Acute coronary syndrome in adult patients with coronary artery lesions caused by Kawasaki disease: review of case reports

Information about acute coronary syndrome caused by Kawasaki disease-related coronary artery lesions in adults is sketchy. We reviewed the clinical features of 50 adult patients who had an acute coronary syndrome caused by coronary artery lesions due to Kawasaki disease or probable Kawasaki disease from 1980 to 2008. Of the 50 patients, 43 (90%) were male and seven were female (10%). Their ages at the onset of acute coronary syndrome ranged from 18 to 69 years, with a median of 28 years. The culprit lesion in 43 patients was thrombotic occlusion of an aneurysm, and 40 patients had giant aneurysms. In the three patients in whom no aneurysms were seen in coronary angiograms performed at the time of acute myocardial infarction, either giant aneurysms or aneurysms had been visualised in childhood. The initial treatment of acute coronary syndrome was as follows: intracoronary thrombolysis, 11; primary percutaneous coronary intervention, 9; emergency coronary artery bypass grafting, 3; and medication, 26. Elective coronary artery bypass grafting was performed in 15 patients. Three patients (6%) died. Of the 27 patients with additional coronary risk factors, 20 were smokers. Giant aneurysms due to Kawasaki disease continued to cause acute coronary syndrome in adult life with onset at a younger age than typifies that due to atherosclerosis in the general population, especially in male population rather than female population. Even when giant aneurysms regressed after the acute phase, a few patients still developed acute coronary syndrome in adult life. Smoking appears to be the most prominent additional risk factor.     

Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset.

A 25-year-old man with a history of Kawasaki disease from the age of 7 had acute inferior myocardial infarction. Emergency right coronary arteriogram showed successive coronary aneurysms at the proximal to middle portion of the right coronary artery, and total occlusion at the proximal segment. Intracoronary thrombolysis was performed and the right coronary artery was recanalized. On left coronary arteriography, coronary aneurysms and mild localized stenoses at the inlet and outlet of the aneurysms were found. It was suggested that the myocardial infarction was caused by thrombotic occlusion of coronary aneurysms complicated with Kawasaki disease.     

Aneurysms of the common trunk, anterior descending and right coronary artery in a 33 years old man with acute myocardial infarction. A case report

Coronary artery aneurysms are often incidental findings during coronary angiography; they are mostly secondary to atherosclerosis or vasculitis, they are rarely congenital. Right coronary circumflex and anterior descending arteries are usually involved but only few cases of aneurysms of left main coronary artery are reported. A case of coronary artery aneurysms is described involving left main, right and anterior descending coronary arteries, probably secondary to atypical Kawasaki disease in a 33 years old man with acute myocardial infarction.     

The role of coronary bypass operation on children with Kawasaki disease

BACKGROUND: Kawasaki disease, initially called mucocutaneous lymph node syndrome was reported 35 years ago as a new inflammatory disease in infants and children and is characterized by a variety of symptoms and signs resulted from systemic vasculitis. Although the etiology of the disease remains unknown, its serious coronary complications have been proved to cause ischemic heart disease in children, and are now the most common cause of pediatric coronary disease in the world. The incidence of serious coronary sequelae is fortunately low (2-3% of patients with Kawasaki disease), but once myocardial infarction occurs in children, the mortality is quite high (22% at the first infarction). Development of surgical treatment for the disease was essential in preventing premature death and improving the quality of life of children. METHODS AND RESULTS: Coronary revascularization surgery was attempted following careful evaluation of characteristic patters of coronary aneurysms and obstructions secondary to Kawasaki disease, although the surgical efficacy was initially questioned because the disease is inflammatory vasculitis in origin. The operation utilizing the pedicled internal thoracic artery has been demonstrated quite successful and now established as a reliable treatment for inflammatory coronary obstructions due to Kawasaki disease (the Kitamura Operation). There is valid evidence for the internal thoracic artery graft being a viable structure, accommodating in length and diameter for the growth of children. Results of the surgery and long-term prognosis are favorable and postoperative quality of life is markedly improved. CONCLUSIONS: Coronary bypass operation utilizing the pedicled internal thoracic artery is a safe and reliable surgical modality for coronary artery sequelae in children due to Kawasaki disease. Long-term follow-up results up to 20-years are quite satisfactory.     

系统性血管炎合并冠心病患者的冠状动脉病变及临床特征

目的 阐述系统性血管炎合并冠状动脉病变患者的临床和冠状动脉病变特征.方法 对北京协和医院1999年1月至2009年10月有冠状动脉造影结果的15例系统性血管炎合并冠心病患者的临床表现及冠状动脉病变进行回顾性分析.结果 15例患者中,贝赫切特综合征(BS)6例、变应性肉芽肿性血管炎(CSS)3例,大动脉炎2例,结节性多动脉炎(PAN)、显微镜下多血管炎(MPA)、Wegener肉芽肿(WG)和川崎病各1例.15例患者出现冠心病表现的平均年龄(39.3±11.9)岁.与在血管炎非活动期出现冠状动脉事件的患者(4例)相比,在血管炎活动期出现冠状动脉事件的患者(9例)有以下趋势:发病年龄小[(32.4±8.1)岁比(47.0±10.2)岁],传统冠心病危险因素少[(1.2±1.5)个比(2.8±1.7)个],血管炎和冠心病发病间隔短[0～7(平均1.6)年比3～30(平均17.7)年].15例患者中,表现为急性心肌梗死12例,心绞痛2例,心包填塞1例;3例发生急性冠状动脉事件时合并严重心律失常,3例合并急性左心功能不全.冠状动脉造影检查8例患者表现为冠状动脉狭窄、闭塞,1例表现为动脉瘤及急性血栓形成,1例表现为多发冠状动脉瘤样扩张伴闭塞,2例表现为冠状动脉痉挛,另有3例急性心肌梗死患者冠状动脉狭窄程度＜70%.8例患者超声心动图检查左心室射血分数＜50%.结论 多种系统性血管炎可合并冠状动脉病变,临床上可以表现为危急重症,冠状动脉狭窄或闭塞、动脉瘤形成、痉挛、急性血栓形成和小血管病变共同参与发病.

Abstract：

Objective To evaluate the clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease. Method Fifteen patients ( 11 male) with systemic vasculitis and coronary artery diseases admitted to our hospital from January 1999 to October 2009 were reviewed. Results There were 6 patients with Behcet's disease, 3 patients with Churg-Strauss syndrome, 2 patients with Takayasu arteritis, 1 patient with polyarteritis nodosa, 1 patient with microscopic polyangiitis, 1 patient with Wegner's granulomatosis and 1 patient with Kawasaki disease. Mean age of this cohort was (39. 3 ± 11.9) years. Adverse coronary events occurred in 4 patients during the inactive phase of systemic vasculitis and in 9 patients during the active phase of systemic vasculitis. Twelve patients were hospitalized with acute myocardial infarction, 2 with angina pectoris and 1 with cardiac tamponade. There were 3 patients with acute left ventricular dysfunction and 3 patients with severe arrhythmias. Compared to patients in the inactive phase, patients in the active phase were younger [(32. 4 ± 8. 1 )years vs. (47.0 ± 10. 2)years],had less risk factors for atherosclerosis ( 1.2 ± 1. 5 to 2. 8 ± 1.7) and the time intervals between coronary artery disease and systemic vasculitis was shorter [0 -7 years( average 1.6 years) to 3 -30 years( average 17.7 years)]. Coronary angiography evidenced coronary stenosis or occlusions in 11 patients, coronary aneurysm and acute thrombosis in 1 patient, coronary aneurysms and occlusions in 1 patient and coronary spasm in 2 patients. LVEF measured by eehocardiography was less than 50% in 8 patients. Conclusion Patients with various systemic vasculitis could develop severe coronary artery disease due to coronary stenosis/occlusion, aneurysma, thrombosis and coronary spasm.     

Long-term follow-up of a patient with Kawasaki disease and coronary aneurysm associated with asymptomatic thrombosis: a case report

A 20-year-old male was first diagnosed with Kawasaki disease at age 2 years 9 months. Coronary angiography in the acute phase revealed coronary aneurysms, so chronic antiplatelet therapy was initiated with aspirin and ticlopidine. The patient was asymptomatic and was followed up. Stress myocardial imaging showed asymptomatic myocardial ischemia at age 20 years. Coronary angiography was performed, and revealed 99% occlusion of the right coronary artery and collateral circulation from the left coronary artery. Occlusion was attributed to coronary aneurysm thrombosis. Much remains unknown about the long-term prognosis in patients with coronary aneurysm associated with Kawasaki disease. Asymptomatic children who are followed up sometimes develop ischemic heart disease as young adults. This case highlights the need for long-term follow-up in patients with Kawasaki disease and coronary aneurysms.     

Remodeling of coronary artery lesions due to Kawasaki disease: comparison of arteriographic and immunohistochemical findings

Since the original report of Kawasaki disease in 1967 more than 150,000 cases have been reported in Japan. Although there have been no nationwide epidemics in Japan since 1987, more than 6,000 newly diagnosed cases are reported every year, and the number has been increasing year by year despite the decreasing birth rate. The etiology of the disease is still unknown. High dose intravenous gammaglobulin is currently used during the acute phase in 84% of the patients in Japan with a concomitant decrease in coronary arterial sequelae. However, 7-13% of the patients still have persistent coronary artery aneurysms after the acute stage. The aneurysms are seen mostly in the proximal coronary arteries, and are often associated with aneurysms in the distal coronary artery segments (Figure 1A, 2A). Most of the patients show a decrease in the size of aneurysms soon after the acute phase (Figure 1B). However, the aneurysms may progress to obstructive lesions even after initial regression (Figures 1C, D, 2B). Such obstructive lesions may cause sudden death or myocardial infarction. Long term follow-up of coronary artery lesions has revealed several characteristic features, including progressive localized stenosis (Figure 1D), extensive recanalizations (Figure 2D) and development of collateral arteries. Progressive increases in aneurysm size and the appearance of new aneurysms in the late phase have also been reported. The basic mechanisms of the coronary arterial remodeling in Kawasaki disease have not yet been elucidated. Only recently has immunohistochemical staining in formalin-fixed specimens become feasible. This is a major technical breakthrough since it is almost impossible to obtain fresh frozen specimens of coronary artery lesions of Kawasaki discase. In this paper, we compare immunohistochemical findings in coronary artery lesions with the corresponding coronary angiographic findings, and attempt to make inferences as to the mechanism of remodeling both in early and late phases of the disease based on the expression of vascular growth factors.     

Kawasaki disease, myocardial infarction and coronary artery revascularization

Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease in North America and Japan. Cardiac sequelae, such as coronary artery aneurysms and myocardial infarction, are the major causes of the morbidity and mortality associated with KD. Three case scenarios are described illustrating the wide range of clinical presentations of myocardial ischemia in children after acute KD, varying from asymptomatic to fatal myocardial infarction. In addition, the present paper provides a review of the literature on myocardial infarction in association with KD and various modalities of coronary artery revascularization in children with myocardial ischemia secondary to KD.     

Giant coronary artery aneurysms in Kawasaki disease--the need for coronary artery bypass

The incidence of coronary artery involvement has fallen markedly following early gammaglobulin infusions in Kawasaki disease. Nevertheless such involvement may still occur and if giant coronary aneurysms develop they are more likely to lead to myocardial ischaemia. Two subjects are described who developed giant aneurysms, one of whom was subjected to successful coronary artery bypass following the detection of myocardial ischaemia on a nuclear perfusion scan 5 years following his acute episode. The other is being followed to detect the first signs of any ischaemia. While all patients who develop coronary artery aneurysms following Kawasaki disease require diligent long-term review, that is especially important in the few with giant aneurysms. Early detection of significant coronary artery stenosis and its successful treatment may prevent myocardial infarction in childhood and adolescence with all its long-term consequences.     

Refractory Progression of Coronary Aneurysms,a Case of Delayed Onset Kawasaki Disease as Depicted by Cardiac Computed Tomography Angiography

Background. Kawasaki disease (KD) is an immune-mediated vasculitis of unknown etiology with self-limited clinical course that was first described in 1967 by Dr. Tomisaku Kawasaki. It is a disease of early childhood and rare past late adulthood but one that can have detrimental consequences when there is a delay in diagnosis and treatment. Cardiovascular complications causing increased morbidity and mortality may include coronary artery aneurysms, myocardial infarction, heart failure, arrhythmias, and peripheral artery occlusion. Case Presentation. Here, we present an atypical case of delayed onset KD in a young teenager. DS had visited three different emergency departments during the course of 2 weeks for unrelenting fevers. Despite multiple treatment protocols including immunoglobulin, steroids, and tumor necrosis factor-alpha antagonists, he continued to have progression of cardiovascular complications. While echocardiographic findings were suspicious for cardiac complications, a cardiac computed tomography (CT) angiography was able to clearly distinguish giant coronary aneurysms. Conclusion. Without prompt therapy, fever and manifestations of acute inflammation can last for several weeks to months with increased risk toward complications. The incidence of coronary artery aneurysms has been noted to be 25% in untreated patients with a mortality rate of up to 2%. Using low-dose protocols along with high spatial and temporal resolution of cardiac CT angiography may provide a useful and complimentary imaging modality in accurate diagnosis and follow-up of patients with KD.     

Successful catheter interventional therapy for acute coronary syndrome secondary to kawasaki disease in young adults.

Acute coronary syndrome occurred in 2 young adults who had a history of Kawasaki disease (KD), but few other coronary risk factors. The first patient was a 27-year-old male with acute myocardial infarction without stenosis detected by coronary arteriography 4 years earlier. Emergency coronary arteriography showed occlusion of the right coronary artery. Aspiration-thrombectomy and rescue balloon angioplasty were successfully performed. The second patient was a 32-year-old male with unstable angina. Right coronary arteriography showed total occlusion with severe calcification. Left coronary arteriography showed 99% stenosis at the proximal site of the circumflex artery, and a directional coronary atherectomy was performed. Histological examination of a specimen from this site revealed a lipid core, macrophages, and smooth muscle cells. Restenosis was not observed on follow-up coronary arteriography after 5-6 months in either case. The coronary stenosis in each case was probably caused by accelerated atherosclerosis at the site without aneurysm as it seemed to be 'normal' on arteriography. Conventional catheter intervention was effective treatment. The sequelae of KD should be recognized as independent coronary risk factors.     

Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction in a Pediatric Patient with Giant Coronary Aneurysm Due to Kawasaki Disease

We report a case of acute myocardial infarction in an 8‐year‐old boy with a history of Kawasaki disease and giant coronary aneurysms in the right and left coronary arteries. We performed coronary angiography and percutaneous coronary intervention 4 hours after the onset of symptoms. This case suggests that primary percutaneous coronary intervention might be safe and effective in the long‐term treatment of acute myocardial infarction due to coronary sequelae of Kawasaki.     

Ring-calcification of coronary artery aneurysms in an adolescent

A 17-year-old asymptomatic boy with a history of Kawasaki disease in infancy was found to have an abnormal ring-calcification as seen in the chest roentgenogram and the electrocardiographic evidence of anteroseptal myocardial infarction. Coronary angiogram revealed aneurysms associated with ring-calcifications in the right coronary artery and subtotal obstruction of the left anterior descending coronary artery. A plain chest roentgenogram may, at times, be useful for identifying coronary aneurysms in patients with a possible history of Kawasaki disease.     

Severe Kawasaki disease in infants: two fatal cases

Kawasaki disease is a systemic vasculitis that manifests itself in many ways. Infants may present as atypical cases and commonly experience severe inflammatory changes. The two cases that are presented here highlight unusual severity and pathology. Patient 1 was a three-month-old infant with atypical Kawasaki disease who developed gangrenous lesions, and coronary and extracoronary artery aneurysms. Multiorgan failure ensued with diffuse cardiac and extracardiac aneurysms and thromboses at autopsy. Patient 2 was a five-month-old infant with Kawasaki disease, cholangitis and peripheral gangrene. Severe coronary artery aneurysms developed and he died following a myocardial infarction, despite multiple doses of intravenous immunoglobulin, acetylsalicylic acid (ASA) and corticosteroids. There is a higher occurrence of atypical disease and more severe vasculitis in infants with Kawasaki disease. Pathological changes are described, including coronary and extracardiac lesions. Patient 1 shows extensive peripheral gangrene and widespread aneurysms, and patient 2 illustrates severe cardiac complications with diffuse organ inflammation. Therapies including intravenous immunoglobulin, ASA, corticosteroids and antithrombotics are reviewed.     

An adult case of kawasaki disease with multiplex coronary aneurysms and0 myocardial infarction: The role of transesophageal echocardiography

Kawasaki disease (mucocutaneous lymph node syndrome) is an acute inflammatory disease that primarily affects infants and young children. in spite of proper therapy, coronary aneurysms develop in 10 to 25% of cases. Adult diagnosis of coronary aneurysm, presumably caused by Kawasaki disease, is rare. A 37-year-old male patient with previous inferior wall myocardial infarction (MI) was admitted with an acute anterior wall MI. Coronary angiography, performed 2 weeks after successful thrombolytic therapy, showed right coronary artery occlusion and multiplex (left main, left anterior descending, left circumflex, right coronary artery) giant coronary aneurysms. Transthoracic echocardiography was unable to detect the aneurysms. Transesophageal echocardiography (TEE) visualized a large left main coronary aneurysm with an occlusive thrombus and measured low flow velocity (0.2 m/s) in the proximal left anterior descending artery. At 4 weeks control, TEE showed marked regression of the thrombus, and it was not detectable after 6 months of oral anticoagulation with acenocumarol (International Normalized Ratio: 3-3.5) and standard postinfarction therapy. After 2 years of follow-up, the patient has no symptoms, and myocardial ischemia could not be provoked by stress tests [treadmill, dipyridamole single-photon emission computed tomography (SPECT)]. We conclude that, for diagnosis and follow-up of adult Kawasaki disease, transesophageal echocardiography is indicated. The importance and efficacy of long-term anticoagulant treatment should be emphasized in this disease.     

Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow‐up

Kawasaki disease is an acquired vasculitis that can affect the coronary arteries placing the patient at risk for coronary artery thrombosis, myocardial ischemia and infarction. The risk of complications related to coronary artery involvement persists for years despite recovery from the acute illness phase. The risk of late coronary disease progression necessitates long term follow‐up generally accomplished by non‐invasive echocardiography in pediatric patients. We review the utility of echocardiography in patients with Kawasaki disease as it relates to initial management, risk stratification and follow‐up of these children.     

Coronary artery aneurysms in a young patient with acute myocardial infarction: a case report

Coronary artery aneurysms are not uncommon. They are usually arteriosclerotic in origin, and may be congenital or secondary to injury, dissection, infection, inflammation, or Kawasaki disease (KD). Herein, we report a case involving a 25-year-old male smoker with acute myocardial infarction (AMI). Coronary angiography showed triple-vessel disease, coronary artery aneurysms, and diffuse ectasia. Coronary artery bypass grafting was performed without complications. Based on his history, serologic examinations, and angiographic findings, we suspected that his coronary artery aneurysms and ectasia were the adult sequelae of KD. This case is a good reminder that KD victims may suffer from young-onset AMI.     

Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile mucocutaneous lymph node syndrome with multisystemic vasculitis affecting mainly infants and children. Although several studies on cardiovascular lesions in KD have been done at the light microscopic level, the ultrastructural characteristics and incidences of these lesions have not been well defined. In order to investigate the myocardial and coronary microvascular sequelae in KD, we performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-up from 54 patients who had typical clinical manifestations of KD, of whom 47 had associated coronary aneurysms as demonstrated by coronary arteriography (CAG) or two-dimensional echocardiography in the acute or healed stage. The average age of onset was 2.2 years old and the duration of illness was from 2 months to 23 years. Follow-up CAG showed that the coronary aneurysms persisted in 33 of the 47 patients (8 with associated stenosis) and resolved in the remaining 14 patients. Ultrastructurally, the myocardial changes revealed hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. The coronary microvascular lesion was characterized by microvascular dilatation, endothelial cell injury, platelet aggregation with thrombosis, and stenotic lumen with thickened walls in the small arterioles. It persisted after convalescent stage even up to 23 years and closely correlated with the myocardial sequelae. Moreover, significantly increased incidences of myocardial and coronary microvascular lesions were found in patients with coronary artery lesion. These findings suggest the coronary microvascular lesion as a possible underlying factor of persistent sequelae in KD.     

Interventional Catheterization in Kawasaki Disease

The experiences of catheter interventional treatment in Kawasaki disease are quite limited. In this article, we report our experiences of catheter intervention. We performed the percutaneous transluminal coronary revascularization (PTCR) in 18 cases, the percutaneous transluminal coronary angioplasty (PTCA) in 12, the stent implantation in 7, and the percutaneous transluminal coronary rotational ablation (PTCRA) in 7, which resulted in success in 55.5%, 75%, 100%, and 100%, respectively. In this article, we discuss the indications and methods for coronary artery lesions of long-term Kawasaki disease. PTCR is useful for treatment of acute myocardial infarction and for prevention of massive thrombus formation, particularly within 2 years from the onset of Kawasaki disease. PTCA is effective in many instances, particularly in patients without severe calcification of the coronary artery. However, neoaneurysm had developed in a certain number of the patients. Stent implantation is more preferable than PTCA, because it may potentially prevent neoaneurysmal formation and restenosis. Rotational ablation is effective for the stiff stenotic lesions with severe calcification, particularly for ring calcification, which frequently develops in the long-term Kawasaki disease patients. The intravascular ultrasound is very useful in evaluating the tissue characterization of the coronary artery and to select the treatment strategy, and to evaluate the catheter interventional treatment.     

Changes in causes of sudden deaths by decade in patients with coronary arterial lesions due to Kawasaki disease

Over a 25-year period, we encountered 12 patients who died suddenly with coronary arterial lesions due to Kawasaki disease. We report their clinical course, and analyze the happenings of their deaths. Of the 12 patients, 10 were dead on arrival at hospital. Their age at death ranged from 13 months to 27 years, with a median of 16 years, and the interval from the onset of Kawasaki disease to death ranged from 2 months to 24 years. In 4 patients, death was found to be due to myocardial infarction, while in the remaining 8, it could not be determined. In 7 patients, coronary angiograms obtained less than 4 months after the acute onset of Kawasaki disease showed lesions bilaterally, most being giant aneurysms. Myocardial infarction had occurred in 6 patients prior to their death. In 1 patient of the late 1970s, who collapsed after running, cardiac sequels had not been suspected prior to autopsy. During the 1980s, 3 infants with bilateral giant aneurysms died within a year of the initial onset of Kawasaki disease, with acute myocardial infarction being the cause in 2 of them. In the late 1990s, and the 2000s, 5 patients died suddenly with left ventricular dysfunction, their ejection fractions being less than 40 percent more than 20 years after the initial onset of Kawasaki disease. Prior to their sudden deaths, they had had no cardiac events for many years, but had suffered previous myocardial infarctions. Multifocal premature ventricular contractions, and non-sustained ventricular tachycardia, are probable risk factors in such patients. Careful follow-up, checking for ventricular arrhythmia, is needed to prevent sudden death in patients suffering left ventricular dysfunction in the setting of Kawasaki disease.