Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure with Preserved Ejection Fraction
Background—Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogenous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, non-obese HFpEF, and controls.
Methods—Subjects with obese HFpEF (BMI≥35kg/m2, n=99), non-obese HFpEF (BMI<30kg/m2, n=96), and non-obese controls free of HF (n=71) underwent detailed clinical assessment, echocardiography and invasive hemodynamic exercise testing.
Results—Compared to both non-obese HFpEF and controls, subjects with obese HFpEF displayed increased plasma volume (3907 [3563,4333] vs. 2772 [2555,3133] and 2680 [2380,3006] ml, p<0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base 34±7 vs. 31±6 and 30±6 mm, p=0.0005; length 66±7 vs. 61±7 and 61±7 mm, p<0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 vs. 7±2 and 6±2 mm, p<0.0001), and greater total epicardial heart volume (945 [831,1105] vs. 797 [643,979] and 632 [517,768] ml, p<0.0001), despite lower NT-proBNP levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF (r=0.22 and 0.27, both p<0.05), but not in non-obese HFpEF (p≥0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right to left heart filling pressures (0.64±0.17 vs. 0.56±0.19 and 0.53±0.20, p=0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 vs 0.99±0.06 and 0.97±0.12, p<0.0001). Interdependence was enhanced as pulmonary artery pressure load increased (interaction p<0.05). As compared to non-obese HFpEF and controls, obese HFpEF subjects displayed worse exercise capacity (peak oxygen consumption 7.7±2.3 vs. 10.0±3.4 and 12.9±4.0 ml/min*kg, p<0.0001), higher biventricular filling pressures with exercise and depressed pulmonary artery vasodilator reserve.
Conclusions—Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments.
- Received December 7, 2016.
- Revision received March 21, 2017.
- Accepted March 24, 2017.