adrenomedullin and Hyperemia

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.. 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.. 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.

Topics: Adrenomedullin; Biomarkers; Heart Failure; Humans; Hyperemia; Prognosis

This study was designed to investigate the pathophysiological significance of adrenomedullin (AM) concentration in volume- and pressure-overloaded cardiac hypertrophy. We measured ventricular AM concentrations and compared them with changes of alpha-actin and myosin heavy chain (MHC) mRNA isoforms after the creation of an aortocaval (AC) shunt as a volume-overload model or the injection of monocrotaline (MCT) as a pressure-overload model, respectively. The left ventricular AM levels after the creation of AC shunt and the right ventricular AM levels after the injection of MCT were significantly increased and correlated with changes of the alpha-actin and MHC mRNA isoforms. However, the ventricular AM mRNA expressions were increased and correlated with ventricular AM concentrations only in the AC shunt model. These results suggest that the ventricular AM levels are upregulated in both the volume- and pressure-overloaded cardiac hypertrophy by differential transcriptional regulation and that the ventricular AM may be a biochemical marker for the volume and pressure overload to the ventricle.

Topics: Adrenomedullin; Animals; Biomarkers; Gene Expression; Heart Ventricles; Hemodynamics; Hyperemia; Hypertension; Immunohistochemistry; Male; Myocardium; Osmolar Concentration; Peptides; Rats; Rats, Wistar; RNA, Messenger