COVID-19-associated spontaneous coronary artery dissection

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is caused by novel coronavirus disease 2019 virus (COVID‐19). Cardiac manifestations and injury were identified in up to 20–28% of patients. Spontaneous coronary artery dissection (SCAD) is one of the cardiac complication of covid-19 and can be either atherosclerotic or non-atherosclerotic resulting from attaching covid-19 to ACE receptos of vessles wall and producing intense inflammation and endothelial dysfunction, sympathetic over-reactivity that are the precursors of intimal dissection. SCAD can be manifested as STEMI or NSTEMI in patients with covid-19 in which high clinical suspicion is warranted before administration of fibrinolysis in such patients. Among nine reported cases of covid-19 associated SCAD there were not found any previous conventional risk factors of SCAD such as fibromuscular disease, steraneous physical exercise, sex hormone, or peripartum period, except one case reported after intense cough in hospitalized covid-19 patients. In reported covid-19 patients associated with SCAD, it was more common in men and all nine cases were survived with consevative therapy or percutaneous coronary intervention based upon the anatomical site of dissection.

• COVID-19 was first reported in Wuhan, Hubei Province, China in December 2019.^[1]
• The World Health Organization declared the COVID-19 outbreak a pandemic on March 12, 2020.
• On June 22, 2020, the first case of COVID-19 with spontaneous coronary artery dissection was reported.^[2]

• Based on origin COVID-19 associated spontaneous coronary artery dissection can be of two types:^[3]
  • Atherosclerotic (A-SCAD)
  • Non-atherosclerotic (NA-SCAD)

• SCAD can be secondary to an atherosclerotic (A-SCAD) or non-atherosclerotic (NA-SCAD) lesion in origin.
• Lessons from the previous coronavirus and influenza epidemics suggest that these viral infections can trigger acute coronary syndrome primarily owing to a combination of a significant systemic inflammatory response plus localized vascular inflammation at the arterial plaque level.

• The exact pathogenesis of spontaneous coronary artery dissection in covid-19 patients is not fully understood.
• It is thought that SCAD in covid-19 patients is the result of either Intense inflammation and endothelial dysfunction causing sympathetic overreactivity leading to intimal dissection.
• High dose of corticosteroid therapy may induce spontaneous rupture of injured arterial wall.
• Covid-19 may causes activation and infiltration of T cells in coronary adventitia and periadventitial fat leading to release of cytokines and protease and dissection of injured wall.
• Covid-19 may enhance angiogenesis and proliferation of vasavasarum.
• Rupture of fragiled vasavasarum is the cause of intramural hematoma.
• Transition of inflammatory cell via vasavasarum to the medial and adventitial layers of the vessels may lead to rupture of vasavasarum.
• Covid-19 may attach to ACE receptors on endothelial and smooth muscle of coronary artery leading to inflammation in the muscle wall, massive death of endotheliocytes, vascular tone impairment, hemostatic impairment, and vulnerability of vessels wall to dissection.

• Coronary artery dissection may be related to intraplaque hemorrhage resulting in an intra-adventitial hematoma, which can spread longitudinally along the coronary artery, dissecting the tunicae.^[2][4]
• In COVID-19 patients, due to high inflammatory load, a localized inflammation of the coronary adventitia and periadventitial fat can occur. This can lead to the development of sudden coronary artery dissection in a susceptible patient with underlying cardiovascular disease.
  ^[5]

• It can result in extensive dissection lengths, especially in the presence of arterial fragility from predisposing arteriopathies.
• NA-SCAD can develop in any layer (intima, media, or adventitia) of the coronary artery wall. However, the initiation and the pattern of dissection in NA-SCAD is different from the pattern observed in patients with pre-existing atherosclerosis.

Common causes of covid-19-associated with spontaneous coronary artery dissection include:

• Inflammation
• sympathetic overreactivity
• Use of corticosteroids
• Underlying coronary artery disease

  For other causes of spontaneous coronary artery dissection, Click here.

• To view the differential diagnosis of COVID-19, click here.
  
• To view a differential diagnosis on the other causes of chest pain, click here.

• The exact prevalence of spontaneous coronary artery dissection in covid-19 is not fully understood yet.

• The range of age of reported cases of spontaneous coronary artery dissection associated covid-19 in literature were between 35-70 years old.

• Women are more commonly affected with Spontaneous coronary artery dissection than men. However, six of the nine patients (77.7%) with covid-19 associated spontaneous coronary artery dissection were men and (22.3%) were women, that can be due to higher incidence of covid-19 in men.^[6]

• There is no racial predilection for spontaneous coronary artery dissection associated with covid-19.

• Among nine reported cases of covid-19 associated SCAD, there were not any previous risk factors of SCAD.^[6]
• Conventionakl risk factors of spontaneous coronary artery dissection include:^[4]
  • Fibromuscular dysplasia
  • Pregnancy
  • Recurrent pregnancies: multiparity or multigravida
  • Connective tissue disorder: Marfan syndrome, Loeys-Dietz syndrome, Ehler-Danlos syndrome type 4, cystic medial necrosis, alpha-1 antitrypsin deficiency, polycystic kidney disease
  • Systemic inflammatory disease: systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, polyarteritis nodosa, sarcoidosis, Churg-Strauss syndrome, Wegener’s granulomatosis, rheumatoid arthritis, Kawasaki, giant cell arteritis, celiac disease
  • Hormonal therapy: oral contraceptive, estrogen, progesterone, beta-HCG, testosterone, corticosteroids
  • Coronary artery spasm
  • Idiopathic^[4]
  • Strenous exercises (isometric or aerobic activities)
  • Intense emotional stress
  • Labor and delivery
  • Intense Valsalva-type activities (e.g., retching, vomiting, bowel movement, coughing)
  • Recreational drugs (e.g., cocaine, amphetamines, metamphetamines)
  • Intense hormonal therapy (e.g., beta-HCG injections, corticosteroids injections)

• There is no established screening method for SCAD in covid-19 patients. However, high clinical suspicion is needed in patients with manifestation of acute coronary syndrome in the context of covid-19 involvement.

• The majority of covid-19 patients with spontaneous coronary artery dissection are diagnosed with myocardial infarction.
• Early clinical features include STEMI, NSTEMI, or symptoms unrelated to ACS.
• If left untreated, covid-19 patients with SCAD may progress to develop hemodynamic instability, ongoing ischemia, malignant arrhythmia.
• High risk angiographic features of coronary artery include:

  Impaired coronary flow

  Multivessles proximal dissections

  Left main lesion

  Ostial LAD lesion

• Prognosis is dependent on the anatomical extension of coronary arteries dissection, and the survival rate of all nine reported cases in literature was 100%.
• Table bellow shown the clinical characteristics of patients with covid-19 related spontaneous coronary artery dissection:^[6]
  

SCAD can present as acute coronary syndrome and STEMI. The symptoms include:^[7]

• Sudden onset of retrosternal pain chest pain which remains persistent in a COVID-19 seropositive patient or in a patient with recent cough and dyspnea raises suspicion of SCAD.
• The chest pain can radiate to the left arm.
• It can be associated with the following symptoms:^[2]
  • Difficulty breathing
  • Loss of consciousness
  • Nausea and vomiting
  • Diaphoresis

  Cough can be the perscipitant factor in the development of SCAD in covid-19 patients. (10.1097/MCA.0000000000000991)

• There is no specific laboratory finding associated SCAD in covid-19 patients. Howere, Elevated serum troponin level was detected in some cases.

Common ECG findings of COVID-19 associated SCAD include:

• ST segment elevation
• Biphasic T waves
• Inverted T waves

• There are no x-ray findings associated with COVID-19-associated spontaneous coronary artery dissection.
• To view the x-ray finidings on COVID-19, click here.
  

• Left ventricular dysfunction with decreased ejection fraction is seen.
• Akinesia or hypokinesia is seen in the affected territory of the heart.

• To view the CT scan findings on COVID-19, click here.

• To view the MRI findings on COVID-19, click here.
  

• Invasive coronary angiography is the “gold standard” used for the diagnosis of SCAD.

• These imaging modalities show detailed morphology about the intramural lesion in situations when angiographic images are not clear. IVUS is important in the followup of the treatment of SCAD patients.
• OCT is superior for visualizing intimal tears, intraluminal thrombi, false lumens, and intramural hematoma, but it is limited by optical penetration and shadowing, and may not depict the entire depth of the Intramural hematoma.OCT is preferred for imaging SCAD due to its superiority and ease in visualizing intramural hematoma , intimal disruption, and double lumens.^[4]

• Antiplatelet therapy: The role of antiplatelet therapy for SCAD is unknown, but on the basis of the totality of evidence for aspirin in ACS and secondary prevention, along with its low side effect profile, aspirin appears reasonable to use for acute and long-term SCAD management. Clopidogrel for acute management of SCAD patients not treated with stents is of uncertain benefit.^[4]
• Statins: The use of statins for SCAD is controversial. The bulk of data for ACS demonstrates significant benefit with lipid lowering, and statins are routinely recommended post-MI. Because of the uncertainty and the general lack of atherosclerosis in SCAD patients, statins tend to only be administered to patients with pre-existing dyslipidemia.
• Beta-blockers: Beta-blocker is associated with decreased recurrence of SCAD.^[8].There is a general agreement that beta blockers take the most important place in the medical management of SCAD patients. These agents may improve the outcomes of SCAD patients with reducing vascular wall shear stress likewise in patients with aortic dissection.Furthermore, beta blockers should be used in these group of patients in order to reduce complications of myocardial infarction.^[9][10]

• Conservative management should be the first choice if emergent revascularization is not necessary.
• To read more about PCI in Spontaneous Coronary Artery Dissection, Click here.

• Coronary Artery Bypass Graft (CABG) should be considered for patients with left main dissections, extensive dissections involving proximal arteries, or in patients in whom PCI failed or who are not anatomically suitable for PCI.^[4]

• Limiting transmission of the SARS-CoV2 virus while protecting patients and members of healthcare team is a prime goal and cardiac catheterization laboratory protocols must be rapidly evolved to maintain high‐quality and safe cardiovascular care amidst the current pandemic.^[7]
• COVID‐19 testing prior to catheterization procedures where feasible
• Adequate PPE to protect team members in COVID‐19 unknown or pending cases to reduce the risk of unplanned aerosol producing procedures such as intubation or CPR.

• There is no secondary measures for COVID-19-associated spontaneous coronary artery dissection.