Editors’
ChoiceORIGINAL PAPER

Nagoya J. Med. Sci. 83. 697–703, 2021
doi:10.18999/nagjms.83.4.697

Prevalence of acute coronary syndrome during the pandemicof COVID-19 in the Tokai Region of Japan
Nobutaka Kudo1,2, Akihito Tanaka1, Hideki Ishii1,2, Yusuke Uemura3,
Kensuke Takagi4, Makoto Iwama5, Ruka Yoshida6, Taiki Ohashi7,
Hideki Kawai8, Yosuke Negishi9, Norio Umemoto10, Miho Tanaka11,
Masato Watarai3, Naoki Yoshioka1,4, Itsuro Morishima4, Toshiyuki Noda5,Yukihiko Yoshida6, Yosuke Tatami7, Takashi Muramatsu8, Toshikazu Tanaka9,Hiroshi Tashiro10, Yasunobu Takada11, Hideo Izawa8, Eiichi Watanabe2and Toyoaki Murohara1
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan2
Department of Cardiology, Fujita Health University Bantane Hospital, Nagoya, Japan
3
Cardiovascular Center, Anjo Kosei Hospital, Anjo, Japan
4
Department of Cardiology, Ogaki Municipal Hospital, Ogaki, Japan
5
Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan
6
Department of Cardiology, Japanese Red Cross Society, Nagoya Daini Hospital, Nagoya, Japan
7
Department of Cardiology, Toyota Kosei Hospital, Toyota, Japan
8
Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan
9
Department of Cardiology, Okazaki Municipal Hospital, Okazaki, Japan10
Department of Cardiology, Ichinomiya Municipal Hospital, Ichinomiya, Japan
11
Department of Cardiology, Konan Kosei Hospital, Konan, Japan
1ABSTRACTThe outbreak of coronavirus disease 19 (COVID-19) has had a great impact on medical care. During theCOVID-19 pandemic, the rate of hospital admissions has been lower and the rate of in-hospital mortality
has been higher in patients with acute coronary syndrome (ACS) in Western countries. However, in Japan,
it is unknown whether the COVID-19 pandemic has affected the incidence of ACS. In the study, elevenhospitals in the Tokai region participated. Among enrolled hospital, we compared the incidence of ACS
during the COVID-19 pandemic (April and May, 2020) with that in equivalent months in the preceding
year as the control. During the study period; April and May 2020, 248 patients with ACS were admitted.
Compared to April and May 2019, a decline of 8.1% [95% confidence interval (CI) 5.2–12.1; P = 0.33]
in admissions for ACS was observed between April and May 2020. There was no significant difference inthe strategy for revascularization and in-hospital deaths between 2019 and 2020. In conclusion, the rate ofadmission for ACS slightly decreased during the COVID-19 pandemic, compared to the same months in
the preceding year. Moreover, degeneration of therapeutic procedures for ACS did not occur.
Keywords: COVID-19, acute coronary syndrome
Abbreviations:
ACS: acute coronary syndrome

Received: September 9, 2020; accepted: February 16, 2021
Corresponding author; Hideki Ishii, MD, PhD
Department of Cardiology, Fujita Health University Bantane Hospital, 3-6-10 Otobashi, Nakagawa-ku, Nagoya454-8509, Japan
Tel: +81-52-323-5656, Fax: +81-52-323-6399, E-mail: hkishii@med.nagoya-u.ac.jp
697

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Nobutaka Kudo et al

COVID-19: coronavirus disease 2019
PCI: percutaneous coronary intervention
STEMI: ST elevation myocardial infarction
This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalLicense. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION
Since the initial detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
virus in 2019, the number of coronavirus disease 19 (COVID-19) cases have been increasing
and more than 6,416,000 cases including approximately 383,000 deaths have been reported
worldwide as of June 4, 2020.1
A report has suggested relationships between COVID-19 and cardiac disease.2 The cytokine
storm due to inflammatory respiratory disease may induce coronary plaque rupture, resulting in
onset of acute coronary syndrome (ACS).3,4 In contrast, reports have suggested a decreased in
the incidence of acute myocardial infarction (AMI) during the COVID-19 outbreak in Westerncountries.5-8 However, limited data are available on the incidence of ACS during the COVID-19
pandemic in Japan.
Moreover, the COVID-19 pandemic might prompt hospitals to suspend or delay medical
services. Because specific factors may greatly affect the clinical outcomes in patients withACS, it is important to evaluate how the pandemic situation has affected the rate of in-hospitalmortality in patients with ACS.
The aim of the present study was to evaluate the influence of the COVID-19 pandemic on
the incidence of ACS in Japan.

METHODSWe performed a retrospective observational study in 11 hospitals in the Tokai area of Japan.
There was at least one board-certified interventionist of the Japanese Association of CardiovascularIntervention and Therapeutics in every participating hospital that had high performance foremergency percutaneous coronary intervention (PCI). We evaluated patients with ACS who wereadmitted to each hospital from April 1 to May 31, 2020.
Some variables were compared between the study period (April 1 to May 31, 2020) and thecontrol: the inter-year period (April 1 to May 31, 2019). ST elevation myocardial infarction(STEMI), non-STEMI, and unstable angina were defined as previously reported.9 Treatment
strategies including revascularization and medical treatment were left to the discretion of theindividual cardiologists in charge. The study protocol and use of registry data were approved by
the institutional ethics committee at each hospital in accordance with the Declaration of Helsinki.
We obtained data on coronary risk factors such as hypertension, diabetes, dyslipidemia andrenal function. In addition, coronary angiographical findings and methods of coronary revascularization were collected. As the in-hospital outcomes, data on door-to-balloon time in STEMI
cases and in-hospital death were also analyzed.

STATISTICAL ANALYSIS
Continuous variables are presented as mean (± standard deviation) or median with the699
ACS and COVID-19 pandemic in Japan

interquartile range. Categorical variables are presented as percentages. As to continuous variables,differences between the study and the control periods were analyzed by a Student unpaired t-test
or Mann-Whitney U test. As to categorical variables, comparisons across the 2 periods wereperformed by a chi-square test. Point differences with 95% confidence intervals are presented
for incidence of ACS.
Statistical analysis was performed using SPSS Version 22 (IBM Corp., Armonk, NY, USA).
Differences were considered significant at P <0.05.

RESULTS
The study included consecutive 248 patients with ACS who were admitted between April1 and May 31, 2020. We compared them to 270 subjects in the preceding year. Compared toApril 1 to May 31, 2019, there was a 8.1% [95% confidence interval (CI) 5.2–12.1; P = 0.33]
reduction of ACS cases between April 1 and May 31, 2020. Except for 2 cases, we performed
coronary angiography (CAG) and decided strategies for coronary revascularization. One in 2019
was a 96 year-old female who presented with typical STEMI. Because of very high age aswell as frailty, we did not perform CAG. One in 2020 who was admitted due to anterior-septal
STEMI suffered from cardiac rupture, resulting in death before CAG.

Table 1

Clinical characteristics of enrolled patients

2019

2020

n=270

n=248

p-value

Age, y70.9±11.5

68.5±12.0

0.02

Male

212 (78.5%)

198 (79.8%)

0.71

23.7±3.4

23.9±4.1

0.69

Hypertension

205 (75.9%)

171 (69.0%)

0.08

Diabetes

99 (36.7%)

90 (36.3%)

0.93

Dyslipidemia

205 (75.9%)

186 (75.0%)

0.81

Current smoking

68 (25.2%)

71 (28.6%)

0.38

estimated glomerular filtration rate
<60 mL/min/1.73m2

118 (43.7%)

119 (48.0%)

0.33

Hemodialysis

12 (4.4%)

14 (5.6%)

0.53

Prior myocardial infarction

32 (11.9%)

35 (14.1%)

0.44

Prior PCI

63 (23.3%)

59 (23.8%)

0.90

Prior CABG

16 (5.9%)

7 (2.8%)

0.09

Body mass index

0.38

Types of ACS
STEMI

147 (54.4%)

120 (48.4%)

Non-STEMI

47 (17.4%)

47 (19.0%)

Unstable angina

76 (28.1%)

81 (32.7%)

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Nobutaka Kudo et al

0.60

Target vessel
LMT

10 (3.7%)

10 (4.0%)

LAD

106 (39.3%)

111 (44.8%)

LCX

41 (15.2%)

38 (15.3%)

RCA

91 (33.7%)

76 (30.6%)

Graft

4 (1.5%)1 (0.4%)Multivessel/ unclear

18 (6.7%)

12 (4.8%)
0.19

Treatment for Revascularization
PCI

242 (89.6%)

233 (94.0%)

CABG

17 (6.3%)8 (3.2%)

Medication

11 (4.1%)

7 (2.8%)Impella®

2 (0.7%)1 (0.4%)

1.00

IABP

39 (14.4%)

36 (14.5%)

0.98

PCPS

7 (2.6%)8 (3.2%)0.67

Mechanical Support

ACS: acute coronary syndrome
CABG: coronary artery bypass graft
IABP: intra-aortic balloon pumping
LAD: left anterior descending artery
LCX: left circumflex artery
LMT: left main trunk
PCI: percutaneous coronary intervention
PCPS: percutaneous cardiopulmonary support
RCA: right coronary artery
STEMI: ST elevation myocardial infarction

Table 1 shows clinical characteristics in both periods. There was no significant difference inbaseline characteristics including various coronary risk factors, except for age. Types of ACS wasalso comparable (Figure 1). Notable, methods of revascularization and mechanical supports wereperformed in usual manner. We collected door-to-balloon time in STEMI cases and in-hospital
death as in-hospital outcomes (Table 2). Direct PCI was performed in 141 and 118 STEMIpatients in 2019 and 2020, respectively. Door-to-balloon time was similar [78.5 (62.0–119.8) in2019 vs. 81.0 (60.0–102.0) min in 2020, P = 0.54]. Rate of in-hospital death was 5.6% of casesin 2019 and in 5.2% in 2020. No significant difference was seen between two periods (p = 0.84).

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ACS and COVID-19 pandemic in Japan

Fig. 1 Comparison of the absolute numbers of acute coronary syndrome in 2019 and 2020
Comparison of the absolute numbers of admissions for all acute coronary syndrome, ST elevation myocardialinfarction (STEMI), non-STEMI and unstable angina (UA) between April and May 2019 (blue bars) and Apriland May 2020 (orange bars).

Table 2Clinical outcomes

20192020
p-value

In-hospital mortality

15 (5.6%)(n=270)13 (5.2%)(n=248)0.84

Door-to-balloon time in STEMI cases
undergoing direct PCI

78.5(62.0–119.8)(n=141)81.0(60.0–102.0)(n=118)0.54

PCI: percutaneous coronary intervention
STEMI: ST elevation myocardial infarction

DISCUSSION
The first cases of COVID-19 was reported in Japan on January 17, 2020. Since then, theCOVID-19 has been widely spread throughout Japan, and the Japanese government declared astate of emergency nationwide on April 16, 2020. In such situations, one of exploring points wasto understand how the pandemic was impacting hospital admissions and the care of patients with
ACS. During the COVID-19 pandemic, to protect the medical care system, the governments inmany countries have given the alarm that people should have social distances as well as refrainfrom going outside as much as possible. Unfortunately, the degeneration of medical performance,
for example, such as the postponement or cancelling of many elective procedures, might havea significant negative impact on society. As of mid-April 2020, some parts of scheduled PCIs
were postponed according to a statement from academic societies such as the Japanese Circula-702
Nobutaka Kudo et altion Society. On the other hand, a recent study suggests that most of the Japanese institutions
normally continued to perform primary PCI for STEMI cases even in the COVID-19 pandemic.10
Our study showed that the incidence of ACS during the COVID-19 pandemic (April and May2020) was similar to that in the equivalent months in 2019. In addition, emergency care forpatients with ACS was performed as usual in the participant hospitals in the Tokai area, centralJapan, during the COVID-19 pandemic. To the best our knowledge, our paper was the firstreport of ACS description in Japan during COVID-19 pandemic. From this point, our findings
are of significance.
A report has suggested that COVID-19 is related to ischemic events such as stroke.11 However,a significant decrease in ACS-related hospitalization rates (approximately 30%) was seen innorthern Italy between February 20, 2020 and March 31, 2020, compared to the same period
in the previous year.5 A similar tendency was also seen in the US and Austria.7,8 There may
be a close association between COVID-19 and out-of-hospital cardiac mortality in Italy.12 Thus,
there is a possibility that many patients with ACS could not reach the hospital, resulting in an
increase of sudden deaths. With regard to in-hospital mortality of the STEMI cases, the fatality
rate was 13.7% during the pandemic in Italy, while that in the equivalent period in 2019 was
4.1% (P < 0.001).6 On the contrast, the medical system in Japan was functioning well even during
the pandemic, despite the fact that there are a limited number of critical care beds per 100,000
people in Japan, compared to Western countries.13 It is noteworthy that the door-to-balloon-timein STEM and in-hospital mortality were similar between the pandemic and control periods inour study. However, we had no data on out-of-hospital cardiac mortality around catchment-areas.
Under the state of emergency declared on April 16, the Japanese government requested
that people to refrain from going outside unless there was an urgent needed. As time passed,
suppression of consultations, which might be associated with the loss of regular medications,raises a social problem. Poor adherence to medications may exacerbate lifestyle diseases such as
hypertension, dyslipidemia and diabetes and may induce thrombotic events.14 In addition, chronicemotional stress induces cardiovascular events.15 During an emergency period, low physicalactivity raises a social problem. Such influences may greatly affect the onset of cardiovasculardiseases over a long period. From this point of view, there are possible increased risks ofcardiovascular disease. Therefore, data on the incidence of cardiovascular events, particularly
ACS, during the chronic phases after the COVID-19 pandemic should be collected. In addition,
it is unclear whether patients with ACS during the COVID-19 pandemic would have similar
prognoses to those in the control period.
The study has some limitations. First, the number of participating hospitals was 11 and all
hospitals were located in the Tokai region. Hence, the results could not be generalized to entire
Japan and it is unknown if it represents a representative result of Japan. Second, as mentioned
above, pre-hospital death due to ACS was not evaluated in the study. Therefore, it was possiblethat onset of ACS was underestimated. Third, we did not evaluate important data such as theonset-to-balloon time, which may affect patients’ prognosis. The parameters might affect clinicaloutcomes in enrolled patients.
In conclusion, compared to the equivalent period in 2019, the rate of admission for ACS
slightly decreased during the COVID-19 pandemic (April and May 2020) in the Tokai Region ofJapan. The in-hospital mortality rate and strategies for ACS did not significantly differ between
the study and control periods. Finally, we must do our best to prevent the degeneration ofmedical care in future outbreaks.

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ACS and COVID-19 pandemic in JapanACKNOWLEDGEMENT
We would like to thank all the participating hospitals for their efforts. We thank Hiroshi
Takahashi, BSc for excellent assistance with the manuscript. This work was supported by thegrants-in-aid of the 24th General Assembly of the Japanese Association of Medical Sciences.

CONFLICT OF INTEREST
There is no conflict of interest regarding the manuscript.

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