Rare Manifestation of COVID-19 Resulting in Coronary Artery Vasculitis

We present the case of a 59-year-old African American female with end-stage renal disease (ESRD) who presented to the emergency department with chest discomfort. She had a coronary angiogram six months ago that showed no occlusive epicardial coronary artery disease. She had elevated troponin I levels and new regional wall motion abnormalities on echocardiogram. Her SARS-CoV-2 returned positive. After a multidisciplinary team approach, she underwent another coronary angiogram that showed new severe multivessel ostial lesions and a left main coronary artery aneurysm. COVID-19-related coronary artery vasculitis was suspected based on her clinical presentation, angiogram findings, and negative autoimmune workup. The patient underwent successful coronary artery bypass grafting and recovered without complications.


Introduction
Since December 2019, there has been growing body of research on coronavirus disease 2019 (COVID-19) and incidence of cardiac complications, including ST-elevation myocardial infarction (STEMI), coronary artery dissection, and myocarditis.A postmortem study revealed histologic evidence of left ventricular myocardial necrosis in up to 35% of patients who died of COVID-19 [1].The proposed pathophysiologic mechanisms of COVID-19-induced acute cardiac syndrome include immune dysregulation, cytokineand complement-mediated vascular wall injury, and microvascular thrombosis [2].Coronary arteritis, characterized by coronary stenosis or aneurysm, is typically associated with systemic primary vasculitides like Takayasu Arteritis, polyarteritis nodosa, or Kawasaki disease (KD) [3].
To the best of our knowledge, there are no reported cases of COVID-19-related vasculitis of the coronary arteries.Moreover, only three cases of COVID-19-associated coronary artery aneurysm (CAA) in adults have been reported, and none of them had left main coronary artery (LMCA) involvement [4][5][6].Herein, we report a case of left main cor-onary aneurysm along with new, rapid onset multivessel ostial coronary artery disease (CAD) in an adult end-stage renal disease (ESRD) patient in the setting of COVID-19 infection.

Case Presentation
A 59-year-old African American female with a past medical history of hypertension, hyperlipidemia, obstructive sleep apnea, and ESRD on hemodialysis presented to the emergency department with pressure-like chest discomfort that initially occurred at rest and resolved spontaneously.The pain recurred on the morning of admission and increased in intensity as she started walking.The progression in her symptoms caused her to seek medical evaluation.She had no known medical history of CAD, congestive heart failure, cardiac or peripheral stents, or stroke.She denied associated shortness of breath, nausea, diaphoresis, palpitations, or syncope.She was a non-smoker and denied illicit substance use.She was being evaluated for kidney transplant, and per preoperative evaluation protocol, she had an invasive coronary angiogram six months ago that showed no occlusive epicardial CAD (Figure 1, July 2021, and Video 1).
On physical examination, she was afebrile, blood pressure was 113/83 mmHg, heart rate was 67 beats per minute, and respiratory rate was 16 breaths per minute.Her body mass index was 39.4 kg/m 2 .Physical examination was unremarkable.
Her initial electrocardiogram (ECG) showed a normal sinus rhythm with no ischemic ST-T wave changes, unchanged compared to prior ECG six months ago.Her complete blood count showed mild leukocytosis (11 4 × 10 9 /L) and no anemia or thrombocytopenia.Her blood chemistry showed a sodium of 135 mmol/L, potassium 4.2 mmol/L, bicarbonate 31 mmol/L, BUN 56 mg/dL, creatinine 8.7 μmol/ L, calcium 10.2 mmol/L, phosphorus 4.2 mmol/L, and magnesium 2.0 mmol/L.Her first troponin I was 0.15 ng/mL (normal < 0 03 ng/mL).Second and third troponins I checked at 2-and 8-hour intervals were 0.52 ng/mL and 0.63 ng/mL, respectively.Her chest X-ray was negative for any pulmonary infiltrates.
At admission, she tested positive for SARS-CoV-2.She did recall exposure to a COVID-19 patient during a hemodialysis session one week ago.Of note, she received COVID-19 immunization booster two months ago.She did not exhibit any classic respiratory or systemic symptoms associated with COVID-19.
She also underwent a thromboembolic workup.Her Ddimer returned negative, and she underwent computed tomography angiogram of her chest and ultrasound Doppler of both lower extremities, both tests returning negative for pulmonary embolism and deep vein thrombosis, respectively.
Transthoracic echocardiogram showed left ventricular ejection fraction (LVEF) 50-55% with new regional wall motion abnormalities in the anterior, apical, and inferior walls suggestive of multivessel territory ischemia.She was diagnosed and appropriately treated for non-ST-elevation myocardial infarction and underwent repeat coronary angiogram under strict COVID-19 isolation precautions after multidisciplinary team discussion.

Treatment
Given ongoing chest pain and borderline hypotension, patient underwent intra-aortic balloon pump placement in the cardiac catheterization laboratory and was transferred to cardiac intensive care unit.She was evaluated by cardiothoracic surgery and underwent coronary artery bypass grafting (CABG) two days later.She received a left internal mammary artery (LIMA) graft to her LAD and a saphenous vein graft (SVG) to the second obtuse marginal (OM2) branch.The posterior descending artery was an acceptable target but was not bypassed due to a paucity of conduit.Radial arteries were not a viable option due to renal failure and fistulas.Right IMA was not used due to patient's significant risk for sternal wound complications.Her bilateral below the knee lower extremity veins had old, healed wounds preventing their use.Saphenous vein was aneurysmal in several segments and 8 mm in size creating a significant size discrepancy between her coronary arteries and the vein conduit.Only one portion of the saphenous vein was viable and sufficient to bypass the left circumflex system.The distal segment of the IMA was sent for a histopathologic examination due to suspicion of vasculitis.Histopathology of LIMA showed normal arterial architecture without any pathologic changes suggestive of vasculitis.Coronary artery samples (LAD or LCX) were not sent for pathology by the operating surgeon, recognizing the challenges of preserving small coronary vessel segments during surgery and concern for obtaining adequate tissue for an accurate histopathologic examination.She fared well postoperatively and was discharged to a rehabilitation facility.
She remained asymptomatic at one-year follow-up; however, nuclear stress test (done for prerenal transplant evaluation) showed a new medium-sized anterior myocardial wall defect with normal poststress ejection fraction of 60%.Considering the patient's lack of symptoms and preserved ejection fraction, the clinical concern for myocarditis or cardiomyopathy was low.Nevertheless, given her history and 3 Case Reports in Cardiology upcoming renal transplant, repeat coronary angiography was (14 months after index hospitalization) for a assessment.It revealed a persistent left main CAA and widely patent LIMA to LAD and SVG to OM2 grafts (Figure 3 and Video 3).The native LAD and LCX were both 100% occluded, and RCA had unchanged ostial disease.

Discussion
The presence of multiple coronary ostial lesions and the CAA suggests a vasculitic process [7].The histopathological evaluation of coronary artery vasculitis can be challenging due to logistical difficulties in obtaining a coronary artery biopsy [8].Biopsy of adjacent vasculature, such as the IMA, may appear normal but can still hold prognostic value when harvested for CABG, as demonstrated in our patient's case.Thus, diagnosis of coronary artery vasculitis is primarily based on a combination of clinical presentation, elevated inflammatory markers, multimodality imaging, and coronary angiography findings [8].Recently, KD-like coronary vasculitis has been reported in adult and pediatric patients with COVID-19 [4].Interestingly, KD-like vasculitis has been observed in patients without active COVID-19 pneu-monia [9].Similarly, our patient did not have any acute viral illness-like symptoms or evidence of COVID-19 pneumonia which makes her presentation likely related to an underlying immunologic process related to COVID-19 that is supported by markedly elevated inflammatory markers.
The exact mechanism of CAAs and ostial lesions in COVID-19 is unknown, but possible mechanisms include either virus-triggered immune response or direct viral damage to the coronary vasculature leading to accelerated atherosclerosis, localized collagenase activation in atheroma, endothelial dysfunction, and hypercoagulability [10].Our patient did not have any manifestation of primary vasculitis.Her ESRD resulted from uncontrolled hypertension, and she did not have chronic symptoms that might point to vasculitis, including skin rash, chronic anemia, thrombocytopenia, or chronically elevated inflammatory markers.Patients with ESRD are at higher risk for atherosclerosis, the most common cause of CAA.However, coincidentally, our patient had a normal coronary angiogram six months ago (as a part of prerenal transplant workup).This, in addition to positive COVID-19 test and symptom onset one week after COVID-19 exposure, suggested that COVID-19-related coronary vasculitis was the likely diagnosis.Patients with ESRD may  Case Reports in Cardiology is characterized as 1.5-fold localized dilation of the coronary artery compared to the nearby normal coronary segments.Common causes of CAA include advanced atherosclerosis, KD and other rheumatologic processes, mycotic infections, and congenital lesions.The management of CAA is usually based on the concomitant presence of obstructive coronary disease, the location and size of the aneurysm, aneurysmal expansion, and associated infectious etiologies.Treatment options include surgical, percutaneous, or medical interventions.Our literature review yielded only three other documented case reports of COVID-19-related CAA.Table 1 summarizes the data on patient characteristics, clinical features, diagnostic studies, and management of CAA in the context of COVID-19.

Conclusion
We report a rare case of accelerated multivessel CAD and new left main CAA in the setting of COVID-19 infection due to presumed COVID-19-related vasculitis that was confined to the epicardial coronary bed for unclear reasons.Patients with ESRD may be at increased risk for accelerated atherosclerosis and immune-related coronary vascular manifestations.

Ethical Approval
Our research has adhered to the relevant ethical guidelines.

Figure 1 :
Figure 1: Invasive coronary angiograms showing patent coronary arteries in July 2021 and multivessel ostial coronary artery disease and left main artery aneurysm in January 2022.

Figure 3 :
Figure 3: Follow-up coronary and bypass angiogram showing persistent left main artery aneurysm and patent left internal mammary artery to left anterior descending artery graft and patent saphenous vein to obtuse marginal artery graft.

Table 1 :
Comparison with the prior reported of coronary artery aneurysm related to COVID-19.