Background Chronic thromboembolic pulmonary hypertension (CTEPH) requires life-long anticoagulant therapy, whereas limited data exist on the safety and efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) along with balloon pulmonary angioplasty (BPA). Objectives To evaluate outcomes and complications in CTEPH following BPA for individuals receiving DOACs or VKAs. Methods Consecutive CTEPH patients underwent BPA from September 2014 to August 2021 were included in a retrospective analysis. Complications during BPA, post-BPA hemodynamics and bleeding events were obtained from patient's medical records. Our routine follow-up “selective” pulmonary angiography, to evaluate all segmental pulmonary arteries one by one at six months and every year after final BPA session, was performed to elucidate the incidence of in-situ fresh floating thrombus. Results Of total 250 individuals, 104 were treated with DOACs and 146 with VKAs following BPA. Mean observation period was 905 (SD ± 660) days. Total 1278 BPA sessions were performed among the period in which 409 sessions were treated with DOACs and 869 sessions with VKAs. Significant improvements in hemodynamics and functional status were observed in both groups following BPA. There was no significant difference of hemoptysis during BPA between DOACs and VKAs (7.1% vs 10.1%, P=0.131). Major bleeding events during observation period were equivalent in those treated with DOACs and VKAs. No significant re-elevation of pulmonary artery pressure was observed in both groups after BPA. Follow-up selective pulmonary angiography identified in-situ fresh floating thrombus in pulmonary artery in 22 cases of total 769 follow-up sessions. The occurrence of fresh thrombus was significantly higher in those receiving DOACs than VKAs in therapeutic range of PT-INR >1.8 (3.9% vs 1.2%, P=0.023) whereas no significant difference between DOACs and overall VKAs (3.9% vs 2.4%, P=0.177) Conclusions Post-BPA hemodynamic outcomes and bleeding events appear unaffected by choice of anticoagulant. However, the incidence of in-situ pulmonary thrombosis detected by selective pulmonary angiography was significantly higher in those receiving DOACs than VKAs in therapeutic range, suggesting inadequate anticoagulation under current dose of DOACs. Our study provides a rationale for further examination to evaluate the efficacy of DOACs in CTEPH. Funding Acknowledgement Type of funding sources: None.

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder characterized by cutaneous capillary malformations, bone hypertrophy, and multiple venous or lymphatic malformations. KTWS is associated with chronic thromboembolic pulmonary hypertension (CTEPH), presumably due to thromboembolism from multiple vascular malformations. Here, we report the first case series of patients with KTWS-CTEPH who underwent balloon pulmonary angioplasty (BPA). Both patients are alive 20 years and 1 year after the initial diagnosis of CTEPH, respectively, and are stable with improved hemodynamics. BPA may be an effective treatment option for patients with KTWS-CTEPH.

Background Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some symptoms, such as dyspnea on exertion, had remained in more than half of the patients even after BPA could decrease mean pulmonary artery pressure (PAP) <25 mmHg in a Japanese multicenter registry. In addition, previous report indicated that impaired exercise capacity was observed in about half of the patients with CTEPH who achieved mean PAP <25 mmHg at rest after BPA. Lowering mean PAP alone would not be sufficient as a treatment goal of BPA to eliminate residual symptoms in the patients. Purpose The purpose of this study was to elucidate the determinants of residual symptom in patients who had achieved mean PAP <25 mmHg after BPA. Methods Among 310 CTEPH patients who received BPA in our center, 217 patients (70.0%) could achieve mean PAP <25mmHg at six months after the final BPA were enrolled in this study. The patients were divided into two groups based on the necessity of additional BPA due to residual symptoms; additional BPA group and non-additional BPA group. Clinical parameters including resting hemodynamics at 6 months follow up were retrospectively investigated between the two groups. Results Additional BPA had been underwent in 67 patients (30.9%). No significant differences in mean PAP were identified between the additional and non-additional BPA groups (20.4±2.5 mmHg vs. 19.7±2.7 mmHg, p=0.106). In additional BPA group, cardiac index (CI), heart rate (HR) and percutaneous oxygen saturation (SpO2) was lower than non-additional BPA group, and pulmonary vascular resistance (PVR) was higher than non-additional BPA group (CI, 2.51±0.41 L/min/m2 vs. 2.72±0.56 L/min/m2, p=0.016, HR, 62.9±9.7 bpm vs. 67.8±10.8 bpm, p=0.003, SpO2, 94.3±3.7% vs. 95.9±3.5%, p<0.001, PVR, 3.67±1.18 W.U. vs. 3.11±1.09 W.U. p=0.001). In a multivariate analysis, CI, SpO2 and PVR were associated with residual symptoms requiring additional treatment in patients with mean PAP <25mmHg after BPA (95% confidence interval: CI; 0.221–0.900, SpO2; 0.825–0.976, PVR; 1.000–1.785). Conclusion Low CI and SpO2 and High PVR were determinants for residual symptoms in CTEPH patients who could achieve mean PAP <25 mmHg after BPA. To eliminate the residual symptoms, treatment goals of BPA in inoperable CTEPH patients should be increasing CI and SpO2 and lowering PVR in addition to normalizing mean PAP. Funding Acknowledgement Type of funding sources: None.