Functional and Structural Myocardial Improvement after LVAD Therapy: The U-NOVA Reverse Remodeling Stages

Background The degree of left ventricular morphological and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is variable. Objectives To evaluate the continuum of left ventricular reverse remodeling after LVAD implantation by serial echocardiographic imaging in an effort to define stages of reverse remodeling. Methods Consecutive patients with heart failure who required mechanical circulatory support with a durable LVAD were enrolled from two programs (UTAH consortium and Inova). Echocardiograms were performed within 1-month preceding LVAD implantation and then 1,2, 3, 6, 9, and 12 months after. Patients were categorized by the degree of morphologic and functional change after LVAD support. Results The study included 358 patients with baseline and at least 6-month follow up measurements. The mean duration of heart failure was 6.9 ± 6.7 years, baseline left ventricular ejection fraction (LVEF) was 19 ± 7%, with mean left ventricular end-diastolic internal dimension (LVIDd) 6.8 ± 1.0 cm. In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥ 40% and LVIDd ≤ 6.0cm and were termed as responders. The remaining patients were categorized as non-responders, borderline responders and partial responders by an increase in LVEF during follow-up (∆) LVEF < 5%, 5-10% and >10%, respectively. Most patients were non-responders (n=212, 59%), followed by borderline responders (n=55, 15%) and partial responders (n=57, 16%). Multivariable logistic regression identified smaller initial LVIDd (OR 1.77 per 1 cm decrease, 95% CI 1.15-2.3, p=0.009), use of an axial flow device (OR 2.57, 95% CI 1.08-6.12, p=0.033), and shorter heart failure duration (OR 1.10 per 1-year decrease, 95% CI 1.01-1.20, p=0.047) as predictors of response. Conclusions Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and as many other biological phenomena manifests as a continuous spectrum. Defining 4 stages across this continuum may have clinical management implications and may also facilitate advancing the field of myocardial plasticity by informing the study design of future investigations.

背景 持续血流左心室辅助装置（LVAD）植入后左心室形态和功能改善的程度是可变的。 目的 通过系列超声心动图成像评估LVAD植入后左心室逆向重构的连续过程，以确定逆向重构的阶段。 方法 从两个项目（犹他联盟和伊诺瓦）招募了需要使用持久LVAD进行机械循环支持的连续性心力衰竭患者。在LVAD植入前1个月内以及植入后1、2、3、6、9和12个月进行超声心动图检查。根据LVAD支持后形态和功能变化的程度对患者进行分类。 结果 该研究包括358名有基线数据且至少有6个月随访测量的患者。心力衰竭的平均持续时间为6.9±6.7年，基线左心室射血分数（LVEF）为19±7%，平均左心室舒张末期内径（LVIDd）为6.8±1.0 cm。在该队列中，34名患者（10%）的LVEF改善≥40%且LVIDd≤6.0 cm，被称为应答者。其余患者根据随访期间LVEF的增加情况（∆LVEF＜5%、5 - 10%和＞10%）分别被归类为无应答者、临界应答者和部分应答者。大多数患者为无应答者（n = 212，59%），其次是临界应答者（n = 55，15%）和部分应答者（n = 57，16%）。多变量逻辑回归分析确定较小的初始LVIDd（每减少1 cm，比值比为1.77，95%置信区间为1.15 - 2.3，p = 0.009）、使用轴流装置（比值比为2.57，95%置信区间为1.08 - 6.12，p = 0.033）以及较短的心力衰竭持续时间（每减少1年，比值比为1.10，95%置信区间为1.01 - 1.20，p = 0.047）是应答的预测因素。 结论 与持久LVAD支持相关的左心室逆向重构不是全有或全无的现象，像许多其他生物学现象一样，表现为一个连续的谱系。在这个连续体上定义4个阶段可能对临床管理有影响，并且通过为未来研究的设计提供信息，也可能有助于推动心肌可塑性领域的发展。