TARGET-LOAD Pilot Study Comparing Hemodynamics-guided LVAD Unloading Vs. Standard of Care

Overview

This study is a prospective, randomized-controlled, non-blinded, multi-center, pilot trial to compare standard-of-care left ventricular assist device (LVAD) unloading plus heart failure (HF) medications reverse-remodeling management versus hemodynamics-guided LVAD unloading with use of the wireless monitoring system CardioMEMS plus HF medications reverse-remodeling management.

LVADs are being increasingly used in end-stage heart failure patients as a bridge to transplant (BTT) or as a destination therapy (DT). Although LVAD recipients are considered to be optimally unloaded with speed optimizations following LVAD implantation, re-hospitalizations due to HF recurrence are far from negligible. Recent studies have reported that at least 35% of hospital readmissions post-LVAD implantation are due to HF exacerbations, volume status changes or other cardiac causes (arrhythmias etc.). This suggests that patients are being sub-optimally unloaded and/or taking inadequate medical therapy and probably this decreases the chances for potential reverse remodeling and myocardial recovery. Moreover, a recent study demonstrated that cardiac dimensions obtained from echocardiography do not adequately reflect the degree of mechanical unloading of the heart. It has also shown strong evidence that pulmonary artery (PA) pressures monitoring can be reliably used to assess the pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP). Symptomatic heart failure exacerbation requiring hospital admission may lie at the end of a spectrum of worsening hemodynamics that are unable to be detected before the manifestation of symptoms and limits the potential for myocardial recovery. Therefore, it is proposed that repeatedly adjusting LVAD pump flow speed and tailoring standard HF medications depending on the patient's PA pressure acquired from the CardioMEMS device can optimize pressure and volume unloading and promote reverse cardiac remodeling and recovery. Clinical experience with LVAD support has shown that a subset of LVAD patients can experience reverse cardiac remodeling and significant improvement of myocardial function suggesting that LVAD-induced mechanical unloading of the failing heart may be a plausible therapeutic strategy aiming at myocardial recovery and device removal. These explanted patients have shown "myocardial plasticity" in clinical studies and that they can be responsive and sensitive to load changes. These patients will be carefully monitored to prevent increased load and wall stress to drive again the detrimental spiral of cardiac remodeling and HF recurrence, which appears to be the case in at least one third of LVAD patients after device weaning. Along the same lines, the results from another clinical study showed a significant and large reduction in hospitalization for HF patients who were managed with CardioMEMS. Therefore, further improvement of patients' HF management will depend mainly on better identification and pro-active management of their fluid and hemodynamic status. It is proposed that chronically adjusting HF medications using CardioMEMS-guided hemodynamic assessment in patients who have weaned from LVAD support could improve long-term durability of cardiac improvement after LVAD weaning.

Conditions

Interventions

Eligibility

Locations (2)

Outcomes