Empel, Vanessa van

Abstract Aims Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. Methods and results The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2. As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e′ were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. Conclusions Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

Background Hypertension is a frequent risk factor for the development of heart failure with preserved ejection fraction ( HFPEF ). Progressive extracellular matrix accumulation has been presumed to be the fundamental pathophysiologic mechanism that leads to the transition to impaired diastolic reserve. However, the contribution of other mechanisms affecting active and passive components of diastolic function has not been comprehensively assessed. In this study, we investigated the potential role of impaired myocardial oxygen delivery in the pathophysiology of HFPEF . Methods and Results Patients with HFPEF , those with controlled hypertension, and healthy controls underwent simultaneous right‐heart catheterization, echocardiography, and paired arterial and coronary sinus blood gas sampling at rest and during supine‐cycle ergometry. Despite a lower workload ( HFPEF vs control, hypertension: 43±8 versus 114±12, 87±14 W; P <0.001 and P <0.05, respectively), peak exercise pulmonary capillary wedge pressure was markedly higher in HFPEF patients compared with healthy and hypertensive controls (32±2 versus 16±1 and 17±1 mm Hg, both P <0.001). During exercise, the transcardiac oxygen gradient increased significantly in all groups; however, the peak transcardiac oxygen gradient was significantly lower in HFPEF patients ( P <0.05). In addition, the left ventricular–work corrected transcardiac oxygen gradient remained significantly lower in HFPEF patients compared with controls ( P <0.001). Conclusion The current study provides unique data suggesting that the abnormal diastolic reserve observed during exertion in HFPEF patients may, in part, be explained by impaired myocardial oxygen delivery due possibly to microvascular dysfunction. Further studies are required to confirm the structural and functional basis of these findings and to investigate the influence of potential therapies on this abnormality.