Background:Improvement of left ventricular function (also called left ventricular reverse remodeling [LVRR]) is an important treatment goal in patients with dilated cardiomyopathy (DCM) and hypokinetic non-DCM (HNDC) and is prognostically favorable. We tested whether genetic DCM mutations impact LVRR independent from clinical parameters.Methods and Results:Patients with DCM and hypokinetic non-DCM (n=346; mean left ventricular ejection fraction, 30%) underwent genotyping for 47 DCM-associated genes in addition to extensive phenotyping. LVRR was defined as improvement of left ventricular ejection fraction >50% or ≥10% absolute increase, with cardiac dimensions (left ventricular end diastolic diameter) ≤33 mm/m² or ≥10% relative decrease. LVRR occurred in 180 (52%) patients after a median follow-up of 12-month optimal medical treatment. Low baseline left ventricular ejection fraction, a hypokinetic non-DCM phenotype, high systolic blood pressure, absence of a family history of DCM, female sex, absence of atrioventricular block, and treatment with β-blockers were all independent positive clinical predictors of LVRR. With the exception of TTN, genetic mutations were strongly associated with a lower rate of LVRR (odds ratio, 0.19 [0.09–0.42]; P<0.0001). TTN and LMNA were independently associated with LVRR (odds ratio, 2.49 [1.09–6.20]; P=0.038 and 0.11 [0.01–0.99]; P=0.049, respectively). Adding mutation status significantly improved discrimination (C statistics) and reclassification (integrated discrimination improvement/net reclassification index) of the clinical model predicting LVRR. Furthermore, the risk for heart failure hospitalization and cardiovascular death is lower in the LVRR patients on the long term (hazard ratio, 0.47 [0.24–0.91]; P=0.009 and 0.18 [0.04–0.82]; P=0.007, respectively), and LVRR is an independent predictor for event-free survival.Conclusions:The genetic substrate is associated with the clinical course and long-term prognosis of patients with DCM/hypokinetic non-DCM.

中文翻译：

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临床表型和基因型关联与扩张型心肌病左心室功能的改善

背景：改善左心室功能（也称为左心室反向重塑[LVRR]）是扩张型心肌病（DCM）和低运动性非DCM（HNDC）患者的重要治疗目标，并且对预后良好。我们测试了遗传性DCM突变是否独立于临床参数而影响LVRR。方法与结果：除DCM和运动减慢的非DCM（n = 346;左心室平均射血分数为30％）的患者外，还对47个与DCM相关的基因进行了基因分型。广泛的表型。LVRR定义为心脏尺寸（左心室舒张末期直径）≤33mm / m ^2时左心室射血分数改善> 50％或≥10％绝对增加或相对降低≥10％。在对12个月最佳药物进行中位随访后，LVRR发生在180名患者中（52％）。低基线左心室射血分数，低运动性非DCM表型，高收缩压，无DCM家族史，女性，无房室传导阻滞和用β受体阻滞剂治疗都是LVRR的独立阳性阳性预测指标。除TTN以外，基因突变与LVRR降低率密切相关（比值比为0.19 [0.09-0.42]；P <0.0001）。TTN和LMNA与LVRR独立相关（比值比为2.49 [1.09-6.20]；P = 0.038和0.11 [0.01-0.99]；P分别为0.049）。添加突变状态显着改善了预测LVRR的临床模型的辨别力（C统计量）和重新分类（综合辨别力改善/净重新分类指数）。此外，从长期来看，LVRR患者发生心力衰竭住院和心血管死亡的风险较低（风险比分别为0.47 [0.24-0.91]；P = 0.009和0.18 [0.04-0.82]；P = 0.007），结论：遗传底物与DCM /低运动性非DCM患者的临床病程和长期预后有关。