Discussion
In the present research, we observe that cirrhotic patients without PAH have higher PAS values than healthy subjects, which may indicate an early change in the pulmonary vascular bed among these cases. To our knowledge, this should be the first study demostarating higher PAS values in cirrhotic patients.
Nowadays, the average life expectancy of cirrhotic patients is prolonged due to early diagnosis and effective treatment modalities. However, complications related to portal hypertension, which is the main cause of mortality, are frequently observed. (1-4). Portal hypertension is included in the WHO PAH group I; PAH caused by portal hypertension is termed PoPH. Even though the underlying pathophysiologic mechanisms of PoPH are somewhat complex and not fully understood, it is hypothesized that the passage of some vasoconstrictive substances, mainly serotonin and endothelin-1, into the lung circulation with portosystemic collaterals and shunts is the main mechanism of developing PoPH (14). Another possible explanation is that thrombi caused by venous thromboembolism can enter the lung circulation through shunts, thereby resulting in PAH (15, 16). Furthermore, hyperdynamic circulation in cirrhotic patients can cause excessive blood flow to the lung circulation, which may promote PAH formation (15). All in all, it is still not clear why PoPH develops in a small proportion of cirrhotic cases with PH.
In previous studies, although different rates have been reported, PoPH was detected in 1-2% of cases with PH and in 5-10% of cases who were candidates for liver transplantation (7, 16). These findings highlight that cirrhotic patients should be evaluated more carefully for the development of PoPH and that a screening plan is needed. In a recent analysis, the importance of early recognition for PAH was noted, and some echocardiographic parameters, including PfAT, RV isovolumic relaxation time and Tei index, were suggested (17). However, measuring such parameters is quite time consuming. In a prospective study that included patients waiting for liver transplantation, 7 out of 17 patients with an echocardiographic diagnosis of PAH were demonstrated by right heart catheterization (RHC) to not show PoPH. In that study, there was a 10 mmHg greater difference between RHC and echocardiographic sPAP (18). In this reseach, there was also no significant dissimilarities between the groups in terms of sPAP. Because the pulmonary vascular bed has high capacitance property, sPAP does not usually develop until the loss in microcirculation reaches 60-70%. After this threshold is exceeded, clinical findings occur and sPAP increases (19). Therefore, we consider that using only echocardiographic measurements of sPAP may be misleading for early diagnosis among these patients.
PAS, which is a simple and easy echocardiographic parameter to determine, is found to be linked with a worse survival in PAH patients (20). In addition, an independent and significant relationship between PAS and RV dysfunction has been demonstrated (21). Previously, PAS was shown to be an significant determinant in the occurrence of PAH in subjects with chronic lung disease (10), as well as an early prognosticator of RV dysfunction in patients with systemic lupus erythematosus and HIV (9,12). However, to our knowledge, no prior research has examined the PAS in cirrhotic patients. This might be the first study to show that the PAS values are significantly elevated in subjects with cirrhosis comparing in healthy participants. Moreover, PAS was an independent predictor that was associated with cirrhosis disease according to multivariate logistic regression analysis. Additionally, we detected a positive correlation between PAS and sPAP values and a negative correlation between PfAT and sPAP values, while observing that there was no difference in terms of PAS values between clinically compensated and decompensated cirrhotic patients.
Our study results are important and valuable in terms of clinical perspectives. Because most cirrhotic patients are usually asymptomatic at the time of recognition of PAH, early diagnosis facilitates treatment as well as reduces the mortality risks in such patients. Similarly, no clear PAH was observed among the cases we investigated; however, the cirrhosis group had higher PAS values. Therefore, we believe that PAS may show us transitions in the pulmonary vascular region before the development of significant PAH.