Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure

Nikola Kozhuharov,Leong L Ng ,Alexandre Mebazaa,Iain B Squire ,Andreas Bergmann,Oliver Hartmann,Zaid Sabti,Christian Puelacher,Pedro López-Ayala ,Tobias Zimmermann,Joachim Struck,Max J Rieger ,Jasmin Martin,Alice Blet,Danielle Menosi Gualandro,Eleni Michou,Mohamed Eltayeb,Desiree Wussler,Samyut Shrestha,Albina Nowak,Maria Belkin,Sabrina Stefanelli,Ivo Strebel,Tobias Breidthardt

doi:10.1007/s00392-021-01909-9

Abstract

BackgroundQuantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity.MethodsThis was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed.ResultsAmong 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57–2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001).ConclusionsQuantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

Highlights

Acute heart failure (AHF) is the most common cause of hospitalisation in patients 50 years or older, and it is still associated with unacceptably high mortality and morbidity [1, 2], Nikola Kozhuharov and Leong Ng have contributed and should be considered the first authors.Extended author information available on the last page of the article with up to 30% of patients dying within 1 year after hospital discharge [1]
A total of 1886 acute heart failure (AHF) patients enrolled between March 2006 and June 2015 were eligible for this analysis (Supplemental Fig. 1); 37.9% were women and the median age was 78 years (Table 1); 34.8% patients had HFpEF, 14.2% had HFmrEF, and 20.1% had HFrEF
Increased bioactive adrenomedullin (bio-ADM) concentrations were associated with increased risk of death at 365 days

Summary

Introduction

Acute heart failure (AHF) is the most common cause of hospitalisation in patients 50 years or older, and it is still associated with unacceptably high mortality and morbidity [1, 2], Nikola Kozhuharov and Leong Ng have contributed and should be considered the first authors.Extended author information available on the last page of the article with up to 30% of patients dying within 1 year after hospital discharge [1]. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/ mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Conclusions Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF

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