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Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

ABSTRACT: Importance:Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective:To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants:Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions:Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n?=?386) or usual care (n?=?402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures:The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results:Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P?=?.59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance:Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration:ClinicalTrials.gov Identifier: NCT00512759.

SUBMITTER: Kozhuharov N

PROVIDER: S-EPMC6990838 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Kozhuharov Nikola N Goudev Assen A Flores Dayana D Maeder Micha T MT Walter Joan J Shrestha Samyut S Gualandro Danielle Menosi DM de Oliveira Junior Mucio Tavares MT Sabti Zaid Z Müller Beat B Noveanu Markus M Socrates Thenral T Ziller Ronny R Bayés-Genís Antoni A Sionis Alessandro A Simon Patrick P Michou Eleni E Gujer Samuel S Gori Tommaso T Wenzel Philip P Pfister Otmar O Conen David D Kapos Ioannis I Kobza Richard R Rickli Hans H Breidthardt Tobias T Münzel Thomas T Erne Paul P Mueller Christian C Mueller Christian Erne Paul Müller Beat Rickli Hans Maeder Micha Tavares de Oliveira Mucio Münzel Thomas Bayés-Genís Antoni Sionis Alessandro Goudev Assen Dimov Bojidar Hartwiger Sabine Arenja Nisha N Glatz Bettina Herr Natascha Isenrich Rahel Mosimann Tamina Twerenbold Raphael Boeddinghaus Jasper Nestelberger Thomas Puelacher Christian Freese Michael Vögele Janine Meissner Kathrin Martin Jasmin Strebel Ivo Wussler Desiree Schumacher Carmela Osswald Stefan Vogt Fabian Hilti Jonas Barata Sara Schneider Deborah Schwarz Jonas Fitze Brigitte Hartwiger Sabine Arenja Nisha Glatz Bettina Herr Natascha Isenrich Rahel Mosimann Tamina Twerenbold Raphael Boeddinghaus Jasper Nestelberger Thomas Puelacher Christian Freese Michael Vögele Janine Meissner Kathrin Martin Jasmin Strebel Ivo Wussler Desiree Schumacher Carmela Osswald Stefan Vogt Fabian Hilti Jonas Barata Sara Schneider Deborah Schwarz Jonas Fitze Brigitte Arenja Nisha Rentsch Katharina Bossa Aline Jallad Sergio Soeiro Alexandre Georgiev Dimitar Jansen Thomas Gebel Gabriele Bossard Matthias Christ Michael

JAMA 20191201 23

<h4>Importance</h4>Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).<h4>Objective</h4>To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF.<h4>Design, setting, and participants</h4>Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF ...[more]

PMID: 31846016

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Project description:AimsThe aim of this study is to determine the impact of diabetes mellitus on all-cause mortality and rehospitalization rates at 3 months and at 1 year in patients admitted with acute heart failure (AHF) stratified by left ventricular ejection fraction (EF).Methods and resultsWe analysed consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012 with AHF who were enrolled in Gulf CARE, a multinational registry of patients with heart failure (HF). AHF patients were stratified into three groups: HF patients with reduced (EF) (HFrEF) (<40%), HF with mid-range EF (HFmrEF) (40-49%), and HF patients with preserved EF (HFpEF) (≥50%). Analyses were performed using univariate and multivariate statistical techniques. The mean age of the cohort was 59 ± 15 years (ranging from 18 to 99 years), and 63% (n = 2887) of the patients were males. A total of 2258 (49%) AHF patients had diabetes mellitus. The mean EF was 37 ± 14%. A reduced EF was observed in 2683 patients (59%), whereas 962 patients (21%) had mid-range and 932 patients (20%) had preserved EF. Multivariable analyses demonstrated no significant differences in all-cause mortality between diabetics and non-diabetics in all the three types of HF; at 3 months follow-up: HFrEF [adjusted odds ratio (aOR), 1.30; 95% confidence interval (CI): 0.94-1.80; P = 0.119], HFmrEF (aOR, 0.98; 95% CI: 0.51-1.87; P = 0.952), and HFpEF (aOR, 0.69; 95% CI: 0.38-1.26; P = 0.225); and at 12-months follow-up: HFrEF (aOR, 1.25; 95% CI: 0.97-1.62; P = 0.080), HFmrEF (aOR, 1.07; 95% CI: 0.68-1.68; P = 0.783), and HFpEF (aOR, 1.07; 95% CI: 0.67-1.72; P = 0.779). There were also no significant differences in rehospitalization rates between diabetics and non-diabetics in all the three types of HF; at 3 months follow-up: HFrEF (aOR, 0.94; 95% CI: 0.74-1.19; P = 0.581), HFmrEF (aOR, 0.82; 95% CI: 0.53-1.26; P = 0.369), and HFpEF (aOR, 1.06; 95% CI: 0.64-1.78; P = 0.812); and at 12-months follow-up: HFrEF (aOR, 0.93; 95% CI: 0.73-1.17; P = 0.524), HFmrEF (aOR, 0.81; 95% CI: 0.56-1.17; P = 0.257), and HFpEF (aOR, 1.29; 95% CI: 0.82-2.05; P = 0.271).ConclusionsThere were no significant differences in 3 and 12 months all-cause mortality as well as rehospitalization rates between diabetics and non-diabetic patients in all the three types of AHF patients stratified by left ventricular ejection fraction.

Project description:AimsThis study aimed to review the performance of machine learning (ML) methods compared with conventional statistical models (CSMs) for predicting readmission and mortality in patients with heart failure (HF) and to present an approach to formally evaluate the quality of studies using ML algorithms for prediction modelling.Methods and resultsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search using MEDLINE, EPUB, Cochrane CENTRAL, EMBASE, INSPEC, ACM Library, and Web of Science. Eligible studies included primary research articles published between January 2000 and July 2020 comparing ML and CSMs in mortality and readmission prognosis of initially hospitalized HF patients. Data were extracted and analysed by two independent reviewers. A modified CHARMS checklist was developed in consultation with ML and biostatistics experts for quality assessment and was utilized to evaluate studies for risk of bias. Of 4322 articles identified and screened by two independent reviewers, 172 were deemed eligible for a full-text review. The final set comprised 20 articles and 686 842 patients. ML methods included random forests (n = 11), decision trees (n = 5), regression trees (n = 3), support vector machines (n = 9), neural networks (n = 12), and Bayesian techniques (n = 3). CSMs included logistic regression (n = 16), Cox regression (n = 3), or Poisson regression (n = 3). In 15 studies, readmission was examined at multiple time points ranging from 30 to 180 day readmission, with the majority of studies (n = 12) presenting prediction models for 30 day readmission outcomes. Of a total of 21 time-point comparisons, ML-derived c-indices were higher than CSM-derived c-indices in 16 of the 21 comparisons. In seven studies, mortality was examined at 9 time points ranging from in-hospital mortality to 1 year survival; of these nine, seven reported higher c-indices using ML. Two of these seven studies reported survival analyses utilizing random survival forests in their ML prediction models. Both reported higher c-indices when using ML compared with CSMs. A limitation of studies using ML techniques was that the majority were not externally validated, and calibration was rarely assessed. In the only study that was externally validated in a separate dataset, ML was superior to CSMs (c-indices 0.913 vs. 0.835).ConclusionsML algorithms had better discrimination than CSMs in most studies aiming to predict risk of readmission and mortality in HF patients. Based on our review, there is a need for external validation of ML-based studies of prediction modelling. We suggest that ML-based studies should also be evaluated using clinical quality standards for prognosis research. Registration: PROSPERO CRD42020134867.

Project description:BackgroundThe relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes.MethodsWe consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).ResultsA total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients.ConclusionBoth elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes.

Project description:BackgroundHeart failure (HF) is associated with a high rate of readmissions within 30 days post-discharge and in the following year, especially in frail elderly patients. Biomarker data are scarce in this high-risk population. This study assessed the value of early post-discharge circulating levels of ST2, NT-proBNP, CA125, and hs-TnI for predicting 30-day and 1-year outcomes in comorbid frail elderly patients with HF with mainly preserved ejection fraction (HFpEF).MethodsBlood samples were obtained at the first visit shortly after discharge (4.9 ± 2 days). The primary endpoint was the composite of all-cause mortality or HF-related rehospitalization at 30 days and at 1 year. All-cause mortality alone at one year was also a major endpoint. HF-related rehospitalizations alone were secondary end-points.ResultsFrom February 2014 to November 2016, 522 consecutive patients attending the STOP-HF Clinic were included (57.1% women, age 82 ± 8.7 years, mean Barthel index 70 ± 25, mean Charlson comorbidity index 5.6 ± 2.2). The composite endpoint occurred in 8.6% patients at 30 days and in 38.5% at 1 year. In multivariable analysis, ST2 [hazard ratio (HR) 1.53; 95% CI 1.19-1.97; p = 0.001] was the only predictive biomarker at 30 days; at 1 year, both ST2 (HR 1.34; 95% CI 1.15-1.56; p < 0.001) and NT-proBNP (HR 1.19; 95% CI 1.02-1.40; p = 0.03) remained significant. The addition of ST2 and NT-proBNP into a clinical predictive model increased the AUC from 0.70 to 0.75 at 30 days (p = 0.02) and from 0.71 to 0.74 at 1 year (p < 0.05). For all-cause death at 1 year, ST2 (HR 1.50; 95% CI 1.26-1.80; p < 0.001), and CA125 (HR 1.41; 95% CI 1.21-1.63; p < 0.001) remained independent predictors in multivariable analysis. The addition of ST2 and CA125 into a clinical predictive model increased the AUC from 0.74 to 0.78 (p = 0.03). For HF-related hospitalizations, ST2 was the only predictive biomarker in multivariable analyses, both at 30 days and at 1 year.ConclusionsIn a comorbid frail elderly population with HFpEF, ST2 outperformed NT-proBNP for predicting the risk of all-cause mortality or HF-related rehospitalization. ST2, a surrogate marker of inflammation and fibrosis, may be a better predictive marker in high-risk HFpEF.

Dataset Information

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Publications

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Similar Datasets

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