In other words, PTX3 may be a sensitive biomarker that indicates the ”existence of inflammation behind the disease” whereas BNP is a biomarker that reflects the severity of mechanical ventricle stress. However, the question remains on the origin of elevated PTX3 levels. A previous study on patients with left heart failure reported a Epimedoside-A negative linear correlation between PTX3 levels and ejection fraction. Leary et al. showed that higher PTX3 levels were associated with greater right ventricle mass and larger right ventricle end-diastolic volume in patients with atherosclerosis. Our study revealed a mild correlation between PTX3 levels and CO in patients with CTEPH. It is therefore possible that PTX3 is derived from inflammation in the right ventricle. On the other hand, Zabini et al. reported an increase in inflammatory cytokine concentration in PEA tissue, so it is possible that the increase in PTX3 is also produced at the organized thrombus. We could not define which tissue is the main producer of PTX3, but we speculate that there may be a complex inflammatory interaction between organized thrombi, the peripheral pulmonary vasculature, and right heart ventricle muscle. However, further investigation is needed to clarify these relationships. Regarding the Dimesna clinical diagnostic efficacies, it has previously been reported that PTX3 level in the healthy 
population is 2.00 ng/mL. That is similar to the PTX3 levels in the control group of this study, which consisted of patients with a history of PTE who had symptom improvement on warfarin therapy. This finding suggests that PTX3 may be a useful screening tool for identifying CTEPH even in patients with a history of PTE. For example, elevated plasma PTX3 levels in this patient population may prompt further work-up for CTEPH, which may lead to an early diagnosis. It should be noted, however, that elevated PTX3 levels have been observed in conditions other than pulmonary hypertension as described above, and careful interpretation of the data is required. Just for information, we also evaluated the PTX3 levels of three PTE patients in acute phase. They showed relatively high PTX3 levels. the elevated PTX3 level decreases as the disease gets relieved. The increased level of PTX3 in some CTEPH patients may be prolonged from the onset of acute PTE as pulmonary vasculature degeneration and/or right heart burden are prolonged. Hence, it may be difficult to distinguish the patients with severe PTE in acute phase from the patients with CTEPH. Tamura et al. previously reported elevated levels of PTX3 in patients with PAH. They found that PTX3 levels did not correlate with mPAP, PVR or BNP, which is similar to our findings. Finally, they found a relatively low level of PTX3 in patients undergoing PAH-specific treatment and suggested that PTX3 may derive from pulmonary vascular degeneration. We found that neither PAH-specific treatment nor PEA has any significant effect on PTX3 levels. It is unclear why the two studies differ in this view, but they had a common suggestion that PTX3 levels may not simply reflect the severity of PAH as described above. Our study had several limitations. First, the ROC curves may have been biased by the high prevalence of patients with CTEPH in our institute, which is considerably greater than the prevalence in most clinical settings. Second, we could not measure plasma PTX3 in a few patients who underwent PEA. There was no significant correlation between post-PEA PTX3 levels and postPEA hemodynamic parameters, and there was also no significant difference between PTX3 levels measured pre- and post-PEA. The sample size is too small to evaluate these data. Third, this study was performed retrospectively at a single institution.