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.

Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. Conclusion:Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk. Case-control studies suggest that patent foramen ovale (PFO) is a common cause of cryptogenic stroke (CS), likely through a paradoxical (venous-to-arterial) embolism.1,2 However, CS has many potential causes, and PFO is a common anatomical variant found in approximately 25% of the general population.3 Thus, a PFO discovered in the setting of a CS may be incidental or stroke-related.Percutaneous mechanical closure of a PFO is frequently considered in patients with CS and PFO. The recently reported CLOSURE trial, however, found no benefit for this approach over medical therapy. 4 Nonetheless, stroke recurrence rates were low overall (limiting statistical power) and most stroke recurrence in both treatment groups was due to stroke of known mechanism, suggesting that many patients with incidental PFOs may have been enrolled.The premise of the Risk of Paradoxical Embolism (RoPE) Study 3 is that only patients with a high attributable recurrence risk have the opportunity to benefit from PFO closure for secondary

Objectives To assess the independent effect of increased body size on left ventricular (LV) diastolic function. Background Obese and overweight individuals are at increased risk of heart failure. LV diastolic dysfunction is an asymptomatic condition associated with future heart failure. It is unclear whether obesity and overweight are independently associated with LV diastolic dysfunction. Methods LV diastolic function was evaluated in 950 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study by traditional and tissue-Doppler imaging. Peak early and late trans-mitral diastolic flow velocities (E, A) and early diastolic mitral annulus velocity (E′) were measured, and E/A and E/E′ were calculated. The study sample was divided into three groups: normal weight [body mass index (BMI)<25.0], overweight (BMI 25.0–29.9) and obese (BMI≥30). Results In multivariate analyses, BMI was independently associated with higher E, A, and E/E′, an indicator of LV filling pressure (all p≤0.01). Overweight and obese had lower E′ (both p<0.01) and higher E/E′ (both p<0.01) than normal weight participants. E/A was lower in obese than normal weight subjects (p<0.01). The risk of diastolic dysfunction was significantly higher in overweight (adjusted odds ratio: 1.52, 95% confidence intervals 1.04–2.22) and obese (adjusted odds ratio: 1.60, 95% confidence intervals 1.06–2.41) compared to normal weight individuals. Conclusions Increased BMI was associated with worse LV diastolic function independent of LV mass and associated risk factors. The increased risk of LV diastolic dysfunction in both overweight and obese individuals may partially account for the increased risk of heart failure associated with both conditions.

Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. Study outcomes The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. Discussion ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

Background and Purpose-Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ischemic stroke patients.

Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

Aims Global longitudinal strain (GLS) assessed by speckle-tracking echocardiography has been proposed as a parameter able to reflect early changes in left ventricular (LV) systolic function at a stage when LV ejection fraction (LVEF) is still normal. This study aimed at assessing prevalence and prognostic value of LV systolic dysfunction (LVSD) assessed by echocardiographic speckle-tracking GLS in a community-based cohort. Methods and Results Participants from the community-based prospective Northern Manhattan Study underwent 2-dimensional transthoracic echocardiography as part of the Cardiovascular Abnormalities and Brain Lesions study. LV systolic function was assessed by LVEF and speckle-tracking GLS. Subjects were followed annually (mean=4.8±1.5 years) and incident vascular events (ischemic stroke, myocardial infarction, and vascular death) were reviewed and adjudicated. Of the 708 study participants, 114 (16.1%) had abnormal GLS but normal LVEF (GLS-LVSD), 30 (4.2%) had abnormal LVEF (LVEF-LVSD), and 564 (79.7%) had normal GLS and LVEF (no-LVSD). In multivariate analysis, risk of events was significantly greater in GLS-LVSD [adjusted hazard ratio (HR)=2.39, 95% confidence intervals (CI)=1.20–4.77] and in LVEF-LVSD (adjusted HR=3.51, 95% CI=1.25–9.88) compared to no-LVSD. Among participants with normal LVEF, lower GLS was significantly associated with events (adjusted HR/unit decrease=1.15, 95% CI=1.03–1.28) whereas LVEF was not (adjusted HR/unit decrease=1.01, 95% CI=0.94–1.07). GLS prognostic value was incremental to risk factors and LVEF both in the overall population (chi-square change=7.406, p=0.006) and in participants with normal LVEF (chi-square change=6.357, p=0.012). Conclusion In a community-based cohort, GLS-LVSD was four times more frequent than LVEF-LVSD. GLS-LVSD was a powerful and independent predictor of cardiovascular events. LV function assessment by GLS may improve cardiovascular risk stratification in subjects with normal LVEF.

for the PFO in Cryptogenic Stroke Study (PICSS) Investigators* Background-Patent foramen ovale (PFO) is associated with stroke, but there are no randomized studies to evaluate the efficacy of antithrombotic therapies. Methods and Results-The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study. In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes. End points were recurrent ischemic stroke or death. PFO was present in 203 patients (33.8%). There was no significant difference in the time to primary end points between those with and those without PFO in the overall population (Pϭ0.84; hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or in the cryptogenic subset (Pϭ0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year event rates 14.3% versus 12.7%). There was no significant difference among those with no, small, or large PFO (Pϭ0.41 for small PFO and Pϭ0.16 for large PFO; 2-year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%, respectively). There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm (Pϭ0.84; 2-year event rates 14.5% versus 15.9%). In patients with PFO, there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin (Pϭ0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2-year event rates 16.5% versus 13.2%). Conclusions-On