SARS-CoV-2 infection increases thrombus load in coronary arteries of patients with AMI: a retrospective study

doi:10.21203/rs.3.rs-3999697/v1

Background:There is a lack of national and international literature on the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on thrombosis or increased risk of thrombosis in patients with acute myocardial infarction(AMI). Therefore, the aim of this retrospective study was to investigate the thrombus load within the coronary arteries of patients with SARS-CoV-2 infection combined with AMI and to provide data support for the clinical management of patients with Coronavirus Disease 2019 (COVID-19) combined with AMI.

Methods:A total of 174 patients with AMI in the cardiovascular internal medicine department of Zhangjiajie People's Hospital and Sangzhi People's Hospital of Sangzhi County were collected from 01 December 2022 to 01 June 2023, and were divided into two groups according to whether or not they were infected with SARS-CoV-2. Among them, 90 cases were in the COVID-19 group, and 84 cases were in the non-COVID-19 group. And the clinical data such as gender, age, hypertension, diabetes mellitus, hyperlipidemia, criminal vascularity, and thrombus load grading were retrospectively analyzed for these two groups of patients.

Results:It was found that there was no significant difference between the two groups in terms of gender, age, hypertension, diabetes, hyperlipidaemia and infarcted offender vessel. Of the 90 patients in the COVID-19 group, 64 formed thrombi, of which the culprit vessels were the right coronary (RCA) 37 (57.8%), left anterior descending artery (LAD) 23 (35.9%), and the left main coronary artery/left circumflex artery (LM/LCX) 4 (6.3%). In the non-COVID-19 group, 49 of 84 patients formed thrombi, of which 28 (57.1%) were right coronary, 11 (22.4%) anterior descending, and 10 (20.4%) left main/revolving branches.

Conclusion:In conclusion, COVID-19 infection combined with AMI leads to an increased risk of thrombosis and a tendency to be in a state of high thrombotic load. And interestingly, RCA is more prone to thrombus formation than LAD, LCX and LM.

the coronavirus disease 2019

Acute myocardial infarction

Morbid blood vessel

Thrombus load

Coronary artery

The outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan since December 2019 and its rapid spread across the country and the world has had a major impact on the world economy and healthcare [1, 2]. COVID-19 is an acute respiratory infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinically, the main manifestations of COVID-19 patients are fever, sore throat, cough, sputum and other respiratory manifestations. Severe COVID-19 not only affects the respiratory system, but also induces multiple systemic complications in the organism, of which the cardiovascular system response is the most obvious. A mass of patients with severe COVID-19 present with symptoms such as palpitations, chest tightness, chest pain, syncope, and in severe cases malignant arrhythmias, cardiogenic shock and even death [3, 4]. It has been shown that elderly patients with underlying cardiovascular diseases, such as hypertension, coronary heart disease and old myocardial infarction, are more susceptible to SARS-CoV-2 infection and have a higher mortality rate [5, 6]. Correspondingly, SARS-CoV-2 also exacerbates the condition of patients with primary cardiovascular disease, leading to increased mortality [7-9]. The current study found that the mechanism by which COVID-19 causes cardiovascular injury may be related to angiotensin-converting enzyme 2 (ACE2)-mediated myocardial injury, cytokine storm and immune response, and imbalance of myocardial oxygen supply [10, 11].

Acute myocardial infarction (AMI) is a series of clinical syndromes caused by myocardial necrosis due to acute ischemia and hypoxia in the coronary arteries. Coronary intervention is the treatment of choice to improve myocardial ischemia and hypoxia in patients with AMI. Coronary interventions generally include percutaneous coronary balloon dilatation and coronary stent implantation, both of which can directly open the blood vessels, dilate the stenotic vessels, improve myocardial ischemia and hypoxia, and provide a prognosis for patients [12, 13]. However, there is often thrombosis within the infarct-related artery and high resistance to coronary blood flow. Placement of a stent in this situation will increase the chance of thrombus formation and metastasis, which can lead to adverse events [14, 15]. At present, there is still a paucity of relevant domestic and international literature on whether SARS-CoV-2 infection causes thrombosis in AMI patients or increases the risk of thrombosis. Therefore, the aim of this retrospective study was to investigate the thrombus load within the coronary arteries of SARS-CoV-2-infected patients with comorbid AMI. And it provides some data to support the clinical management of patients with COVID-19 and AMI.

Study population

A total of 174 patients diagnosed with AMI in the Department of Cardiovascular Medicine of Zhangjiajie People's Hospital and Sangzhi County People's Hospital during the period from 01 December 2022 to 01 June 2023 were selected. Among them, 90 cases were infected with COVID-19 and 84 cases were not infected with COVID-19.

Inclusion criteria

(1) Compliance with AMI disease diagnostic criteria: 4th edition of the Global Definition of Myocardial Infarction [16]. (2) Positive COVID-19 nucleic acid test: Nucleic acid had been collected at the time of admission and the result was positive, confirming the diagnosis of COVID-19 infection. (3) Completed coronary angiography with complete clinical data.

Exclusion criteria

(1) Those who did not collect nucleic acids and did not complete coronary angiography after admission. (2) Missing clinical information. (3) Patients with their own combined coagulation disorders, active bleeding or suffering from bleeding disorders. (4) Patients who have previously taken long-term oral warfarin or new anticoagulant drugs. (5) Patients with hematological systemic diseases, including hematological malignancy, severe anemia. (6) Patients with severe hepatic or renal insufficiency (patients with uremia). (7) Patients with a history of major trauma surgery within the last 6 months. (8) Patients with rheumatic immune system diseases (9) Patients with mental disorders: unconsciousness, language communication disorders.

Data collection

Clinical data of the patients including gender, age, hypertension, diabetes mellitus, hyperlipidemia, coronary angiography (culprit vessel, thrombus grading), treatment modalities (aspiration, thrombolysis, combined aspiration + thrombolysis, neither + elective + death) were collected and analyzed.

Measurement of thrombus score

All patients were admitted to the hospital to complete coronary angiography to evaluate the intracoronary thrombosis in both groups. The thrombus score (TS) was used to assess the thrombus load [17]: (1) 0 point: no thrombus; (2) 1 point: vague thrombus image; (3) 2 point: definite thrombus image, the length of which was less than 1/2 of the inner diameter of the vessel; (4) 3 point: definite thrombus, the length of which was 1/2 to 2 times the inner diameter of the vessel; (5) 4 point: definite thrombus, the length of which was >2 times the inner diameter of the vessel. A high thrombus load is defined as a thrombus score of > 2 point, and a low thrombus load is defined as a thrombus score of ≤ 2 point.

Treatment

In the COVID-19 infected group, 8 were treated with thrombus aspiration, 22 with thrombolysis, 10 with combined aspiration + thrombolysis, and the remaining 50 with neither, elective or death. In the non-COVID-19 group, 16 of them were treated with thrombus aspiration, 12 with thrombolysis, 8 with combined aspiration + thrombolysis, and the remaining 48 were neither, elective, or dead.

Data analysis

SPSS 25.0 statistical analysis software was applied to analyze the collected data. Measurement data were expressed as mean ± standard deviation (X̅ ± S) and count data were expressed as percentage [n (%)]. The χ² test was used between groups. The p-value <0.05 was considered statistically significant.

Baseline characteristics

164 AMI patients were divided into non-COVID-19 and COVID-19 groups according to whether they were infected with COVID-19. The characteristics of the patients in the two groups are shown in Table 1. There were 90 patients in the COVID-19 group with a male/female ratio of 64/26 and a mean age of 65.53 ± 12.73 years. And there were 54 patients with hypertension, 49 with diabetes mellitus and 58 with hyperlipidemia. There were 84 patients in the non-COVID-19 group, with a male/female ratio of 60/24 and a mean age of 62.40 ± 11.30 years. These included 40 patients with hypertension, 53 patients with diabetes mellitus and 55 patients with hyperlipidemia. There were no significant differences in all baseline parameters between the non- COVID-19 and COVID-19 groups (P > 0.05).

Comparison of infarcted culprit vessels

Based on coronary angiographic findings, 36 (40.0%) patients had the culprit vessels in the right coronary artery (RCA), 42 (46.7%) in the left anterior descending artery (LAD), and 12 (13.3%) in the left main coronary artery/left circumflex artery (LM/LCX) among the 90 COVID-19 patients. Correspondingly, in the non-COVID-19 group, 32 (38.1%) patients had the RCA as the culprit vessels, 38 (45.2%) patients had a LAD, and 14 (16.7%) patients had a LM/LCX. There was no significant difference in culprit vessels between the two groups (P > 0.05) (see as Table 2).

Comparison of thrombosis

In the COVID-19 group, there were 64 thrombus formers, including 26 patients with a light thrombotic load and 38 patients with a heavy thrombotic load. And 49 people in the non-COVID-19 group formed thrombi, including 29 patients with a light thrombotic load and 20 with a heavy thrombotic load. The incidence of thrombosis and the incidence of high-load thrombosis were higher in the COVID-19 group than in the non-COVID-19 group (P < 0.05). The specific grading of the thrombus load in the two groups is shown in Table 3. More interestingly, the results of the study found that the RCA was more prone to thrombus formation compared to the left coronary artery (LAD, LM, LCX) (P < 0.05) (see as Table 4).

In this study, AMI patients were grouped according to whether they were infected with SARS-CoV-2 or not, and the general data and coronary angiography results of the two groups were compared to analyze whether infection with SARS-CoV-2 had an effect on AMI patients. The results of the study showed that there was no statistically significant difference between the two groups in terms of gender, age, hypertension, diabetes mellitus and hyperlipidemia rates. However, it is not directly proved that these factors have no effect on thrombosis in patients with COVID-19 combined with AMI. This may be related to the small sample size of this study.

Thrombosis is a complex pathophysiological process associated with a number of factors, the main factor being an imbalance between the coagulation and anticoagulation systems. The three main conditions for thrombosis include vascular endothelial cell damage, abnormal blood flow status, and increased blood coagulability [18, 19]. With the myocardial damage in AMI patients, it affects the expression of ACE-2 receptors in the myocardium and coronary vasculature, which triggers local inflammation, hypercoagulability and thrombus formation [20, 21]. The results of this study showed that AMI patients infected with COVID-19 had a significantly increased risk of thrombosis compared with AMI patients not infected with COVID-19. SARS-CoV-2 infection can lead to the release of a large number of inflammatory cytokines, such as interleukin-6, interleukin-8 and tumor necrosis factor, which can reduce the activity of the micro-vessels, thereby affecting microcirculatory hemodynamics and promoting thrombosis [22-24]. In addition, the SARS-CoV-2 virus invades the organism and binds to the ACE-2 receptor, which activates the renin-angiotensin system, leading to an increase in Angiotensin II, vasoconstriction, and damage to the vascular endothelium, thus causing platelet aggregation. After platelet adhesion, hypercoagulability is enhanced and thrombosis is increased [25-29].

This paper concludes that those whose infarct-related artery is the RCA are more prone to thrombosis compared to the left coronary artery. Previous studies have shown that anatomical factors also have a greater influence on the development of atherosclerotic plaques in the coronary arteries. From an anatomical point of view, the right and left coronary arteries are jointly responsible for the blood supply of the heart, but the thin wall thickness of the right ventricle results in lower intracavity pressure in its right chamber and weak myocardial contraction, and the coronary arteries in the right side have a smaller blood flow and fewer branches of the RCA than the left coronary artery [30]. This may lead to a higher rate of thrombosis in the RCA than in the left coronary artery. It has also been shown that the RCA-Aorta (RCA-AO) pinch angle is associated with coronary atherosclerotic plaque production [31], and that the smaller the RCA-AO pinch angle, the easier it is for plaque to form and thus inducing thrombosis. These results corroborate with the results of the present study and improve the plausibility of the results of the present study.

In conclusion, COVID-19 infection combined with AMI leads to an increased risk of thrombosis and a tendency to be in a state of high thrombus load. In addition, this study found that the RCA was more prone to thrombus formation than the LAD, LCX, and LM. However, whether COVID-19 infection has an effect on the prevalence of AMI in the population is still unknown and more in-depth studies are needed to follow to validate this question.

ACE2 Angiotensin-converting enzyme 2

AMI Acute myocardial infarction

COVID-19 The coronavirus disease 2019

LAD Left anterior descending artery

LCX Left circumflex artery

LM Left circumflex artery

RCA Right coronary artery

RCA-AO RCA-Aorta

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2

Acknowledgements

Not applicable.

Authors’ contributions

QZ, JY, JD, LD and ZL designed the study and collected the patients’ data. QZ and JY analyzed and interpreted the data. QZ, JY, JD and LD performed wrote the manuscript. QZ and ZL revised important intellectual content. All authors read and approved the final manuscript.

Funding

The work was not funded by any funding.

Data Availability

The experimental data used to support the findings of this study are available from the corresponding author upon request.

Ethics approval and consent to participate

The study was approved by the Medical Research Ethics Committee of Zhangjiajie People's Hospital. And all patients provided written and verbal informed consent at the time of admission.

Conflicts of Interest

The authors declared that they have no conflicts of interest regarding this work.

Ruiz Estrada MA, Koutronas E, Park D, Khan A, Tahir M. The impact of COVID-19 on the economic performance of Wuhan, China (2019-2021). Qual Quant. 2023;57(1):847-862.
Chavda VP, Kapadia C, Soni S, Prajapati, R, Chauhan, SC, Yallapu MM, et al. A global picture: therapeutic perspectives for COVID-19. Immunotherapy. 2022;14(5):351-371.
Boytsov SA, Pogosova NV, Paleev FN, Ezhov MV, Komarov AL, Pevsner DV, et al. Clinical Characteristics and Factors Associated with Poor Outcomes in Hospitalized Patients with Novel Coronavirus Infection COVID-19. Kardiologiia. 2021;61(2):4-14.
Chen W. Association of myocardial injury with the severity and mortality of patients infected with novel coronavirus disease 2019 (COVID-19): A meta- analysis. 2023.
Bilehjani E, Fakhari S, Farzin H, Tajlil A, Nader ND. Diagnosis and treatment of cardiovascular manifestations of COVID-19: a narrative review. Acta Cardiol. 2023; 1–7.
Genc Yavuz B, Colak S, Guven R, Altundag İ, Seyhan AU, Gunay Inanc R. Clinical Features of the 60 Years and Older Patients Infected with 2019 Novel Coronavirus: Can We Predict Mortality Earlier? Gerontology. 2021;67(4):433-440.
Mohseni A, Di Girolamo A, Cangiano R, Ascione M, di Marzo L, Mansour W. High-Grade Infection after Branched Endovascular Aortic Repair in Patient with Recent COVID-19 Hospitalization. Diagnostics (Basel). 2024;14(2):205.
Pillai A, Lawson B. Coronavirus disease 2019 and cardiovascular diseases: collateral damage?. Curr Opin Anaesthesiol. 2022;35(1):5-11.
Lim HJ, Park J, Song J, Moon S, Kim J, Cho H, et al. Changes in clinical features and outcomes in three major critical diseases after COVID-19 pandemic: acute myocardial infarction, stroke, and cardiac arrest[J]. Signa vitae. 2022; 18(5):86-94.
Zavyalova MV, Neklyudov AA, Zavyalov AV, Andryukhova ES, Paderov YM, Balakhonova MV, et al. Clinical and Morphological Features of Myocardial Infarction in Patients With a New Coronavirus Infection COVID-19. Kardiologiia. 2023;63(8):19-25.
Yuan S, Cheng T. Clinical characteristics, mechanisms and countermeasures of COVID-19 complicated with cytokine storm. Scientia Sinica Vitae. 2020; 50(06):675-678.
Chen LJ, Song H. Effect of intracoronary thrombolysis combined with percutaneous coronary intervention on patients with acute myocardial infarctio. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine. 2023; 33(11):69-72.
Jia H, Zhang W, Jia X, Song W, Sun W, Wang. Prognostic analysis of acute myocardial infarction with different timing of percutaneous coronary intervention. Medical Research and Education. 2023; 40(02): 25-32.
Zhou J Y. Thrombus burden and pathological characteristics of coronary culprit lesions in acute myocardial infarction. Peking Union Medical College. 2023.
Wang R, Mao L, Jiang Z, Liu K, Zhang Y, Ling W, et al. Study on factors associated with the occurrence of microcirculatory occlusion after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction. Journal of the PLA Medical College. 2021; 42(12):1254-1258.
The fourth global unified definition of myocardial infarction (139). Clinical Electrocardiography. 2019; 28(01):73.
Xie H, Jin J, Zhou P. Application of delayed stent implantation in acute STEMI patients with high thrombus burden. Journal of Chengdu Medical College. 2017; 12(02):228-231.
Díez Vidal A, Gómez López J, Rivera Núñez MA, Martínez Virto AM, Tung Chen Y. Risk factors and complications associated with superficial venous thrombosis. Eur J Intern Med. 2023; 20:S0953-6205(23)00431-4.
Llobet D, Vallvé C, Tirado I, Vilalta N, Carrasco M, Oliver A, et al. Platelet hyperaggregability and venous thrombosis risk: results from the RETROVE project. Blood Coagul Fibrinolysis. 2021; 32(2):122-131.
Qi B, Li Y, Han X. Expression of angiotensin Ⅱ type 1 receptor in platelets and its role in thrombosi. Thrombosis and Haemostasis. 2021; 27(01):176-178.
Kohno T, Anzai T, Naito K, Sugano Y, Maekawa Y, Takahashi T, et al. Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling. Circ J. 2008;72(10):1685-1692.
Zhang M, Yang T, Xu H, et al. Research progress on the mechanism of inflammatory factors in the process of venous thrombosis. Chinese Journal of Vascular Surgery. 2021; 13(03):284-288.
Liontos A, Biros D, Matzaras R, sarapatsani KH, Kolios NG, Zarachi A, et al. Inflammation and Venous Thromboembolism in Hospitalized Patients with COVID-19. Diagnostics (Basel). 2023;13(22):3477.
Rajapaksha H, Perera TB, Meepage J, et al. Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemical. European Journal of Chemistry. 2020; 11(4):351-363.
Cancro FP, Bellino M, Esposito L, Romei S, Centore M, D'Elia D, et al. Acute Coronary Syndrome in Patients with SARS-CoV-2 Infection: Pathophysiology and Translational Perspectives. Transl Med UniSa. 2022;24(2):1-11.
Parker S, Mahomed O. Hypoxia and thrombosis in COVID-19: new considerations for air passengers. J Travel Med. 2020; 27(8):taaa122.
Manolis AS, Manolis TA, Manolis AA, Melita H. Cardiovascular implications and complications of the coronavirus disease-2019 pandemic: a world upside down. Curr Opin Cardiol. 2021; 36(2):241-251.
Guo Y, Bu J. Research progress on the role of angiotensin converting enzyme 2 in coronavirus infection. Journal of Xiamen University. 2020; 59(03):334-340.
Zhang Y, Zeng B. Effects of novel coronavirus on cardiovascular syste. Chinese Journal of Medical Research. 2021; 50(06):169-172.
Wang W, Gu J, Zhang H, et al. The relationship between right coronary initiation-aortic Angle and plaque composition and degree of stenosis in the right coronary artery. Tianjin Medicine. 2020; 48(06):527-530.
Sun XL. Analysis of the relationship between right coronary artery plaque characteristics and RCA-AO Angle and diameter index. Shenyang Medical College. 2023.

Table 1 Clinical characteristics at baseline

Group	Gender		Age	Hypertension	Diabetes	Hyperlipidemia
Group	Male [n (%)]	Female [n (%)]	(Years，X̅ ± S)	[n (%)]	[n (%)]	[n (%)]
COVID-19 (n=90)	64 (71.1)	26 (28.9)	65.53 ± 12.73	54（60.0）	49（54.4）	58（64.4）
Non-COVID-19 (n=84)	60 (71.4)	24 (28.7)	62.40 ± 11.30	40（47.6）	53（63.1）	55（65.5）
χ²	0.002			2.681	1.34	0.02
P	＞ 0.05			＞ 0.05	＞ 0.05	＞ 0.05

Table 2 Comparison of infarcted culprit vessels

Group	Culprit vessels [n (%)]
Group	RCA	LAD	LM/LCX
COVID-19 (n=90)	36（40.0）	42（46.7）	12（13.3）
Non-COVID-19 (n=84)	32（38.1）	38（45.2）	14（16.7）
χ²	0.383
P	＞ 0.05

Table 3 Comparison of thrombus load classification

Group	Thrombus load classification [n (%)]
Group	0	1级	2	3	4
COVID-19 (n=90)	26（28.7）	10（11.1）	16（17.8）	20（22.2）	18（20.0）
Non-COVID-19 (n=84)	35（41.7）	15（17.7）	14（16.7）	12（14.3）	8（9.5）
χ²	30.637
P	＜0.05

Table 4 Comparison of infarcted culprit vessels in patients with thrombosis

Group	Culprit vessels [n (%)]
Group	RCA	LAD	LM/LCX
COVID-19 (n=64)	36（57.8）	24（35.9）	4（6.3）
Non-COVID-19 (n=49)	28（57.1）	11（22.4）	10（20.4）
χ²	6.17
P	＜0.05

No competing interests reported.

SARS-CoV-2 infection increases thrombus load in coronary arteries of patients with AMI: a retrospective study

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Abstract

Background

Methods

Result

Discussion

Conclusions

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