Hemodynamic pulmonary response to exercise according to different resting pulmonary hypertension thresholds in chronic thromboembolic pulmonary disease
Authors: Huertas Nieto S , Velazquez Martin M T , Sarnago Cebada F , Manerio Melon N , Jimenez Lopez Guarch C , Segura De La Cal T , 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
Chronic thromboembolic pulmonary disease (CTEPD) defines all symptomatic patients who present mismatched perfusion defects on ventilation/perfusion (V/Q) scan and specific signs of organized fibrotic clots on computed tomography after at least three months of adequate anticoagulation in the absence of pulmonary hypertension (PH) at rest. Exercise limitation in CTED has been attributed either to an abnormal hemodynamic response to exercise or increased dead space ventilation. The proposal to decrease the PH threshold to mean pulmonary arterial pressure (mPAP) ≥20 mmHg and pulmonary vascular resistance (PVR) &gt;3 uWood (uW) in all PH groups could identify a subgroup of patients with borderline PH criteria, and an abnormal response at exercise in CTEPD.

Aim
We sought to determine the hemodynamic behaviour at exercise according to different resting pulmonary pressures in a cohort of patients with CTEPD.

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.Significant PH were ruled out with right heart catheterization (RHC): inclusion criteria implied mPAP &lt;25 mmHg and PVR &lt;3 uW and pulmonary arterial wedge pressure (PWAP) &lt;15 mmHg. Exercise RHC was performed in supine following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and cardiac output (CO) estimated by thermodilution were collected in each exercise level. Abnormal hemodynamic exercise response was defined when a value of multipoint mPAP/CO slope &gt;3 mmHg L–1 min–1 was reached. Patients were stratified in three groups according to resting mPAP and PVR: 1) Normal-no PH (mPAP &lt;20 mmH + RVP &lt;2 uW), 2) Borderline (mPAP ≥20 + RVP &lt;3 uW), 3) mild PH (mPAP ≥20 mmHg + RVP &gt;3 uW).

Results
Twenty-two CTEPD patients were stratified into three groups 1) mild PH: 3 patients, 2) borderline PH: 11 patients and 3) no PH: 8 patients. Median age between groups did not reveal differences. At rest, the mild PH group showed higher mPAP, higher total pulmonary resistance (TPR) and lower compliance, relative to borderline and normal groups without significant differences in PWAP and stroke volume (Figure 1). At peak exercise, no differences in the estimated flow between the three groups were found, despite a substantial increase of mPAP with respect to resting pressures (57.3±11 mmHg Vs 47.7±10.0 mmHg vs 34.1±5.7 mmHg, p trend = 0.006). The prevalence of an abnormal hemodynamic response the mild, borderline and normal groups was 100%, 63.6% and 37.5% respectively. Figure 2 summarizes exercise RHC parameters.

Conclusion
In patients with CTEPD, the presence of borderline or mild PH at rest, predicts an abnormal hemodynamic response to exercise, when compared with patients with no PH at rest. Nevertheless, in this latter group, more than a third of patients showed an abnormal response, suggesting the presence of established pulmonary vasculopathy

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