Abstract
Aims
The aim of this study was to assess clinical and prognosis differences in patients with COVID-19 and STEMI.
Methods and results
Using a nationwide registry of consecutive patients managed within 42 specific STEMI care networks, we compared patient and procedure characteristics and in-hospital outcomes in two different cohorts, according to whether or not they had COVID-19. Among 1,010 consecutive STEMI patients, 91 were identified as having COVID-19 (9.0%). With the exception of smoking status (more frequent in non-COVID-19 patients) and previous coronary artery disease (more frequent in COVID-19 patients), clinical characteristics were similar between the groups, but COVID-19 patients had more heart failure on arrival (31.9% vs 18.4%, p=0.002). Mechanical thrombectomy (44% vs 33.5%, p=0.046) and GP IIb/IIIa inhibitor administration (20.9% vs 11.2%, p=0.007) were more frequent in COVID-19 patients, who had an increased in-hospital mortality (23.1% vs 5.7%, p<0.0001), that remained consistent after adjustment for age, sex, Killip class and ischaemic time (OR 4.85, 95% CI: 2.04-11.51; p<0.001). COVID-19 patients had an increase of stent thrombosis (3.3% vs 0.8%, p=0.020) and cardiogenic shock development after PCI (9.9% vs 3.8%, p=0.007).
Conclusions
Our study revealed a significant increase in in-hospital mortality, stent thrombosis and cardiogenic shock development after PCI in patients with STEMI and COVID-19 in comparison with contemporaneous non-COVID-19 STEMI patients.
Introduction
The impact of COVID-19 on outcomes of ST-elevation myocardial infarction (STEMI) patients undergoing reperfusion has barely been explored. Two small series of 18 and 28 COVID-19 STEMI patients have been reported showing extremely high in-hospital mortality rates of 70% and 50%, respectively1,2. The lack of contemporaneous non-COVID-19 STEMI patients precludes a definite conclusion on the contribution of STEMI to the poor prognosis.
Here we present a nationwide cohort of consecutive STEMI patients admitted in 42 high-volume percutaneous coronary intervention (PCI) centres across Spain during the seven weeks that followed the country lockdown in March 2020. We aimed to study clinical and prognosis differences in patients with COVID-19.
Methods
SPANISH STEMI REGISTRY
In Spain there are 17 regional public service STEMI care networks which comprise 83 hospitals capable of performing primary percutaneous coronary interventions (PPCI) in 24/7/365 programmes. In 2018, 21,261 interventions in STEMI (91.6% PPCI, 3.2% rescue PCI and 5.1% routine early PCI strategy after fibrinolysis) were performed, representing 417 PPCI per million inhabitants3.
During the current COVID-19 outbreak, the Spanish Interventional Cardiology Association called for a registry to collect information on all consecutive STEMI patients retrospectively. Since March 2020, just after the activation of the “State of Alarm” and the country lockdown in Spain4, information on incidence, clinical characteristics, clinical management and outcomes has been recorded retrospectively.
The research protocol was approved by the Working Group on the Infarct Code of the Spanish Interventional Cardiology Association and by one central ethics committee.
STUDY DESIGN
The present report is a multicentre, retrospective, observational cohort study which evaluates procedures included in the Spanish Infarct Code Registry database. Supplementary Appendix 2 provides a checklist of items that should be included in reports of cohort studies. Between 14 March and 30 April 2020, a total of 42 hospitals with at least one patient with confirmed STEMI and a positive SARS-CoV-2 polymerase chain reaction (PCR) assay were identified and included in the analysis.
In these centres, all consecutive STEMI patients admitted were divided into COVID-19 and non-COVID-19 STEMI groups to compare clinical characteristics, in-hospital management and in-hospital clinical outcomes. Patients with a final diagnosis different from STEMI were not included in the final analysis. COVID-19 was defined when a PCR assay for SARS-CoV-2 was positive. Delay times were defined according to the European guidelines5. Data were collected reviewing clinical records. Cardiogenic shock diagnosis was based on clinical examination on admission and was defined as systolic blood pressure less than 90 mmHg or the need for vasopressors to maintain blood pressure above 90 mmHg combined with signs of peripheral hypoperfusion (coldness and/or pallor in the extremities, oliguria, or a decrease in level of consciousness)6.
We did not include patient and public involvement in this study.
INCIDENCE OF COVID-19 IN SPAIN
At the time the “State of Alarm” was declared in Spain, on 14 March 2020, 5,753 cases of COVID-19 had been diagnosed and there were 136 deaths. On 3 May 2020, when this analysis ended, there were 217,466 cases diagnosed (positive PCR assay), with 25,264 deaths and 118,902 recovered patients. At that moment, Spain was the leading European country in terms of the number of cases and mortality adjusted for population, ahead of the United Kingdom and Italy7.
STATISTICAL ANALYSIS
Frequencies (percentages) and means (±SD) were used to describe the population. Comparisons were performed using a t-test or non-parametric tests for continuous variables and a chi-square test or Fisher’s exact test for categorical variables. The association between COVID-19 and in-hospital mortality was assessed using both unadjusted and adjusted logistic regression models, estimating odds ratios (OR) and their 95% confidence interval (95% CI). In the latter, estimations were adjusted for age, gender, Killip class and time from symptom onset to reperfusion. All tests were two-sided. A p-value of 0.05 was considered to set statistical significance. All analyses were performed using Stata 15.0 (StataCorp, College Station, TX, USA).
Results
PATIENTS
A total of 1,130 patients with suspected STEMI were cared for at 42 high PCI-volume hospitals that were hubs of regional networks for STEMI treatment, with 109 patients having a positive PCR assay (9.6%). The final study sample is made up of 1,010 patients with confirmed STEMI, with 91 patients who had a positive PCR assay (9.0%). Figure 1 shows the flow chart of patients. Baseline clinical characteristics are provided in Table 1.
Figure 1.
Flow chart of patients. STEMI. NSTEMI: non-ST-elevation myocardial infarction; PCR: polymerase chain reaction; STEMI: ST-elevation myocardial infarction
Table 1. Comparison of clinical features in patients with confirmed ST-segment elevation myocardial infarction according to whether they had confirmed COVID-19 or not.
| Non-COVID-19 STEMI N=919 | COVID-19 STEMI N=91 | p-value | |
| Age, years | 62.5±13.1 | 64.8±11.8 | 0.95 |
| Male gender - no./total no. (%) | 717/915 (78.4) | 76/90 (84.4) | 0.18 |
| Clinical history - no./total no. (%) | |||
| Hypertension | 489/919 (53.3) | 47/91 (51.7) | 0.28 |
| Diabetes | 192/917 (20.9) | 21/91 (23.1) | 0.06 |
| Hyperlipidaemia | 429/915 (46.9) | 44/91 (48.4) | 0.27 |
| Current smoker | 415/913 (45.5) | 17/91 (18.7) | <0.001 |
| Previous coronary artery disease | 119/916 (13.0) | 14/90 (15.6) | 0.04 |
| First medical contact – no./total no. (%) | |||
| Out-of-hospital emergency medical service | 417/913 (45.7) | 29/91 (31.9) | <0.001 |
| Primary care centres | 189/913 (20.7) | 6/91 (6.6) | |
| Non-PCI hospitals | 179/913 (19.6) | 24/91 (26.4) | |
| PCI hospitals | 125/913 (13.7) | 30/91 (33.0) | |
| N.A. | 3/913 (0.3) | 2/91 (2.2) | |
| COVID-19 status on admission – no./total no. (%)* | |||
| Neither symptoms nor close contacts | 731/914 (80.0) | 16/91 (17.6) | <0.001 |
| Symptoms of COVID-19 | 47/914 (5.1) | 29/91 (31.9) | |
| Confirmed diagnosis | 0/914 (0) | 43/91 (47.3) | |
| Unknown/not available | 136/914 (14.9) | 3/91 (3.3) | |
| Reperfusion strategy at first medical contact – no./total no. (%) | |||
| PPCI | 838/919 (91.2) | 87/90 (96.7) | 0.19 |
| Fibrinolysis | 23/919 (2.5) | 3/90 (3.3) | |
| Diagnosis doubt, hospital transfer for decision | 54/919 (5.9) | 0/90 (0) | |
| Not available | 4/919 (0.4) | 0/90 (0) | |
| Complications before PCI – no. (%) | |||
| Ventricular fibrillation | 55/919 (6.0) | 6/91 (6.8) | 0.82 |
| Asystole | 9/919 (1.0) | 1/91 (1.1) | 0.91 |
| Mechanical ventilation | 42/919 (4.6) | 6/91 (6.6) | 0.39 |
| Heart failure on admission – no./total no. (%) | 169/919 (18.4) | 29/91 (31.9) | 0.002 |
| Plus-minus values are means±SD. * All patients were eventually diagnosed with COVID-19 by PCR. PCI: percutaneous coronary intervention; PCR: polymerase chain reaction; PPCI: primary percutaneous coronary intervention | |||
With the exception of smoking status (higher in non-COVID-19 patients) and previous coronary artery disease (higher in COVID-19 patients), the clinical characteristics were not different between the groups. The mode of presentation differed significantly between the groups, COVID-19 patients presenting more frequently at the hospital and less frequently via extra-hospital emergency medical services. Patients with COVID-19 more frequently had heart failure on arrival at the catheterisation laboratory. On admission, only 43 patients (4.3%) had a confirmed COVID-19 diagnosis; during admission, COVID-19 was diagnosed in 48 additional patients (4.8%), with a final sample of 91 patients (9.0%). Up to 96% of patients with clinical suspicion of COVID-19 during admission had a PCR assay. Figure 2 shows the COVID-19 status diagnosis path.
Figure 2.
COVID-19 diagnostic status path. Patients were categorised on admission according to their COVID-19 status into four groups: unknown, no symptoms compatible with COVID-19 or previous PCR test, symptoms compatible with COVID-19 but no previous PCR test or previous positive PCR test. Although it is essential to perform a PCR assay at admission in all patients, it should be noted that at the beginning of the pandemic, when this study was carried out, PCR was not available in many facilities. PCR: polymerase chain reaction
ANGIOGRAPHIC AND PROCEDURAL CHARACTERISTICS
Table 2 shows angiographic and procedural characteristics. Absence of significant stenosis on coronary angiography was present in 2.6% in patients with STEMI as the final diagnosis and 59.2% in patients with other diagnoses. In the whole cohort, 8.6% of patients did not have significant coronary stenosis (8.2% in patients without COVID-19 and 11.9% in COVID-19 patients). Patients with confirmed COVID-19 less frequently received pre-treatment with acetylsalicylic acid (ASA) and P2Y12 inhibitors (87.9% vs 95.1%, p=0.004, for ASA, and 84.6% vs 93.8%, p=0.001, for P2Y12 inhibitors). Conversely, mechanical thrombectomy (44% vs 33.5%, p=0.046) and glycoprotein (GP) IIb/IIIa inhibitors during the procedure (20.9% vs 11.2%, p=0.007) were more frequently used in COVID-19 patients.
Table 2. Comparison of angiographic and procedural characteristics in patients with confirmed ST-segment elevation myocardial infarction according to whether they had confirmed COVID-19 or not.
| Non-COVID-19 STEMI N=919 | COVID-19 STEMI N=91 | p-value | |
| Patient reception site at PPCI hospital – no./total no. (%) | |||
| Previously admitted to the hospital | 6/907 (0.7) | 8/89 (9.0) | <0.001 |
| Emergency room | 192/907 (21.2) | 23/89 (25.8) | |
| Critical care unit | 65/907 (7.2) | 8/89 (9.0) | |
| Direct to cath lab | 640/907 (70.6) | 50/89 (56.2) | |
| Killip class on cath lab arrival – no./total no. (%) | |||
| I | 750/895 (83.8) | 62/88 (70.5) | 0.011 |
| II | 68/895 (7.6) | 10/88 (11.4) | |
| III | 16/895 (1.8) | 4/88 (4.6) | |
| IV | 61/895 (6.8) | 12/88 (13.6) | |
| Coronary artery disease extent – no./total no. (%) | |||
| 1-vessel disease | 554/919 (60.3) | 55/91 (60.4) | 0.67 |
| 2-vessel disease | 259/919 (28.2) | 22/91 (24.2) | |
| 3-vessel disease | 82/919 (8.9) | 12/91 (13.2) | |
| Radial access | 821/905 (90.7) | 77/87 (88.5) | 0.50 |
| Location of culprit vessel – no./total no. (%) | |||
| Left main coronary artery | 15/919 (1.6) | 1/91 (1.1) | 0.70 |
| Left anterior descending | 414/919 (45.1) | 45/91 (49.5) | 0.42 |
| Left circumflex | 150/919 (16.3) | 12/91 (13.2) | 0.44 |
| Right coronary artery | 328/919 (35.7) | 35/91 (38.5) | 0.59 |
| Bypass graft | 3/919 (0.3) | 0/91 (0) | 0.59 |
| Basal TIMI flow – no./total no. (%) | |||
| 0 | 654/899 (72.8) | 62/89 (69.6) | 0.18 |
| 1 | 55/899 (6.1) | 10/89 (11.2) | |
| 2 | 85/899 (9.6) | 5/89 (5.6) | |
| 3 | 105/899 (11.7) | 12/89 (13.5) | |
| Final TIMI flow – no./total no. (%) | |||
| 0 | 16/903 (1.7) | 1/88 (1.7) | 0.66 |
| 1 | 9/903 (1.0) | 2/88 (1.1) | |
| 2 | 41/903 (4.5) | 5/88 (5.7) | |
| 3 | 837/903 (92.7) | 80/88 (90.9) | |
| PCI characteristics – no./total no. (%) | |||
| Balloon angioplasty | 378/919 (41.1) | 33/91 (36.3) | 0.37 |
| Mechanical thrombectomy | 308/919 (33.5) | 40/91 (44.0) | 0.046 |
| Bare metal stent implantation | 26/919 (2.8) | 4/91 (4.4) | 0.40 |
| Drug-eluting stent implantation | 803/919 (87.4) | 73/91 (80.2) | 0.06 |
| Pharmacological treatment during coronary angiography– no./total no. (%) | |||
| Aspirin | 874/919 (95.1) | 80/91 (87.9) | 0.004 |
| P2Y12 inhibitors | 863/919 (93.9) | 77/91 (84.6) | 0.001 |
| Clopidogrel | 282/919 (30.7) | 32/91 (35.2) | |
| Ticagrelor | 448/919 (47.9) | 36/91 (39.6) | |
| Prasugrel | 159/919 (17.3) | 11/91 (12.1) | |
| IIb/IIIa inhibitors | 103/919 (11.2) | 19/91 (20.9) | 0.007 |
| Unfractionated heparin | 708/919 (77.0) | 64/91 (70.3) | 0.17 |
| Low molecular weight heparin | 40/919 (4.4) | 5/91 (5.5) | 0.61 |
| Bivalirudin | 5/919 (0.5) | 0/91 (0) | 0.48 |
| Cangrelor | 7/919 (0.8) | 1/91 (1.1) | 0.73 |
| Decision after coronary angiography – no./total no. (%) | |||
| PPCI | 861/908 (94.8) | 87/89 (97.8) | 0.60 |
| Rescue PCI | 14/908 (1.5) | 1/89 (1.1) | |
| Routine early PCI after fibrinolysis | 12/908 (1.3) | 0/89 (0) | |
| Coronary angiography without PCI | 21/908 (2.3) | 1/89 (1.1) | |
| PCI: percutaneous coronary intervention; PPCI primary percutaneous coronary intervention | |||
DELAYS TO REPERFUSION
Table 3 shows the main delays to reperfusion intervals. Time between symptom onset and first medical contact trended to be shorter in COVID-19 patients (70 [30-240] vs 100 [40-211] minutes, p=0.15); there were no differences in time between symptom onset and reperfusion (231.5 [150-383] vs 240 [126-385] minutes, p=0.29). The time between first medical contact and reperfusion was similar in both groups (110 [80-157] vs 105 [80-151] minutes, p=0.29).
Table 3. Time intervals between onset of symptoms and reperfusion according to whether the patients had confirmed COVID-19 or not.
| Median [interquartile range] | p-value | |
| Onset of symptoms to first medical contact, minutes | ||
| Non-COVID-19 STEMI (n=879) | 100 [40-211] | 0.15 |
| COVID-19 STEMI (n=86) | 70 [30-240] | |
| Onset of symptoms to reperfusion, minutes | ||
| Non-COVID-19 STEMI (n=854) | 231.5 [150-383] | 0.29 |
| COVID-19 STEMI (n=83) | 240 [126-385] | |
| First medical contact to reperfusion, minutes | ||
| Non-COVID-19 STEMI (n=839) | 110 [80-157] | 0.29 |
| COVID-19 STEMI (n=81) | 105 [80-151] | |
| STEMI: ST-elevation myocardial infarction | ||
IN-HOSPITAL OUTCOMES
Figure 3 summarises in-hospital outcomes. Patients with COVID-19 had an increased in-hospital mortality (23.1% vs 5.7%, p<0.0001), driven by both non-cardiovascular (9.9% vs 0.5%, p<0.001) and cardiovascular causes (13.2% vs 5.1%, p=0.002). This association remained consistent after adjustment for age, sex, Killip class and time from symptom onset to reperfusion (OR 4.85, 95% CI: 2.04-11.51; p<0.001).
Figure 3.
In-hospital outcomes. MACE: major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction or stent thrombosis)
Interestingly, an increase of in-hospital stent thrombosis was observed (4.1% vs 0.8%, p=0.015) as well as an increase in cardiogenic shock after PCI (9.9% vs 3.8%, p=0.007). Stent thrombosis in patients with COVID-19 was acute and over drug-eluting stents in all cases; all patients were on aspirin and clopidogrel. Major cardiovascular events, defined as cardiovascular mortality, non-fatal acute myocardial infarction or acute stent thrombosis, were also more frequent in patients with COVID-19 (16.5% vs 6.0%, p<0.001).
Discussion
To our knowledge, this is the first study to have evaluated the influence of COVID-19 on early outcomes in patients with STEMI cared for in specific care networks in comparison with contemporaneous non-COVID-19 STEMI patients, as well as the largest series of COVID-19 STEMI patients thus far. It has the advantages of being multicentre and multi-region, providing a more balanced approach than the previously published manuscripts. Compared to non-COVID-19 patients, there was a higher percentage of heart failure on arrival and increased in-hospital mortality in COVID-19 patients with a hazard risk of 4.85 after controlling for age, sex, class and time from symptom onset to reperfusion. In addition, patients had evidence of more thrombotic lesions with higher use of mechanical thrombectomy and GP IIb/IIIa inhibitors and an increase in in-hospital stent thrombosis and cardiogenic shock development after PCI.
PREVALENCE OF COVID-19 IN STEMI
On 3 May 2020, confirmed COVID-19 cases in Spain were 217,416, implying a prevalence of confirmed cases (positive PCR assay) of 0.5%7. The reported prevalence of COVID-19 in STEMI patients at the beginning of the pandemic all over the country was 6.3%8, but these data included many hospitals without any case diagnosed. In our series we found a prevalence of 9.0%; 43 patients (4.3%) were already COVID-19 confirmed cases at the time of STEMI. PCR was performed during admission in 456 out of the remaining 967 patients. Thus, 511 STEMI patients never had PCR and therefore it is plausible that the prevalence of COVID-19 in our cohort is underestimated. In fact, it is estimated that more than half of SARS-CoV-2 infected patients are asymptomatic9. Nevertheless, up to 96% of patients with clinical suspicion of COVID-19 during admission had a PCR assay. Of the 823 patients with clinical information on the presence or absence of symptoms related to COVID-19 on admission and without previous diagnosis, only 45 (5.5%) had a positive PCR assay (2.1% asymptomatic and 38.2% with any symptom suggestive of the disease). Although in the current situation it is essential to perform a PCR assay on admission in every patient, it should be noted that, at the beginning of the pandemic, when this study was carried out, PCR was not readily available in many facilities.
ANGIOGRAPHIC CHARACTERISTICS
A recent case series of STEMI patients with PCR-confirmed COVID-19 from several hospitals in Lombardy, Italy, reported up to 39.3% of patients without obstructive coronary artery disease. In fact, PCI was performed in only 60.7% of STEMI cases2. It is not clear if those were consecutive patients or selected cases. Our data show a very different scenario, with an incidence of non-obstructive coronary artery disease in COVID-19 STEMI patients of only 2.2%, not different to COVID-19 negative patients. In our case, all patients were cared for in STEMI code networks. The criteria for STEMI code activation were chest pain and an ECG with ST-segment elevation. There were 120 patients with a final diagnosis different from STEMI (10.7%), which is very similar to what we found when compared with STEMI activity during 2019 in Spain; among patients with a final diagnosis different from STEMI, non-obstructive coronary artery disease was also similar to what was found during 2019, when there was no COVID-198. Between 1-14% of STEMI occur in the absence of obstructive coronary artery disease. We analysed only patients with a confirmed STEMI diagnosis and so we excluded other causes of myocardial infarction with non-obstructed coronary arteries such as myocarditis, Takotsubo syndrome, non-ST-elevation myocardial infarction or pulmonary embolism which, in our series, represented 10.6% of patients.
Choudry et al recently reported a single-centre experience in patients with confirmed STEMI and COVID-1910. Their findings are in line with our findings and suggest a strong signal towards a higher thrombus burden and poorer outcomes in patients with COVID-19 and STEMI. Interestingly, they performed an angiographical analysis and found that COVID-19 patients presented higher multivessel thrombosis, higher thrombus grade and poorer myocardial blush grade after PCI. Levels of D-dimer were found to correlate with thrombus grade, myocardial blush grade, and levels of heparin requirement during the primary PCI procedure, with a suggestion of higher heparin doses required to achieve therapeutic activated clotting times (ACT) in this cohort.
REPERFUSION STRATEGY
Different scientific societies have developed recommendations on reperfusion strategy during the COVID-19 outbreak, with advice that differs, depending on the conditions in each country. In China, the Pekin Union Medical College Hospital recommended thrombolysis as the first choice of treatment, and only recommended coronary intervention after ruling out COVID-19, even in case of contraindications to fibrinolysis11. The American College of Cardiology Interventional Council and the Society for Cardiovascular Angiography and Interventions stated that fibrinolysis could be considered an option for relatively stable STEMI patients with active COVID-19 to prevent staff exposure12. The recommendation of the Spanish Society of Cardiology was to maintain PPCI as the reperfusion strategy of choice in all patients during the COVID-19 crisis13. In agreement with this recommendation, >90% of patients in both groups underwent mechanical reperfusion. Delays to reperfusion were similar in both groups, but the time between symptom onset and first medical contact tended to be shorter in patients with COVID-19. This is probably due to the fact that 9% of COVID-19 patients who presented a STEMI were already admitted to a hospital, compared to 0.7% of the non-COVID-19 patients. Furthermore, up to 5.9% of non-COVID-19 patients were transferred to another centre to decide whether or not they had a STEMI, while this did not occur in any patient with COVID-19.
Pre-treatment with platelet inhibitors was also less frequent in patients with COVID-19, probably due to a worse clinical scenario (higher incidence of heart failure on admission) but use of thrombectomy devices and administration of GP IIb/IIIa inhibitors during PCI was more frequent. Of note, the incidence of acute and subacute stent thrombosis was significantly higher in the COVID-19 group (4.1% vs 0.8%, p=0.015). Although the lower rate of pre-treatment with antiplatelet therapies in these patients could have played a role, the heightened inflammatory and prothrombotic state reported in COVID-19 patients14 could also explain this alarmingly high rate of stent thrombosis. Anyway, we believe that, among STEMI patients, antithrombotic treatment should be more aggressive in those with concomitant COVID-19 infection.
IN-HOSPITAL OUTCOMES
We found a high in-hospital mortality (23.1%) in patients with COVID-19 and STEMI. They presented a higher incidence of heart failure on admission. Mortality remained higher for patients with COVID-19 after adjusting for confounding factors. Undoubtedly, COVID-19 infection is a serious disease with a high mortality rate, that could explain the higher non-cardiovascular mortality in COVID-19 positive STEMI patients. However, additionally, these patients had a higher incidence of cardiac events (cardiovascular death, reinfarction, or stent thrombosis). In fact, recent reports also suggest a higher thrombus burden and stent thrombosis risk in patients with COVID-19 and STEMI10. Although this is speculative, COVID-19 disease could reduce haemodynamic tolerance to complications related to the infarction, and additionally some drugs that have been used against COVID-19 infection could have a deleterious effect on cardiovascular function and could have interacted with antithrombotic and cardiovascular drugs prescribed in STEMI patients.
A recent trial evaluating antiviral medication in patients with confirmed SARS-CoV-2 infection and severe respiratory involvement showed a 19.2% to 25% 30-day mortality15. Data from the north of Italy suggested an even higher in-hospital mortality in STEMI patients with COVID-19 - up to 35.3% in patients treated with PCI and 45.4% in patients who did not have a culprit lesion on coronary angiography. In this series of cases, the high incidence of advanced heart failure or cardiogenic shock (75%) suggests a highly selected population that could explain this elevated mortality2. Another case series from the New York area also reported a very high mortality in patients with COVID-19 who presented ST-segment elevation on electrocardiography, with 50% in-hospital mortality in eight patients with STEMI and 90% in-hospital mortality in patients with non-coronary myocardial injury. In this series, 83% of STEMI patients were treated with PPCI, 12% suffered previous cardiac arrest and 25% presented cardiogenic shock1. We think that, although with a limited number of patients, our non-selected data probably best reflect the reality of patients with COVID-19 and STEMI, in line with the recent results of a series of 39 patients that found a 17.9% in-hospital mortality10.
Limitations
The limitations of this study are those of any multicentre registry. It is impossible to presume that every operator interpreted variables in the same way. Also, there is no way to determine inter-observer and inter-centre differences in denoting any particular variable. However, these definitions are a standard used in interventional practice and were originally designed to be intuitively applied by the clinician. PCR assays were not systematically performed in all patients, but it should be noted that, at the beginning of the pandemic, when this study was carried out, PCR was not available in many facilities, and it was performed in the vast majority of patients who had clinical symptoms of COVID-19 upon admission (96.1%). The data collected are not specific for patients with COVID-19 but for patients with STEMI and, unfortunately, we do not have available data on analytical parameters or on other clinical variables that could affect the evolution of patients with COVID-19. In any case, what is clear is that these patients have a higher risk of adverse cardiovascular events during hospital admission for STEMI.
Conclusions
Our study revealed a significant increase in in-hospital mortality in patients with STEMI and COVID-19, in comparison with contemporaneous non-COVID-19 STEMI patients. We did not find differences in the extent of coronary artery disease, and PPCI was the reperfusion strategy in the vast majority of patients. COVID-19 patients presented a higher rate of stent thrombosis and cardiogenic shock development after PCI.
Impact on daily practice
Despite a similar risk profile and similar total ischaemic time, COVID-19 patients presented more frequently with heart failure and had significantly higher in-hospital mortality (driven both by cardiovascular and by non-cardiovascular causes) than non-COVID-19 patients. The incidence of acute stent thrombosis and cardiogenic shock development after PCI was significantly higher in COVID-19 patients. Antithrombotic treatment should probably be more aggressive in those with concomitant COVID-19 infection to prevent stent thrombosis.
Supplementary data
Working Group on the Infarct Code of the Spanish Interventional Cardiology Association Investigators.
STROBE Statement — Checklist of items that should be included in reports of cohort studies.
Visual summary.
In-hospital outcomes of COVID-19 ST-elevation myocardial infarction patients.
Acknowledgments
Conflict of interest statement
A. Perez de Prado has received personal fees from iVascular, Boston Scientific, Terumo, B. Braun, and Abbott, outside the submitted work. A. Cequier has received grants and personal fees from Abbott Vascular, Medtronic and Biosensors; grants from Boston Scientific, Biomenco, Cordis, OrbusNeich and Spanish Society of Cardiology; personal fees from Ferrer International, Terumo and AstraZeneca, all outside the submitted work. The other authors have no conflicts of interest to declare.
Abbreviations
- PCI
percutaneous coronary intervention
- PCR
polymerase chain reaction
- PPCI
primary percutaneous coronary intervention
- STEMI
ST-segment elevation myocardial infarction
Contributor Information
Oriol Rodriguez-Leor, Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain.
Ana Cid Alvarez, Cardiology Department, Hospital Clínico de Santiago de Compostela, Santiago de Compostela, Spain.
Armando Pérez de Prado, Cardiology Department, Hospital de León, León, Spain.
Xavier Rossello, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain; Cardiology Department, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son Espases, Palma, Spain.
Soledad Ojeda, Cardiology Department, Hospital Universitario Reina Sofía, IMIBIC, Universidad de Córdoba, Córdoba, Spain.
Ana Serrador, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Cardiology Department, Hospital Clínico de Valladolid, Valladolid, Spain.
Ramon López-Palop, Cardiology Department, Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Javier Martin-Moreiras, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Cardiology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Jose Rumoroso, Cardiology Department, Hospital de Galdakao-Usansolo, Galdakao, Vizcaya, Spain.
Angel Cequier, Cardiology Department, Hospital de Bellvitge - IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain.
Borja Ibáñez, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain; Cardiology Department, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain.
Ignatio Cruz-González, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Cardiology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain.
Rafael Romaguera, Cardiology Department, Hospital de Bellvitge - IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain.
Raul Moreno, CIBER de Enfermedades CardioVasculares (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain; Cardiology Department, Hospital de La Paz, Madrid, Spain.
References
- Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, Ibrahim H, Friedman GH, Thompson C, Alviar CL, Chadow HL, Fishman GI, Reynolds HR, Keller N, Hochman JS. ST-Segment Elevation in Patients with Covid-19 - A Case Series. N Engl J Med. 2020;382:2478–80. doi: 10.1056/NEJMc2009020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stefanini GG, Montorfano M, Trabattoni D, Andreini D, Ferrante G, Ancona M, Metra M, Curello S, Maffeo D, Pero G, Cacucci M, Assanelli E, Bellini B, Russo F, Ielasi A, Tespili M, Danzi GB, Vandoni P, Bollati M, Barbieri L, Oreglia J, Lettieri C, Cremonesi A, Carugo S, Reimers B, Condorelli G, Chieffo A. ST-Elevation Myocardial Infarction in Patients with COVID-19: Clinical and Angiographic Outcomes. Circulation. 2020;141:2113–6. doi: 10.1161/CIRCULATIONAHA.120.047525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cid-Alvarez AB, Rodriguez-Leor O, Moreno R, Perez de Prado A. Spanish Cardiac Catheterization and Coronary Intervention Registry. 28th Official Report of the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (1990-2018). Rev Esp Cardiol (Engl Ed) 2019;72:1043–53. doi: 10.1016/j.recesp.2019.07.023. [DOI] [PubMed] [Google Scholar]
- Boletín Oficial del Estado núm. 67, de 14 de marzo de 2020, páginas 25390-25400. Sección I. Disposiciones generales. [Text in Spanish]. 2020. Jun 29, https://www.boe.es/eli/es/rd/2020/03/14/463.
- Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P ESC Scientific Document Group. 2017 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). Eur Heart J. 2018;39(2):119–77. doi: 10.1093/eurheartj/ehx393. [DOI] [PubMed] [Google Scholar]
- Khot UM, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, Topol EJ. Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. JAMA. 2003;290:2174–82. doi: 10.1001/jama.290.16.2174. [DOI] [PubMed] [Google Scholar]
- Datos de coronavirus en España. Departamento de Seguridad Nacional. Gobierno de España. [Text in Spanish]. 2020. Jul 4, https://www.dsn.gob.es/es/actualidad/sala-prensa.
- Rodriguez-Leor O, Cid-Álvarez B, Perez de Prado A, Rossello X, Ojeda S, Serrador A, Lopez-Palop R, Martín-Moreiras J, Rumoroso JR, Cequier A, Ibanez B, Cruz-Gonzalez I, Romaguera R, Moreno R Working Group on the Infarct Code of the Interventional Cardiology Association of the Spanish Society of Cardiology Investigators, Villa M, Ruíz-Salmerón R, Molano F, Sánchez C, Muñoz-García E, Íñigo L, Herrador J, Gómez-Menchero A, Gómez-Menchero A, Caballero J, Ojeda S, Cárdenas M, Gheorghe L, Oneto J, Morales F, Valencia F, Ruíz JR, Diarte JA, Avanzas P, Rondán J, Peral V, Pernasetti LV, Hernández J, Bosa F, Lorenzo PLM, Jiménez F, Hernández JMT, Jiménez-Mazuecos J, Lozano F, Moreu J, Novo E, Robles J, Moreiras JM, Fernández-Vázquez F, Amat-Santos IJ, Gómez-Hospital JA, García-Picart J, Blanco BGD, Regueiro A, Carrillo-Suárez X, Tizón H, Mohandes M, Casanova J, Agudelo-Montañez V, Muñoz JF, Franco J, Del Castillo R, Salinas P, Elizaga J, Sarnago F, Jiménez-Valero S, Rivero F, Oteo JF, Alegría-Barrero E, Sánchez-Recalde Á, Ruíz V, Pinar E, Pinar E, Planas A, Ledesma BL, Berenguer A, Fernández-Cisnal A, Aguar P, Pomar F, Jerez M, Torres F, García R, Frutos A, Nodar JMR, García K, Sáez R, Torres A, Tellería M, Sadaba M, Mínguez JRL, Merchán JCR, Portales J, Trillo R, Aldama G, Fernández S, Santás M, Pérez MPP. Impact of COVID-19 on ST-segment elevation myocardial infarction care. The Spanish experience. Rev Esp Cardiol (Engl Ed) 2020;73:994–1002. [Google Scholar]
- Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, Taylor J, Spicer K, Bardossy AC, Oakley LP, Tanwar S, Dyal JW, Harney J, Chisty Z, Bell JM, Methner M, Paul P, Carlson CM, McLaughlin HP, Thornburg N, Tong S, Tamin A, Tao Y, Uehara A, Harcourt J, Clark S, Brostrom-Smith C, Page LC, Kay M, Lewis J, Montgomery P, Stone ND, Clark TA, Honein MA, Duchin JS, Jernigan JA Public Health–Seattle and King County and CDC COVID-19 Investigation Team. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. N Engl J Med. 2020;382:2081–90. doi: 10.1056/NEJMoa2008457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Choudry FA, Hamshere SM, Rathod KS, Akhtar MM, Archbold RA, Guttmann OP, Woldman S, Jain AK, Knight CJ, Baumbach A, Mathur A, Jones DA. High Thrombus Burden in Patients With COVID-19 Presenting With ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2020;76:1168–76. doi: 10.1016/j.jacc.2020.07.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jing ZC, Zhu HD, Yan XW, Chai WZ, Zhang S. Recommendations from the Pekin Union Medical College Hospital for the management of acute myocardial infarction during the COVID-19 outbreak. Eur Heart J. 2020;14:1791–4. doi: 10.1093/eurheartj/ehaa258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welt FGP, Shah PB, Aronow HD, Bortnick AE, Henry TD, Sherwood MW, Young MN, Davidson LJ, Kadavath S, Mahmud E, Kirtane AJ American College of Cardiology’s (ACC) Interventional Council and the Society of Cardiovascular Angiography and Intervention (SCAI) Catheterization laboratory considerations during the coronavirus (COVID-19) pandemic: from ACC’s Interventional Council and SCAI. J Am Coll Cardiol. 2020;75:2372–5. doi: 10.1016/j.jacc.2020.03.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romaguera R, Cruz-Gonzalez I, Jurado-Román A, Ojeda S, Fernándz-Cisnal A, Jorge-Pérez P, Burgos-Palacios V, Ariza-Solé A, López-de-Sa E, Moreno R. Considerations on the invasive management of ischemic and structural heart disease during the COVID-19 coronavirus outbreak. Consensus statement of the Interventional Cardiology Association and the Ischemic Heart Disease and Acute Cardiac Care Association of the Spanish Society of Cardiology. REC Interv Cardiol. 2020;2:112–7. [Google Scholar]
- Vivas D, Roldan V, Esteve-Pastor MA, Roldán I, Tello-Montoliu A, Ruiz-Nodar JM, Cosín-Sales J, María Gámez J, Consuegra L, Luis Ferreiro J, Marín F Expert reviewers. Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology. Rev Esp Cardiol (Engl Ed) 2020;73:749–57. doi: 10.1016/j.rec.2020.04.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382:1787–99. doi: 10.1056/NEJMoa2001282. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Working Group on the Infarct Code of the Spanish Interventional Cardiology Association Investigators.
STROBE Statement — Checklist of items that should be included in reports of cohort studies.