Kübrich Marion, Petrakopoulou Paraskevi, Kofler Sieglinde, Nickel Thomas, Kaczmarek Ingo, Meiser Bruno M, Reichart Bruno, von Scheidt Wolfgang, Weis Michael
Divisions of Cardiology and Cardiovascular Surgery, University Hospital Grosshadern, Ludwig-Maximilians University of Munich, Munich, Germany.
Transplantation. 2008 Jun 15;85(11):1580-7. doi: 10.1097/TP.0b013e318170b4cd.
Coronary vasomotor dysfunction is a common finding in cardiac transplant recipients and is an early marker for the development of graft atherosclerosis. The present prospective study tested whether endothelial dysfunction independently predicts cardiovascular-related events and death after heart transplantation (HTx).
Functional and structural coronary changes were evaluated in 185 consecutive patients 25+/-33 months after HTx. The following potential risk factors for graft survival were assessed at baseline: hypertension, diabetes, dyslipidemia, donor and recipient characteristics (age, gender, cytomegalovirus-infection, human leukocyte antigen-mismatch), pretransplantation diagnosis, ischemic time, treated rejection episodes, immunosuppressive regimens, and medication.The prespecified prospectively defined endpoints were cardiovascular-related events with progressive heart failure, acute myocardial infarction, coronary revascularization, retransplantation, and death. Patients were followed-up for 60+/-17 months.
Event-free survival for the entire group was 73% (25 cardiovascular-related events, 25 deaths). Using multivariate analysis, epicardial endothelial dysfunction (relative risk [RR] 1.97; P=0.028), angiographic cardiac allograft vasculopathy (RR 2.11; P=0.023), diabetes (RR 2.32; P=0.022), high serum levels of CyA (RR 3.54; P=0.006) and Tac (RR 6.82; P=0.002), uncommon reasons for transplantation (RR 4.69; P=0.002), and the absence of statin therapy (RR 0.33; P=0.025) were detected as independent predictors of cardiovascular-related events and death.
This is the first study showing that epicardial endothelial dysfunction independently predicts outcome in HTx patients providing functional and prognostic information that complete angiographic risk factor assessment.
冠状动脉血管舒缩功能障碍在心脏移植受者中很常见,是移植物动脉粥样硬化发展的早期标志物。本前瞻性研究旨在检验内皮功能障碍是否能独立预测心脏移植(HTx)后心血管相关事件和死亡。
对185例HTx术后25±33个月的连续患者进行冠状动脉功能和结构变化评估。在基线时评估以下移植物存活的潜在危险因素:高血压、糖尿病、血脂异常、供体和受体特征(年龄、性别、巨细胞病毒感染、人类白细胞抗原错配)、移植前诊断、缺血时间、治疗的排斥反应、免疫抑制方案和药物治疗。预先设定的前瞻性定义终点为伴有进行性心力衰竭、急性心肌梗死、冠状动脉血运重建、再次移植和死亡的心血管相关事件。对患者进行了60±17个月的随访。
整个组的无事件生存率为73%(25例心血管相关事件,25例死亡)。通过多变量分析,心外膜内皮功能障碍(相对风险[RR]1.97;P=0.028)、血管造影显示的心脏移植物血管病变(RR 2.11;P=0.023)、糖尿病(RR 2.32;P=0.022)、高血清环孢素A(CyA)水平(RR 3.54;P=0.006)和他克莫司(Tac)水平(RR 6.82;P=0.002)、不常见的移植原因(RR 4.69;P=0.002)以及未使用他汀类药物治疗(RR 0.33;P=0.025)被检测为心血管相关事件和死亡的独立预测因素。
这是第一项表明心外膜内皮功能障碍能独立预测HTx患者预后的研究,提供了功能和预后信息,完善了血管造影危险因素评估。