Kawasaki Disease is associated with early and late coronary abnormalities. Coronary calcifications have been noted on long-term follow ups in the region of the initial abnormalities. We present the first case of an asymptomatic adolescent with Kawasaki Disease and normal stress testing in whom the coronary calcium was associated with severe four vessel narrowing.
1.
Introduction
Kawasaki Disease (KD) is the most common cause of acquired heart disease in children within developed countries [1]. An acute vasculitis of childhood leads to coronary aneurysms in approximately 25% of the untreated cases. Even with treatment, 20% will develop a transient coronary dilation, while 1% will develop either large or giant aneurysms (>8 mm, Z-score ≥ +10). Large or giant aneurysms are at risk for rupture, and a myocardial infarction can occur from an acute or progressive thrombosis or stenosis [1]. Patients with a history of coronary artery aneurysms are at risk of late morbidity and mortality [2], and coronary aneurysms are associated with late calcifications [3]. Coronary artery calcifications (CAC) have been associated with stenosis in the area of calcifications [4]. Clinical criteria are used to diagnose Kawasaki Disease. Classic Kawasaki Disease is diagnosed in the presence of at least 5 days of fever together with 4 of the 5 following principle clinical features: (1) erythema and cracking of the lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa; (2) bilateral bulbar conjunctival injection without exudate; (3) rash: maculopapular, diffuse erythroderma, or erythema multiforme-like; (4) erythema and edema of the hands and feet in the acute phase and/or periungual desquamation in the subacute phase; and (5) a cervical lymphadenopathy (≥1.5 cm diameter), which is usually unilateral. Incomplete Kawasaki Disease can be diagnosed with 2 or 3 clinical criteria and either certain laboratory criteria or coronary artery abnormalities (dilation/aneurysms) [1].
2.
Case report
We present the first case of an adolescent with a history of KD and giant coronary aneurysms with significant CACs and a normal cardiac stress magnetic resonance imaging (MRI). He was diagnosed with Kawasaki's disease at 6 months of age and received an appropriate therapy with intravenous immunoglobulin and aspirin. Throughout his life, he had no cardiac symptoms except for one episode of syncope at 8 years of age while standing in the hot sun, which was attributed to dehydration. However, he did not perform any significant vigorous physical activities as an adolescent. He had a progressive increase in his body mass index (BMI) throughout his life. A chronologic history/evaluation is shown in Table 1.
3.
Discussion and conclusions
KD is considered a “rare” disease, and the etiology remains speculative. Coronary abnormalities are the primary long-term complications, and echocardiography is considered the gold standard for a routine evaluation in the pediatric population. This case describes an adolescent KD patient with a normal stress MRI, and whose severe multivessel coronary narrowing was diagnosed after a cardiac CT identified CAC. While a cardiac CT is not recommended in the acute phase, it can be useful for the evaluation of distal coronary artery aneurysms, which are not well visualized echocardiographically [5]. The best long term follow-up approach remains under debate.
In any patient with concerns for coronary narrowing, some form of functional assessment is necessary. Per the 2017 American Heart Association Diagnosis, Treatment and Long-Term Management of Kawasaki Disease Guidelines, for giant aneurysms that regressed to small aneurysms, it is reasonable to assess for inducible myocardial ischemia every 1–2 years (Class IIa, level of evidence B) [1]. However, pediatric patients are not typically able to fully participate in stress testing until around 10 years of age. Additionally, radionuclide stress imaging in pediatric institutions is typically not available. Additionally, radionuclide stress imaging would expose pediatric patients to repetitive radiation-based procedures throughout their lifetimes. A stress MRI is a relatively new modality in pediatrics with increasing availability that does not require radiation. A stress MRI in adults is felt to “accurately assess myocardial ischemia, myocardial viability, and cardiac function without exposure to ionizing radiation” [6], and can repetitively assess a patient for regional wall abnormalities and myocardial perfusion without radiation. Therefore, this patient underwent a stress MRI for a functional assessment, which was normal. A stress MRI is limited by its inability to be combined with exercise and several patient related factors: claustrophobia, obesity, the possible need for sedation, and any patient with a ferromagnetic device may not be an ideal candidate [6]. Additionally, a stress MRI is a relatively new modality and professional experience with its interpretation may be limited (particularly in pediatric institutions). A possible explanation for the normal results of the stress MRI could be a balanced myocardial ischemia, which is a condition where the blood flow is equally reduced to the myocardium during stress. Additionally, there was a 16-month interval between the stress MRI and the cardiac CT, which could have been a progressive coronary artery stenosis. Myocardial scintigraphy could be used to further map the myocardial blood flow. However, myocardial scintigraphy and other cardiac radionuclide-based testing are not available in most pediatric institutions and were not able to be performed.
Moreover, patients with coronary narrowing require some form of anatomic/angiographic assessment. Per the 2017 American Heart Association Diagnosis, Treatment and Long-Term Management of Kawasaki Disease Guidelines, further imaging with angiography (i.e., CT, MRI, invasive) may be considered for periodic surveillance every 2–5 years (Class IIb, level of evidence C) [1]. In order to reduce frequent invasive cardiac catheterizations, a contrast enhanced CT is often the modality of choice, which this patient subsequently underwent. This revealed multiple areas of severe CAC. Since the degree of stenosis cannot be seen within a severe calcification, the patient underwent cardiac catheterization, which revealed his severe 4 vessel disease.
CAC is a feature that may increase the long-term risk of myocardial ischemia in KD patients [1]. The exact etiology of CAC remains unknown. Yokouchi (2022) histologically studied 24 KD patients with coronary aneurysms who died within 3 years of their diagnosis [7]. The autopsies revealed 14 out of the 24 patients had CAC. This was seen in the organized portion of the thrombus (n = 12) and in the thickened tunica of the intima (n = 3). It was noted that as the duration after diagnosis of KD increased, the calcified lesion increased in size. Additionally, the calcified area tended to increase as the diameter of the aneurysm increased. It was concluded that coronary artery aneurysm calcification starts early in the remote phase of KD, and it is closely related to the organization of the thrombi.
Ino (1990) studied 116 KD patients by angiography (average ~7.2 years after diagnosis), where 9.1% of those with an angiographic coronary abnormality demonstrated CAC [8]. Chakraborty (2020) evaluated 21 KD patients >10 years after an initial diagnosis via a cardiac CT [9]. None of the patients with initially normal coronaries demonstrated any abnormality. However, 2 out of the 4 patients with initial echocardiographic coronary abnormalities had persistent CT abnormalities and 1 had CAC (25% of those with an initial abnormality and 5% of total). It was speculated that CAC was likely to be dystrophic rather than atherosclerotic. Kahn (2017) reviewed 166 patients with a history of KD (median interval from KD to CT 15.1 years) [10]. Coronary arteries classified as either normal, persistently dilated, or with a remodeled aneurysm had no CACs. 19 out of the 24 patients (79%) with coronary aneurysms had CAC (median volume 542 mm3). For subjects imaged ≥9 years after their acute KD (n = 144), the presence of CAC had a sensitivity of 95% and a specificity of 100% for detecting coronary artery abnormalities (defined as coronary artery aneurysm and/or stenosis). They concluded that CAC scanning may be a useful tool to screen patients with either a remote history of KD or suspected KD and unknown coronary artery status [10].
Additionally, there is data correlating the initial size of a coronary artery aneurysm with the development of a stenotic lesion. Tsuda (2018) showed the cutoff points of the coronary artery diameter within the first 100 days after the onset of KD, which led to a stenotic lesion in the late period, with a diameter of ≥6.1 mm (BSA of <0.50 m2) and ≥8.0 mm (BSA of ≥0.50 m2) [11]. Those cutoff points would have corresponded with a Z-score of at least +10.0 on 2-dimensional echocardiography. A similar study by Tsujii (2017) in 65 patient (median interval from diagnosis to cardiac CT 16 years) had similar results and concluded that an acute coronary dilation that exceeds ~5 mm can lead to late abnormalities of the coronary wall and that CAC increases with age [12]. Kaichi (2008) demonstrated that the coronary arterial diameters of all branches that eventually calcified in 79 KD patients were 6 mm or greater. The incidence of CAC in branches measuring 6 mm or greater on the initial coronary angiogram were 12% at 5 years, 44% at 10 years, and 94% at 20 years (n = 141) [3].
Nikolaou (2011) described a CT as indicated for CAC scoring (or coronary vessel wall imaging in general), MRI for stress, cine MRI, stress perfusion MRI, and both CT and MRI for non-invasive coronary angiography and myocardial viability imaging [13]. Similarly, Dietz (2015) described CAC as being easily identified by a cardiac CT and a cardiac MRI as the most useful methods for functional imaging [14]. This was supported by Stijn (2021), who compared 54 KD patients who underwent both a cardiac CT and a cardiac MRI, and concluded the CT was more sensitive than the MRI for the diagnosis of coronary artery aneurysms [15]. There are numerous modalities to assess CAC. However, CAC cannot be detected by a cardiac MRA, because the signal for calcium drops and a coronary artery stenosis with calcification is seen as a coronary narrowing with signal drop [16]. Angiography is felt to have a high detection specificity for CAC, but with moderate to low detection sensitivity [17]; moreover, it is invasive. A cardiac CT is felt to have both a high specificity and sensitivity for CAC detection and is noninvasive [17]. This makes it a common choice to evaluate CAC. Both modalities involve radiation exposure. Although there is no role for CAC scoring in the acute phase of KD, some studies suggest that CAC can be used to screen those with a questionable history of KD with an unknown coronary involvement [10]. For long term KD, a follow-up cardiac CT is a technique that can identify CAC without the need of an intravenous contrast [18]. While the 2017 American Heart Association Diagnosis, Treatment and Long-Term Management of Kawasaki Disease Guidelines do not have specific recommendations for CAC scoring, they do state “low-dose, non-contrast CT calcium scoring also has been demonstrated to be useful in KD patients to guide selection for further evaluation with coronary angiography.” [1].
In this case, the patient had two normal stress tests (one routine and one cardiac stress MRI). He was asymptomatic, and the degree of his coronary pathology was diagnosed only after the cardiac CT revealed the CAC. This study highlights the need to evaluate all chronic KD patients with a history of giant coronary aneurysms with a combination of some form of functional testing and anatomic testing (i.e., a cardiac CT that will not only to assess coronary anatomy, but is also able to assess for a CAC). Additionally, there is data to suggest a cardiac CT is a useful screening tool in patients with suspected remote KD and an unknown coronary artery status [10].
Author contributions
All authors participated to varied degrees in the prepartion of this manuscript and consented to the published version of the manuscript.
Use of AI tools declaration
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
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