Abstract 4147677: Exercise Pulmonary Vascular Resistance relates to impaired RV-PA coupling and effort intolerance in HFpEF

Introduction: Elevated pulmonary vascular resistance (PVR) during exercise is a proposed marker of negative prognosis in patients with heart failure with preserved ejection fraction (HFpEF), however its pathophysiology is incompletely characterised. We investigate here the relative contribution to exercise-induced PVR on right ventricular (RV) functional and structural remodelling and pulmonary artery (PA) coupling during exercise in HFpEF patients. Methods: We included 67 consecutive patients from the Johns Hopkins HFpEF Clinic where supine bicycle exercise right heart catheterisation (RHC) was available. In agreement with previous studies, we defined 2 distinct subgroups: patients with elevated exercise-induced PVR (HFpEF-highPVR), including patients with PVR ≥ 1.74 WU at maximal effort and those without exercise-induced PVR (HFpEF-normalPVR) patients with PVR < 1.74 WU at maximal effort. Echocardiography and RV endomyocardial biopsy (EMB) data were analysed to assess cardiac structural and functional remodelling associated with HFpEF-highPVR. Results: From the total of 67 patients, 23 (34%) had elevated PVR at rest (PVR≥2 WU) of which 17 (74%) continued on to have exercise-induced PVR (PVR≥1.74 WU). From 44 (66%) patients without elevated PVR at rest, 4 (9.1%) further developed PVR at maximal exercise. ( Figure1A ). HFpEF-highPVR were older, had lower eGFR and higher NT-proBNP, than HFpEF-normalPVR. Maximal exercise tolerance was severely reduced in the HFpEF-highPVR group (14.0±13.7 vs 31.4±16.9 watts, P<0.001; Figure 1B ). HFpEF-highPVR was associated with lower PA compliance (2.7±1.0 vs 5.2±1.7 mL/mmHg, P<0.001), higher PA elastance (840±320 vs 441±138 mmHg/mL, P<0.001) and higher diastolic pulmonary gradient (4.71±4.23 vs 2.07±2.69 mmHg, P=0.014). Patients with HFpEF-highPVR had a higher frequency of RV dilatation (OR=5.42, 95%CI 1.36-21.70, P=0.012), LV restrictive diastolic filling (OR=3.80, 95%CI 1.08-13.37, P=0.031) by echocardiography, and, higher frequency of moderate and severe hypertrophy (OR=4.80, 95%CI 1.48-15.61, P=0.007) and presence of fibrosis (OR=4.71, 95%CI 1.18-18.80, P=0.021) on EMB. Conclusion: Patients with elevated PVR during exercise had more pronounced maladaptive RV remodelling and less compliant PA, which contributed to impaired hemodynamic and lower endurance. Assessing exercise PVR can offer an important distinct insight into HFpEF phenotype classification and further stratify clinical risk.