key: cord-0935263-5d52w55j
authors: Kobayashi, Satomi; Sakakura, Kenichi; Jinnouchi, Hiroyuki; Taniguchi, Yousuke; Tsukui, Takunori; Watanabe, Yusuke; Yamamoto, Kei; Seguchi, Masaru; Wada, Hiroshi; Fujita, Hideo
title: Comparison of door-to-balloon time and in-hospital outcomes in patients with ST-elevation myocardial infarction between before versus after COVID-19 pandemic
date: 2022-01-10
journal: Cardiovasc Interv Ther
DOI: 10.1007/s12928-022-00836-4
sha: b9a12ed486948d796f2a4d6e2870fb184d548fc9
doc_id: 935263
cord_uid: 5d52w55j

The situation around primary percutaneous coronary intervention (PCI) has dramatically changed since coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 pandemic on clinical outcomes as well as door-to-balloon time (DTBT), which is known as one of the indicators of early reperfusion, has not been fully investigated in patients with ST-elevation acute myocardial infarction (STEMI). The purpose of this study was to compare DTBT and in-hospital outcomes in patients with STEMI between before versus after COVID-19 pandemic. The primary interest was DTBT and the incidence of in-hospital outcomes including in-hospital death. We included 330 patients with STEMI who underwent primary PCI, and divided them into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121). DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group (p < 0.001), whereas the incidence of in-hospital death was comparable between the 2 groups (p = 0.238). In the multivariate logistic regression analysis, chest CT before primary PCI (OR 4.64, 95% CI 2.58–8.34, p < 0.001) was significantly associated with long DTBT, whereas chest CT before primary PCI (OR 0.76, 95% CI 0.29–1.97, p = 0.570) was not associated with in-hospital death after controlling confounding factors. In conclusion, although DTBT was significantly longer after COVID-19 pandemic than before COVID-19 pandemic, in-hospital outcomes were comparable between before versus after COVID-19 pandemic. This study suggests the validity of the screening tests including chest CT for COVID-19 in patients with STEMI who undergo primary PCI.

Primary percutaneous coronary intervention (PCI) has significantly improved the outcomes of ST-elevation acute myocardial infarction (STEMI) [1] . In primary PCI, early reperfusion is critically important, and door-to-balloon time (DTBT) is one of the indicators of early reperfusion [2] . Since DTBT was related to the long-term prognosis in patients with STEMI [3, 4] , clinical guidelines recommended short DTBT for patients with STEMI [1, 5] . However, DTBT is influenced by various factors such as atypical clinical presentation, unstable medical condition, and patient's mis-triage [6, 7] .

On the other hand, the situation around primary PCI has dramatically changed since coronavirus disease 2019 (COVID- 19) pandemic. First, it was reported that the number of primary PCI cases decreased during January-March 2020 in the USA [8] . In addition, even if primary PCI was performed, delayed DTBT has been reported from Singapore and China [9, 10] . Although there were a few reports regarding DTBT in COVID-19 pandemic from Japan [11] , the impact of COVID-19 pandemic on clinical outcomes as well as DTBT has not been fully investigated in patients with STEMI. The purpose of this study was to compare DTBT and in-hospital outcomes in patients with STEMI between before versus after COVID-19 pandemic.

We reviewed all acute myocardial infarction (AMI) patients treated at our institution (Saitama Medical Center, Jichi Medical University) between March 2018 and June 2021. The inclusion criteria were (1) patients with AMI and (2) STEMI. The exclusion criteria were (1) non-STelevation myocardial infarction, (2) delayed admission (> 24 h from the onset of AMI to hospital arrival) (3) patient with undetermined onset time, (4) nosocomial case, (5) patients who visited outpatient clinic or emergency room on foot, and (6) patient without primary PCI.

In Japan, community-acquired COVID-19 cases began to be reported around February 2020, and the total number of patients had exceeded 200 at the end of February 2020. Then, the Japanese government requested to reduce or cancel large-scale events, and to close schools temporarily. The WHO declared a pandemic of COVID-19 on March 11. Based on these circumstances, we divided our study population into pre COVID-19 group (before the outbreak of COVID-19: from March 2018 to February 2020) and post COVID-19 group (after the outbreak of COVID-19: from March 2020 to June 2021). The primary interest was DTBT and the incidence of in-hospital outcomes including in-hospital death. Our institution was the university hospital which accommodate both secondary and tertiary emergency patients in Saitama city (more than 1.3 million residents), Japan [12] , and physicians in other divisions (the division of general medicine, the division of anesthesiology and critical care medicine, and the division of emergency and critical care medicine) have treated many COVID-19 patients including patients required venovenous extracorporeal membrane oxygenation since the beginning of the pandemic [13] . This study was approved by the institutional review board of the Saitama Medical Center, Jichi Medical University (S21-076), and written informed consent was waived because of the retrospective study design. The data collection and storage were performed anonymously, according to the Japan Ministry of Health, Labour and Welfare guidelines.

AMI was defined according to the universal definition [14, 15] . Diagnostic ST elevation was defined as new ST elevation at the J point in at least two contiguous leads of 2 mm (0.2 mV), and the AMI patients with ST elevation were diagnosed as STEMI [16] . The definitions of hypertension, diabetes mellitus, and dyslipidemia are described elsewhere [17, 18] . We used the laboratory data at admission. Since we could not measure some laboratory data such as hemoglobin A1c level or LDL cholesterol levels at off-hours (night or holidays), we substituted the earliest data since admission for the laboratory data at admission [19] . Left ventricular ejection fraction (LVEF) was measured by transthoracic echocardiography during the index hospitalization. LVEF was calculated through either modified Simpson's method, Teichholz method, or eyeball estimation. A Teichholz method was adopted only when a modified Simpson's method was not available. An eyeball estimation was adopted only when both modified Simpson's method and Teichholz method were not available [19] . We also calculated estimated glomerular filtration rate (eGFR) using serum creatinine (Cr), age, weight, and gender according to the following formula: eGFR = 194 × Cr −1.094 × age −0.287 (male), or eGFR = 194 × Cr −1.094 × a ge −0.287 × 0.739 (female) [20] . The initial thrombolysis in myocardial infarction (TIMI) flow grade and final TIMI flow grade were recorded from coronary angiography [21] . We investigated an onset time from our hospital records. In cases when the time of onset was described in ambiguous terms as just getting up, morning, noon, evening, bedtime, or mid-night in clinical records, those expressions were converted to specific times to calculate onset-to-balloon time as follows: Getting up as 6:00 am, morning as 9:00 am, noon as 12:00 pm, evening as 18:00 pm, bedtime as 21:00 pm, mid-night as 0:00 am [22] . We calculated onsetto-balloon time by 2 ways: (1) using all data as mentioned above and (2) using only the exact onset time, which excluded cases without the exact onset time. We defined a DTBT as the time from hospital arrival to the time of balloon dilation or thrombus aspiration [22] .

We performed some screening tests for COVID-19 as follows ( Fig. 1 ). In the beginning (March 2020 to April 2020), only medical interview regarding COVID-19 and chest X-ray were must as screening tests for COVID-19 before moving to catheter rooms. Since May 2020, chest computed tomography (CT) has been added as a must screening test for COVID-19 before moving to catheter rooms, and chest X-ray has downgraded from must test to optional test. Our emergency department had 2 CT rooms dedicated for emergent patients. Since January 2021, nicking endonuclease amplification reaction (NEAR) test has been added as a must screening test for COVID-19 before moving to catheter rooms, because the result of NEAR test was available within 15-20 min. Although we could perform other COVID-19 screening tests such as antigen test during the study period, those tests were not must, but optional before moving to catheter rooms, because the results of those tests were not available in a short time.

Our hospital has two catheter rooms dedicated for the cardiology department, where most of primary PCI were performed during the study period. Our hospital also has one catheter room dedicated for the radiology department, which could be used for primary PCI when two catheter rooms were not available, typically when two catheter rooms were occupied by elective procedures. Patients with STEMI received 162 mg of aspirin at emergency room (before transferring to catheter rooms) and received 300 mg of clopidogrel or 20 mg of prasugrel at catheter laboratories before coronary stenting (typically after coronary angiography). After the outbreak of COVID-19, staffs inside catheter room such as interventional cardiologists, nurses, medical engineers, and radiological technologists wore personal protective equipment including N95 mask in all emergent cases. Primary PCI was performed using standard techniques via radial artery, femoral artery, or rarely brachial artery. First, we advanced a conventional guidewire across the lesion, and used a small balloon or thrombus aspiration catheter (balloon time). Activated coagulation time (ACT) was maintained > 250 s during PCI.

Data are presented as a percentage for categorical variables, a mean ± standard deviation (SD) for normally distributed continuous variables, and median (quartile 1-quartile 3) for nonparametric variables. Categorical variables were presented as numbers (percentage) and were compared using Chi-square test. For continuous variables, the Shapiro-Wilk test was performed to determine whether the continuous variables were normally distributed or not. Normally distributed continuous variables were compared using a student's t test. Otherwise, continuous variables were compared using a Mann-Whitney U test. We performed a multivariate logistic regression analysis to find factors associated with long doorto-balloon time (DTBT), which was defined as > 90 min. We created two models in this analysis. In both models, we entered age [2] , chronic renal failure on hemodialysis [2] , Killip class 4 [2] , left main-left anterior descending artery as the culprit lesion [22] , triple vessel disease [6] , and the use of mechanical support [16] as independent variables. In model 1, we also adopted chest CT before primary PCI as an independent variable, because chest CT before primary PCI was a must screening test in most patients in the post COVID-19 group. In model 2, we adopted post COVID-19 instead of chest CT before primary PCI as an independent variable to investigate whether the pandemic of COVID-19 itself was an independent factor of long DTBT or not. We also performed another multivariate logistic regression Screening tests for COVID-19 before moving to catheter rooms. COVID-19 coronavirus disease 2019, CT computed tomography, NEAR nicking endonuclease amplification reaction analysis to find factors associated with in-hospital death. In this analysis, we entered age [23, 24] , Killip class 4 [24] , final TIMI flow ≤ 2 [25, 26] , and chest CT before PCI as independent variables. Odds ratios and the 95% confidence intervals (CI) were calculated. p value < 0.05 was considered statistically significant. All analyses were performed using statistical software, SPSS 25/Windows (SPSS, Chicago, Illinois).

From March 2018 to June 2021, a total of 963 AMI patients were admitted to our medical center. After excluding 633 patients who were compatible with the exclusion criteria, the final study population consisted of 330 STEMI patients, which were divided into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121) (Fig. 2 ). There were no STEMI patients who were diagnosed as COVID-19 during the study period.

The comparison of patient's characteristics between the 2 groups is shown in Table 1 . All variables were comparable between the 2 groups. Table 2 shows the comparison of lesion and procedural findings between the 2 groups. DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group. Rapid inspection of COVID-19 before PCI was only performed in the post COVID-19 group. There were no cases that underwent both antigen test and NEAR test. Chest CT before primary PCI was more frequently performed in the post COVID-19 group than in the pre COVID-19 group. Table 3 shows the comparison of clinical outcomes between the 2 groups. The incidence of in-hospital death was not significantly different between the 2 groups. Of 330 all study patients, 256 patients (77.6%) achieved DTBT within 90 min. Of 209 pre COVID-19 patients, 171 patients (81.8%) achieved DTBT within 90 min, whereas, of 121 post COVID-19 patients, 85 patients (70.2%) achieved DTBT within 90 min. When we divided the study population into a short DTBT (< 60 min) group (n = 123), an intermediate DTBT (60-< 120 min) group (n = 168), and a long DTBT (≥ 120 min) group (n = 39), the incidence of in-hospital death was least (4.1%) in the short DTBT group, followed by the intermediate group (13.1%), and highest (15.4%) in the long DTBT group (p = 0.020).

The multivariate logistic regression analysis regarding long DTBT was performed in The multivariate logistic regression analysis regarding inhospital death was performed in Table 5 . Killip class 4 (OR 75.01, 95% CI 21.38-263.2, p < 0.001) was significantly associated with in-hospital death after controlling multiple confounding factors, whereas chest CT before PCI (OR 0.76, 95% CI 0.29-1.97, p = 0.570) was not associated with inhospital death after controlling multiple confounding factors.

We included 330 STEMI patients who underwent primary PCI and divided those into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121). DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group. However, in-hospital outcomes were not significantly different between the 2 groups. In multivariate analysis, we focused on chest CT before primary PCI, which has been a must screening test in our hospital since May 2020. Chest CT before primary PCI was significantly associated with long DTBT (OR 4.64, 95% CI 2.58-8.34, p < 0.001), whereas chest CT before PCI was not associated with in-hospital death (OR 0.76, 95% CI 0.29-1.97, p = 0.570) after controlling multiple confounding factors.

We should discuss the reason why DTBT was longer in the post COVID-19 group than in the pre COVID-19 group. Although the antigen test might require additional time, we did not consider that the antigen test was the main cause of delayed DTBT, because we did not wait for the results of antigen test before moving to the catheter rooms. Furthermore, although we had to wait for 15-20 min before moving to catheter rooms when we ordered a NEAR test in the emergency department, we could perform other works such as echocardiography in waiting time. Our results showed that chest CT before primary PCI would be the most significant cause for delayed DTBT. Chest CT required additional 10-15 min including moving time, and we could not perform other works when a patient underwent chest CT. Therefore, those additional 10-15 min should directly affect DTBT. The reasons why we decided to perform chest CT for all emergent PCI cases were (1) the rapid screening test was not available in the beginning of COVID-19 pandemic, (2) the sensitivity and specificity of screening tests have not been calculated from a large sample size, (3) chest CT has the greater sensitivity for pneumonia as compared to chest X-ray, (4) plain chest CT was useful to detect pericardial effusion and to rule out other diseases such as aortic dissection, and (5) our emergency department had 2 CT rooms dedicated for emergent patients.

Although there was a significant difference in DTBT, inhospital death and other in-hospital outcomes were not significantly different between the pre COVID-19 group and the post COVID-19 group. These results were inconsistent with earlier literatures that DTBT was associated with clinical outcomes [3, 4] . A possible explanation is the small sample size in the present study, which poses a risk of beta-error. In fact, Nallamothu, et al. included 150,116 procedures to show the association between short DTBT and lower mortality [3] . Another explanation is that onset-to-balloon time was not significantly different between the 2 groups. Shiomi et al. reported that not DTBT, but onset-to-balloon time was related to the long-term prognosis of patients with STEMI [27] . Although the difference in DTBT was statistically significant in the present study, such difference might not be so large to bear the difference in clinical outcomes.

Clinical implications of the present study should be noted. Screening tests for COVID-19 would be important to prevent secondary infection to medical staffs, followed by the hospital cluster infections. Although DTBT was extended when we performed several tests for COVID-19, clinical outcomes of patients with STEMI remained unchanged. Our results may support that our screening strategy for COVID-19 was acceptable in terms of preventing excess mortality of patients with STEMI. In addition, plain chest CT may be useful to detect aortic dissection as well as COVID-19

Data were expressed as mean ± SD, median (Q1-Q3) or numbers (percentages). A Student's t test was used for normally distributed continuous variables and Mann-Whitney U test was used for abnormally distributed continuous variables. A Chi-square test was used for categorical variables COVID-19 coronavirus disease 2019, PCI percutaneous coronary intervention, CABG coronary artery-bypass grafting, eGFR estimated glomerular filtration rate, ACE inhibitors angiotensin-converting enzyme inhibitors, ARBs angiotensin receptor blockers pneumonia. In clinical practice, STEMI can be a primary presentation of acute aortic dissection, and those patients may undergo emergent coronary angiography without awareness of aortic dissection [28, 29] . The Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) reported the results of national survey of PCI during the COVID-19 pandemic in Japan, and showed that approximately 10% of PCI-capable facilities performed chest CT as screening for COVID-19 in STEMI [30] . If chest CT is easily accessible for patients with STEMI in each hospital, chest CT before moving to catheter rooms may be an option as screening test for COVID-19 pneumonia without sacrificing patient's cardiovascular outcomes. However, we should remember that chest CT cannot detect COVID-19 without organic damage in the lung field.

As the current study was a single-center, retrospective study, there was a potential selection bias. Our study results would not directly translate to other facilities in different settings. Since the sample size was small, the results of statistical comparisons poses a possibility of beta (type II) error. Therefore, our study might be under-powered to Data were expressed as mean ± SD or numbers (percentages). Mann-Whitney U test was used for abnormally distributed continuous variables.

A Chi-square test was used for categorical variables. In cases when the time of onset was described in ambiguous terms as just getting up, morning, noon, evening, bedtime, or mid-night in clinical records, those expressions were converted to specific times to calculate onset-to-balloon time as follows: Getting up as 6:00 am, morning as 9:00 am, noon as 12:00 pm, evening as 18:00 pm, bedtime as 21:00 pm, mid-night as 0:00 am. We calculated onset-to-balloon time both using all data as mentioned (*) and using only the exact onset time, which excluded cases without the exact onset time COVID-19 coronavirus disease 2019, TIMI thrombolysis in myocardial infarction, CTO chronic total occlusion, PCI percutaneous coronary intervention, NEAR nicking endonuclease amplification reaction, CT computed tomography, IABP intra-aortic balloon pumping, V-A ECMO venoarterial extracorporeal membrane oxygenation, POBA plain old balloon angioplasty 

Door-to-balloon time was significantly longer in the post COVID-19 group than in the pre COVID-19 group. However, in-hospital outcomes including in-hospital death were comparable between before versus after COVID-19 pandemic. This study suggests the validity of the screening tests including chest CT for COVID-19 in patients with STEMI who undergo primary PCI. 

ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)

Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction

Relation between door-to-balloon times and mortality after primary percutaneous coronary intervention over time: a retrospective study

Coronary intervention door-to-balloon time and outcomes in ST-elevation myocardial infarction: a meta-analysis

ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

Causes of delay in door-to-balloon time in south-east Asian patients undergoing primary percutaneous coronary intervention

Door-to-balloon time and factors associated with delayed door-to-balloon time in ST-segment elevation myocardial infarction at Thailand's largest tertiary referral centre

STEMI during the COVID-19 pandemic-an evaluation of incidence

Impact of the COVID-19 pandemic on door-to-balloon time for primary percutaneous coronary intervention-results from the Singapore western STEMI network

The number of patients with acute myocardial infarction decreased and door-to-balloon time delayed in COVID-19

Impact of the COVID-19 pandemic on ST-elevation myocardial infarction from a single-center experience in Tokyo

Comparison of in-hospital death following ST-elevation myocardial infarction between secondary emergency and tertiary emergency

Comprehensive infection control measures prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection: a single-center prospective cohort study and seroprevalence survey

Fourth universal definition of myocardial infarction

Contemporary use and trends in percutaneous coronary intervention in Japan: an outline of the J-PCI Registry

Determinants of short and long door-to-balloon time in current primary percutaneous coronary interventions

Comparison of the cost in percutaneous coronary intervention between ST-segment elevation myocardial infarction vs. non-ST-segment elevation myocardial infarction. Cardiovasc Interv Ther

Factors associated with aorto-ostial stent coverage during intravascular ultrasound-guided percutaneous coronary intervention to severely narrowed non-ostial right coronary artery lesions

Association of Asymptomatic Low Ankle-Brachial Index with Long-Term Clinical Outcomes in Patients after Acute Myocardial Infarction

Revised equations for estimated GFR from serum creatinine in Japan

Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase

Association between the door-to-balloon time and mid-term clinical outcomes in patients with ST-segment elevation myocardial infarction

Noutsias M. In-hospital mortality after acute STEMI in patients undergoing primary PCI

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

Impact of postprocedural TIMI flow on long-term clinical outcomes in patients with acute myocardial infarction

Predictors of suboptimal coronary blood flow after primary angioplasty and its implications on short-term outcomes in patients with acute anterior STEMI

Association of onset to balloon and door to balloon time with long term clinical outcome in patients with ST elevation acute myocardial infarction having primary percutaneous coronary intervention: observational study

STEMI could be the primary presentation of acute aortic dissection

The frequency of initial misdiagnosis of acute aortic dissection in the emergency department and its impact on outcome

Implementation of percutaneous coronary intervention during the COVID-19 pandemic in Japan-Nationwide Survey Report of the Japanese Association of Cardiovascular Intervention and Therapeutics for Cardiovascular Disease

The authors acknowledge all staff in the catheter laboratory, cardiology units, and emergency and critical care units in Saitama Medical Center, Jichi Medical University for their technical support in this study.

Conflict of interest Dr. Sakakura has received speaking honoraria from Abbott Vascular, AstraZeneca, Astellas, AMGEN, Boehringer Ingelheim, Boston Scientific, Daiichi-sankyo, Japan Lifeline, Kaneka, Kowa, Medtronic Cardiovascular, NIPRO, OrbusNeich, Otsuka, Sanofi, Shimadzu, Takeda, and Terumo. Dr. Jinnouchi has received speaking honoraria from Abbott Vascular. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc.