Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance

Background Post-acute sequelae of COVID-19 (PASC) affect a significant proportion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom. This study aimed to characterise the invasive haemodynamic abnormalities of PASC-related exertional intolerance using invasive cardiopulmonary exercise testing (iCPET). Study design and intervention 55 patients were recruited from the Yale Post-COVID-19 Recovery Program, with most experiencing mild acute illness. Supine right heart catheterisation and iCPET were performed on all participants. Main results The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO 2 ) during iCPET in conjunction with supranormal cardiac output (CO) ( i.e. , PASC alone group). On average, the PASC alone group exhibited a “normal” peak exercise capacity, V′ O 2 (89±18% predicted). ∼25% of patients had evidence of central cardiopulmonary pathology ( i.e. , 12 with resting and exercise heart failure with preserved ejection fraction (HFpEF) and two with exercise pulmonary hypertension (PH)). PASC patients with HFpEF ( i.e. , PASC HFpEF group) exhibited similarly impaired pEO 2 with well compensated PH ( i.e. , peak V′ O 2 and CO >80% respectively) despite aberrant central cardiopulmonary exercise haemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m −2 . To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group comprising obese non-PASC group (n=61) derived from a historical iCPET cohort was used. The non-PASC obese patients with preserved peak V′ O 2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10% predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO 2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19). Conclusions This study highlights the importance of considering impaired pEO 2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of the current study also highlight the prevalence of a distinct high output HFpEF phenotype in PASC with a primary peripheral limitation to exercise.