Biventricular Pacing After Cardiopulmonary Bypass

描述（由申请人提供）：双心室起搏（BiVP）逆转扩张型心肌病（DCM）的心室内传导延迟（IVCD）和左心室（LV）功能障碍。BiVP可改善LV功能和心脏指数（Cl），且无能量消耗。在DCM、IVCD和LV射血分数<35%的患者中进行的MIRACLE试验显示，BiVP改善了运动耐量和心功能的主观和客观指标。BiVP使许多人受益，但选择标准尚未完全制定，30%的接受者是“无反应者”，每年的成本超过20亿美元。初步数据表明，BiVP可使心脏手术后低输出状态的患者获益。我们计划评估BiVP的手术应用，同时评估作用机制和优化。我们将190例术前左室功能不全的心脏手术患者随机分为起搏组和非起搏组。BiVP将在术后进行优化并持续，直至患者稳定。将在3个时间点对所有患者进行短暂性BiVP评估。主要终点是在重症监护室（ICU）中测量的热稀释Cl改善15%。将使用随机数据采集序列评估心率、房室延迟、心室起搏部位和W时间对CI的影响。次要终点包括心律失常的发生率、正性肌力支持、尿量、体重增加、发病率、死亡率和ICU费用。在三组14名心脏移植受者中进行的相关研究将评估BiVP对DCM或缺血性肌病伴或不伴正性肌力支持的原位衰竭心脏力学的影响。主要终点也是Cl增加，但每例患者将接受随机序列的数据收集，在14分钟内收集6个左心室起搏部位和9个W定时的54点矩阵，同时记录Cl、收缩性、心室内和室间同步性和二尖瓣返流的测量值。结果将显示在二维响应面上，以定义BiVP优化的最佳技术。将对Cl增加< 20%的患者进行详细评估，以确定无效的病因。这些研究很重要，因为临床获益的可能性很高。所采用的方法将提供优于任何其他设置的精确度、测量宽度和起搏部位范围上级。该方案将提供新的重要科学信息，不仅有利于手术患者，也有利于BiVP接受者的一般人群。

DESCRIPTION (provided by applicant): Biventricular pacing (BiVP) reverses intraventricular conduction delay (IVCD) and left ventricular (LV) dys- function in dilated cardiomyopathy (DCM). BiVP improves LV function and cardiac index (Cl) at no energy cost. The MIRACLE trial, in patients with DCM, IVCD and LV ejection fraction <35%, demonstrated improved subjective and objective measures of exercise tolerance and cardiac function with BiVP. BiVP benefits many, but selection criteria are not fully developed, and 30% of recipients are "nonresponders," at a cost of more than $2 billion/year. Preliminary data suggest that BiVP can benefit patients with low output states after cardiac surgery. We plan to assess surgical application of BiVP while assessing mechanisms of action and optimization. We will randomize 190 cardiac surgery patients with LV dysfunction preoperatively to paced and unpaced groups. BiVP will be optimized and continued postoperatively until patients are stable. BiVP will be assessed transiently in all patients at three time points. The primary end point is a 15% improvement in thermal dilution Cl measured in the intensive care unit (ICU). Effects of heart rate, atrioventricular delay, ventricular pacing site, and W timing on Cl will be assessed using a randomized sequence of data collection. Secondary end points include incidence of arrhythmias, inotropic support, urine output, weight gain, morbidity, mortality, and ICU costs. Related studies in three groups of 14 cardiac transplant recipients will assess BiVP effects on mechanics of in situ failing hearts with DCM or ischemic myopathy with or without inotropic support. The primary end point again is an increase in Cl, but each patient will undergo a randomized sequence of data collection for a 54-point matrix of six left ventricular pacing sites and nine W timings over 14 minutes, while measurements of Cl, contractility, intraventricular and interventricular synchrony and mitral regurgitation are recorded. Results will be displayed on two-dimensional response surfaces to define the best techniques for BiVP optimization. Patients with an increase in Cl < 20% will be assessed in detail to determine the etiology of failure to respond. These studies are important because of a high probability of clinical benefit. The methods employed will provide precision, breadth of measurement, and range of pacing sites superior to any other setting. The protocol will provide new and important scientific information that will benefit not only surgical patients but also the general population of BiVP recipients.