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Literature Review

Impact of Ischemic Heart Failure Etiology on Cardiac Recovery During Mechanical Unloading

Wever-Pinzon J, Selzman CH, Stoddard G, et al. J Am Coll Cardiol. 2016;68(16):1741-1752.

Reviewers: Brendan T. Inouye, MD1; Yong G. Peng, MD PhD FASE1

  1. Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL

Left ventricular assist device (LVAD) implantation for patients with advanced heart failure has been successfully demonstrated as an effective means of therapeutic options to improve patient quality of life and prolong survival. Interestingly, a subset of LVAD-supported patients have shown reverse remodeling, with cellular, molecular, genetic, and tissue level mechanisms being currently explored. The focus of the majority of the current investigations are those patients who have developed heart failure via nonischemic cardiomyopathy (NICM) etiologies. Patients who developed heart failure as a result of ischemic cardiomyopathies (ICM) have largely been excluded from current investigations, as it is believed the resultant irreversible scarring compromises chances for a similar recovery seen with NICM patients. However, some ICM patients have shown functional recovery following LVAD implantation, but a structured prospective monitoring of the natural history of these patients has not been investigated.


A prospective cohort study was performed between 2008 and 2014 at a large tertiary referral center and its affiliates where a cohort of 154 patients underwent LVAD implantation. This cohort of advanced chronic heart failure patients were then classified into either the ischemic or nonischemic study arms. Patients were monitored beginning 1 week prior to LVAD implantation and then surveilled 2 weeks, and 1, 2, 3, 4, 6, 9, and 12 months postimplantation with trans-thoracic echocardiography and a standardized set of functional parameters. These echo parameters were then compared between intragroup baselines and between the ICM and the NICM arms to determine if patients achieved a defined, operational sustained recovery.


The authors demonstrated that a significant number of patients (P=.034), 5% of ICM and 21% of NICM, achieved a left ventricular ejection fraction (LVEF) >40% when supported by LVAD unloading for 6 months or more, while controlling for significant differences in baseline clinical profiles with respect to age, diabetes mellitus, hypertension, baseline LVEF, and left ventricular end diastolic diameter (LVEDD), but no significant differences between baseline hemodynamic, biochemical profiles, or overall postimplantation pharmacologic regimens. Overall, LVEF significantly increased from 20% to 24% by 6 months in the ICM arm (P=.03) and from 17% to 27% by 9 months in the NICM arm (P<.01). Despite the significant changes from baseline LVEF, there was no significant difference between groups (unadjusted odds ratio: 0.67; 95% CI: 0.22 to 2.04; P=.49) when comparing the number of patients who achieved the operational sustained recovery, even when applying propensity score analysis (odds ratio: 0.77; 95% CI: 0.22 to 2.69; P=.68). There also was no significance between the ICM and NICM groups when analyzing maximum LVEF achieved post-LVAD implantation compared to baseline.

Significant decreases from baseline LV end-diastolic, end-systolic volumes, and LV mass index (P<.001) were noted in both groups. Additionally, diastolic function significantly improved for both groups with respect to LA volume index, septal E’, and E/E’ ratios following LVAD implantation.

Further analysis for the ICM group revealed no differences between pre-LVAD LVEF or maximum LVEF achieved and the duration of time between LVAD implantation from index ischemic events. Analysis with increased loading conditions showed improved function, but not significantly, for both the ICM and NICM patient groups with both systolic and diastolic parameters.


Mechanical unloading with LVAD implantation was shown to increase cardiac function via serial pre- and post-LVAD implantation echocardiographic exams in both a large NICM patient cohort and smaller cohort of ICM patients suffering from advanced chronic heart failure. This functional increase plateaued at 6 months postimplantation without evidence of functional regression for patients achieving functional improvement.


LVAD implantation is available for patients with advanced heart failure as a bridge to transplant, myocardial recovery, or as a destination therapy. A hypothesis of reverse remodeling is currently being elucidated with basic, translational, and clinical investigations. However, the majority of these investigations have concentrated on heart failure patients with nonischemic etiologies. ICM heart failure patients have largely been excluded from these studies due to the believed resultant irreversible scarring that prevent those patients from a similar recovery profile. This study aimed to elucidate the benefit of mechanical unloading via LVAD implantation on a large cohort of heart failure patients as a result of both ischemic and non-ischemic cardiomyopathies via serial echocardiographic examinations. Improvement with both LVEF and diastolic function were shown for both ICM and NICM patient cohorts, but a significant sustained functional recovery as defined by the authors was not demonstrated in either group.

There were some limitations to this study. First, there is acknowledgement in the difficulty to control for concomitant medical management and being able to demonstrate LVAD implantation as a mutually exclusive factor for functional recovery and reverse remodeling. Although there were no significant difference between cohorts’ pharmacologic regimens; the overall management and dosing regimens of the patients was ultimately left to the discretion of an outside provider. Additionally, it is particularly difficult to control for patient variability with respect to response and compliance to medical therapy.

Another limitation to the study is the temporal nature of the results and the attrition rate of the patient groups due to death, transplant, other postoperative complications, or inability to tolerate turn-down studies. At the longest time point there was a loss of 30 and 39 patients in the ICM and NICM arms, respectively, from the respective original 61 and 93 patients. With the attrition rate of patients, the authors decreased their ability to make robust claims at farther time points and further investigation, perhaps with a larger initial patient population through a larger multicenter investigation, may provide the necessary power to provide significance at the later time points.

Third, investigation of patient clinical status and echocardiographic results would provide additional support or refinement of the author’s definition of operational sustained recovery as there can be notable differences between a patient’s subjective clinical status and echo findings.