Abstract
Background: Even though hospital admissions for acute myocardial infarction (AMI) decreased globally during the COVID-19 pandemic in early 2020, limited information is available on subsequent demographic trends in the number of cases and management of AMI through the first 12 months of the COVID-19 pandemic.
Methods and Results: We assessed demographic trends, patient characteristics, and AMI outcomes (n=730) during the first 12 months of the COVID-19 pandemic and compared them with corresponding months during the control period (February 2016–January 2020; n=2,742) using data from the Mie ACS Registry. Although a 25.8% reduction in hospitalizations for AMI was observed in the 3 months following the declaration of a state of emergency (47.7 vs. 64.3/month; P=0.002), the total number of AMI patients was similar between the 12-month COVID-19 and control periods (60.8 vs. 57.2/month; P=0.58). The number of patients requiring direct ambulance transport was lower in the first half of the COVID-19 than control period (44.4% vs. 51.5; P=0.028). In-hospital mortality was higher in the second half of the COVID-19 than control period (8.9% vs. 5.8%; P=0.032).
Conclusions: Through the first 12 months of the COVID-19 pandemic, the number of AMI cases was similar to that in previous years. The COVID-19 pandemic changed the behavior of AMI patients and both pre- and in-hospital medical management, which significantly affected the severity and prognosis of AMI.
Since late 2019, COVID-19 has spread worldwide.1 The World Health Organization declared COVID-19 a pandemic on March 11, 2020 and lockdowns were implemented in several major cities around the world to control infection.
In Japan, the first case of COVID-19 was confirmed in the middle of January 2020. The first case of COVID-19 in Mie prefecture, the location of the Mie ACS Registry, was confirmed at the end of January 2020. A state of emergency was declared on April 7, 2020 in Tokyo, Osaka, Kanagawa, Saitama, Chiba, Hyogo, and Fukuoka prefectures, and was expanded to the entire nation, including Mie prefecture, on April 16, 2020. This led to behavioral changes in patients and affected access to medical facilities.2,3
The COVID-19 pandemic has increased the complexity of managing acute myocardial infarction (AMI). In several countries, the COVID-19 pandemic was associated with a reduction in the number of AMI patients in early 2020 because of fears surrounding seeing a doctor or visiting a hospital, or difficulties accessing medical facilities.4–8 Significant increases in the rate of out-of-hospital cardiac arrests among AMI patients and in AMI severity and mortality were reported after the outbreak of COVID-19.5,7,9–13
The number of COVID-19 cases increased markedly in late 2020 and the pandemic has continued into 2022 in Japan. Limited information is currently available as to the effects of the COVID-19 pandemic on AMI through the first 12 months of the pandemic or on the pre- and in-hospital management of AMI patients in the COVID-19 era. Therefore, the present study investigated the frequency, patient characteristics, management, and clinical outcomes of AMI in the 12-month period after the start of the COVID-19 pandemic in Mie prefecture in Japan.
Methods
Study Population
This study enrolled 3,472 AMI patients registered with the Mie ACS Registry between February 2016 and January 2021, including 730 AMI patients registered during the COVID-19 period (between February 2020 and January 2021). The Mie ACS Registry is a prospective, ongoing, multicenter registry for acute coronary syndrome (ACS) that was started in 2013 in Mie prefecture, Japan.14–16 We compared patient characteristics, pre- and in-hospital medical management, and clinical outcomes of AMI during the COVID-19 period with a control period (February 2016–January 2020). The first 12-months of the COVID-19 pandemic was divided into halves: February–July 2020 (first half) and August 2020–January 2021 (second half; Supplementary Figure). We compared the frequency of AMI and its characteristics in these 2 periods with those during the control period. We also investigated the frequency of screening tests for COVID-19 at the time of hospital admission and the use of full personal protective equipment (PPE) during percutaneous coronary intervention (PCI). The screening tests for COVID-19 were chest computed tomography (CT) to exclude COVID-19 pneumoniae, an antigen test, or a polymerase chain reaction (PCR) test.
The Mie ACS Registry was approved by the Institutional Review Board of the Mie University Graduate School of Medicine (Reference no. 2881) and the ethics committees of all participating institutions.14–16 The Mie ACS Registry is registered with University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000036020).14–16
Definitions
All ACS patients who were admitted to each of the participating hospitals and diagnosed with ACS were eligible for inclusion in the Mie ACS Registry. The present study included all myocardial infarction (MI) patients, including those with recent MI, with and without PCI. The diagnosis of AMI was based on the Fourth Universal Definition of Myocardial Infarction.17 Emergency PCI was defined as primary PCI performed within 6 h of hospital admission. Direct ambulance transport was defined as direct transport from the field to a PCI-capable institution by emergency medical services. Interfacility transport was defined as indirect transport via the office of a family physician or non-PCI-capable institutions to PCI-capable institutions.
Statistical Analysis
Normally distributed continuous variables are presented as the mean±SD, whereas those that were no normally distributed are presented as the median and interquartile range. Categorical variables are presented as numbers and percentages. The Chi-squared test or Mann-Whitney U test was used to compare categorical variables according to a nominal or ordinal scale. Student’s t-test or the Wilcoxon rank-sum test was used for continuous variables, as appropriate. Linear regression analysis was performed on the cumulative number of AMI hospitalizations in the first 12 months of the COVID-19 pandemic and the control period, and analysis of covariance (ANCOVA) was used to compare the slopes of the 2 regression lines. Statistical analyses were conducted using SPSS Version 26.0 (IBM Corp., Armonk, NY, USA).
Results
Number of AMI Patients During the COVID-19 Period
Figure 1 shows monthly percentage changes in the incidence of AMI during the first 12 months of the COVID-19 pandemic compared with previous years, as well as the number of COVID-19 cases per 100,000 population in Mie prefecture and Japan. In response to the spread of COVID-19 infection, a state of emergency was declared in Japan from April 7 to May 25. The number of AMI patients decreased markedly from April to May 2020 compared with previous years. However, the number of AMI patients increased, despite the spread of COVID-19 infection, during the second half of the COVID period.
The cumulative incidence of AMI throughout the 12-month COVID-19 pandemic and control periods is shown by linear regression trend lines in Figure 2. There were no significant differences in the slopes of the regression lines between the COVID-19 and control periods (60.8 vs. 57.2 patients/month; ratio of slopes: 1.06; P=0.58). In the first half of the COVID-19 period, the slopes of the regression lines did not significantly differ between the COVID-19 and control periods (52.5 vs. 55.8 patients/month; ratio of slopes: 0.94; P=0.23). However, after a state of emergency was declared, there was a 25.8% reduction in the 3 months after the declaration in the number of cases of AMI (Figure 2B), with a significant difference in the slopes of the regression lines between the COVID-19 and control periods (47.7 vs. 64.3 patients/month; ratio of slopes: 0.74; P<0.001). In the second half of the COVID-19 period, despite an increase in the number of confirmed cases of COVID-19, the number of patients with AMI was higher than in the control period (69.2 vs. 58.5 patients/month; ratio of slopes 1.18; P=0.001; Figure 2C).
The number of patients ST-elevation MI (STEMI) was slightly lower in the COVID-19 than control period, with a marked reduction in STEMI patients noted in the first 3 months after the declaration of a state of emergency (31.3 vs. 41.5 patients/month; P=0.001; Figure 3A,B). However, in the second half of the COVID-19 period, even with a higher number of confirmed cases of COVID-19, the number of STEMI patients increased and was higher than in the control period (47.8 vs. 43.0 patients/month; P<0.001; Figure 3C). Conversely, the number of non-STEMI (NSTEMI) patients increased throughout the year and was higher in the COVID-19 than in the control period (18.6 vs. 14.8 patients/month; P<0.01; Figure 3A). Unlike STEMI, the number of NSTEMI patients continued to increase, even after the declaration of a state of emergency (Figure 3B).
Clinical Characteristics and Pre- and In-Hospital Medical Management of AMI Patients During the COVID-19 and Control Periods
The clinical characteristics of AMI patients in the COVID-19 and control periods are summarized in Tables 1 and 2. The mean age of patients was higher during the COVID-19 than control period (71.3 vs. 69.6 years; P=0.002). The frequency of STEMI decreased significantly during the COVID-19 period (69.1% vs. 74.2%; P=0.007), particularly during the first half (68.3% vs. 74.7%; P=0.023). The proportion of AMI patients who were transported directly to hospital by ambulance was significantly lower in the first half of the COVID-19 period than in the control period (44.4% vs. 51.5%; P=0.028), and the onset-to-door time was significantly longer during the COVID-19 than control period (146.5 vs. 131.0 min; P=0.041). Conversely, the door-to-balloon (DTB) time was similar during the 12-month COVID-19 and control periods (82 vs. 78 min, respectively; P=0.121). However, the DTB time was significantly longer during the second half of the COVID-19 period than during the control period (85.5 vs. 77 min, respectively; P=0.032). The out-of-hospital cardiac arrest rate was higher during the COVID-19 than control period (6.4% vs. 4.5%; P=0.034). Furthermore, the prevalence of a more severe Killip class was significantly higher during the COVID-19 period, particularly the second half (P<0.001), than during the control period.
Table 1. Patient Characteristics in the Control and COVID-19 Periods
| |
12-month observation period
(February–January) |
First half
(February–July) |
Second half
(August–January) |
| Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
| No. patients |
2,742 |
730 |
|
1,340 |
315 |
|
1,402 |
415 |
|
| Age (years) |
69.6±12.7 |
71.3±12.9 |
0.002 |
69.6±12.9 |
71.7±13.3 |
0.012 |
69.5±12.5 |
70.9±12.6 |
0.049 |
| Male sex |
2,109 (76.9) |
546 (74.8) |
0.239 |
1,014 (75.7) |
224 (71.1) |
0.097 |
1,095 (78.1) |
322 (77.6) |
0.840 |
| BMI (kg/m2) |
23.2
[21.2–25.5] |
23.5
[21.3–25.9] |
0.219 |
23.2
[21.2–25.6] |
23.4
[21.1–25.7] |
0.992 |
23.2
[21.2–25.4] |
23.6
[21.5–25.9] |
0.120 |
| Cardiovascular risk factors |
| Hypertension |
1,709 (62.3) |
454 (62.2) |
0.966 |
839 (62.6) |
196 (62.2) |
0.897 |
870 (62.1) |
258 (62.2) |
1 |
| Diabetes |
930 (33.9) |
250 (34.2) |
0.895 |
444 (33.1) |
98 (31.1) |
0.505 |
486 (34.7) |
152 (36.6) |
0.482 |
| Dyslipidemia |
1,257 (45.8) |
353 (48.4) |
0.226 |
616 (46.0) |
157 (49.8) |
0.233 |
641 (45.7) |
196 (47.2) |
0.614 |
| Current smoker |
707 (25.8) |
196 (26.8) |
0.569 |
335 (25.0) |
75 (23.8) |
0.717 |
372 (26.5) |
121 (29.2) |
0.315 |
| Hemodialysis |
50 (1.8) |
18 (2.5) |
0.292 |
29 (2.2) |
8 (2.5) |
0.673 |
21 (1.5) |
10 (2.4) |
0.201 |
| Prior MI |
218 (8.0) |
70 (9.6) |
0.152 |
108 (8.1) |
23 (7.3) |
0.728 |
110 (7.8) |
47 (11.3) |
0.029 |
| Prior PCI |
283 (10.3) |
75 (10.3) |
1 |
146 (10.9) |
27 (8.6) |
0.260 |
137 (9.8) |
48 (11.6) |
0.309 |
| Prior CABG |
21 (0.8) |
6 (0.8) |
0.815 |
8 (0.6) |
3 (1.0) |
0.448 |
13 (0.9) |
3 (0.7) |
1 |
Prior cerebral
infarction |
141 (5.1) |
42 (5.8) |
0.514 |
70 (5.2) |
15 (4.8) |
0.887 |
71 (5.1) |
27 (6.5) |
0.266 |
Unless indicated otherwise, data are given as the mean±SD, median [interquartile range], or n (%). The control period was from February 2016 to January 2019 and the COVID-19 period was from February 2020 to January 2021. BMI, body mass index; CABG, coronary artery bypass grafting; MI, myocardial infarction; PCI, percutaneous coronary intervention.
Table 2. Details of Acute Myocardial Infarction Patients During the Control and COVID-19 Periods
| |
12-month observation period
(February–January) |
First half
(February–July) |
Second half
(August–January) |
| Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
| No. patients |
2,742 |
730 |
|
1,340 |
315 |
|
1,402 |
415 |
|
| Diagnosis |
| STEMI |
2,035 (74.2) |
502 (69.1) |
0.007 |
1,001 (74.7) |
215 (68.3) |
0.023 |
1,034 (73.8) |
287 (69.8) |
0.130 |
| Pathway for transport |
Direct
ambulance |
1,456 (53.1) |
360 (49.3) |
0.073 |
690 (51.5) |
140 (44.4) |
0.028 |
766 (54.6) |
220 (53.0) |
0.575 |
Interfacility
transport |
723 (26.4) |
225 (30.8) |
0.017 |
352 (26.3) |
111 (35.2) |
0.002 |
371 (26.5) |
114 (27.5) |
0.705 |
| Walk in |
502 (18.3) |
132 (18.1) |
0.914 |
263 (19.6) |
57 (18.1) |
0.579 |
239 (17.0) |
75 (18.1) |
0.657 |
| In-hospital |
61 (2.2) |
13 (1.8) |
0.564 |
35 (2.6) |
7 (2.2) |
0.843 |
26 (1.9) |
6 (1.4) |
0.676 |
Onset-to-door
time (min) |
131
[67–334.5] |
146.5
[70.3–413.3] |
0.041 |
134
[65–343] |
144
[72–466] |
0.076 |
128
[68–327.5] |
147
[70–390] |
0.250 |
STEMI
setting |
121
[64–287] |
124
[63.8–333] |
0.455 |
122
[61–294.5] |
123
[61–330] |
0.509 |
121
[67–281.3] |
124
[65–338] |
0.698 |
NSTEMI
setting |
180
[84–541] |
249
[90–655.5] |
0.068 |
176
[86.5–514.8] |
293.5
[93.8–671.8] |
0.047 |
181
[82.5–560] |
208
[88–648] |
0.476 |
| DTB time (min) |
78
[59–114] |
82
[60–122] |
0.121 |
78.5
[58–115] |
79
[57–119] |
0.907 |
77
[60–114] |
85.5
[63–123.5] |
0.032 |
STEMI
setting |
73
[56–97] |
76
[56–103] |
0.362 |
73
[55–100.8] |
73
[52.3–102] |
0.541 |
72
[57–93.5] |
77
[59–103.5] |
0.069 |
NSTEMI
setting |
121
[80–193.3] |
119
[75–198] |
0.887 |
116
[73.3–184.5] |
108
[71.5–193.5] |
0.644 |
128.5
[83–195.5] |
128.5
[80.3–197.8] |
0.915 |
Onset-to-door
time <24 h |
2,363 (86.2) |
611 (83.8) |
0.108 |
1,152 (86.0) |
264 (83.8) |
0.328 |
1,211 (86.4) |
347 (83.8) |
0.200 |
| OOHCA |
123 (4.5) |
47 (6.4) |
0.034 |
59 (4.4) |
21 (6.7) |
0.107 |
64 (4.6) |
26 (6.3) |
0.159 |
Emergency
PCI |
2,461 (89.8) |
661 (90.5) |
0.580 |
1,204 (89.9) |
282 (89.5) |
0.837 |
1,257 (89.7) |
379 (91.3) |
0.351 |
| Hemodynamics |
| Killip 1 |
2,113 (77.1) |
520 (71.6) |
0.001 |
1,021 (76.2) |
2,225 (71.4) |
0.256 |
1,092 (77.9) |
295 (71.8) |
0.001 |
| Killip 2 |
251 (9.2) |
73 (10.1) |
|
1,021 (9.2) |
33 (10.5) |
|
128 (9.1) |
40 (9.7) |
|
| Killip 3 |
146 (5.3) |
35 (4.8) |
|
66 (4.9) |
16 (5.1) |
|
80 (5.7) |
19 (4.6) |
|
| Killip 4 |
232 (8.5) |
98 (13.5) |
|
130 (9.7) |
41 (13.0) |
|
102 (7.3) |
57 (13.9) |
|
| STEMI setting |
| Killip 1 |
1,550 (76.2) |
348 (69.3) |
0.001 |
748 (74.7) |
146 (67.9) |
0.175 |
802 (77.6) |
202 (70.4) |
<0.001 |
| Killip 2 |
198 (9.7) |
55 (11.0) |
|
96 (9.6) |
27 (12.6) |
|
102 (9.9) |
28 (9.8) |
|
| Killip 3 |
99 (4.9) |
21 (4.2) |
|
46 (4.6) |
10 (4.7) |
|
53 (5.1) |
11 (3.8) |
|
| Killip 4 |
188 (9.2) |
78 (15.5) |
|
111 (11.1) |
32 (14.9) |
|
77 (7.4) |
46 (16.0) |
|
| NSTEMI setting |
| Killip 1 |
563 (79.6) |
172 (76.8) |
0.541 |
273 (80.5) |
79 (79.0) |
0.604 |
290 (78.8) |
93 (75.0) |
0.617 |
| Killip 2 |
53 (7.5) |
18 (8.0) |
|
27 (8.0) |
6 (6.0) |
|
26 (7.1) |
12 (9.7) |
|
| Killip 3 |
47 (6.6) |
14 (6.2) |
|
20 (5.9) |
6 (6.0) |
|
27 (7.3) |
8 (6.5) |
|
| Killip 4 |
44 (6.2) |
20 (8.9) |
|
19 (5.6) |
9 (9.0) |
|
25 (6.8) |
11 (8.9) |
|
| IABP use |
355 (13.0) |
111 (15.3) |
0.112 |
176 (13.2) |
52 (16.5) |
0.123 |
179 (12.8) |
59 (14.3) |
0.408 |
| VA-ECMO use |
61 (2.2) |
19 (2.6) |
0.578 |
32 (2.4) |
8 (2.5) |
0.839 |
29 (2.1) |
11 (2.7) |
0.449 |
| Ventilation use |
185 (6.8) |
69 (9.5) |
0.016 |
96 (7.2) |
31 (9.8) |
0.126 |
89 (6.4) |
38 (9.2) |
0.048 |
| Angiographic characteristics |
| LAD culprit |
1,208 (44.3) |
347 (48.6) |
0.043 |
593 (44.5) |
144 (46.9) |
0.446 |
615 (44.2) |
203 (49.9) |
0.048 |
| LMT culprit |
75 (2.8) |
22 (3.1) |
0.613 |
44 (3.3) |
9 (2.9) |
0.859 |
31 (2.2) |
13 (3.2) |
0.275 |
| RCA culprit |
986 (36.2) |
234 (32.8) |
0.095 |
481 (36.1) |
102 (33.2) |
0.356 |
505 (36.3) |
132 (32.4) |
0.158 |
| LCX culprit |
429 (15.7) |
103 (14.4) |
0.416 |
198 (14.8) |
49 (16.0) |
0.658 |
231 (16.6) |
54 (13.3) |
0.122 |
| Other culprit |
18 (0.7) |
5 (0.7) |
0.802 |
11 (0.8) |
2 (0.7) |
1.000 |
7 (0.5) |
3 (0.7) |
0.703 |
Multivessel
disease |
841 (30.9) |
222 (31.0) |
0.964 |
405 (30.4) |
96 (31.2) |
0.784 |
436 (31.3) |
126 (30.8) |
0.903 |
| Strategy |
| PCI |
2,608 (95.1) |
694 (95.1) |
0.923 |
1,279 (95.4) |
296 (94.0) |
0.306 |
1,329 (94.8) |
398 (95.9) |
0.440 |
| Aspiration |
1,597 (63.2) |
365 (55.3) |
<0.001 |
794 (64.0) |
157 (55.3) |
0.008 |
803 (62.5) |
208 (55.3) |
0.014 |
Distal
protection |
219 (8.9) |
35 (5.3) |
0.003 |
115 (9.6) |
13 (4.6) |
0.006 |
104 (8.2) |
22 (5.9) |
0.151 |
Final TIMI 3
flow |
2,266 (91.9) |
579 (88.4) |
0.006 |
1,098 (91.4) |
248 (87.9) |
0.086 |
1,168 (92.4) |
331 (88.7) |
0.033 |
| CABG |
69 (2.5) |
16 (2.2) |
0.688 |
32 (2.4) |
14 (4.4) |
0.056 |
37 (2.6) |
2 (0.5) |
0.006 |
| Peak CPK (U/L) |
1,474.0
[595.5–
3,028.0] |
1,288.0
[466.0–
2,955.0] |
0.012 |
1,557.5
[596.8–
3,093.8] |
1,299
[447–
3,222] |
0.069 |
1,432
[593.5–
2,999] |
1,260.5
[476–
2,893.8] |
0.090 |
STEMI
setting |
1,889
[870–
3,576] |
1,850.5
[682.5–
3,610] |
0.276 |
1,938
[869–
3,616] |
2,076.5
[659–
3,760.5] |
0.872 |
1,823
[877–
3,535.8] |
1,717
[676.8–
1,514.3] |
0.116 |
NSTEMI
setting |
633
[268.5–
1,561.3] |
556
[229.5–
1,293.5] |
0.191 |
693
[296–
1,646.5] |
532
[219.5–
1,111] |
0.043 |
547
[251.5–
1,454.5] |
595
[233.8–
1,514.3] |
0.925 |
Unless indicated otherwise, data are given as the median [interquartile range] or n (%). The control period was from February 2016 to January 2019 and the COVID-19 period was from February 2020 to January 2021. CABG, coronary artery bypass grafting; CPK, creatine phosphokinase; DTB, door-to-balloon; IABP, intra-aortic balloon pumping; LAD, left anterior descending coronary artery; LCX, left circumflex artery; LMT, left main trunk; NSTEMI, non-ST-elevation myocardial infarction; OOHCA, out-of-hospital cardiac arrest; PCI, percutaneous coronary intervention; RCA, right coronary artery; STEMI, ST-elevation myocardial infarction; TIMI, Thrombolysis in Myocardial Infarction; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.
As indicated in Table 3, the in-hospital mortality rate of AMI was significantly higher during the COVID-19 than control period (8.8% vs. 6.2%; P=0.016), particularly during the second half (8.9% vs. 5.8%; P=0.032), and among STEMI patients (9.4% vs. 5.9%; P=0.009). The incidence of ventricular septal rupture was higher during the COVID-19 than control period (1.1% vs. 0.3%; P=0.014), whereas overall mechanical complication rates were similar (Table 3).
Table 3. Patient Outcomes During the Control and COVID-19 Periods
| |
12-month observation period
(February–January) |
First half
(February–July) |
Second half
(August–January) |
| Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
Control |
COVID-19 |
P value |
| No. patients |
2,742 |
730 |
|
1,340 |
315 |
|
1,402 |
415 |
|
| In-hospital mortality |
169 (6.2) |
64 (8.8) |
0.016 |
87 (6.5) |
27 (8.6) |
0.215 |
82 (5.8) |
37 (8.9) |
0.032 |
| STEMI setting |
121 (5.9) |
47 (9.4) |
0.009 |
67 (6.7) |
20 (9.3) |
0.189 |
54 (5.2) |
27 (9.4) |
0.012 |
| NSTEMI setting |
48 (6.8) |
17 (7.6) |
0.654 |
20 (5.9) |
7 (7.0) |
0.642 |
28 (7.6) |
10 (8.1) |
0.847 |
| Mechanical complications |
33 (1.2) |
13 (1.8) |
0.206 |
17 (1.3) |
5 (1.6) |
0.592 |
16 (1.1) |
8 (2.0) |
0.220 |
| Free wall rupture |
20 (0.7) |
4 (0.6) |
0.802 |
11 (0.8) |
1 (0.3) |
0.482 |
9 (0.6) |
3 (0.7) |
0.740 |
| Ventricular septal rupture |
9 (0.3) |
8 (1.1) |
0.014 |
5 (0.4) |
3 (1.0) |
0.182 |
4 (0.3) |
5 (1.2) |
0.032 |
| Papillary muscle rupture |
5 (0.2) |
1 (0.1) |
1 |
2 (0.2) |
1 (0.3) |
0.470 |
3 (0.2) |
0 (0) |
1 |
Unless indicated otherwise, data are given as n (%).The control period was from February 2016 to January 2019 and the COVID-19 period was from February 2020 to January 2021. NSTEM, non-ST segment elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
The frequency of screening tests for COVID-19 increased with the spread of the pandemic (Figure 4). Antigen or PCR tests were performed on 11.7% of AMI patients prior to PCI and 2.8% of PCIs were performed under full PPE during the second half of the COVID-19 period, which was a significant increase from the first half. In the present study, all antigen and PCR tests were negative. In addition, AMI patients who underwent screening tests for COVID-19 and/or primary PCI under full PPE had a lower rate of achieving a DTB time of ≤90 min and higher in-hospital mortality (P<0.001; Figure 5).
Discussion
This is the first study to report demographic trends in the number of AMI patients in the first 12 months of the COVID-19 pandemic and the effects of COVID-19 on the pre- and in-hospital management of AMI throughout a whole prefectural medical area.
The significant findings in the present study are that: (1) the number of cases of AMI and the frequency of emergency PCI throughout the COVID-19 period were similar to those during the control period, although the number of AMI patients decreased in the first half of the COVID-19 period, particularly after the declaration of a state of emergency; (2) the proportion of AMI patients who were transported directly to hospital by ambulance was significantly lower in the first half of the COVID-19 period than in the control period; (3) there was a higher proportion of patients with more severe Killip class and higher rates out-of-hospital cardiac arrest and in-hospital mortality during the COVID-19 period; and (4) screening tests for COVID-19 and full PPE management were more often performed during the second half of the COVID-19 period.
In the present study, the number of AMI patients decreased markedly in the first half of the COVID-19 period, particularly after the declaration of a state of emergency, which is consistent with previous findings in Japan and worldwide.4,7,11,18 A study conducted in England reported that the number of AMI cases decreased only in the first 2–3 months after the outbreak of the COVID-19 pandemic and then began to increase.4 The decline started before the lockdown was imposed and increased thereafter.4 In our analysis, the number of STEMI patients started to decrease after the declaration of a state of emergency, continued to decrease even after the state of emergency was lifted, and started to increase approximately 3 months later, which is consistent with the findings reported in England. These results suggest that a decrease in physical activity and mental stress due to social conditions, such as the declaration of a state of emergency, may have temporarily delayed the onset of STEMI for 2–3 months; however, no significant changes were observed in the number of cases throughout the year.5,7 This result is reasonable because the development of STEMI is largely due to the formation of an intravascular plaque over many years and thrombus occlusion from plaque rupture. Even if the onset of STEMI is delayed for several months with rest, it will inevitably occur with resumption of physical activity and social stress.19,20 In addition, AMI patients refrained from visiting hospitals and hesitated to call an ambulance because of the risk of COVID-19 infection and preferentially visited local clinics.11 These factors may have contributed to the increased out-of-hospital cardiac arrest rate, prolonged onset-to-door time, and increase in both the number of patients with severe AMI and the in-hospital mortality rate in the present study, which are consistent with the findings of previous studies.12,21,22
Patients’ behavioral changes also affected the transport pathway in the first half of the COVID-19 period with the spread of infection. During the 12-month observational periods, in-hospital mortality rates for AMI patients increased due to a prolonged onset-to-balloon time resulting from a decrease in direct ambulance transfers. Direct transfers decreased in the first half of the COVID-19 period; however, a reduction was also observed in the frequency of STEMI, which is considered to have a high mortality rate. Therefore, despite the increase in the onset-to-balloon time, the overall mortality rate for AMI was only slightly higher in the COVID-19 than control period. In contrast, there were no significant differences in the rates of STEMI or direct ambulance transport between the second half of the COVID-19 period and the control period, whereas there were significant increases in the chest CTs, PCR tests before PCI, and the use of full PPE, which predominantly accounted for the prolonged DTB time. This may have contributed to the significantly higher in-hospital mortality rate observed during the COVID-19 period. Preventing delays in the DTB time is one of the pressing issues that needs to be addressed during the COVID-19 period.
The number of patients with the left anterior descending artery (LAD) as the culprit artery was higher during the COVID-19 than control period, especially during the second half of the COVID-19 period. Although there is no clear reason for this phenomenon based on the data available in the Mie ACS Registry, similar findings have been reported from a national registry in Japan, in which there were significantly more AMI patients with LAD and left main trunk culprits during the COVID-19 than control period.23 This may contribute to the poor prognosis of AMI patients in later years.23
The recovery of hospital admission rates among AMI patients in England suggests that the British Heart Foundation and British Cardiovascular Society publicity campaign, in which individuals with symptoms of MI were encouraged to visit a hospital, may have allayed fears of infection. Similarly, in April 2020 in Japan, the Cardiovascular Intervention and Therapeutics (CVIT) and Japanese Circulation Society academic societies revealed a strategy for AMI during the COVID-19 pandemic and primary PCI for STEMI was recommended under PPE. Moreover, the CVIT encouraged all individuals with symptoms of AMI to immediately go to a hospital instead of “staying at home”. In Mie prefecture, primary PCI for AMI patients was not restricted during the COVID-19 period, which may be reflected by the similar total number of primary PCIs between the COVID-19 and control periods. Conversely, elective PCI was not performed as frequently after the declaration of the state of emergency in Japan.24 Presumably a certain number of angina patients who did not undergo PCI became unstable and developed NSTEMI, leading to an increase in the number of NSTEMI patients during the COVID-19 period. Japanese national registry data confirmed an increase in the number of NSTEMI patients in 2020 during COVID-19 compared with 2019.23 This increase is not only an increase in the percentage of NSTEMI patients, but also an increase in their absolute number. In the present study, as well as in the Japanese national registry data,23 the number of NSTEMI patients during COVID-19 increased compared with the period of interest. The reason for this is assumed to be that, during the COVID-19 period, patients with unstable or stable angina who were prevented from accessing hospitals due to emergency declarations or other reasons developed NSTEMI due to a worsening of their medical condition.23
In contrast with our data from Japan, Lavie et al reported that, in Israel, the number of AMI patients during the first 12 months of the pandemic was lower than the average of the previous 3 years.25 The variability in the rates of decline in the number of AMI patients across countries during the pandemic is evidence of the multiplicity of underlying factors, like the non-uniform intensity of the pandemic, variations in the stringency of lockdowns, and public health-related factors.
This study has some strengths. Although there have been a few papers reporting on the 12-month follow-up of the number of AMI patients after the COVID-19 pandemic, the analyses used national databases and did not present detailed patient data.25 The data in this study provide detailed patient information over a 12-month period for AMI patients in an entire prefectural medical area.
Study Limitations
In this study we collected data in a relatively rural area, which was a non-epidemic area. Studies on urban areas that include epidemic areas will provide more detailed information on AMI during the COVID-19 pandemic. Further studies are warranted to examine changes in AMI during the COVID-19 pandemic. In addition, the main reason for the decline in the direct transfer rate is unknown and detailed information of indirect transfers is not available from the current registration data.
Conclusions
The number of AMI cases during the COVID-19 pandemic period was similar to that in previous years. The COVID-19 pandemic induced behavioral changes in AMI patients and altered pre- and in-hospital medical management, significantly affecting severity and prognosis of AMI patients.
Acknowledgment
The authors thank Medical English Service (https://www.med-english.com/proofreading) for editing a draft of this manuscript.
Sources of Funding
The Mie ACS Registry was funded by the incorporated non-profit organization Mie Cardiovascular and Renal Disease Network (http://www.medic.mie-u.ac.jp/miecrnet/). This study did not receive any specific funding.
Disclosures
K.D. received departmental research grant support from Otsuka Pharmaceutical Co., Ltd., DAIICHI SANKYO Co., Ltd., Novartis Pharma K.K., AstraZeneca K.K., Kowa Co., Ltd., Bayer Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. in 2021; lecture fees from Otsuka Pharma Inc. and departmental research grant support from Otsuka Pharmaceutical Co., Ltd. in 2020; and lecture fees from Otsuka Pharmaceutical Co., Ltd. in 2019. The remaining authors have no conflicts of interest to disclose.
IRB Information
The Mie ACS Registry was approved by the Institutional Review Board of the Mie University Graduate School of Medicine (Reference no. 2881) and the ethics committees of all participating institutions. It has been registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000036020).
Data Availability
Individual deidentified participant data (including data dictionaries), the Excel data used for analysis, and the study protocol will be shared upon request to the corresponding author. The data will be available for 1 year after publication.
Supplementary Files
Please find supplementary file(s);
http://dx.doi.org/10.1253/circrep.CR-22-0050
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