Invasive Cardiopulmonary Exercise Testing Identifies Distinct Physiologic Endotypes in Postacute Sequelae of SARS-CoV-2 Infection
Michael G. Risbano, Corrine R. Kliment, D.G. Dunlap, Carl Koch, Luiz Campedelli, K. Yoney, Mehdi Nouraie, Frank C. Sciurba, Alison Morris
Abstract
Background: Exercise intolerance and dyspnea on exertion are prominent symptoms in Post-Acute Sequelae of COVID-19 (PASC) that significantly impact quality of life, but underlying physiologic contributors are not well-understood.Invasive cardiopulmonary exercise testing (iCPET) employs right heart catheterization, arterial access and standard cardiopulmonary exercise testing to identify pathophysiology in undifferentiated exercise intolerance.Research Question: What are the distinguishing clinical and physiologic features of exercise intolerant PASC and associated physiologic endotypes?Study Design and Methods: We performed a cross-sectional observational study with prospective enrollment of consecutive dyspneic and/or exercise-intolerant PASC patients who were referred for iCPET >3 months after SARS-CoV-2 infection.All patients underwent a history, physical examination, pulmonary function testing, echocardiogram, lab work, and chest imaging.We completed a detailed cardiopulmonary and hemodynamic analysis of 37 patients with iCPET to categorize PASC endotypes. Results:We evaluated 37 PASC subjects a median of 323 days after COVID-19 diagnosis with dyspnea on exertion and/or exercise intolerance.We compared 12 subjects (32.4%) that demonstrated a normal exercise capacity (normal V ̇O2 ) with 25 patients (67.6%) that had a reduced peak oxygen consumption (reduced V ̇O2 ) .We then identified distinct PASC endotypes with iCPET including preload insufficiency, decreased oxygen extraction, mixed preload insufficiency with decreased oxygen extraction, exercise pulmonary hypertension, chronic pulmonary embolism, deconditioning, and ventilatory limitation, which included physiologic abnormalities in PASC patients with normal exercise capacity.Nine of the 12 normal V ̇O2 patients had normal exercise physiology (one had evidence of exercise pulmonary hypertension and two with decreased oxygen extraction) yet still presented with symptoms of exercise intolerance. Conclusions: iCPET identified heterogeneous physiologic endotypes in PASC patientspresenting with similar symptoms of exercise intolerance or dyspnea on exertion.Future studies J o u r n a l P r e -p r o o f are needed to define associated pathogenesis and target effective therapies based on these physiological endotypes.