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.

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for ≥ 14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day + 100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day + 100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

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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.