The present study introduced a new variable to assess RA function and added new implications into evaluation of functional status in PH subjects. The main findings were summarized as follow: (1) RAFI represented an easily accessible method of RA function assessment with good repeatability; (2) RAFI had remarkable correlation with indices of pulmonary arterial pressure, RV dimension, RV overload and cardiac function; (3) RAFI emerged as an independent factor in predicting WHO FC III or IV which indicated clinical deterioration. RAFI < 9.7 was the best cutoff to identify patients with WHO FC III or IV.
RA seems to play multiple roles (reservoir, conduit and contraction function) in regulating RV function. To date, there is now growing concern on RA function in patients suffering from PH. With the development of speckle-tracking echocardiography and three-dimensional echocardiography, it is feasible for investigating RA deformation and phasic function and the prognostic value of the mentioned variables has been well studied in PH [13–16]. However, analysis of RA deformation and phasic function requires special software which is not conducive to popularization. In contrast, RAFI is an easily obtainable echocardiographic variable of RA function assessment with good repeatability according to the present study. Moreover, compensatory changes in RA function might occur with abnormal RA size and/or RV systolic function. Compared with other indices of RA function, RAFI synthesizes the information on RA size (expressed by RA volumes), RA reservoir function (expressed by RAEF) and cardiac output (expressed by RVOT-VTI). These characteristics make RAFI promising for use in PH patients.
Previous studies have demonstrated the respective role of these 3 properties (RA size, RA reservoir function and cardiac output) on PH progression. A study with speckle tracking echocardiography showed that RA volume and reservoir function significantly correlated with functional status and exercise capacity in PH patients . According to Sato et al , RA volume and reservoir function are predictors of clinical worsening in patients with pre-capillary PH during a mean follow-up period of 24 months. Alenezi et al  emphasized that RA reservoir function is an independent predictor of death and hospitalizations in PAH after adjusting for age, sex, and RA area. However, comprehensive analysis of RA function based on RAFI in patients with PH has not been well described. Our study revealed that patients with lower RAFI exhibited increased NT-proBNP, decreased CO and worsen echocardiographic indices of cardiac function such as TAPSE, RVFAC, RIMP, S’ and RA strain. RAFI was also markedly related to pulmonary arterial pressure, PVR, RV dimension and RV overload in our study. Mouratoglou et al  also confirmed the correlation of RAFI with 6-minute walk distance, NT-proBNP and echocardiographic RV function. In addition, RAFI carried incremental prognostic value beyond that of established risk factors. Nevertheless, a single-plane algorithm in their study led to underestimation of RA volumes since it assumed RA enlargement was symmetrical. In the present study, standard orthogonal views at the same cardiac cycle of RA were available by using the XPlane function. Quantification of RA volumes with biplane area-length method was likely to be more robust and accurate for determination.
The mechanism of impaired RAFI and correlation of RAFI with other indices in PH patients may be explained as follows: Initially, RV hypertrophy develops to compensate for the increased RV afterload which may lead to RV diastolic dysfunction and RV filling pressure abnormal. As PH progression, RV chamber dilation accompanied with RV contractile dysfunction contributes to insufficient cardiac output, RV volume overload and RV filling abnormality. On the other hand, the dilation of tricuspid annular contributing to tricuspid regurgitation aggravates the RV volume overload and subsequently adds to an extra increase in RV filling pressure. Finally, right atrial pressure (RAP) elevates, RA enlarged and RA dysfunction existed.
WHO FC remains the most frequently used variable for prognostic evaluation and risk classification at diagnosis as well as during follow-up in PH centers [19, 20]. Generally, a worsening WHO FC is the principle indicator of disease progression and poor prognosis, which should trigger further diagnostic studies to identify the causes of clinical deterioration [19, 21, 22]. According to the recent guideline, patients with WHO FC III or IV were categorized as intermediate or high risk with an estimated 1-year mortality > 5% . Studies have been conducted to investigate the impact of RA function on WHO FC. RA reservoir function reduced gradually in PH patients with worsening WHO-FC [3, 17, 23, 24]. Moreover, RA reservoir function exhibited a better correlation with WHO FC than RV strain and RAA, suggesting that RA function might be a more sensitive indicator to identify clinical deterioration [17, 24]. However, no correlation of RAFI with WHO FC was observed according to Mouratoglou . The lack of correlation was mainly due to a high proportion of patients with congenital heart disease associated PH who were known to subjectively underestimate their functional capacity. Similar to most prior studies, our findings revealed that RAFI was associated with disease severity determined based on WHO FC. We also found that among the clinical and echocardiographic variables of right heart function including RA strain, RAFI emerged as an independent factor in predicting WHO FC III or IV which indicated an intermediate or high risk for clinical worsening or death. These results demonstrated the crucial implications of RAFI evaluation in revealing functional status and disease severity over other cardiac functional variables.
4.1 Study limitations
There were several potential limitations in our study. First, the present study was a retrospective analysis in a single-center. Second, the small sample remained as a limitation towards further subgroup analysis. Future prospective studies in a larger patient population are necessary to validate the application of RAFI in PH. Third, we included PH patients with diverse etiologies in this study. However, patients included in our study were mainly PAH and CTEPH which had similar pathophysiologic features. Therefore, the impact of etiology on the results was greatly minimized. Forth, we used biplane method rather than three-dimensional echocardiography to assess RA volumes when calculated RAFI. Although three-dimensional echocardiography has advantages over two-dimensional method in quantifying right heart volumes, biplane method using XPlane technique is easier to performed and less affected by image quality, which is easy for promotion and application.