Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire.

OBJECTIVES: To assess the pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables, we regionally evaluated the flow velocity dynamics and flow reserve in coronary vessels with lesions using an intracoronary Doppler flow guide wire. BACKGROUND: The pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables have not been completely clarified, and we previously reported some discrepancies between coronary angiographic findings and exercise stress tests in Kawasaki disease. METHODS: Doppler phasic coronary flow velocity was determined using an 0.018-in. (0.046-cm) intracoronary Doppler flow guide wire at rest and during the adenosine triphosphate-induced hyperemic response in 95 patients (75 male, 20 female, mean age 9.8+/-6.2 years) with Kawasaki disease. RESULTS: In 25 patients with coronary aneurysms in 29 vessels, the average peak velocity and diastolic to systolic velocity ratio were significantly (p < 0.05) decreased in the moderate-sized and large-sized aneurysms. Significantly lower values in coronary flow reserve (CFR) were noted in 3 of 10 vessels with moderate aneurysms and in 4 of 7 vessels with large aneurysms. A significant positive correlation (y = 0.53x + 14.6, r2 = 0.91) was observed between the percent diameter stenosis evaluated by angiography and that calculated from the flow velocity measurement. However, the percent diameter stenosis calculated from the flow velocity measurement was underestimated compared with that determined by angiography in the stenotic lesions of intermediate severity. A reduced CFR was noted in five of seven vessels with intermediate stenosis ranging from 50% to 75%, and also in three vessels with mild stenosis ranging from 30% to 40%. A reduced CFR was also observed in six of the eight angiographically normal vessels associated with the area of reduced perfusion on exercise thallium-201 myocardial scintigraphy. CONCLUSIONS: Abnormalities in flow dynamics and a reduction in flow reserve were revealed in coronary aneurysms of intermediate to large size and in stenotic lesions, even of mild to intermediate severity, in patients with Kawasaki disease. Abnormalities in the coronary microcirculation, as well as epicardial lesions, contribute to the pathophysiologic responses in Kawasaki disease.

Transformation of coronary artery aneurysm to obstructive lesion and the role of collateral vessels in myocardial perfusion in patients with Kawasaki disease.

OBJECTIVES: The aim of this study was to examine the transformation of coronary artery aneurysms to obstructive lesions and to assess the role of collateral vessels in patients with Kawasaki disease. BACKGROUND: Coronary artery aneurysms, especially giant aneurysms, are known to become obstructive lesions in patients with Kawasaki disease. However, the process of transformation is not yet clear. METHODS: Thirty patients (average age 9.9 years) with obstructive lesions secondary to Kawasaki disease underwent repeated coronary artery angiography and thallium myocardial scintigraphy over a mean period of 7.7 years after the acute onset of Kawasaki disease. RESULTS: In the 27 patients who were enrolled in the acute phase of the disease because of coronary artery aneurysms, the later transformation to obstructive lesions was not significantly different between the 61 large and 6 medium-sized aneurysms. Obstructive transformation of aneurysms was more rapid in the right than in the left coronary artery (p < 0.001). From the last coronary angiogram obtained, the obstructive lesions were classified as localized stenosis > 90% in 10 vessels, occlusions in 6 vessels and segmental stenosis in 26 vessels. Both localized and segmental stenosis occurred significantly more often in the left anterior descending and the right coronary artery than in other vessels (p < 0.05). The incidence of collateral vessels was significantly correlated with a younger age at onset of Kawasaki disease, especially in patients with segmental stenosis (p < 0.001). Collateral vessels did not develop in the presence of localized stenosis regardless of the occurrence of myocardial ischemia. All occluded vessels had collateral development regardless of the presence of myocardial infarction. CONCLUSIONS: The treatment of localized stenosis may play an important role in preventing myocardial infarction in the chronic phase of Kawasaki disease.

Effect of coenzyme Q10 on experimental atherosclerosis and chemical composition and quality of atheroma in rabbits.

The effects of the administration of coenzyme Q10 (3 mg/kg per day) (group A, n=10) and placebo (aluminum hydroxide, 3 mg/kg per day) (group B, n=10) were compared over 24 weeks in a randomized, single-blind, controlled trial. There were two groups of rabbits receiving a trans fatty acid (TFA)-rich diet (5-8 g/day) for 36 weeks. Oxidized rabbit chow with vitamin C plus ferric chloride was administered for 4 weeks in all rabbits. Intervention with coenzyme Q10 after feeding of TFA-rich diet was associated with a significant decline in thiobarbituric acid reactive substances (TBARS), diene conjugates and malondialdehyde, and an increase in plasma levels of vitamin E in the coenzyme Q group compared to placebo group. These changes, which were indicators of a decrease in oxidative damage, were independent of lipid lowering. The aortic and coronary artery plaque sizes, coronary atherosclerosis index, aortic and coronary atherosclerosis scores were significantly lower in the coenzyme Q group than placebo group. Aortic and coronary plaque frequencies, as well as frequencies of ulceration, thrombosis or hemorrhage, and cracks and fissures, were also significantly lower in the coenzyme Q group, indicating a better quality of atheroma compared to those in the control group. Aortic cholesterol, triglycerides and sudanophilia were significantly lower and vitamin E significantly higher in the coenzyme Q group in comparison to the placebo group indicating that coenzyme Q10 can have beneficial effect on the chemical composition of atheroma. The findings suggest that antioxidant therapy with coenzyme Q10 may be used as an adjunct to lipid lowering for additional beneficial effects related to chemical composition and quality of atheroma independent of hypolipidemic agents.

Effects of coronary artery aneurysms on intracoronary flow velocity dynamics in Kawasaki disease.

In coronary artery aneurysms associated with Kawasaki disease, a significant decrease in coronary flow velocity together with an abnormal flow profile and a reduction in coronary flow reserve were observed, and were significantly correlated with the size of the aneurysm. These results suggest that coronary arterial aneurysms impair coronary circulation.

Overview of pharmacological treatment of Kawasaki disease.

Kawasaki disease has been researched for 32 years but its aetiology is still unknown. Conventional therapy for the disease includes corticosteroids and aspirin (acetylsalicylic acid) as anti-inflammatory and/or antithrombotic agents but they have not been proven to prevent coronary artery aneurysms. Although a high incidence of liver dysfunction in Japanese patients with Kawasaki disease receiving high dose aspirin (> or =80 mg/kg/day) suggests racial differences in salicylate sensitivity, the duration of fever in patients receiving high dose aspirin is shorter than that in patients receiving moderate dosages (30 to 50 mg/kg/day). Furthermore, most corticosteroid-resistant patients were found to develop coronary artery aneurysms, many of which were large. With the clarification of the pathogenesis and clinical features of Kawasaki disease, advances in its treatment have been achieved. The introduction of high-dose intravenous gamma-globulin (IVGG) was an epoch in this field and IVGG is now a standard therapy with the incidence of persistent coronary aneurysms 1.9% in children with the disease receiving IVGG. Today, research is mainly directed toward the treatment of IVGG-resistant patients. One to 3 days of pulsed doses of methylprednisolone (30 mg/kg/day) or readministration of IVGG 1 g/kg (once to several times) has been recommended for patients with IVGG-resistant Kawasaki disease.

Cardiac involvement and prognosis in acute mucocutaneous lymph node syndrome.

Cardiac involvement and prognosis were studied in the acute febrile mucocutaneous lymph node syndrome which recently has been found among Japanese infants and younger children. The reason for its particular predilection for the main coronary arteries and the pathologic process are discussed in relation to the pathogenesis and nutrient of the main coronary arteries.

Effect of CABG on coronary flow reserve in atresia of the left coronary ostium.

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.

Assessment of effects of intravenous dipyridamole on regional myocardial perfusion in children with Kawasaki disease without angiographic evidence of coronary stenosis using positron emission tomography and H2(15)O.

BACKGROUND: Positron emission tomography and H2(15)O were used to characterize regional myocardial blood flow and distribution at rest and in response to dipyridamole in children with Kawasaki disease but without angiographic evidence of coronary stenosis. METHOD: Patients were classified into two groups on the basis of the results of selective coronary angiography: subjects in group I had normal coronary angiograms (n = 4): subjects in group II had aneurysms (n = 5). RESULTS: Myocardial perfusion, assessed with H2(15)O, was homogeneous over all regions at rest and at peak flow in groups I and II. Dipyridamole infusion significantly reduced myocardial perfusion reserve in group II (average 3.56 +/- 1.03 fold versus 5.06 +/- 1.37 fold in group I, P < 0.001). CONCLUSION: Our results suggest that aneurysms associated with Kawasaki disease may reduce myocardial reserve. Non-invasive quantitative assessment of myocardial blood flow with positron emission tomography and H2(15)O was useful in assessing the functional capacity of coronary artery lesions and the extent of myocardial damage in children with Kawasaki disease.

Development of acquired cystic disease and adenocarcinoma of the kidney in glomerulonephritic chronic hemodialysis patients.

The fate of the contracted kidney in long-term hemodialysis patients was examined. Total kidney volume was measured by computer assisted tomography in 96 chronically hemodialyzed patients with chronic renal failure due to chronic glomerulonephritis. The presence of cysts and/or tumor in the renal parenchyma was evaluated. Kidney volume decreased progressively up to 3 years after the start of dialysis. However, after 4 years of dialysis, it then increased in a number of cases. Multiple cysts were found in 43.5% of patients on dialysis for less than 3 years and in 79.3% of patients who had been on dialysis for more than 3 years. They were found in 100% of those whose total kidney volume exceeded 50 ml despite more than 3 years dialysis. Bilateral nephrectomy was performed in 4 cases who had been dialyzed for more than 5 years and all showed acquired cystic disease of the kidney. Three out of 4 resected cases had adenocarcinoma and multiple adenomas in addition to acquired cystic disease of the kidneys. The other had intracystic epithelial hyperplasia. These results suggest that long-term hemodialysis is associated with a very high incidence of acquired cystic disease of the kidney. There is frequent enlargement of the contracted kidney, and a high incidence of renal adenocarcinoma in patients with glomerulonephritis leading to treatment with hemodialysis.

R-wave voltage in the right precordial leads in anthracycline cardiomyopathy: a clinical study.

It was observed that the QS pattern in the right precordial leads of electrocardiograms of patients treated with anthracycline antibiotics resulted in congestive heart failure. In a review of the literature dealing with patients with anthracycline cardiomyopathy, terminal electrocardiograms, when available, showed the QS pattern in the right precordial leads in all patients. The relationship between a decreased R-wave voltage in lead V1 and an increase of the anthracycline dose was evaluated by a clinical study of ten patients. Analysis was subdivided into two categories (group A and B). In group A, there was a dose-response relationship. Electrocardiograms in group B, on the other hand, did not show low R-waves. The present study suggests that increased injury to myocardial cells in the regions of the anterior septum and anterior left ventricular wall might be important in the pathogenesis of anthracycline cardiomyopathy. Patients in group B seemed to be able to tolerate chronic anthracycline cardiac toxicity.

Coronary artery aneurysms develop in weanling rabbits with serum sickness but not in mature rabbits. An experimental model for Kawasaki disease in humans.

The involvement of the cardiovascular system in rabbits with serum sickness is similar of that in Kawasaki disease, both with respect to the histologic changes of the myocardium, the valves, the coronary arteries, and the aorta and to the sequence with which they appear. Although coronary arteritis appears the same histologically, aneurysms did not occur in mature rabbits, even in case of necrosis of an arterial segment with deletion of muscle and elastic tissue. On the other hand, weanling rabbits with serum sickness had a tendency to develop aneurysms of coronary arteries, despite little cellular infiltration and reactive fibrocellular hyperplasia. The age factor thus appears to play an important role in the development of coronary aneurysms in Kawasaki disease, irrespective of the underlying mechanism, be it a markedly increased permeability to mediators through degenerated endothelial cells, or primary degenerated muscle cells with marked thinning of the media without much inflammatory cellular reaction. Furthermore, this study provides an insight into the long-term prognosis of transient dilatation of coronary arteries in the acute stage of Kawasaki disease.

Postoperative management of children with biliary atresia and heart failure.

The postoperative course in two children with extrahepatic biliary atresia and cardiovascular disease was reviewed and the correlation between biliary drainage and cardiac function was analyzed. Both patients obtained satisfactory biliary drainage after Kasai's hepatic portoenterostomy. One patient developed heart failure postoperatively due to severe viral myocarditis. This child's total serum bilirubin concentration remained elevated for eight months, despite adequate bilirubin excretion, until her cardiac function returned to normal. Another patient died of cardiac failure due to congenital heart disease 83 days after Kasai's operation, but his postoperative biliary drainage was satisfactory as long as cardiac function remained compensated. In both cases, fluid intake was restricted severely (30 to 70 ml/kg body weight/day), as titrated by echocardiographic assessment of cardiac function, but biliary excretion was satisfactory as long as the cardiac fractional shortening ratio was greater than 30% and the ejection fraction was greater than 55%. This suggests that cardiac decompensation affects postoperative biliary excretion in patients with biliary atresia; however, with careful medical management satisfactory biliary drainage can be achieved even in patients with severe heart diseases.

Pulmonary hypertension as a fatal complication of extrahepatic portal hypertension.

Pulmonary hypertension is an uncommon complication of portal hypertension seen in cirrhotic as well as noncirrhotic patients. We report a 10-year-old girl who presented with extrahepatic portal hypertension and pulmonary hypertension in the absence of intrinsic liver disease. Further investigations revealed high serum concentrations of prostaglandin F2 alpha, thromboxane B2 in the inferior vena cava, and angiotensin I in the inferior vena cava and right ventricle. The increased levels of these vasoconstrictive substances strongly suggest that the possible mechanism for the pulmonary hypertension in such patients with extrahepatic portal hypertension include shunting of vasoactive agents from the splanchnic circulation to the pulmonary vascular bed.

R-wave voltage in the right precordial leads in anthracycline cardiomyopathy: experimental animal model.

Electrocardiographic abnormality, similar to that observed in cancer patients during chemotherapy with the anthracycline antibiotics daunomycin and adriamycin, was produced in rabbits. They were chronically treated with adriamycin, and before each administration of the drug an electrocardiogram was recorded. They were subdivided into two categories with respect to the R-wave voltage in lead V1, on the same basis as our previous investigation in humans. In group A, there was a dose-response relationship, and they ultimately showed a QS pattern in the right precordial leads with or without ST-T changes in the left precordial leads. In group B, the electrocardiograms did not show a low R-wave in lead V1, but ST-T changes in the left precordial leads. The similarity of these electrocardiographic changes to those produced by myocardial infarction that we observed in humans suggests that more severe injury to the myocardium at the anterior septum and anterior left ventricular wall may be important in the pathogenesis of anthracycline cardiomyopathy.

[The supracardiac type of total anomalous pulmonary venous return in a ten-day-old neonate: report of a successfully treated case].

A case of a ten-day-old neonate weighing 3,867 g with the supracardiac type of total anomalous pulmonary venous return (TAPVR) is reported. The preoperative diagnosis was determined mainly by digital subtraction angiography. Surgical correction was carried out in this patient as an emergency operation. Under cardiopulmonary bypass on beating which required 3 hours and 7 minutes, anastomosis between the common pulmonary vein and the left atrium, ligation of both the anomalous vertical vein and the persistent ductus arteriosus, and closure of the atrial septal defects were successfully performed. Postoperatively cardiac failure was markedly improved, although 5 days were required for the weaning from the artificial respirator. The angiographic and hemodynamic examinations showed a complete repair of TAPVR. At present, 2 months after the operation, the patient shows an average development.

[Exercise and dipyridamole-loading in evaluation of ischemic coronary lesion and coronary reserve in children with Kawasaki disease].

In order to compare the clinical effects of exercise-loading and intravenous dipyridamole-loading tests in evaluating ischemic coronary lesion and coronary reserve, we evaluated changes in ECG, 201-Tl scintigraphy, coronary flow and myocardial metabolism in 10 patients with Kawasaki disease (age range: 7-16 years). Although both loading tests affect coronary hemodynamics and myocardial metabolism by different mechanisms, both were equally effective in detecting ischemic coronary lesion and reduced coronary reserve. On the other hand, when considered on the basis of clinical examination methods used, the dipyridamole-loading test was more effective for evaluating clinical symptoms and ECG, while exercise-loading was more effective for evaluating 201Tl scintigraphy and supply-demand balance. These results suggest that, in the evaluation of ischemic coronary lesion, assessment of clinical effects by a combination of several examination methods is required.

[Effects of isosorbide dinitrate on coronary and systemic circulation in children].

The effects of isosorbide dinitrate (ISDN) on the coronary and systemic circulation were evaluated in 8 children with angiographically normal coronary arteries. ISDN, 100 micrograms/kg, was given as a intracoronary injection. The pulmonary artery pressure, pulmonary capillary wedge pressure and left ventricular end diastolic pressure which are related to the pre-load were significantly reduced 1 min after the ISDN injection. The systolic blood pressure was reduced, and heart rate increased. The cardiac output, pressure-rate product and systemic vascular resistance showed no significant change. The systolic work index, however, was significantly reduced. ISDN induced a significant dilatation, ranging from 4.0% to 12.9%, in the diameter of the coronary vessels. There was, however, no change in the coronary blood flow, coronary perfusion pressure and coronary vascular resistance. The grade of the dilatation of the coronary vessels by ISDN in children was lower as compared with that in adult.