Dataset Information

Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure.

ABSTRACT: BACKGROUND:Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1beta is associated with disease severity and clinical outcomes in chronic heart failure. METHODS AND RESULTS:Serum NRG-1beta was quantified in 899 outpatients in the Penn Heart Failure Study, a referral cohort representing a broad spectrum of systolic heart failure. Circulating NRG-1beta was significantly elevated in patients with worse disease severity (median, 6.2 ng/mL for New York Heart Association class IV versus 4.4 ng/mL for class I; P=0.002). In adjusted models, NRG-1beta was independently associated with an increased risk of death or cardiac transplantation over a median follow-up of 2.4 years (adjusted hazard ratio, 1.58; 95% confidence interval, 1.04 to 2.39; P=0.03 comparing fourth versus first NRG-1beta quartile). Associations with outcome differed by heart failure cause and symptom severity, with the strongest associations observed in patients with ischemic cardiomyopathy (interaction P=0.008) and New York Heart Association class III/IV symptoms (interaction P=0.01). These findings were all independent of brain natriuretic peptide, and assessment of NRG-1beta and brain natriuretic peptide jointly provided better risk stratification than each biomarker individually in patients with ischemic or New York Heart Association class III/IV heart failure. CONCLUSIONS:Circulating NRG-1beta is independently associated with heart failure severity and risk of death or cardiac transplantation. These findings support a role for NRG-1/ErbB signaling in human heart failure and identify serum NRG-1beta as a novel biomarker that may have clinical applications.

SUBMITTER: Ky B

PROVIDER: S-EPMC2741393 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure.

Ky Bonnie B Kimmel Stephen E SE Safa Radwan N RN Putt Mary E ME Sweitzer Nancy K NK Fang James C JC Sawyer Douglas B DB Cappola Thomas P TP

Circulation 20090713 4

<h4>Background</h4>Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1beta is associated with disease severity and clinical outcomes in chronic heart failure.<h4>Methods and results</h4>Serum NRG-1beta was quantified in 899 outpatients in the Penn Heart Failure ...[more]

PMID: 19597049

Similar Datasets

Project description:ImportanceChronic heart failure (CHF) is associated with increased sympathetic drive and may increase expression of the cotransmitter neuropeptide Y (NPY) within sympathetic neurons.ObjectiveTo determine whether myocardial NPY levels are associated with outcomes in patients with stable CHF.Design, setting, and participantsProspective observational cohort study conducted at a single-center, tertiary care hospital. Stable patients with heart failure undergoing elective cardiac resynchronization therapy device implantation between 2013 and 2015.Main outcomes and measuresChronic heart failure hospitalization, death, orthotopic heart transplantation, and ventricular assist device placement.ResultsCoronary sinus (CS) blood samples were obtained during cardiac resynchronization therapy (CRT) device implantation in 105 patients (mean [SD] age 68 [12] years; 82 men [78%]; mean [SD] left ventricular ejection fraction [LVEF] 26% [7%]). Clinical, laboratory, and outcome data were collected prospectively. Stellate ganglia (SG) were collected from patients with CHF and control organ donors for molecular analysis. Mean (SD) CS NPY levels were 85.1 (31) pg/mL. On bivariate analyses, CS NPY levels were associated with estimated glomerular filtration rate (eGFR; rs = -0.36, P < .001); N-terminal-pro hormone brain natriuretic peptide (rs = 0.33; P = .004), and LV diastolic dimension (rs = -0.35; P < .001), but not age, LVEF, functional status, or CRT response. Adjusting for GFR, age, and LVEF, the hazard ratio for event-free (death, cardiac transplant, or left ventricular assist device) survival for CS NPY ≥ 130 pg/mL was 9.5 (95% CI, 2.92-30.5; P < .001). Immunohistochemistry demonstrated significantly reduced NPY protein (mean [SD], 13.7 [7.6] in the cardiomyopathy group vs 31.4 [3.7] in the control group; P < .001) in SG neurons from patients with CHF while quantitative polymerase chain reaction demonstrated similar mRNA levels compared with control individuals, suggesting increased release from SG neurons in patients with CHF.Conclusions and relevanceThe CS levels of NPY may be associated with outcomes in patients with stable CHF undergoing CRT irrespective of CRT response. Increased neuronal traffic and release may be the mechanism for elevated CS NPY levels in patients with CHF. Further studies are warranted to confirm these findings.Trial registrationClinicalTrials.gov identifier: NCT01949246.

Project description:The purpose of this retrospective propensity score-matched study was to evaluate the superiority of different application approaches [continuous diuretics use (CDU) vs. intermittent diuretics use (IDU)] and types [loop diuretics (LDs) vs. thiazide diuretics (TDs)] of diuretics on long-term outcomes for rheumatic heart disease (RHD) patients with compensated chronic heart failure (CHF). A total of 494 RHD patients with compensated CHF were analysed after propensity score matching. Cox proportional hazards regression model was used to investigate the associations of different diuretic application approaches and types with all-cause mortality, cardiovascular death (CVD), and cerebrovascular death. Binary logistic regression analyses were used to evaluate the associations of different diuretic application approaches and types with 1-, 3-, and 5-year heart failure (HF) re-hospitalization as well as new-onset atrial fibrillation (AF). In the comparison between IDU and CDU strategies for RHD patients with compensated CHF, CDU was associated with increased risks of all-cause mortality [adjusted hazard ratio (HR) = 2.47, 95% confidence interval (CI): 1.54-3.97, P < 0.001] and CVD (adjusted HR = 3.67, 95% CI: 1.95-6.89, P < 0.001) except cerebrovascular death (adjusted HR = 1.07, 95% CI: 0.34-3.41, P = 0.905). CDU was also associated with increased risks of 3-year [adjusted odds ratio (OR) = 1.80, 95% CI: 1.09-2.96, P = 0.022] and 5-year (adjusted OR = 2.02, 95% CI: 1.18-3.45, P = 0.010) HF re-hospitalization risk and new-onset AF (adjusted OR = 2.34, 95% CI: 1.31-4.20, P = 0.004) except 1-year HF re-hospitalization risk (adjusted OR = 1.54, 95% CI: 0.88-2.70, P = 0.130). In the comparison between TDs and LDs among study participants receiving IDU strategy, LDs were only associated with decreased 1-year HF re-hospitalization risk (adjusted OR = 0.30, 95% CI: 0.12-0.77, P = 0.012) rather than all-cause mortality, CVD, cerebrovascular death, 3- and 5-year HF re-hospitalization, and new-onset AF (all adjusted P > 0.05). In the comparison between TDs and LDs among study participants receiving CDU strategy, LDs were not associated with cerebrovascular death and 1-year HF re-hospitalization (both adjusted P > 0.05) but with increased risks of all-cause mortality (adjusted HR = 1.80, 95% CI: 1.09-2.99, P = 0.023), CVD (adjusted HR = 1.89, 95% CI: 1.04-3.44, P = 0.037), 3-year (adjusted OR = 1.91, 95% CI: 1.06-3.43, P = 0.031) and 5-year (adjusted OR = 2.16, 95% CI: 1.12-4.19, P = 0.022) HF re-hospitalization, and new-onset AF (adjusted OR = 2.66, 95% CI: 1.25-5.68, P = 0.012). Continuous diuretics use (especially LDs) was associated with increased risks of all-cause mortality, CVD, medium-term/long-term HF re-hospitalization, and new-onset AF in RHD patients with compensated CHF.

Dataset Information

Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure.

Publications

Neuregulin-1 beta is associated with disease severity and adverse outcomes in chronic heart failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets