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 The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Conclusion:Thyroid hormone use can have important implications for organ selection and cardiac function before and after transplantation. Protocols vary widely with respect to why and how to use and wean thyroid hormone. We believe there should be more detailed reporting of thyroid hormone use for future studies to ensure appropriate donor management. ( 585)Purpose: Brain-stem-death (BSD) causes cardiac injury and dysfunction that is sometimes reversible. The optimum time after BSD at which to assess the function of donor hearts is unknown. We hypothesized that a longer interval may be associated with a higher transplantation rate due to improved function. Methods: Data on adult DBD solid organ donors were obtained retrospectively from the UK Transplant Registry for the period 1 January 2008 to 31 December 2012. Donors above the age of 65 with a past history of cardiothoracic disease, consent for heart donation was refused or whose cause of death was myocardial infarction were excluded. The time when fixed dilated pupils were first noted in the donor was considered as the time of BSD. Retrieval was defined as the time when the abdominal organs were perfused. Results: BSD to retrieval duration was available for 1,839 donors. Of these donors, 461 (25%) donated their heart. The median (IQR) BSD to retrieval duration was 35.6 hours (27.6, 48.7). BSD to retrieval durations differed (p< 0.0001) depending on the time of day when BSD was diagnosed (separated in to four quartiles). A multivariate logistic regression was then performed. Donor age, blood group, gender, cause of death, heart rate, body mass index, past history of hypertension, cardiac arrest and use of prednisolone were all found to influence the probability of donation. Adjusting for these factors, there was evidence to suggest that the BSD to retrieval duration had a non-linear effect upon heart donation (p= 0.047).The effect was such that, longer durations were associated with a higher probability of donation. However, the odds ratio for the probability of heart donation began to plateau at a value of 1 after approximately 1.5 days suggesting that durations beyond this have no impact on the chance of donation. Analysis of a subset of donors attended by a cardiothoracic retrieval team showed a similar pattern. Conclusion: This data suggest that time interval from BSD to retrieval influences the heart retrieval rate. A longer time interval may allow the heart to recover from the BSD induced injury. When the sole reason for decline a donor heart is poor function, a period of further observation and optimisation up to 1.5 days should be considered.

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