The evaluation of French risk stratification at baseline and follow-up in the JAPHR cohort revealed that the risk stratification score correlated with mPAP at follow-up. It was also found that improvements in the risk stratification score correlated with those in mPAP.
The most important point in this study is that improvement in the risk stratification score and hemodynamic parameters are closely related, especially in mPAP, in the JAPHR cohort. NIH registry data [6] indicated that not only increased RAP and decreased CI but also increased mPAP were associated with increased mortality in patients with primary PH. However, until now, most randomized controlled trials found mPAP improvement to be a poor prognosis factor [7]. One possible reason is that multiple monotherapy studies only showed minor improvements in mPAP, meaning that monotherapy itself has less capacity to improve mPAP. However, a report of triple combination therapy suggests that combination therapy including epoprostenol may improve not only the CI but also mPAP [8]. In addition, a JAPHR study reported that 85% of patients on upfront combination therapy had a ≥ 20% reduction in mPAP at the follow-up period, resulting in beneficial outcomes [5]. Therefore, in treatment with combination therapy, it is expected that lowering the risk stratification score will lead to a hemodynamic improvement in pulmonary circulation associated with not only right ventricular function but also mPAP. Regarding a novel treatment algorithm targeting risk stratification proposed in Nice 2018 [3], the results of the present study suggest that this algorithm improves not only risk stratification scores but also mPAP.
This study has some limitations. First, this cohort has data from advanced PH centers in Japan; as previously reported, the mortality and lung transplant events were less frequent and the prognosis was better than those of existing reports [5]. Therefore, it was difficult to verify any correlations between risk stratification score and prognosis at the initial visit or follow-up, as reported previously in other studies. However, absolute improvements in hemodynamics, as well as in right heart failure and symptoms contained in the risk stratification score, may indicate that patients in this cohort had a better prognosis. Second, a decrease in mPAP sometimes originate from worsening heart failure or decreases in cardiac output. However, since the risk stratification score includes indices such as CI and RAP, it is not expected that the decrease in mPAP was due to the progression in cardiac dysfunction. Moreover, only rare cases suffered from decreased mPAP associated with cardiac output impairment in our cohort because this cohort had better prognosis concomitant with hemodynamic improvements [5]. Third, this study was conducted in the cohort up to 2013, and the number of cases was small compared to the original French report [2]. However, compared with the French cohort, the distribution of patients in each risk score after the initial treatment did not differ, which validates the risk score in Japanese patients. Therefore, this study may contribute to the future universalization of evaluation methods for therapeutic interventions.