In this study, PSP on DE-CT was observed in more than half of the patients with CTEPH; however, it was rarely observed in patients with PAH. PSP on DE-CT, which is one of the specific imaging findings of CTEPH, might suggest a mechanism of microvasculopathy in CTEPH (microvasculopathy of extensive distal thrombosis) different from that in PAH. DE-CT might be useful in assessing microvasculopathy of diffuse distal thrombosis with PSP in CTEPH.
4.1 The evaluation for CTEPH by DE-CT
For the diagnosis of CTEPH, digital subtraction pulmonary angiography is considered the gold standard for characterizing vessel morphology; it is an invasive imaging modality.
Current guidelines for CTEPH indicate the usefulness of ventilation/perfusion scintigraphy as a CTEPH screening tool with its high sensitivity of 95-97 % and a specificity of 90-95 % [13, 15]. Recent studies have shown the diagnostic accuracy of computed tomography pulmonary angiography or dynamic contrast-enhanced lung perfusion magnetic resonance imaging as non-invasive modalities [16-18]. DE-CT is also emerging as a valuable modality for outlining the pulmonary vasculature. Several reports have supported the diagnostic accuracy of DE-CT and concur with the usefulness of ventilation/perfusion scintigraphy or computed tomography pulmonary angiography [19, 20]. Lung vascular perfusion can be quantified by examining the lung PBV score, which is calculated as the sum of the iodine density scores of each lung segment. PBV maps could calculate the iodine distribution in the lung parenchyma and could be surrogate markers of the underlying vascular reserve . Takagi et al., reported that lung PBV score, which was significantly associated with hemodynamic parameters including mean PAP and PVR, could be a noninvasive way of estimating the clinical severity of CTEPH . Onishi et al., reported the possibility of using DE-CT not only to quantify pulmonary vascular perfusion with the lung PBV score but also to qualitatively evaluate microvasculopathy by a more sensitive analysis of PSP in three dimensions . DE-CT might be useful for evaluating CTEPH severity, pulmonary vascular perfusion, and microvasculopathy.
4.2 Poor subpleural perfusion in CTEPH
This study is based on the assessment of subpleural perfusion on DE-CT, and the existence of microvasculopathy in CTEPH was not verified by histological examination. PSP reflects diffusely reduced pulmonary flow in the peripheral microvessels; it was observed in 58 of the 113 patients in this study. Although a wedge-shaped segmental defect, which is considered to be due to proximal vessel occlusion, would be the typical DE-CT finding , PSP on DE-CT was observed in more than half of the patients with CTEPH; this might be one of the specific imaging findings of CTEPH.
PSP on digital subtraction angiography or DE-CT might suggest the presence of microvasculopathy and/or diffuse distal thrombosis [6, 7, 12]. Indeed, patients with PSP showed poor hemodynamics; this was disproportionate to the degree of pulmonary vascular obstruction. Not only pulmonary vascular obstruction, microvasculopathy may also contribute to severe hemodynamic instability[3, 4]. However, PSP is rarely observed in patients with PAH. PAH is a disease characterized by obliteration and remodeling of the small pulmonary arteries [2, 13]. PSP in CTEPH may not suggest the same kind of microvasculopathy in PAH. It has been reported that microvasculopathy in CTEPH also comprises diffuse distal thrombosis . PSP on DE-CT, reflecting diffusely reduced pulmonary flow in peripheral microvessels, might represent diffuse peripheral microthrombosis.
Simonneau et al. suggested that distal thrombosis in CTEPH could be diffuse when the patency of small pulmonary arterioles distal to complete obstructions are not maintained because bronchial arteries and anastomoses fail to develop . Taniguchi et al., reported that PSP in digital subtraction angiography was also associated with less developed bronchial arteries, suggesting that bronchial-pulmonary anastomoses have the role of maintaining the patency of the pulmonary capillary bed distal to the obstructed pulmonary artery in CTEPH . In this study, we demonstrated that more than half of the patients with CTEPH had proximal organized thrombi and diffuse peripheral microthrombosis.
4.3 Clinical impact of diffuse distal thrombosis in CTEPH
The clinical impact of diffuse distal thrombosis in CTEPH remains unknown. In this study, the lung PBV score, which could represent lung vascular perfusion of the pulmonary artery bed, showed a strong inverse correlation with PVR in CTEPH without PSP; however, there was no significant correlation between the lung PBV score and PVR in PAH, as well as in CTEPH with PSP suggesting extensive distal thrombosis. This might suggest that extensive distal thrombosis is strongly involved in the hemodynamics of CTEPH. Lower DLCO/VA was observed in patients with PAH, as well as in those with CTEPH and PSP. Thus, extensive diffuse distal thrombosis in CTEPH may be pathophysiologically similar to small vessel disease in PAH.
However, this study demonstrated that hemodynamics at rest improved significantly after adequate BPA in patients with or without PSP (Poorly perfused group: mean PAP 20.0 ± 5.0 mmHg, PVR 270 ± 118 dynes-sec/cm5; Normally perfused group: mean PAP 19.0 ± 3.3 mmHg, PVR 220 ± 88 dynes-sec/cm5). Several reports have revealed that PAP at rest does not increase unless more than 50% of the pulmonary microcirculation is lost . In patients with CTEPH, pulmonary circulation does not completely return to normal even after optimal, and apparently successful surgical endarterectomy, or interventional, or medical treatment, [22, 23]. The European Respiratory Society Task Force on CTEPH stated that in many patients with CTEPH, resting mean PAP is normalized by surgery or multimodal treatment and patients feel healthy, but it is unlikely to return all pulmonary vessels back to normal . VE/VCO2, which is a marker of ventilatory inefficiency and reflects ventilation perfusion mismatch , remained elevated, and %DLCO/VA, which was associated with poor outcomes in patients with CTEPH and might indicate a pronounced microvasculopathy [7, 25], remained low in the PSP group, even though all accessible lesions had been treated after adequate BPA. However, in patients in the poorly perfused group, it is believed that hemodynamics at rest improved to nearly normal despite being poor at baseline; the proximal pulmonary artery flow improved following BPA even though pulmonary microcirculation remained impaired. Therefore, BPA should be considered a first-line treatment for inoperable CTEPH, regardless of the existence of PSP on DE-CT. Further investigations are needed to better understand peripheral microcirculation in CTEPH.