endothelin-1 and Heart-Failure--Systolic

To define the role of single or serial measurement of endothelin 1 (ET-1) for prognostication beyond traditional and modern markers of risk in heart failure (HF).. In total, 115 patients with chronic systolic HF were followed for 10 months. Clinical assessment and ET-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), highly sensitive troponin I (hsTnI), soluble ST2 (sST2), and galectin 3 were measured at each visit.. Elevated ET-1 was associated with worse HF, lower right ventricular function, higher pulmonary pressure, and higher left atrial volume index despite similar left ventricular function. ET-1 correlated with angiotensin-converting enzyme inhibitor use. A model containing traditional risk factors, ET-1, NT-proBNP, hsTnI, and sST2 best predicted cardiovascular events, and ET-1 improved reclassification. In an adjusted time-integrated model, percent time spent with ET-1 of 5.90 pg/mL or less was predictive of fewer cardiovascular events (odds ratio, 0.75; 95% confidence interval, 0.62-0.91). ET-1 reduction over time was associated with a lower rate of cardiovascular events compared with increasing or stable ET-1 (24.4% vs 50.0%).. ET-1 may be a unique predictor of HF prognosis, complementing other biomarkers in a multimarker profile. Serial measurement of ET-1 may provide additional prognostic information.

Topics: Aged; Biomarkers; Chronic Disease; Echocardiography; Endothelin-1; Female; Heart Failure, Systolic; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models

Neurohormonal activation is a pathophysiological hallmark of acute and chronic heart failure (HF). The clinical significance of more recently discovered endogenous vasoactive hormones has not been well-characterized.. In 154 subjects with stable, chronic systolic HF (New York Heart Association Class I-IV, left ventricular [LV] ejection fraction or=12.1 pM (HR: 2.02, 95% CI: 1.08-3.93, P = .029) and ET-1 >or=2.29 pM (HR: 2.52, 95% CI: 1.24-5.03, P = .011) remained significant independent risk factors for adverse clinical events.. Higher levels of plasma levels of UCN-1 and ET-1 but not UT-II were associated with worse LV diastolic performance and poorer long-term clinical outcomes in patients with chronic systolic HF.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Corticotropin-Releasing Hormone; Endothelin-1; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Prospective Studies; Urocortins

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

Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aimed to characterize ET-1 and transpulmonary aldosterone levels in HFrEF and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2).. Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively.. Radial ET-1 levels (median [interquartile range]) were higher in HFrEF patients compared with controls (17.5 [11.5-31.4] vs 11.5 [4.4-19.0] pg/ml, p = 0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (p < 0.001) but not in controls (p = 0.24). Compared with controls, aldosterone levels (median [interquartile range]) were increased in HFrEF patients in the PA (364 [250-489] vs 581 [400-914] ng/dl, p < 0.01) and radial compartments (366 [273-466] vs 702 [443-1223] ng/dl, p < 0.001). Akin to ET-1, a transpulmonary increase (median [interquartile range]) in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [-54 to 40] vs 61.6 [-13.6 to 165] ng/dl, p = 0.01) and peak exercise (-20.7 [-39.6 to 79.1] vs 25.8 [-29.2 to 109.3] ng/dl, p = 0.02). The adjusted pVO2 correlated inversely with aldosterone levels at peak activity in the PA (r = -0.31, p = 0.01) and radial artery (r = -0.32, p = 0.01).. These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone and pVO2. Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve capacity in HFrEF.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldosterone; Endothelin-1; Exercise; Female; Fractional Flow Reserve, Myocardial; Heart Failure, Systolic; Humans; Male; Middle Aged; Pilot Projects; Pulmonary Artery; Retrospective Studies; Young Adult