Message From the Editor-in-Chief
Circulation Journal Awards for the Year 2024
2025 Volume 89 Issue 3 Pages 257-271
Details
2025 Volume 89 Issue 3 Pages 257-271
Dear Colleagues,
On behalf of the Editorial Team of Circulation Journal, I am pleased to announce the Circulation Journal Awards for the Year 2024.
The aim of these Awards is to recognize papers published in 2024, both clinical and experimental studies, that were highly appreciated by the Editorial Team. The selection process comprises 2 steps. In the first step, from 160 original papers published in the journal in 2024, our 47 Japanese Associate Editors selected papers with a high scientific level in their respective fields. In the second step, 5 groups each consisting of 6–11 Japanese Associate Editors further evaluated the selected papers in terms of originality, contribution to cardiovascular science, manner of paper preparation, and future possibilities.
In the year of 2024, the following 7 papers have been selected for the Circulation Journal Awards.
(Circ J 2024; 88: 146–156)1
| Deep Learning Models for Predicting Left Heart Abnormalities From Single-Lead Electrocardiogram for the Development of Wearable Devices Masataka Sato, Satoshi Kodera, Naoto Setoguchi, Kengo Tanabe, Shunichi Kushida, Junji Kanda, Mike Saji, Mamoru Nanasato, Hisataka Maki, Hideo Fujita, Nahoko Kato, Hiroyuki Watanabe, Minami Suzuki, Masao Takahashi, Naoko Sawada, Masao Yamasaki, Shinnosuke Sawano, Susumu Katsushika, Hiroki Shinohara, Norifumi Takeda, Katsuhito Fujiu, Masao Daimon, Hiroshi Akazawa, Hiroyuki Morita, Issei Komuro Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo (M. Sato, S. Kodera, S.S., S. Katsushika, H.S., N.T., K.F., M.D., H.A., H. Morita, I.K.); Division of Cardiology, Mitsui Memorial Hospital, Tokyo (N. Setoguchi, K.T.); Department of Cardiovascular Medicine, Asahi General Hospital, Asahi (S. Kushida, J.K.); Department of Cardiology, Sakakibara Heart Institute, Fuchu (M. Saji, M.N.); Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama (H. Maki, H.F.); Department of Cardiology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu (N.K., H.W.); Department of Cardiology, JR General Hospital, Tokyo (M. Suzuki, M.T.); Department of Cardiology, NTT Medical Center Tokyo, Tokyo (N. Sawada, M.Y.); and Department of Advanced Cardiology, The University of Tokyo, Tokyo (K.F.), Japan |
 |
Machine learning procedures and model architecture. The Lead I electrocardiogram (ECG) was taken from the 12-lead ECG and assigned to the Convolutional Neural Network model. The structure of the model is shown. The model consists of temporal blocks, a spatial convolution block, and fully connected layers. BatchNorm2d, batch normalization for 2-dimensional inputs; Conv2d, 2-dimensional convolution; MaxPool2d, 2 dimensional max pooling.
Area under the receiver operating characteristic curves (AUC) of Lead I models and 12-lead models to detect abnormalities of left heart morphology for the internal test dataset. The receiver operating characteristic (ROC) curves for each of the 5 morphological features (low ejection fraction [EF], wall motion abnormality [WMA], left ventricular hypertrophy [LVH], left ventricular dilatation [LVD], and left atrial dilatation [LAD]) are shown.
Background: Left heart abnormalities are risk factors for heart failure. However, echocardiography is not always available. Electrocardiograms (ECGs), which are now available from wearable devices, have the potential to detect these abnormalities. Nevertheless, whether a model can detect left heart abnormalities from single Lead I ECG data remains unclear.
Methods and Results: We developed Lead I ECG models to detect low ejection fraction (EF), wall motion abnormality, left ventricular hypertrophy (LVH), left ventricular dilatation, and left atrial dilatation. We used a dataset comprising 229,439 paired sets of ECG and echocardiography data from 8 facilities, and validated the model using external verification with data from 2 facilities. The area under the receiver operating characteristic curves of our model was 0.913 for low EF, 0.832 for wall motion abnormality, 0.797 for LVH, 0.838 for left ventricular dilatation, and 0.802 for left atrial dilatation. In interpretation tests with 12 cardiologists, the accuracy of the model was 78.3% for low EF and 68.3% for LVH. Compared with cardiologists who read the 12-lead ECGs, the model’s performance was superior for LVH and similar for low EF.
Conclusions: From a multicenter study dataset, we developed models to predict left heart abnormalities using Lead I on the ECG. The Lead I ECG models show superior or equivalent performance to cardiologists using 12-lead ECGs.
(Circ J 2024; 88: 1679–1688)2
| Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/ Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease Ichiro Mizushima, Noriyasu Morikage, Eisaku Ito, Fuminori Kasashima, Yasushi Matsumoto, Naoki Sawa, Hajime Yoshifuji, Takako Saeki, Yukako Shintani- Domoto, Shogo Shimada, Toshio Takayama, Eisuke Amiya, Makiko Ozawa, Masaaki Takahashi, Yasunari Fujinaga, Takahiro Katsumata, Yukio Obitsu, Atsushi Izawa, Hiroyuki Kanno, Noriko Oyama-Manabe, Nobukazu Ishizaka, Tasuku Nagasawa, Hiroki Takahashi, Takao Ohki, Mitsuhiro Kawano, Satomi Kasashima, Joint Working Group from the Japanese Circulation Society and the Ministry of Health, Labour and Welfare Study Group Department of Nephrology and Rheumatology, Kanazawa University Hospital, Kanazawa (I.M., M.K.); Division of Vascular Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube (N.M.); Division of Vascular Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo (E.I., T.O.); Department of Cardiovascular Surgery, Kanazawa Medical Center, Kanazawa (F.K., Y.M.); Department of Nephrology and Rheumatology, Toranomon Hospital, Kawasaki (N.S.); Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto (H.Y.); Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka (T.S.); Department of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo (Y.S.-D.); Department of Cardiac Surgery, The University of Tokyo, Tokyo (S.S.); Division of Vascular Surgery, Department of Surgery (T.T.), Department of Cardiovascular Medicine (E.A.), Graduate School of Medicine, The University of Tokyo, Tokyo; Department of Internal Medicine, Matsumoto Dental University Hospital, Shiojiri (M.O.); Department of Radiology (M.T., Y.F.), Department of Pathology (H.K.), Shinshu University School of Medicine, Matsumoto; Department of Thoracic and Cardiovascular Surgery, Osaka Medical and Pharmaceutical University, Takatsuki (T.K.); Department of Vascular Surgery, International University of Health and Welfare Mita Hospital, Tokyo (Y.O.); School of Health Sciences, Shinshu University, Matsumoto (A.I.); Department of Radiology, Jichi Medical University Saitama Medical Center, Saitama (N.O.-M.); Health Check-up Center, Doai Memorial Hospital, Tokyo (N.I.); Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai (T.N.); Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo (H.T.); and Department of Clinical Laboratory Science, Graduate School of Health Science, Kanazawa University, Kanazawa (S.K.), Japan |
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Performance of the 2018 Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis and Each of the Revisions in the Validation Group
| Sensitivity (%) |
Specificity (%) |
PLR | NLR | |
|---|---|---|---|---|
| Definite and probable diagnosis as “IgG4-RD” | ||||
| 2018 original criteria | 68.4 | 97.4 | 26.31 | 0.32 |
| Revision E (Revisions A–C combined) | 71.9 | 97.4 | 27.65 | 0.29 |
| Revision G (Revisions A, C, and D combined) | 77.2 | 94.7 | 14.57 | 0.24 |
| Revision I (Revisions A–D combined) | 77.2 | 94.7 | 14.57 | 0.24 |
| Definite, probable, and possible diagnosis as “IgG4-RD” | ||||
| 2018 original criteria | 100 | 92.1 | 12.66 | 0 |
| Revision E (Revisions A–C combined) | 100 | 89.5 | 9.52 | 0 |
| Revision G (Revisions A, C, and D combined) | 100 | 92.1 | 12.66 | 0 |
| Revision I (Revisions A–D combined) | 100 | 89.5 | 9.52 | 0 |
Revision A: addition of “pericardial thickening and/or effusion” to the items of radiologic cardiovascular/retroperitoneal findings. Revision B: change in the serological item “Elevated serum IgG4 concentration (IgG4 ≥135 mg/dL)” to “Elevated serum IgG4 concentration (IgG4 ≥135 mg/dL) or elevated serum IgG4/IgG ratio (IgG4/IgG >8%)”. Revision C: addition of “eosinophilic infiltration” and “lymphoid follicles” to the histologic items. Revision D: addition of “probable diagnoses of extra-cardiovascular/retroperitoneal organ involvement based on the comprehensive diagnostic criteria and/or organ-specific criteria for each organ” to the other organ involvement item. IgG4-RD, IgG4-related disease; NLR, negative likelihood ratio; PLR, positive likelihood ratio.
Revised 2023 Diagnostic Criteria for IgG4-Related Cardiovascular/Retroperitoneal Disease
| A. Diagnostic factors |
| 1. Abnormal radiologic findings |
| a. Low-density hypertrophic thickening or soft tissue masses surrounding the aorta and its major branches *1, *2, *3, *4 |
| b. Soft tissue masses in renal pelvic wall and/or around the ureter *5 |
| c. Soft tissue masses in the pelvis and paravertebral area |
| d. Pericardial thickening or pericardial effusion *6 |
| 2. Elevated serum IgG4 concentration (IgG4 ≥135 mg/dL) |
| 3. Histologic findings of the periaortic/periarterial and/or retroperitoneal regions |
| a. (i), (ii), (iii)/(iv) |
| a′. (i), (ii), (v)/(vi) |
| b. (i), (ii) |
| (i) Marked lymphocyte and plasmacyte infiltration and fibrosis *7, *8, *9 |
| (ii) IgG4-positive plasma cell infiltration: |
| Surgical samples: IgG4-positive plasma cells >30/HPF and ratio of IgG4/IgG positive cells >40% |
| Biopsy samples: IgG4-positive plasma cells >10/HPF and ratio of IgG4/IgG positive cells >40% |
| (iii) Storiform fibrosis |
| (iv) Obliterative phlebitis |
| (v) Eosinophilic infiltration: eosinophils >5/HPF |
| (vi) Lymphoid follicles |
| 4. Other organ involvement |
| When a definitive or probable diagnosis of IgG4-related disease is made in the ophthalmic region, salivary glands, pancreas, bile duct, kidney or lung by comprehensive diagnostic criteria or organ-specific diagnostic criteria for the indicated organs |
| B. Diagnosis |
| Definite diagnosis (definite): 1(a/b/c/d) + 3a or 1(a/b/c/d) + 3a′ or 1(a/b/c/d) + 2 + 4 |
| Probable diagnosis (probable): 1(a/b/c/d) + 3b or 1(a/b/c/d) + 4 or 3a or 3a′ |
| Possible diagnosis (probable): 1(a/b/c/d) + 2 or 3b |
| C. Appendix |
| *1. Stenosis of the vessel lumen is not present in the aorta; however, lumen narrowing may be observed in medium-sized vessels |
| *2. Occasionally accompanied by lumen dilatation or aneurysm formation |
| *3. It is necessary to exclude atherosclerosis, arterial dissection, infectious diseases (bacteria, tuberculosis, syphilis, etc.), other forms of vasculitis, malignant diseases, such as malignant lymphoma and cancers, and Erdheim-Chester disease |
| *4. The lesions may, in general, involve medium-to-large-sized vessels |
| *5. It is common in the renal pelvis and upper ureter |
| *6. It is necessary to exclude infectious diseases (bacteria, tuberculosis, virus, etc.), autoimmune or autoinflammatory diseases, and malignancy such as malignant lymphoma and cancers |
| *7. Infiltration of lymphocytes and plasma cells is observed in the periarterial regions; vasculitis in the medial layer may be present in the thoracic aorta |
| *8. Findings of obliterative phlebitis may be more easily assessed by Elastica van Gieson staining than hematoxylin-eosin staining |
| *9. Necrosis, granuloma, and neutrophil infiltration are not usually observed; when these findings are present, differential diagnosis should be carefully undertaken |
Note, “/” indicates “or”. HPF, high-power field.
Background: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version.
Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients (“mimickers”) identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts’ diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating “radiologic findings of pericarditis”, “eosinophilic infiltration or lymphoid follicles”, and “probable diagnosis of extra-PA/-RPF lesions”, improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively.
Conclusions: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.
(Circ J 2024; 88: 285–294)3
| Organ Damage and Quality of Life in Takayasu Arteritis ― Evidence From a National Registry Analysis ― Hajime Yoshifuji, Yoshikazu Nakaoka, Haruhito A. Uchida, Takahiko Sugihara, Yoshiko Watanabe, Sohei Funakoshi, Mitsuaki Isobe, Masayoshi Harigai, Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS) Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto (H.Y., S.F.); Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita (Y.N.); Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (H.A.U.); Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo (T.S.); Department of General Medicine, Kawasaki Medical School, Kurashiki (Y.W.); Sakakibara Heart Institute, Tokyo (M.I.); and Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo (M.H.), Japan |
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Factors associated with high levels of nursing care (Level ≥2) identified by logistic regression analysis. Bars indicate the 95% confidence intervals of the odds ratio. Red dots indicate significant factors associated with high nursing care levels. For age at surveillance and disease duration, odds ratios per 1-year increase are presented. Numerical data are presented in Supplementary Table 4. “Aortic lesions” refers to aortic aneurysm or dissection.
Comparison of employment rates between patients with Takayasu arteritis (TAK) and the Japanese (JPN) general population in the 2013 fiscal year stratified according to age for (A) females and (B) males. The analysis included 1,874 continuously registered patients aged ≥15 years with descriptions of social situations. A significant difference in employment rates was observed for females (P=4.25×10−38), but not males (P=0.217). Numerical data are presented in Supplementary Table 5.
Background: Takayasu arteritis, affecting primarily young women, damages large arteries and organs. We examined the impact of disease duration and sex on organ damage and quality of life using Japan’s Intractable Disease Registry.
Methods and Results: After refining data, 2,013 of 2,795 patients were included in the study. Longer disease duration was related to a lower prevalence of disease activity symptoms, a higher prevalence of organ damage, and a higher proportion of patients requiring nursing care. Compared with men, women tended to have an earlier onset age, exhibiting longer disease duration. A higher proportion of women had aortic regurgitation and required nursing care. The proportion of female patients in employment was lower than that of the general female population, whereas no difference was observed between male patients and the general male population. Logistic regression analysis revealed that age at surveillance, brain ischemia, visual impairment/loss, and ischemic heart disease were significant factors associated with high nursing care needs (Level ≥2, with daily activity limitations).
Conclusions: Early diagnosis and effective treatment, particularly to prevent brain ischemia, visual impairment, and ischemic heart disease, may improve the quality of life of patients with Takayasu arteritis, especially women.
(Circ J 2024; 88: 1788–1797)4
| Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis Tadashi Murai, Hiroyuki Hikita, Masao Yamaguchi, Aki Ito, Takayuki Warisawa, Hiroshi Ikeda, Ken Takahashi, Hirotaka Yano, Joonmo Chang, Takahiro Watanabe, Hiroshi Yoshikawa, Yoshinori Kanno, Keiichi Hishikari, Atsushi Takahashi, Hiroyuki Fujii, Taishi Yonetsu, Tetsuo Sasano, Tsunekazu Kakuta Cardiovascular Center, Yokosuka Kyosai Hospital, Kanagawa (T.M., H.H., A.I., H.I., K.T., H. Yano, J.C., T. Watanabe, K.H., A.T.); Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama (M.Y., H.F.); Department of Cardiology, NTT Medical Center, Tokyo (T. Warisawa); Department of Cardiovascular Medicine, Tokyo Medical Dental University Hospital, Tokyo (H. Yoshikawa, Y.K., T.Y., T.S.); and Department of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki (T.K.), Japan |
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Kaplan-Meier plots of the primary and secondary endpoints for patients with and without abnormal values for basal microvascular resistance (b-IMR). The primary endpoint, comprising the incidence of all-cause death and heart failure, is significantly different between patients with low and high b-IMR values (P<0.001) (A), but b-IMR does not significantly predict the secondary endpoint, which includes the incidence of cardiovascular death, acute coronary syndrome, any coronary revascularization, cerebral infarction, and peripheral vascular events (B).
Kaplan-Meier plots of the primary and secondary endpoints for patients with and without abnormal values of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Patients with low CFR showed a significant higher incidence of both endpoints (A,B), whereas high IMR was associated with the occurrence of the secondary endpoint but not the primary endpoint (C,D).
Background: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.
Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively).
Conclusions: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.
(Circ J 2024; 88: 1778–1787)5
| Long-Term Effects of Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention in High-Risk Subgroups Ko Yamamoto, Erika Yamamoto, Takeshi Morimoto, Hiroki Shiomi, Takenori Domei, Ryoji Taniguchi, Hiroshi Sakai, Mamoru Toyofuku, Shuichiro Kaji, Ryuzo Nawada, Takafumi Yokomatsu, Satoru Suwa, Yutaka Furukawa, Kazushige Kadota, Kenji Ando, Takeshi Kimura, on behalf of the CREDO- Kyoto PCI/CABG Registry Investigators Department of Cardiology, Kokura Memorial Hospital, Kitakyushu (K.Y., T.D., K.A.); Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto (E.Y., H. Shiomi); Department of Clinical Epidemiology, Hyogo College of Medicine, Hyogo (T.M.); Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo (R.T.); Department of Cardiovascular Medicine, Shiga University of Medical Science Hospital, Shiga (H. Sakai); Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama (M.T.); Department of Cardiology, Kansai Electric Power Hospital, Osaka (S.K.); Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka (R.N.); Department of Cardiology, Mitsubishi Kyoto Hospital, Kyoto (T.Y.); Department of Cardiology, Juntendo University Shizuoka Hospital, Shizuoka (S.S.); Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe (Y.F.); Department of Cardiology, Kurashiki Central Hospital, Okayama (K.K.); and Department of Cardiology, Hirakata Kohsai Hospital, Osaka (T.K.), Japan |
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Kaplan-Meier curves for (A) upper gastrointestinal bleeding, (B) myocardial infarction or ischemic stroke, and (C) all-cause death in patients with and without treatment with a proton pump inhibitor (PPI). Cumulative incidence was estimated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the univariate Cox proportional hazard model.
Subgroup Analysis
| No. patients with event/no. patients (cumulative 5-year incidence; %) |
Crude HR (95% CI) |
P value | Adjusted HR (95% CI) |
P value | Pinteraction | ||
|---|---|---|---|---|---|---|---|
| PPI (n=11,202) | No PPI (n=13,361) | ||||||
| Primary bleeding outcome measure: UGIB | |||||||
| Age | |||||||
| ≥75 years | 91/3,854 (2.6) | 96/3,978 (2.6) | 1.01 (0.76–1.35) | 0.94 | 0.67 (0.47–0.96) | 0.03 | 0.11 |
| <75 years | 93/7,348 (1.3) | 161/9,383 (1.6) | 0.75 (0.58–0.97) | 0.03 | 0.61 (0.45–0.84) | 0.002 | |
| Sex | |||||||
| Male | 131/8,141 (1.7) | 200/9,869 (2.0) | 0.81 (0.65–1.01) | 0.06 | 0.59 (0.45–0.77) | <0.001 | 0.27 |
| Female | 53/3,061 (1.8) | 57/3,492 (1.5) | 1.10 (0.76–1.60) | 0.62 | 0.76 (0.47–1.24) | 0.27 | |
| Acute coronary syndrome | |||||||
| Yes | 80/5,345 (1.5) | 74/4,479 (1.7) | 0.92 (0.67–1.26) | 0.61 | 0.66 (0.43–1.01) | 0.054 | 0.69 |
| No | 104/5,857 (1.9) | 183/8,882 (2.0) | 0.89 (0.70–1.13) | 0.33 | 0.66 (0.50–0.88) | 0.01 | |
| ARC-HBR | |||||||
| Yes | 132/5,369 (2.6) | 159/5,367 (3.2) | 0.86 (0.68–1.08) | 0.19 | 0.67 (0.50–0.88) | 0.01 | 0.56 |
| No | 52/5,833 (0.9) | 98/7,994 (1.1) | 0.73 (0.52–1.02) | 0.07 | 0.59 (0.39–0.90) | 0.01 | |
| Oral anticoagulants useA | |||||||
| Yes | 32/1,234 (2.7) | 36/1,067 (3.8) | 0.79 (0.49–1.27) | 0.34 | 0.76 (0.47–1.22) | 0.26 | 0.80 |
| No | 152/9,968 (1.6) | 221/12,294 (1.7) | 0.87 (0.71–1.07) | 0.18 | 0.80 (0.64–0.98) | 0.03 | |
| P2Y12 inhibitor | |||||||
| Ticlopidine | 39/2,779 (1.5) | 135/8,321 (1.5) | 0.92 (0.65–1.32) | 0.66 | 0.68 (0.46–1.01) | 0.06 | 0.48 |
| Clopidogrel | 141/8,187 (1.8) | 117/4,717 (2.5) | 0.71 (0.55–0.90) | 0.01 | 0.63 (0.47–0.86) | 0.003 | |
| Study | |||||||
| Cohort-2 | 42/3,089 (1.4) | 140/9,133 (1.5) | 0.96 (0.68–1.35) | 0.81 | 0.72 (0.49–1.05) | 0.09 | 0.19 |
| Cohort-3 | 142/8,113 (1.8) | 117/4,228 (2.8) | 0.65 (0.51–0.83) | <0.001 | 0.62 (0.46–0.83) | 0.001 | |
| Primary ischemic outcome measure: MI or ischemic stroke | |||||||
| Age | |||||||
| ≥75 years | 376/3,854 (10.1) | 424/3,978 (10.8) | 0.94 (0.82–1.09) | 0.42 | 0.99 (0.83–1.19) | 0.93 | 0.16 |
| <75 years | 559/7,348 (6.9) | 675/9,383 (6.5) | 1.07 (0.96–1.20) | 0.22 | 1.00 (0.86–1.15) | 0.95 | |
| Sex | |||||||
| Male | 688/8,141 (8.0) | 835/9,869 (7.8) | 1.02 (0.92–1.13) | 0.70 | 1.00 (0.87–1.13) | 0.94 | 0.70 |
| Female | 247/3,061 (7.8) | 264/3,492 (7.4) | 1.11 (0.93–1.32) | 0.25 | 1.01 (0.80–1.26) | 0.95 | |
| Acute coronary syndrome | |||||||
| Yes | 444/5,345 (7.8) | 368/4,479 (8.0) | 1.03 (0.90–1.19) | 0.64 | 1.04 (0.86–1.27) | 0.68 | 0.50 |
| No | 491/5,857 (8.1) | 731/8,882 (7.6) | 1.05 (0.93–1.17) | 0.43 | 0.99 (0.86–1.14) | 0.87 | |
| ARC-HBR | |||||||
| Yes | 585/5,369 (11.5) | 598/5,367 (11.0) | 1.01 (0.90–1.14) | 0.83 | 1.03 (0.89–1.19) | 0.69 | 0.81 |
| No | 350/5,833 (5.1) | 501/7,994 (5.7) | 0.96 (0.83–1.10) | 0.51 | 0.95 (0.80–1.14) | 0.60 | |
| Oral anticoagulant use | |||||||
| Yes | 132/1,234 (11.1) | 106/1,067 (9.5) | 1.11 (0.86–1.44) | 0.41 | 0.99 (0.69–1.40) | 0.94 | 0.99 |
| No | 803/9,968 (7.6) | 993/12,294 (7.6) | 1.02 (0.93–1.12) | 0.66 | 0.99 (0.88–1.12) | 0.92 | |
| P2Y12 inhibitor | |||||||
| Ticlopidine | 254/2,779 (9.3) | 689/8,321 (7.8) | 1.20 (1.04–1.38) | 0.01 | 1.11 (0.94–1.31) | 0.24 | 0.54 |
| Clopidogrel | 662/8,187 (7.5) | 387/4,717 (7.6) | 1.04 (0.92–1.18) | 0.54 | 0.95 (0.81–1.11) | 0.49 | |
| Study | |||||||
| Cohort-2 | 251/3,089 (8.8) | 729/9,133 (7.6) | 1.12 (0.97–1.30) | 0.11 | 1.09 (0.92–1.28) | 0.32 | 0.98 |
| Cohort-3 | 684/8,113 (7.7) | 370/4,228 (7.9) | 1.04 (0.92–1.18) | 0.55 | 0.93 (0.80–1.09) | 0.38 | |
| All-cause death | |||||||
| Age | |||||||
| ≥75 years | 1,190/3,854 (28.6) | 1,146/3,978 (25.1) | 1.12 (1.03–1.21) | 0.01 | 1.14 (1.02–1.26) | 0.02 | 0.20 |
| <75 years | 816/7,348 (9.6) | 862/9,383 (7.8) | 1.23 (1.12–1.35) | <0.001 | 1.27 (1.12–1.43) | <0.001 | |
| Sex | |||||||
| Male | 1,411/8,141 (15.4) | 1,493/9,869 (13.1) | 1.18 (1.09–1.26) | <0.001 | 1.16 (1.06–1.28) | 0.002 | 0.53 |
| Female | 595/3,061 (17.7) | 515/3,492 (12.4) | 1.37 (1.22–1.55) | <0.001 | 1.24 (1.06–1.44) | 0.01 | |
| Acute coronary syndrome | |||||||
| Yes | 880/5,345 (14.8) | 661/4,479 (12.9) | 1.14 (1.03–1.27) | 0.01 | 1.17 (1.02–1.35) | 0.03 | 0.98 |
| No | 1,126/5,857 (17.1) | 1,347/8,882 (12.9) | 1.31 (1.21–1.42) | <0.001 | 1.18 (1.07–1.30) | 0.001 | |
| ARC-HBR | |||||||
| Yes | 1,575/5,369 (27.2) | 1,449/5,367 (23.8) | 1.13 (1.06–1.22) | 0.001 | 1.20 (1.09–1.31) | <0.001 | 0.86 |
| No | 431/5,833 (6.0) | 559/7,994 (5.7) | 1.06 (0.93–1.20) | 0.40 | 1.11 (0.94–1.31) | 0.22 | |
| Oral anticoagulant use | |||||||
| Yes | 300/1,234 (22.3) | 248/1,067 (20.0) | 1.07 (0.91–1.27) | 0.40 | 1.16 (0.92–1.47) | 0.20 | 0.95 |
| No | 1,706/9,968 (15.3) | 1,760/12,294 (12.3) | 1.23 (1.15–1.31) | <0.001 | 1.18 (1.08–1.28) | <0.001 | |
| P2Y12 inhibitors | |||||||
| Ticlopidine | 556/2,779 (18.7) | 1,196/8,321 (12.7) | 1.52 (1.37–1.68) | <0.001 | 1.27 (1.13–1.42) | <0.001 | 0.07 |
| Clopidogrel | 1,401/8,187 (15.1) | 757/4,717 (13.1) | 1.13 (1.04–1.24) | 0.01 | 1.10 (0.98–1.23) | 0.10 | |
| Study | |||||||
| Cohort-2 | 597/3,089 (18.8) | 1,291/9,133 (12.8) | 1.54 (1.39–1.69) | <0.001 | 1.24 (1.11–1.39) | <0.001 | 0.12 |
| Cohort-3 | 1,409/8,113 (15.0) | 717/4,228 (13.2) | 1.12 (1.02–1.22) | 0.02 | 1.12 (0.996–1.25) | 0.06 | |
The number of patients with an event was counted throughout the entire follow-up period. The cumulative 5-year incidence was estimated by the Kaplan-Meier method. HRs and 95% CIs were estimated throughout the entire follow-up period by Cox proportional hazard models. AIn the multivariable analysis, we used a parsimonious model adjusting for 10 variables (age ≥75 years, male sex, acute coronary syndrome, hypertension, prior MI, eGFR <30 mL/min/1.73 m2 or HD, atrial fibrillation, hemoglobin <11.0 g/dL, platelet count <100×109/L, malignancy) due to the small number of patients with events. Abbreviations as in Tables 1,2.
Background: Proton pump inhibitors (PPIs) reportedly reduce upper gastrointestinal bleeding (UGIB) in patients undergoing percutaneous coronary intervention (PCI). However, whether the benefits of PPIs differ in high-risk subgroups is unknown.
Methods and Results: Among 24,563 patients undergoing first PCI in the CREDO-Kyoto registry Cohort-2 and -3, we evaluated long-term effects of PPI for UGIB, defined as GUSTO moderate/severe bleeding, in several potential high-risk subgroups. In the study population, 45.6% of patients were prescribed PPIs. Over a median 5.6-year follow-up, PPIs were associated with lower adjusted risk of UGIB (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.50–0.80; P<0.001) and a non-significant but numerically lower risk of any gastrointestinal bleeding (HR 0.84; 95% CI 0.71–1.01; P=0.06). PPIs were not associated with a lower risk of GUSTO moderate/severe bleeding (HR 1.04; 95% CI 0.94–1.15; P=0.40) or a higher adjusted risk of myocardial infarction or ischemic stroke (HR 1.00; 95% CI 0.90–1.12; P=0.97), but were associated with higher adjusted mortality risk (HR 1.18; 95% CI 1.09–1.27; P<0.001). The effects of PPIs for UGIB, myocardial infarction or ischemic stroke, and all-cause death were consistent regardless of age, sex, acute coronary syndrome, high bleeding risk, oral anticoagulant use, and type of P2Y12 inhibitor.
Conclusions: PPIs were associated with a lower risk of UGIB and a neutral risk of ischemic events regardless of high-risk subgroup.
(Circ J 2024; 88: 425–433)6
| Exosomal miR206 Secreted From Growing Muscle Promotes Angiogenic Response in Endothelial Cells Hiroya Hayashi*, Yasuhiro Izumiya, Toshifumi Ishida, Yuichiro Arima, Ou Hayashi, Minoru Yoshiyama, Kenichi Tsujita, Daiju Fukuda Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka (H.H., Y.I., O.H., M.Y., D.F.); Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (T.I., K.T.); and Laboratory of Developmental Cardiology, International Research Center for Medical Sciences, Kumamoto University, Kumamoto (Y.A.), Japan *Current affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka |
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MicroRNA (miRNA) profile of circulating exosomes. (A,B) Real-time polymerase chain reaction (PCR) array analysis of miRNAs extracted from serum exosomes. (C) Target gene prediction using TargetScan and miRDB. (D) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the predicted target genes. (E) Significant upregulation of miR-133 and miR-206 in Akt-TG mice compared with control (Cont) mice, as assessed using droplet digital PCR. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range. “x” represents the average value, and “o” represents the sample.
Exogenous supplementation of miR206 promotes angiogenic response in human umbilical vein endothelial cells (HUVEs). (A) Representative images of HUVEC spheroids formed with or without exogenous miR206 supplementation. (B) Quantitative analysis of sprout length and the number of sprouts per spheroid. (C) Expression of angiogenesis-related transcripts in HUVECs. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range. “x” represents the average value, and “o” represents the sample.
Background: Resistance exercise is beneficial in patients with lower extremity arterial disease. Muscle-derived exosomes contain many types of signaling molecules, including microRNAs (miRNAs). Here, we tested the hypothesis that exosomal miRNAs secreted by growing muscles promote an angiogenic response in endothelial cells (ECs).
Methods and Results: Skeletal muscle-specific conditional Akt1 transgenic (Akt1-TG) mice, in which skeletal muscle growth can be induced were used as a model of resistance training. Remarkable skeletal muscle growth was observed in mice 2 weeks after gene activation. The protein amount in exosomes secreted by growing muscles did not differ between Akt1-TG and control mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway frequency analysis of 4,665 target genes, identified using an miRNA array miRNAs, revealed a significant increase in Akt and its downstream signaling pathway genes. Among the upregulated miRNAs, miR1, miR133, and miR206 were significantly upregulated in the serum of Akt1-TG mice. miR206 was also increased in insulin-like growth factor (IGF)-1-stimulated hypertrophied myotubes. Exogenous supplementation of exosomal miR206 to human umbilical vein ECs promoted angiogenesis, as assessed using the spheroid assay, and increased the expression of angiogenesis-related transcripts.
Conclusions: Exosomal miR206 is upregulated in the blood of Akt1-TG mice and in IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted an angiogenic response in ECs. Our data suggest that miR206 secreted from growing muscles acts on ECs and promotes angiogenesis.
(Circ J 2024; 88: 2010–2020)7
| Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation ― Implications for Treatment in Asian Populations ― Kuan-Yu Lai, Masashi Amano, Yosuke Nabeshima, Chien-Chang Lee, Chin-Hua Su, Kang Liu, Tetsuji Kitano, Chih-Hsien Wang, Hsien-Li Kao, Yi-Lwun Ho, Maurice Enriquez-Sarano, Masaaki Takeuchi, Chisato Izumi, Li-Tan Yang Division of Cardiology, Department of Internal Medicine (K.-Y.L., K.L., H.-L.K., Y.-L.H., L.-T.Y.), Department of Emergency Medicine (C.-C.L., C.-H.S.), Department of Surgery (C.-H.W.), Cardiovascular Center (H.-L.K., Y.-L.H., L.-T.Y.), Telehealth Center (Y.-L.H., L.-T.Y.), National Taiwan University Hospital, Taipei, Taiwan; Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Osaka (M.A., C.I.); Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu (Y.N., T.K.), Japan; Valve Science Center, Minneapolis Heart Institute Foundation, Minneapolis, MN (M.E.-S.), USA; and Department of Laboratory and Transfusion Medicine, Hospital of University of Occupational and Environmental Health, School of Medicine, Kitakyushu (M.T.), Japan |
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Surgical incidence and survival. (A,B) The 10-year rate of surgery was lower among women than men (A), but 10-year post-surgical survival was similar between the sexes (B). (C,D) Ten-year survival for all-cause (C) and cardiovascular (D) deaths was poorer among women than men. Solid lines show relative risks (RR), shaded areas show 95% confidence intervals (CI). ACD, all-cause death; CVD, cardiovascular death.
Adjusted spline curves for the risk of all-cause death during the total follow-up in women and men. The hazard ratio (HR)=1 line represents average cohort mortality, with excess mortality for values >1. (A–D) In women, spline curves adjusted for aortic valve surgery and race (Japanese or Taiwanese) showed increased all-cause death when left ventricular ejection fraction (LVEF) was below 53% (A), the left ventricular (LV) end-systolic dimension index (LVESDi) was above 24.8 mm/m2 (B), the LV end-systolic volume index (LVESVi) above 44 mL/m2 (C), and the indexed maximal ascending aorta size (AoDi) was above 25.5 mm/m2 (D). (E–H) In men, the corresponding cut-off values were 52% for LVEF (E), 23.4 mm/m2 for LVESDi (F), 52 mL/m2 for LVESVi (G), and 23.2 mm/m2 for AoDi (H).
Background: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.
Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008–2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3–7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamax cut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men.
Conclusions: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.
Congratulations to the seven Circulation Journal Award winners. We will be presenting the awards to the seven honored authors at the 89th Annual Scientific Meeting of the Japanese Circulation Society, and we look forward to receiving submissions of papers with high scientific impact for publication in the Circulation Journal in 2025.
