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.

Three patients with left atrial myxoma presented with prominent neurologic symptoms and signs (cerebrovascular disease and/or syncope) within the past year. Two patients died because antemortem diagnosis was late or missed. One patient was successfully treated. Cardiac myxoma produces protean clinical manifestations that do not always include cardiac signs and symptoms. Neurologists may be called on for diagnostic consultation in patients who will prove to have cardiac myxoma. Unexplained transient ischemic attacks, cerebral infarction, or syncope (with possible features of seizure activity) are common neurologic manifestations of this disease. Additionally, systemic symptoms, signs, and laboratory data suggestive of collagen vascular disease or vasculitis are also often present. Echocardiography is a dependable noninvasive procedure for a confirmation of diagnosis in suspected cases.

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.

Miller and Gold et al. provide additional pearls that may help clinicians suspect a central origin of a fourth nerve palsy. In response to Yufe, Saposnik et al. clarify the methodology of their study on Stroke Prognostication using Age and NIH Stroke Scale (NIHSS). The latter 2 combined are, according to the authors, the 2 major predictors of stroke outcomes.

Regional intravascular injections of d-tubocurarine (0.3 mg) were administered in the hands of 23 normal subjects and 19 patients with multiple sclerosis. The degree of neuromuscular block and rate of recovery were determined by measuring the amplitude of the first dorsal interosseus muscle action potential which was evoked periodically by trains of five stimuli (3 Hz each) to the ulnar nerve. In normal subjects, the first response to the train returned to its preinjection level after 20.0 +/- 8.5 minutes and the fifth response after 27.6 +/- 7.8 minutes. Multiple sclerosis patients showed a significantly delayed recovery of the first response (58 percent of patients) and of the fifth response (42 percent), suggesting a latent defect of neuromuscular transmission.