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Page 2 of 14 Barioli et al. Vessel Plus 2024;8:13 https://dx.doi.org/10.20517/2574-1209.2023.68

[1]
vessel length, while the term ectasia refers to more diffuse dilations . Aneurysms are defined as giant if their
[2]
diameter is > 8 mm or when it is > 4 times the reference vessel diameter .
[3]
The incidence of the disease ranges between 0.3% and 5% . This wide range reflects the different reporting
methods, where the highest incidences are found when CAA and CAE are considered together. In recent
studies, the incidence of true CAA appears to be less than 1% .
[4-6]
All three coronary arteries may be affected by the disease, but in most cases, only one major coronary artery
is involved. The right coronary artery is the most frequently affected (40%), followed by the left anterior
descending (32%) and the circumflex artery (23%). Aneurysms of the left main coronary artery have rarely
been reported . The disease mainly involves the proximal segments of the coronary tree and is often
[1]
associated with coronary artery disease (CAD). Men appear to have higher incidence rates of CAAs than
women (2.2% vs. 0.5%, respectively) .
[7]
Classifications
Aneurysmal coronary artery disease can be classified in different ways. The etiopathogenetic classification
[8]
identifies atherosclerotic, inflammatory, and non-inflammatory mechanisms leading to CAA formation .
From an anatomical perspective, aneurysms can be classified according to the integrity of the vascular wall.
We can therefore distinguish true aneurysms when the three layers (intima, media, and adventitia) of the
vessel wall are preserved, and false aneurysms or pseudoaneurysms, which are characterized by loss of one
or two layers. According to morphology, aneurysms can also be classified into saccular, when the transverse
diameter exceeds the longitudinal diameter, and fusiform in the opposite case. The former most frequently
follow proximal stenosis, are often multifocal, and are more likely to present with thrombosis or rupture. In
contrast, fusiform aneurysms tend to be bilateral, are associated with aneurysms of the abdominal aorta and
cerebral circulation and less frequently with obstructive CAD [9,10] . The classification proposed by
Markis et al. distinguishes four types of coronary aneurysms based on the coronary distribution of dilations:
Type 1, when ectasia is present in two or three vessels; Type 2, when ectasia involves only one vessel and is
associated with localized disease in a second vessel; Type 3, when dilation affects only one vessel; and Type
[11]
4, when the ectasia is localized or segmental . Classifications of aneurysmal dilatations and ectasia are
shown in Figure 1.

Pathogenesis, etiology and natural history of the disease
The etiopathogenesis of coronary aneurysms is poorly understood and remains a matter of debate. A strong
association between aneurysmal disease and CAD has been observed in adults, suggesting a possible
common underlying etiology [10,12] . In addition, a partly overlapping genetic predisposition to both
aneurysmal disease and atherosclerosis has been observed, as they share an altered proliferative phenotype
that promotes adverse vascular remodeling associated with variants on chromosome 9p21.3 .
[9]
Kawasaki disease (KD), a rare inflammatory condition that can result in vasculitis of the coronary arteries, is
the leading cause of CAAs in childhood [9,13] . Ten to fifteen percent of KD patients develop CAAs during the
acute phase of the disease. Inflammatory response mediated by cytokines such as TNF-alpha leads to
increased levels of matrix metalloproteinase (MMP) and decreased levels of their tissue-specific inhibitors
(TIMP) and thus drives the degradation of the vessel wall-originating CAAs. CAAs have also been
associated with other inflammatory diseases (e.g., Takayasu arteritis), collagenosis (e.g., scleroderma heart
disease, polyarteritis nodosa, systemic lupus erythematosus), and connective tissue disorders (e.g., Marfan
syndrome, Ehlers-Danlos disease).