Yasuo Ono

Coronary arterial lesions of Kawasaki disease: cardiac catheterization findings of 1100 cases.

SummaryIn our institute, 1100 patients with a history of Kawasaki disease have been catheterized for selective coronary arteriography. Their age at examination ranged from four months to 13 years. Coronary artery lesions (CAL) were found in 262 patients. As far as the type of the CAL was concerned, occlusion was noted in 20 (7.6%), segmental stenosis in 15 (5.7%), localized stenosis in 62 (23.7%), aneurysm in 93 (35.5%), and dilatation in 72 patients (27.5%). In terms of the total number of lesions, there were 23 occlusions, 19 segmental stenoses, 109 localized stenoses, 449 aneurysms and 307 dilatations.The 262 patients with CAL were analyzed according to the interval from the onset to the time of selective coronary arteriography. The incidence of both occlusion and segmental stenosis was lowest in the group who were catheterized shortly after the onset of disease, whereas the prevalence of aneurysm was highest in this group. But the prevalence of dilatation was highest in the group of patients who were catheterized late. A total of 12 patients had to undergo femoral arterial thrombectomy for arterial thrombosis following the catheterization, but no other major complication was experienced.

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.

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%).

Follow-up study of coronary artery lesions due to Kawasaki disease by serial selective coronary arteriography in 200 patients

SummaryIn a follow-up study of coronary artery lesions (CAL) due to Kawasaki disease, 200 patients were examined by serial coronary arteriography 1 year after first detection of the condition. On comparing the findings of the two coronary angiographic studies, a worsening of stenotic lesions was detected in 30 patients (15%; 40 of 139 stenotic lesions, 29%), while improvement of stenotic lesions was seen in 24 patients (12%; 40 lesions, 29%). Relating these changes in CAL to the interval from the onset of disease to the first coronary arteriography showed the rate of increased or new stenotic lesions (37%) to be higher in the late group, in which the first study was performed 5 months after the onset of the disease, than in the early group (21%), in which the study was done within 4 months from the disease onset. The frequency of decrease in aneurysm size was higher in the early group (70%) than in the late group (19%).

Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers

Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the activin receptor-like kinase 1 (ALK1) gene have been reported in heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH). However, the relation between clinical characteristics and each gene mutation in IPAH and HPAH is still unclear, especially in childhood. The aim of this study was to determine, in a retrospective study, the influence and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four patients with IPAH or HPAH whose onset of disease was at <16 years of age were included. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p = 0.1205). In conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers.

Clinical significance of morphologic classification of coronary arterial segmental stenosis due to Kawasaki disease

Coronary arteriograms obtained in 1,392 patients from a cohort of 4,562 with Kawasaki disease showed 395 to have coronary arterial lesions. The specific lesions, known as segmental stenoses, were observed in 62 patients, involving 68 coronary arterial branches. The lesions involved the right coronary artery in 56 cases (14.2% of the group with arterial lesions) and the left coronary artery in the other 12 (3% of the overall group with arterial lesions). Three morphologic variations were observed. Braid-like lesions accounted for 15 lesions, involving the right coronary artery and occurring < 2 years after the onset of Kawasaki disease. Bridging vessels were observed in 40 of 68 arterial lesions, 30 of which involved the right coronary artery. Of these bridging vessels, 86% were present within 4 years of onset of the disease. Pericoronary communications were observed in the remaining 13 of 68 lesions, 11 involving the right coronary artery and appearing at variable intervals, but usually significantly later than the other lesions. Myocardial ischemia was found at the first study in 60% of braid-like lesions, but in only 29% of the lesions at follow-up studies. Of bridging vessels or pericoronary communications, 95 and 77%, respectively, were found to have produced ischemia in the initial study, which persisted in 78 and 77%, respectively. There are 3 different mechanisms involved in the formation of segmental stenosis, with different prognoses for the clinical course of myocardial ischemia.

Myocardial ischemia in Kawasaki disease: follow-up study by cardiac catheterization and coronary angiography.

SummaryThe clinical course of ischemic heart disease due to Kawasaki disease was analyzed. The subjects (children aged two months to eight years) were divided into two groups. Group 1 (n=23) consisted of children who had sustained myocardial infarction (MI) and group 2 (n=13) of those without clinical symptoms or signs of MI, but in whom signs of an obstructive lesion had appeared on coronary arteriography during the follow-up period. Changes in the left ventricular ejection fraction (LVEF) and the appearance of coronary arterial lesions on first and second angiography were analyzed in the two groups. It was found that (a) LVEF (51.4±13.4%, mean ± SD) at the first study, obtained after MI in group 1, was significantly lower than that (64.3±3.7%) at the second one in group 2, which revealed recently developed obstructive lesions; (b) there was no significant difference between the two groups as to the severity of stenotic lesions on coronary arteriography; and (c) comparison of LVEF at the first angiography with that at the second study showed significant improvement in group 1 (1st, 54.2±12.0%; and 2nd, 60.8±9.7%) and significant depression in group 2 (1st, 68.1±4.4%; and 2nd, 64.3±3.7%).

Simultaneous microdetermination of bosentan, ambrisentan, sildenafil, and tadalafil in plasma using liquid chromatography/tandem mass spectrometry for pediatric patients with pulmonary arterial hypertension

A simultaneous, selective, sensitive, and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of bosentan, ambrisentan, sildenafil, and tadalafil in 50μL of human blood plasma. Diluted plasma samples were extracted using a solid-phase extraction procedure with 2% formic acid and methanol. The four drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2mL/min for 5min. The drugs were detected by a tandem mass spectrometer with electrospray ionization using deuterated compounds as internal standards. Calibration curves were generated over the linear concentration range of 2-1000ng/mL in plasma with a lower limit of quantification of 2ng/mL for all compounds. Finally, this validated method was applied to a clinical pharmacokinetic study in pediatric patients with pulmonary arterial hypertension (PAH) following the oral administration of PAH drugs. These results indicate that this method is suitable for assessing the risk/benefit of combination therapy in the pediatric population and useful for therapeutic drug monitoring for PAH treatment.

Thrombolysis in the treatment of patients with Kawasaki disease

Thrombolysis was used in 13 procedures to treat eight patients with massive thrombosis of coronary aneurysms due to Kawasaki disease. The patients have now been followed for periods ranging from 2.5 years to 7.4 years subsequent to treatment. The procedures included intracoronary or intravenous infusion of urokinase and intravenous administration of tissue plasminogen activator. Thallium myocardial imaging, coronary arteriography and echocardiography were used for evaluation of the efficacy of the therapy and for follow-up studies. The latest time of treatment was 17 months after the onset of the disease. No new formation of massive thrombus was observed in any of the aneurysms. In five patients, eight of 13 procedures were judged to be successful. In the four patients with symptoms of myocardial ischemia, thrombolysis was undertaken immediately after the onset of symptoms. In the other patient, thrombolysis was attempted 36 days after the onset and produced remarkable improvement in the degree of ischemia. In the other four patients with no symptoms of ischemia, the therapy was undertaken when thrombus was detected in a coronary aneurysm. Aortocoronary bypass surgery was undertaken subsequent to the thrombolytic therapy in three patients, but proved satisfactory in only one patient. At follow-up, five patients have shown improvement in the degree of myocardial ischemia after treatment. Our results suggest that careful observation is needed to detect formations of thrombus in large coronary arteries for at least 1½ years after the onset of Kawasaki disease. Even if repeated thrombolytic therapy is required, it seems to be effective in checking the progression of ischemic heart disease.

Improvement of Left Ventricular Function After Changing the Pacing Site in a Child with Isolated Congenital Complete Atrioventricular Block and Dilated Cardiomyopathy

We report a case of isolated congenital complete atrioventricular block with left ventricular dysfunction after pacemaker implantation that improved after the pacing site was changed. During the neonatal period, a pacemaker wire was implanted on the right ventricular epicardium and pacing was initiated. Decreased ejection fraction and a perfusion defect around the septum on myocardial scintigraphy were observed during follow-up. Induced left bundle branch block was thought to be causing interventricular asynchrony, and the pacing site was change to the left ventricular epicardium. Ejection fraction improved and the perfusion defect resolved. Lead relocation may be useful for left ventricular dysfunction that develops during right ventricular pacing.