MO452: The Protecting Role of Renin-Angiotensin System Inhibitors on Renal Function and All-Cause Mortality in Patients With Heart Failure Supported by Left Ventricular Assist Devices: Analysis From the Intermacs Registry
Authors: Lombardi Gianmarco , Gambaro Alessia , Manuel Ferraro Pietro , Gambaro Giovanni 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Heart failure (HF) is a clinical problem highly prevalent in the general population (1–2%) and much more so among patients with chronic kidney disease (CKD) (17–21%). The left ventricular assist device (LVAD) is a type of mechanical circulatory support device (MCSD) used to support heart function in severe HF patients. CKD is often observed in patients requiring LVAD implantation in the well-known clinical setting of the cardio-renal syndrome (CRS). Although implanting an LVAD may alleviate CRS, it can also be responsible for renal damage in the long term. The lack of pulsatility on most LVADs seems to have important effects on sympathetic activity and renin-angiotensin system (RAS) activation. This physiological phenomenon, confirmed in experimental models, could be responsible for renal damage often observed in such a complex population. The aim of our study was to investigate the effect of RASi therapy on long-term renal outcomes and mortality in patients with HF supported by LVAD.

METHOD
We performed a retrospective observational study on LVAD patients collected in the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) registry (North American multicentre prospective database of data for adults who received an FDA approved mechanical circulatory support device (MCSD) due to advanced heart failure).
After LVAD implantation all patients were followed for at least a 3-months window period. We included all adult patients (aged ≥ 18 years) who underwent implantation of the first permanent CF-LVAD device from 2006 to 2017. Only patients with normal renal function [estimated glomerular filtration rate (eGFR) &gt; 60 mL/min/1.73 m2] or with mild renal impairment (eGFR 45–60 mL/min/1.73 m2) at 3 months after LVAD implantation were included in the analysis.
The main outcome of interest was a composite of all-cause mortality and renal events. Secondary, we investigated secondary outcomes, all-cause mortality and renal events, taken separately. The renal event was defined as a composite of doubling sCr, eGFR drop ≥ 40%, need for dialysis. The primary exposure of interest was RASi therapy at the start and during the follow-up period.
Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the association between RASi therapy and the main outcomes of interest. Given that the RASi therapy that patients receive, MAP and eGFR change over time, we treated these variables as a time-dependent variable in a Cox proportional hazards regression.

RESULTS
During a median follow-up of 12.6 months (IQR 5.3, 24.7), 1356 patients developed the main composite outcome of interest. RASi therapy was associated with a reduced risk of the composite outcome. A significant association was observed both in unadjusted and multivariable-adjusted models (Table 1). The significant association was also confirmed for renal outcomes (HR 0.79, 95% CI 0.65, 0.97, P = 0.022, Table 1) and all-cause mortality (HR 0.54, 95% CI 0.48, 0.61, P &lt; 0.001, Table 1), taken separately.

CONCLUSION
This study demonstrates for the first time the protective role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD. In patients with preserved or mild impairment renal function, RASi medication significantly improve kidney outcome.