对于有或没有 TTNtv 的患者，心血管死亡、心力衰竭或心律失常事件的复合主要结局没有差异（根据主要终点调整的风险比：0.92 [95% 置信区间：0.45 至 1.87]；p = 0.82） . 结论 在这项针对动态 DCM 患者的大型、前瞻性、基因型-表型研究中，我们表明全因 DCM 的预后因素也可以预测 TTNtv DCM 的结果，