Supplementary Material for: Comparison of clinical course and outcomes between dilated and hypokinetic non-dilated cardiomyopathy

Background: By definition, dilated cardiomyopathy (DCM) is characterized by enlargement of the left ventricular (LV) cavity, and systolic dysfunction. However, in 2016 ESC introduced a new clinical entity – hypokinetic non-dilated cardiomyopathy (HNDC). HNDC is defined as LV systolic dysfunction without LV dilatation. However, the diagnosis of HNDC has so far rarely been made by a cardiologist, and it is unknown whether “classic” DCM differs from HNDC in terms of clinical course and outcomes. Objectives: Comparison of heart failure profiles and outcomes between patients with “classic” dilated (DCM) and hypokinetic non-dilated cardiomyopathies (HNDC). Method: We retrospectively analysed 785 DCM patients, defined as impaired left ventricle (LV) systolic function (ejection fraction [LVEF] <45%) in the absence of coronary artery disease, valve disease, congenital heart disease and severe arterial hypertension. “Classic” DCM was diagnosed when LV dilatation was present (LV end-diastolic diameter >52mm/58mm in women/men); otherwise, HNDC was diagnosed. After 47±31 months, the all-cause mortality and composite endpoint (all-cause mortality, heart transplant – HTX, left ventricle assist device implantation - LVAD) were assessed. Results: There were 617 (79%) patients with LV dilatation. Patients with “classic” DCM differed from HNDC in terms of clinically relevant parameters [hypertension (47% vs. 64%, p=0.008), ventricular tachyarrhythmias (29% vs. 15%, p=0.007), NYHA class (2.5±0.9 vs. 2.2±0.8, p=0.003), had lower cholesterol (LDL: 2.9±1.0 vs. 3.2±1.1mmol/l, p=0.049) and higher NT-proBNP (3351±5415 vs. 2563±8584pg/ml, p=0.0001); and required higher diuretics dosages (57.8±89.5 vs. 33.7±48.7mg/day, p=<0.0001). All of their chambers were larger (LVEDd: 68.3±4.5 vs. 52.7±3.5mm, p<0.0001) and they had lower LVEF (25.2±9.4 vs. 36.6±11.7%, p<0.0001). During the follow-up, there were 145 (18%) composite endpoints (“classic” DCM vs. HNDC: 122 [20%] vs. 26 [18%], p=0.22): deaths (97 [16%] vs. 24 [14%], p=0.67), HTX (17 [4%] vs. 4 [4%], p=0.97) and LVAD (19 [5%] vs 0 [0%], p=0.03). Both groups did not differ in terms of all-cause mortality (p=0.70), CV mortality (p=0.37) and composite endpoint (p=0.26). Conclusions: LV dilatation was absent in more than one-fifth of DCM patients. HNDC patients had less severe HF symptoms, less advanced cardiac remodelling, and required lower diuretics dosages. On the other hand, “classic” DCM and HNDC patients did not differ in terms of all-cause mortality, CV mortality and composite endpoint.

背景：根据定义，扩张型心肌病（dilated cardiomyopathy, DCM）以左心室（left ventricular, LV）腔扩大及收缩功能障碍为特征。2016年，欧洲心脏病学会（European Society of Cardiology, ESC）提出了一种全新的临床病种——运动功能减退性非扩张型心肌病（hypokinetic non-dilated cardiomyopathy, HNDC），其被定义为无左心室扩大的左心室收缩功能障碍。然而迄今为止，心内科医师极少诊断HNDC，目前尚不清楚“经典型”DCM与HNDC在临床病程及预后方面是否存在差异。

研究目的：对比“经典型”扩张型心肌病与运动功能减退性非扩张型心肌病患者的心力衰竭表型及预后情况。

研究方法：本研究回顾性分析了785例DCM患者，这类患者被定义为排除冠状动脉疾病、瓣膜病、先天性心脏病及重度动脉高压后，存在左心室收缩功能障碍（左心室射血分数[left ventricular ejection fraction, LVEF]<45%）。若患者存在左心室扩大（女性左心室舒张末期内径>52mm，男性>58mm），则诊断为“经典型”DCM；否则诊断为HNDC。本研究随访时长为47±31个月，评估患者的全因死亡率及复合终点事件（全因死亡率、心脏移植[heart transplant, HTX]、左心室辅助装置植入术[left ventricular assist device implantation, LVAD]）。

研究结果：本队列中共617例（79%）患者存在左心室扩大。“经典型”DCM患者与HNDC患者在多项临床相关参数上存在显著差异：高血压患病率（47% vs. 64%，p=0.008）、室性快速性心律失常患病率（29% vs. 15%，p=0.007）、纽约心脏协会（New York Heart Association, NYHA）心功能分级（2.5±0.9 vs. 2.2±0.8，p=0.003）均更高；低密度脂蛋白（low-density lipoprotein, LDL）胆固醇水平更低（2.9±1.0 vs. 3.2±1.1mmol/L，p=0.049）、N末端B型利钠肽原（N-terminal pro B-type natriuretic peptide, NT-proBNP）水平更高（3351±5415 vs. 2563±8584pg/ml，p=0.0001）；且利尿剂使用剂量更高（57.8±89.5 vs. 33.7±48.7mg/日，p<0.0001）。两组患者的各心腔内径及左心室射血分数均存在显著差异：“经典型”DCM患者的左心室舒张末期内径（LVEDd：68.3±4.5 vs. 52.7±3.5mm，p<0.0001）更大，且LVEF更低（25.2±9.4% vs. 36.6±11.7%，p<0.0001）。随访期间共发生145例（18%）复合终点事件：“经典型”DCM组与HNDC组分别为122例（20%）与26例（18%），组间差异无统计学意义（p=0.22）；其中死亡病例分别为97例（16%）与24例（14%，p=0.67）、心脏移植分别为17例（4%）与4例（4%，p=0.97）、左心室辅助装置植入术分别为19例（5%）与0例（0%，p=0.03）。两组患者的全因死亡率（p=0.70）、心血管（cardiovascular, CV）死亡率（p=0.37）及复合终点事件发生率（p=0.26）均无显著差异。

研究结论：超过五分之一的DCM患者不存在左心室扩大。HNDC患者的心力衰竭症状更轻微、心脏重构程度更低，且所需利尿剂使用剂量更低。但“经典型”DCM与HNDC患者在全因死亡率、心血管死亡率及复合终点事件发生率方面均无显著差异。