田邉 信宏

Advances in chronic thromboembolic pulmonary hypertension (CTEPH) treatment have improved prognosis, shifting focus towards symptom management. This study aimed to identify factors influencing the World Health Organization functional class (WHO-FC) in CTEPH patients. The CTEPH AC registry is a prospective, multicenter database from 35 Japanese institutions, analyzing data from August 2018 to July 2023. We examined factors associated with achieving WHO-FC I and WHO-FC changes over time in 1,270 patients. Significant factors for WHO-FC I achievement included male sex (odds ratio: 1.86, p = 0.019), age (0.98, p = 0.007), pulmonary vasodilator use (0.51, p = 0.001), post-balloon pulmonary angioplasty (BPA) (1.93, p = 0.010), lower mean pulmonary arterial pressure (0.94, p = 0.004), and lower pulmonary vascular resistance (PVR) (0.78, p = 0.006). Multivariate analysis showed that WHO-FC improvement correlated with male sex, baseline PVR, and BPA during follow-up. WHO-FC deterioration was associated with cancer, history of pulmonary endarterectomy and/or BPA at registration, bleeding risks, and thyroid disease or hormone therapy. BPA implementation is closely linked to symptomatic improvement and achieving WHO-FC I, while symptom worsening is often associated with patient-specific, difficult-to-control conditions.

BACKGROUND: Quality indicators (QIs) are used to standardize care and improve outcomes in patients with pulmonary arterial hypertension (PAH). It is important that QIs are validated within specific healthcare contexts. Therefore, this study aimed to validate QIs for PAH management in Japan using a modified Delphi consensus method. METHODS: QI candidates were identified from published European QIs and clinical practice guidelines. An expert panel of 11 PAH specialists from diverse Japanese institutions anonymously rated the 36 initial QI candidates in two rounds using a nine-point appropriateness scale. RESULTS: In the first round, 35 QIs received a median score of ≥7 points. A panel discussion was held between rounds to address the single low-scored QI, biomarker modifications, and invasive examinations, resulting in 36 modified QIs. In the second round, all modified QIs received median scores of ≥7 points and were judged to be valid as the final Japanese set of QIs. CONCLUSIONS: The findings of this study validated a set of QIs for PAH management tailored to the Japanese healthcare context. These QIs can be used to standardize care, identify areas for improvement, and ultimately enhance outcomes for Japanese patients with PAH.

BACKGROUND: The INCREASE trial, conducted in the United States, showed that inhaled treprostinil improved exercise capacity in pulmonary hypertension associated with interstitial lung disease (PH-ILD). However, hemodynamic and pharmacokinetic measurements were not performed in the trial. The objective of this trial was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with PH-ILD. METHODS: This trial was a multicenter, non-randomized, open-label, single-arm trial of patients with PH-ILD. Inhaled treprostinil was administered at 3 breaths (18 μg)/session four times daily, and the dose was gradually increased to a maximum of 12 breaths (72 μg)/session. The primary endpoints were the change of pulmonary vascular resistance index (PVRI) and peak 6-min walking distance (6MWD) from baseline to week 16. Endpoints also included other efficacy parameters, safety, and PK. RESULTS: Twenty patients received inhaled treprostinil. At week 16, PVRI decreased from baseline by -40.1% (95% CI, -53.1 to -27.2) and peak 6MWD increased by 13.0 m (95% CI, -15.0 to 49.0). The most frequently reported adverse events related with treprostinil were cough, malaise and blood pressure decreased. PK was similar to those in pulmonary arterial hypertension (PAH) patients. CONCLUSIONS: Treatment with inhaled treprostinil using the same dosing regimen as in the INCREASE trial resulted in improvements in hemodynamics and exercise capacity with a favorable tolerability and safety profile in Japanese patients with PH-ILD.

BACKGROUND: The contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear. OBJECTIVES: This study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan. METHODS: Among 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated. RESULTS: The BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m2; P = 0.030). CONCLUSIONS: BPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784).

BACKGROUND: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. OBJECTIVES: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. METHODS: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. RESULTS: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. CONCLUSIONS: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).