P2617Activity of the adrenomedullin system to personalize post-discharge treatment in acute heart failure

Abstract

Abstract Objectives Activity of the adrenomedullin system was quantified by using bioactive-adrenomedullin (bio-ADM), the biologically active moiety, and midregional proadrenomedullin (MR-proADM), a prohormone fragment, to 1) identify acute heart failure (AHF) phenotypes with disproportional benefit or harm from specific treatments at hospital discharge, 2) predict mortality, and 3) compare the prognostic utility of both biomarkers. Methods This prospective multicentre study using central adjudication of AHF measured bio-ADM in all patients and MR-proADM in a predefined subgroup in a blinded fashion on admission. Both biomarkers were measured at discharge as well. Interaction with specific treatments at hospital discharge and the biomarkers' prognostic utility during 365 days' follow-up were assessed. Results Among 1,886 patients with adjudicated AHF, 514 patients (27.3%) died during the 365 days' follow-up. Patients with bio-ADM plasma concentrations above the median were at a much higher risk of death (HR 1.87, 95% CI 1.57–2.24; p<0.001). After adjusting for age, creatinine plasma concentrations, and medical treatment at discharge, those patients derived disproportional benefit if treated with diuretics and/or angiotensin-converting-enzyme inhibitors/angiotensin receptor blocker (interaction p-values <0.05). These findings were confirmed only for the diuretics treatment when quantifying the adrenomedullin system using MR-proADM plasma concentrations (n=764). For predicting mortality, both biomarkers performed well and MR-proADM had a higher predictive accuracy as compared to bio-ADM (p<0.001). Table 1. Interaction p-values in multivariate models using a cox proportional hazard analysis for predicting all-cause mortality at 365 days including age, bio-ADM or MR-proADM, creatinine at discharge, and medication at discharge Diuretics ACE inhibitors or ARB Beta blockers Aldosterone antagonists lg bio-ADM*, ng/l <0.001 0.011 0.760 0.175 lg bio-ADM†, ng/l <0.001 0.020 0.807 0.396 lg MR-proADM*, nmol/l 0.031 0.095 0.169 0.441 lg MR-proADM†, nmol/l 0.001 0.126 0.741 0.272 *At admission; †at discharge. ACE: Angiotensin-converting-enzyme; ARBs: Angiotensin receptor blocker; bio-ADM: bioactive adrenomedullin; MR-proADM: midregional proadrenomedullin. Figure 1 Conclusion Quantifying the activity of the adrenomedullin system helps to personalize post-discharge treatment and risk-prediction in AHF. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, University of Base, Sphingotec