In the present study, a statistically significant increase of PAS was demonstrated in patients with SSc without overt PAH. Our results are important in terms of providing data for early deformation in pulmonary vascular bed in this patient group. As a result of our study, we demonstrate that deformation in the pulmonary vascular bed starts from the early period of the SSc and increases progressively.
To the best of our knowledge, this is the first study using TTE to evaluate the influence of PAS in patients with SSc. SSc, one of the most complicated autoimmune diseases, involves mainly the organ systems. The underlying pathogenetic process includes endothelial damage, inflammation, overexpression of specific adhesion molecules, abnormal neurovascular control, and tissue fibrosis . Several clinical manifestations such as PAH, Raynaud phenomenon, digital ulcers, the hypertensive renal crisis occurs due to these alterations, which are present even in the earliest stages of the disease . An imbalance occurs between the mediators which control vasomotor tone that leads to irreversible remodeling of the pulmonary vessels as a result of vasoconstriction, vascular endothelial cell proliferation, vascular smooth muscle hypertrophy during PAH progression. . Remodeling of the pulmonary vessels causes impairment in pulmonary elasticity . Previous studies demonstrated that changes in elasticity are primarily due to an increase in PAP . In their research, Friesen et al. examined 56 patients with PAH and found that PAS assessed by cardiac magnetic resonance non-invasively is a major contributor to right ventricle dysfunction .
SSc patients can be presented with dyspnea, or shortness of breath due to cardiopulmonary involvement especially increased sPAP. However, there is a silent pre-clinical period with an unknown duration in SSc [6, 20]. As the highest prevalence of PAH amongst the various CTD is observed in SSc, patients should be evaluated more carefully, and screening must be planned . Current guidelines suggest at least annually echocardiographic evaluation for all SSc patients [1, 21, 22]. It is clinically hard to diagnose early changes in pulmonary vasculature because most diagnostic tools focus on sPAP. As long as cardiopulmonary involvement, especially PAH, is the most important cause of death in SSc patients, diagnosing the early stages of the disease is crucial .
The early microvasculature changes in SSc patients, such as increased pulmonary elasticity, could be examined by PAS [9, 12]. PAS and other abnormal flow hemodynamics in PAH are strongly associated with impaired elevated right ventricular functions and also with disease severity and poor clinical outcomes in patients with PAH . Singh et al., in their research, investigated pulmonary hemodynamics invasively in patients with PAH and found pulmonary vascular distensibility is an early and sensitive hemodynamic marker of pulmonary vascular disease . The gold-standard assessment of PAS, which is a determiner of pulmonary vascular distensibility, is right heart catheterization. Because of its complexity, risks, and widespread inaccessibility, non-invasive methods have been developed of diagnostic techniques [8, 25]. PAS could be determined easily by TTE. The clinical implication of PAS has been validated by several studies. Early detection of impaired pulmonary elasticity and increased PAS evaluated in polycystic ovary syndrome patients by Abacioglu et al. , in cirrhosis patients by Oz et al. , in heart failure patients by Yenercag et al., and Yildirim et al. , in asthma patients Baysal et al. , and in human immunodeficiency virus-infected patients Cerik et al. .
Dogan et al., in their study of 25 SSc patients without overt PAH, found that pulmonary pulse transit time was a predictor of the development of PAH . Consistent with this, we revealed that PAS increased in SSc patients compared to healthy volunteers, and we also determined a positive correlation between Scl duration and PAS. In addition, there was also a positive correlation between C - reactive protein, ESR, and mRSS, which are other parameters showing disease severity and PAS .
In all these studies, the researchers evaluated the value of PAS for early detection of PAH in risky populations as in our study. It is unclear how the clinical approach should be in these patients in whom a change in the pulmonary vascular bed has been demonstrated, but no overt PAH has occurred. The studies can shed light on the planning of clinical studies on this evidence gap.
The present study has some limitations that need to be addressed:
First of all, the small number of patients and the cross-sectional observational nature of the study are the main limitations. Second, although many clinical studies have proved the validation of clinical efficacy, our data could be confirmed by MRI or RCH. Third, there is no data about the patients' development of overt PAH in clinical follow-up.