Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome

Background
Arrhythmias are frequent in Systemic Sclerosis (SSc) and portend a bad prognosis, accounting alone for 6% of total deaths. Many of these patients die suddenly, thus prevention and intensified risk-stratification represent unmet medical needs. The major goal of this study was the definition of ECG indexes of poor prognosis.
Methods
We performed a prospective cohort study to define the role of 24h-ECG-Holter as an additional risk-stratification technique in the identification of SSc-patients at high risk of life-threatening arrhythmias and sudden cardiac death (SCD). One-hundred SSc-patients with symptoms and/or signs suggestive of cardiac involvement underwent 24h-ECG-Holter. The primary end-point was a composite of SCD or need for implantable cardioverter defibrillator (ICD).
Results
Fifty-six patients (56%) had 24h-ECG-Holter abnormalities and 24(24%) presented frequent ventricular ectopic beats (VEBs). The number of VEBs correlated with high-sensitive cardiac troponin T (hs-cTnT) levels and inversely correlated with left-ventricular ejection fraction (LV-EF) on echocardiography. During a mean follow-up of 23.1±16.0 months, 5 patients died suddenly and two required ICD-implantation. The 7 patients who met the composite end-point had a higher number of VEBs, higher levels of hs-cTnT and NT-proBNP and lower LV-EF (p = 0.001 for all correlations). All these 7 patients had frequent VEBs, while LV-EF was not reduced in all and its range was wide. At ROC curve, VEBs>1190/24h showed 100% of sensitivity and 83% of specificity to predict the primary end-point (AUROC = 0.92,p<0.0001). Patients with VEBS>1190/24h had lower LV-EF and higher hs-cTnT levels and, at multivariate analysis, the presence of increased hs-cTnT and of right bundle branch block on ECG emerged as independent predictors of VEBs>1190/24h. None of demographic or disease-related characteristics emerged as predictors of poor outcome.
Conclusions
VEBS>1190/24h identify patients at high risk of life-threatening arrhythmic complications. Thus, 24h-ECG-Holter should be considered a useful additional risk-stratification test to select SSc-patients at high-risk of SCD, in whom an ICD-implantation could represent a potential life-saving intervention.

背景
系统性硬化症（Systemic Sclerosis, SSc）患者常伴发心律失常，此类病症预示不良预后，仅心律失常一项即可占总死亡人数的6%。该类患者多发生猝死，因此心律失常的预防与强化风险分层仍存在未被满足的临床需求。本研究的核心目标为明确与不良预后相关的心电图（Electrocardiogram, ECG）指标。

方法
本研究开展一项前瞻性队列研究，旨在明确24小时动态心电图（24h-ECG-Holter）作为补充风险分层手段，在识别存在威胁生命的心律失常及心源性猝死（Sudden Cardiac Death, SCD）高风险SSc患者中的应用价值。研究共纳入100例存在疑似心脏受累症状和/或体征的SSc患者，所有受试者均接受24h-ECG-Holter检查。本研究的主要终点为心源性猝死或需植入型心律转复除颤器（Implantable Cardioverter Defibrillator, ICD）的复合终点。

结果
共有56例患者（56%）的24h-ECG-Holter检查结果存在异常，其中24例（24%）出现频发室性早搏（Ventricular Ectopic Beats, VEBs）。室性早搏数量与高敏心肌肌钙蛋白T（high-sensitive cardiac troponin T, hs-cTnT）水平呈正相关，与超声心动图检测的左心室射血分数（Left Ventricular Ejection Fraction, LV-EF）呈负相关。在平均23.1±16.0个月的随访周期内，共有5例患者发生猝死，2例患者接受了ICD植入。达到复合终点的7例患者，其室性早搏数量、hs-cTnT及N末端B型利钠肽原（NT-proBNP）水平均显著更高，而LV-EF则更低（所有相关性的p值均为0.001）。上述7例患者均存在频发室性早搏，但并非所有患者的LV-EF均出现降低，且其LV-EF的波动范围较广。受试者工作特征曲线（Receiver Operating Characteristic curve, ROC curve）分析显示，当室性早搏数量>1190次/24h时，预测主要复合终点的灵敏度为100%，特异度为83%（受试者工作特征曲线下面积AUROC=0.92，p<0.0001）。室性早搏数量>1190次/24h的患者，其LV-EF更低、hs-cTnT水平更高；多因素分析结果表明，hs-cTnT水平升高及心电图提示右束支传导阻滞，是室性早搏数量>1190次/24h的独立预测因素。人口统计学特征及疾病相关特征均未被证实为不良预后的独立预测因素。

结论
室性早搏数量>1190次/24h可识别出存在威胁生命的心律失常并发症高风险的SSc患者。因此，24h-ECG-Holter可作为有效的补充风险分层检测手段，用于筛选心源性猝死高风险的SSc患者，此类患者植入ICD或可成为潜在的救命治疗方案。