Harris & Waxman (2026)
- Authors: Emily A. Harris, Aaron B. Waxman
- Institutes: Dyspnea and Performance Evaluation Center, Brigham and Women’s Hospital, Boston, MA, Harvard Medical School, Boston, MA
- Publisher: Respiratory Physiology & Neurobiology
- Link: DOI
Summary
This review establishes invasive cardiopulmonary exercise testing (iCPET) as a vital diagnostic tool for patients whose fatigue and breathlessness remain a mystery after standard medical exams. By identifying ‘occult’ conditions like preload failure and mitochondrial dysfunction, this research provides a biological explanation for symptoms often dismissed in ME/CFS and Long COVID. The findings enable clinicians to move beyond symptom management toward targeted physiological treatments.
What was researched?
The study provides a comprehensive physiologic framework for using iCPET to diagnose the underlying causes of unexplained dyspnea and exercise intolerance.
Why was it researched?
Standard non-invasive tests frequently fail to detect abnormalities in patients with ME/CFS and Long COVID, necessitating more sophisticated methods to measure hemodynamics and oxygen utilization during physical exertion.
How was it researched?
Researchers utilized iCPET, which involves placing catheters in the pulmonary and radial arteries to collect continuous data on heart pressures, blood flow, and gas exchange while patients cycle on a stationary bike.
What has been found?
The assessment identifies several distinct ‘endotypes’ of exercise limitation, including preload failure (insufficient blood returning to the heart) and impaired peripheral oxygen extraction (mitochondrial or neurovascular issues). These findings often coexist with normal resting heart and lung function, explaining why typical clinical screenings are inconclusive.
Discussion
While iCPET is considered the gold standard for phenotyping exercise intolerance, its invasive nature requires specialized clinical centers. The study highlights the method’s unique ability to differentiate between central cardiac limitations and peripheral vascular or metabolic dysfunction.
Conclusion & Future Work
Accurate diagnosis via iCPET allows for personalized treatment strategies, such as volume expansion with saline 💊 or the use of pyridostigmine 💊 to improve neurovascular regulation. Future research aims to further refine these physiological profiles to predict treatment responses in larger patient cohorts.