SEARCH
検索詳細
谷口 悠大学院医学系研究科 医科学専攻助教
研究活動情報
■ 論文- 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.2025年11月, ERJ open research, 11(6) (6), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Both pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) can be considered for the invasive treatment of chronic thromboembolic pulmonary hypertension (CTEPH). However, the technique applied to treat pulmonary vessels differs between PEA and BPA. While PEA removes lesions with thickened intima and organized thrombus, BPA improves pulmonary arterial flow by dilating stenosis and obstruction without removing the lesions. There have been limited reports on the differential efficacy between PEA and BPA. This study aimed to compare the baseline characteristics and efficacy of both treatments in CTEPH. METHODS: Between November 2001 and May 2019, 55 patients underwent PEA and 77 had only BPA performed. We evaluated clinical parameters before performing PEA and BPA, and on follow-up. RESULTS: The patients who underwent BPA were older and had fewer proximal lesions and milder pulmonary hemodynamics compared with those who underwent PEA (mean pulmonary arterial pressure: 34.0 ± 8.6 vs. 43.0 ± 9.9 mm Hg, p < 0.001). Although both groups showed improvement in most of their clinical data, cardiac index was not improved by BPA as opposed to PEA (2.5 ± 0.6 to 2.5 ± 0.6 L/min/m2, p = 0.99, 2.0 ± 0.6 to 2.6 ± 0.8 L/min/m2, p < 0.001, respectively). Furthermore, RC (resistance-compliance) time was significantly decreased by PEA (0.54 ± 0.16 to 0.45 ± 0.12 s, p < 0.001), but unchanged by BPA (0.54 ± 0.16 to 0.51 ± 0.13 s, p = 0.21). CONCLUSIONS: BPA did not change RC time and cardiac index, while PEA reduced RC time and improved cardiac index. The technical approach of removing intra-vascular organized thrombi and thickened intima by PEA could have a more profound impact on pulmonary circulation and cardiac function improvements compared with BPA.2025年08月, BMC pulmonary medicine, 25(1) (1), 376 - 376, 英語, 国際誌研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2025年05月, BMC Pulmonary Medicine, 25(1) (1)研究論文（学術雑誌）
- 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.2025年01月, BMC pulmonary medicine, 25(1) (1), 2 - 2, 英語, 国際誌研究論文（学術雑誌）
- 2024年09月, CIRCULATION JOURNAL, 88(9) (9), 1502 - 1508, 英語研究論文（学術雑誌）
- 2024年09月, CIRCULATION JOURNAL, 88(9) (9), 1502 - 1508, 英語研究論文（学術雑誌）
- BACKGROUND AND PURPOSE: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH. METHODS: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets. RESULTS: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG. CONCLUSION: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables.2024年, PloS one, 19(4) (4), e0300716, 英語, 国際誌研究論文（学術雑誌）
- Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy-related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH.2024年01月, Pulmonary circulation, 14(1) (1), e12359, 英語, 国際誌研究論文（学術雑誌）
- 2023年10月, European heart journal. Case reports, 7(10) (10), ytad473, 英語, 国際誌
- Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.2023年02月, Journal of the American Heart Association, 12(3) (3), e026466, 英語, 国際誌研究論文（学術雑誌）
- Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.2022年08月, Life (Basel, Switzerland), 12(8) (8), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. METHODS: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. RESULTS: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005-1.048; p = 0.017). CONCLUSIONS: RC time was decreased after PEA, and might be a possible indicator for predicting PEA success.2022年06月, International journal of cardiology. Heart & vasculature, 40, 101031 - 101031, 英語, 国際誌研究論文（学術雑誌）
- 2021年09月, International journal of cardiology, 338, 237 - 237, 英語, 国際誌
- BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.Elsevier BV, 2021年06月, International Journal of Cardiology, 333, 188 - 194, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era. METHODS AND RESULTS: We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments. The 1- and 5-year survival rates of operated patients (n = 41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n = 102), respectively (p = 0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5 ± 6.7, 17.9 ± 4.9, and 20.7 ± 4.6 mmHg, respectively (p = 0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was -73.7 ± 11.3%, -74.3 ± 11.8%, and - 54.9 ± 22.5%, respectively (p < 0.01, one-way ANOVA). CONCLUSION: There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.Elsevier BV, 2021年03月, International Journal of Cardiology, 326, 170 - 177, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Oxford University Press, 2021年01月, European Heart Journal - Case Reports, 5(1) (1), 英語研究論文（学術雑誌）
- W.B. Saunders Ltd, 2021年01月, Respiratory Medicine Case Reports, 33, 英語研究論文（学術雑誌）
- The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused (n = 49) or normally perfused group (n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score-0.793, R2 = 0.225, p < 0.01), but lung perfusion of blood volume score in poorly perfused group was not. Poorly perfused group had higher pulmonary vascular resistance (879 ± 409 dynes-s/cm5 vs. 574 ± 279 dynes-s/cm5, p < 0.01) and lower lung perfusion of blood volume score (22.1 ± 5.4 vs. 26.4 ± 6.6, p < 0.01) and % diffusing capacity for carbon monoxide divided by the alveolar volume (59.9 ± 15.4% vs. 78.8 ± 14.2%, p < 0.01). Perfusion of blood volume score in the normally perfused group showed an inverse correlation with pulmonary vascular resistance; however, that in poorly perfused group did not. Microvasculopathy might contribute to severe hemodynamics, apart from pulmonary vascular obstruction. In our experience, more than half of treatment-naïve chronic thromboembolic pulmonary hypertension patients have microvasculopathy.Wiley, 2021年01月, Pulmonary Circulation, 11(1) (1), 1 - 9, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Remodeling in the right-sided heart plays an important role in the management of pulmonary hypertension (PH) patients. However, the effect of balloon pulmonary angioplasty (BPA) on right ventricular (RV) and right atrial (RA) morphology of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. This study involved 45 CTEPH patients who underwent BPA with mean pulmonary artery pressure (mPAP) of 37.0 mmHg (all ≥ 25 mmHg). All patients underwent echocardiography and right-heart catheterization at baseline and 3 months after BPA. RV and RA remodeling was assessed as RV and the RA area, and RV systolic function was calculated by averaging peak speckle-tracking longitudinal strain of the RV free-wall (RV free-wall strain). Significant reverse remodeling in the right-sided heart was observed after BPA, resulting in improvement of mPAP and pulmonary vascular resistance (RV area: from 15.0 ± 5.3 to 9.6 ± 3.0 cm2, p < 0.0001; RA area: from 17.3 ± 6.6 to 13.4 ± 3.8 cm2, p = 0.0002; RV free-wall strain: from 15.9 ± 5.6 to 21.2 ± 4.9%, p < 0.0001). Furthermore, multiple regression analysis showed that the baseline RV area was an independent predictor of post-BPA normalization of RV systolic function defined as RV free-wall strain ≥ 20% (odds ratio = 1.16, p = 0.0305). Interestingly, significant RV reverse remodeling was also observed after additional BPA even in 18 CTEPH patients with residual pulmonary arterial stenosis, whose mPAP was normalized after BPA (RV area: from 11.5 ± 3.8 to 9.2 ± 3.8 cm2, p = 0.0045; RV free-wall strain: from 17.2 ± 4.8 to 22.8 ± 7.4%, p = 0.0216). Significant reverse remodeling in the right-sided heart, as well as hemodynamic improvement, was observed in CTEPH patients after BPA.2020年02月, The international journal of cardiovascular imaging, 英語, 国際誌[査読有り]
- SAGE Publications Ltd, 2019年10月, Pulmonary Circulation, 9(4) (4), 英語研究論文（学術雑誌）
- Elsevier BV, 2019年08月, The Journal of Heart and Lung Transplantation, 38(8) (8), 833 - 842[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2019年05月, Respiratory Medicine and Research, 75, 26 - 28研究論文（学術雑誌）
- European Respiratory Society (ERS), 2019年05月, European Respiratory Journal, 53(5) (5), 1802095 - 1802095
Aims To evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH).Methods From 2014 to 2017, 184 inoperable CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months.Results Overall, there was a significant improvement in New York Heart Association functional class, 6-min walk distance (mean change +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decreases of mean PAP and PVR were 22% and 37% in the initial periodversus 30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury, which occurred in 9.1% of 1006 sessions (13.3% in the initial periodversus 5.9% in the recent period; p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recentversus initial period) were the strongest factors related to the occurrence of lung injury. 3-year survival was 95.1%.Conclusion This study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and haemodynamics in inoperable CTEPH patients with an acceptable risk–benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure.[査読有り]研究論文（学術雑誌） - Background: While hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) can be improved by invasive therapy such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), there has been little data on the health-related quality of life (HRQOL) in such patients. Methods and Results: This single-center and observational study compared the impact of invasive therapy on HRQOL. We utilized the Medical Outcome Study 36-Item Short Health Survey (SF-36) to measure HRQOL and compared HRQOL changes after PEA and BPA. A total of 48 patients were diagnosed with CTEPH. Of these, 39 patients completed questionnaires before and after invasive therapy. The PEA group (n=15) and the BPA group (n=24) had similar improvements in clinical parameters. With regard to HRQOL score, both groups had fairly low scores in physical functioning (PF), role physical (RP), general health (GH), social functioning (SF), role emotional (RE), and physical component summary (PCS) at baseline. PF, GH, vitality (VT), mental health (MH), and PCS had significant improvements in the PEA group while PCS and all subscales except for bodily pain (BP) had significant improvements in the BPA group. Furthermore, changes between baseline and follow-up were not significantly different between the 2 groups. Conclusions: BPA for patients who are ineligible for PEA can recover HRQOL to a similar level to that achieved by PEA.2019年04月, Circulation reports, 1(5) (5), 228 - 234, 英語, 国内誌研究論文（学術雑誌）
- Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.2018年12月, Heart and vessels, 33(12) (12), 1423 - 1433, 英語, 国内誌研究論文（学術雑誌）
- 2018年09月, Chest, 154(3) (3), 521 - 531, 英語Poor Subpleural Perfusion Predicts Failure After Balloon Pulmonary Angioplasty for Nonoperable Chronic Thromboembolic Pulmonary Hypertension[査読有り]研究論文（学術雑誌）
- 2018年06月, Journal of the American Heart Association, 7(13) (13)[査読有り]
- 2018年02月, Circulation, 137(7) (7), 693 - 704, 英語Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension[査読有り]研究論文（学術雑誌）
- AIMS: Although pathological studies have indicated the development of neoatherosclerosis (NA) after stenting, its risk factors and impact on future clinical events remain unclear. We aimed to clarify the possible risk factors for NA development and to evaluate the impact of NA in a large Japanese observational OCT database of patients with coronary heart disease. METHODS AND RESULTS: One hundred and seventy-five consecutive patients (314 lesions) who underwent OCT examination >1 year after bare metal or drug-eluting stent implantation were enrolled. We assessed the presence of NA by follow-up OCT and compared adverse clinical events between NA+ and NA- patients. Forty-six patients had NA at the follow-up OCT. These patients had higher low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) levels at follow-up. In multivariate logistic analysis, LDL cholesterol and CRP levels at follow-up were independently associated with the presence of NA (odds ratio [OR]: 1.022, p=0.008, OR 1.022, p=0.001, respectively). Moreover, patients with NA had a higher incidence of major adverse cardiac events (MACE) at follow-up. Multivariate Cox hazard analysis showed that the presence of NA was an independent risk factor for MACE (hazard ratio: 2.909, p=0.012). CONCLUSIONS: High LDL cholesterol and CRP levels may be risk factors for NA development in patients treated with coronary stents. Moreover, the presence of NA was independently associated with MACE, suggesting the need for careful clinical follow-up of these patients.2016年12月, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 12(11) (11), e1366-e1374, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Clinical efficacy of balloon pulmonary angioplasty (BPA) to the patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) for improving pulmonary hemodynamics and exercise tolerance has been reported in these several years. However, reperfusion pulmonary injury (RPI) remains to be a major complication of BPA to overcome. This study elucidated the local predictor of RPI. METHODS: Twenty-eight consecutive patients with non-operable CTEPH underwent BPA for lesions in the segmental or sub-segmental vessels. Pre- and post-BPA pulmonary arterial pressures at proximal (Pp) and distal (Pd) to the stenosis were measured by a 0.014-in. pressure wire. Positive or negative RPI was evaluated by chest computed tomography in each re-perfused segment separately 4 h after BPA. RESULTS: Pressure measurements pre- and post-BPA were obtained from 110 lesions, where Pd and pressure ratio (Pd/Pp) increased after BPA in all lesions. Among them, RPI was observed in 49 lesions (44.5%). In the RPI-positive lesions, post-BPA Pd and post-BPA Pd/Pp were higher compared with the RPI-negative lesions. Multivariate logistic analysis revealed that the post-BPA Pd was independently associated with RPI incidence. Receiver operating characteristic curve analysis demonstrated the best cut-off value of 19.5 mm Hg for post-BPA Pd to predict RPI. CONCLUSIONS: High reperfusion pressure after BPA could be a predictor of RPI. Monitoring local pressure during BPA procedure may have a potential to reduce the incidence of RPI.2016年06月, International journal of cardiology. Heart & vasculature, 11, 1 - 6, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy. BACKGROUND: There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD. METHODS: This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated. RESULTS: In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007). CONCLUSIONS: Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.2015年05月, JACC. Cardiovascular interventions, 8(6) (6), 800 - 811, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Previous reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES). METHODS: We evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus. RESULTS: Although the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, -0.06±0.36 vs. -0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups. CONCLUSION: Although both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation.2015年04月, Journal of cardiology, 65(4) (4), 298 - 304, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The contribution of clopidogrel response due to cytochrome P450 (CYP) 2C19 loss-of-function polymorphism after drug-eluting stent (DES) implantation is unclear. METHODS: A total of 196 patients who had undergone optical coherence tomography (OCT) at 8 months following first-generation DES (120 lesions) and current-generation everolimus-eluting stent (EES) implantation (127 lesions) were enrolled. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs). OCT findings were compared among the 3 groups. Responsiveness to clopidogrel was assessed by VerifyNow platelet reactivity unit (PRU). RESULTS: The incidence of intra-stent thrombi was significantly higher after first-generation DES implantation compared with EES implantation (35% vs 13%, respectively; p=0.0001). In the first-generation DES group, the incidence of intra-stent thrombi significantly increased among EMs, IMs, and PMs (21% vs 36% vs 63%, respectively; p=0.007), while there was no significant difference among the 3 groups after EES implantation (10% vs 13% vs 20%, respectively; p=0.55). The PRU significantly increased among EMs, IMs, and PMs in each stent group. In multivariate analyses, although PMs had a 3-fold higher risk of thrombi formation compared with non-PMs after first-generation DES implantation, there were no significant differences in thrombi formation between the 2 groups after EES implantation. The optimal PRU cutoff values for the prediction of intra-stent thrombi with first-generation DES and EES were 234 and 256, respectively. CONCLUSION: CYP2C19 loss-of-function polymorphism is associated with a higher incidence of intra-stent thrombi after first-generation DES implantation, while the impact is attenuated following EES implantation.2015年01月, International journal of cardiology, 179, 476 - 83, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs. METHODS: We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima. RESULTS: At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents. CONCLUSIONS: Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs.2014年08月, The Canadian journal of cardiology, 30(8) (8), 904 - 11, 英語, 国際誌研究論文（学術雑誌）
- AIMS: To evaluate the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) using the results of pulmonary endarterectomy (PEA) for operable patients as a reference, and annotate the role of BPA in the management of CTEPH. METHODS AND RESULTS: Data from 53 CTEPH patients were collected retrospectively. Twenty-four operable patients underwent PEA, and 29 non-operable patients underwent BPA. Patients who underwent BPA showed improved mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (39.4±6.9 to 21.3±5.6 mmHg, 763±308 to 284±128 dyn·s-1·cm-5, 3.47±0.80 to 4.26±1.15 L/min, respectively); patients who received PEA showed similar efficacy (44.4±11.0 to 21.6±6.7 mmHg, 781±278 to 258±125 dyn·s-1·cm-5, 3.35±1.11 to 4.44±1.58 L/min, respectively). The mortality rates of BPA and PEA patients were 3.4% and 8.3%, respectively. CONCLUSIONS: The efficacy and safety of BPA for non-operable cases were similar to those achieved using PEA for operable cases. BPA could be an additional treatment option for non-operable CTEPH patients, and most CTEPH patients can be satisfactorily treated by BPA or PEA.Europa Digital & Publishing, 2014年08月, EuroIntervention, 10(4) (4), 518 - 525, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: Although hemodialysis (HD) is a suggested risk factor for stent thrombosis, its contribution to local vessel healing after drug-eluting stent (DES) implantation is unclear. METHODS: A total of 121 patients (152 lesions treated with DES) who underwent 8-month follow-up coronary angiography with optical coherence tomography (OCT) were enrolled, and the findings were compared between patients with and without HD. To match baseline differences, mid-term OCT findings of 42 propensity score-matched lesions (21 non-HD vs. 21 HD) were compared. Effects of HD on the efficacy of antiplatelet therapy were also evaluated by VerifyNow assay (Accumetrics, San Diego, CA, USA). RESULTS: Patients with HD had a significantly higher rate of thrombus formation than those without (64% vs. 33%, p = 0.007), although the baseline parameters and lesion characteristics differed between the groups. Multivariate logistic regression analysis revealed that HD was associated with an increased risk of thrombus formation (odds ratio 5.991, 95% confidence interval: 1.972-18.199, p = 0.002). Even after propensity-matching for patient background and balancing of angiographic and OCT variables, the risk of thrombus formation remained significantly higher in HD patients. The P2Y12-reaction unit was significantly increased after HD (Pre HD: 211 ± 75 vs. Post HD: 262 ± 59, p = 0.01), but patients without HD showed no increase during the same elapsed time (221 ± 88 vs. 212 ± 96, p = 0.19). CONCLUSIONS: HD is a potential risk factor for subclinical thrombus attachment after DES therapy. Systemic problems, such as residual platelet reactivity, associated with HD as well as local vessel features in HD patients might contribute to the increased incidence of thrombus attachment and subsequent onset of thrombotic event after DES implantation.2014年07月, Journal of cardiology, 64(1) (1), 25 - 31, 英語, 国際誌研究論文（学術雑誌）
- The consequences of acute strut malapposition in everolimus-eluting stents (EES) are unknown. This study investigated the impact of strut-vessel (S-V) distance and plaque type underneath acute strut malapposition on the mid-term vessel response in EES. Twenty-nine patients (35 EES) underwent optical coherence tomography (OCT) immediately after percutaneous coronary intervention and at 8-month follow-up. S-V distance and plaque type (lipid, calcified, or fibrous) underneath acute strut malapposition were evaluated. Follow-up OCT classified acute strut malapposition as persistent or resolved. The S-V cutoff value for predicting resolved strut malapposition and the incidence of intra-stent thrombi were determined. Among 569 cases of acute strut malapposition, involving 29,168 struts, 139 (24.4 %) were persistent. Mean S-V distance was significantly longer in persistent than in resolved strut malapposition (600 ± 294 vs. 231 ± 95 μm; P < 0.0001). S-V distance ≤380 μm was the best cutoff value for predicting resolved strut malapposition (sensitivity 93.5 %, specificity 69.8 %, area under curve 0.878). Acute strut malapposition with S-V distance ≤380 μm remained persistent more frequently over lipid/calcified than over fibrous plaques (lipid: 13.4 %, calcified: 18.2 %, fibrous: 4.2 %; lipid vs. fibrous, P = 0.001; calcified vs. fibrous, P = 0.02). Intra-stent thrombi were more frequent in stents with ≥1 persistent strut malapposition than in those without [4/11 stents (36.3 %) vs. 0/24 (0 %); P = 0.006]. Lipid and calcified plaque, together with S-V distance, affect the resolution of acute strut malapposition in EES. Persistent strut malapposition is associated with the presence of thrombi at follow-up, which could be the substrate for late stent thrombosis.2014年06月, The international journal of cardiovascular imaging, 30(5) (5), 857 - 65, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The addition of highly purified eicosapentaenoic acid (EPA) to statin therapy prevents cardiovascular events. However, the impact of this treatment on vulnerable plaques remains unclear. The aim of this study was to assess the impact of adding EPA to a standard statin therapy on vulnerable plaques by serial optical coherence tomography (OCT). METHODS: Forty-nine non-culprit thin-cap fibroatheroma (TCFA) lesions in 30 patients with untreated dyslipidemia were included. Patients were randomly assigned to EPA (1800 mg/day) + statin (23 TCFA, 15 patients) or statin only (26 TCFA, 15 patients) treatment. The statin (rosuvastatin) dose was adjusted to achieve a target low-density lipoprotein (LDL) level of <70 mg/dL. Post-percutaneous intervention and 9-month follow-up OCT were performed to evaluate morphological changes of TCFAs. The EPA/arachidonic acid (EPA/AA) ratio and pentraxin-3 (PTX3) levels were also evaluated. RESULTS: Despite similar follow-up LDL levels, the EPA + statin group had higher EPA/AA ratios and lower PTX3 levels than the statin group. OCT analysis showed that the EPA + statin group had a greater increase in fibrous-cap thickness, with a greater decrease in lipid arc and lipid length. Macrophage accumulation was less frequently detected in the EPA + statin group than in the statin group at follow-up. When the patients were categorized according to their follow-up PTX3 tertiles, fibrous-cap thickness showed significant increase, and the incidence of macrophages accumulation decreased with lower PTX3 levels. CONCLUSION: The concomitant use of EPA and rosuvastatin may stabilize vulnerable plaques better than the statin alone, possibly by suppressing arterial inflammation.2014年05月, Atherosclerosis, 234(1) (1), 114 - 9, 英語, 国際誌研究論文（学術雑誌）
- Secundum atrial septal defect (ASD) is the most common form of congenital heart disease in adults. Surgical and transcatheter closures of ASD are widely accepted therapeutic approaches. In patients with severe pulmonary arterial hypertension (PAH), however, the closure of the defect is still controversial. We report two cases of ASD patients with severe PAH successfully repaired subsequent to effective medical therapy. Subsequent shunt closure after targeted medical therapy can be an effective strategy in selected ASD patients with severe PAH.2014年03月, Heart and vessels, 29(2) (2), 282 - 5, 英語, 国内誌研究論文（学術雑誌）
- Neoatherosclerosis and mural thrombus detection after sirolimus-eluting stent implantation.BACKGROUND: Although both optical coherence tomography (OCT) and angioscopy are robust tools for detecting intrastent thrombi and neoatherosclerosis in vivo, whether OCT findings are comparable with angioscopy findings remains unclear. METHODS AND RESULTS: 22 patients presenting with de novo lesions underwent 26 sirolimus-eluting stent (SES) implantations, with follow-up OCT and angioscopy at 10 months post-implantation for segmental assessment of the proximal, mid-, and distal SES segments (66 segments). The mean signal intensity index (signal intensity of the neointima/signal intensity of fibrous intimal hyperplasia) was quantified for angioscopically detected in-stent yellow and white segments. The detection rate for red thrombi was numerically higher with angioscopy than with OCT (17% vs. 9%; P=0.053). Angioscopically detected in-stent yellow segments were categorized into 3 OCT patterns: "high-attenuation tissue covering struts" (OCT-defined neoatherosclerosis), "high-attenuation tissue underneath struts," and "low-attenuation and low-intensity tissue covering struts"; further, macrophage-like appearance was most frequently observed with OCT-defined neoatherosclerosis (56%, 6.3%, and 0%, respectively, P<0.001). The mean signal intensity index of neoatherosclerosis was significantly lower than that of angioscopically detected in-stent white segments (0.929 vs. 0.997, P=0.004). CONCLUSIONS: Current OCT-based definitions for thrombus detection may underestimate the presence of subclinical red thrombi. Qualitative and quantitative OCT assessments of the neointima may enhance the detection of neoatherosclerosis over SES in vivo.2014年, Circulation journal : official journal of the Japanese Circulation Society, 78(1) (1), 92 - 100, 英語, 国内誌研究論文（学術雑誌）
- Favorable vessel healing after nobori biolimus A9-eluting stent implantation-6- and 12-month follow-up by optical coherence tomography.BACKGROUND: Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6-9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear. METHODS AND RESULTS: We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72 ± 23 to 82 ± 25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96 ± 3.97% to 1.51 ± 1.63%, P=0.001, and 0.50 ± 1.84% to 0.06 ± 0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24). CONCLUSIONS: Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months.2014年, Circulation journal : official journal of the Japanese Circulation Society, 78(8) (8), 1882 - 90, 英語, 国内誌研究論文（学術雑誌）
- Vascular responses in patients with and without diabetes mellitus after everolimus-eluting stent implantation.BACKGROUND: Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM). METHODS AND RESULTS: We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients. CONCLUSIONS: Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients.2014年, Circulation journal : official journal of the Japanese Circulation Society, 78(9) (9), 2188 - 96, 英語, 国内誌研究論文（学術雑誌）
- 2013年11月, THROMBOSIS RESEARCH, 132(5) (5), 558 - 564, 英語[査読有り]研究論文（学術雑誌）
- 2013年10月, JACC: Cardiovascular Imaging, 6(10) (10), 1121 - 1123, 英語[査読有り]研究論文（学術雑誌）
- 2013年09月, EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, 14(9) (9), 865 - 875, 英語[査読有り]研究論文（学術雑誌）
- 2013年09月, CIRCULATION JOURNAL, 77(9) (9), 2383 - 2389, 英語[査読有り]研究論文（学術雑誌）
- 3, 2013年, Circulation Journal, 77(3) (3), 652 - 660, 英語[査読有り]研究論文（学術雑誌）
- Potential benefit of final kissing balloon inflation after single stenting for the treatment of bifurcation lesions--insights from optical coherence tomography observations.BACKGROUND: Treatment of coronary bifurcation lesions using a single stenting strategy is preferable over that using a 2-stent technique. The benefit of final kissing inflation (FKI), however, has not been established. METHODS AND RESULTS: Seventy-two patients (76 lesions) with true bifurcation lesions treated with a single drug-eluting stent with FKI (n=33 lesions) or without FKI (non-FKI, n=43 lesions) were enrolled in this study. Optical coherence tomography (OCT) was performed at 6-12 months after implantation. Based on the OCT findings, the percentage of jailing struts (number of jailing struts/total number of struts at the bifurcation lesion) was calculated. Percentage of uncovered struts and frequency of thrombus attachment were each evaluated at the proximal, bifurcation, and distal segments. Major adverse cardiac events (MACE) were also evaluated. The percentage of jailing struts was significantly lower in the FKI than in the non-FKI group (5.8±6.2% vs. 17.3±6.1%, P<0.01). Thrombus attachment was less frequent in the FKI group (24.2% vs. 46.5%, P=0.046), especially at side-branch orifices (3.0% vs. 27.9%, P<0.001). The percentage of uncovered struts was lower in the FKI than non-FKI group at the proximal, bifurcation, and distal segments. The incidence of MACE was not different in this small cohort. CONCLUSIONS: FKI might reduce the frequency of subclinical thrombus possibly by reducing the number of jailing struts.2013年, Circulation journal : official journal of the Japanese Circulation Society, 77(5) (5), 1193 - 201, 英語, 国内誌研究論文（学術雑誌）
- 2012年11月, JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION, 32(6) (6), 379 - 385, 英語研究論文（学術雑誌）
- 2012年08月, CIRCULATION JOURNAL, 76(8) (8), 1880 - 1888, 英語[査読有り]研究論文（学術雑誌）
- Effect of cytochrome P450 2C19 polymorphism on target lesion outcome after drug-eluting stent implantation in japanese patients receiving clopidogrel.BACKGROUND: Cytochrome P450 (CYP) 2C19 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after drug-eluting stent (DES) implantation, but its contribution to lesion outcome after DES implantation is unclear. METHODS AND RESULTS: The study included 160 Japanese patients who received clopidogrel and underwent DES implantation with follow-up angiography. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The incidence of major adverse cardiac events (MACE) and target lesion revascularization (TLR) were compared among the 3 groups. Optical coherence tomography (OCT) was performed for 120 patients to evaluate the incidence of intra-stent thrombi. Of the 160 patients, the proportion of EM, IM, and PM was 37.5%, 48.1%, and 14.4%, respectively. The incidence of TLR and MACE was more frequent in IM and PM than EM (TLR: 18.2% and 26.1% vs. 3.3%, P=0.008, MACE: 22.1% and 30.4% vs. 5.0%, P=0.005). Among the 120 patients who underwent follow-up OCT, intra-stent thrombi were more frequently detected in IM and PM than in EM (45.6% and 63.2% vs. 20.5%, P=0.005). The incidence of TLR was significantly higher in patients with than in those without intra-stent thrombi (27.7% vs. 6.8%, P=0.003). CONCLUSIONS: CYP2C19 loss-of-function polymorphism might be associated with the incidence of MACE and TLR in association with intra-stent thrombi.2012年, Circulation journal : official journal of the Japanese Circulation Society, 76(10) (10), 2348 - 55, 英語, 国内誌研究論文（学術雑誌）
- 2025年, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 10th慢性血栓塞栓性肺高血圧症に対するハイブリッド治療の最前線
- 2020年, 日本循環器学会学術集会(Web), 84th介入治療後の慢性血栓塞栓性肺高血圧症における微小血管障害の評価
- 2015年08月, EUROPEAN HEART JOURNAL, 36, 784 - 785, 英語The assessment of exercise tolerance and oxygenation after balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension研究発表ペーパー・要旨（国際会議）
- 2014年09月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 64(11) (11), B115 - B116, 英語Serial Optical Coherence Tomography Evaluation 6-, 12-and 24-month Follow-up after Nobori Biolimus A9-eluting Stent Implantation研究発表ペーパー・要旨（国際会議）
- 2014年09月, EUROPEAN HEART JOURNAL, 35, 208 - 208, 英語Either balloon pulmonary angioplasty or surgical pulmonary endarterectomy can cover most of patients with chronic thromboembolic pulmonary hypertension as treatment option研究発表ペーパー・要旨（国際会議）
- 2014年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 63(12) (12), A1797 - A1797, 英語LONG-TERM CLINICAL IMPACT OF THIN-CAP FIBROATHEROMA ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY AND VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND ANALYSIS研究発表ペーパー・要旨（国際会議）
- 2014年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 63(12) (12), A1795 - A1795, 英語IMPACT OF DAILY GLUCOSE FLUCTUATION ON CORONARY PLAQUE VULNERABILITY IN PATIENTS PRETREATED WITH LIPID LOWERING THERAPY研究発表ペーパー・要旨（国際会議）
- 2013年10月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 62(18) (18), B140 - B140, 英語The Impact of Atherogenic Neointima on Long-term Clinical Outcomes: An Observational Study from the Optical Coherence Tomography Registry研究発表ペーパー・要旨（国際会議）
- 2013年10月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 62(18) (18), B178 - B178, 英語Impact of Immediate Vessel Reactions to Stent Deployment on Periprocedural Troponin Leakage and Mid-term Vascular Healing: Serial Optical Coherence Tomography Study after Everolimus-eluting Stent Implantation研究発表ペーパー・要旨（国際会議）
- 2013年08月, EUROPEAN HEART JOURNAL, 34, 155 - 155, 英語Efficacy and safety of balloon pulmonary angioplasty for inoperable patients with peripheral type chronic thromboembolic pulmonary hypertension研究発表ペーパー・要旨（国際会議）
- 2013年08月, EUROPEAN HEART JOURNAL, 34, 50 - 50, 英語Hemodynamic improvement through beneficial vessel reaction following balloon pulmonary angioplasty for distal-type chronic thromboembolic pulmonary hypertension研究発表ペーパー・要旨（国際会議）
- 2013年03月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 61(10) (10), E1673 - E1673, 英語DIFFERENT TIME COURSE OF NEOATHEROSCLEROSIS DEVELOPMENT IN BARE METAL STENTS, SIROLIMUS-ELUTING STENTS AND PACLITAXEL-ELUTING STENTS研究発表ペーパー・要旨（国際会議）
- 2012年10月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 60(17) (17), B83 - B83, 英語Temporal Course of Vessel Healing after Everolimus-eluting Stent Implantation研究発表ペーパー・要旨（国際会議）
- 2012年10月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 60(17) (17), B220 - B220, 英語Efficacy and Safety of Balloon Pulmonary Angioplasty for Peripheral Type Chronic Thromboembolic Pulmonary Hypertension研究発表ペーパー・要旨（国際会議）
- 2012年10月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 60(17) (17), B220 - B221, 英語Beneficial Vascular Remodeling and Hemodynamic Improvement following Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension研究発表ペーパー・要旨（国際会議）
- 2011年11月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 58(20) (20), B180 - B180, 英語Uniform Vessel Healing after Everolimus-eluting Stent implantation: Detailed Comparison with Paclitaxel-eluting Stent by Optical Coherence Tomography研究発表ペーパー・要旨（国際会議）
- 2011年11月, CIRCULATION, 124(21) (21), 英語Comparison of Angioscope and Optical Coherence Tomography findings for the Assessment of Intra-stent Thrombus and Neointima at 8 months After Sirolimus-Eluting Stent Implantation研究発表ペーパー・要旨（国際会議）
- 2011年11月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 58(20) (20), B49 - B49, 英語The impact of paraoxonase-1 activity on the incidence of intra-stent thrombus after drug-eluting stent implantation in the Japanese CYP2C19*2 carriers receiving clopidogrel研究発表ペーパー・要旨（国際会議）
- 2011年11月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 58(20) (20), B181 - B181, 英語In-vivo Assessment of Neoatherosclerosis after Sirolimus-eluting Stent implantation: Comparisons of Serial Optical Coherence Tomography Findings between Early and Late Follow-up研究発表ペーパー・要旨（国際会議）
- 2011年11月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 58(20) (20), B82 - B83, 英語Long-term follow up of sirolimus-eluting stent(SES) implanted in coronary bifurcation lesion: Insight from OCT observations研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1860 - E1860, 英語A NOVEL RADIOFREQUENCY SIGNAL ANALYSIS FOR CORONARY PLAQUE CHARACTERIZATION AT CULPRIT LESION USING IMAPTM: HOW CAN WE USE THE NEW PARAMETER: CONFIDENCE LEVEL?研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1744 - E1744, 英語NATURAL CONSEQUENCE OF STENT MALAPOSITION ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1210 - E1210, 英語INFLUENCE OF PROTON PUMP INHIBITORS (PPIS) ON THE FORMATION OF INTRA-STENT THROMBUS IN JAPANESE PATIENTS RECEIVING CLOPIDOGREL WITH OR WITHOUT CYTOCHROME P450 2C19*2 POLYMORPHISM研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1723 - E1723, 英語POTENTIAL BENEFIT OF FINAL KISSING INFLATION AFTER SINGLE STENTING TO BIFURCATION LESIONS: DIFFERENCE OF OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN SIROLIMUS AND PACLITAXEL-ELUTING STENTS研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1731 - E1731, 英語ASSESSMENT OF YELLOW NEOINTIMA AND MURAL THROMBI AFTER 1ST GENERATION SIROLIMUS-ELUTING STENTS USING ANGIOSCOPE AND OPTICAL COHERENCE TOMOGRAPHY研究発表ペーパー・要旨（国際会議）
- 2011年04月, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57(14) (14), E1299 - E1299, 英語IMPACT OF CYTOCHROME P450 2C19*2 POLYMORPHISM ON THE TARGET LESION OUTCOME AFTER DRUG-ELUTING STENT IMPLANTATION IN JAPANESE PATIENTS RECEIVING CLOPIDOGREL.研究発表ペーパー・要旨（国際会議）
- 第83回日本循環器学会学術集会, 2019年03月, 日本語, 日本循環器学会, 横浜, 国内会議Predictors of survival in patients with not-operated chronic thromboembolic pulmonary hypertension口頭発表（一般）
- 第83回日本循環器学会学術集会, 2019年03月, 英語, 日本循環器学会, 横浜, 国内会議Evaluation of Microvasculopathy using Dual-Energy CT in Chronic Thromboembolic Pulmonary Hypertensionポスター発表
- Asia Pacific Advanced Heart Failure Forum, 2018年11月, 英語, Asia Pacific Advanced Heart Failure Forum, 香港, 国際会議Advances in Medical and Interventional Treatments for CTEPH[招待有り]口頭発表（招待・特別）
- 第66回日本心臓病学会学術集会, 2018年09月, 日本語, 日本心臓病学会, 大阪, 国内会議日本と海外のCTEPH疾患/治療の違い[招待有り]シンポジウム・ワークショップパネル（指名）
- ストラクチャークラブ・ジャパン ライブデモンストレーション2018, 2018年09月, 日本語, ストラクチャークラブ・ジャパン, 岡山, 国内会議PEAの進化とBPAとの共存 内科から[招待有り]シンポジウム・ワークショップパネル（指名）
- South Side of the Hearts 2018, 2018年09月, 英語, The Portuguese Cardiovascular Society, リスボン, 国際会議Meet the Experts BPA sessions[招待有り]シンポジウム・ワークショップパネル（指名）
- European Respiratory Society 2018, 2018年09月, 英語, European Respiratory Society, パリ, 国際会議Factors associated with survival in patients with not-operated chronic thromboembolic pulmonary hypertension (CTEPH) in the modern management era口頭発表（一般）
- 第27回日本心血管インターベンション治療学会, 2018年08月, 日本語, 日本心血管インターベンション治療学会, 神戸, 国内会議慢性血栓塞栓性肺高血圧に対する肺動脈内膜血栓摘除術及びバルーン肺動脈形成術の特性を活かしたハイブリッド療法シンポジウム・ワークショップパネル（公募）
- 第27回日本心血管インターベンション治療学会学術集会, 2018年08月, 日本語, 日本心血管インターベンション治療学会, 神戸, 国内会議慢性血栓塞栓性肺高血圧に対する肺動脈内膜血栓摘除術及びバルーン肺動脈形成術の特性を活かしたハイブリッド療法シンポジウム・ワークショップパネル（公募）
- European Society of Cardiology 2018, 2018年08月, 英語, European Society of Cardiology, ミュンヘン, 国際会議Factors associated with survival in patients with not-operated chronic thromboembolic pulmonary hypertension (CTEPH) in the modern management eraポスター発表
- 第3回日本肺高血圧・肺循環学会学術集会, 2018年06月, 日本語, 日本肺高血圧・肺循環学会, 大阪, 国内会議The 6th WSPH速報 左心疾患・CTEPH 治療の変更について[招待有り]シンポジウム・ワークショップパネル（指名）
- 第3回 日本肺高血圧・肺循環学会学術集会, 2018年06月, 日本語, 日本肺高血圧・肺循環学会, 大阪, 国内会議CTEPHに対する治療効果及びRC timeの臨床的意義について口頭発表（一般）
- 第3回日本肺高血圧・肺循環学会学術集会, 2018年06月, 日本語, 日本肺高血圧学会日本肺循環学会共催, 大阪, 国内会議CTEPH に対する治療効果の比較及びRC time の臨床的意義について口頭発表（一般）
- 日本学術振興会, 科学研究費助成事業, 国際共同研究加速基金(国際共同研究強化(B)), 神戸薬科大学, 2020年10月27日 - 2024年03月31日心房中隔欠損症に伴う肺動脈性肺高血圧症の分子疫学的国際共同研究本研究は、日本とインドネシアの国際共同研究として、以下の3つの課題について研究を遂行する予定であった。しかしながら、2021年度は依然として世界的なCovid19感染拡大のために研究の遂行が著しく妨げられた。インドネシアの共同研究者は感染の拡大に伴い臨床業務に忙殺され、研究遂行は著しく遅延した。また、渡航制限により研究代表者らによる現地での研究活動は不可能であった。よって、複数回にわたるオンライン会議システムを利用したディスカッションと日本およびインドネシアそれぞれが国内で遂行した研究が今年度の研究実績となる。 課題1：心房中隔欠損症に合併する肺高血圧症（ASD-PH）に関する臨床疫学データ収集・解析については、インドネシアで症例登録を継続している。進捗状況についてはオンライン会議で確認している。また、心房中隔欠損症のうち肺高血圧症合併の有無を心電図から判定する基準を作成し、現在論文を作成中である。 課題2：インドネシアにおける学校心臓検診システムの確立ならびにその有用性の評価として、インドネシア側スタッフが学校心臓検診を実施する予定であったが、2021年度も感染拡大防止の観点からも学校心臓検診を実施できなかった。これまでに収集した心電図を用いて日本で提唱された心電図判定基準の妥当性の検討について準備を進めている。 課題3：ASD-PHの病態に関与する新規原因遺伝子同定と治療標的の探索として、これまでのインドネシアで収集した患者検体を用いて実施した全エキソンシークエンスの解析を進めた。2021年度は、2020年度に同定した疾患候補遺伝子から真に意味のある病原遺伝子をさらに絞り込むために年齢、性別を適合させたインドネシア人の健常人検体を対照群として収集した。同時に、これらの遺伝子変異と疾患との相関が再現できるかどうかを確認する目的で他のグループのASD-PHの検体を収集した。
- 日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2021年04月01日 - 2023年03月31日血管老化に着目した慢性血栓塞栓性肺高血圧症における血栓器質化機序の解明1)二光子顕微鏡を用いたPEAサンプルのホールマウントイメージング 血栓の線維化は二光子顕微鏡ではSHG(第2高調波発生光)技術により、染色ステップ なしで、直接可視化できる。これによって、摘除サンプル全体を俯瞰的に観察し、異なる器 質化ステージ(軽度―高度)の病変を同定し、イメージング、病理解析を行う。さらに、PEAサンプルは血管平滑筋様細胞、血管内皮様細胞・間葉系様細胞、血球系様 細胞など、様々な細胞種から構成されているが、これらの細胞群をisolectinによる血管壁の 描出と同時にそれぞれの細胞マーカー(αSMA, CD34, CD133など)の蛍光標識抗体を用 いて可視化する。これによって、種々の器質化ステージにおいて、どのような細胞群がどの ような局所性をもって、器質化に関わっているのかを可視化、解明する。これにより、既存の盲目的な病理解析では未解明であった、CTEPHにおいて、新鮮血 栓が器質化していく過程の解明につながる可能性が高い。今年度は二光子顕微鏡の故障があり、進めることができなかった。 2)血管老化マウスにおける血栓器質化反応の解析 下大静脈結紮により静脈血栓を形成させる。野生型マウスでは結紮後4日程度から血栓の線維化が始まり、14日目にはほぼ線維化が完成することが知られている。血管老化マウスに おいて、この血栓線維化の速度が野生型マウスより早いことを二光子顕微鏡によるSHG技術 により生体下に明らかにする。病理学的にマッソン染色による線維化の評価でも確認を行う。 また、線維化に先行して、好中球やマクロファージが血栓内に浸潤することも知られている が、血管老化マウスにおいて、より早期におこっていることを病理学的に検証する。これまでの解析結果では、血管老化マウスでは大型の血栓が形成されることが明らかになりつつある。
- 日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2019年04月01日 - 2021年03月31日慢性血栓塞栓性肺高血圧症の発症・進展の分子メカニズムの解明慢性肺血栓塞栓性肺高血圧症（CTEPH）は器質化した血栓により肺動脈が狭窄・閉塞し、肺動脈圧が上昇して心不全を発症する疾患である。今回、CTEPHの病態を形成する細胞群（CTEPH細胞）の性状や増殖の分子メカニズムを肺動脈内膜摘除術で得られた患者検体を用いて解明を試みた。その結果、CTEPH細胞は血管平滑筋細胞に類似した性質を持ち、進展刺激によって増殖抑制をきたすことを明らかにすることができた。