Non-invasive multimodal prediction of exercise precapillary pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Introduction Chronic thromboembolic pulmonary disease (CTEPD) refers to exercise limitation due to chronic thrombi in the pulmonary arteries after a pulmonary embolism, absence of resting pulmonary hypertension (PH) but exercise precapillary PH (exprecapPH). Diagnosis of CTEPD requires exercise right heart catheterization (exRHC), but it is not widely available. Since persistent perfusion defects in lung scintigraphy after a pulmonary embolism appear in 30-50%, patients who might benefit from exRHC due to a higher probability of exprecapPH could be stratified by non-invasive diagnostic tests. Purpose The aim of this study was to identify non-invasive parameters that predict exprecapPH among a group of symptomatic patients with chronic thromboembolism. Methods Data come from a prospective cohort of 53 patients with perfusion defects in lung scintigraphy despite anticoagulation after a pulmonary embolism without or mild resting PH, undergoing exRHC via supine cycle ergometry and concomitant echocardiography. A multipoint mean pulmonary artery pressure (mPAP)/cardiac output (CO) slope was calculated. Cardiopulmonary exercise testing (CPET) was performed 24 hours before exRHC. Results Mean age was 50.8±13.5 years, 35 (66.0%) were males. Fifteen (28.3%) developed exprecapPH. Mean mPAP/CO slope was 4.5±1.6 vs 0.9±0.5 mmHg/l/min; p0.001 in patients with versus without exprecapPH. Table 1 depicts comparisons between groups. Patients with exprecapPH were older. In CPET, patients with exprecapPH had significantly lower peak oxygen saturation and higher ventilatory inefficiency (PETCO2 at VT1, ventilatory equivalents for CO2 at VT1 and VE/VCO2 slope). In resting echocardiography patients with exprecapPH had greater right atrial area, right ventricular basal diameter and tricuspid annular plane systolic excursion (TAPSE). Exercise unmasked a significant elevation of tricuspid regurgitation peak velocity in exprecapPH. Right ventricular basal diameter remained higher in patients with exprecapPH, while peak exercise TAPSE did not differ between groups. The non-invasive surrogate of ventricular-arterial coupling TAPSE/pulmonary artery systolic pressure (PASP) was lower at rest and peak exercise in exprecapPH. Univariable and multivariable regression models were built with resting and exercise echocardiography and CPET (Table 2). In the first multivariable model age at the time of exRHC, VE/VCO2 slope 30 and resting right atrial area were independently associated with exprecapPH. The AUC of the model was 0.85. In the second multivariable model age at the time of exRHC, VE/VCO2 slope 30 and TAPSE/PASP ≤0.38 at peak exercise were independently associated with the presence of exprecap PH. The AUC of the model was 0.91. Conclusions Non-invasive stratification by resting and exercise echocardiography and CPET might aid selection of patients with chronic thromboembolism who might benefit from further invasive diagnostic workup via exRHC and treatment.Table 1 Table 2