Resting RV-PA uncoupling as predictor of exercise induced pulmonary hypertension in patients with chronic thromboembolic pulmonary disease

Abstract Background and aim Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with exercise limitation caused by established vasculopathy. Symptoms after an acute pulmonary embolism (PE) with persistent lung perfusion defects need a complete diagnostic approach. Screening these symptomatic patients with resting echocardiography (echo) is challenging. The aim of this study is to analyze the echocardiographic predictors at rest of exercise induced PH (ex-PH) in patients with suspected CTED. Methods Symptomatic patients with confirmed perfusion defects in lung V/Q scintigraphy despite optimal anticoagulant therapy for at least 3 months after an acute PE were selected. Structural heart disease or pulmonary disease were excluded. Relevant PH at rest was ruled-out (mPAP <25 mmHg, PVR <3 Wu, PAWP <15 mmHg according to available definition at the time). A right heart catheterization with incremental exercise protocol (cycle ergometer), and simultaneous transthoracic echo were performed. Hemodynamic and echo parameters were collected at each exercise level. A mPAP/CO slope >3 mmHg·L−1·min−1 was considered an abnormal hemodynamic response to exercise. Right V-PA coupling was estimated as TAPSE/sPAP and RV free wall global longitudinal strain (RV-GLS)/sPSP ratios. Results 31 patients (32% women, mean age 51.8 ± 14.7 y) were included. Fourteen patients (45%) developed ex-PH. Baseline characteristics according to invasive hemodynamic response are shown in Table 1. Resting RV function (TAPSE and RV-GLS), but not size, was significatively impaired in the ex-PH cohort. Resting echo sPAP or TR max velocity did not achieve any difference between groups, although invasive sPAP did. Resting TAPSE/sPAP and RV-GLS/sPAP were significantly reduced in the ex-PH group. In ROC curve, resting TAPSE/sPAP showed an AUC 0.75 (CI 95% 0.56-0.95) to predict ex- PH. A cutoff point of <0.62 mm/mmHg at rest, showed a S 88% / E 71%, PPV 78.9 % and NPV 83.3%. Resting RV-GLS/sPAP ratio showed an AUC 0.859 (CI 95% 0.708 – 0.990) to predict ex- PH. A cutoff point of > - 0.67 %/mmHg, showed a S 75.0% / E 87.5%, PPV 78.2 % and NPV 82.4%. to predict ex- PH. Conclusions Exercise limitation appears to be attributable to ex-PH in up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE without relevant PH at rest. Echo derived parameters at rest, surrogates of RV-PA uncoupling, such as TAPSE/sPAP and RV-GLS/sPAP, could be of great interest to identify patients with abnormal hemodynamic response to exercise, and help in the initial non invasive diagnostic workup of these increasingly group of patients.ROC curvesTable 1Resting Echo values