Etsuko Tsuda

Another critical region for deletion of 22q11 : A study of 100 patients

Deletions at 22q11.1-q11.2 present with variable manifestations usually referred to as DiGeorge or velo-cardio-facial syndrome. We previously reported that deletions observed in patients with the syndrome can be subgrouped into three types (common large deletion, proximal deletion, and distal deletion) and demonstrated the presence of a second critical region for the syndrome. In order to characterize further the second critical region, a 22q11 deletion map was constructed from the data of 100 patients, using 12 DNA markers scattered in the common large deletion, and then a phenotype-genotype correlation was analyzed. The second critical region was found to correspond to the distal deletion encompassing the HCF2, cHKAD26, and D22S935 loci, and the proximal and distal deletions do not overlap each other. Although it seems that this condition is a contiguous gene syndrome, the phenotype of patients with these two types of deletion was indistinguishable from that of patients with the common large deletion. Thus, it is plausible that several genes located in the two segments corresponding to the two deleted regions are involved in the same developmental pathway or in an extremely long-range position effect.

Late death after arterial switch operation for transposition of the great arteries

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Twenty-Five-Year Outcome of Pediatric Coronary Artery Bypass Surgery for Kawasaki Disease

Background— The long-term outcome of pediatric coronary artery bypass for patients with severe inflammatory coronary sequelae secondary to Kawasaki disease is unknown. Methods and Results— One hundred fourteen children and adolescents ranging in age from 1 to 19 (median, 10) years at operation were followed up for as long as 25 years with a median of 19 years. The number of distal anastomoses was 1.7±0.8 per patient, and the internal thoracic artery was used in all but 3, most frequently for left anterior descending artery lesions. Saphenous vein grafts were used in 24 patients, mostly for non–left anterior descending artery lesions. Patients underwent multiple angiograms to evaluate their coronary and graft status. There was no operative or hospital mortality. Both 20- and 25-year survival rates were 95% (95% confidence interval [CI], 88 to 98). Five deaths occurred, all cardiac in origin. Cardiac event–free rates at 20 and 25 years were 67% and 60% (95% CI, 46 to 72), respectively. Percutaneous coronary intervention and reoperation were the most common events. Overall, the 20-year graft patency rate was 87% (95% CI, 78 to 93) for internal thoracic artery grafts (n=154) and 44% (95% CI, 26 to 61) for saphenous vein grafts (n=30) (P<0.001), and the rate for non–left anterior descending artery lesions was also significantly better for arterial grafts (87% [95% CI, 73 to 94]; n=59) than for saphenous vein grafts (42% [95% CI, 23 to 60]; n=27) (P=0.002). Eighty-eight patients (77%) remain on medications, but all 109 survivors are presently symptom free in their daily activities. Conclusions— Although the 25-year survival was excellent after pediatric coronary bypass for Kawasaki disease, the event-free rate declined progressively. This reality mandated continued follow-up. Reinterventions successfully managed most cardiac events. An internal thoracic artery graft was the most favorable for children.

Coronary Artery Dilatation Exceeding 4.0 mm During Acute Kawasaki Disease Predicts a High Probability of Subsequent Late Intima-Medial Thickening

We used intravascular ultrasound (IVUS) to compare the degree of coronary artery dilatation during the acute phase of Kawasaki disease with the extent of intima-medial thickening more than 10 years later. We wanted to determine if there was a threshold degree of dilatation that was highly predictive of later thickening. Twenty-eight patients with a mean age of 17.3 ± 1.7 years were studied; the mean interval from the initial selective coronary angiography to the IVUS study was 15.0 ± 1.6 years. We measured the maximum intima-medial thickness of selected coronary arterial segments in IVUS images and measured the largest diameters of the corresponding coronary arterial segments in the initial coronary angiograms. A significant correlation was found between the initial diameters of the coronary arteries and the intima-medial thickness more than 10 years later in the right coronary, the left anterior descending coronary, and the left circumflex arteries. The coefficient of correlation was 0.77 (n = 120, p < 0.0001), and for the bifurcation of the left coronary artery it was 0.50 (n = 26, p < 0.01). For this study, abnormal intima-medial thickness was defined as more than 0.40 mm. When the initial coronary arterial dilatation exceeded 4.0 mm, the sensitivity was 28/31 (90%) and the specificity was 87/89 (98%) in the right coronary, the left anterior descending coronary, and the left circumflex arteries. For the bifurcation of the left coronary artery, the sensitivity was 14/21 (67%) and the specificity was 5/5 (100%).

National Survey of Coronary Artery Bypass Grafting for Coronary Stenosis Caused by Kawasaki Disease in Japan

Background—We surveyed the national experience of coronary artery bypass grafting (CABG) for coronary sequelae of Kawasaki disease (kDa) in 2002. Methods and Results—A questionnaire was returned from 323/552 (59%) institutions. Two hundred forty-four patients (188 male 56 female) since 1975 were identified. The mean number of grafts was 1.8 and the age at operation ranged from 1 to 44 years (median 11 years). The interval from the onset of kDa to operation ranged from 1 month to 42 years (median 8 years), whereas the follow-up period was from 7 days to 25 years (median 5 years). Previous myocardial infarction was found in 70 patients (28%). When the age at operation was older than 12 years, patency rates for internal thoracic artery grafts (ITA) at 1, 5, and 15 years were 95%, 91%, and 91%, respectively (n=156). When the age at operation was younger than 12 years, the corresponding values were significantly lower, with 1, 5, and 15 years being 93%, 73%, and 65%, respectively (n=146) (P<0.05). Reoperation was performed in 14 patients (6%). Death occurred in 15 patients (6%). Nine of the 14 late deaths were sudden. Six of 8 patients with a left ventricular ejection fraction (LVEF) <40% died. Conclusion—The results of ITA in those aged 12 years or older were favorable. LVEF influenced prognosis.

Result of surgical treatments in patients with coronary-arterial obstructive disease after Kawasaki disease.

OBJECTIVE To determine the efficacy of coronary artery bypass grafting (CABG) in young patients with coronary-arterial obstructive disease subsequent to Kawasaki disease. METHODS CABG was employed in 100 patients. Age at operation ranged from 1 to 23 years at a mean of 10+/-5 years. The number of bypass grafts placed was 1-5/patient (a mean of 1.7+/-0.8). The left internal-thoracic artery (ITA) was used as a graft in 99 patients; the right internal thoracic artery in 39, the gastroepiploic artery in nine and the saphenous vein in 21. RESULTS All patients survived the procedures. In the follow-up of 6.7+/-4.5 years, two patients died, one because of a traffic accident and the other due to sudden death. Considerable myocardial ischemia recurred postoperatively in 15, because of either obstruction of the bypass grafts or progression of other coronary-arterial obstructions. Of these, symptoms spontaneously regressed without interventional procedures in four, reoperation was indicated in four and catheter intervention was efficiently carried out in the remaining seven. Another two patients had episodes of critical ventricular arrhythmia; one of them with severe left ventricular dysfunction subsequently underwent cardiac transplantation. The patency rates of the arterial grafts were 94, 82 and 78% at 1, 5 and 10 years, respectively, and this was higher than that of the venous grafts (82, 63 and 36%, respectively). Strenuous exercise is currently prohibited in 15 patients, while the remaining 83 patients are doing well with no obvious restriction in their daily lives. CONCLUSION Collaborating with catheter interventions, CABG using the arterial grafts can provide attractive results in patients with obstructive coronary arteries associated with Kawasaki disease.

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.

Guidelines for catheter intervention in coronary artery lesion in Kawasaki disease.

Abstract The Research Committee of Ministry of Health, Labour and Welfare ‘Study of treatment and long‐term management in Kawasaki disease’ reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.

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.

A survey of the 3-decade outcome for patients with giant aneurysms caused by Kawasaki disease

BACKGROUND Our purpose was to determine the outcome in patients with a more-than-20-year history of giant coronary aneurysms (GAs) caused by Kawasaki disease (KD). METHODS Between 2010 and 2011, the incidence and outcome of cardiac events (CEs) in patients with GA was surveyed by questionnaire by the Kinki area Society of KD research. Death, acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), percutaneous coronary catheter intervention, syncope, and ventricular tachycardia were considered as CEs. Survival rate and CE-free rate were analyzed by the Kaplan-Meier method. RESULTS We enrolled 245 patients (187 were male, 58 were female), 141 with bilateral GA and 104 with unilateral GA. The interval between the onset of acute KD to the time of survey ranged from 0.2 to 51 years, and the median was 20 years. Death, AMI, and CABG occurred in 15 (6%), 57 (23%), and 90 patients (37%), respectively. The CE-free rate and the survival rate at 30 years after KD were 36% (95% CI 28-45) and 90% (95% CI 84-94), respectively. The 30-year survival rate for bilateral GA was 87% (95% CI 78-93), and for unilateral GA, it was 96% (95% CI 85-96; hazard ratio 4.60, 95% CI 1.27-29.4, P = .027). The 30-year survival rate in patients with AMI was 49% (95% CI 27-71), and the 25-year survival rate in patients undergoing CABG was 92% (95% CI 81-98). CONCLUSIONS The outcome differed significantly between bilateral GA and unilateral GA. The results focus attention on the need to preserve myocardial perfusion, especially in high-risk patients with bilateral GA. An understanding of the optimal CABG would be useful in bilateral GA.