Bioactive Adrenomedullin for Assessment of Venous Congestion in Heart Failure

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Abstract
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.
Funding Information
  • Swedish Research Council (2017-02554)
  • Swedish Research Council (Dnr 2009-1039)
  • Swedish Research Council (Dnr 349-2006-237)
  • Swedish Foundation for Strategic Research (Dnr IRC15-0067)
  • Knut and Alice Wallenberg Foundation
  • Skåne University Hospital
  • Crafoord Foundation
  • European Research Council (ERC-STG-2015-679242)
  • Swedish Heart-Lung Foundation (2016-0134)
  • Swedish Heart-Lung Foundation (2016-0315)
  • Swedish Heart-Lung Foundation (2019-0526)
  • Stig and Ragna Gorthon Foundation (2020-2676)
  • Vetenskapsrådet (2017‐02554)
  • Vetenskapsrådet (Dnr 2009‐1039)
  • Vetenskapsrådet (Dnr 349‐2006‐237)
  • Stiftelsen för Strategisk Forskning (Dnr IRC15‐0067)
  • Knut och Alice Wallenbergs Stiftelse
  • Skånes universitetssjukhus
  • Crafoordska Stiftelsen
  • European Research Council (ERC‐STG‐2015‐679242)
  • Hjärt-Lungfonden (2016‐0134)
  • Hjärt-Lungfonden (2016‐0315)
  • Hjärt-Lungfonden (2019‐0526)

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