Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism

Abstract

Introduction: Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment.

Materials and methods: Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria.

Results: Physiological dead space (Vd/Vt) (34.5±11.4 vs 50.8±6.6 %, p<0.001) and alveolar-arterial oxygen gradient (29±16 vs 46±12mmHg, p <0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC>0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p=0.08).

Conclusions: Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting.

Keywords: AT; Anaerobic threshold; CI; CPET; CTED; CTEPH; Cardiac Index; Cardiopulmonary exercise testing; Chronic thromboembolic disease; Chronic thromboembolic pulmonary hypertension; Cr; Creatinine Clearance; EDP; End diastolic pressure; FEV1; FVC; Forced expiratory volume (1second); Forced vital capacity; HR; Heart rate; Mean pulmonary artery pressure; Mixed venous oxygen saturations; N terminal pro brain natriuretic peptide; NT proBNP; PCWP; PE; PVR; Pulmonary capillary wedge pressure; Pulmonary circulation; Pulmonary embolism; Pulmonary vascular resistance; RA; RER; RV; Respiratory exchange ratio; Right atrium; Right ventricle; SvO(2); TPVO Index; Total pulmonary vascular obstruction index; mPAP.