Peak oxygen consumption as a modifier of the obesity paradox in patients with obesity with heart failure with reduced ejection fraction

Background: Obesity is linked to adverse health effects, but paradoxically improves survival in heart failure (HF). Peak oxygen consumption (VO 2 ), a measure of exercise capacity, is a key prognostic indicator in HF. We examined the interaction between obesity and peak VO 2 in predicting survival in patients with HF with reduced ejection fraction (HFrEF). Methods: We retrospectively reviewed 18,879 patients who underwent maximal cardiopulmonary exercise testing using the modified Bruce ramp protocol between 2012 and 2020. The inclusion criteria were left ventricular ejection fraction <40% and body mass index (BMI) > 18.5 kg/m 2 . Patients were classified as those with normal weight (BMI: 18.5–22.9 kg/m 2 ), overweight (23.0–24.9 kg/m 2 ), or obesity (≥25.0 kg/m 2 ) per 2020 Korean Society for the Study of Obesity guidelines. Results: For the 819 included patients (292 with normal weight, 197 with overweight, 330 with obesity), median age was 59 (interquartile range [IQR]: 49–67) years, 75.2% were male, and the median BMI was 24.1 (IQR: 22.1–26.5) kg/m 2 . Patients with obesity achieved the highest workload, peak VO 2 , and exercise time (all P < 0.001). They also had lower all-cause mortality versus patients with normal weight (hazard ratio 0.46, 95% confidence interval 0.25–0.82, P = 0.009). In patients with obesity, elevated peak VO 2 was associated with a U-shaped mortality curve, unlike the linear relationship in other groups ( P for interaction = 0.001). Conclusions: Patients with obesity and HFrEF showed better survival, consistent with the obesity paradox. However, the U-shaped relationship between peak VO 2 and mortality in this group suggests the survival advantage may diminish at higher levels of exercise capacity, warranting further investigation.