Obesity is a major risk factor for heart failure with preserved ejection fraction (HFpEF), but its impact on limitations in peak oxygen uptake (VO 2 peak) and its Fick determinants remains unclear. We assessed these factors in obese and non-obese patients with HFpEF, and non-HFpEF controls. Patients with HFpEF were sub-grouped by body mass index (BMI ≥30 or <30 kg/m 2 ) into HFpEF with (HFpEF Obese , n=139) or without obesity (HFpEF Non-Obese , n=317), and non-HFpEF controls (CON, n=270). Cardiopulmonary exercise testing with simultaneous echocardiography assessed VO 2 peak, cardiac output (CO), stroke volume (SV), heart rate (HR), mean pulmonary artery pressure (mPAP) dynamics and arterio-venous oxygen difference (a-vO 2 diff). HFpEF Obese tended to have higher absolute VO 2 peak (+7%, P=0.069), and significantly higher peak exercise CO and SV, with no differences in HR or a-vO 2 diff. Resting and exercise mPAP and mPAP/CO slopes did not differ between HFpEF obesity phenotypes. In contrast, bodyweight-indexed VO 2 peak was markedly lower in HFpEF Obese (−23%) despite comparable indexed peak CO and SV. Regardless of HFpEF sub-group, VO 2 peak, central (CO, HR, mPAP) and peripheral factors (a-vO 2 diff) were markedly impaired in HFpEF versus CON (P<0.05 for all). Therefore, while HFpEF Obese patients have preserved absolute VO 2 peak and cardiac reserve, bodyweight-indexing reveals that these adaptations are insufficient for the heightened metabolic and functional demands induced by obesity. Alternatively, several physiologic HFpEF features are not exacerbated by obesity. This highlights the importance of incorporating weight loss alongside multi-component therapeutic strategies to address exercise intolerance in HFpEF.
Foulkes et al. (Tue,) studied this question.