Background Obesity is associated with heart failure with preserved ejection fraction (HFpEF). Weight loss can improve exercise capacity in HFpEF. However, previously reported methods of weight loss are impractical for widespread clinical implementation. We tested the hypothesis that an intensive lifestyle modification program would lead to relevant weight loss and improvement in functional status in patients with HFpEF and obesity. Methods and Results Patients with ejection fraction >45%, at least 1 objective criteria for HFpEF, and body mass index ≥30 kg/m 2 were offered enrollment in an established 15‐week weight management program that included weekly visits for counseling, weight checks, and provision of meal replacements. At baseline, 15 weeks, and 26 weeks, Minnesota Living With Heart Failure score, 6‐minute walk distance, echocardiography, and laboratory variables were assessed. A total of 41 patients completed the study (mean body mass index, 40.8 kg/m 2 ), 74% of whom lost >5% of their baseline body weight following the 15‐week program. At 15 weeks, mean 6‐minute walk distance increased from 223 to 281 m ( P =0.001) and then decreased to 267 m at 26 weeks. Minnesota Living With Heart Failure score improved from 59.9 to 37.3 at 15 weeks ( P <0.001) and 37.06 at 26 weeks. Changes in weight correlated with change in Minnesota Living With Heart Failure score ( r =0.452; P =0.000) and 6‐minute walk distance ( r =−0.388; P <0.001). Conclusions In a diverse population of patients with obesity and HFpEF, clinically relevant weight loss can be achieved with a pragmatic 15‐week program. This is associated with significant improvements in quality of life and exercise capacity. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02911337.

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Background: Obesity is associated with incident heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Weight loss is difficult to achieve in patients with limited physical capacity and the benefits remain uncertain in established HF. Methods: Patients with EF > 50% and at least 1 objective criteria for HFpEF (BNP 200 pg/ml, elevated resting or exercise wedge pressure (15 or 25 mmHg) or pulmonary edema on CXR) and BMI 30 kg/m2 were enrolled in a 15-week weight management program that entailed weekly counseling, weight checks, and meal replacement (twice daily weeks 1-8, once daily weeks 9-12). Primary endpoints were change from baseline to 15-weeks for weight, Minnesota Living With HF (MLWHF) score and 6 minute walk (6MW). Paired t-test was used to test for differences from baseline to the 15 week clinical endpoint, and one-way ANOVA was used to evaluate if these differences persisted at 26 week follow up. Results: 65 patients signed consent, 41 completed the 15-week program and 37 had 26-week follow up. Mean age was 67±9 years, BMI 41±6 kg/m 2 , 65% were female, and 43% black. Mean weight decreased by 8.1±6.6 kg at the 15-week endpoint (p<0.001) and persisted at 26-week follow up (p<0.001). 74% of patients lost more than 5% of their baseline body weight at week 15. Blacks lost a mean of 6±6% body weight compared to 9±4% in Caucasians (p<0.05). At 15 weeks, mean 6MW distance increased from 221±111 m to 286±99 m (p<0.001) and then fell to 275±144 m at 26 weeks (p=0.043). MLWHF score improved from 60±24 to 38±27 (p<0.001) and 38±26 (p<0.001) at 15 and 26 weeks, respectively. BNP did not change (109 to 114 pg/ml). E/e’ decreased significantly from 13.9±6.8 to 11.9±5.6 at 26 weeks follow up (p<0.01). BNP levels decreased by 39±103 pg/ml in blacks vs. an increase of 17±53 mg/dl in Caucasians (p<0.05) at 15-week follow up. Conclusions: Clinically relevant weight loss is possible in patients with established HFpEF and when it occurs, this is associated with significant improvements in quality of life and exercise capacity. There may be racial differences in the biochemical response to weight management in this population.

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