Bioactive adrenomedullin for assessment of venous congestion in heart failure

AIMS: Bioactive adrenomedullin (bio‐ADM) is a vascular‐derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio‐ADM for HF in comparison to amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), with decision thresholds derived from invasive haemodynamic and population‐based studies. METHODS AND RESULTS: Normal reference ranges for bio‐ADM were derived from a community‐based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio‐ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8–39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67–0.79) and 0.70 (95% CI = 0.64–0.75), respectively, with optimal bio‐ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT‐proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68–0.79] and 0.68 [95% CI = 0.61–0.75]). Bio‐ADM correlated with (mRAP, r = 0.55) while NT‐proBNP correlated with PAWP. Finally, a bio‐ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two‐fold increased odds of HF diagnosis, independently from NT‐proBNP. CONCLUSIONS: Bio‐ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT‐proBNP. Our findings support utility of bio‐ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.