Time Course of Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVES: To determine the timeframe in which coronary artery aneurysms (CAAs) caused by Kawasaki disease reach their maximum diameter, the timeframe in which they regress to normal size, and the cutoff point of the diameter for CAA regression. STUDY DESIGN: We reviewed 195 CAAs of the right coronary artery, left anterior descending artery, and left coronary artery measured by 2-dimensional echocardiography ≥5 times for 1 year after Kawasaki disease in 84 patients using medical records from 1995. The maximum diameters of CAAs were investigated retrospectively. The time to CAA regression using both absolute diameter and Z score were investigated. The cutoff points of the diameter of CAA regression in the 2 classifications were identified using receiver operator characteristic curve analysis. One year after Kawasaki disease, a CAA of <3.0 mm in absolute diameter and a Z score of <2.5 were defined as CAA regression. RESULTS: The time when CAAs reached their maximum diameter ranged from 11 days to 87 days, with a median of 35 days (n = 195). The time to CAA regression ranged from 41 to 386 days, with a median of 136 days in the absolute diameter classification (n = 92); 78% of CAA regression regressed by 200 days. The cutoff point for CAA regression at one year was 5.7 mm for the absolute diameter (area under the curve, 0.887; P < .0001; n = 190) and 9.5 for the Z score (area under the curve, 0.815; P < .0001; n = 195). CONCLUSIONS: CAAs with a smaller diameter regressed earlier, and most CAAs of <6 mm regressed by 6 months after Kawasaki disease.

Cardiac Valvular Lesions due to Kawasaki Disease: A Japanese Nationwide Survey.

OBJECTIVES: To clarify the characteristics of valvular lesions after Kawasaki disease with a Japanese nationwide survey. STUDY DESIGN: Among 137 026 patients in the nationwide Japanese surveys between 2007 and 2016, 290 (0.2%) with valvular sequelae were investigated by questionnaires. RESULTS: Among the 290 patients with valvular sequelae, mitral regurgitation (MR), tricuspid regurgitation, aortic regurgitation, and pulmonary regurgitation were present 1 month after the development of Kawasaki disease in 183 (63%), 112 (39%), 39 (13%), and 49 (17%) patients, respectively. The numbers of patients with MR during the acute phase and 1 year after developing Kawasaki disease were 208 (72%) and 95 (33%), respectively. MR improved significantly during the late period (P < .0001). Although aortic regurgitation and tricuspid regurgitation also improved significantly (P < .001), pulmonary regurgitation did not change. Ruptured mitral valves chordae tendineae occurred in 6 infants by 6 months of age, within 4 months after the onset of Kawasaki disease. Three patients needed mitral valve plasty, and 1 patient died of acute heart failure. Another 4-month-old girl died of an acute myocardial infarction with MR. In the acute phase, there was a significant difference in the MR severity between the intravenous immunoglobulin-responder group and the intravenous immunoglobulin-resistant group (P < .05). CONCLUSIONS: The inflammation caused by acute Kawasaki disease affects the function of the mitral valves. Most cases of MR improve with the alleviation of inflammation. Severe MR may have decreased with the development of treatment for acute vasculitis. However, ruptured mitral valves chordae tendineae rarely occurs in infants younger than 6 months old, within 4 months after Kawasaki disease.

Stenotic Lesions and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVES: To determine the prevalence of subsequent stenotic lesions based on the maximum diameter of the largest coronary artery aneurysm in patients with Kawasaki disease and the threshold value of coronary artery diameter associated with risk of developing stenotic lesion. STUDY DESIGN: There were 214 patients (160 males) who had at least 1 aneurysm in a selective coronary angiogram (CAG) done <100 days after the onset of Kawasaki disease were studied. We measured the maximal coronary artery aneurysm diameter in 3 major branches in the initial CAGs. Branches were classified into 3 groups according to their maximal coronary artery aneurysm diameter: large, ≥8.0 mm; medium, ≥6.0 mm but <8.0 mm; and small, <6.0 mm. Subsequent CAGs were performed in the late follow-up period. We investigated the stenotic lesion in the follow-up CAGs, and evaluated the prevalence of stenotic lesion in each group based on body surface area (BSA) by the Kaplan-Meier method. Localized stenosis of ≥25% and complete occlusion were included as stenotic lesion in this study. We also determined the cutoff point for stenotic lesion. RESULTS: The median interval from the initial CAGs to the latest CAG was 8 years, with a maximum of 32 years. For a BSA of <0.50 m2, the 20-year prevalence of large and medium stenotic lesions was 78% (n = 62; 95% CI, 63-89) and 81% (n = 40; 95% CI, 63-89), respectively. For a BSA of ≥0.50 m2, large and medium stenotic lesions were 82% (n = 75; 95% CI, 67-91) and 40% (n = 56; 95% CI, 20-64), respectively (P < .0001). CONCLUSION: The cutoff points of the coronary artery diameter within the first 100 days after the onset of Kawasaki disease leading to a stenotic lesion in the late period, were a diameter of ≥6.1 mm with a BSA of <0.50 m2 and a diameter of ≥8.0 mm with a BSA of ≥0.50 m2. Those cutoff points would have corresponded with a Z score of at least 10 on 2-dimensional echocardiography. Careful follow-up and antithrombotic therapy should be provided to patients who meet these criteria.

Cardiac Events and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVES: To clarify the occurrence of cardiac events based on the maximal diameter of the maximal coronary artery aneurysm (CAA) in Kawasaki disease (KD). STUDY DESIGN: Two hundred fourteen patients (160 male and 54 female) who had had at least 1 CAA in the selective coronary angiogram less than 100 days after the onset of KD were studied. We measured the maximal CAA diameters in the major branches of the initial coronary angiograms. Death, myocardial infarction and coronary artery revascularization were included as cardiac events in this study. We divided the patients into three groups based on the maximal CAA diameter (large ≥8.0 mm; medium ≥6.0 mm and <8.0 mm; small <6.0 mm). Further, we also analyzed the cardiac events based on laterality of maximal CAA (bilateral, unilateral) and body surface area (BSA). RESULTS: Cardiac events occurred in 44 patients (21%). For BSA < 0.50 m2, the 30-year cardiac event-free survival in the large and medium groups was 66% (n = 38, 95% CI, 49-80) and 62% (n = 27, 95% CI, 38-81), respectively. For BSA ≥ 0.50 m2, that in large group was 54% (n = 58, 95% CI, 40-67). There were no cardiac events in the medium group for BSA ≥0.50 m2 (n = 36) and the small group (n = 56). In the large analyzed group, the 30-year cardiac event-free survival in the bilateral and unilateral groups was 40% (n = 48, 95% CI, 27-55) and 78% (n = 48, 95% CI, 63-89), respectively (P < .0001). CONCLUSIONS: The group with the highest risk of cardiac events was the patient group with the maximal CAA diameter ≥6.0 mm with BSA < 0.50 m2 and the maximal CAA diameter ≥8.0 mm with BSA ≥ 0.50 m2. At 30 years after the onset of KD, cardiac event-free survival was about 60%. Given the high rate of cardiac events in this patient population, life-long cardiovascular surveillance is advised.

Late Wall Thickening and Calcification in Patients After Kawasaki Disease.

OBJECTIVES: To evaluate the relationship between the initial diameters of the coronary arteries immediately after the onset of Kawasaki disease (KD) and late increased coronary wall thickening/coronary artery calcification (CAC). STUDY DESIGN: Sixty-five patients (50 males and 15 females) who had undergone selective coronary angiography (CAG) <100 days after the onset of KD were studied late in disease by dual-source computed tomography (DSCT). The maximum diameters of each segment were measured in the initial CAGs, and the relationship between the maximum diameters and the appearance of increased wall thickening/CAC was analyzed. The study cohort was divided into 2 groups: the branches group (BG) and bifurcation at the left coronary artery (LCA) group. The cutoff point of acute coronary artery dilatation for increased wall thickening/CAC was calculated for each group. Risk factors for the appearance of CAC in each group were investigated, as was the sex difference related to the prevalence of CAC in coronary artery lesions (CALs) of the initial CAGs. RESULTS: The cutoff points of acute coronary dilatation for increased wall thickening were 4.8 mm in the BG (n = 344; area under the curve [AUC], 0.89; P < .001) and 5.3 mm in the LCA group (n = 65; AUC, 0.87; P < .001). The interval from the onset of KD (P < .0001) and sex (P = .0084) were also related to the appearance of CAC in the BG. CONCLUSION: Acute coronary dilatation of exceeding ~5.0 mm can lead to late abnormalities of the coronary artery wall. The prevalence of CAC increases with age. There was a sex-based difference in the late incidence of CAC in the CALs.

Characteristics and Fate of Systemic Artery Aneurysm after Kawasaki Disease.

OBJECTIVE: To determine the long-term outcome of systemic artery aneurysms (SAAs) after Kawasaki disease (KD). STUDY DESIGN: We investigated the characteristics and the fate of SAAs in 20 patients using medical records and angiograms. The age of onset of KD ranged from 1 month to 20 months. The interval from the onset of KD to the latest angiogram ranged from 16 months to 24 years. The regression rate of peripheral artery aneurysm and the frequency of stenotic lesions were analyzed by the Kaplan-Meier method in 11 patients who had undergone initial angiography within 4 months. RESULTS: The mean duration of fever was 24 ± 12 days. All 20 patients had at least 1 symmetric pair of aneurysms in bilateral peripheral arteries, and 16 patients had multiple SAAs. The distributions of SAAs was as follows: brachial artery, 30; common iliac artery, 20; internal iliac artery, 21; abdominal aortic aneurysm, 7; and others, 29. The frequencies of regression of SAA and of the occurrence of stenotic lesions at 20 years after the onset of KD were 51% and 25%, respectively (n = 42). The diameter of all SAAs in the acute phase leading to stenotic lesions in the late period was >10 mm. CONCLUSION: SAAs occurred symmetrically and were multiple in younger infants and those with severe acute vasculitis. The fate of SAAs resembles that of coronary artery aneurysms, and depends on the diameter during the acute phase. Larger SAAs can lead to stenotic lesions in the late period.