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.

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.

Prospective validation of prognostic and diagnostic syncope scores in the emergency department.

BACKGROUND: Various scores have been derived for the assessment of syncope patients in the emergency department (ED) but stay inconsistently validated. We aim to compare their performance to the one of a common, easy-to-use CHADS2 score. METHODS: We prospectively enrolled patients ≥ 40 years old presenting with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of the treating ED-physician regarding the probability of cardiac syncope was quantified. Two independent physicians adjudicated the final diagnosis after 1-year follow-up. Major cardiovascular events (MACE) and death were recorded during 2 years of follow-up. Nine scores were compared by their area under the receiver-operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac syncope. RESULTS: 1490 patients were available for score validation. The CHADS2-score presented a higher or equally high accuracy for death in the long- and short-term follow-up than other syncope-specific risk scores. This score also performed well for the prediction of MACE in the long- and short-term evaluation and stratified patients with accuracy comparative to OESIL, one of the best performing syncope-specific risk score. All scores performed poorly for diagnosing cardiac syncope when compared to the ECJ. CONCLUSIONS: The CHADS2-score performed comparably to more complicated syncope-specific risk scores in the prediction of death and MACE in ED syncope patients. While better tools incorporating biochemical and electrocardiographic markers are needed, this study suggests that the CHADS2-score is currently a good option to stratify risk in syncope patients in the ED. TRIAL REGISTRATION: NCT01548352.