Acute Myocardial Infarction with Multiple Giant Coronary Artery Aneurysms in a Juvenile with Kawasaki Disease

Myocardial infarction due to atherosclerosis is predominantly observed in older patients with classical cardiovascular risk factors. In contrast, the occurrence of MI in younger individuals remains under-researched and presents a distinct risk profile characterized by fewer traditional cardiovascular risk factors compared to the older population. What’s more, as adolescents or young adults are predisposed to developing collateral circulation, their symptoms and signs of myocardial ischemia may be masked and sometimes even ignored. However, the risk of adverse cardiovascular events, such as MI, heart dysfunction and sudden cardiac death, is persistent. In other words, these young individuals require longer and more consistent follow-up than adults throughout their lifetime, which places a greater socioeconomic burden. While plaque rupture continues to be the most common etiology of MI across all age groups, younger individuals exhibit a higher prevalence of rare causes and syndromes [7]. This case aims to highlight an uncommon etiology of MI in juveniles—coronary artery aneurysms resulting from KD in childhood—thereby drawing attention to the need for further investigation into early-onset cardiac events due to these unique risk factors. When a patient develops significant coronary artery ectasia or aneurysm formation at a young age and with minimal risk factors for atherosclerotic coronary artery disease (CAD), KD should be speculated as a potential diagnosis [8]. Kawasaki disease, also known as mucocutaneous lymph node syndrome, has been reported in more than 60 countries and regions worldwide since first reported by doctors in Japan in 1967. This disease is most prevalent in Japan, followed by Korea, and its incidence has been increasing recently in various countries around the world[9]. Though the etiology and pathogenesis of KD remain unclear, it is generally considered to be a self-limiting disease with acute systemic vasculitis, primarily affecting small and mediun-sized arteries, such as the coronary arteries. KD predominantly, but not exclusively, affects children aged 6 months to 5 years. In developed countries, KD with coronary artery lesions, including coronary artery stenosis, dilation and the formation of CAAs, has now surpassed rheumatic fever as the leading cause of acquired heart disease in children [10]. It has been reported that the familial history of CVD, including hypertension, dyslipidemia, myocardial infarction, stroke and diabetes, is associated with increased risk of KD for newborns [11], which seems to be the only risk factor for our patient to suffer from KD. Coronary artery aneurysm represents the most common and hazardous late complication of KD, typically manifesting several years post-onset. Notably, up to 25% of untreated KD juveniles develop coronary aneurysms. Even with treatment, the incidence of persistent aneurysms remains between 3% and 5% [12]. The most frequent sites of aneurysm formation, in descending order of prevalence, are the proximal LAD, proximal RCA, left main coronary artery, LCX, and, finally, the distal RCA. [13]. These young patients with persistent coronary ectasia face a lifelong risk of thrombosis and the development of stenotic lesions during vascular remodeling, which can lead to myocardial ischemia, infarction or even cardiac death. As children with KD-induced CAAs age, the risk of acute ischemic events escalates, particularly in those with large or giant aneurysms [14], as observed in our patient. Giant CAAs are relatively rare, with an incidence of only 0.02% in patients with coronary aneurysms [15]. Notably, cases involving simultaneous multiple giant CAAs in two or more major coronary arteries are exceedingly uncommon. Our patient presents a rare instance of large CAAs, with dimensions of approximately 9 mm in LAD and more than 12 mm in LCX. This case underscores the diagnostic and therapeutic challenges associated with giant CAAs in KD patients. According to Z-score and diameter, the aneurysms are categorised as small (2.5 ≤ Z score < 5), medium (5 ≤ Z score < 10, and absolute dimension <8 mm), and giant (absolute dimension ≥ 8 mm or Z score ≥ 10). Large or giant CAAs do not “resolve”, “regress”, or “remodel”, and while they rarely rupture, they almost always contain thrombi, which can calcify and become occlusive [4,16,17]. Consequently, complications such as stenotic lesions, thrombosis, and major cardiac events, including MI, are more likely to occur in giant CAAs [18]. A long-term study involving 1215 KD patients found that 64(5%) developed giant CAAs. Subgroup analysis revealed that 3(5%) of these cases showed regression, 30(47%) experienced occlusion or stenosis and 15 (23%) suffered from MI [19]. Therefore, it is evident that the larger the aneurysm, the poorer the prognosis. This case was a typical example of multiple giant CAAs in more than one major coronary artery and sudden thrombotic occlusion of an aneurysm precipitating MI. ECG, echocardiography, computed tomographic angiography (CTA), magnetic resonance imaging (MRI) and CAG are the main methods to examine coronary arteries. Among these, CAG is the most invasive imaging examination for KD and is the gold standard for evaluating the severity, prognostic prediction and therapeutic indications of CAAs [4,16]. CAG provides detailed image assessment of the coronary artery lumen and characteristic angiographic findings suggestive of KD, such as marked proximal ectasia followed by a sudden transition to an angiographically normal distal segment. Another pathognomonic feature is the presence of calcification along the arterial wall at sites where former aneurysms have been remodeled [8]. A better estimation of luminal size and arterial wall changes can be achieved through intravascular ultrasound (IVUS), which aids in evaluating the severity of intimal hyperplasia, as well as detecting thrombi, calcification, and luminal narrowing[20]. In our case, the young boy underwent CAG twice. Initially, an ECG showed acute inferior myocardial infarction and then emergency CAG revealed distinct ectasias in all three coronary arteries. During the second CAG, combined with IVUS, we confirmed the presence of giant CAAs in both the LAD and LCX. Given the typical ECG results, elevated myocardial injury markers, severe hemodynamic disorder, and most importantly, the features of coronary lesions, it was retrospectively further clarified that the definitive diagnosis was MI secondary to giant coronary aneurysms associated with KD. Patients diagnosed with giant CAAs are recommended to undergo long-term follow-up assessments with echocardiography frequently and possibly angiography to monitor for increases in luminal dimensions, thrombotic risk, and signs of ventricular dysfunction, enabling timely intervention [4]. Unfortunately, this patient could not provide detailed echocardiogram results of the coronary arteries since his last MI. The standard medical protocol for CAA, particularly giant ones, remains inadequately addressed. Despite the absence of fixed guidelines for managing giant CAAs in acute settings, it is imperative to prevent further dilatation and even rupture, as well as thrombus formation. Several case reports have documented the successful management of patients with super-giant CAAs during the acute phase by stabilizing hemodynamic status and maintaining anticoagulation [21]. According to the Japanese Circulation Society guideline, patients with KD who develop angina or MI are treated similarly to those with such conditions due to other causes [16]. For KD patients with large or giant aneurysms (≥8 mm or Z score ≥ 10) and a high risk of coronary artery thrombosis, available therapeutic options include double antiplatelet agents such as aspirin and clopidogrel, as well as anticoagulants like warfarin or LWMH [20,22], which also helps prevent severe cardiovascular complications at the early stage. What’s more, the combination of warfarin and aspirin is known to have been associated with high cardiac-event-free survival in patients with giant CAA caused by KD [23]. However, in our case, frequent massive epistaxis indicated the patient’s intolerance to aspirin. Finally, we chose clopidogrel instead of aspirin, which is also consistent with the current guidelines for antithrombotic medication[4]. Hemodynamic forces play a crucial role in the further dilation of aneurysms, necessitating strict control of blood pressure and heart rate through β-blockers and other antihypertensive medications. The AHA scientific statement incorporates β-blocking agents into the long-term management algorithm for KD patients with large or giant aneurysms. It was reported that KD is associated with accelerated atherosclerosis and early-onset heart failure [4,24]. For the juvenile in our case, there was no history of diabetes or hypertension, he had never smoked, maintained a normal body mass index (BMI) of 22.2, and his lipid panel was within normal limits. A familial history of CVD was considered to be the only risk factor. However, it is still crucial for him to accept the early intervention and aggressive medical management of CAD, even without a typical risk profile. Consequently, empirical treatment with low-dose statins is recommended for these KD patients with past or current aneurysms regardless of age or sex, on account of the pleiotropic effects of statins on inflammation, endothelial function, oxidative stress, platelet aggregation, coagulation, and fibrinolysis. Effective medical treatment of angina pectoris and heart failure is also beneficial for our patients [4]. For patients with coexisting obstructive lesions and ongoing ischemia, percutaneous and/or surgical coronary revascularization are available options [20]. However, percutaneous coronary intervention (PCI) and stent placement have limited roles in managing ectatic infarction-related arteries compared to non-ectatic coronary disease [25]. It is always too difficult to select an appropriate scaffold size to match the aneurysmal coronary lesions. Such patients are also at high risk for stent malapposition, evagination or migration in the future [26]. Thus, in our case, thrombolytic therapy with urokinase-type plasminogen activator was administered for occlusive coronary artery thrombosis to re-establish blood flow as rapidly as possible. Moreover, the long-term prognosis of CABG in young KD patients with severe coronary lesions remains uncertain [27]. At present, there is not a standard guidline on the selection of revascularization methods against thrombosis caused by CAA. According to our case, it may be beneficial for such patients to accept early thrombolytic therapy as soon as possible. Fortunately, during the patient’s second CAG in our hospital, no severe stenosis or total occlusion was found in any of the three coronary arteries, and the TIMI blood flow level was adequate. Hence, neither PCI nor CABG is urgently required. Current guidelines about CAAs associated with KD recommend that it is reasonable to stratify patients according to their risk of myocardial ischemia related to thrombosis and stenosis, which mainly depends on the extent of maximal involvement in coronary arteries, together with the evolution of coronary abnormalities over time [4]. The risk stratification varies as a result of follow-up changes. Therefore, it is essential to conduct close follow-up with cardiology assessments, including echocardiography, electrocardiography, and CCTA, for the boy in our case to monitor for future major adverse cardiovascular events (MACE) post-discharge.