Determinants of exercise-induced pulmonary arterial hypertension in systemic sclerosis
Introduction
Systemic sclerosis (SSc) is a rare and complex disease, characterized by an extensive vasculopathy associated with auto-antibodies and fibrosis, with a multifactorial etiology [1]. Pulmonary arterial hypertension (PH), resulting from a pre-capillary mechanism, may be frequent in SSc with an approximated incidence of 8% to 13%, leading to an increased morbidity and mortality [2]. Echocardiography is an accurate non-invasive tool for the daily-life screening of patients at risk of PH [3]. Exercise echocardiography assessment of the pulmonary circulatory system has evolved over these last few years [4], [5], [6] and exercise-induced PH (EIPH) has recently been suggested as a potential useful tool for the early identification of patients with SSc at risk of developing resting PH [7], [8]. It seems however, that the incidence of EIPH may overestimate the percentage of onset of resting PH during follow-up [9]. Some recent studies have underlined that the origin of EIPH in SSc could be secondary, not only to pulmonary vasculopathy, but also to myocardial [10] and/or pulmonary impairment [11], [12]. Therefore, a post-capillary involvement in EIPH has been hypothesized in the literature [13], [14]. Hitherto, the echocardiographic determinants of EIPH in SSc remain unclear. The present study sought to evaluate the incidence of EIPH and its determinants in patients with SSc.
Section snippets
Methods
We prospectively studied 68 consecutive patients from January 2008 to November 2012 with a diagnosis of SSc, followed in the rheumatology center of CHU Sart-Tilman in Liège. Five patients refused the study protocol. Exclusion criteria were: (1) inability to provide informed consent, (2) previous ischemic heart or valvular heart diseases and (3) inability to perform an exercise test. Eighteen patients were excluded, 15 due to poor echogenicity and unquantifiable sPAP secondary to severe thinness
Population characteristics
Fifteen patients were excluded due to unquantifiable sPAP, 1 for moderate mitral regurgitation and 2 for known coronary artery diseases. Among the remaining 45 patients, 47% developed EIPH (n = 21). The sPAP increased significantly during exercise (from 25 ± 7 to 46 ± 14 mm Hg; p < 0.0001). Patients with EIPH had higher resting sPAP (29 ± 6 vs. 21 ± 5 mm Hg; p < 0.001), resting mPAP (20 ± 4 vs. 14 ± 3 mm Hg; p < 0.0001), exercise sPAP (58 ± 9 vs. 36 ± 8 mm Hg; p < 0.0001, Fig. 1), exercise mPAP (37 ± 6 vs. 24 ± 5 mm Hg; p < 0.0001) and
Discussion
The present study shows that (1) EIPH is common in patients with SSc (47%), (2) main mechanisms explaining EIPH are increased estimated exercise LV filling pressure and increased PVR and (3) taking into account the main factors generally considered as influencing sPAP (e.g. age, CO or pulmonary disease), the relationship between estimated exercise LV filling pressure, exercise PVR and exercise sPAP remains significant.
Conclusion
EIPH is frequent in patients with SSc (47%) and may be detected using exercise echocardiography. In patients with EIPH, our results suggest the potential role of increased exercise LV filling pressure and increased PVR. Exercise echocardiography could be useful for the screening and the understanding of the pathophysiological mechanisms leading to PH in patients with SSc. Further studies are needed to confirm these results and their impact on the outcome.
Source of funding
Damien Voilliot is supported by a research grant of the European Association of Cardiovascular Imaging.
Acknowledgments
We specially thank Carmine Celentano for his precious help and support for investigations in this study.
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