Reverse Remodeling With Neurohormonal Blockade Following Left Ventricular Assist Device Implantation

Abstract

<h3>Introduction</h3> Mechanical unloading with an LVAD can induce myocardial reverse remodeling. Neurohormonal blockade (NHB) reduces mortality in LVAD patients, and NHB exposure (dose/duration) may further contribute to reverse remodeling in the presence of LVAD. <h3>Hypothesis</h3> Among durable LVAD recipients, reduction in LVEDD and NT-proBNP will be associated with total NHB exposure with beta blockers (BB), inhibitors of renin-angiotensin aldosterone system (RAASi), and mineralocorticoid receptor antagonists (MRA). <h3>Methods</h3> This multicenter, retrospective, cohort study included ambulatory LVAD recipients from 2010-2020. To capture total NHB exposure, drug and dose were collected at 7-, 30-, 90-, and 180-days post-implant and transformed to percentage of target dose based on practice guidelines. Percentage target dose at each time point was used to calculate an area under the curve (AUC) for each drug class based on the trapezoidal rule. The maximum possible AUC for each drug class at 3 and 6 months was 86.5 and 176.5, respectively. Each AUC was entered into multivariable linear regression models to assess their association with LVEDD and NT-proBNP at 3- and 6-months post-implant. Age, sex, HF etiology, pre-LVAD LVEDD, pre-LVAD serum creatinine, presence of ICD, and pre-LVAD NT-proBNP were selected as <i>a priori</i> covariates. <h3>Results</h3> A total of 262 patients were included. Median age was 57.1 (IQR 49-65) years. Most patients were white (58.5%) and male (80.5%), had nonischemic cardiomyopathy (60.3%), and received an HVAD (57.6%). At 6 months of follow-up, 74% were on RAASi, 78.6% on BB, and 71.6% on MRA. NT-proBNP was lower in patients on NHB, and LVEDD was lower in those on BB (Table 1). At 3 months, median AUC exposure for RAASi, BB, and MRA was 10.8, 5.5, and 50.8, respectively. At 6 months, the exposure was 16.9, 17.8, and 116.5. In multivariate analysis, RAASi AUC was independently associated with reduced LVEDD at 6 months (ß-coefficient, -0.01; 95% CI, -0.01, -0.001; p=0.046). For NT-proBNP, MRA AUC was associated with a decrease at 3 months (ß-coefficient, -34.04; 95% CI, -67.59, -0.49; p=0.047). There was no association with decreased NT-proBNP at 6 months. <h3>Conclusions</h3> Exposure to NHB within 6 months post-LVAD implant may be associated with reverse remodeling. Longer follow-up and higher NHB exposure are needed to adequately assess the impact of NHB on LV remodeling in the presence of LVAD.