Vasculitis is a general term for inflammation of blood vessel walls which can result in stenosis, occlusion, aneurysm or rupture. Although the definition itself may appear initially straightforward, the conditions encompassed within this category are challenging to diagnose and manage due to their rarity, complexity, vascular distribution and multi-organ involvement. A comprehensive knowledge of the possible etiologies is necessary because vasculitis can be primary or secondary to another autoimmune disease or can be associated with other precipitants such as drugs, infections or malignancy.^1-3 Cardiac manifestations in the primary systemic vasculitides occur with variable frequency and can affect any of the cardiac layers.⁴ In a patient with vasculitis, cardiac involvement portends a poor prognosis.⁵ Therefore an understanding of when to consider vasculitis among patients with coronary abnormalities, how to initiate workup, and whom to refer for further evaluation is paramount in managing these patients efficiently and effectively.

The prevalence of coronary arteritis among patients with systemic vasculitis is largely unknown because of the relative rarity of these conditions as well as a lack of standardized prospective imaging studies systematically evaluating the coronary vasculature. Furthermore, involvement of the subepicardial coronary microcirculation may result in symptoms of myocarditis or cardiomyopathy but these blood vessels are below the detection of conventional coronary angiography as well as non-invasive cardiac imaging modalities.⁶ In addition, coronary arteritis may be asymptomatic in some patients and in others, clinically significant coronary artery disease may be secondary to accelerated atherosclerosis rather than active inflammation of the arterial wall.⁷ As such, not all coronary artery disease in patients with vasculitis is due to active, uncontrolled coronary artery inflammation.

The clinical, laboratory and physical examination features of the primary systemic vasculitides are quite diverse and can have significant overlap. The more common findings associated with some of these conditions are highlighted in Table 1. Isolated coronary arteritis without any other systemic symptomatology is considered extremely rare.⁸ However, patients with vasculitis may have non-specific symptoms that are attributed to other etiologies or go unrecognized for several months or years prior to diagnosis; therefore, a high index of suspicion is needed among primary care, cardiology and vascular medicine providers.

Table 1: Highlighted Conditions With Arteritis or Periarteritis of the Coronaries

Clinical features that should raise alarm for the possibility of underlying vasculitis in patients with coronary symptoms include: unexplainable elevated inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) or constitutional symptoms (fever, chills, night sweats, weight loss); asymmetric or absent radial pulses; subclavian or aortic bruits; multifocal visceral infarcts in the absence of embolic etiology; clinically significant coronary artery stenosis in patients ≤40 years of age or in patients without cardiac risk factors. However, because patients with coronary arteritis may present acutely with cardiac ischemic symptoms, it may not be feasible in such circumstances to investigate for symptoms suggestive of systemic vasculitis prior to proceeding to emergent coronary reperfusion.

Although there are no specific features on conventional coronary angiography that are diagnostic of coronary arteritis certain features may be suggestive. For example, tapered smooth narrowing has been described in cases of giant cell arteritis (GCA) with coronary involvement.⁹ In Takayasu's arteritis, three main types of coronary lesions have been described from angiographic and histologic analysis: Type 1, stenosis or occlusion of the ostia or proximal segments; Type 2, diffuse or focal coronary arteritis that may extend diffusely to all epicardial branches or may involve focal segments (so-called skip lesions); and Type 3, coronary aneurysms.¹⁰ Among patients with coronary lesions, Type 1 is the most commonly observed (60-80%), whereas Type 2 is less frequent (10-20%) and Type 3 is considered rare (0-5%).^10-12 Large aneurysms should raise suspicion for prior damage to the epicardial coronary arteries from Kawasaki disease that failed to regress or suggests the possibility of polyarteritis nodosa (PAN).¹³ The latter should be considered particularly if there are multifocal aneurysms with a "beads on a string" or nodular appearance.⁵ Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and Bechet's disease can have any combination of the aforementioned findings.¹⁴

While evaluation of the lumen with conventional coronary angiography aids in understanding the coronary anatomical abnormalities, it is insufficient to assess for inflammation or thickening of the coronary artery wall or to identify extra-coronary arterial abnormalities. Since isolated coronary arteritis is rarely seen without other arterial or systemic findings present, computed tomography (CT) or magnetic resonance (MR) angiography should be considered in patients with suspicion for, or diagnosis of, coronary arteritis. In patients with large (GCA and Takayasu's arteritis), medium (PAN) or variable (Behcet's disease) vessel vasculitis, evaluation with non-invasive angiography of the chest, abdomen, and pelvis is strongly recommended. For patients with concern for small vessel vasculitis (i.e., ANCA-associated), a CT chest with and without contrast to assess for pulmonary parenchymal changes and a cardiac MRI to assess for non-coronary abnormalities (pericarditis, myocarditis) is advised. The above modalities are also beneficial in assessing for diseases that result in luminal narrowing from periarterial soft tissue thickening or extrinsic compression as can be seen in Immunoglobuin G4 (IgG4)-related disease or more rare conditions such as Erdheim-Chester disease.^15-16 Positron emission tomography (PET) can assist in evaluating for hypermetabolism in the large vessels (aorta and first order branches) which may aid in diagnosis of GCA and Takayasu's arteritis but has lower utility for assessing inflammation in the coronaries and poor sensitivity for medium or small vessel vasculitis. Nuclear medicine myocardial perfusion studies can assist in determining myocardial viability but cannot distinguish between reduced perfusion from vasculitic or atherosclerotic etiology.¹⁷ As such perfusion studies are of less benefit in the diagnosis of coronary arteritis but may provide useful information in determining if coronary artery bypass grafting would be beneficial and if so what targets should be considered.

Data regarding interventions in patients with coronary arteritis, regardless of the etiology, are limited to case reports and retrospective cohort studies. To date no prospective randomized trial has been performed to determine the optimal timing or revascularization method. While limited in sample size, the most comprehensive outcome data has been generated in patients with Takayasu's arteritis. A recent meta-analysis performed comparing revascularization type based on lesion location noted that coronary restenosis/failure occurred more often with endovascular intervention than with open surgical approach (Odds ratio 7.38, 95% CI 2.36-23.10, p = 0.01).¹⁸ While conventional coronary artery bypass grafting, patch angioplasty and transaortic coronary ostial endarterectomy have all been performed with reasonable outcomes in patients with Takayasu's arteritis, no study has shown definitive benefit of one approach over the other. As such, decisions regarding approach should be tailored to the patient based on the location(s) and extent of coronary artery lesion(s). In addition, the distribution and severity of aortic and arch vessel inflammation must be considered when determining the suitable location of proximal graft anastomosis. Special attention to the choice of graft conduit also needs to be carefully weighed in patients with Takayasu's arteritis as avoidance of internal mammary artery grafts may be necessary if there is presence of subclavian or innominate artery involvement.¹⁹ In general, observational studies suggest that surgery should be avoided during the active stage of inflammation to increase the likelihood of successful outcome.²⁰ In circumstances where patients are not deemed a surgical candidate and percutaneous coronary intervention is considered necessary, limited data suggests that drug-eluting stents may have less risk of restenosis compared to bare metal stents.²¹ Regardless of whether endovascular or surgical approach is pursued, ongoing medical treatment of the underlying vasculitis with immunosuppressive therapy is essential.

The individual treatment regimens for systemic vasculitis are beyond the scope of this review but general considerations are noted in Table 1. If the diagnosis of vasculitis is suspected or confirmed, referral to a rheumatologist with expertise in managing vasculitis is requisite to assist in the appropriate workup, treatment, and monitoring of response to therapy. If surgery is deemed necessary in high-risk patients or those with complex anatomical abnormalities, such procedures should be performed at a high-volume center with experience managing such conditions and often requires a multi-disciplinary approach from cardiology, thoracic surgery, and rheumatology.

In summary, vasculitis of the coronary arteries is uncommon but can be life-threatening. A knowledge of the clinical characteristics associated with the more common vasculitides, suggestive findings on angiography and appropriate complementary imaging can aid in the efficient evaluation and diagnosis. Further research is needed to provide guidance on the best long-term approaches for management of clinically significant coronary stenosis.

References

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3. Belizna CC, Hamidou MA, Levesque H, Guillevin L, Shoenfeld Y. Infection and vasculitis. Rheumatology 2009;48:475-82.
4. Miloslavsky E, Unizony S. The heart in vasculitis. Rheum Dis Clin North Am 2014;40:11-26.
5. Pagnoux C, Guillevin L. Cardiac involvement in small and medium-sized vessel vasculitides. Lupus 2005;14:718-22.
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8. Noma M, Sugihara M, Kikuchi Y. Isolated coronary ostial stenosis in Takayasu's arteritis: case report and review of the literature. Angiology 1993;44:839-44.
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10. Matsubara O, Kuwata T, Nemoto T, Kasuga T, Numano F. Coronary artery lesions in Takayasu arteritis: pathological considerations. Heart Vessels Suppl 1992;7:26-31.
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13. Friedman KG, Gauvreau K, Hamaoka-Okamoto A, et al. Coronary artery aneurysms in Kawasaki disease: risk factors for progressive disease and adverse cardiac events in the US population. J Am Heart Assoc 2016;5:e003289.
14. Demirelli S, Degirmenchi H, Inci S, Arisoy A. Cardiac manifestations in Behcet's disease. Intractable Rare Dis Res 2015;4:70-5.
15. Guo Y, Ansdell D, Brouha S, Yen A. Coronary periarteritis in a patietn with multi-organ IgG4-related disease. J Radiol Case Rep 2015;9:1-17.
16. Nicolazzi MA, Carnicelli A, Fuorlo M, Favuzzi AM, Landolfi R. Cardiovascular involvement in Erdheim-Chester disease: a case report and review of the literature. Medicine 2015;94:e1365.
17. Hashimoto Y, Numano F, Maruyama Y, et al. Thallium-201 stress scintigraphy in Takayasu arteritis. Am J Cardiol 1991;67:879-82.
18. Jung JH, Lee YH, Song GG, Jeong HS, Kim JH, Choi SJ. Endovascular versus open surgical intervention in patients with Takayasu's arteritis: a meta-analysis. Eur J Vasc Endovasc Surg 2018;55:888-99.
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Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pericardial Disease, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Heart Failure and Cardiac Biomarkers, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Computed Tomography, Magnetic Resonance Imaging, Nuclear Imaging, Chronic Angina

Keywords: Angioplasty, Antibodies, Antineutrophil Cytoplasmic, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Arteritis, Aorta, Atherosclerosis, Blood Sedimentation, Brachiocephalic Trunk, Constriction, Pathologic, Chills, Coronary Aneurysm, Coronary Angiography, Coronary Artery Disease, Coronary Artery Bypass, Coronary Restenosis, Coronary Vessels, Coronary Stenosis, C-Reactive Protein, Drug-Eluting Stents, Erdheim-Chester Disease, Giant Cell Arteritis, Endarterectomy, Inflammation, Diabetes Mellitus, Type 2, Magnetic Resonance Spectroscopy, Magnetic Resonance Imaging, Immunoglobulin G, Mammary Arteries, Mucocutaneous Lymph Node Syndrome, Myocardial Reperfusion, Myocarditis, Neoplasms, Microcirculation, Odds Ratio, Percutaneous Coronary Intervention, Pericarditis, Nuclear Medicine, Positron-Emission Tomography, Polyarteritis Nodosa, Physical Examination, Prognosis, Prospective Studies, Primary Health Care, Referral and Consultation, Retrospective Studies, Rheumatology, Risk Factors, Takayasu Arteritis, Thoracic Surgery, Systemic Vasculitis, Tomography, X-Ray Computed, Weight Loss

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