Recent studies on the development of the heart6 have increased markedly our appreciation of the disposition of the specialized conduction tissues, showing how some rests of tissues in unexpected locations are remnants of a well organized system found throughout avian and mammalian species. These studies also help us to account more logically for the distribution of the conduction tissues in congenitally malformed hearts. On the basis of our overall studies, therefore, combined with these recent advances, we are able to understand the normal and abnormal disposition of the conduction tissues. These understandings then permit us to offer explanations for those arrhythmias which have a “natural” basis, such as the grossly abnormal patterns found in hearts with isomerism of the atrial appendages or univentricular atrioventricular connection, and the accessory pathways found in the setting of ventricular preexcitation. We are also able to understand the changes affecting these tissues as part of acquired disease, such as the fibrosis of the long atrioventricular bundles found in atrioventricular septal defect and corrected transposition and the immunologic damage underscoring congenitally complete heart block in infants of mothers with collagen disease. We are only beginning to explore the possibility that abnormalities of the myocardiutn itself, or the fibrous tissue matrix, can also underscore the existence of abnormal rhythms. With all this knowledge, it is to be hoped that, in the future, we will see far fewer of those arrhythmias which have an “unnatural” basis, such as those related to direct surgical damage to the conduction tissues and their arterial supply, or those produced by abnormal loading conditions which are themselves the consequence of congenital malformations. Although we have learned, and applied, a great deal, there is still much to be done before we unravel all the secrets of the causes of arrhythmias in childhood.

Sudden death occurs in patients after repair of congenital heart disease. In those with tetralogy of Fallot, or a similar lesion, ventricular tachycardia has been hypothesized as the major arrhythmic mechanism for sudden death. It would be desirable to identify individuals at risk for sudden death, to determine which arrhythmia would be likely to cause sudden death, and to treat those individuals with an appropriate antiarrhythmic to prevent sudden death. For the last 10 years, physicians have been treating patients with antiarrhythmic drugs, based on a number of criteria, the most common of which is the presence of premature ventricular contractions.1,2 The practice has recently been called into question by the CAST trial. It is the purpose of this paper to review the evidence that repair causes ventricular arrhythmias, that ventricular arrhythmias cause sudden death, and that ventricular arrhythmias should be treated prophylactically.

In this review, I have outlined the clinical picture, epidemiology, pathology, etiology, and current treatment and management of Kawasaki disease. The disease in question has unique features which cannot be classified into any of the categories of conventional pediatric diseases, and thus the elucidation of the etiology and mode of onset may well raise many new medical problems. It is hoped that young practitioners of clinical and fundamental medicine will be able to resolve the problems relating to the disease which remain as quickly as possible.

There are a number of abnormalities of the immune system seen in children with Kawasaki disease that are widely integrated and lead eventually to the inflammatory response seen clinically as fever, rash, arthritis, coronary arteritis, etc. The initiating event remains a mystery, however the cascade of immune responses involves both T and B lymphocytes, lymphokine production, and cell adhesion. Until the etiologic agent(s)/ of Kawasaki disease is identified, therapeutic intervention must be directed at controlling the effects of the abnormal immunoregulation.

In about 1967, a new clinical entity in infants and children was described in Japan. It was an acute febrile illness associated with engorgement of the conjunctivas, labial erythema, and swelling of the deep cervical lymph nodes without suppuration. This disease is usually called the acute febrile mucocutaneous lymph node syndrome or, more simply, Kawasaki disease.

Cross-sectional echocardiography is an essential tool in the evaluation ofchildren with Kawasaki disease, both in the acute and chronic stages. In the acute phase of the illness, it is valuable for diagnosis and management of pancarditis and for the long-term monitoring of pericardial effusions, left ventricular function, and the rare cases of chronic valvar dysfunction. When coronary arterial abnormalities are detected, echocardiography can serially evaluate long-term treatment with drugs which prevent the aggregation of platelets and monitor the resolution of coronary aneurysms. The value of cross-sectional echocardiography, nonetheless, is very limited in the detection of coronary arterial stenosis. Coronary arteriography is still important for the diagnosis of obstructive lesions in the coronary arteries and should be used in conjunction with cross-sectional echocardiography for the appropriate long- term management of children with Kawasaki disease at high risk of developing coronary arterial stenosis. Perhaps, in the future, high resolution transesophageal echocardiography will allow clear delineation of coronary arterial anatomy and specifically stenosis, but its role in the evaluation and management of children with Kawasaki disease remains to be explored.

Formation of coronary aneurysms is often seen on the patients in the acute phase of Kawasaki disease by echocardiography, and after the convalescent phase, some patients show disappearance of aneurysms but some of them show combining stenotic lesions at inlets and/or outlets of aneurysms on coronary arteriography. According to follow-up studies of coronary arterial lesions, the degree of stenosis quite frequently increases and progresses over a period up to 10 years or more after the onset of the disease. The severe stenosis appears the most frequently at the proximal portion of the left anterior descending artery and secondly at the main trunk of the main coronary artery. They die suddenly or suffer from severe myocardial infarction unless they are treated with aortocoronary bypass surgery. However, it is rare to have symptoms of ischemic heart disease even in patients with severe obstructive lesions. In fact, the sensitivity of exercise testing in diagnosis of myocardial ischemia is very low. Dipyridamole thallium myocardial imaging is reasonably useful, but dipyridamole can he dangerous when it is given without the precise information of the patient's stenosis. Coronary arteriography is, therefore, essential not only to determine the appropriate treatment of the c ronary arterial lesions but also for follow-up. According to the histopathologic study, even the patients in whom coronary arterial lesions were not visualized on coronary arteriography often show some intimal proliferation. These patients may well present a problem in the future due to the sequels of angiitis. Because of this, continuous regular follow-up should be necessary, even in patients with no evidence of coronary arterial lesion.

Summary Mucocutaneous lymph node syndrome, now called Kawasaki disease, affects children of all ages and races. The cause of this systemic vasculitis is unknown, thus the diagnosis is based solely on clinical criteria. Coronary arteritis and the formation of coronary arterial aneurysms are the most serious early cardiac complications, while long term sequels, such as coronary stenosis and myocardial infarction, may occur. Current medical therapy is aimed solely at preventing or decreasing the occurrence of these cardiovascular complications in patients with this disease. Past treatment included antibiotics, steroids, and nonsteroidal anti-inflammatory agents. Aspirin remains the most widely used drug, although the use of intravenous gammaglobulin has also become common. When used in combination, these two agents may reduce the incidence of coronary arterial aneurysms. The optimal dosage and duration of treatment has not yet been determined.

Summary Myocardial revascularization is now an accepted therapeutic modality for severe coronary arterial obstructive disease produced by Kawasaki disease which is amenable to usual medical treatment. The mortality rate of myocardial infarction is surprisingly high in this setting, and surgery may be able to prevent many of these deaths. This article focuses on current issues in surgical treatment of ischemic heart disease in children secondary to Kawasaki disease. Coronary arterial obstructive disease is, apparently, a leading problem followed by valvar and myocardial involvements. Introduction of bypass grafting using the internal thoracic artery in children was a major recent advance, because this graft has an excellent capability to adapt to the increments of increased flow and growth of the patient. The saphenous vein is less satisfactory when used as a graft in terms of its long-term patency, particularly in young children less than 8 years old. Although longer follow-up is certainly required, the current results of surgery have been excellent in improving myocardial perfusion, in ameliorating symptoms, and improving the quality of life.

Kawasaki disease is an acute vasculitis of unknown etiology that occurs predominantly in infancy and early childhood. It is characterize by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy.1,2 Coronary arterial aneurysms, or ectasia, develop in approximately 15 to 25% of children with the disease, and may lead to myocardial infarction, sudden death, or chronic coronary arterial insufficiency.2–4

Sixteen very premature babies, born prior to term at gestational ages from 26–30 weeks, who required ventilation, were randomly assigned to groups, which did or did not receive treatment with surfactant. They were then studied prospectively with respect to the hemodynamic significance of the patency of the arterial duct. The velocity of end-diastolic flow in the celiac trunk was measured by Doppler echocardiography. Reduced values were assumed to represent the effect ofa large duct. The volume of systemic and pulmonary flows were estimated by means of Doppler echocardiographic studies at the tricuspid and mitral valvar orifices. Patency of the duct was diagnosed in all patients. Time to subsequent closure and the incidence of necrotizing enterocolitis and intracranial hemorrhage did not differ between the groups. The size of the shunt across the duct was measured as approximately 19% in patients with and without treatment. Velocity of end-diastolic flow, however, and the volumes of systemic flow, were markedly decreased in both, indicating the presence of an arterial duct ofhemodynamic significance. In contrast, in a control group of 20 normal newborns, end-diastolic flow velocities and systemic flows were normal when an arterial duct was diagnosed as patent. These results suggest that treatment with surfactant does not alter shunting across the arterial duct, but that gestational age may be the main factor influencing the hemodynamic significance of the duct. Due to the serious reduction of volumes of systemic flow in preterni babies with a patent duct, early closure should be considered in this population.