Frequency of and sex differences in cancer treatment-related cardiac dysfunction in trastuzumab-treated patients with salivary gland cancer: a retrospective cohort study.

BACKGROUND: Trastuzumab treatment for salivary gland, gastric, and breast cancer commonly causes cancer treatment-related cardiac dysfunction (CTRCD). CTRCD incidence by sex has not been well studied. METHODS: This retrospective cohort study investigated frequency of and sex differences in CTRCD in patients with salivary gland cancer treated with trastuzumab at our hospital from April 2017 to March 2022. All patients underwent echocardiography at baseline and after the first, third, and sixth trastuzumab courses. We measured changes in global and regional longitudinal strain (LS) after trastuzumab administration. CTRCD was defined by left ventricular ejection fraction (LVEF) or global LS (GLS). The results were compared by sex. RESULTS: We recorded clinical data of 49 patients (median age [IQR], 65 [55-71] years; males [75.5%]). The median follow-up period after the sixth trastuzumab course was 120 (111-128) days. One female patient and no male patient had CTRCD defined by LVEF, and two female patients (16.7%) and seven male patients (18.9%) had CTRCD, defined by GLS. The Kaplan-Meier curves showed no significant difference in CTRCD frequency, defined by GLS (log-rank, p = 0.88), between female and male patients. In the univariate analysis, sex was not associated with CTRCD, defined by GLS. A significant difference in apical LS was observed between baseline and the third follow-up results of male patients. CONCLUSIONS: In this study, CTRCD incidence was not significantly different between male and female patients with salivary gland cancer treated with trastuzumab. Although most previous studies have looked at female patients with breast cancer, a male patient may be found to be at similar risk of myocardial damage.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.

Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry.

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).

Switching from Beraprost to Selexipag in the Treatment of Pulmonary Arterial Hypertension: Insights from a Phase IV Study of the Japanese Registry (The EXCEL Study: EXChange from bEraprost to seLexipag Study).

Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3-6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.

Digitalomics, digital intervention, and designing future: The next frontier in cardiology.

The discipline of cardiology stands at a transformative juncture, primarily influenced by the surge in digital health technologies. These innovations hold the promise to redefine the realms of cardiovascular research and patient care, ushering in an era of individualized and data-driven treatments. This review delves into the heart of this evolution, introducing a comprehensive design for the future of cardiology. Emphasizing the emerging domains of "digitalomics" and "digital intervention", it explores how the integration of patient data, artificial intelligence-enabled diagnostics, and telehealth can lead to more streamlined and personalized cardiovascular health. The "digital-twin" model, a highlight of this approach, encapsulates individual patient characteristics, allowing for targeted treatments. The role of interdisciplinary collaboration in cardiovascular medicine is also underlined, emphasizing the importance of merging traditional cardiology with technological advancements. The convergence of traditional cardiology methods and digital health technologies, facilitated by a transdisciplinary approach, is set to chart a new course in cardiovascular health, emphasizing individualized care and improved clinical outcomes.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Case report: Pathological differences in pulmonary arterial hypertension in long-term responders to calcium channel blockers.

Background: This study investigates the pulmonary arterial histopathology in patients with idiopathic pulmonary arterial hypertension (IPAH) and acute vasoreactive phenotype, who demonstrated long-term survival (>30 years) and incidental death from causes other than PAH progression. The pathological changes observed in these patients were compared with those in patients with bone morphogenetic protein receptor type 2 (BMPR2) mutation. Case Presentation: We present two cases of patients with pulmonary arterial hypertension (PAH) who died incidentally from causes unrelated to PAH progression. We report compares pulmonary arterial histopathology in long-term survivors of CCB-responsive PAH patient and a hereditary PAH patient with a BMPR2 mutation. Lung specimens were analyzed using the Heath and Edwards (HE) classification and percentage muscular wall thickness (%MWT) of pulmonary arterioles. A significant difference in the severity of grading (p = 0.0001) and distribution between grades 1-2, 4 (p = 0.001), and 5 (p = 0.014) was observed between both patients. These findings suggest differential vascular pathology between the two cases, with CCB responders displaying more mild illness lesions compared to BMPR2 mutant patients. Conclusion: The study revealed that CCB responders exhibit more mild illness vascular lesions than BMPR2 mutant patients despite their long-term survival, suggesting a difference in vascular pathology between the two phenotypes.

Usefulness of Longitudinal Strain to Assess Cancer Therapy-Related Cardiac Dysfunction and Immune Checkpoint Inhibitor-Induced Myocarditis.

Longitudinal strain (LS) measured by echocardiography has been reported to be useful not only for the diagnosis and risk stratification of various cardiac diseases, but also in cardio-oncology. Most previous studies have been conducted on patients undergoing treatment with anthracyclines and human epidermal growth factor receptor 2-targeted therapies. Existing guidelines recommend that global LS (GLS) should be measured before and after the administration of cancer drugs. This recommendation is based on many reports showing that a decline in GLS is indicative of early or mild cancer therapy-related cardiac dysfunction. The main purpose of this article is to provide insight into the importance of LS in patients undergoing cancer treatment and highlight the role of LS evaluation in patients undergoing immune checkpoint inhibitor (ICI) treatment, which is being used with increasing frequency. Among cancer drug therapies, immune checkpoint inhibitors (ICIs) have an important place in cancer treatment and are used for the treatment of many types of cancer. Although the efficacy of ICIs in cancer treatment has been reported, immune-related adverse events (irAEs) have also been reported. Among these irAEs, cardiovascular complications, although rare, are recognized as important adverse events that may result in ICI treatment discontinuation. Myocarditis is one severe adverse event associated with ICIs, and it is important to standardize diagnostic and therapeutic approaches to it. Several studies have reported a relationship between LS and cardiac complications associated with ICIs which may contribute to the early diagnosis of ICI-induced cardiac complications.

How do the 2022 European Society of Cardiology/European Respiratory Society guidelines modify the diagnosis of portopulmonary hypertension in patients with cirrhosis complicated by portal hypertension? A post hoc analysis.

The vertical and horizontal broken lines indicate the pre-revised criteria, whereas the vertical and horizontal solid lines indicate the 2022 European Society of Cardiology/European Respiratory Society criteria.

Evaluation of the efficacy and safety of an integrated telerehabilitation platform for home-based cardiac REHABilitation in patients with heart failure (E-REHAB): protocol for a randomised controlled trial.

INTRODUCTION: Cardiac rehabilitation (CR) is strongly recommended as a medical treatment to improve the prognosis and quality of life of patients with heart failure (HF); however, participation rates in CR are low compared with other evidence-based treatments. One reason for this is the geographical distance between patients' homes and hospitals. To address this issue, we developed an integrated telerehabilitation platform, RH-01, for home-based CR. We hypothesised that using the RH-01 platform for home-based CR would demonstrate non-inferiority compared with traditional centre-based CR. METHODS AND ANALYSIS: The E-REHAB trial aims to evaluate the efficacy and safety of RH-01 for home-based CR compared with traditional centre-based CR for patients with HF. This clinical trial will be conducted under a prospective, randomised, controlled and non-inferiority design with a primary focus on HF patients. Further, to assess the generalisability of the results in HF to other cardiovascular disease (CVD), the study will also include patients with other CVDs. The trial will enrol 108 patients with HF and 20 patients with other CVD. Eligible HF patients will be randomly assigned to either traditional centre-based CR or home-based CR in a 1:1 fashion. Patients with other CVDs will not be randomised, as safety assessment will be the primary focus. The intervention group will receive a 12-week programme conducted two or three times per week consisting of a remotely supervised home-based CR programme using RH-01, while the control group will receive a traditional centre-based CR programme. The primary endpoint of this trial is change in 6 min walk distance. ETHICS AND DISSEMINATION: The conduct of the study has been approved by an institutional review board at each participating site, and all patients will provide written informed consent before entry. The report of the study will be disseminated via scientific fora, including peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: jRCT:2052200064.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol.

Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular-targeted drugs. Since interleukin-6 (IL-6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL-6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL-6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL-6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator-initiated clinical study using satralizumab, a recycling anti-IL6 receptor monoclonal antibody, for patients with an immune-responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti-IL6 therapy.

Cardiovascular events after the initiation of immune checkpoint inhibitors.

We sought to clarify the incidence of major adverse cardiac events (MACE) after the initiation of immune checkpoint inhibitors (ICIs). We analyzed the JMDC Claims Database between 2005 and 2021. The study included 2972 patients with no history of cardiovascular disease and a prescription for an ICI. The primary outcome was the incidence of MACE, including myocarditis, pericarditis, Takotsubo cardiomyopathy, atrio-ventricular block, heart failure, myocardial infarction, and stroke. The median age of study participants was 59 (Q1-Q3 53-65) years, and 2163 participants (72.8%) were male. Lung cancer was the most common cancer site (n = 1603). Among ICIs, programmed cell death-1 (PD-1) was most frequently used, and a combination ICI treatment was conducted in 110 patients (3.7%). During a mean follow-up of 358 ± 327 days, 419 MACE events were recorded. The incidence rate of myocarditis, pericarditis, Takotsubo cardiomyopathy, atrio-ventricular block, heart failure, myocardial infarction, and stroke was 3.4, 142.3, 10.3, 17.2, 1191.2, 55.2, and 278.5 per 10,000 person-years, respectively. The incidence of cardiovascular events was higher within 180 days after the initial prescription of ICI. The continuation rate of ICI after MACE was 38.4%. In conclusion, our analysis of a nationwide epidemiological dataset demonstrated the incidence of MACE after the initiation of ICI treatment. The incidence of heart failure was higher than expected, and the continuation rate of ICI treatment after MACE was low. Our results indicated the importance of monitoring and prevention of cardiovascular events in cancer patients requiring ICI treatment.

Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. OBJECTIVES: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. PATIENTS/METHODS: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. RESULTS: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). CONCLUSION: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Current clinical understanding and effectiveness of portopulmonary hypertension treatment.

Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic.

Prospective screening for myocarditis in cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve clinical outcomes in various cancers, but sometimes induce autoimmune adverse effects, including myocarditis, which is the most serious complication. There are many reports on ICI-induced myocarditis; however, only a few prospective surveillance reports exist. Therefore, we developed a prospective screening protocol and performed monitoring clinically suspected myocarditis in every patient treated with ICIs. METHODS: We prospectively enrolled 126 consecutive patients treated with ICIs in this cohort. Outcomes of patients were determined and analyzed between April 2017 and May 2020. We evaluated vital signs, biomarkers, electrocardiograms, chest radiographs, and echocardiographs before and at 7 ±â€¯3, 14 ±â€¯3, 21 ±â€¯3, and 60 ±â€¯7 days after ICI initiation. RESULTS: Eighteen (14.3 %) presented troponin I elevation and 13 of them presented signs of clinically suspected myocarditis (10.3 %). Among the 13 patients, ICI was discontinued in four cases (3.2 %) without fatal events. Myocarditis appeared at an early stage of ICI treatment, regardless of severity (median, 44 days). CONCLUSIONS: We observed the frequency of patients with myocarditis or myocardial damage through a prospective screening program in the real world. Although the frequency was higher than expected, most cases were mild and ICI treatment could be continued under careful observation.

Changes in the Characteristics and Initial Treatments of Pulmonary Hypertension Between 2008 and 2020 in Japan.

Background: Pulmonary arterial hypertension (PAH) is a rare, progressive disease. The treatment landscape for PAH in Japan has evolved considerably in recent years, but there is limited knowledge of the changes in treatment practices or patient characteristics. Objectives: The aim of this study was to evaluate the changes in characteristics and initial treatments for PAH in Japan over time. Methods: This study used data from the Japan Pulmonary Hypertension Registry (JAPHR) to compare patient characteristics and treatment practices between 2008-2015 (n = 316) and 2016-2020 (n = 315). Results: The mean ± standard deviation age at diagnosis increased from 47.9 ± 16.7 years in 2008-2015 to 52.7 ± 16.9 years in 2016-2020. The mean pulmonary arterial pressure decreased from 45.4 ± 15.0 to 38.6 ± 13.1 mm Hg. Idiopathic/hereditary PAH was the most common etiology in both periods (50.0% and 51.1%, respectively). The proportion of patients prescribed oral/inhaled combination therapies increased from 47.8% to 57.5%. Oral/inhaled combination therapies were frequently prescribed to patients with congenital heart disease-related PAH (81.8%). There was no significant trend in prescribing practices based on French low-risk criteria: among patients with 0, 1, 2, 3, or 4 criteria, 53.8%, 68.8%, 52.8%, 66.7%, and 39.4% were prescribed oral/inhaled combination therapies, and 0%, 16.7%, 27.0%, 17.3%, and 15.2% were prescribed oral/inhaled monotherapies. Macitentan, tadalafil, selexipag, and epoprostenol were the most frequently prescribed drugs. Conclusions: The severity of PAH decreased over time in Japan. Oral/inhaled combination therapies were generally preferred. Physicians generally prescribed therapies after considering the patients' hemodynamics and clinical severity. (Japan Pulmonary Hypertension Registry [JAPHR]; UMIN000026680).