Different diagnostic criteria agreement for exercise pulmonary hypertension in chronic thromboembolic pulmonary disease
Authors: Huertas Nieto S , Sarnago Cebada F , Velazquez Martin M T , Jimenez Lopez Guarch C , Segura De La Cal T , Manerio Melon N , Cruz Utrilla A , Olazabal Valiente A , Ropero Cristo M J , Flox Camacho A , Nuche Berenguer J , Arribas Ynsaurriaga F , Escribano Subias P 
Published: October 2022

Abstract

Background
Hemodynamic changes during exercise have emerged as a diagnostic tool in patients with suspected pulmonary hypertension, considering that an abnormal response may reveal an incipient vasculopathy, particularly in chronic thromboembolic disease (CTED). Since mean arterial pressure (mPAP) is considered a flow-dependent variable, diagnosis of an abnormal pulmonary hemodynamic response has changed over time. Different methods to determine a pathological mPAP to Cardiac Output (CO) ratio have been proposed. Multipoint mPAP – CO Slope &gt;3 mmHg/L/min has reached board consensus for determining an abnormal pulmonary response to exercise as this method can characterize mPAP–CO response across all exercise stages. Given the technic difficulties to obtain this parameter, other criteria have been proposed.

Aim
To investigate the diagnostic concordance and the reproducibility of the different abnormal pulmonary exercise hemodynamic response criteria in a cohort of patients with CTED.

Methods
We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism. The thrombotic burden was assessed with computed tomography (CT). Lelf Heart Disease (LHD) and significant PH were ruled out with RHC (inclusion criteria implied resting mean pulmonary arterial pressure (mPAP) &lt;25 mmHg and pulmonary vascular resistance (PVR) &lt;3 uW and pulmonary arterial wedge pressure (PAWP) &lt;15 mmHg). Exercise RHC was performed in supine position following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and CO estimated by thermodilution were collected at each exercise level. Total pulmonary resistance (TPR) was calculated by dividing mPAP by CO. The abnormal hemodynamic response according to the more viable proposed criteria: 1) mPAP &gt;30 mmHg and TPR &gt;3uW at peak exercise, 2) ΔmPAP/ ΔCO &gt;3 mmHg/L/min at rest and peak exercise; was compared to the pathological reference threshold multipoint PAPm/ CO slope &gt;3 mmHg/L/min.

Results
22 patients (median age of 54.5±14.8 years old) were recruited. Baseline characteristics and RHC values are summarized in Figure 1. Positive agreement was 93% (77% – 98%) in case of mPAP30peak+ TPR3peak versus mPAP/CO slope (k=0.810) and 91% (74% – 97%) in case of ΔmPAP/ΔCO versus mPAP/CO slope (k=0.801). Both criteria showed high diagnostic accuracy for an abnormal response diagnosis compared with the reference. Figure 2 summarizes their respective sensitivities and specificities. Patients misdiagnosed were those whose hemodynamic response was close to the reference cut-off values (mPAP/CO slope between 2 and 4 mmHg//L/min).

Conclusion
In a cohort of patients with CTED without significant PH at rest or LHD,the three methods proposed to diagnose an abnormal pulmonary exercise hemodynamic response show accurate concordance. Disagreement was higher in patients with a borderline pathological response.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia