Circadian Variability and Its Influence on Infarct Size and Clinical Outcome Among Japanese Patients With Acute Myocardial Infarction

Abstract

Background: There is significant circadian variation in the frequency of myocardial infarction onset, with a notable increase during the early morning. However, it remains unclear whether this circadian rhythm influences post-acute myocardial infarction (AMI) clinical outcomes and infarct size.

Methods and Results: This study included 2,251 patients enrolled in the Japan AMI Registry (JAMIR) who had ST-elevation myocardial infarction (STEMI) with a documented time of onset, stratified into 4 time periods: 00:00–06:00, 06:00–12:00, 12:00–18:00, and 18:00–00:00 h. The primary outcome measure, used as an indicator of infarct size, was peak creatine kinase (CK) level. The median peak CK level among patients was 1,978 IU/L. No significant differences in peak CK levels were observed among the 4 time period groups (P=0.117). Similarly, the relationship between onset time and peak CK levels was not significant (P=0.215). There were no significant differences among the 4 time period groups in secondary endpoints of in-hospital mortality (P=0.788) and 1-year clinical outcomes, including all-cause mortality (P=0.544), myocardial infarction (P=0.636), stroke (P=0.943), stent thrombosis (P=0.344), and a composite endpoint (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke; P=0.430).

Conclusions: Circadian variation had no effect on infarct size or clinical outcomes in patients with STEMI.

Central Figure

Previous studies have shown that the circadian rhythm influences cardiovascular system physiology, inducing diurnal variations in blood pressure, heart rate, cardiac output, and endothelial function, among other physiological parameters.¹ It is also known that the incidence of cardiovascular events (e.g., myocardial infarction [MI], sudden cardiac death, and arrhythmias) exhibits circadian variation, with a higher incidence around the sleep-to-wake transition period.²

The effects of circadian variation on onset, infarct size, and the clinical outcome of acute MI (AMI) have been reported.³ Circadian variation in the frequency of onset of AMI was detected, with a peak in the early morning.^4–8 The mechanism for this circadian variation in AMI onset has been considered to be disruption of atherosclerotic plaques through coronary vasoconstriction and activation of increased sympathetic tone.^2,8 Conversely, despite a morning peak in the incidence of AMI, differences in the circadian variation in the onset of AMI have been suggested in different ethnic groups, with a second peak reported to occur in the evening in the Japanese population.⁹ However, previous reports on the effects of circadian variation on infarct size and clinical prognosis are not consistent.^10–16 The time of patient presentation and treatment in hospital have been shown to be associated with differences in clinical outcomes for various medical conditions and procedures.^17–25 The present study examined the association between ST-elevation MI (STEMI) onset time and both infarct size and clinical course with more recent data from Japan, where there is a large number of facilities available for emergency percutaneous coronary intervention (PCI) per population (1 facility per 100,000 people).²⁶

The aim of the present study was to investigate the effects of the circadian variation on infarct size and clinical outcomes in Japanese patients with AMI who were enrolled in the nation-wide Japan AMI Registry (JAMIR).²⁷

Methods

Study Population

The design of the JAMIR has been described in detail previously.²⁷ Briefly, JAMIR is a multicenter, nationwide, prospective registry enrolling consecutive patients with spontaneous onset of AMI at 50 institutions between December 2015 and May 2017. For the diagnosis of AMI, either the universal definition of MI criteria or the Monitoring Trends and Determinants in Cardiovascular disease (MONICA) criteria were used.^28,29 We excluded patients who had non-STEMI, those with an unknown date of onset, those who had not been treated with early reperfusion therapy, those who had been treated with coronary artery bypass grafting (CABG) or veno-arterial extracorporeal membrane oxygenation, and those with an out-of-hospital cardiac arrest (OHCA). The management of patients was at the discretion of the treating physician. Primary data were collected from the medical records of patients. Information was collected on patient demographics, medical history, ambulance use, details about coronary angiography and invasive therapy, cardiac medications, and outcomes. The JAMIR registration system was used for data registration by investigators, clinical research coordinators, or local data managers at each study site. Follow-up data were collected 1 year after the onset of AMI based on the medical information available at each study site. When patients’ medical information was unavailable at the study sites 1 year after the onset of AMI due to hospital transfer or for other reasons, a letter requesting follow-up information was sent to patients.

This study was conducted in accordance with the ethical guidelines for medical research on humans laid out in the Declaration of Helsinki. The research protocol was approved by the Institutional Review Board of the Tohoku University School of Medicine Ethics Committee (Receipt no. 2024-1-321) or local institutional review board at each study site. Although informed consent was not obtained because of the observational nature of this registry, we used an opt-out method via a website and information provided at the study sites to inform patients of the content and timeline of the study, and to ensure that they had the opportunity to refuse inclusion in the registry. In addition, the research secretariat confirmed compliance with the opt-out procedures at each study site.

This study has been registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN00019479).

Study Endpoints

The primary endpoint of the study was myocardial infarct size, which was defined according to peak creatine kinase (CK). Secondary endpoints included in-hospital death (all-cause death), Killip classification ≥II, 1-year clinical outcome (all-cause death, MI, stroke, stent thrombosis, and a composite endpoint of cardiovascular death, non-fatal MI or non-fatal stroke). The median follow-up for all-cause death was 357 days.

The time of STEMI onset was divided into four 6-h periods according to previous studies (Period 1, 00:00–06:00 h; Period 2, 06:00–12:00 h; Period 3, 12:00–18:00 h; Period 4, 18:00–00:00 h).^{2,4,6,30–32}

Statistical Analysis

Baseline continuous variables are presented as the mean±SD for normally distributed variables or as the median with interquartile range (IQR) for skewed variables. Categorical variables are presented as numbers and percentages. Normally distributed continuous variables were compared using analysis of variance, whereas skewed continuous variables were compared using the Kruskal-Wallis test. Categorical variables were compared using the Chi-squared test. The Kaplan-Meier method and log-rank test were used to assess event-free survival for all-cause death in the 4 onset-time groups. All statistical analyses were performed using JMP Pro version 17.0 for Mac (SAS Institute, Cary, NC, USA).

Results

Baseline Patient Characteristics

In all, 3,411 patients were registered in the JAMIR from the 50 participating sites. Patients meeting the following criteria were excluded from the present study because it was considered inappropriate to use peak CK as an indicator of infarct size in these cases: non-STEMI diagnosis (n=785); unknown date of onset (n=194); no early reperfusion therapy treatment (n=318); CABG treatment (n=93); veno-arterial extracorporeal membrane oxygenation treatment (n=72); and OHCA or unknown (n=139). Finally, 2,251 patients with STEMI were included in this analysis (Figure 1). These patients were divided into 4 groups according to the time of onset as follows: Period 1, 00:00–06:00 h (435 patients; 19.3%); Period 2, 06:00–12:00 h (704 patients; 31.2%); Period 3, 12:00–18:00 h (573 patients; 25.4%); and Period 4, 18:00–00:00 h (539 patients; 23.9%). There was a significantly higher number of patients in the Period 2 group than in the other groups (Figure 2).

Figure 1.

Study flowchart. CABG, coronary artery bypass grafting; JAMIR, Japan Acute Myocardial Infarction Registry; NSTEMI, non-ST segment elevation myocardial infarction; OHCA, out-of-hospital cardiac arrest; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

Figure 2.

Distribution of patients according to the time of day of ST-elevation myocardial infarction onset.

The baseline characteristics of patients overall and in each of the four 6-h periods separately are presented in Table 1. Overall, the mean patient age was 67±13 years, and 509 (22.6%) were women. There were no significant differences in age, sex, body mass index, use of ambulance, shock on arrival, medical history (hypertension, dyslipidemia, previous MI episode, previous PCI/CABG, cerebrovascular disease, peripheral artery disease, malignancy, atrial fibrillation), current smoking, estimated glomerular filtration rate, hemoglobin, low-density lipoprotein cholesterol, culprit lesion, medication during hospitalization, medical complication, length of hospital stay among the 4 time-period groups. In the Period 1 (onset 00:00–06:00 h) group, the time from onset to admission and the door-to-device time were significantly longer than in the other groups.

Table 1.

Baseline Patient Characteristics Overall and According to Symptom Onset Time

	Overall (n=2,251)	Symptom onset time				P value
		00:00–6:00 h (n=435)	06:00–12:00 h (n=704)	12:00–18:00 h (n=573)	18:00–00:00 h (n=539)
Age (years)	67±13	67±13	68±13	68±13	67±13	0.37
Female sex	509 (22.6)	90 (20.7)	161 (22.9)	132 (23.0)	126 (23.4)	0.757
BMI (kg/m2)	24.0±3.9	24.1±4.0	23.9±3.8	24.1±4.2	23.9±3.9	0.886
Use of ambulance	1,941 (86.2)	377 (86.7)	589 (83.7)	497 (86.7)	478 (88.7)	0.078
Shock on arrival (SBP <90 mmHg)	121(5.4)	21 (4.8)	49 (6.3)	30 (5.2)	26 (4.8)	0.74
Killip class ≥II	460 (20.4)	94 (21.6)	138 (19.6)	119 (20.8)	109 (20.2)	0.868
Time from onset to admission (min)	129 [62–281]	182 [86–453]	128 [64–225]	120 [60–220]	115 [55–363]	<0.0001
Door-to-device time (min)	65 (50–87)	69 (54–100)	64 (50–84)	63 (47–87)	64 (50–87)	0.0036
Hypertension	1,591 (70.7)	304 (69.9)	510 (72.4)	397 (69.3)	380 (70.5)	0.629
Diabetes	763 (33.9)	155 (35.6)	243 (34.5)	190 (33.2)	175 (32.5)	0.721
Dyslipidemia	1,582 (70.3)	311 (71.3)	480 (68.2)	410 (71.6)	381 (70.7)	0.517
Previous MI	166 (7.4)	38 (8.7)	52 (7.4)	32 (5.6)	44 (8.2)	0.225
Previous PCI	198 (8.8)	43 (9.9)	67 (9.5)	44 (7.7)	44 (8.2)	0.52
Previous CABG	37 (1.6)	6 (1.4)	17 (2.4)	8 (1.4)	6 (1.1)	0.269
Previous cerebrovascular disease	197 (8.8)	38 (8.7)	60 (8.5)	41 (7.2)	58 (10.8)	0.204
Peripheral artery disease	61 (2.7)	11 (2.5)	18 (2.6)	18 (3.1)	14 (2.6)	0.908
Malignancy	186 (8.3)	35 (8.1)	60 (8.5)	49 (8.6)	42 (7.8)	0.958
Atrial fibrillation	134 (6.0)	20 (4.6)	49 (7.0)	33 (5.8)	32 (5.9)	0.433
Current smoking	961 (42.7)	189 (43.5)	289 (41.1)	250 (43.6)	233 (43.2)	0.766
eGFR (mL/min/1.73 m2)	67.0±24.1	68.7±24.1	66.9±24.7	67.0±23.7	65.9±23.6	0.311
Hemoglobin (g/dL)	14.0±2.1	14.1±2.3	14.0±2.1	14.0±2.1	13.9±2.1	0.432
LDL-C (mg/dL)	122±39	126±39	120±36	123±39	122±41	0.345
Peak CK (IU/L)	1,978 [918–3,690]	2,186 [1,006–4,126]	1,815 [907–3,605]	1,962 [848–3,566]	2,053 [955–3,739]	0.117
Peak CK-MB (IU/L)	193 [86–364]	212 [93–398]	189 [81–359]	193 [84–356]	187 [87–354]	0.464
Culprit lesion
LMT	24 (1.1)	4 (0.9)	6 (0.9)	7 (1.2)	7 (1.3)	0.849
LAD	1,125 (50.0)	222 (51.0)	337 (47.9)	298 (52.0)	268 (49.7)	0.493
LCX	234 (10.4)	46 (10.6)	69 (9.8)	57 (10.0)	62 (11.5)	0.774
RCA	907 (40.3)	169 (38.9)	302 (42.9)	214 (37.4)	222 (41.2)	0.203
LVEF (%)	51.6±11.6	51.2±11.6	52.4±11.7	51.9±11.4	50.6±11.8	0.055
Medication during hospitalization
Aspirin	2,229 (99.0)	431 (99.1)	697 (99.0)	568 (99.1)	533 (98.9)	0.98
Clopidogrel	332 (14.8)	70 (16.1)	101 (14.4)	89 (15.5)	72 (13.4)	0.61
Prasugrel	1,985 (88.2)	381 (87.6)	626 (88.9)	499 (87.1)	479 (88.9)	0.7
ACE inhibitors	1,258 (55.9)	234 (53.8)	392 (55.7)	338 (59.0)	294 (54.6)	0.332
ARBs	608 (27.0)	132 (30.3)	174 (24.7)	152 (26.5)	150 (27.8)	0.205
β-blockers	1,515 (67.3)	283 (65.1)	462 (65.6)	398 (69.5)	372 (69.0)	0.281
Statins	2,091 (92.9)	399 (91.7)	664 (94.3)	527 (92.0)	501 (93.0)	0.283
Oral anticoagulants	288 (12.8)	56 (12.9)	83 (11.8)	76 (13.3)	73 (13.5)	0.793
Mechanical complications
Cardiac rupture	13 (0.58)	2 (0.46)	4 (0.57)	2 (0.35)	2 (0.93)	0.62
Ventricular septal perforation	2 (0.09)	0 (0)	1 (0.14)	0 (0)	1 (0.19)	0.64
Right ventricular infarction	89 (3.95)	16 (3.68)	25 (3.55)	23 (4.01)	25 (4.64)	0.787
Length of hospital stay (days)	12 [9–17]	12 [9–17]	12 [9–17]	12 [9–16]	12 [9–17]	0.529

Unless indicated otherwise, data are given as the mean±SD, median [interquartile range], or n (%). ACE, angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers; BMI, body mass index; CABG, coronary artery bypass grafting; CK, creatine kinase; CK-MB, creatine kinase-myocardial bundle; eGFR, estimated glomerular filtration rate; LAD, left anterior descending artery; LCX, left circumflex artery; LDL-C, low-density lipid cholesterol; LMT, left main trunk; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; RCA, right coronary artery; SBP, systolic blood pressure; STEMI, ST-elevation myocardial infarction.

Clinical outcomes are presented in Table 2. There were no significant differences in peak CK, peak CK-MB, or clinical outcomes among the 4 groups. The median peak CK for the 2,251 patients was 1,978 IU/L (IQR 918–3,690 IU/L). Although there was a trend for slightly higher peak CK levels in the Period 1 (onset 00:00–06:00 h) group (median 2,185 IU/L; IQR 1,006–4,126 IU/L) than in the other groups, there were no significant differences among the groups (P=0.117; Figure 3A). Analysis of peak CK levels according to the hour of onset revealed no significant differences across the time of day (P=0.215; Figure 3B).

Table 2.

Clinical Outcomes of Patients Overall and According to Time of Symptom Onset

	Overall (n=2,251)	Onset time				P value
		00:00–6:00 h (n=435)	06:00–12:00 h (n=704)	12:00–18:00 h (n=573)	18:00–00:00 h (n=539)
Outcomes during hospitalization
Peak CK (IU/L)	1,978 [918–3,690]	2,186 [1,006–4,126]	1,815 [907–3,605]	1,962 [848–3,566]	2,053 [955–3,739]	0.117
Peak CK-MB (IU/L)	193 [86–364]	212 [93–398]	189 [81–359]	193 [84–356]	187 [87–354]	0.464
Killip class ≥II	460 (20.4)	94 (21.6)	138 (19.6)	119 (20.8)	109 (20.2)	0.868
In-hospital death	73 (3.24)	16 (3.68)	24 (3.41)	15 (2.62)	18 (3.34)	0.788
1-year clinical outcome
CV mortality+non-fatal MI/non-fatal stroke	130 (5.8)	30 (6.9)	43 (6.1)	26 (4.5)	31 (5.8)	0.43
All-cause mortality	127 (5.6)	28 (6.4)	44 (6.3)	27 (4.7)	28 (5.2)	0.544
MI	55 (2.4)	11 (2.5)	20 (2.8)	10 (1.8)	14 (2.6)	0.636
Stroke	21 (0.9)	3 (0.7)	7 (1.0)	6 (1.1)	5 (0.9)	0.943
Stent thrombosis	20 (0.9)	2 (0.5)	6 (0.9)	4 (0.7)	8 (1.5)	0.344

Unless indicated otherwise, data are presented as the median [interquartile range] or n (%). CV, cardiovascular. Other abbreviations as in Table 1.

Figure 3.

(A) Relationship between peak creatine kinase (CK) levels and ST-elevation myocardial infarction (STEMI) onset time divided into 4 periods. (B) Relationship between peak CK and STEMI onset time for each hour over a 24-h period. The boxes show the interquartile range, with the median value indicated by the horizontal line; whiskers show the range.

The in-hospital mortality rate overall was 3.24%. There were no significant differences in in-hospital mortality rates across Periods 1, 2, 3, and 4 (3.68%, 3.41%, 2.62%, and 3.34%, respectively). There were 127 deaths during the 1-year follow-up: 28 (6.4%), 44 (6.3%), 27 (4.7%), and 28 (5.2%) in Periods 1, 2, 3, and 4, respectively. Kaplan-Meier curves of all-cause mortality are shown in Figure 4. There were no significant differences among the 4 groups (log-rank test, P=0.527). In addition, there were no significant differences among the 4 groups in any of the other endpoints, namely MI, stroke, stent thrombosis, and the composite endpoint (cardiovascular death and non-fatal MI or non-fatal stroke; Table 2).

Figure 4.

Kaplan-Meier survival curves for mortality according to onset time in patients with ST-elevation myocardial infarction. There were no significant differences in mortality among the 4 onset-time groups (log-rank P=0.527).

Peak CK levels were significantly higher in patients who died in hospital, had Killip class ≥II on admission, and experienced major cardiovascular events or death within 1 year than in those without these events (Supplementary Table).

Discussion

In this study we investigated the effects of AMI onset time on infarct size, as indicated by peak CK levels, and clinical outcomes (including in-hospital/1-year death, MI, stroke, stent thrombosis, and a composite of cardiovascular death and non-fatal MI or non-fatal stroke). Our analysis used data from the prospective multicenter JAMIR. The key findings of the present study are that: (1) AMI onset frequently occurred between 06:00 and 12:00 h; and (2) there were no significant circadian fluctuations in terms of infarct size or clinical outcomes among patients based on STEMI onset time.

Almost all previous studies have reported a circadian variation in the onset of AMI, characterized by a morning peak between 06:00 and 12:00 h.^2,3 Interestingly, in the JAMIR retrospective study of Japanese patients with AMI who were hospitalized between January 2011 and December 2013, an onset pattern with a single peak at 08:00 h was noted.³³ In the present prospective JAMIR study, we identified a sole peak in AMI onset during the morning h. Conversely, some studies in Japan have reported a bimodal frequency of AMI occurrence, with peaks during the morning and evening.^9,34

Cardiovascular physiology is significantly modulated by the circadian rhythm.^1,35 The mechanism underlying increased cardiac events in the morning is attributed to heightened sympathetic activity mediated by autonomic nervous system modulation.³⁶ In addition, morning hypercoagulability leads to elevated blood viscosity, thrombogenicity, and hypofibrinolysis, thereby increasing the likelihood of AMI onset during this period. Conversely, the mechanism behind the evening peak remains unclear. Evening activities, such as alcohol consumption and social engagement, may augment sympathetic activity, contributing to the increased frequency of AMI onset at night.³⁴ Consequently, physiological and socioeconomic factors may affect evening peaks of AMI onset, potentially accounting for variations observed across different populations.³⁷

There is conflicting evidence regarding the impact of the time of AMI onset on clinical outcomes.^{10–12,14–16,38} De Luca et al. observed that patients with STEMI treated with primary PCI between 04:00 and 08:00 h had worse outcomes than those treated at other times, whereas those treated between 08:00 and 16:00 h had improved myocardial perfusion and survival.¹⁰ Assali et al. reported increased in-hospital mortality in patients with anterior STEMI undergoing primary PCI between 18:00 and 08:00 h.¹¹ A study from the Singapore Myocardial Infarction Registry found that patients with symptom onset between 00:00 and 06:00 h had larger infarct sizes and higher rates of heart failure, although associations with mortality were not significant after adjustment.¹⁵ In contrast, a study from 6 Arabian Gulf countries found a significant association between time of symptom onset and in-hospital mortality, with the lowest mortality rates occurring for those with symptom onset between 04:00 and 10:00 h.¹⁶ Conversely, recent studies, including a Korean registry and large-scale analyses from England and Wales, reported no significant differences in mortality based on time of symptom onset.^12,14,38 Although patients admitted at night had longer symptom onset to reperfusion times and higher mortality between 20:00 and 00:00 h, no differences were observed in clinical outcomes or infarct size across different the time periods.³⁸ These discrepancies may have arisen from variations in transportation conditions, emergency medical systems (including the availability of experienced medical staff and their skills), technological advances resulting from modernization, and changes in guidelines over time across different countries and regions.

Study Limitations

This study has several limitations. First, although the study was conducted in 50 institutions nationwide in Japan, there may be selection bias in terms of the hospitals chosen to take part in the registry. Therefore, it may not be possible to extrapolate the results of this study to all institutions in Japan. Second, the blood sampling interval for patients with MI varies by hospital, therefore peak CK values may vary between hospitals. However, this study showed that peak CK was associated with clinical outcome (death in-hospital, Killip class ≥II on admission, and major cardiovascular events/death within 1 year). Third, multiple factors could have affected the circadian variation and clinical outcomes in this population. Fourth, because the onset of STEMI was self-reported by patients, the time of onset may be inaccurate. Fifth, the population size of this study may not be sufficient to detect differences between circadian variations and primary or secondary endpoints. Finally, this study was performed using data from a multicenter nationwide registry, and lacked detail on regional factors, such as the availability of emergency PCI services, the number of tertiary emergency hospitals, the adequacy of interventionalists, and the sufficiency of hospital equipment.

Conclusions

The incidence of MI was notably higher between 06:00 and 12:00 h, indicating a peak occurrence during this time period, although the difference was not statistically significant. Despite this circadian variation, there were no discernible effects of time of symptom onset on in-hospital or 1-year clinical outcomes. These findings suggest that improvements in healthcare systems may have mitigated the previously observed differences in diurnal variability concerning clinical outcomes with time.

Acknowledgments

The authors thank all the investigators, clinical research coordinators, and data managers involved in the JAMIR study for their contributions. The JAMIR study group institutions and members are listed in the Appendix.

Sources of Funding

This work was planned by the Japan Cardiovascular Research Foundation and funded by Daiichi Sankyo Co., Ltd.

Disclosures

K.M. reports lecture fees from Daiichi Sankyo, Novartis, and Takeda, and scholarship donations from Daiichi Sankyo. M. Takayama reports lecture fees from Daiichi Sankyo. H.O. reports lecture fees and research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, and Sanofi. S.Y. reports remuneration for lectures from Takeda, Daiichi Sankyo, and Bristol-Myers Squibb, and trust research/joint research funds from Takeda and Daiichi Sankyo. K.M., Y.S., and S.Y. are members of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Tohoku University School of Medicine Ethics Committee (Receipt no. 2024-1-321).

Data Availability

The data for this study will not be shared to avoid compromising the privacy of the research participants.

Appendix

The JAMIR study group institutions and members are as follows:

• Hokkaido Medical Center: Takashi Takenaka

• Hirosaki University: Hirofumi Tomita, Hiroaki Yokoyama

• Iwate Medical University: Tomonori Ito, Masaru Ishida, Yorihiko Koeda

• Yamagata University: Masafumi Watanabe, Tetsu Watanabe, Taku Toshima

• Tohoku University: Hiroaki Shimokawa, Yasuhiko Sakata, Jun Takahashi, Kiyotaka Hao

• Sakakibara Heart Institute: Tetsuya Sumiyoshi, Masamori Takayama

• Yokohama City University Hospital: Kazuo Kimura, Masami Kosuge, Toshiaki Ebina

• Showa Medical University Fujigaoka Hospital: Hiroshi Suzuki, Atsuo Maeda

• Mie University Hospital: Masaaki Ito, Tairo Kurita, Jun Masuda

• Matsuzaka Central General Hospital: Takashi Tanigawa

• Ehime University Hospital: Jitsuo Higaki, Kazuhisa Nishimura

• Oita University: Naohiko Takahashi, Hidefumi Akioka, Kyoko Kawano

• Nagasaki University: Koji Maemura, Satoshi Ikeda, Yuji Koide, Shuntaro Sato

• Kumamoto University: Sunao Kojima, Kenichi Tsujita

• National Cerebral and Cardiovascular Center: Hisao Ogawa, Satoshi Yasuda, Yasuhide Asaumi, Kensaku Nishihira, Yoshihiro Miyamoto, Misa Takegami, Satoshi Honda

• Nagasaki Harbor Medical Center: Hiroshi Nakajima

• Isahaya General Hospital: Kenji Yamaguchi

• Sapporo City General Hospital: Takao Makino

• Sapporo Cardiovascular Clinic: Daitarou Kannno

• Teine Keijinkai Hospital: Yasuhiro Omoto

• Hokkaido Cardiology Hospital: Daisuke Otta

• Sapporo Kosei General Hospital: Toshiya Sato

• Nippon Medical School Musashi Kosugi Hospital: Naoki Sato, Arifumi Kikuchi, Michiko Sone, Koji Takagi

• Ayase Heart Hospital: Imun Tei

• Tokyo Metropolitan Hiroo General Hospital: Takashi Shibui, Sho Nagamine

• Nippon Medical School Hospital: Wataru Shimuzu, Takeshi Yamamoto

• Tokyo Saiseikai Central Hospital: Toshiyuki Takahashi

• Tokyo Medical Center: Yukihiko Momiyama

• St. Luke’s International Hospital: Atsushi Mizuno

• Edogawa Hospital: Hiroshi Ohira

• Kyorin University Hospital: Hideaki Yoshino, Youhei Shigeta

• Nihon University Itabashi Hospital: Atsushi Hirayama, Yasuo Okurmura, Daisuke Fukamachi, Tadateru Takayama

• Toho University Omori Medical Center: Hiroki Niikura, Hiroki Takenaka

• Mitsui Memorial Hospital: Shuzo Tanimoto, Kazuyuki Yahagi

• Tokyo Metropolitan Tama Medical Center: Hiroyuki Tanaka

• Disaster Medical Center: Yasuhiro Sato, Ohno Masakazu

• Musashino Red Cross Hospital: Takamichi Miyamoto, Nobuhiro Hara

• NTT Medical Center: Mikio Kishi

• Oume Municipal General Hospital: Sigeo Shimizu, Ken Kurihara

• Oghikubo Hospital: Yasuhiro Ishii

• Teikyo University Hospital: Ken Kozuma, Yusuke Watanabe

• Fraternity Memorial Hospital: Yasuhiro Takahashi

• Jikei University Hospital: Michihiro Yoshimura, Satoshi Morimoto

• Tokyo Women’s Medical University Hospital: Nobuhisa Hagiwara, Yuichiro Minami

• Tokyo Medical University Hospital: Jun Yamashita

• Osaki Citizen Hospital: Kaoru Iwabuchi, Takeshi Yamauchi

• Sendai Open Hospital: Atsushi Kato, Shigeto Namiuchi

• Sendai Medical Center: Tsuyoshi Shinozaki, and Kesennuma City Hospital: Kazunori Ogata, Ryuji Tsuburaya

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0112

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