COVID-19-associated myocardial infarction

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Haddadi, M.D.[2]

Synonyms and keywords: Novel coronavirus, covid-19, COVID-19, SARS-CoV-2, Wuhan coronavirus, myocardial infarction, MI, Acute coronary syndrome, ACS

Overview

COVID-19 patients with cardiovascular comorbidities have higher mortality. According to a recent systematic review and meta-analysis,acute cardiac injury with troponin levels greater than 28 pg/ml was detected in 12.4% of confirmed COVID-19 patients. Acute Myocardial Infarction is defined as an acute myocardial injury with clinical evidence of acute myocardial ischemia plus rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit and at least one of the following:Symptoms of myocardial ischemia including new ischemic ECG changes, development of pathological Q waves, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology. Identification of a coronary thrombus by angiography or autopsy (not for type 2 or 3 MI). In regards to COVID-19 most of the MIs are type 2 indicating the causes to be the primary infection, hemodynamic disturbance, or respiratory deterioration.

Historical Perspective

  • COVID-19 (SARS-CoV-2) outbreak initiated and was discovered in December, 2019 in Wuhan, Hubei Province, China.[1]
  • On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
  • Even before the pandemic declaration, concerns about the management of Acute Myocardial Infarction in COVID-19 era started to rise and on March 11, 2020, Zeng et al addressed this issue by introducing Protocols From Sichuan Provincial People's Hospital for Acute MI diagnosis and treatment protocol adjustment during COVID-19.[2]
  • "Be Prepared" is the title of a paper published on March 15, 2020, discussing the longer time from symptom onset to first medical contact in STEMI patients due to the COVID-19 outbreak.The call for maximizing acute care resources, maintaining access to services while limiting nosocomial COVID-19 infection was one of the earliest in regards to COVID-19-associated myocardial infarction[3]
  • On Apr 13, 2020, Frankie Tam 'et al.' compared Time Components of STEMI Care Before and After COVID-19 Outbreak[4]
  • On March 31, 2020, Kang discussed underlying diseases such as cardiovascular disease as a risk factor developing a serious and severe COVID-19.[5]
  • On June 9, 2020, Fried et al. discussed 4 cases showing a variety of cardiovascular presentations of COVID-19 and one of the uncertainties as whether or not the staff should proceed to coronary angiography in response to ECG changes and positive troponin[6]

Classification

Myocardial infarction may be classified according to two subtypes:

Pathophysiology

The mechanism of COVID-19 myocardial infarction has not been fully understood and is likely multifactorial.

  • Two potential mechanisms for myocardial infarction in the setting of COVID-19 infection include:[7]
    • Plaque rupture in the setting of the inflammatory condition/shear stress caused by the virus
    • Exacerbation of pre-existing coronary artery disease
  • The cytokine release caused by the virus may lead to vascular inflammation, plaque instability, myocardial inflammation, a hypercoagulable state, or direct myocardial suppression. For hypercoagulable state in COVID-19, click here
  • Increased inflammatory response may also lead to endothelial dysfunction causing the microthrombi formation.[8]
  • ACE-2 is the receptor of SARS-CoV 2 which is highly expressed on cardiac pericytes. Therefore it can be speculated that the pericyte damage by the virus results in endothelial cell damage which at the end leads to microvascular impairment.[9]

Pathological changes:

  • In the level of cardiac tissue: findings include a range of minimal change to interstitial inflammatory infiltration and myocyte necrosis
  • In the level of vasculature: micro-thrombosis and vascular inflammation[10]

Causes

According to the Fourth Universal Definition of MI, there are two clinical classifications of the disease based on the causes:

Most of the MIs associated with COVID-19 are type 2 indicating the causes to be the primary infection, hemodynamic disturbance, or respiratory deterioration.[11] [12][8]

Differentiating Myocardial infarction from other Diseases

  • For further information about the differential diagnosis, click here.
  • To view the differential diagnosis of COVID-19, click here.
  • To view the differential diagnosis of STEMI, click here

Epidemiology and Demographics

  • The data on the incidence of myocardial infarction in the setting of COVID-19 infection is limited.
  • Hospitalized patients with COVID-19 and Cardiovascular disease seem to be more prevalent in both the USA and China. [10]
  • Studies have shown a reduction of incidence and hospitalization of acute MI during COVID-19 Pandemic.[13][14][15][16]
  • A study in Italy showed up to a 49.4 percent reduction in admissions for acute MI to coronary care units from March 12th to 19th in 2020 compared to the equivalent time in 2019. [13]

Based on incidence rate of hospitalization among adults with STEMI and non-STEMI in Kaiser Permanente system before and after the first reported death from Covid-19 in Northern California on March 4, 2020:

  • The incidence rate (IR) of MI increases with age:
    • The IR between Jan 1-Mar 3 2020 for patients Age <65 with AMI was 1.5 which decreased to 1 during Apr 8-14 2020
    • The IR between Jan 1-Mar 3 2020 for patients Age >65 with AMI was 12.9 which decreased to 6 during Apr 8-14 2020
  • Males are more commonly affected by [MI] than females:
    • The IR between Jan 1-Mar 3 2020 among male patients was 5.1 which decreased to 2.9 during Apr 8-14 2020
    • The IR between Jan 1-Mar 3 2020 among female patients was 3.1 which decreased to 1.5 during Apr 8-14 2020[17]

ST-Elevation Myocardial Infarction (STEMI) and COVID-19:
A US model from 9 major centers showed a 38% drop in total STEMI activations during the COVID-19 pandemic. There is a 40% reduction noted in Spain as well. there was also a delay between the first presentation to a medical encounter up to 318 min. This is important since COVID-19 can potentially be a cause of STEMI through microthrombi, cytokine storm, coronary spasm, or direct endothelial injury.[18][19]

  • Potential etiologies for the reduction in STEMI PPCI activations:
    • avoidance of medical care due to social distancing or concerns of contracting COVID-19 in the hospital
    • STEMI misdiagnosis
    • increased use of pharmacological reperfusion due to COVID-19

It is very important to realize if patients' anxiety is the reason behind decreasing the presentation of STEMI to U.S. hospitals.[14][11]

Risk Factors

Common risk factors in the development of acute coronary syndrome including STEMI and non-STEMI are listed below:[20]

For Risk factors associated with COVID-19 please click here

Screening

Due to the higher mortality of patients with COVID-19 and cardiovascular comorbidities, it advisable to triage patients with COVID-19 based on their underlying CVD for a more aggressive treatment plan.[19]

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

There are no specific symptoms associated with COVID-19-associated-Myocardial infarction. Common symptoms in patients with acute MI is listed below:[23]

For non-ST elevation myocardial infarction history and symptoms please click here
For ST elevation myocardial infarction history and symptoms please click here

Physical Examination

  • For non-ST elevation myocardial infarction physical examination please click here
  • For STEMI physical examination please click here

Laboratory Findings

Elevated cardiac Troponin levels has been detected in 10-30 percent of COVID-19 patients and studies have shown an association between mortality and higher troponin in COVID-19. However, the clinical value of troponin to assess suspected ACS based on clinical presentation has not been established. [24]

  • For COVID-19 laboratory findings please click here
  • For non ST elevation myocardial infarction biomarkers please click here
  • For ST elevation myocardial infarction laboratory findings please click here

Electrocardiogram

There are no specific ECG findings associated with both COVID-19 and Myocardial infarction.

  • For non-ST-elevation myocardial infarction electrocardiogram please click here
  • For ST-elevation myocardial infarction electrocardiogram please click here
  • For COVID-19 electrocardiogram findings please click here

X-ray

There are no specific X-ray findings associated with both COVID-19 and Myocardial infarction.

  • For X-ray findings in COVID-19 please click here
  • For X-ray findings in Myocardial Infarction please click here

Echocardiography

  • In a study done among 28 patients with COVID-19 with STEMI, the following echocardiographic findings were reported:[21]
    • Localized wall motion abnormalities
    • Diffuse hypokinesia  
    • Left ventricular ejection fraction was lower than 50% in about 61% of the individuals.
  • For COVID-19 echocardiography please click here
  • For non-STEMI Echocardiography please click here
  • For STEMI Echocardiography please click here

CT scan

There are no specific CT scan findings related to COVID-19-associated myocardial infarction.

MRI

There are no MRI findings related to COVID-19-associated myocardial infarction.

Other Imaging Studies

Coronary Angiography

Other Diagnostic Studies

There are no specific other diagnostic studies related to COVID-19-associated myocardial infarction.

Treatment

Medical Therapy

In patients with ACS, and COVID-19, treatment should follow the guidelines of the updated Society for Cardiovascular Angiography and Interventions.[10] [25]

  • Treatment of STEMI & COVID-19:
    • The specific protocols for the treatment have been evolving. Early recommendations showed intravenous thrombolysis as first-line therapy for STEMI patients with confirmed COVID-19 since most hospitals do not have protected cardiac catheterization labs.[18]
    • According to the latest European Society of Cardiology (ESC) guidance for the management of cardiac complications related to COVID-19, if STEMI is diagnosed timely primary percutaneous intervention should be performed as stated by current ESC guidelines, irrespective of COVID-19 diagnosis. Fibrinolysis should be the first treatment choice when percutaneous intervention is not feasible within 12 hours of symptom onset.
  • Treatment of non-ST-STEMI, should be based on risk stratification:
    • high-risk cases: immediate invasive strategy, SARS-CoV-2 testing should be delayed.
    • intermediate/low-risk cases: non-invasive strategies such as coronary CT-angiography with regular follow-ups should be the treatment of choice.[8]

Primary Prevention

  • There are no available vaccines against COVID-19 and studies are going on for finding an effective vaccine.
  • Other primary prevention strategies include measures to reduce the occurrence of myocardial injury among COVID-19 patients. Recent studies have suggested the use of medications improving microcirculation, especially for the high-risk group such as males, smokers, diabetic patients, and patients with established cardiovascular disease comorbidities.[8]
    • For Risk factors associated with COVID-19 please click here

Secondary Prevention

  • There are no established measures for the secondary prevention of COVID-19-associated myocardial infarction.
  • For ST-elevation myocardial infarction secondary prevention please click here

References

  1. Meng X, Deng Y, Dai Z, Meng Z (June 2020). "COVID-19 and anosmia: A review based on up-to-date knowledge". Am J Otolaryngol. 41 (5): 102581. doi:10.1016/j.amjoto.2020.102581. PMC 7265845 Check |pmc= value (help). PMID 32563019 Check |pmid= value (help).
  2. Zeng, Jie; Huang, Jianxin; Pan, Lingai (2020). "How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People’s Hospital". Intensive Care Medicine. 46 (6): 1111–1113. doi:10.1007/s00134-020-05993-9. ISSN 0342-4642.
  3. Ardati, Amer K.; Mena Lora, Alfredo J. (2020). "Be Prepared". Circulation: Cardiovascular Quality and Outcomes. 13 (4). doi:10.1161/CIRCOUTCOMES.120.006661. ISSN 1941-7713.
  4. Tam, Chor-Cheung Frankie; Cheung, Kent-Shek; Lam, Simon; Wong, Anthony; Yung, Arthur; Sze, Michael; Lam, Yui-Ming; Chan, Carmen; Tsang, Tat-Chi; Tsui, Matthew; Tse, Hung-Fat; Siu, Chung-Wah (2020). "Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment–Elevation Myocardial Infarction Care in Hong Kong, China". Circulation: Cardiovascular Quality and Outcomes. 13 (4). doi:10.1161/CIRCOUTCOMES.120.006631. ISSN 1941-7713.
  5. Kang, Yun-Jung (2020). "Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease". Disaster Medicine and Public Health Preparedness: 1–3. doi:10.1017/dmp.2020.60. ISSN 1935-7893.
  6. Fried, Justin A.; Ramasubbu, Kumudha; Bhatt, Reema; Topkara, Veli K.; Clerkin, Kevin J.; Horn, Evelyn; Rabbani, LeRoy; Brodie, Daniel; Jain, Sneha S.; Kirtane, Ajay J.; Masoumi, Amirali; Takeda, Koji; Kumaraiah, Deepa; Burkhoff, Daniel; Leon, Martin; Schwartz, Allan; Uriel, Nir; Sayer, Gabriel (2020). "The Variety of Cardiovascular Presentations of COVID-19". Circulation. 141 (23): 1930–1936. doi:10.1161/CIRCULATIONAHA.120.047164. ISSN 0009-7322.
  7. Bansal, Manish (2020). "Cardiovascular disease and COVID-19". Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 14 (3): 247–250. doi:10.1016/j.dsx.2020.03.013. ISSN 1871-4021.
  8. 8.0 8.1 8.2 8.3 Montone, Rocco A; Iannaccone, Giulia; Meucci, Maria Chiara; Gurgoglione, Filippo; Niccoli, Giampaolo (2020). "Myocardial and Microvascular Injury Due to Coronavirus Disease 2019". European Cardiology Review. 15. doi:10.15420/ecr.2020.22. ISSN 1758-3764.
  9. Xiong, Chenglong; Feng, Yi; Chen, Mingquan; Li, Xiangjie; Chen, Liang (2020). "The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2". Cardiovascular Research. 116 (6): 1097–1100. doi:10.1093/cvr/cvaa078. ISSN 0008-6363.
  10. 10.0 10.1 10.2 Kang Y, Chen T, Mui D, Ferrari V, Jagasia D, Scherrer-Crosbie M; et al. (2020). "Cardiovascular manifestations and treatment considerations in covid-19". Heart. doi:10.1136/heartjnl-2020-317056. PMC 7211105 Check |pmc= value (help). PMID 32354800 Check |pmid= value (help).
  11. 11.0 11.1 11.2 Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA; et al. (2018). "Fourth Universal Definition of Myocardial Infarction (2018)". J Am Coll Cardiol. 72 (18): 2231–2264. doi:10.1016/j.jacc.2018.08.1038. PMID 30153967.
  12. 12.0 12.1 Template:Cite website
  13. 13.0 13.1 De Rosa S, Spaccarotella C, Basso C, Calabrò MP, Curcio A, Filardi PP; et al. (2020). "Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era". Eur Heart J. 41 (22): 2083–2088. doi:10.1093/eurheartj/ehaa409. PMC 7239145 Check |pmc= value (help). PMID 32412631 Check |pmid= value (help).
  14. 14.0 14.1 Garcia S, Albaghdadi MS, Meraj PM, Schmidt C, Garberich R, Jaffer FA; et al. (2020). "Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic". J Am Coll Cardiol. 75 (22): 2871–2872. doi:10.1016/j.jacc.2020.04.011. PMC 7151384 Check |pmc= value (help). PMID 32283124 Check |pmid= value (help).
  15. Solomon MD, McNulty EJ, Rana JS, Leong TK, Lee C, Sung SH; et al. (2020). "The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction". N Engl J Med. doi:10.1056/NEJMc2015630. PMID 32427432 Check |pmid= value (help).
  16. De Filippo O, D'Ascenzo F, Angelini F, Bocchino PP, Conrotto F, Saglietto A; et al. (2020). "Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy". N Engl J Med. doi:10.1056/NEJMc2009166. PMC 7224608 Check |pmc= value (help). PMID 32343497 Check |pmid= value (help).
  17. Solomon, Matthew D.; McNulty, Edward J.; Rana, Jamal S.; Leong, Thomas K.; Lee, Catherine; Sung, Sue-Hee; Ambrosy, Andrew P.; Sidney, Stephen; Go, Alan S. (2020). "The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction". New England Journal of Medicine. doi:10.1056/NEJMc2015630. ISSN 0028-4793.
  18. 18.0 18.1 Ullah W, Sattar Y, Saeed R, Ahmad A, Boigon MI, Haas DC; et al. (2020). "As the COVID-19 pandemic drags on, where have all the STEMIs gone?". Int J Cardiol Heart Vasc. 29: 100550. doi:10.1016/j.ijcha.2020.100550. PMC 7261452 Check |pmc= value (help). PMID 32550258 Check |pmid= value (help).
  19. 19.0 19.1 Guo T, Fan Y, Chen M, Wu X, Zhang L, He T; et al. (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiol. doi:10.1001/jamacardio.2020.1017. PMC 7101506 Check |pmc= value (help). PMID 32219356 Check |pmid= value (help).
  20. Fuster V, Badimon L, Cohen M, Ambrose JA, Badimon JJ, Chesebro J (1988). "Insights into the pathogenesis of acute ischemic syndromes". Circulation. 77 (6): 1213–20. PMID 3286036.
  21. 21.0 21.1 21.2 Stefanini, Giulio G.; Montorfano, Matteo; Trabattoni, Daniela; Andreini, Daniele; Ferrante, Giuseppe; Ancona, Marco; Metra, Marco; Curello, Salvatore; Maffeo, Diego; Pero, Gaetano; Cacucci, Michele; Assanelli, Emilio; Bellini, Barbara; Russo, Filippo; Ielasi, Alfonso; Tespili, Maurizio; Danzi, Gian Battista; Vandoni, Pietro; Bollati, Mario; Barbieri, Lucia; Oreglia, Jacopo; Lettieri, Corrado; Cremonesi, Alberto; Carugo, Stefano; Reimers, Bernhard; Condorelli, Gianluigi; Chieffo, Alaide (2020). "ST-Elevation Myocardial Infarction in Patients With COVID-19". Circulation. 141 (25): 2113–2116. doi:10.1161/CIRCULATIONAHA.120.047525. ISSN 0009-7322.
  22. Nasiri, Mohammad Javad; Haddadi, Sara; Tahvildari, Azin; Farsi, Yeganeh; Arbabi, Mahta; Hasanzadeh, Saba; Jamshidi, Parnian; Murthi, Mukunthan; Mirsaeidi, Mehdi (2020). doi:10.1101/2020.03.24.20042903. Missing or empty |title= (help)
  23. 23.0 23.1 Abidov A, Rozanski A, Hachamovitch R, Hayes SW, Aboul-Enein F, Cohen I; et al. (2005). "Prognostic significance of dyspnea in patients referred for cardiac stress testing". N Engl J Med. 353 (18): 1889–98. doi:10.1056/NEJMoa042741. PMID 16267320. Review in: Evid Based Med. 2006 Jun;11(3):91
  24. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z; et al. (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).
  25. Szerlip M, Anwaruddin S, Aronow HD, Cohen MG, Daniels MJ, Dehghani P; et al. (2020). "Considerations for cardiac catheterization laboratory procedures during the COVID-19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates". Catheter Cardiovasc Interv. doi:10.1002/ccd.28887. PMID 32212409 Check |pmid= value (help).


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