Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity

Aims Patient-reported quality of life (QOL) is a highly prognostic and clinically relevant endpoint in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The relationships between QOL and different markers of HF severity remain unclear, particularly as they relate to functional capacity and directly measured activity levels. We hypothesized that QOL would demonstrate a stronger relationship with measures of exercise capacity and adiposity compared to other disease measures. Methods and results This is a secondary analysis of the National Heart, Lung, and Blood Institute-sponsored RELAX, NEAT-HFpEF and INDIE-HFpEF trials to determine the relationships between QOL (assessed by the Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire) and different domains reflecting HF severity, including maximal aerobic capacity (peak oxygen consumption), submaximal exercise capacity (6-min walk distance), volume of daily activity (accelerometry), physician-estimated functional class, resting echocardiography, and plasma natriuretic peptide levels. A total of 408 unique patients with chronic HFpEF were split into tertiles of QOL scores defined as QOL(worst,)QOL(intermediate), QOL(best). The QOL(worst)HFpEF group was youngest, with a higher body mass index, greater prevalence of class II obesity and diabetes, and the lowest N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. After adjustment for age, sex and body mass index, poorer QOL was associated with worse physical capacity and activity levels, assessed by peak oxygen consumption, 6-min walk distance and actigraphy, but was not associated with NT-proBNP or indices from resting echocardiography. QOL was similarly reduced in patients with and without prior HF hospitalization. Conclusions Quality of life in HFpEF is poorest in patients who are young, obese and have diabetes, and is more robustly tied to measures reflecting functional capacity and daily activity levels rather than elevations in NT-proBNP or prior HF hospitalization. These findings have major implications for the understanding of QOL in HFpEF and for the design of future clinical trials targeting symptom improvement in HFpEF. Clinical Trial Registration: RELAX, NCT00763867; NEAT-HFpEF, NCT02053493; INDIE-HFpEF, NCT02742129.