Literature DB >> 34565777

Impact of the COVID-19 Pandemic on ST-elevation Myocardial Infarction from a Single-center Experience in Tokyo.

Yukihiro Watanabe1,2, Hideki Miyachi1, Kosuke Mozawa1, Kenta Yamada1, Eiichiro Oka1, Reiko Shiomura1, Yoichiro Sugizaki1, Junya Matsuda1, Jun Nakata1, Shuhei Tara2, Yukichi Tokita2, Yu-Ki Iwasaki2, Takeshi Yamamoto1, Hitoshi Takano2, Wataru Shimizu1,2.   

Abstract

Objective The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global healthcare systems. Some studies have reported the negative impact of COVID-19 on ST-elevation myocardial infarction (STEMI) patients; however, the impact in Japan remains unclear. This study investigated the impact of the COVID-19 pandemic on STEMI patients admitted to an academic tertiary-care center in Tokyo, Japan. Methods In this retrospective, observational, cohort study, we included 398 consecutive patients who were admitted to our institute from January 1, 2018, to March 10, 2021, and compared the incidence of hospitalization, clinical characteristics, time course, management, and outcomes before and after March 11, 2020, the date when the World Health Organization declared COVID-19 a pandemic. Results There was a 10.7% reduction in hospitalization of STEMI patients during the COVID-19 pandemic compared with that in the previous year (117 vs. 131 cases). During the COVID-19 pandemic, the incidence of late presentation was significantly higher (26.5% vs. 12.1%, p<0.001), and the onset-to-door [241 (IQR: 70-926) vs. 128 (IQR: 66-493) minutes, p=0.028] and door-to-balloon [72 (IQR: 61-128) vs. 60 (IQR: 43-90) min, p<0.001] times were significantly longer than in the previous year. Furthermore, the in-hospital mortality was higher, but the difference was not significant (9.4% vs. 5.0%, p=0.098). Conclusion The COVID-19 pandemic significantly impacted STEMI patients in Tokyo and resulted in a slight decrease in hospitalization, a significant increase in late presentation and treatment delays, and a slight but nonsignificant increase in mortality. In the COVID-19 era, the acute management system for STEMI in Japan must be reviewed.

Entities:  

Keywords:  COVID-19; ST-elevation myocardial infarction; acute coronary syndrome; acute myocardial infarction; coronavirus disease; percutaneous coronary intervention

Mesh:

Year:  2021        PMID: 34565777      PMCID: PMC8710378          DOI: 10.2169/internalmedicine.8220-21

Source DB:  PubMed          Journal:  Intern Med        ISSN: 0918-2918            Impact factor:   1.271


Introduction

Coronavirus disease (COVID-19) has significantly impacted healthcare worldwide, and the World Health Organization (WHO) declared it a pandemic on March 11, 2020 (1). COVID-19 is also prevalent across Japan. In response to the first wave of the COVID-19 pandemic, the Japanese government declared the first state of emergency in the Tokyo metropolitan area on April 7, 2020, which ended on May 14, 2020, as the situation improved (2). However, a second state of emergency was declared on January 7, 2021, to curb the second and third waves of COVID-19, as the incidence of COVID-19 drastically increased again (3). The government called for social distancing and urged people to stay home and refrain from non-essential, non-urgent outings to prevent virus spread. As a result, patients hesitated to visit medical institutions due to fears of contracting COVID-19. During this pandemic, a decrease in the number of hospitalizations, treatment delays, and worsened cardiac outcomes in cases of ST-elevation myocardial infarction (STEMI) have been observed (4-8). In Japan, few studies have reported the impact of the COVID-19 pandemic and state of emergency on STEMI patients. A previous study from Tokyo revealed that the time course of STEMI management and mortality was comparable before and after the pandemic (9). Another study from Osaka reported similar mortality rates before and after the pandemic, despite an increased incidence of mechanical complications of STEMI (10). However, these studies may have underestimated the impact of the pandemic, as data were limited to the early pandemic period, thereby excluding data from the third and largest wave in Japan; thus, the impact of the COVID-19 pandemic on STEMI patients in Japan remains unclear. We examined the long-term impact of the COVID-19 pandemic on STEMI patients in Tokyo. We retrospectively compared the incidence, time course, and outcomes of patients with STEMI before and during the COVID-19 pandemic.

Materials and Methods

Study design, population, and data collection

This study was a retrospective, observational cohort study that included consecutive STEMI patients admitted to the Cardiovascular Intensive Care Unit (CICU) at Nippon Medical School Hospital between January 1, 2018, and March 10, 2021. We categorized the study population into two groups according to the COVID-19 pandemic time course: the pre-COVID-19 period (from January 1, 2018, to March 10, 2020), and the COVID-19 period (from March 11, 2020, when the WHO declared a pandemic, to March 10, 2021). We compared the clinical characteristics, time course, management, and outcomes of STEMI patients between the groups. All patients were followed up until hospital discharge or death. We analyzed the number of hospitalizations for STEMI during the COVID-19 period (from March 11, 2020, to March 10, 2021) and the equivalent period each year from March 11, 2016, to March 10, 2020. The following data were collected from medical records: demographics, medical history, clinical presentation including vital signs, Killip classification, out-of-hospital cardiac arrest, peak creatine kinase level, left ventricular ejection fraction (LVEF), culprit vessel, time course from the onset of symptoms to coronary revascularization, management during hospitalization, length of stay, and outcomes (mechanical complication rate and in-hospital mortality). STEMI was defined based on the Japanese Circulation Society Guideline (11). The time course terms were defined as follows: onset-to-first medical contact (FMC), FMC-to-door, onset-to-door, and door-to-balloon times were defined as the time from symptom onset to FMC, from FMC to hospital arrival, from symptom onset to hospital arrival, and from hospital arrival to the first passage of an intracoronary device, respectively. Late presentation was defined as an onset-to-door time >24 hours; the LVEF was assessed using echocardiography on admission. Furthermore, to clarify the changes in time course to treatment during the COVID-19 pandemic period, we compared the time courses of two groups: the early pandemic period (from March 11 to September 10, 2020) group and the late pandemic period (from September 11, 2020, to March 10, 2021) group. This study was approved by the Institutional Review Board of Nippon Medical School (Reference no. B-2020-338) and conducted as per the revised Declaration of Helsinki. The first and second authors take complete responsibility for the data integrity and accuracy of the data analysis.

Statistical analyses

Categorical variables were presented as numbers and percentages and compared using the chi-square or Fisher's exact test. Continuous variables were presented as medians with interquartile ranges (IQRs) and tested using Student's t-test or the Mann-Whitney U test. The 30-day mortality rate was estimated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. A two-sided p<0.05 was considered significant. Statistical analyses were conducted using the SPSS software program, version 26 (IBM, Armonk, USA).

Results

Incidence of hospitalization

From March 11, 2016, to March 10, 2021, the number of hospitalizations for STEMI each year were 96, 123, 123, 131, and 117, respectively (Fig. 1). There was a 10.7% reduction in hospitalization during the COVID-19 period (from March 11, 2020, to March 10, 2021) compared to the previous year (from March 11, 2019, to March 10, 2020).
Figure 1.

A comparison of the number of admissions for STEMI during the COVID-19 period (from March 11, 2020, to March 10, 2021) and the equivalent period each year from March 11, 2016, to March 10, 2020. There was a 10.7% reduction in STEMI patients during the COVID-19 period compared to the previous year (from March 11, 2019, to March 10, 2020). COVID-19: coronavirus disease 2019, STEMI: ST-elevation myocardial infarction

A comparison of the number of admissions for STEMI during the COVID-19 period (from March 11, 2020, to March 10, 2021) and the equivalent period each year from March 11, 2016, to March 10, 2020. There was a 10.7% reduction in STEMI patients during the COVID-19 period compared to the previous year (from March 11, 2019, to March 10, 2020). COVID-19: coronavirus disease 2019, STEMI: ST-elevation myocardial infarction

Clinical characteristics

From January 1, 2018, to March 10, 2021, 398 consecutive STEMI patients were included: 281 before and 117 during the COVID-19 period. Table 1 shows the clinical characteristics, time course, management, and outcomes of patients in both groups. Although patients in the COVID-19 period had a higher prevalence of hypertension than those in the earlier period (73.6% vs. 84.5%, p=0.019), the incidence of other conditions was similar. There were no significant differences in clinical presentation, including Killip class distribution, between the groups.
Table 1.

Patient’s Clinical Characteristics, Time Course, Management, and Outcomes.

Pre-COVID-19 period (n=281)COVID-19 period (n=117)p value
Age (years)70 [59-79]69 [59-79]0.369
Male sex212 (75.4)82 (70.1)0.268
Medical history
Hypertension203 (73.6)98 (84.5)0.019
Diabetes mellitus104 (37.5)42 (36.2)0.802
Dyslipidemia175 (63.4)79 (68.7)0.318
Hyperuricemia51 (18.5)24 (20.9)0.584
Smoking167 (61.7)78 (67.2)0.305
Previous myocardial infarction17 (6.7)10 (8.6)0.502
Previous PCI22 (8.6)8 (6.9)0.584
Previous CABG2 (0.8)1 (0.9)0.674
Clinical presentation
Killip classification0.506
Killip I189 (67.3)77 (65.8)
Killip II34 (12.1)8 (6.8)
Killip III20 (7.1)10 (8.5)
Killip IV38 (13.5)22 (18.8)
OHCA18 (6.4)5 (4.3)0.406
Peak CK (IU/L)1,787 [737-3,992]1,898 [740-2,949]0.352
LVEF (%)50 [40-60]50 [40-59]0.828
LVEF ≤20%13 (4.7)9 (7.8)0.221
Culprit vessel0.887
Left main coronary artery5 (1.9)2 (1.8)
Left anterior descending artery116 (43.8)64 (58.2)
Left circumflex artery36 (13.6)6 (5.5)
Right coronary artery108 (40.8)38 (34.5)
Time course
Emergency medical services234 (83.3)95 (81.2)0.618
Late presentation34 (12.1)31 (26.5)<0.001
Onset-to-door time (min)128 [66-493]241 [70-926]0.028
Time course (onset-to-door time ≤24 h)
Onset-to-FMC timen=125n=52
Median time (min)84 [31-221]137 [23-313]0.883
FMC-to-door timen=129n=55
Median time (min)30 [26-37]35 [29-41]0.009
Door-to-balloon timen=139n=66
Median time (min)60 [43-90]72 [61-128]<0.001
Door-to-balloon time ≤90 min104 (74.8)42 (63.6)0.098
Therapeutic interventions
Radial approach186 (71.0)81 (71.7)0.892
Emergency PCI246 (87.5)102 (87.2)0.920
Drug-eluting stent233 (82.9)95 (81.2)0.681
Thrombus aspiration175 (70.3)68 (64.2)0.255
CABG14 (5.1)5 (4.3)0.736
Mechanical supports
Mechanical circulatory supports61 (21.9)26 (22.2)0.951
IABP44 (15.9)8 (6.9)0.016
Impella17 (6.1)14 (12.2)0.043
VA-ECMO11 (4.0)10 (8.6)0.060
Ventilator61 (21.7)33 (28.2)0.164
NPPV28 (10.0)15 (12.8)0.403
Medications
Anticoagulants30 (10.7)15 (12.8)0.538
Antiplatelets261 (94.6)112 (95.7)0.632
Aspirin256 (92.8)110 (94.0)0.651
P2Y12 inhibitor229 (83.0)104 (88.9)0.136
β blocker228 (81.1)93 (79.5)0.704
ACEI/ARB218 (77.6)95 (81.2)0.423
CCB37 (13.2)27 (23.1)0.014
Statin261 (92.9)112 (95.7)0.287
Nitrate83 (29.5)26 (22.2)0.136
Nicorandil24 (8.5)17 (14.5)0.073
Diuretic97 (34.5)48 (41.0)0.219
Outcomes
Length of CICU stay (days)4 [2-7]4 [3-7]0.128
Length of hospital stay (days)15 [11-26]13 [10-22]0.054
Mechanical complications5 (1.8)1 (0.9)0.436
Cardiac rupture3 (1.1)1 (0.9)0.666
Papillary muscle dysfunction2 (0.7)0 (0.0)0.500
In-hospital mortality14 (5.0)11 (9.4)0.098
In-hospital mortality (onset-to-door time ≤24 h)n=247n=86
14 (5.7)8 (9.3)0.243

Categorical data presented as n (%). Continuous data presented as median values [interquartile range].

ACEI: angiotensin-converting enzyme inhibitor, ARB: angiotensin II receptor blocker, CABG: coronary artery bypass grafting, CCB: calcium channel blocker, CICU: cardiovascular intensive care unit, CK: creatine kinase, FMC: first medical contact, IABP: intra-aortic balloon pump, LVEF: left ventricular ejection fraction, NPPV: noninvasive positive pressure ventilation, OHCA: out of hospital cardiac arrest, PCI: percutaneous coronary intervention, VA-ECMO: venoarterial extracorporeal membrane oxygenation

Patient’s Clinical Characteristics, Time Course, Management, and Outcomes. Categorical data presented as n (%). Continuous data presented as median values [interquartile range]. ACEI: angiotensin-converting enzyme inhibitor, ARB: angiotensin II receptor blocker, CABG: coronary artery bypass grafting, CCB: calcium channel blocker, CICU: cardiovascular intensive care unit, CK: creatine kinase, FMC: first medical contact, IABP: intra-aortic balloon pump, LVEF: left ventricular ejection fraction, NPPV: noninvasive positive pressure ventilation, OHCA: out of hospital cardiac arrest, PCI: percutaneous coronary intervention, VA-ECMO: venoarterial extracorporeal membrane oxygenation

Time course

The incidence of late presentation was significantly higher during the COVID-19 period than before the COVID-19 period (12.1% vs. 26.5%, p<0.001). The onset-to-door time was significantly longer during the COVID-19 period than before the COVID-19 period [128 (66-493) vs. 241 (70-926) minutes, p=0.028]. When limiting the analysis to cases with an onset-to-door time ≤ 24hours, FMC-to-door [30 (26-37) vs. 35 (29-41) minutes, p=0.009] and door-to-balloon [60 (43-90) vs. 72 (61-128) minutes, p<0.001] times were significantly longer during the COVID-19 period than before the COVID-19 period; furthermore, the proportion of cases with a door-to-balloon time ≤90 minutes was lower during the COVID-19 period than before the COVID-19 period (74.8% vs. 63.6%, p=0.098), although this difference was not significant. Fig. 2 shows a comparison of the median time course between the groups.
Figure 2.

A comparison of the time course in patients whose onset-to-door time was ≤24 hours before and during the COVID-19 pandemic. The FMC-to-door [30 (26-37) vs. 35 (29-41) minutes, p=0.009] and door-to-balloon [60 (43-90) vs. 72 (61-128) minutes, p<0.001] times were significantly longer during the COVID-19 period than the pre-COVID-19 period. The onset-to-FMC time was longer during the COVID-19 period than in the pre-COVID-19 period, although not to a significant degree [84 (31-221) vs. 137 (23-313) minutes, p=0.883]. COVID-19: coronavirus disease 2019, FMC: first medical contact

A comparison of the time course in patients whose onset-to-door time was ≤24 hours before and during the COVID-19 pandemic. The FMC-to-door [30 (26-37) vs. 35 (29-41) minutes, p=0.009] and door-to-balloon [60 (43-90) vs. 72 (61-128) minutes, p<0.001] times were significantly longer during the COVID-19 period than the pre-COVID-19 period. The onset-to-FMC time was longer during the COVID-19 period than in the pre-COVID-19 period, although not to a significant degree [84 (31-221) vs. 137 (23-313) minutes, p=0.883]. COVID-19: coronavirus disease 2019, FMC: first medical contact Table 2 shows the comparison of the time course between the early and late pandemic. The onset-to-door time was significantly longer in the late pandemic period than in the early pandemic period [213 (52-491) vs. 489 (128-1,307) minutes, p=0.031]. When limiting the analysis to cases with an onset-to-door time ≤24 hours, the onset-to-FMC time was significantly longer in the late pandemic period than in the early pandemic period [69 (13-195) vs. 263 (29-743) minutes, p=0.014], with FMC-to-door [33 (29-39) vs. 36 (32-45) minutes, p=0.235] and door-to-balloon [69 (54-100) vs. 85 (63-135) minutes, p=0.179] times being longer as well but not to a significant degree.
Table 2.

Comparison of the Time Course between Early and Late Pandemic.

Early pandemic period (March 11, 2020-September 10, 2020)Late pandemic period (September,11 2020-March,10 2021)p value
Time course n=65n=52
Emergency medical services54 (83.1)41 (78.8)0.561
Late presentation16 (24.6)15 (28.8)0.606
Onset-to-door time (min)213 [52-491]489 [128-1,307]0.031
Time course (onset-to-door time ≤24 h)
Onset-to-FMC timen=32n=20
Median time (min)69 [13-195]263 [29-743]0.014
FMC-to-door timen=34n=21
Median time (min)33 [29-39]36 [32-45]0.235
Door-to-balloon timen=37n=29
Median time (min)69 [54-100]85 [63-135]0.179
Door-to-balloon time ≤90 min25 (67.6)17 (58.6)0.453

Categorical data presented as n (%). Continuous data presented as median values [interquartile range]. FMC: first medical contact

Comparison of the Time Course between Early and Late Pandemic. Categorical data presented as n (%). Continuous data presented as median values [interquartile range]. FMC: first medical contact Clinical Characteristics of Suspected COVID-19 Patients. * This patient underwent emergency CAG under PPE. After confirming negative PCR test, the patient underwent CABG due to triple vessel disease. Door-to-CABG time was shown. CABG: coronary artery bypass grafting, CAG: coronary angiography, COVID-19: coronavirus disease 2019, PCI: percutaneous coronary intervention, PCR: polymerase chain reaction, PPE: personal protective equipment

Management

There were no marked differences in therapeutic interventions or in the overall mechanical circulatory use rate between groups. Since the implementation of Impella (Abiomed, Danvers, USA) at our CICU in January 2018, the proportion of intra-aortic balloon pump usage decreased significantly (15.9% vs. 6.9%, p=0.016), and that of Impella usage increased (6.1% vs. 12.2%, p=0.043). Regarding medications during hospitalization, a higher rate of calcium channel blocker use was noted during the COVID-19 period than before the COVID-19 period (13.2% vs. 23.1%, p=0.014); however, the use of other medications remained similar.

Outcomes

The length of hospital stay was shorter during the COVID-19 period than before the COVID-19 period, although not significantly so [15 (11-26) vs. 13 (10-22) days, p=0.054]. Although the in-hospital mortality and the 30-day cumulative mortality rates were higher during the COVID-19 period than before the COVID-19 period (5.0% vs. 9.4%, p=0.098, chi-square test; 6.6% vs. 13.7%, p=0.074, log-rank test, Fig. 3; respectively), these differences were not significant. When we limited the analysis to cases with an onset-to-door time ≤24 hours, the in-hospital mortality was higher during the COVID-19 period than before the COVID-19 period (5.7% vs. 9.3%, p=0.243), although the difference was not significant.
Figure 3.

Kaplan-Meier curves of the 30-day cumulative mortality. The 30-day cumulative mortality increased more during the COVID-19 period than during the pre-COVID-19 period, although not to a significant degree (6.6% vs. 13.7%, p=0.074 by log-rank test). COVID-19: coronavirus disease 2019

Kaplan-Meier curves of the 30-day cumulative mortality. The 30-day cumulative mortality increased more during the COVID-19 period than during the pre-COVID-19 period, although not to a significant degree (6.6% vs. 13.7%, p=0.074 by log-rank test). COVID-19: coronavirus disease 2019

Management of patients with suspected COVID-19

Regarding the infection control measures implemented during the study period at our institution, patients with a fever, a temperature over 37.5 °C, and either cough, dyspnea, smell disorder, or taste disorder were defined as suspected COVID-19 patients. Suspected COVID-19 patients underwent COVID-19 polymerase chain reaction (PCR) testing in the designated emergency room, and we treated them using personal protective equipment (PPE), including N95 respirators, goggles, gowns, gloves, and surgical caps. When performing emergency catheterization in patients with COVID-19 or suspected COVID-19 patients, healthcare workers were required to wear PPE. We treated patients with a low probability of COVID-19 infection with surgical masks, goggles, and gloves. During the COVID-19 period, six patients suspected of having COVID-19 underwent a COVID-19 PCR test, with negative findings obtained. Two of these six patients underwent emergency coronary angiography (CAG), and healthcare workers wore PPE before the PCR test results were available. One patient underwent percutaneous coronary intervention (PCI), and the other underwent coronary artery bypass grafting. The remaining four patients underwent CAG after confirmation of a negative PCR test to ensure the safety of health workers. Table 3 shows the clinical characteristics of suspected COVID-19 patients in our cohort.
Table 3.

Clinical Characteristics of Suspected COVID-19 Patients.

No.Age (years)Male sexKillip classificationPeak CK (IU/L)Late presentationDoor-to-balloon time (min)Primary PCI under PPEThe reason for suspicion of COVID-19Outcome
155(+)I180(-)475(-)Fever and coughAlive
237(+)III417(+)258(+)Fever and dyspneaAlive
377(+)III1,001(-)940(-)Fever and dyspneaAlive
446(+)III2,041(+)1,561(-)Fever and dyspneaAlive
5*79(+)IV1,915(+)6,060(+)Fever and dyspneaAlive
689(+)IV1,941(+)1,576(-)Fever and dyspneaDeath

* This patient underwent emergency CAG under PPE. After confirming negative PCR test, the patient underwent CABG due to triple vessel disease. Door-to-CABG time was shown. CABG: coronary artery bypass grafting, CAG: coronary angiography, COVID-19: coronavirus disease 2019, PCI: percutaneous coronary intervention, PCR: polymerase chain reaction, PPE: personal protective equipment

Discussion

This retrospective observational cohort study explored the long-term impact of the COVID-19 pandemic on STEMI patients in Tokyo, Japan. The following major findings were observed during the pandemic: 1) a 10.7% reduction was seen in STEMI hospitalization rates; 2) a significantly higher incidence of late presentations and significantly longer onset-to-door, FMC-to-door, and door-to-balloon times were noted; 3) a higher in-hospital mortality was observed among STEMI patients, although this difference was not significant; and 4) the onset-to-door time was significantly longer during the late pandemic period than in the early pandemic period. To our knowledge, this is the first study to reveal the long-term impact of the COVID-19 pandemic, including the third and largest wave, on STEMI patients in Japan. Our findings showed a 10.7% reduction within 1 year after the start of the COVID-19 pandemic. This reduction is consistent with the findings of previous studies, which report 10.1%, 40%, 38%, and 27% reductions in Tokyo (12), Spain (5), the United States (7), and Italy (8), respectively. The mechanism underlying the decline in STEMI hospitalizations is multifactorial, with the major cause being avoidance of medical care due to fear of not being able to maintain social distancing and contracting COVID-19 in medical institutions (4,6-8,13). Other causes include a true reduction in the incidence of STEMI, possibly due to low physical stress under lockdown and stay-home orders (14) and fewer misdiagnoses of STEMI (7). The reduction rate of STEMI in our cohort is considerably smaller than that reported in other countries. In Japan, the pandemic has had a different impact from that seen in other regions, such as Europe and the United States, in that the number of patients affected by COVID-19 is markedly lower. Therefore, there are significant differences between Japan and other countries in governmental measures that have been implemented against the pandemic; for example, in contrast to the lockdowns and stay-home orders seen in other countries, the state of emergency in Japan had no restrictive powers under law. In Taiwan, which succeeded in controlling the virus during the early pandemic, no marked reduction in STEMI hospitalizations was observed (15). These observations suggest an association between the degree of severity of the COVID-19 pandemic and STEMI reduction. In Japan, limited studies have reported the time course and STEMI outcomes during the early COVID-19 pandemic. A single-center retrospective cohort study from Tokyo showed no significant differences in the time course or 30-day mortality in STEMI patients before and after the COVID-19 outbreak (9), while another study from Osaka reported that the in-hospital mortality was comparable, despite an increased incidence of late presentation and mechanical complications of STEMI (10). In contrast, we demonstrated treatment delays and a tendency toward increased STEMI mortality during this pandemic; however, the increment in mortality was not significant. Our findings are similar to those of previous studies from other countries (4,8,16). Treatment delays during the pandemic may have worsened cardiac outcomes, as time delays in primary PCI for STEMI affect mortality (17). The increase in late-presenting STEMI patients is associated with a worse long-term mortality (18). Thus, time delays in STEMI management during the COVID-19 pandemic may have negative impacts on the short- and long-term prognosis. While the previous study did not suggest a significant difference in the onset-to-door time [median (control period vs. COVID-19 period): 205 vs. 266 minutes, p=0.20] (9), our study revealed a significantly longer time during the COVID-19 period (128 vs. 241 minutes, p=0.028). Regarding the prognosis, while the 30-day cumulative mortality rates were comparable in the previous study (8.3% vs. 9.4%, p=0.772, log-rank test), they were found to be higher during the COVID-19 pandemic in the present study (6.6% vs. 13.7%, p=0.074, log-rank test). The difference of results between our study and the previous study seemed to be mainly due to the observation period. Our study included data from the third wave of the COVID-19 pandemic, which has had the worst impact in Tokyo so far. The previous study suggested that the prognosis was comparable because the time course of STEMI management remained unchanged. This finding is consistent with our opinion that time delays in treatment may lead to a poor prognosis. Our findings might be more robust due to the larger sample size and long-term observation period compared with the previous study. Our findings also suggested that the FMC-to-door time was significantly longer after the COVID-19 outbreak than before it. The FMC-to-door time essentially depends on the emergency medical service (EMS). The EMS in Tokyo has developed a system that cooperates with the Tokyo CCU network (19). However, it should also be recognized that the emergency transportation time has increased recently because of the COVID-19 pandemic. The Tokyo CCU network reported that while the number of hospitalizations for acute myocardial infarction (AMI) from October to December 2020 in Tokyo decreased by 10.1% compared to the previous year, the incidence of out-of-hospital cardiac arrest (OHCA) in December 2020 was significantly higher than that in the previous year (12). There were similar reports from Italy (20) and France (21) concerning increases in OHCA during the COVID-19 pandemic. This may suggest that patients' reluctance to seek medical attention during the COVID-19 pandemic was associated with an increase in cardiac arrest before arrival at a hospital. Therefore, since patients with OHCA are not included in the analysis, the prognosis of STEMI patients during the COVID-19 pandemic period may be underestimated. In the COVID-19 era, delays in the timeline of STEMI management are a critical issue. Public health and social measures for COVID-19 may affect healthcare systems. We described increased late presentation as “patient delay” and prolonged FMC-to-door and door-to-balloon times as “healthcare system delay”. The fear of not being able to maintain social distancing and contracting COVID-19 made patients reluctant to visit medical institutions. Therefore, information about the risk of refusing medical attention and symptoms of myocardial infarction should be shared in order to reduce patient delay. In England, a national campaign to encourage citizens experiencing symptoms of AMI to call an ambulance have produced an effect during the COVID-19 pandemic (22). Healthcare system delays are caused by infection control measures, such as recording a detailed contact history, performing regular temperature measurements and chest X-ray, and wearing PPE. Furthermore, of note, several patients in our cohort underwent CAG after a confirmed negative PCR test had been conducted to ensure the safety of medical professionals. Transportation systems have experienced strain during the COVID-19 pandemic. Many hospitals refused to accept STEMI patients because all beds are designated for COVID-19 management, thereby increasing delays in transportation to hospitals. Our study also revealed that the time course of STEMI patients was more markedly delayed during the late pandemic phase, including the third wave of COVID-19, than in the early phase. Of the 73 hospitals participating in the Tokyo CCU network, 11 had stopped accepting patients who were transported via the Tokyo CCU network. Furthermore, while the acceptance rate for ambulances in the Tokyo CCU network was usually about ≥70%, it dropped to <50% in January 2021 (23). Therefore, the transportation system during the third wave of COVID-19 in Tokyo almost completely collapsed in the wake of the pandemic. The best way to achieve both rapid management of STEMI and the enaction of control measures for COVID-19 should be determined. Healthcare professionals should recognize the existence of treatment delays and poor STEMI outcomes during the COVID-19 pandemic, even in Japan, and an acute management system for STEMI must be reconsidered in case further waves of the pandemic should appear.

Study limitations

Several limitations associated with the present study warrant mention. First, this was a retrospective, observational, single-center study conducted in Tokyo. Our findings may not be applicable to other regions or countries. Second, our analysis did not include non-ST-elevation myocardial infarction (NSTEMI); NSTEMI patients are more strongly affected by the COVID-19 pandemic than STEMI patients (8,22). Third, during this study period, COVID-19 PCR tests were performed markedly less frequently in Japan than in Europe or the United States because the resources, transportation, and qualified staff for COVID-19 tests remained low (24); therefore, these tests were performed only in suspected patients with a fever, respiratory symptoms, pneumonia, or close contact with confirmed COVID-19 patients. In this regard, we might have underestimated the incidence of COVID-19 in our cohort. Finally, the geographical distribution of the STEMI population might have changed before and after the COVID-19 outbreak as medical facilities in hotspots were overwhelmed with COVID-19 patients, which might have affected the management and outcomes. Further large-scale studies should evaluate the impact of the COVID-19 pandemic on STEMI patients in Japan.

Conclusion

A slight decrease in hospitalization, an increased late presentation, treatment delay, and mortality of STEMI patients were noted during the COVID-19 pandemic. The STEMI management system in Japan must be reconsidered in case further waves of the COVID-19 pandemic appear. The authors state that they have no Conflict of Interest (COI).
  21 in total

Review 1.  JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome.

Authors:  Kazuo Kimura; Takeshi Kimura; Masaharu Ishihara; Yoshihisa Nakagawa; Koichi Nakao; Katsumi Miyauchi; Tomohiro Sakamoto; Kenichi Tsujita; Nobuhisa Hagiwara; Shunichi Miyazaki; Junya Ako; Hirokuni Arai; Hideki Ishii; Hideki Origuchi; Wataru Shimizu; Hirofumi Takemura; Yoshio Tahara; Yoshihiro Morino; Kenji Iino; Tomonori Itoh; Yoshitaka Iwanaga; Keiji Uchida; Hirohisa Endo; Ken Kongoji; Kenji Sakamoto; Hiroki Shiomi; Takao Shimohama; Atsushi Suzuki; Jun Takahashi; Ichiro Takeuchi; Akihito Tanaka; Toshihiro Tamura; Takahiro Nakashima; Teruo Noguchi; Daisuke Fukamachi; Tomohiro Mizuno; Junichi Yamaguchi; Kenji Yodogawa; Masami Kosuge; Shun Kohsaka; Hideaki Yoshino; Satoshi Yasuda; Hiroaki Shimokawa; Atsushi Hirayama; Takashi Akasaka; Kazuo Haze; Hisao Ogawa; Hiroyuki Tsutsui; Tsutomu Yamazaki
Journal:  Circ J       Date:  2019-03-29       Impact factor: 2.993

2.  Covid-19: Japan declares state of emergency as Tokyo cases soar.

Authors:  Mun-Keat Looi
Journal:  BMJ       Date:  2020-04-09

3.  Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction.

Authors:  Elisabeth Mahase
Journal:  BMJ       Date:  2020-03-12

4.  Physical Activity and Anger or Emotional Upset as Triggers of Acute Myocardial Infarction: The INTERHEART Study.

Authors:  Andrew Smyth; Martin O'Donnell; Pablo Lamelas; Koon Teo; Sumathy Rangarajan; Salim Yusuf
Journal:  Circulation       Date:  2016-10-11       Impact factor: 29.690

5.  Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts.

Authors:  Giuseppe De Luca; Harry Suryapranata; Jan Paul Ottervanger; Elliott M Antman
Journal:  Circulation       Date:  2004-03-08       Impact factor: 29.690

6.  Current characteristics and management of ST elevation and non-ST elevation myocardial infarction in the Tokyo metropolitan area: from the Tokyo CCU network registered cohort.

Authors:  Hideki Miyachi; Atsushi Takagi; Katsumi Miyauchi; Masao Yamasaki; Hiroyuki Tanaka; Masatomo Yoshikawa; Mike Saji; Makoto Suzuki; Takeshi Yamamoto; Wataru Shimizu; Ken Nagao; Morimasa Takayama
Journal:  Heart Vessels       Date:  2016-01-12       Impact factor: 2.037

7.  Management and Outcomes of Patients With STEMI During the COVID-19 Pandemic in China.

Authors:  Dingcheng Xiang; Xin Xiang; Wei Zhang; Shaodong Yi; Jinxia Zhang; Xiaolong Gu; Yawei Xu; Kai Huang; Xi Su; Bo Yu; Yan Wang; Weiyi Fang; Yong Huo; Junbo Ge
Journal:  J Am Coll Cardiol       Date:  2020-08-19       Impact factor: 24.094

8.  Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy.

Authors:  Enrico Baldi; Giuseppe M Sechi; Claudio Mare; Fabrizio Canevari; Antonella Brancaglione; Roberto Primi; Catherine Klersy; Alessandra Palo; Enrico Contri; Vincenza Ronchi; Giorgio Beretta; Francesca Reali; Pierpaolo Parogni; Fabio Facchin; Davide Bua; Ugo Rizzi; Daniele Bussi; Simone Ruggeri; Luigi Oltrona Visconti; Simone Savastano
Journal:  N Engl J Med       Date:  2020-04-29       Impact factor: 91.245

9.  Assessment of ST-Segment Elevation Myocardial Infarction Volume Trends During The COVID-19 Pandemic.

Authors:  Amir S Lotfi; Alina Capatina; Aaron D Kugelmass
Journal:  Am J Cardiol       Date:  2020-06-27       Impact factor: 2.778

10.  COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.

Authors:  Marion M Mafham; Enti Spata; Raphael Goldacre; Dominic Gair; Paula Curnow; Mark Bray; Sam Hollings; Chris Roebuck; Chris P Gale; Mamas A Mamas; John E Deanfield; Mark A de Belder; Thomas F Luescher; Tom Denwood; Martin J Landray; Jonathan R Emberson; Rory Collins; Eva J A Morris; Barbara Casadei; Colin Baigent
Journal:  Lancet       Date:  2020-07-14       Impact factor: 79.321

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  3 in total

Review 1.  Cardiovascular considerations during the COVID-19 pandemic: A focused review for practice in Japan.

Authors:  Daiki Tomidokoro; Yukio Hiroi
Journal:  Glob Health Med       Date:  2022-04-30

Review 2.  COVID's Impact on Non-communicable Diseases: What We Do Not Know May Hurt Us.

Authors:  Karl Gordon Patti; Payal Kohli
Journal:  Curr Cardiol Rep       Date:  2022-05-07       Impact factor: 3.955

3.  Impact of the COVID-19 pandemic on the hospitalizations, time course, presenting symptoms, and mid-term outcomes in patients with myocardial infarctions in a Japanese multi-center registry.

Authors:  Riku Arai; Murata Nobuhiro; Keisuke Kojima; Korehito Iida; Daisuke Kitano; Daisuke Fukamachi; Yoji Watanabe; Michiaki Matsumoto; Naoya Matsumoto; Shu Hirata; Kazumiki Nomoto; Yusuke Sasa; Eizo Tachibana; Masaru Arai; Ken Arima; Hironori Haruta; Yasuo Okumura
Journal:  Heart Vessels       Date:  2022-10-17       Impact factor: 1.814

  3 in total

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