Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
JAMA Cardiol. 2017 Mar 1;2(3):293-302. doi: 10.1001/jamacardio.2016.5034.
Considerable research has described the arrhythmic course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, objective data characterizing structural progression, such as ventricular enlargement and cardiac dysfunction, in ARVD/C are relatively scarce.
To define the extent of structural progression, identify determinants of structural progression, and determine the association between structural progression and electrocardiographic (ECG) changes in patients with ARVD/C.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, first- and last-available echocardiograms of 85 patients with ARVD/C fulfilling 2010 Task Force diagnostic criteria (TFC) from a transatlantic ARVD/C registry were retrospectively compared to assess structural disease progression. Right ventricular (RV) size and systolic function between baseline and last follow-up were compared. The RV size was determined by RV outflow tract dimension, and RV and left ventricular (LV) systolic function were determined by RV fractional area change (RV-FAC) and LV ejection fraction (LVEF), respectively. Multivariable logistic regression was used to study associations between baseline characteristics and the occurrence of structural progression.
The main outcome was the change in variables indicating structural progression. Secondary outcomes were the correlation with electrical progression and identification of the association between baseline characteristics and occurence structural progression.
Among the 85 patients with ARVD/C, mean (SD) age at baseline was 42.8 (14.4) years and 47 (55%) were men. After a mean (SD) follow-up of 6.4 (2.5) years, RV outflow tract dimension increased from 35 mm (interquartile range [IQR], 31 to 39) to 37 mm (IQR, 33 to 41) (P < .001), RV-FAC decreased from 39% (IQR, 33% to 44%) to 34% (IQR, 24% to 42%) (P < .001) (rate -3.3% per 5 years; IQR, -8.9% to 1.2%), indicating large interpatient variability. The LVEF decreased from 55% (IQR, 52% to 60%) to 54% (IQR, 49% to 57%) (P = .001) (rate, -0.2% per 5 years; IQR, -6.5% to 1.7%). Forty examinations were reanalyzed to establish the measurement error. Patients exceeding the measurement error by ±2 SDs were identified with significant progressive disease for RV, with a decrease in RV-FAC greater than 10% (n = 21) and, for LV, a decrease in LVEF greater than 7% (n = 23). Progression of RV disease was associated with depolarization criteria at baseline (odds ratio [OR], 9.0; 95% CI, 1.1-74.2; P = .04), whereas progression of LV disease was associated with phospholamban (PLN) mutation (OR, 8.8; 95% CI, 2.1-37.2; P = .003). There was no association between progressive RV/LV structural disease and newly developed ECG TFC.
Structural dysfunction in ARVD/C is progressive with substantial interpatient variability. Significant structural RV progression was associated with prior depolarization abnormalities, whereas LV progression is modified by genetic background. Structural progression was not associated with development of new ECG TFC. The results of this study pave the way for designing and launching trials aimed at reducing structural progression in patients with ARVD/C.
大量研究已经描述了致心律失常性右室心肌病/发育不良（ARVD/C）的心律失常过程。然而，在 ARVD/C 中，描述结构性进展的客观数据，如心室扩大和心功能障碍，相对较少。
定义结构性进展的程度，确定结构性进展的决定因素，并确定 ARVD/C 患者结构性进展与心电图（ECG）变化之间的关联。
设计、地点和参与者：在这项队列研究中，回顾性比较了来自大西洋两岸 ARVD/C 注册中心的符合 2010 年工作组诊断标准（TFC）的 85 名 ARVD/C 患者的首次和末次可获得的超声心动图，以评估结构性疾病进展。比较了基线和末次随访时的右心室（RV）大小和收缩功能。RV 大小由 RV 流出道直径确定，RV 和左心室（LV）收缩功能分别由 RV 分数面积变化（RV-FAC）和 LV 射血分数（LVEF）确定。多变量逻辑回归用于研究基线特征与结构性进展发生之间的关联。
主要结局是表示结构性进展的变量变化。次要结局是与电进展的相关性以及确定基线特征与结构性进展发生之间的关联。
在 85 名 ARVD/C 患者中，基线时平均（SD）年龄为 42.8（14.4）岁，47 名（55%）为男性。在平均（SD）6.4（2.5）年的随访后，RV 流出道直径从 35mm（IQR，31 至 39）增加到 37mm（IQR，33 至 41）（P<0.001），RV-FAC 从 39%（IQR，33%至 44%）降低到 34%（IQR，24%至 42%）（P<0.001）（每年下降 3.3%；IQR，-8.9%至 1.2%），表明患者间存在较大差异。LVEF 从 55%（IQR，52%至 60%）降至 54%（IQR，49%至 57%）（P=0.001）（每年下降 0.2%；IQR，-6.5%至 1.7%）。对 40 次检查进行了重新分析，以确定测量误差。通过 ±2SD 超过测量误差的患者被确定为 RV 有明显进行性疾病，RV-FAC 下降超过 10%（n=21），而对于 LV，LVEF 下降超过 7%（n=23）。RV 疾病的进展与基线时的去极化标准相关（比值比[OR]，9.0；95%CI，1.1-74.2；P=0.04），而 LV 疾病的进展与磷酸化酶蛋白（PLN）突变相关（OR，8.8；95%CI，2.1-37.2；P=0.003）。在 RV/LV 结构性疾病的进展与新出现的 ECG TFC 之间没有关联。
ARVD/C 的结构性功能障碍是进行性的，患者间存在较大差异。显著的 RV 结构性进展与先前的去极化异常相关，而 LV 进展则受遗传背景的影响。结构性进展与新出现的 ECG TFC 无关。这项研究的结果为设计和开展旨在减少 ARVD/C 患者结构性进展的试验铺平了道路。
