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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2018, Heart Failure ClinicsCitation Excerpt :However, the exact clinical relevance of abnormal responses in healthy patients with a known increased risk of developing PH and right heart failure remains unclear. The current state of knowledge based on reported exercise TTE studies of the pulmonary circulation and the RV in different populations are presented in Tables 1–3.19–64 Thus, the available literature shows great disparities in sample sizes (from n = 8 to n = 113), exercise protocols (leg press, cycle, or treadmill ergometry), timing of measurements, selection of variables of interest, and different work rates (ranging from 23 ± 7 WU up to 175 ± 50 WU).
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2018, Heart Failure ClinicsCitation Excerpt :In a population of 164 SSc patients, the authors demonstrated that exercise PH (defined as an exercise sPAP ≥50 mm Hg and exercise PVR ≥3 Wood units during echocardiography) was present in approximately half of the patients with normal resting sPAP and was affected by age, ILD, and RV and LV diastolic dysfunction, whereas only a minority (5%) of these patients had an increase in PVR during exercise, suggesting high heterogeneity of the pathophysiologic background.69 These data were further confirmed in a smaller population of 45 patients, where exercise PH was present in 21 patients, with a positive correlation between exercise sPAP and both exercise left atrial pressure and exercise PVR (respectively, r2 = 0.61 and r2 = 0.57; P<.05), again suggesting that exercise PH was related to both increased exercise LV filling pressure and exercise PVR.70 Thereby, exercise echocardiography allows identification of those patients with an abnormal increase in PAP as well as a better understanding of the mechanism leading to abnormal pulmonary hemodynamic response during exercise.
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2018, Journal of the American Society of EchocardiographyCitation Excerpt :The percentage of exercise increase in sPAP is high in SSc and clearly overestimates the subset of patients who will develop resting PAH.79-81 Because elevated sPAP in SSc may occur also as a consequence of interstitial lung disease or LV systolic and/or diastolic dysfunction, caution should be taken to distinguish the different etiologies of PH. Echocardiographic assessment of increased PVR during exercise has been proposed to detect patients at higher risk for developing resting PAH but warrants further confirmation.76,82-84 Additional information can be found in Supplemental Figures 1-7 and Videos 1-2 (available at www.onlinejase.com).
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2018, Autoimmunity ReviewsCitation Excerpt :Nevertheless, in the subset of patients with interstitial lung disease, exercise can result in desaturation. Furthermore, SSc patients are at a higher risk of developing exercise induced PAH which occurs subsequent to increased ventricular filling pressure, and increased pulmonary vascular resistance associated with exercise [261,262]. The body of evidence regarding the impact of exercise in SSc remains limited, yet there exists a modest number of studies discussing the influence of aerobic and resistance exercise in SSc patients with and without pulmonary hypertension.
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2017, Journal of the American Society of EchocardiographyCitation Excerpt :Annual screening with rest transthoracic echocardiography has been proposed for patients with either known heritable mutations for PAH or a first-degree relative of familial PAH, patients with scleroderma, patients with portal hypertension, adults with sickle cell disease, or those with HIV infection.197 While the role for SE in the screening evaluation should be considered on a case-by-case basis, there is emerging evidence that SE identifies patients at risk or early in development of disease.186,188,198-200 Rather than simply focusing on PAP with exercise, studies have suggested that an assessment of PVR is more sensitive.201