Prognostic value of exercise-induced pulmonary hypertension in patients with systemic sclerosis with borderline pulmonary hypertension

Abstract Background/Introduction Pulmonary hypertension (PH) is one of the strongest prognostic factors in patients with systemic sclerosis (SSc). In the early stage of PH, pulmonary artery pressure (PAP) is often normal at rest due to the pulmonary vascular reserve capacity, but increases abnormally during exercise. However, little is known whether exercise-induced pulmonary hypertension (EIPH) could be associated with subsequent progression of PH at rest in SSc. Purpose We aimed to clarify whether EIPH in exercise stress echocardiography is associated with the progression of resting PH in patients with SSc and borderline PH. Methods Consecutive patients with SSc who underwent echocardiography at our university hospital between September 2019 and October 2024 were screened. We identified patients who underwent cardiopulmonary exercise testing combined with simultaneous exercise stress echocardiography (CPETecho). Then, we divided them into two groups based on the presence of EIPH, defined as an estimated mean PAP 30mmHg during exercise and a mean PAP/cardiac output 3 Woods units (Figure 1). Patients who did not undergo CPETecho and had a mean PAP 20mmHg at rest were included as controls. Systolic PAP was estimated as the tricuspid pressure gradient and right atrial pressure, and mean PAP was calculated as 0.6 × systolic PAP + 2 mmHg. The primary outcome was the change in resting systolic PAP from baseline to follow-up echocardiography. Results We screened 1575 studies (543 patients). The final study cohort included 127 patients who underwent CPETecho and 198 controls. Mean PAP was 19.9 mmHg in the 127 patients and 15.4 mmHg in 198 controls. We divided 127 patients into 56 patients with EIPH and 71 without EIPH. There were no differences in sex, body mass index, disease type (diffuse or limited type), disease duration, or positive rate of anticentromere antibody among the groups. Patients with EIPH had a higher prevalence of diabetes and interstitial lung disease than other groups. Left ventricular mass index, left atrial volume index, and E/e' ratio were similar between the patients with and without EIPH. Compared with patients without EIPH, those with EIPH had higher systolic PAP and mean PAP/cardiac output slope. The median follow-up duration was 2.4 years. The change in systolic PAP was slightly but significantly higher in patients with EIPH than those without EIPH (+1.2 mmHg vs -1.0 mmHg, p=0.04) and controls (+0.6 mmHg). When excluding cases in which pulmonary vasodilators and heart failure medications were initiated after baseline echocardiography, systolic PAP decreased in patients without EIPH while it increased in those with EIPH (Figure 2, 27.4 to 25.8 mmHg p=0.04 in EIPH (-) vs 30.2 to 32.1 mmHg p=0.04 in EIPH (+), p=0.005 between the groups). Conclusion The elevation in PAP estimated by exercise stress echocardiography was associated with a slight increase in PAP at follow-up in patients with SSc and borderline PAP.Study flow chart Primary outcome