Yu Taniguchi

Background: Balloon pulmonary angioplasty (BPA) is promising for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, its use in atypical CTEPH with respiratory disorders remains uncertain because of concerns about worsening oxygenation. This study aimed to evaluate the effects of BPA on hemodynamics and oxygenation according to baseline respiratory dysfunction. Methods: We retrospectively analyzed 234 patients with CTEPH who underwent BPA between 2011 and 2025. Patients were categorized by spirometry into four groups: normal (n=122), restrictive (%VC <80%; n=43), obstructive (FEV1/FVC <70%; n=48), and combined impairment (n=21). Hemodynamic and respiratory parameters before and after BPA were compared. Multivariable linear regression was used to identify predictors of improvement in arterial oxygen partial pressure (PaO2). Results: Hemodynamic improvement after BPA was similar across groups, with reductions in pulmonary vascular resistance of −56.7±23.0%, −46.4±28.7%, −53.8±26.6%, and −46.7±30.6%, respectively (p=NS). Oxygenation also improved regardless of respiratory impairment, with increases in PaO2 of 11.5±13.1, 11.1±10.8, 12.9±11.9, and 7.5±13.1 mmHg, respectively (p=NS). In patients with restrictive physiology, higher baseline DLCO (p=0.011) and lower PaO2 (p<0.01) were associated with greater PaO2 improvement. In those with obstructive physiology, higher DLCO (p<0.01), lower PaO2 (p<0.01), and higher alveolar–arterial oxygen gradient (p=0.046) were significant predictors. Conclusion: BPA improved hemodynamics and oxygenation similarly in patients with CTEPH, irrespective of baseline respiratory dysfunction. Among patients with impaired lung mechanics, DLCO-but not spirometric indices-was strongly associated with oxygenation improvement.

We aimed to evaluate the role of medical therapy before and after balloon pulmonary angioplasty (BPA) for non‐operable chronic thromboembolic pulmonary hypertension (CTEPH) in the modern management era. This Japanese nationwide, multicenter, prospective observational registry, including 37 centers, analyzed data newly registered from August 2018–December 2023. Pretreatment before BPA was analyzed in patients who were treatment naïve or received medical therapy only at registration ( n = 557). De‐escalation or escalation of medical therapy after BPA was analyzed in patients who underwent BPA ( n = 966). The BPA pretreatment analysis in 557 patients showed that approximately 70% of the patients received medical therapy, of which 18% received combination therapy. Patients who received monotherapy or combination therapy had more severe baseline hemodynamics than those who did not. The 3‐year survival did not significantly differ between the no, mono, and combination pretreatment groups (94%, 98%, and 97%, respectively; p = 0.852). The BPA post‐treatment analysis in 966 patients showed that 20% of patients underwent de‐escalation of medical therapy. Patients with de‐escalation of medical therapy had lower mean pulmonary artery pressure (PAP) (20.9 ± 5.8 vs. 24.1 ± 7.3 mmHg, p < 0.01); however, they had a lower cardiac index at last follow‐up compared to patients without de‐escalation (2.66 ± 0.61 vs. 2.84 ± 0.70 L/min/m ² , p = 0.01). Patients with severe disease tended to undergo pre‐treatment before BPA; however, patient survival did not differ across pretreatment types. De‐escalation of medical therapy after BPA can affect cardiac index. Therefore, de‐escalation or continuation of medical therapy should be carefully considered even after mean PAP normalizes after BPA.

Background: Group 2 pulmonary hypertension ( PH ), defined as PH caused due to left heart disease, remains a challenging condition. However, its prognostic impact and implications for emerging therapies are unclear. We aimed to evaluate the real‐world relationship between pulmonary vascular resistance ( PVR ) and prognosis in Group 2 PH and assess the efficacy of emerging therapies. Methods: Two prospective registries supported by Japanese PH societies were analyzed: a current (2018–2024; n=563) and a previous (2012–2016; n=425) registry. The composite end points were hospitalization for heart failure, all‐cause death, ventricular assist device implantation, or cardiac transplantation. Results: Stratified analyses using propensity score–matched data demonstrated a significant association between PVR >3 Wood units and prognosis in patients with Group 2 PH (6‐year event‐free rates, PVR > 3 Wood units versus PVR ≦ 3 Wood units, previous registry: 72.9% versus 61.4%; current registry: 75.2% versus 55.4%). Consistent patterns were observed in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction subgroups. The use of SGLT2 (sodium‐glucose cotransporter‐2) inhibitors in the current registry was associated with improved outcomes in patients with elevated PVR , showing event‐free rates of 73.8% versus 35.5% in those without treatment. Among multivariate analyses including major treatment options, SGLT2 inhibitor treatment exhibited significant associations with improvement of composite end points. Conclusions: Elevated PVR (>3 Wood units) identified a high‐risk subset of patients with Group 2 PH . The association between the use of SGLT2 inhibitors and better outcomes suggests a potential therapeutic role that warrants further investigation through controlled studies.

BACKGROUND: Over the past decade, balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension has shown improved outcomes with procedural refinement in expert hospitals with high procedural volume. Whether the outcomes of BPA are reproducible in hospitals with limited procedural volumes remains unknown. The Japan BPA registry was designed to assess the outcomes of contemporary BPA from a nationwide perspective, including hospitals with low treatment volume. METHODS: This prospective multicenter registry enrolled 1202 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent BPA at 44 hospitals between April 2018 and March 2023. We assessed the efficacy and safety of BPA and survival rates, comparing high- and low-volume hospitals based on the BPA center definition (≥50 procedures per year) from the seventh World Symposium on Pulmonary Hypertension. RESULTS: A total of 5207 procedures were performed. Thirty-five low-volume hospitals (79.5%) performed 40.8% of all BPA procedures. BPA significantly improved symptoms, clinical parameters, and hemodynamics (55.6% reduction in pulmonary vascular resistance), with 0.2% periprocedural BPA-related mortality. Severe lung injury (0.3%), balloon overdilatation (0.67%), and mechanical ventilation (0.3%) were less common in high-volume hospitals than in low-volume hospitals (1.3%, 1.7%, and 1.5%, respectively; P <0.001). In the Kaplan-Meier analysis, the survival rate of all patients at 3 years was 94.7% (95% CI, 92.5%–96.3%). Multivariable Cox regression analysis showed an increased mortality risk with higher right atrial pressure, and high-volume hospitals were associated with a reduced mortality risk. CONCLUSIONS: This nationwide registry demonstrated the outcomes of contemporary BPA in patients with chronic thromboembolic pulmonary hypertension. No significant differences were observed in efficacy and periprocedural mortality between low- and high-volume hospitals. However, the significantly lower rate of severe complications in high-volume hospitals indicates that BPA may be safer in high-volume hospitals.

The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed dramatically over the past two decades, with improved prognosis owing to the availability of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and approved medications. Recently, treatment strategies combining these options have been determined by a multidisciplinary team according to localisation, characteristics, haemodynamics and comorbidities. This review summarises recent advances in hybrid therapy, combining PEA and BPA as a treatment approach for CTEPH, and discusses future perspectives.

Nocturnal desaturation is occasionally observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) despite the absence of parenchymal lung disease; however, the underlying mechanism remains unclear. This study aimed to clarify the clinical features of nocturnal desaturation in patients with CTEPH. Data of 163 patients with CTEPH who underwent balloon pulmonary angioplasty (BPA) between March 2011 and December 2022 were retrospectively analyzed. We evaluated their hemodynamics using right heart catheterization, arterial blood gas examination, respiratory function tests, nocturnal oximetry, and cardiopulmonary exercise testing, which were routinely performed at baseline and after BPA. A higher ratio of dead space to tidal volume (VD/VT) (p < 0.001) and higher alveolar-arterial oxygen difference (A-aDO2) (p = 0.026) at baseline were associated with greater nocturnal desaturation in the multivariable linear analysis. After BPA, nearly normal hemodynamics was achieved (mean pulmonary arterial pressure: 37.5 ± 10.0 to 20.2 ± 4.9 mmHg, p < 0.01). Nocturnal desaturation also improved from − 13.3 ± 5.8% at baseline to -10.3 ± 5.4% after BPA (p < 0.01). Improvement in VD/VT correlated well with improvement in nocturnal desaturation after BPA (p < 0.001, R2 linear = 0.18). Nocturnal desaturation often coexists with CTEPH. VD/VT, a marker of physiologic dead-space fraction, A-aDO2, a marker of ventilation-perfusion mismatch, and lung diffusing capacity were strongly associated. Nocturnal desaturation improved slightly after BPA, which was associated with a decrease in the physiological dead- space fraction. Our study emphasizes the importance of including nocturnal oximetry in routine evaluations and continuation of nocturnal oxygen therapy, if necessary, in patients with CTEPH. Nocturnal desaturation often coexisted with chronic thromboembolic pulmonary hypertension despite the absence of parenchymal lung disease. The ratio of dead space to tidal volume (a marker of the physiologic dead-space) and alveolar-arterial oxygen difference (a marker of ventilation-perfusion mismatch and lung diffusing capacity) were strongly associated with nocturnal desaturation. Nocturnal desaturation improved slightly after balloon pulmonary angioplasty, which was associated with a decrease in the physiological dead-space fraction.

Background: Prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) has improved after the availability of balloon pulmonary angioplasty (BPA) and approved drugs. However, the clinical effects of cancer, which is one of the associated medical conditions of CTEPH, remain unclear. We aimed to investigate prognosis in patients with CTEPH and comorbid cancer. Methods: Between January 2011 and December 2022, data of 264 consecutive patients with CTEPH who were treated with pulmonary endarterectomy, BPA, or medical therapy were retrospectively analyzed. The patients were allocated, based on the comorbidity of cancer as of December 2022, into the cancer (n = 47) and non-cancer (n = 217) groups. In the cancer group, active and non-active cancers were identified in 30 (64%) and 17 (36%) patients, respectively. Results: The baseline characteristics, hemodynamics, and treatments were similar between the groups. More than half of the cancer were diagnosed within two years before or after CTEPH diagnosis. Twenty-seven patients died during the study period. Among them, 13 (48%) and 7 (26%) died of cancer and right heart failure, respectively. The 5-year survival rate was lower in the cancer group than in the non-cancer group (67.8% vs. 94.5%, p < 0.001). In the active cancer group, the 5-year survival rate was also lower than that in the non-active cancer and non-cancer groups (52.0% vs. 99.5%, p < 0.001 and 52.0% vs. 92.3%, p < 0.001, respectively). Multivariate Cox hazard analysis revealed that hemodialysis (p < 0.001) and cancer (p < 0.001) were independently associated with poor survival. Conclusion: Patients with CTEPH rarely die of right heart failure, even if hemodynamically severe at diagnosis in the modern management era. However, patients with CTEPH frequently have comorbid cancer, which may be a strong prognostic factor.

Background: Balloon pulmonary angioplasty (BPA) is promising for non-operable chronic thromboembolic pulmonary hypertension (CTEPH). Almost normal hemodynamics at rest could be achieved. Oxygenation also improved; however, improvement was limited. We aimed to clarify the clinical mechanism of oxygenation improvement after BPA in non-operable CTEPH. Methods: Data from 173 patients with CTEPH, who underwent BPA from 2011 to 2022, were retrospectively analyzed. We evaluated hemodynamics with right heart catheterization, arterial blood gas, respiratory function tests, and exercise capacity (cardiopulmonary exercise testing) which were routinely performed at baseline and after BPA. Results: Nearly normal hemodynamics achieved (mean pulmonary artery pressure: 37.5±10.0 to 20.6±4.9 mmHg, p<0.01). Oxygenation slightly improved (partial pressure of arterial oxygen [PaO2]; 61.5±12.3 to 67.7±12.7mmHg, p<0.01). Baseline lower PaO2 (p<0.001), higher alveolar arterial gradient for oxygen (A-aDO2) (p=0.006), and higher diffusing capacity for lung carbon monoxide (p=0.047) were associated with greater improvement in PaO2 after BPA in the multivariable linear analysis. Moreover, the decrease in A-aDO2 was correlated to the improvement in PaO2 after BPA in multivariable analysis (p<0.001). Conclusions: The decrease of A-aDO2; the marker of ventilation-perfusion mismatch and lung diffusing capacity, was strongly correlated with the improvement of oxygenation after BPA. The decrease of ventilation-perfusion mismatch by BPA contributed most, however normalized oxygenation would be still difficult to achieve.