Impact of systemic inflammation on exercise haemodynamics in unexplained dyspnoea and heart failure with preserved ejection fraction

Aim: Systemic inflammation in heart failure with preserved ejection fraction (HFpEF) predicts worse outcomes. This study investigates its impact on exercise haemodynamics in patients with unexplained dyspnoea. Methods: This prospective cohort study includes subjects referred for unexplained dyspnoea to a multidisciplinary dyspnoea clinic between January 2021 and August 2023 for cardiopulmonary exercise testing with concomitant exercise echocardiography. Systemic inflammation was defined as a high-sensitivity C-reactive protein level ≥2 mg/L. HFpEF was diagnosed with an H2FPEF score ≥6, HFA-PEFF score ≥5, or in case of exercise pulmonary hypertension together with a left atrial reservoir strain <24.5% at rest or positive diastolic stress test during exercise. Results: A total of 70/191 consecutively evaluated subjects (37%) had systemic inflammation, which was linked with anthropometrics of increased adiposity. Subjects with vs. without systemic inflammation had smaller end-diastolic volume indices (40.9 ± 9.7 vs. 47.2 ± 13.3 mL/m2, respectively; p =.002), a lower tricuspid annular plane systolic excursion over pulmonary artery systolic pressure ratio [0.96 (0.75–1.10) vs. 1.04 (0.85–1.28) mm/mmHg, respectively; p =.033], but otherwise similar echocardiography findings at rest. For a similar respiratory exchange ratio at peak exercise, they had lower peak oxygen consumption (16.9 ± 5.3 vs. 20.6 ± 6.6 mL/min/kg, respectively; p <.001). The right ventricular end-systolic pressure area ratio change with exercise indicated less right ventricular contractile reserve when systemic inflammation was present. In the HFpEF subgroup, patients with vs. without systemic inflammation had a decreased cardiac output reserve with exercise. Conclusion: In subjects with dyspnoea, systemic inflammation is linked to increased adiposity and lower exercise capacity because of impaired right ventricular reserve.