TAPSE/sPAP at peak exercise as a surrogate of RV-PA uncoupling can predict exercise-induced pulmonary hypertension in symptomatic patients with chronic thromboembolic pulmonary disease
Authors: Jimenez Lopez Guarch M C , Huertas-Nieto S , Sarnago Cebada F , Aguilar R , Segura De La Cal T , Maneiro Melon N , Garcia Robles J A , Cruz Utrilla A , Velazquez Martin M , Martin De Miguel I , Solis Martin J , Arribas-Ynsaurriaga F , Escribano Subias P 
Published: November 2023

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. Exercise echocardiography (ex-echo), with surrogate parameters of ventricular-arterial (VA) coupling could be of interest to non-invasively assess a pathological hemodynamic response. The aim of this study is to analyze the role of ex-echo and non-invasive assessment of VA coupling by echocardiography in predicting an abnormal hemodynamic response in symptomatic patients with chronic thrombotic pulmonary vascular occlusion.

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. Relevant PH at rest was ruled-out (mPAP &lt;25 mmHg, PVR &lt;3 Wu, PAWP &lt;15 mmHg, according to available definition at the time). Right heart catheterization with incremental exercise protocol (adapted cycle ergometer), with simultaneous transthoracic echo were performed. Parameters were collected at each exercise level. A mPAP/CO slope &gt;3 mmHg·L−1·min−1 measured invasively was considered an abnormal hemodynamic response to exercise. Right VA coupling was estimated as TAPSE/sPAP ratio. A non invasive echo mPAP/CO slope was obtained from Doppler measurements.

Results
31 patients (32% women, mean age 51.8 ± 14.7 y.) were included. Fourteen patients (45%) developed ex-PH. Baseline and peak exercise characteristics and parameters according to hemodynamic response are shown in Table 1. Moderate significative correlations between invasive hemodynamics and echo derived parameters at peak exercise were observed: sPAP: r=0.793 (p &lt;0.001), CO r=0.532 (p 0.003), mPAP/CO slope r=0.458 (p 0.012). Peak exercise TAPSE/sPAP showed an AUC=0.85 (CI95% 0.70-1.00, fig. 1), and a cutoff point of &lt;0.52 mm/mmHg, showed a S 80% / E 93% PPV 92% and NPV 81%, to predict an abnormal response. The echo derived mPAP/CO slope showed an AUC=0.78 (CI95% 0.59-0.96), and a cutoff point of &gt; 2.44 mmHg·L−1·min−1 showed a S and E of 85% and 67% PPV 71 % and NPV of 83% to predict ex-PH. Abnormal septal motion at peak exercise showed a S 90%, E 78%, PPV 71% and NPV of 93% to predict ex-PH.

Conclusions
In our study cohort, up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE, without relevant PH at rest, developed ex-PH. New echo-derived parameters such as TAPSE/sPAP, a surrogate RV-PA coupling parameter, and echo-mPAP/CO slope, showed a good performance to predict an abnormal hemodynamic response. Ex-echo, feasible, non invasive and widely available, might represent a useful tool for the selection of patients for invasive hemodynamic workup.Peak exercise TAPSE/sPAP ROC curveTable 1