Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease.
Mancini, Donna M, Brunjes, Danielle L, Lala, Anuradha et al. · JACC. Heart failure · 2021 · DOI
Quick Summary
This study looked at 41 people who had long-lasting breathing problems after COVID-19, even though their standard lung and heart tests appeared normal. Researchers used a special exercise test to measure how well their bodies could use oxygen and how they breathed during activity. They found that most patients had unusual breathing patterns or reduced exercise capacity, and about half met the criteria for ME/CFS.
Why It Matters
This work demonstrates that objective physiological abnormalities—circulatory impairment and dysfunctional breathing—underlie unexplained dyspnea in PASC and ME/CFS, validating patient symptoms and providing measurable diagnostic tools. It bridges post-COVID syndrome and ME/CFS, suggesting shared pathophysiological mechanisms in both populations.
Observed Findings
58.5% of PASC patients had peak VO₂ <80% predicted, indicating reduced exercise capacity with circulatory limitation
88% of the cohort demonstrated ventilatory abnormalities, including dysfunctional breathing (63%), elevated VE/VCO₂ (41%), or resting hypocapnia (61%)
46% met diagnostic criteria for ME/CFS
Left ventricular ejection fraction was normal (59% ± 9%) despite exercise impairment, ruling out systolic heart dysfunction
Patients with normal peak VO₂ predominantly showed ventilatory rather than circulatory defects
Inferred Conclusions
Circulatory and ventilatory abnormalities are common pathophysiological features in PASC that can occur despite normal standard cardiac and pulmonary testing
Dysfunctional breathing patterns and resting hypocapnia may contribute to dyspnea and exercise limitation in post-COVID patients
ME/CFS overlaps substantially with PASC physiology, suggesting shared mechanisms
CPET is superior to standard testing for identifying objective abnormalities in PASC patients with unexplained dyspnea
Remaining Questions
Are these physiological abnormalities specific to PASC or do they also appear in other post-viral syndromes and in the general population?
What This Study Does Not Prove
This study does not establish causation—whether dysfunctional breathing causes ME/CFS or vice versa. It cannot determine the prevalence of these findings in the general population, as it lacks a control group. The cross-sectional design cannot track whether these abnormalities persist, improve, or worsen over time.