Invasive cardiopulmonary exercise testing: Physiologic assessment of unexplained dyspnea and exercise intolerance

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.