Clinical Framework for the Staging of Reverse Cardiac Remodeling with Mechanical Unloading and Circulatory Support

Abstract

The variability of left ventricular structural and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is poorly understood. The study consecutively enrolled 358 patients with confirmed chronic heart failure who required a durable LVAD across four study sites. Echocardiograms were performed preceding LVAD implantation and serially up to a year after. Patients were categorized by the degree of structural (left ventricular internal diastolic diameter, LVIDd) and functional (left ventricular ejection fraction, LVEF) change after LVAD. In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥40% and LVIDd ≤6.0cm and were termed responders. The rest of the patients were distinguished in 3 groups based on the absolute change (Δ) in LVEF during follow up: Partial Responders had Δ-LVEF ≥10% (n=57, 16%), Borderline Responders Δ-LVEF 5-10% (n=55, 15%), Non-Responders Δ-LVEF <5% (n=212, 59%, Figure). The LVEF absolute change following mechanical unloading was: -3.2±5.9%, 6.3±1.4%, 15.5±5.4%, 27.7±9.7% in Non-Responders, Borderline Responders, Partial Responders and Responders, respectively (p<0.001). Structural changes in terms of LV dimensions followed a different pattern with significant improvements even in patients that had minimal systolic functional improvement. Multivariate logistic regression identified the following clinical characteristics as predictive of favorable reverse myocardial remodeling: smaller pre-LVAD implantation LVIDd, use of an axial flow device, and shorter heart failure duration preceding LVAD implant. Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and manifests in a continuous spectrum. Defining four stages across this continuum can inform clinical management and facilitate advancing the field of myocardial plasticity by informing the design of future investigations.