Impact Of Cardiorespiratory Fitness On The Obesity Paradox In Heart Failure With Reduced Ejection Fraction

Background: Higher body mass index (BMI) has been associated with improved outcomes in heart failure with reduced ejection fraction. This finding has led to the concept of the obesity paradox.Objective: To investigate the impact of exercise tolerance and cardiorespiratory capacity on the obesity paradox.Methods: Outpatients with symptomatic heart failure and left ventricular ejection fraction (LVEF) <= 40%, followed up in our center, prospectively underwent baseline comprehensive evaluation including clinical, laboratorial, electrocardiographic, echocardiographic, and cardiopulmonary exercise testing parameters. The study population was divided according to BMI (< 25, 25 - 29.9, and >= 30 kg/m(2)). All patients were followed for 60 months. The combined endpoint was defined as cardiac death, urgent heart transplantation, or need for mechanical circulatory support. P value < 0.05 was considered significant.Results: In the 282 enrolled patients (75% male, 54 +/- 12 years, BMI 27 +/- 4 kg/m(2), LVEF 27% +/- 7%), the composite endpoint occurred in 24.4% during follow-up. Patients with higher BMI were older, and they had higher LVEF and serum sodium levels, as well as lower ventilatory efficiency (VE/VCO2) slope. VE/VCO2 and peak oxygen consumption (pVO(2)) were strong predictors of prognosis (p < 0.001). In univariable Cox regression analysis, higher BMI was associated with better outcomes (HR 0.940, CI 0.886 - 0.998, p 0.042). However, after adjusting for either VENCO2 slope or pVO(2), the protective role of BMI disappeared. Survival benefit of BMI was not evident when patients were grouped according to cardiorespiratory fitness class (VE/VCO2, cut-off value 35, and pVO(2), cut-off value 14 mL/kg/min).Conclusion: These results suggest that cardiorespiratory fitness outweighs the relationship between BMI and survival in patients with heart failure.