Harris EA; Center for Pulmonary Heart Disease, Boston,  United States.
Waxman AB

Respiratory Physiology & Neurobiology. 341:104550, 2026 Apr.

Unexplained dyspnea and exertional intolerance are common, burdensome
clinical problems that may persist despite routine resting cardiopulmonary
testing. Invasive cardiopulmonary exercise testing (iCPET) integrates
breath-by-breath gas exchange with invasive hemodynamic and blood gas
assessment during incremental exercise, enabling evaluation of physiologic
abnormalities that may be unapparent at rest. This review summarizes
practical considerations for iCPET performance (including upright cycle
ergometry, catheter-based pressure measurements, direct Fick cardiac
output, and symptom assessment using separate visual analog Modified Borg
ratings for dyspnea and leg fatigue at peak exercise), and presents a
structured approach to interpretation using pressure-flow relationships
and age-related reference ranges. Emphasis is placed on how characteristic
iCPET patterns inform mechanistic contributors to exertional dyspnea by
identifying upstream physiologic triggers-such as abnormal rises in
pulmonary arterial wedge pressure (exercise-HFpEF), abnormal pulmonary
vascular pressure-flow responses (exercise-PAH), impaired preload
augmentation associated with autonomic dysfunction, and impaired
peripheral oxygen extraction consistent with mitochondrial myopathy. The
review also highlights evolving applications in post-pulmonary embolism
syndromes and acknowledges that exercise hemodynamic thresholds and
protocols vary across centers, underscoring the need for broader
standardization.