Intentional Weight Loss as a Novel Treatment for Heart Failure with Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) is frequent in obesity and both conditions are projected to increase in prevalence. We sought to investigate if weight loss is an effective treatment for patients with HFpEF and obesity. Hypothesis: Intentional weight loss improves symptoms, serum markers and imaging markers in patients with HFpEF and obesity. Methods: 12 obese HFpEF patients (BMI 33.5±5 kg/m 2 ; NYHA I-III) were assessed before and after a very low energy diet (VLED; 800 calories per day) for 10 weeks and compared to 10 weight-matched, obese controls (BMI 31.8±1.5 kg/m 2 ). We evaluated cardiac function using cardiovascular magnetic resonance (CMR) imaging, diastolic function with echocardiography and cardiac energetics (PCr/ATP) using 31 P-spectroscopy. Serum samples were drawn to measure N-terminal pro-brain natriuretic peptide (NTpro-BNP). Results: After 10 weeks of VLED, there was a highly significant reduction in body weight (BMI -2.7kg/m 2 ± 0.38, p<0.001) paralleled by a significant drop in NTpro-BNP (-239pg/mL ± 149, p<0.05) and heart failure symptoms (NYHA median pre II vs. I post). Echocardiography revealed a significantly lower left atrial volume (-29mL ± 28, p<0.05) and a trend towards improved diastolic function (lateral E/E’ -0.68 ± 0.5, p=0.08). CMR demonstrated a significantly lower LV mass (-9g ± 2.9, p<0.05) but no changes in PCr/ATP at rest (Δ0.015±0.1, p=ns) or during dobutamine stress (Δ0.087±0.06, p=ns). Except NTpro-BNP, all parameters returned to comparative levels of obese weight-matched patients without HFpEF. Conclusions: In obese HFpEF, intentional weight loss improves prognostic serum markers for HF, decreases symptom severity, reduces atrial size and LV mass, and improves diastolic function. These findings underscore the potential for weight loss as an effective treatment for HFpEF and the need for larger trials.