Coronary artery vasculitis: a review of current literature

Vasculitis is a general term that encompasses a group of disorders characterised by inflammation of blood vessels [1]. The majority of vasculitic disorders affect multiple organ systems and therefore can have a myriad of presentations necessitating the need for a high index of clinical suspicion. Whilst cardiac manifestations of systemic vasculitis are rarely seen in practice, their presence often serve as a poor prognostic factor [2]. Cardiac manifestations that are frequently described in literature include pericarditis, myocarditis, valvular heart disease and less commonly, coronary artery vasculitis (CAV) [3].

CAV represent an important differential diagnoses to consider, in younger patients with unexplained acute coronary syndromes (ACS) or congestive cardiac failure, especially in the setting of a known primary or secondary vasculitis [4]. These events may be principal manifestations in the younger population, who do not have traditional Framingham cardiovascular risk factors [5]. A high index of clinical suspicion is required for appropriate work-up, especially as initial investigative modalities carry variable levels of diagnostic sensitivity or specificity.

The most frequently described aetiologies of CAV include Polyarteritis Nodosa (PAN), Kawasaki’s Disease (KD), Takayasu’s Arteritis (TA) and Giant Cell Arteritis (GCA) [6]. In lieu of the high morbidity and mortality associated with CAV, early diagnosis and appropriate treatment are crucial to curb the trajectory of the unique disease process. This requires integration of appropriate cardiac-specific pharmacotherapy, immunosuppressive agents and interventional therapies [2‐7].

There remains a paucity of data on the global epidemiology of CAV, and this largely stems from various factors including under-diagnosis, low incidence rates and variable levels of sensitivity and specificity amongst current diagnostic tools [2]. Primary medium-vessel vasculitides such as PAN (incidence rate 4–10 per million) and KD (incidence rate 2 per million), may have coronary involvement of up to 50% and 20% respectively [2, 8] See Table 1. Furthermore, large vessel vasculitides such as TA and GCA with an estimated annual incidence of 1–2 per million and 1–3 per million respectively, also have contrasting frequencies of coronary involvement (10–30% and < 1% respectively). Other rarer diagnoses such as Erdheim Chester Disease, whilst described less than a hundred times in literature, are associated with high rates of coronary involvement (> 50% in index cases) [2, 9, 10].

The clinical presentation of CAV is complex, reflective of its unique underlying pathophysiology. The presentation of CAV may manifest with typical angina, acute myocardial infarction (AMI), atrial and ventricular arrhythmias, conduction disturbances or cardiac failure [3]. The pathogenesis that belies atherosclerotic coronary artery disease (CAD) compared to CAV lends to different treatment approaches and thus it is crucial to identify the classic features of implicative vasculitides. For example, patients with TA have a high burden of constitutional symptoms, limb claudication and cerebrovascular involvement [11]. Contrastingly in GCA, patients will often have concomitant headaches, jaw claudication and acute visual loss [2]. In KD, patients often have associated conjunctivitis, lymphadenopathy, rash and hyperaemia of the lips and extremities [12]. Finally, in PAN, patients can typically present with abdominal pain, livedo reticularis or peripheral neuropathy [2]. It is therefore extremely important to perform a complete multi-organ assessment in these patients, to decipher the underlying aetiology for targeted therapy.

The pathogenesis of CAV is complex and involves an interplay of many host factors including immune-mediated inflammation and auto-antibody dependant processes [13]. Importantly, the overproduction of pro-inflammatory cytokines, specifically interferon-gamma (IFN-γ), Tumour necrosis factor-alpha (TNF-α) and Th-1 interleukins have been observed in such vasculitic processes [14]. Each vasculitis presents with varying histopathological findings on biopsy. PAN associated CAV presents with pan-arteritis with intramural, perivascular lymphocyte and macrophage infiltration, with a resultant destructive coronary vasculitis and classic fibrinoid necrosis [15]. TA and GCA patients show evidence of intimal hyperplasia, granulomatous arteritis, and coronary atherosclerosis. In patients with KD, there is an infiltration of the arterial wall with a multi-cellular infiltrate with subsequent necrosis of the internal elastic lamina [15, 16]. Whilst the phenotypic result is frequently similar amongst these pathologies, the underlying pathogenesis is different and requires consideration of varying therapeutic approaches. As such, chronic inflammation results in scar tissue formation, necrosis and may result in coronary artery aneurysmal (CAA) formation [14]. CAA’s are a rare entity that occurs secondary to localised dilatation of a coronary artery from vessel wall weakening [17]. The underlying pathology stems from overactivity of the metalloproteinases and metalloelastases which primarily degrade elastin and collagen [18]. Arterial Thrombosess (i.e. coronary artery thrombosis) may also occur in CAV, possibly leading to vascular occlusion and consequently myocardial oschaemia, for instance in KD, where CAA formation may predispose to this mechanism [19, 20]. CAV also increases predisposition to typical CAD with resultant myocardial ischaemia, through atherosclerotic inflammatory changes [21]. There are several mechanisms involved in this process; namely coronary artery inflammation and extension from adjacent aortitis [22]. Furthermore, the development of coronary artery embolism from aortic valvulitis, complicating CAV, has also been described in the literature [23].

Prompt diagnosis and early institution of treatment lead to improved patient outcomes. This is of key importance as a large proportion of cardiac manifestations of vasculitis can be clinically silent during the early stages of the disease process, along with logistical difficulty in conducting a coronary artery biopsy for histo-pathological assessment [24]. Important laboratory investigations, other than baseline laboratory investigations, include elevated inflammatory markers such as C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), high sensitivity troponin assay and an extended vasculitis panel [25]. In addition to laboratory investigations, multi-modality imaging has a growing role in the diagnostics of CAV, despite their limitations. These investigations should be performed in patients who present with acute coronary syndrome on the background of known or suspected vasculitis.

The management of CAV is largely predicated on accurate diagnostics and the identification of the implicative pathology. The decision on appropriate treatment is dependent on the degree of cardiac involvement, namely of the myocardium, epicardium, endocardium and conducting system [8]. The majority of current literature has focused on four disease processes; namely KD, TA, PAN, and GCA. See Fig. 2: Illustration.

While CAV and its sequelae portend a poor prognosis, prompt diagnosis and early institution of therapy can result in higher survival rates. The role of multi-modality imaging as a non-invasive diagnostic tool is pivotal in this disease entity, and its role in conjunction with emerging medical, interventional and surgical therapies continues to grow. Further larger-scale studies are required to deduce the optimal approach for this niche population, thereby facilitating more concrete treatment paradigms to improve patient outcomes.