STOP-HF Trial: Higher Endogenous BNP and Cardiovascular Protection in Subjects at Risk for Heart Failure.
Ontology highlight
ABSTRACT:
SUBMITTER: Cannone V
PROVIDER: S-EPMC8246026 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure.We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure.Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001).Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.
| S-EPMC4703764 | biostudies-literature
Project description:AimsThe globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date.Methods and resultsWe looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.6 (95% CI 11.7-15.7) WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions.ConclusionThere were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
| S-EPMC5106574 | biostudies-literature
Project description:BackgroundAccording to the current guidelines, implantable cardioverter-defibrillators (ICD) for primary prevention in patients with heart failure and reduced ejection fraction (HFrEF) should not be considered until optimal guideline-directed medical therapy (GDMT) has been achieved for a minimum of 3 months. Optimization of GDMT often needs time beyond 3 months after diagnosis. The aim of the Heart Failure Optimization Study (HF-OPT) is to evaluate the recovery of left ventricular function beyond 3 months after diagnosis of newly diagnosed HFrEF.MethodsThe HF-OPT multicenter study is comprised of two non-randomized phases (registry and study). During the first 90 days a wearable cardioverter-defibrillator (WCD) is prescribed and patients are enrolled in an observational pre-study registry. Registry subjects meeting inclusion criteria for the study portion at day 90 have ongoing left ventricular ejection fraction (LVEF) reassessment at 90, 180 and 360 days after the index hospital discharge, regardless of continued WCD use. Approximately 600 subjects will be enrolled in the study portion. Of those, one-third are anticipated to start the study phase at day 90 with reduced LVEF. The primary objective of this study is to observe the rate of recovery of LVEF > 35% between 90 and 180 days, while key secondary endpoints include mortality and WCD recorded arrhythmias and shocks.DiscussionThe HF-OPT study will provide important information on the rate of additional recovery of LVEF > 35%, between 90 and 180 days, in newly diagnosed HF with reduced LVEF patients being titrated with GDMT. The results of the study may impact indications for primary prophylactic ICD implantation.
| S-EPMC9950163 | biostudies-literature
Project description:B-type natriuretic peptide (BNP) has prognostic significance in heart failure (HF), and reductions in BNP may predict clinical improvement. However, there are limited data regarding the prognostic value of BNP during short-term follow-up. The aim of this study was to evaluate the relationship between short-term follow-up BNP and mortality after discharge in patients with HF.We analyzed 427 patients hospitalized with HF from the Wonju Severance Christian Hospital Heart Failure Registry from April 2011 to December 2013, with a planned follow-up period through February 2016. Of the 427 patients, 240 (mean age, 75 years; 102 males, 42.5%) had BNP measured on admission and within the short-term follow-up period (3 months). We compared all-cause mortality during the clinical follow-up period (median length of follow-up, 709.5 days) according to the median value of BNP on admission (as a baseline value) and over a short-term follow-up period after discharge.Median BNP at admission was 816.5 pg/ml, and median follow-up BNP was 369.7 pg/ml. Multivariate analysis revealed a positive association between risk of death and high BNP. High BNP during follow-up was significantly associated with a greater risk of all-cause mortality compared to low BNP (P < 0.001). Initial BNP was not significantly associated with all-cause mortality. A multivariate model showed that follow-up BNP and percent change in BNP were independently associated with all-cause mortality after adjustment for covariates. Of the 3 BNP measurement strategies, BNP after discharge (IDI of 0.072, P < .0001 and NRI of 0.707, P < .0001) and percent change in BNP (IDI of 0.113, P < .0001 and NRI of 0.782, P < .0001) demonstrated the greatest increase in discrimination and net reclassification for mortality. Unfortunately, we did not find any significant value with initial BNP. Kaplan-Meier survival analysis was performed to assess mortality stratified by BNP according to the median value, high median of follow-up BNP and percent change in BNP were associated with significantly higher mortality compared to the below median (log-rank, p < 0.001).Short-term follow-up BNP and percent change in BNP level are significant prognostic factors of all-cause mortality. These values will be clinically useful when evaluating prognosis in hospitalized patients with heart failure.
| S-EPMC5543427 | biostudies-other
Project description:AimsCeramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.Methods and resultsIn a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure (GISSI-HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow-up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high-risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin-3 levels, and, especially, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P-threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).ConclusionsHigher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT-proBNP concentrations.
| S-EPMC7754905 | biostudies-literature
Project description:BackgroundThe ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides.MethodsWe examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746). The primary outcome was a composite of heart failure hospitalization or cardiovascular death.ResultsCompared with the lowest tertile of baseline ucGMP/BNP ratio, patients in the higher tertiles had a lower risk of the primary outcome (tertile 1, reference; tertile 2, hazard ratio 0.57 [95% CI, 0.45-0.71]; tertile 3, hazard ratio, 0.54 [0.43-0.67]). Compared with baseline, the ucGMP/BNP ratio at 1 month and 8 months after randomization was higher with sacubitril/valsartan than with enalapril: ratio of geometric mean ratios at 1 month, 1.38 (95% CI, 1.27-1.51) and 8 months, 1.32 (95% CI, 1.20-1.45), and this difference was consistent across tertiles of ucGMP/BNP ratio at baseline (Pinteraction=0.19 and 0.91, respectively). The effect of sacubitril/valsartan, compared with enalapril, was consistent across tertiles of ucGMP/BNP ratio at baseline for all outcomes (Pinteraction ≥0.31).ConclusionsIn patients with heart failure and reduced ejection fraction, higher ucGMP/BNP ratio was associated with better outcomes. Sacubitril/valsartan increased the ucGMP/BNP ratio, compared with enalapril, and the effect of sacubitril/valsartan on clinical outcomes was not modified by baseline ucGMP/BNP ratio.RegistrationURL: https://www.Clinicaltrialsgov; Unique Identifier: NCT01035255.
| S-EPMC10022671 | biostudies-literature
Project description:N-terminal pro-brain natural peptide (NT-pro-BNP) is a well-established biomarker of tissue congestion and has prognostic value in patients with heart failure (HF). Nonetheless, there is scarce evidence on its predictive capacity for HF re-admission after an acute coronary syndrome (ACS). We performed a prospective, single-center study in all patients discharged after an ACS. HF re-admission was analyzed by competing risk regression, taking all-cause mortality as a competing event. Results are presented as sub-hazard ratios (sHR). Recurrent hospitalizations were tested by negative binomial regression, and results are presented as incidence risk ratio (IRR). Of the 2133 included patients, 528 (24.8%) had HF during the ACS hospitalization, and their pro-BNP levels were higher (3220 pg/mL vs. 684.2 pg/mL; p < 0.001). In-hospital mortality was 2.9%, and pro-BNP was similarly higher in these patients. Increased pro-BNP levels were correlated to increased risk of HF or death during the hospitalization. Over follow-up (median 38 months) 243 (11.7%) patients had at least one hospital readmission for HF and 151 (7.1%) had more than one. Complete revascularization had a preventive effect on HF readmission, whereas several other variables were associated with higher risk. Pro-BNP was independently associated with HF admission (sHR: 1.47) and readmission (IRR: 1.45) at any age. Significant interactions were found for the predictive value of pro-BNP in women, diabetes, renal dysfunction, STEMI and patients without troponin elevation. In-hospital determination of pro-BNP is an independent predictor of HF readmission after an ACS.
| S-EPMC8069470 | biostudies-literature
Project description:ObjectivesThis study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF.BackgroundThe endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload.MethodsANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study's goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3',5'cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects.ResultsIn cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003).ConclusionsAmong a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.
| S-EPMC6778016 | biostudies-literature
Project description:BackgroundPatients with heart failure (HF) and reduced ejection fraction will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (ie, first and repeat) hospitalizations for heart failure in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure).MethodsThe total number of HF hospitalizations and cardiovascular deaths was examined by using the proportional-rates approach of Lei-Wei-Yang-Ying and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable Lei-Wei-Yang-Ying model.ResultsOf 2371 participants randomly assigned to placebo, 318 experienced 469 hospitalizations for HF; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model, factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. In the Lei-Wei-Yang-Ying model, the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or cardiovascular death was 0.75 (95% CI, 0.65-0.88), P=0.0002. In the joint frailty model, the rate ratio for total HF hospitalizations was 0.71 (95% CI, 0.61-0.82), P<0.0001, whereas, for cardiovascular death, the hazard ratio was 0.81 (95% CI, 0.67-0.98), P=0.0282.ConclusionsDapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HF and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
| S-EPMC8126492 | biostudies-literature
Project description:AimsCirculating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF).Methods and resultsPIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome.ConclusionBiomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks.Clinical trials registrationNCT02554890 clinical.trials.gov.
| S-EPMC6801941 | biostudies-literature