adrenomedullin and Mitral-Valve-Insufficiency

Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.. A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up.. Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54).. Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Endothelin-1; Female; Glycopeptides; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prognosis; Protein Precursors; Risk Assessment; Stroke Volume

Topics: Adrenomedullin; Aged; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Severity of Illness Index

Adrenomedullin (AM), a peptide identified to have vasodilating and natriuretic effects, is involved in the regulation of the cardiovascular system. To evaluate plasma AM concentration in dogs with myxomatous mitral valvular disease (MMVD), and to investigate the associations between the concentrations of plasma AM and natriuretic peptides and the echocardiographic data, we evaluated plasma AM concentrations in 31 healthy control dogs and 57 dogs with MMVD. Plasma AM concentrations in dogs with MMVD were higher than that in the control subjects. The plasma AM concentration increased in conjunction with the severity of heart failure according to the International Small Animal Cardiac Health Council (ISACHC). The AM concentrations were 25.1 ± 5.0 fmol/ml (ISACHC class Ia), 29.9 ± 11.0 fmol/ml (ISACHC class Ib), 43.4 ± 19.8 fmol/ml (ISACHC class II) and 73.5 ± 21.7 fmol/ml (ISACHC class III) and 7.5 ± 5.1 fmol/ml (control group), respectively. The receiver operating characteristic curve indicated an area of 0.93 (95% CI, 0.8801-0.9889; <0.0001), a cutoff value of 30.5 fmol/ml, a sensitivity of 87.1%, and a specificity of 82.5% for the determination of congestive heart failure. Plasma AM concentrations correlated with atrial natriuretic peptide concentrations, LA/Ao ratio, and left ventricular diameter. In conclusion, AM may be a potential diagnostic marker for canine MMVD and possibly plays a pathophysiological role in collaboration with the other neurohumoral factors such as natriuretic peptides.

Topics: Adrenomedullin; Age Factors; Animals; Dog Diseases; Dogs; Echocardiography; Female; Linear Models; Male; Mitral Valve Insufficiency; Natriuretic Peptides; ROC Curve; Species Specificity

The purposes of this study were to determine the tissue distribution of canine adrenomedullin (AM) and to determine whether increased canine AM mRNA expression is associated with congestive heart failure (CHF) due to mitral regurgitation (MR). Canine AM mRNA expression was detectable in various normal tissues, including cardiovascular tissues. In addition, the AM mRNA expression in the left atrium of dogs with MR was significantly higher than that in normal subjects. In conclusion, AM is a potential neurohumoral factor in dogs with CHF due to MR.

Topics: Adrenomedullin; Animals; Atrial Natriuretic Factor; Dog Diseases; Dogs; Gene Expression; Heart Failure; Mitral Valve Insufficiency; Myocardium; Natriuretic Peptide, Brain; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric

Adrenomedullin is an intrinsic vasodilator which is metabolized mainly in the pulmonary circulation. We measured plasma levels of adrenomedullin in children with congenital cyanotic heart disease (CY group, n = 6), children with high pulmonary blood flow due to congenital heart disease (PH group, n = 8), and in adults with mitral valve disease (MV group, n = 7) before and 3 h after cardiopulmonary bypass (CPB). Before CPB, the adrenomedullin level was the highest in the MV group, possibly due to chronic heart failure. Three hours after CPB, the plasma adrenomedullin level (pg/ml) increased to 1712.7 +/- 498.4 in the CY group, 167.6 +/- 26.4 in the PH group, and 1404.3 +/- 313.7 in the MV group, the level in the PH group being significantly lower than the rest. In the PH group, there was statistically significant negative correlation between the mean pulmonary arterial pressure at the preoperative catheter study, and the adrenomedullin level 3 h after CPB. These results illustrate that the adrenomedullin level increased after CPB, but that the increase was less marked in the PH group, implying that where the pulmonary vasculature was damaged most, this results in increased vasoconstriction.

Topics: Adrenomedullin; Adult; Aged; Cardiopulmonary Bypass; Child, Preschool; Female; Heart Failure; Humans; Infant; Male; Middle Aged; Mitral Valve Insufficiency; Peptides; Postoperative Complications; Vasoconstriction