All the 12 included studies were cohort studies published between 2006 and 2016. NOS scores are all over 5 points, as listed in Table 2, which suggests the reliability of our results. The Egger test for the control, no PAH and EIPH group was associated with P values of .21, .31 and .34, respectively, suggesting low likelihood of publication bias.
The term “exercise-induced PAH” (EIPH) has been reported as a preclinic asymptomatic phase of resting PAH in SSc patients.[28,29,43] Stress echocardiography is considered to be an effective tool in predicting the development of PAH at rest in SSc patients.[29,43] Voilliot et al[29] reported 11 (64.7%) of 17 SSc patients with exercise PASP > 50 mmHg developed PAH during follow-up (25 ± 15 months). Codullo et al[43] described that ΔPASP > 18 mmHg could be used as a cutoff value with a sensitivity of 50% and specificity of 90% [N = 170] for predicting the development of PH during follow-up (3.5 ± 0.2 years). Additionally, Yagi et al[44] reported bosentan ameliorated an EIPH patient with no PAH-related symptom and ΔPASP > 30 mmHg. Consequently, EIPH is a major predictive factor for onset of resting PAH in SSc patients, and it may provide evidence for bosentan therapy in future.
Based on our results and relevant studies, we suggest that a SSc patient with ΔPASP > 24 mmHg should have regular follow-ups every 3 to 6 months as recommended by the guideline;[9] when ΔPASP is more than 29 mmHg, there should be a high degree of suspicion for PAH, and such patient should be advised to have right heart catheterization for pulmonary vascular hemodynamics assessment. However, further investigation is required to clarify validity and efficacy of these results. Moreover, a large-scale prospective study is also needed to confirm whether SSc patients with ΔPASP > 30 mmHg could benefit from bosentan therapy for PAH treatment.
Some limitations of this study should be highlighted. Due to limited reported data, several hemodynamic parameters (pulmonary vascular resistance, right ventricular contractile reserve, left ventricular systolic, diastolic dysfunction, etc.) could not be analyzed. Due to lack of evidence supporting the accuracy of ΔPASP in detecting PAH, the validity and role of ΔPASP is unclear. Moreover, the stress protocols of exercise electrocardiography test are different in different study groups.
The accuracy and validity of ΔPASP for the detection of early PAH should be discussed in a further large-scale prospective study. Additionally, further research is required for comparing accuracy and risk between different exercise tests (such as ergometer exercise test, treadmill exercise test and master's 2-step exercise test) in detecting PAH.
ΔPASP in SSc patients may increase as their illness progresses, and it may also be a useful parameter for predicting and detecting early PAH. Further research is required to assess both its validity and efficacy.
Song Yang contributed to drafting this work, writing and revising this paper, searching relevant literatures, assessing the quality of each included article, data extraction, analysis and interpretation of data for this work.
Jing Wu contributed to searching relevant literatures, assessing the quality of each included studies, and revising this work
Si Lei, Rong Song and Ye-yu Cai contributed to revising this work.
Shang-jie Wu contributed to revising this work, and providing the outline, conception and direction of this study.
All authors have approved the submitted version of the manuscript.
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