EXERCISE DOPPLER ECHOCARDIOGRAPHY (EX-ECHO) AS A TOOL TO DETECT PULMONARY ARTERIAL HYPERTENSION (PAH) IN SYSTEMIC SCLEROSIS (SSC) PATIENTS IN A PRE-CLINIC ASYMPTOMATIC PHASE

Background: In SSc, the involvement of interstitium or vascular system of the lung may lead to PAH, regarded as the most important negative prognostic factor for survival of the disease. PAH, defined as a mean pulmonary artery pressure (PAP) > 25 mmHg at rest and > 30 mmHg during exercise measured by right heart catheterisation (RHC), is often asymptomatic or olygosymptomatic in the early phase of SSc and, when it becomes symptomatic, severe vascular damages of lung vessels are already present. Doppler echocardiography is a reliable non invasive screening test of systolic PAP, but it is not as specific and sensitive as RHC in detecting PAH, especially in early SSc with minimal increases of PAP values. Ex-echo, measuring PAP during exercise and allowing to differentiate physiologic from altered PAP responses, is regarded as an useful technique to identify sub-clinical PAH in patients with exercise intolerance. Objectives: 1) To evaluate by ex-echo the change of PAP in patients with SSc without signs of clinical, instrumental and bio-umoral evidence of lung involvement; 2) to correlate PAP after exercise (PAP-ex) values to clinical and bio-umoral parameters of lung involvement. Methods: 27 SSc patients [mean age: 50.0 ± 16.0 years; mean disease duration: 7.0 ± 7.85 years; 25 females, 2 males, all affected by the limited cutaneous subset of the disease (lSSc)], in which clinical and instrumental examination (high resolution computerised tomography of the chest, pulmonary function tests) ruled out lung involvement were enrolled. The patients underwent standard 2-dimensional and Doppler echocardiography, basal and after Exercise Doppler echocardiography (ex-echo) [evaluated by a supine cycloergometer (Ergometrics 900, Esaote, Florence, Italy)]. Bioumoral markers potentially related to PAH (troponine I, D-dimer, pro-BNP, uric acid, Endothelin 1, CD40 ligand) were also assessed. The values of PAP-ex exceeding 45 mmHg at Ex-echo were considered as abnormal. Results: 14/27 lSSc patients (52%) presented a PAP-ex > 45 mmHg, while in 13/27 patients (48%) PAP-ex values remained < 45 mmHg (45.8 ± 4.5 mmHg versus 36.2 ± 3.1 mmHg; p< 0.001). The groups were not different nor in all the other echographic and ergometric parameters assessed neither in the clinical tests and bioumoral markers considered. PAP-ex significantly correlated with D-dimer values (p=0.0125; r2= 0.2029), but not with any other clinical, instrumental and bioumoral variable. Conclusion: Exercise doppler echocardiography is an useful tool for identifying a cluster of lSSc patients with sub-clinical PAH, that, possibly, could be treated early with a therapy able to reverse PAH and to halt the progression of pulmonary vessel involvement.