Acute coronary syndrome in young adult patients with a history of Kawasaki disease
Corresponding author: Takashi Higaki, Department of Pediatrics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan, Tel: 81-89-960-5068; Fax: +81-89-960-5071; e-mail: firstname.lastname@example.org
- Recently there have been several reports of acute coronary syndrome (ACS) in adult patients with a history of Kawasaki disease. However, the actual situations and clinical conditions are unclear.Objective and Methods: We retrospectively analyzed the clinical course and prognosis retrospectively for adult (≥20 years old) patients in Ehime Prefecture who developed ACS and those who were diagnosed with or suspected of having Kawasaki disease sequelae
Results and Discussion: Twelve ACS episodes were observed in nine patients. Five out of nine patients were continuously followed up regularly with anticoagulant therapy since the onset of Kawasaki disease, the remaining four patients who did not followed. They were diagnosed with sequela of Kawasaki disease for the first time by coronary angiography when admitted to ACS. Giant coronary artery aneurysms were recognized in six patients. All follow-up patients who developed ACS had giant coronary artery aneurysm, and AMI occurred based on stenotic lesions in cases without follow-up. As a characteristic finding in one case of thrombotic occlusion, fibrotic-fatty wall thickening by intravascular ultrasound (IVUS) unsuitable for the age were recognized, at coronary artery which had no coronary artery aneurysm and appeared normal. It was concern of early arteriosclerosis progression.
Conclusions: The number of the patients with ACS who had sequelae of undiagnosed Kawasaki disease may increase in the future. It is important to establish the system of stratify the risks of ACS in patients with a history of Kawasaki disease.
Fifty years have passed since the discovery of Kawasaki disease. Approximately half of patients with a history of Kawasaki disease (362,710 patients) have reached adulthood [1-3]. Recently there have been several reports of coronary events corresponding to acute coronary syndrome (ACS) in adult patients with a history of Kawasaki disease. However, the actual situations and clinical conditions are unclear [4-6]. To predict and prevent coronary events, it is important to understand the current status of coronary events in patients with a history of Kawasaki disease. We investigated and reported the current state of ACS in adult patients with a history of Kawasaki disease.
Subjects and Methods
The subjects included the following adult (≥20 years old) patients in Ehime Prefecture who were treated in the Departments of Pediatric Cardiology and Cardiovascular medicine: patients with a history of Kawasaki disease who developed ACS and those who were diagnosed with or suspected of having Kawasaki disease sequelae based on emergent coronary angiography findings at the onset of ACS. The examination items were as follows: a history of Kawasaki disease (presence or absence of history, age at onset, and acute care); coronary artery disorders (presence or absence of coronary artery aneurysm and the site of coronary artery disorder); follow-up (e.g., condition of regular clinic visits, internal medicine such as anticoagulant therapy,); presence or absence of coronary risk factors such as smoking; situation at onset of ACS (acute myocardial infarction, AMI; unstable angina pectoris, UAP; sudden cardiac death, SCD); laboratory findings on admission (electrocardiography, echocardiography, and coronary arteriography, among others); treatment for coronary events (thrombectomy; percutaneous transluminal coronary recanalization, PTCR; plain old balloon angioplasty, POBA; pulse infusion thrombolysis, PIT; stent placement, STENT; coronary artery bypass graft, CABG). Additionally, the clinical course and prognosis were retrospectively examined. The population of Ehime prefecture is 1.3 million and the number of births is 10 thousand a year, about 1% of Japan.
Twelve ACS episodes were observed in nine patients (seven men and two women) with a history of Kawasaki disease (Table 1). The patients’ ages ranged from 22-41 years. The ages at the onset of ACS were between 12 and 40. Five patients were continuously followed up in the Departments of Pediatrics or Pediatric Cardiology since the onset of Kawasaki disease. One patient received acute care subsequent to a diagnosis of Kawasaki disease and underwent no treatment because of self-determined discontinuation of follow-up. Three patients with no apparent history of Kawasaki disease were diagnosed with Kawasaki disease for the first time based on coronary angiography conducted upon admission for ACS. One of these three patients had a history of fever of unknown etiology in early childhood. In terms of results, Kawasaki disease was suspected based on his history (case 8). Of the five patients who underwent follow-up regularly, four received warfarin and aspirin and the fifth received aspirin. Patients who did not undergo follow-up received no medicine.
The types of ACS onset were AMI (seven patients), UAP (four patients), and SCD (one patient). Of the seven patients who developed AMI, the area responsible for ACS was the right coronary artery (RCA) in six events. Three out of four patients who developed UAP had lesions in the left coronary artery (LCA). The onset of all cases without follow-up occurred AMI. On the other hand, three out of five patients who have been followed were intervened at the UAP. Giant coronary artery aneurysms (GA³8mm) were recognized in six patients. All follow-up patients who developed ACS had GA, and thrombotic occlusion caused by GA was observed. In case 3 (reported to JACC Cardiovasc Interv. 2010) , he had a sausage-like giant coronary aneurysm at segment (Seg) 1-4 of the RCA; additionally, medium-sized aneurysms were detected at Seg 5, 6, and 7 of the LCA (Figure 1A).
Although this patient had a giant coronary aneurysm, no stenotic lesion was detected and ischemia was not observed. Therefore, he was followed up with anticoagulant therapy comprising aspirin plus warfarin. However, he developed AMI due to thrombotic occlusion with a large thrombus of the right giant coronary aneurysm (Figure 1B).
Despite regular follow-up, ACS occurred in this case with GA. The patient with SCD had a GA in the left coronary artery. In cases without follow-up, AMI occurred based on stenotic lesions. Regarding treatment, three patients underwent PTCR; three patients with acute thrombotic occlusion of the RCA were treated with thrombectomy, PIT, and POBA; and four patients with lesions of the left coronary artery were treated with CABG.
No patients who had been followed up since childhood had smoking history, whereas two of the patients who did not undergo follow-up had a smoking history. In case 6, the patient is a valuable case suggesting the pathogenic mechanism of ACS in Kawasaki disease patients who reached adulthood. He was diagnosed with AMI because of continuous chest pain and dyspnea, and immediately underwent cardiac catheterization. A giant coronary aneurysm was detected at Seg 1 of the right coronary angiography, and 90% stenosis was found in its proximal part. In addition, complete occlusion due to thrombus was found at Seg 3 (Figure 2A).
Repeat thrombus aspiration, recanalization was achieved (Figure 2B)
Intravascular ultrasonography (IVUS) was performed simultaneously and exhibited fibrotic-fatty wall thickening in an area that otherwise appeared normal and without a coronary artery aneurysm in Seg 3, which was an unusual finding for a patient of this age (Figure 3).
In this research, we clarified the current state of ACS of Kawasaki disease. Among adults who have not been followed as the sequelae of Kawasaki Disease, there are cases in which ACS caused by Kawasaki Disease has developed. Future studies of follow – up observation of Kawasaki disease had been suggested.
As the presence of intimal thickening is known as a coronary sequela after Kawasaki disease, there is concern that arteriosclerosis may occur soon after inflammation. Recently, there have been reports of endothelial dysfunction associated with the clinical conditions of arteriosclerosis, oxidative stress, and increased inflammation in patients with a history of Kawasaki disease [4-6,8,9]. For clinical condition analyses, IVUS and multi-slice cardiac CT are considered useful, and intimal thickening, including arteriosclerosis-like components and advanced calcification, has been reported. However, the association with coronary events is unknown. In addition, coronary events due to arteriosclerosis in adulthood occur regardless of the degree of coronary artery stenosis and are known as ACS associated with rapid thrombogenesis, with a mechanism such as coronary plaque rupture and erosion. More than 50 years have passed since Kawasaki disease was discovered, and more than 100,000 patients with a history of Kawasaki disease have reached adulthood [2,3]. Recently, there have been several reports of adult patients with a history of Kawasaki disease who developed ACS thought to be associated with abnormalities in the coronary wall structure, abnormal hemodynamics in the coronary artery aneurysm, and coronary risk factors. However, there is no definitive report, and the actual situation and clinical conditions are unknown. Therefore, clarification regarding pathology is awaited.
In our study, no young adult patients with a history of Kawasaki disease and without morphological abnormalities such as coronary artery aneurysm developed ACS. In Case 6, a giant coronary aneurysm was detected via right coronary angiography at Seg 1, and 90% stenosis was shown in its proximal part. This finding is in accordance with the sequelae of Kawasaki disease. A complete occlusion due to thrombus was found at Seg 3. Coronary arteriography after recanalization found no coronary artery aneurysm or stenotic lesion in the coronary arteries in this area, which appeared to be normal at a glance. However, the IVUS findings indicated fibrotic-fatty wall thickening, which was unusual at this site for a patient of this age. There is a possibility of early arteriosclerosis progression. Although the mechanism by which thrombotic occlusion occurred at this site was unclear, it might suggest an ACS development factor in patients with a history of Kawasaki disease . The thrombus, which occurred in the coronary artery aneurysm at Seg 1, might have flowed into and blocked Seg 3. However, although coronary arteriography indicated that the site was normal, there is a possibility of latent coronary artery disorders such as arteriosclerosis or endothelial dysfunction.
Five of the nine patients who developed ACS had been followed up in pediatric departments since developing Kawasaki disease. As we reported previously, a review of the management and treatment strategy is required for adult patients with sequelae of Kawasaki disease and giant coronary aneurysm, given that these patients developed ACS while under maintenance with anticoagulant and antiplatelet therapies [11,12]. Asymptomatic patients without stenotic lesions and ischemia require antithrombotic therapy but have few daily-life limitations. The decision whether to select active treatment for such patients is controversial. It has been reported that early coronary bypass causes occlusion because of competition with antegrade blood flow. Another report stated that CABG is not recommended for patients with antegrade blood flow . The patency of the CABG itself and prognosis during the convalescent phase remain unidentified because the subjects were relatively younger patients. Therefore, the treatment strategy should be determined carefully.
Another four patients were not followed up for Kawasaki disease. These patients were diagnosed with Kawasaki disease based on coronary angiography findings at the onset of ACS. Two patients had no childhood episodes indicating suspected Kawasaki disease. Accordingly, they had no follow-up opportunities with careful monitoring for Kawasaki disease-related vascular disease. In all four patients who were initially diagnosed with sequelae of Kawasaki disease upon developing ACS as a presenting symptom, the age at onset was 40 years or younger. It is necessary to consider a history of Kawasaki disease when a younger patient develops ACS. However, the number of potential patients is unknown. In Ehime Prefecture, the population is 1.3 million. Since the population of Ehime prefecture is about 1% in Japan, it is estimated that there will be about 1,000 Kawasaki disease predecessors. Of that, having experienced twelve ACSs for nine patients admitted ACS to approximately 1% of adult-age old Kawasaki disease predecessors.
Patients with sequelae of Kawasaki disease as well as residual coronary artery aneurysms and stenotic lesions after the onset of Kawasaki disease account for a considerable percentage of all patients with Kawasaki disease and are usually followed up with oral treatment administration. Most patients with a history of Kawasaki disease represented cases with coronary arteries that were normal at an early stage and determined not to have coronary artery disorder in the acute phase, cases of transient coronary dilation in which coronary dilation or coronary artery aneurysm in the acute phase was determined to be normal during follow-up, or cases of coronary artery aneurysm regression. Periodic follow-up is important in patients with a history of Kawasaki disease. For adult patients, it is important to establish an evaluation system to judge whether they are at a high risk of ACS and whether any kind of intervention is necessary. Management stratification is also required during the convalescent phase by extracting high-risk patients [12,14].
ACS in young people is mostly caused by Kawasaki Disease Coronary Artery Disorder or has a history of smoking. In this survey, we admitted smoking history to two patients. The involvement of smoking history in the onset of ACS by Kawasaki Disease remains unclear, but it is clear that guidance for smoking cessation is one of the important guidance in follow-up.
We reported the actual situation regarding coronary events in patients with a history of Kawasaki disease who live in Ehime Prefecture. Patients with ACS included those who had not been followed up or had sequelae of undiagnosed Kawasaki disease. Therefore, the number of the patients may increase in the future.
It is important to establish a coronary artery disorder evaluation system and a long-term management method that stratifies the risks of ACS for patients with a history of Kawasaki disease. This makes it possible to prevent coronary artery events of extracted high-risk patients.
We thank the participating physicians for graciously enrolling their patients.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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