This is the first study that has suggested a correlation between the change rate in 6MWD and hospital readmission and hospital visits in patients with PAH. This study demonstrated that changes and the change rate in 6MWD were correlated with unplanned hospital readmission, ED visits, and hospital visits.
6MWD has been used to evaluate cardiorespiratory fitness and prognosis in patients with PAH2–5. Kholdani et al. have reported that hospital readmissions within 30 and 90 days after discharge were 16.9% and 4.2%, respectively, in patients with PAH17. 6MWD is an independent predictor of readmission rate and a shorter 6MWD is associated with higher readmission rates in patients with CHF13,18. In this study, the average age frequency of hospital admissions showed a difference between the three groups, and group 1, which had an improved 6MWD of more than 15%, had the highest readmission rate compared with other groups. This suggests that a higher increase in 6MWD in the long-term follow-up period (mean 3.88 years) is not associated with a reduction in the hospital readmission rate in patients with PAH. This finding conforms to that of a previous study by Savarese G et al., who have reported that improvements in 6MWD are not related to positive clinical outcomes in patients with PAH5,11. Previous studies5,11 have focused on the effects of changes in 6MWD on clinical events, including mortality, hospitalization, and survival rate. In this respect, this study with a long-term follow-up is meaningful to confirm the positive correlation between the change rate in 6MWD and hospital readmission rate in patients with PAH. A study19 has reported that % predicted 6MWD was predictive of all-cause mortality, but its prognostic value was not superior to that of absolute 6MWD. Therefore, it should be considered that the criteria for grouping in this study are different from those of previous studies5,11 and the difference may affect the results in terms of clinical events.
A high number of previous ED visits serves as a predictor for unplanned hospital readmissions21. Unscheduled ED visits are an important quality indicator of patient safety and prognosis; the rate of unscheduled ED revisits varied ranging from 0.4–49.3%21. The frequency of ED visits in adult individuals with PAH was reported to be 12.8 per 100,00022. In this study, the average annual number of ED visits showed no difference between the three groups, although group 1 had the highest frequency with 0.41. However, in the correlation analysis, the average annual number of ED visits was inversely associated with changes in 6MWD. The result indicates that the greater the improvement in the 6MWD, the fewer the number of ED visits. This result was contrary to the results of previous studies5,11, which have reported no significant correlation between changes in 6MWD and long-term clinical outcomes. However, the parameters used in previous studies such as mortality and hospitalization, were different from those used in this study. Therefore, future studies should identify the correlation between improvements in 6MWD and clinical outcomes in the long-term follow-up period.
A history of hospital use serves as a main risk factor for unplanned hospital use, including inpatient admission and ED visits [23]. Studies3,5,11,13,14,17 comparing 6MWD have focused on mortality, hospitalization, hospital readmission, and ED visits. In this study, the average annual number of hospital visits was used as a factor to identify the correlation between different the change rate in 6MWD and hospital visits. We confirmed the positive correlation between changes in 6MWD and the rate of hospital visits, indicating that a higher improvement in 6MWD is not correlated with the reduction in the average annual number of hospital visits in patients with PAH. This result conforms to the hospital readmission rate reported in this study. Studies5,11 have reported that changes in 6MWD are not associated with long-term outcomes (at 6 months), including PAH-related death or hospitalization and all-cause death. Although the parameters used for clinical outcomes were different between previous studies and this study, the results where no association was observed between the change rate in 6MWD and clinical outcomes was similar among the studies. This is the first study that has assessed the correlation between the change rate in 6MWD and hospital visits in patients with PAH, but additional studies are needed to confirm the effects of different grouping methods on changes in 6MWD.
PVR is the resistance to blood flow from the pulmonary artery to the left atrium and changes according to body position; in the supine position, PVR is higher than that in the upright position. However, it decreases more prominently during moderate exercise in healthy adults24,25. A higher PVR value (> 5 Wood unit (WU)) is associated with a poor prognosis and lower LVEF values in patients with heart failure26. In pulmonary hypertension, PVR is an independent predictor of PAH and a parameter to predict early mortality27,28. In this study, PVR showed a significant difference between the three groups, and group 3 (a median value of 3.35 WU) with decreased 6MWD during the follow-up period had the highest PVR value. Cardiac output is inversely related to PVR and is associated with exercise capacity in patients with PAH2,24. We thought that the higher PVR values in group 3 during the long-term follow-up period contributed to the reduction in 6MWD. Further studies with larger sample sizes are needed to identify the correlation between PVR and changes in 6MWD.
Although this study revealed the correlation between the change rate in 6MWD and long-term clinical outcomes, this retrospective study has some limitations. First, the patients included in this study were divided into the three groups according to a change rate of 15% in 6MWD. Several studies3,5,6,7,9,11 have reported various parameters, including change, endpoint, and cutoff value of 6MWD. This may have affected the results of changing 6MWD between the studies. Therefore, this point should be considered when comparing the results between studies. Second, the dependent variables were calculated by dividing the total frequency of readmissions, ED visits, and hospital visits by the number of years of follow-up period because the follow-up period varied between studies. Most studies13,14,17,20 conducted for evaluating the correlation between changes in 6MWD and clinical outcomes had short-term follow-up periods (within 1–3 months). Randomized controlled trials are needed to confirm the results of this study. In conclusion, this study demonstrated that the change rate in 6MWD may relate to the reduction in the frequency of ED visits in patients with PAH. This is the first study to confirm the effects of the change rate in 6MWD on clinical outcomes for a long-term period.