key: cord-0821111-fukpes4r
authors: Leng, Wen-Xiu; Yang, Jin-Gang; Li, Xiang-Dong; Jiang, Wen-Yang; Gao, Li-Jian; Wu, Yuan; Yang, Yan-Min; Yuan, Jin-Qing; Yang, Wei-Xian; Qiao, Shu-Bin; Yang, Yue-Jin
title: Impact of the shift to a fibrinolysis-first strategy on care and outcomes of patients with ST-segment–elevation myocardial infarction during the COVID-19 pandemic—The experience from the largest cardiovascular-specific centre in China()
date: 2020-12-08
journal: Int J Cardiol
DOI: 10.1016/j.ijcard.2020.11.074
sha: 9f62d931b5b1ea4a65a755f7808ebf8173b72320
doc_id: 821111
cord_uid: fukpes4r

BACKGROUND: The impact of fibrinolysis-first strategy on outcomes of patients with ST-segment-elevation myocardial infarction (STEMI) during the COVID-19 pandemic was unknown. METHODS: Data from STEMI patients presenting to Fuwai Hospital from January 23 to April 30, 2020 were compared with those during the equivalent period in 2019. The primary end-point was net adverse clinical events (NACE; a composite of death, non-fatal myocardial reinfarction, stroke, emergency revascularization, and bleeding over BARC type 3). The secondary outcome was a composite of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. RESULTS: The final analysis included 164 acute STEMI patients from 2020 and 240 from 2019. Eighteen patients (20.2% of those with indications) received fibrinolysis therapy in 2020 with a median door-to-needle time of 60.0 (43.5, 92.0) minutes. Patients in 2020 underwent primary PCI less frequently than their counterparts (14 [14.2%] vs. 144 [86.8%] in 2019, P < 0.001), and had a longer median door-to-balloon time (175 [121,213] minutes vs. 115 [83, 160] minutes in 2019, P = 0.009). Patients were more likely to undergo elective PCI (86 [52.4%] vs. 28 [11.6%] in 2019, P < 0.001). The in-hospital NACE was similar between 2020 and 2019 (14 [8.5%] vs. 25 [10.4%], P = 0.530), while more patients developed a secondary outcome in 2020 (20 [12.2%] vs. 12 [5.0%] in 2019, P = 0.009). CONCLUSIONS: The fibrinolysis-first strategy during the COVID-19 pandemic was associated with a lower rate of timely coronary reperfusion and increased rates of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. However, the in-hospital NACE remained similar to that in 2019.

care for COVID-19 patients and minimize potential contamination of medical facilities and exposure of healthcare workers, a balance must be struck in identifying appropriate patients for invasive approaches to acute myocardial infarction (AMI), regardless of their status. Although the consensus statement from the Society for Cardiovascular Angiography and Interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) continues to recommend primary percutaneous coronary intervention (PCI) as the standard of care for ST-segment-elevation myocardial infarction (STEMI) patients at PCI-capable hospitals during the COVID-19 pandemic(1), reports suggest a decline in primary PCI (PpPCI) volumes worldwide (2) . The tertiary cardiac centres were obliged to formulate emergency plans in preparation for the impending surge in demand on the hospital, but nofew data on the outcomes of these proposed strategies for the management of STEMI during the COVID-19 crisis have been reported yet. in preparation for critical cardiovascular situations in regions of different risk (3) . As the capital of China, the Beijing district took the strictest measures to contain the spread of the epidemic. As no real-world data has been investigated to assess the effect of the current strategies on the management of AMI during the COVID-19 pandemic. Therefore, we aimed to investigate the effect of the fibrinolysis-first pattern of treatment under the circumstances of the pandemic in contemporary era of pPCI, we conducted this historical controlled study by reviewing the complete and detailed medical record resources of this large center.

We screened all patients who visited the emergency department of Fuwai Hospital from January 23, 2020, when the Chinese government took measures to curb people's trips outside (a nationwide first-level public health emergency response activated), to April 30, 2020, when the public health emergency response was downgraded to the second level in Beijing. Patients who visited the emergency department of Fuwai Hosptial during the equivalent period of time in 2019 (from January 23 to April 30, 2019) were also screened as the control group. Patients J o u r n a l P r e -p r o o f Journal Pre-proof who presented to the emergency department with a primary diagnosis of acute STEMI according to the fourth universal definition of MI were included in this analysis (4) . Type 2 MI, MI complicated with aortic dissection, myocardial injury without evidence of ischaemia, and those transferred after fibrinolysis or PCI at other hospitals were excluded from the final analysis (4). Information on baseline demographic and clinical characteristics, processes of care, discharge medications, and in-hospital outcomes throughout the stay in the emergency department and the index hospitalization of each patient was collected.

For patients of 2020, screening for COVID-19 initiated immediately upon arrival at the emergency room including close contact tracing, body temperature monitoring, and chest X-ray. According to CSC expert consensus on principles of clinical management of patients with severe emergent cardiovascular diseases during the COVID-19 epidemic(3), all COVID-19 patients (confirmed and suspected) should be transferred to hospitals designated by the local government. All patients with fever should be directly transferred to the fever clinic of the comprehensive hospitals. Pulmonary CT scan was a routine if coronary catheterization or hospitalization was considered and the nucleic acid testing was required after April when the testing kit supply became adequate. CT scan images should be reviewed by radiologists immediately to exclude the possibility of COVID-19 infection and results of nucleic acid testing was necessary before admission to hospital except for emergency PCI. 

The primary endpoint was in-hospital net adverse clinical events (NACE), a composite of death or leaving hospital at the family's request before dying, non-fatal myocardial reinfarction, stroke, emergency revascularization, and bleeding over BARC type 3. The secondary outcome was a composite of recurrent ischaemia, which was defined as the presence of angina and changes in haemodynamics or the electrocardiogram on intensive care and medication, cardiogenic shock, and exacerbated heart failure. 

Hospital during the study period. Emergency room attendance for cardiovascular diseases There were 4 patients with detectable ventricular septal rupture on arrival, and they were all transferred from another hospital after 12 hours.

As shown in Table 2 , 18 patients received fibrinolysis therapy with a median door-to-needle time of 60.0 minutes during the study period, among whom 3 patients underwent rescue PCI. Fibrinolysis therapy was absent in patients who arrived at the emergency room over 12 hours after symptom onset and in all patients from 2019. The patients from 2020 underwent primary PCI less frequently than their counterparts, and the median door-to-balloon time was longer in 2020. Patients from 2020 were more likely to receive an elective PCI, and the procedure was more likely to be performed later in 2020.

The guidelines recommending medication at discharge are also shown in Table 2 . No significant difference was found overall or in subgroup patients arriving <12 hours after symptom onset in dual antiplatelet therapy, statins, β-blockers, and angiotensin-converting-enzyme or angiotensin receptor blockers. Ticagrelor was more frequently used in patients arriving <12 hours after onset in 2020.

In-hospital outcomes were shown in Table 3 . The hospital stay of STEMI patients was longer in 2020. The in-hospital NACE were similar between patients in 2020 and 2019, while more events of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure 

This was a single-centre, retrospective, observational, historical controlled study. We focused on the care and in-hospital outcomes of STEMI patients during the 3-month period when hospitals in mainland China instituted the strictest emergency infection protocols to contain COVID-19. Our main findings were that the fibrinolysis-first strategy was associated with a significantly lower rate of timely reperfusion of STEMI patients during the pandemic period and a higher rate of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. However, in-hospital NACE, including death or leaving the hospital at the family's request before dying, non-fatal myocardial reinfarction, stroke, emergency revascularization, and bleeding over BARC type 3, was similar to that in 2019 when primary PCI was routine. Although obtaining STEMI morbidity was beyond this single-centre study, the dramatic drop in STEMI cases in this centre was consistent with other reports from various parts of the world affected by the virus(7-9). There are some potential reasons that may explain the lower incidence of STEMI in China. Compared with the previous year, people were encouraged to stay at home for a much-prolonged spring festival holiday, and a great number of jobs ceased or shifted online. People were 'forced' to live a healthier life without eating out and participating in unnecessary social activities. All the above factors definitely resulted in a significant decrease in stress and anxiety, which promote atherosclerotic plaque rupture.

Patients may also feel reluctant to present to hospitals due to fear of contracting COVID-19, which explained the decrease in the overall cases in addition to STEMI. Moreover, transferred cases from other lower-level hospitals were significantly reduced due to transportation restrictions.

Despite the decreased attendance of STEMI patients, the proportion of patients who arrived at the emergency room within the reperfusion time increased. This could also be explained by the decrease in transferred patients from lower-level hospitals in Beijing and its surrounding districts, which consume more time than local patients. On the other hand, the local patients arrived at hospitals more quickly due to the extremely light traffic inside Beijing city.

Several different patterns of management of STEMI patients have been reported since the pandemic outbreak. West countries persisted in the priority of pPCI, and a recent small sample size study showed a dedicated and specific organizational approach during pandemic may be effective to maintain pPCI as the treatment of choice for STEMI patients (10) .

However, as the first nation hit by the novel virus, the fibrinolysis-first strategy was established by China based on the following considerations. Fibrinolytic therapy is an important reperfusion strategy in settings where primary PCI cannot be offered in a timely manner within 6 hours after symptom onset.(11) Therefore, it is recommended within 12 hours of symptom onset if primary PCI cannot be performed within 120 minutes from STEMI diagnosis. (12) After the Chinese government implemented the strictest restrictions in response to the epidemic, the Chinese Society of Cardiology issued a consensus statement on the management of STEMI patients. In brief, protecting the medical staff and other patients from infection was always the priority, followed by compliance with the principle of saving the greatest amount of myocardium possible(3). Therefore, excluding potentially infected patients was set to be the first and mandatory protocol throughout all medical practice. Considering the prolonged time for rapid nucleic acid testing and pulmonary CT scans, fibrinolysis therapy should be initiated first to decrease the reperfusion time. However, a catherization laboratory therapy. The leading cause was patient refusal. Many patients who had relieved symptoms were reluctant to receive such a therapy for its potential bleeding risk and chose conservative medical treatment instead. The low rate of fibrinolysis certainly caused the low rate of timely reperfusion in 2020 patients. Although 3 patients received rescue PCI for failed fibrinolysis, all patients with fibrinolysis were free from any events during the index hospitalization. (14) . Since shortening the D2B time can significantly improve outcomes, the benefit of primary PCI over fibrinolysis may be attenuated. Apart from inadequate professional emergency medical services and the collaboration of interdisciplinary teams, the failure to provide timely consent is a core reason for the prominent D2B delay in China (13, The above reasons can also explain the delay of the D2N time in patients from 2020.

The fatality in 2019 seemed higher than that in 2020 (15 [5.2%] vs. 6 [3.6] ), but after excluding those arriving >12 hours after onset, the difference diminished (2 [1.8%] vs. Reperfusion therapy benefits patients within the reperfusion window most. Therefore, we performed a subgroup analysis and confirmed the similar NACE between the two years. The insignificant trend of a higher incidence of recurrent ischaemia, cardiogenic shock and exacerbated heart failure in the subgroup analysis may be due to the small sample size.

First, this was a single-centre experience with limited patient numbers in a short period of time, and the conclusions need to be interpreted with caution. Since our centre is located in a district with a relatively low case burden of COVID-19, further extension of our findings to other districts or countries should be made with caution. However, compared with multiple-centre studies in such a pandemic that drained most hospital resources, we obtained full access to all the data of patients, and we included data of the equivalent months of the 

Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic

CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic

How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People's Hospital

Recommendations from the Peking Union Medical College Hospital for the management of acute myocardial infarction during the COVID-19 outbreak

COVID-19 era

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong

Impact of COVID-19 on STEMI: Second youth for fibrinolysis or time to centralized approach?

Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group

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)

Factors associated with delay of reperfusion-decision for patients with ST-segment elevation myocardial infarction

Improvements in door-to-balloon time in the United States