Optical Coherence Tomography in a 9-Year-Old Kawasaki Disease Patient with Giant Coronary Artery Aneurysms and Acute Myocardial Infarction

Background

Kawasaki disease (KD), a systemic vasculitis, primarily affects children aged <5 years and is the leading acquired cardiovascular disease in developed countries [1,2]. The coronary sequelae comprise coronary dilatation, coronary aneurysms, giant aneurysms, coronary stenosis, and myocardial infarction [1–3]. Acute coronary syndrome (ACS) is one of the most severe consequences associated with thrombotic occlusion of coronary lesions. In young patients with giant aneurysms and ACS, there is no evidence to suggest the most optimal percutaneous coronary intervention (PCI) strategy. Here, we present the case of a 9-year-old boy with KD and giant aneurysm in the right coronary artery (RCA). Acute thrombotic occlusion of the giant RCA aneurysm caused ACS. We intervened promptly and obtained optical coherence tomography (OCT) images.

Case Report

A 9-year-old boy was diagnosed with KD in December 2015, when he was 6 years old. At the age of 6, he received intravenous immunoglobulin (IVIG) on day 5 of KD and high-dose aspirin (1600 mg/day, divided into 4 doses) on days 5 to 13 of KD. Nevertheless, he experienced acute-phase complications including an RCA aneurysm (7.84 mm), dilated left main coronary artery (3.57 mm), left anterior descending artery aneurysm (4.99 mm), and pericardial effusion. In the convalescent stage, computed tomography revealed a giant RCA aneurysm (8.8 mm) and medium left anterior descending artery aneurysm (Figure 1A). Aspirin and warfarin were prescribed in our Outpatient Department, but the patient had poor drug compliance. At the age of 9 years, he presented to our Emergency Department because of acute chest pain for 8 h. Electrocardiography revealed a newly appeared incomplete right bundle branch block and ST-T change over right and inferior leads (Figure 1B–1E). There was also elevated troponin I (5.405 ng/mL). Echocardiography found a dilated right ventricle with moderate tricuspid valve regurgitation. Cardiac catheterization with coronary angiography revealed acute thrombotic occlusion of the RCA giant aneurysm with thrombolysis in myocardial infarction (TIMI) grade 2 flow (Video 1, Figure 2A). Using a 6 Fr guiding catheter, aspiration thrombectomy was repeated along the proximal and distal RCA. We successfully removed much red thrombi. The RCA coronary flow returned to TIMI grade 3 flow after PCI. Nevertheless, there were still residual small thrombi within the distal RCA, where the aspiration catheter could not reach. He was thus prescribed intravenous tirofiban for 24 h, combined with heparin, aspirin, and clopidogrel to prevent further thrombus formation. After 1 week, a repeated coronary angiography showed TIMI grade 3 flow, without obstruction, stenosis, and dissection (Figure 1B). OCT images revealed the presence of small white thrombi, calcification, destruction of media layer, irregular intimal thickening, and uneven intima edge (Video 2, Figure 2A, 2B). Because of satisfactory revascularization and relief of chest discomfort, we did not perform the second intervention. Eventually, the patient was discharged with antiplatelet therapy and warfarin. He was doing well at a 3-year follow-up, without a bleeding event or recurrent ACS.

Discussion

KD, named after Tomisaku Kawasaki, who described his first patient in 1967, has become one of the leading acquired cardiovascular diseases in developed countries [1,2]. The highest mean prevalence of KD in Japan was 330.2 per 100 000 children aged 0 to 4 years in 2015 [1,2]. Although IVIG decreases the rate of cardiovascular complications, some patients still develop coronary sequelae, including coronary dilatation, coronary aneurysms, coronary stenosis, and myocardial infarction [2–4]. In the acute phase of KD, coronary arteritis continues from day 6 to 25 and subsides by day 40 after onset. Reportedly, arterial dilatation and aneurysm formation occur during inflammation. The Japanese Circulation Society guidelines define coronary aneurysms by either a Z-score or diameter. Giant coronary aneurysms are a Z-score ≥10 or diameter ≥8 mm; medium aneurysms are a Z-score between 5 and 10 or diameter between 4 and 8 mm; and small aneurysms are a Z-score between 2.5 and 5 or diameter between 3 and 4 mm [2]. Giant coronary aneurysms with diffuse calcification, intimal hyperplasia, and organized thrombus formation occur in 0.18% to 0.22% of patients. Furthermore, regression of small or medium coronary aneurysms likely occurs within 1 to 2 years but persists in 0.72% to 0.78% of patients [2–5].

To date, several diagnostic tools have been used to evaluate the severity, hemodynamics, and morphology of the coronary sequelae, including blood tests, electrocardiogram, echocardiography, myocardial perfusion scintigraphy, computed tomography, magnetic resonance imaging, and cardiac catheterization. During cardiac catheterization, intravascular ultrasonography (IVUS) reveals the severity of intimal hyperplasia and the presence of calcification and thrombi and facilitates determining the means of intervention [2]. IVUS has a higher depth but more obscure image resolutions. The minimum guide catheter is 5 Fr for IVUS with Philips Visions PV 0.014P, which could be utilized in small children. Another alternative intravascular imaging technique using a 5 Fr guide catheter is the OCT scan, with higher resolution but relatively shallow depth. OCT catheters emit infrared light and measure the reflection and scattering from the coronary wall. The red blood cells interfere with infrared light. We thus need to clear the blood from the coronary artery during the OCT scan. The method of clearance includes occlusive and non-occlusive techniques. Occlusive methods use balloon inflation with normal saline flushing proximally to displace the blood; however, iatrogenic myocardial ischemia and ventricular arrhythmia are well-documented risks [6]. Therefore, in our case, we applied non-occlusive techniques that flushed contrast media to displace the blood during examination. We advanced an angioplasty guide wire (0.014”) into the RCA. While pulling back along the coronary artery, we performed scans of cross sections of interest. We obtained the anatomic data about the lumen, intima, and media and about the presence of calcification and thrombi.

In our patient, who had a massive thrombus within the giant CAA in the first angiography, it took a higher risk and inferior image quality to obtain the OCT image before decreasing the thrombus burden. Therefore, for the patient’s safety, we decided on aspiration thrombectomy plus medication first, and subsequently performed the OCT scan 1 week later, to decide whether this patient needed further PCI and medical treatments.

Harris et al performed OCT in 5 patients with KD (youngest age, 1.1 years), revealing white thrombi, calcification, intimal thickening, neovascularization, possible macrophage infiltration, and probable lipid pool [7]. Dionne et al performed OCT in 33 patients with KD (age, 3.5–22.2 years), of whom 16 (53%) patients had a giant aneurysm. In patients with coronary sequelae, the authors found intimal hyperplasia, fibrosis, cellular infiltrate, calcification, destruction of the media layer, neovascularization, and white thrombi. In addition, the measurements of the thickest intima directly correlated with the diameter of coronary aneurysms, and the authors found white thrombi in 4 cases of persistent aneurysms and 4 in regressed aneurysms [8]. Dionne et al also reported 18 patients with KD and coronary sequelae, of which 7 had giant CAA. These 2 series found more features of vascular wall abnormalities present in patients with giant CAA, including intimal hyperplasia, destroyed media, fibrosis, calcification, macrophage infiltration, white thrombi, and neovascularization [8,9].

For children with any size aneurysm, current guidelines recommend low doses of aspirin (3–5 mg/kg/day, once daily). In patients with giant aneurysms, a combination of aspirin and warfarin is recommended to prevent thrombotic occlusion of aneurysms [1,2]. ACS is one of the most severe consequences associated with thrombotic occlusion of coronary lesions. Initial therapies are anticoagulant therapy, antiplatelet therapy, and hemodynamic supports. PCI strategies include stent implantation, balloon angioplasty, and percutaneous transluminal coronary rotational ablation in patients with giant aneurysms [2]. Nevertheless, Suda et al reported higher reintervention and treatment failure rates in patients who received PCI (including intracoronary thrombolytic therapy, balloon angioplasty, percutaneous transluminal coronary rotational ablation, and stenting), compared with those of coronary artery bypass graft surgery, implying the relative incompleteness of catheter coronary intervention [10]. Although coronary artery bypass graft exhibits a better outcome and lower reintervention rate, it is preferred in older children (>12 years) and adults. Moreover, patients with left main CAD, multivessel CAD with decreased left ventricular function, and CAD not amenable to PCI are preferred candidates [2,11]. In young patients with single-vessel CAD, no evidence suggests which intervention strategy is optimal. In our patient, with acute thrombotic occlusion of the right coronary aneurysm, coronary artery bypass graft surgery was not indicated. Intracoronary thrombolytic therapy displays a relatively higher reintervention and treatment failure rate. Percutaneous transluminal coronary rotational ablation or balloon angioplasty are not durable and are preferred for narrow or stenotic segments. Stenting is also preferred in a stenotic coronary artery, and it is difficult to deploy a stent within an acutely occluded giant aneurysm. Zheng et al reported an adult with a history of KD. RCA stenosis and thrombotic occlusion resulted in ACS. They performed aspiration thrombectomy initially. After the first OCT scan, they subsequently performed a scoring balloon and non-compliance balloon for plaque modification. A repeated OCT pull-back found intimal dissection, and they subsequently used a drug-coated balloon. Their case report implies that OCT is a useful modality in decision making during PCI, especially in patients with KD and a complicated coronary anatomy [12].

Aspiration thrombectomy and intravenous tirofiban are other novel strategies. By using a 6 Fr coronary catheter, thrombectomy could be achieved by aspiration along the guidewire. In cases with a giant aneurysm and large thrombus burden, repeat aspiration is mandatory. We used intravenous tirofiban for 24 h, combined with heparin, aspirin, and clopidogrel to prevent further thrombus formation after aspiration thrombectomy. Tirofiban is a glycoprotein IIb/IIIa inhibitor that can have intravenous or intracoronary administration; however, its pediatric experiences in ACS are limited. In adult ACS, tirofiban has a satisfactory outcome and low incidence of bleeding in combination of dual antiplatelet therapy [13].

In our case, OCT at 1 week after revascularization revealed the presence of white thrombi, calcification, destruction of media layer, irregular intimal thickening, and uneven intima edge.

The giant aneurysm could not be observed fully, probably because of the lower depth in the OCT scan. In a patient with a giant CAA, combined OCT and IVUS, if available in the future, could be helpful to observe the giant CAA anatomy in detail. In other parts of the coronary artery, the depth of the OCT scan is adequate, with fair resolution, for further decision making.

The OCT findings in our case share similar features with the series reported by Dionne et al [9]. However, the uneven edge and destruction of medial layers were more severe in our case (Figure 3). This could have resulted from coronary sequelae of KD or previous PCI, which was potentially another risk for future plaque formation or stenosis. The risk of further vascular damage during PCI outweighs the benefit of removing small white thrombi, which can be fibrin-rich, old thrombi. Also, white thrombi could be a common finding in patients with CAA [8,9]. Instead of performing aspiration again, we continued antiplatelet therapy plus anticoagulant therapy. There was no luminal stenosis, therefore we did not perform further balloon angioplasty or stenting.

In the Japanese Circulation Society guidelines, warfarin is recommended for KD with a giant aneurysm, history of myocardial infarction, and thrombosis in CAA [2]. A retrospective study of KD patients with giant CAA in Japan showed that ACS is significantly less with the combination therapy of aspirin and warfarin than with aspirin alone [14]. In our case, the patient had been prescribed aspirin plus warfarin, but there was poor compliance. He had ACS and possible higher risk of future thrombogenesis because of the giant aneurysm, with severe vascular wall damage on the OCT scan. We decided on anti-platelet therapy and warfarin with strict follow-ups. The patient was doing well at a 3-year follow-up, without a bleeding event or recurrent ACS.

Conclusions

This report focuses on the treatment management and the use of OCT images in KD complicated with giant CAA and ACS. We utilized aspiration thrombectomy as the PCI strategy, in combination with medical treatments, to restore coronary perfusion to TIMI grade 3 flow. After the initial PCI, the OCT images showed vascular wall abnormalities, including white thrombi, calcification, irregular intimal thickening with uneven edge, and destruction of media layer, which suggested the risk factors and further treatment options. Using OCT images in KD is a new field that requires more cases and further research to determine the pathophysiology, correlations of disease severity, and optimal interventions.