BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

Women with heart failure due to nonischemic causes had significantly better survival than men with or without coronary disease as their primary cause of heart failure.

Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Aims This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS‐986231, a novel second‐generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). Methods and results Forty‐six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose‐escalation cohorts in this double‐blind, randomized, placebo‐controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6‐h i.v. infusion of BMS‐986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS‐986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time‐averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS‐986231 increased non‐invasively measured time‐averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug‐related arrhythmia or symptomatic hypotension with BMS‐986231. Analyses of adverse events throughout the 30‐day follow‐up did not identify any toxicities specific to BMS‐986231, with the potential exception of infrequent mild‐to‐moderate headaches during infusion. There were no treatment‐related serious adverse events. Conclusions BMS‐986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS‐986231 should be further assessed in patients with heart failure.