The role of early CPET follow-up after acute PE in predicting long-term outcomes

Background Persistent functional impairment affects nearly half of patients following acute pulmonary embolism (PE), often leading to post-PE syndrome and, rarely, chronic thromboembolic pulmonary hypertension (CTEPH). While resting assessments frequently underestimate functional deficits, cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of the integrated response to effort. Early identification of ventilatory inefficiency and impaired gas exchange at the 3-month mark may serve as a critical window for predicting long-term morbidity. Purpose This study aimed to evaluate ventilatory efficiency and gas exchange abnormalities using CPET in post-pulmonary embolism (PE) patients at 3 months after the acute episode, to differentiate mechanisms of exercise intolerance and to identify the possible long-term clinical outcomes. Methods We prospectively enrolled 98 patients at 3 months after the acute pulmonary embolism episode, and 87 symptomatic (dyspnea) controls, with relatively normal CPET after examination. All subjects underwent maximal incremental cycle ergometry. Measurements included peak oxygen consumption (VO2/kg), ventilatory efficiency (VE/VCO2 slope, VE/VCO2 at AT), end-tidal CO2 pressure (PETCO2), and oxygen saturation (SpO2) dynamics. Results were correlated with NT-proBNP and right ventricular (RV) longitudinal strain. Results At 3-month follow-up, post-PE patients exhibited significantly lower aerobic capacity (median 18 vs 27 ml/min/kg; p<0.05). Integrated analysis identified three distinct phenotypes: 18% at risk for developing chronic thromboembolic pulmonary hypertension (CTEPH) (defined by VE/VCO2 slope >40, PETCO2 <28 mmHg, and peak SpO2 <90%), 35% with physical deconditioning, and 47% functionally recovered. We identified a "red triad" of vascular limitation: VE/VCO2 slope >30, PETCO2 <30 mmHg, and SpO2 <92% at peak effort. Notably, post-PE patients faced a 4-fold higher probability of physical deconditioning (OR 4.0). Impaired RV free wall strain occurred in 68.2% of patients, correlating with ventilatory inefficiency and elevated NT-proBNP, despite normal resting TAPSE values. Conclusions CPET unmasks vascular limitations 3 months post-PE that remain undetected at rest. Identifying the triad of respiratory inefficiency, impaired gas exchange, and deconditioning is vital for early CTEPH screening and initiating personalised rehabilitation to break the cycle of post-embolic inactivity.