nova página do texto(beta)
Inglês (pdf)
Artigo em XML
Referências do artigo
Tradução automática
Enviar este artigo por email
Citado por SciELO 
Similares em
SciELO 
Permalink
Introduction
Coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 infection, has a broad clinical spectrum, ranging from asymptomatic individuals to patients experiencing life-threatening illness. Several nationwide surveys reported that hospital admissions for acute coronary syndromes (ACS) decreased by 40-50% during the 1st year of the pandemic1,2. However, studies using a self-controlled case/cohort design have shown a 3- to 6-fold increased risk of acute myocardial infarction (MI) among patients with COVID-193-5. In addition, the ST-segment elevation MI (STEMI) mortality rate has been found to be three times higher in patients admitted to coronary care units during 2020, compared to 20196.
Apart from open population-based information, there are currently still insufficient data on the extent of myocardial damage and the occurrence of major adverse cardiovascular events (MACE) in well-characterized patients experiencing STEMI during recent SARS-CoV-2 infection. To shed light on this, we conducted an observational study on the hypothesis that patients who develop STEMI during recent SARS-CoV-2 infection may have fewer traditional cardiovascular risk factors and lower coronary atherosclerotic burden compared to their non-infected counterparts. Likewise, recent SARS-CoV-2 infection could have a deleterious impact on the severity of STEMI and the occurrence of MACE.
Materials and methods
Study design
The present study was carried out at the National Institute of Cardiology in Mexico City, an academic center devoted to the study and management of cardiovascular diseases. Since our aim was to assess ACS in the setting of recent or concurrent SARS-CoV-2 infection in unvaccinated patients to avoid a possible confounding role of anti-COVID-19 vaccines, we recruited all patients admitted to coronary care unit for STEMI according to the fourth universal definition of MI (2018) from August 6, 2020, to February 2, 2021, who also underwent cardiac catheterization7. We consider the registration timely since no more than 6 months had elapsed since the arrival of SARS-CoV-2 in our country and open vaccination for the general population had not yet begun.
Patients were considered to have recent or concurrent SARS-CoV-2 infection when they had elevated IgG antibodies against the nucleocapsid protein in serum using the Elecsys anti-SARS-CoV-2 assay (Roche diagnostics), or a positive polymerase chain reaction (PCR) test on nasopharyngeal swab. After receiving a STEMI diagnosis, patients intentionally underwent both tests as part of the evaluation of this protocol. Patients with active infection other than COVID-19 (including a rapid influenza test), pregnancy or puerperium, autoimmune disease, neoplasia, chronic kidney disease on dialysis, organ transplant, acute myocarditis, chronic heart failure, or Takotsubo cardiomyopathy were excluded from the study. Data from patients who did not undergo cardiac catheterization or whose hemodynamic study had ruled out acute MI were eliminated from the analysis.
Patients or their legal representatives authorized the use of their clinical data for research purposes. This study was approved by the local Ethics Committee and the procedures were carried out in accordance with the Declaration of Helsinki, its annexes, and local regulations.
Data collection
Based on a previously established format, the main demographic and clinical data were collected at hospital admission, with special emphasis on comorbidities, which were scored according to the Charlson comorbidity index. Other data were collected by accessing the electronic medical record, which contains a detailed record from hospital admission to discharge or death. All clinimetric tools were calculated with resources available online at the time of admission to the coronary care unit. The cardiac catheterization findings were obtained directly from the report generated by the hemodynamicist who performed the procedure, which is also available in the electronic medical record.
The previous risk of having an ACS was assessed using the QRISK-3 algorithm. STEMI severity was scored using various clinimetric tools, including the Killip classification, the Global registry of acute coronary events (GRACE) ACS risk score, and the thrombolysis in MI score (TIMI) risk score. The extent of the atherosclerotic burden was assessed by the number of coronary vessels showing > 50% occlusion on cardiac catheterization. Finally, the MACE composite outcome was scored according to the hospital occurrence of any of the following: acute heart failure, pulmonary edema, cardiogenic shock, or death. The requirement for invasive mechanical ventilation, intra-aortic balloon counter pulsation, and the number of days of hospital stay (until discharge or death) were also recorded.
Statistical analysis
Frequencies and percentages were used to describe categorical data and differences were analyzed using the Fisher’s exact test. Continuous variables were expressed as medians with interquartile range (IQR) and compared using the Mann-Whitney U test. Analyzes were 2-tailed and significance was set at p < 0.05. The GraphPad Prism v.9 software (GraphPad Software, La Jolla, CA, USA) was used for the calculations.
Results
A total of 89 patients (87% men, ages 49 to 65 years) were included in the study, of whom 14 tested positive for SARS-CoV-2 infection (93% by serum antibody test and 7% by PCR on nasopharyngeal swab), compared to 75 patients who were negative in both tests. No differences were found in the clinical examination on arrival at respiratory triage. Table 1 summarizes the main clinical data. Notably, oxygen saturation at room air was similar in both groups. When evaluating the history of comorbidities, we noted a higher prevalence for each of the conditions in the SARS-CoV2 negative group; however, we only found a statistically significant difference in the prevalence of hypertension for the SARS-CoV-2 negative group compared to the SARS-CoV-2 positive group (55% vs. 21%; p = 0.03). Consequently, the Charlson comorbidity index was higher in SARS-CoV-2 negative patients (median 2, [IQR] 1-3 vs. 2, 1-2; p = 0.12) even though this difference did not reach statistical significance.
Table 1 Baseline characteristics and clinical data at hospital admission
| SARS-CoV-2 positive (n = 14) | SARS-CoV-2 negative (n = 75) | p | |
|---|---|---|---|
| Age, years | 58 (49-61) | 61 (54-65) | 0.11 |
| Male, n (%) | 11 (78) | 67 (89) | 0.36 |
| Heart rate, beats/min | 79 (71-95) | 80 (65-92) | 0.74 |
| Respiratory rate, breaths/min | 19 (18-21) | 18 (17-20) | 0.23 |
| Systolic blood pressure, mmHg | 123 (110-149) | 129 (120-142) | 0.71 |
| Diastolic blood pressure, mmHg | 71 (66-81) | 80 (70-90) | 0.16 |
| SaO2, % at room air | 95 (95-97) | 95 (93-95) | 0.09 |
| Body mass index, kg/m2 | 22.7 (17.8-25.4) | 22.1 (20.1-23.3) | 0.72 |
| Coexisting conditions, n (%) | |||
| Hypertension | 3 (21) | 41 (55) | 0.03 |
| Diabetes mellitus | 6 (40) | 30 (40) | > 0.99 |
| Dyslipidemia | 3 (20) | 20 (26) | > 0.99 |
| Hyperuricemia | 0 | 3 (4) | > 0.99 |
| Current smoker | 4 (28) | 28 (37) | 0.76 |
| Previous myocardial infarction | 2 (14) | 10 (13) | > 0.99 |
| Previous stroke | 0 | 1 (1) | > 0.99 |
| Autoimmune disease | 0 | 2 (3) | > 0.99 |
| Charlson comorbidity index | 2 (1-2) | 2 (1-3) | 0.12 |
| Killip classification | 1 (1-2) | 1 (1-2) | 0.94 |
| GRACE risk score | 100 (92-123) | 118 (96-138) | 0.17 |
| TIMI risk score | 3 (2-5) | 4 (2-5) | 0.49 |
| Q-RISK3 score | 15.2 (6.4-21.8) | 19.5 (10.6-26.6) | 0.18 |
All data are presented as median (interquartile range) unless otherwise specified. Significant p value is in bold. SaO2: oxygen saturation by pulse oximetry; GRACE: global registry of acute coronary events risk score; TIMI: thrombolysis in myocardial infarction score.
Laboratory studies at hospital arrival also showed no difference between patients with a recent infection and those uninfected patients (Table 2). This included both leukocyte count and differential analysis, as well as inflammatory, endothelial activation, and tissue injury molecules. Likewise, clinimetric instruments used to assess both the risk of acute MI (QRISK-3) and the severity of the disease (Killip classification, TIMI score, and GRACE score) also showed no significant differences according to SARS-CoV-2 status (Table 1).
Table 2 Main laboratory findings at hospital admission
| SARS-CoV-2 positive (n = 14) | SARS-CoV-2 negative (n = 75) | p | |
|---|---|---|---|
| Leukocytes × 103/mm3 | 13.7 (10.6-16.4) | 11.2 (9.4-13.6) | 0.12 |
| Neutrophils × 103/mm3 | 10.7 (7.3-14.1) | 9.2 (7.3-11.5) | 0.22 |
| Lymphocytes × 103/mm3 | 1.4 (1.2-1.6) | 1.3 (1.0-1.7) | 0.22 |
| Platelets × 103/mm3 | 262 (223-282) | 226 (192-268) | 0.12 |
| Hemoglobin, g/dL | 15.6 (14.7-16.3) | 15.5 (14.5-16.4) | 0.95 |
| Neutrophil-to-lymphocyte ratio | 7.1 (4.8-10.4) | 7.5 (5.2-10.1) | 0.75 |
| Platelet-to-lymphocyte ratio | 184 (137-220) | 178 (129-245) | 0.91 |
| Albumin, g/dL | 4.1 (4.0-4.3) | 4.1 (3.8-4.3) | 0.92 |
| Serum creatinine, mg/dL | 0.9 (0.7-1.1) | 1.1 (0.9-1.3) | 0.06 |
| Troponin I, ng/mL | 15.5 (2.1-100.0) | 5.8 (0.8-100.0) | 0.62 |
| Creatine kinase, U/L | 1445 (252-2671) | 786 (257-1483) | 0.57 |
| D-dimer, ng/mL | 0.22 (0.19-0.33) | 0.22 (0.15-0.63) | 0.97 |
| Lactic dehydrogenase, U/L | 490 (197-526) | 305 (201-698) | 0.96 |
| C-reactive protein, mg/L | 5.4 (4.3-9.6) | 5.1 (2.0-21.1) | 0.98 |
| Ferritin, mg/L | 222 (131-287) | 158 (83-223) | 0.24 |
| NT-proB natriuretic peptide ng/L | 785 (167-2344) | 572 (226-2646) | 0.96 |
All data are presented as median (interquartile range).
Regarding the treatment schemes used for each group, no differences were found in pharmacotherapy or in the chosen intervention methods. As shown in table 3, the findings during cardiac catheterization in terms of degree of atherosclerotic occlusion or affected vascular sites were similar in both groups. Finally, the frequency of adverse outcomes, either individually or as a composite outcome (MACE), was not significantly different when the groups were compared.
Table 3 In-hospital treatment and major outcomes
| SARS-CoV-2 positive (n = 14) | SARS-CoV-2 negative (n = 75) | p | |
|---|---|---|---|
| Drugs use, n (%) | |||
| Acetylsalicylic acid | 14 (100) | 72 (96) | > 0.99 |
| P2Y12 inhibitors | 14 (100) | 75 (100) | > 0.99 |
| Statins | 14 (100) | 72 (96) | > 0.99 |
| RAAS inhibitors | 12 (85) | 65 (86) | 0.92 |
| Fibrinolytic therapy | 4 (28) | 16 (21) | 0.55 |
| Primary PCI | 12 (85) | 69 (92) | 0.60 |
| Coronary artery occlusion > 50% in cardiac catheterization, n (%) | |||
| Left main trunk | 1 (7) | 4 (5) | 0.58 |
| Left anterior descending artery | 10 (71) | 49 (65) | 0.76 |
| Circumflex artery | 5 (35) | 29 (38) | > 0.99 |
| Right coronary artery | 5 (35) | 41 (54) | 0.24 |
| Three-vascular disease | 1 (7) | 12 (16) | 0.68 |
| Invasive mechanical ventilation, n (%) | 1 (7) | 3 (4) | 0.50 |
| Intra-aortic balloon pump, n (%) | 3 (21) | 6 (8) | 0.14 |
| Major clinical outcomes, n (%) | |||
| Acute heart failure | 2 (14) | 13 (17) | > 0.99 |
| Pulmonary edema | 1 (7) | 3 (4) | 0.50 |
| Cardiogenic shock | 0 | 6 (8) | 0.58 |
| Death | 0 | 4 (5) | > 0.99 |
| MACE | 2 (14) | 15 (20) | > 0.99 |
| Days of hospital stay, median (IQR) | 4.5 (3-9.2) | 4 (2-7) | 0.58 |
RAAS: renin-angiotensin-aldosterone system; PCI: percutaneous coronary intervention; MACE: major adverse cardiovascular events; IQR: interquartile range.
Discussion
This study was conducted to assess the impact of recent SARS-CoV-2 infection on ACS. Our results show that STEMI patients who have had recent SARS-CoV-2 infection have fewer traditional cardiovascular risk factors, specifically hypertension, compared to patients in whom no evidence of recent COVID-19 has been found. However, recent SARS-CoV-2 infection does not appear to have an impact on the severity or extent of STEMI, nor on the occurrence of MACE.
The association between traditional cardiovascular risk factors and the severity of COVID-19 has been established. Indeed, hypertension, diabetes mellitus, obesity, and a history of coronary heart disease are significantly more frequent among COVID-19 patients with severe disease than among those with mild-to-moderate disease8. In contrast, the impact that COVID-19 may have on the severity of ACS has been poorly investigated. In a retrospective cohort study of patients admitted between January 2019 and December 2020 with out-of-hospital or in-hospital STEMI in the United States, it was shown that a concomitant diagnosis of COVID-19 was associated with higher rates of in-hospital mortality compared to patients with STEMI but not diagnosed with COVID-19 in the past year9. Notably, STEMI patients with COVID-19 were less likely to undergo coronary angiography or receive primary percutaneous coronary intervention, which was associated with 4 times higher mortality. Our study provides valuable information as all patients underwent cardiac catheterization and access to primary percutaneous coronary intervention and advanced life support was similar among STEMI patients, regardless of their COVID-19 status. Under these conditions of equality, the development of STEMI in patients with recent SARS-CoV-2 infection occurred in a context of lower baseline cardiovascular risk, as evidenced by the lower frequency of systemic hypertension and the trend towards a lower Charlson comorbidity index and Q-RISK3 score. This parallels the recent demonstration of myocardial injury and coagulopathy as a complication of COVID-1910. Although the durability of these complications and their real contribution to the development of ACS are still being investigated, the evidence suggests that recent SARS-CoV-2 infection could already be considered an independent cardiovascular risk factor, albeit parallel to those considered traditional. Recently, a multicenter European registry characterized 57 unvaccinated patients with COVID-19 referred for coronary angiography, reporting a high thrombus burden as well as an elevated incidence of MACE (28%)11. Potential mechanisms linking COVID-19 to STEMI include hypoxemic myocardial injury, stress cardiomyopathy, antiphospholipid antibodies, thromboinflammatory syndrome, and cytokine storm, all of which may destabilize atherosclerotic coronary plaques, activating platelet-endothelium interaction and facilitating coronary thrombosis6,12.
As limitations of our study, we have patients from a single center specialized in cardiovascular care, located in a country with an unusually high prevalence of hypertension, which may overestimate its impact both on the frequency of ACS and on COVID-19 infection. Furthermore, our results cannot be directly extrapolated to COVID-19 caused by emerging viral variants. Finally, the impact of universal vaccination against SARS-CoV-2 on the appearance of ACS remains to be elucidated.
Conclusions
Recent SARS-CoV-2 infection can occasionally lead to the development of hyperinflammation and an immune-mediated prothrombotic state. This pathological environment caused by acute COVID-19 seems to be a factor that facilitates the triggering of STEMI, especially in individuals with relatively few traditional cardiovascular risk factors.
Although recent SARS-CoV-2 infection gives rise to a thromboinflammatory syndrome, the clinical impact that this has on the evolution of STEMI and the occurrence of MACE is null or imperceptible.
