C. Elise Duffy

The Treatment of Kawasaki Syndrome with Intravenous Gamma Globulin

We compared the efficacy of intravenous gamma globulin plus aspirin with that of aspirin alone in reducing the frequency of coronary-artery abnormalities in children with acute Kawasaki syndrome in a multicenter, randomized trial. Children randomly assigned to the gamma globulin group received intravenous gamma globulin, 400 mg per kilogram of body weight per day, for four consecutive days; both treatment groups received aspirin, 100 mg per kilogram per day, through the 14th day of illness, then 3 to 5 mg per kilogram per day. Two-dimensional echocardiograms were interpreted blindly and independently by two or more readers. Two weeks after enrollment, coronary-artery abnormalities were present in 18 of 78 children (23 percent) in the aspirin group, as compared with 6 of 75 (8 percent) in the gamma globulin group (P = 0.01). Seven weeks after enrollment, abnormalities were present in 14 of 79 children (18 percent) in the aspirin group and in 3 of 79 (4 percent) in the gamma globulin group (P = 0.005). No child had serious adverse effects from receiving gamma globulin. We conclude that high-dose intravenous gamma globulin is safe and effective in reducing the prevalence of coronary-artery abnormalities when administered early in the course of Kawasaki syndrome.

A Single Intravenous Infusion of Gamma Globulin as Compared with Four Infusions in the Treatment of Acute Kawasaki Syndrome

BACKGROUND Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.

Incomplete Kawasaki disease with coronary artery involvement

We report four patients with Kawasaki disease in whom characteristic coronary artery abnormalities developed after illnesses that did not meet diagnostic criteria. An additional patient lacked a history of acute manifestations of Kawasaki disease, but severe Kawasaki-like arterial changes were noted at autopsy. Fever was present in four of the five patients, in three lasting from 7 to 14 days. Despite manifestation of few classic acute clinical features of Kawasaki disease, three of four patients had desquamation of the fingers and toes 10 to 14 days after onset of illness, and the fifth had desquamation several months prior to death. These patients were seen over a 2-year period during which 22 other children were seen with Kawasaki disease with coronary artery abnormalities. Thus, strict adherence to currently accepted criteria for diagnosis of Kawasaki disease may lead to failure to recognize incomplete forms of this illness, with potential sequelae of myocardial infarction or sudden death. This finding suggests that children with prolonged unexplained febrile illnesses, especially those associated with subsequent peripheral desquamation, should undergo echocardiography 3 to 4 weeks after onset of the illness. This practice would help to identify those patients with illnesses characterized by incomplete diagnostic criteria but in whom significant coronary abnormalities develop.

Pediatric coronary artery bypass for Kawasaki, congenital, post arterial switch, and iatrogenic lesions

BACKGROUND Pediatric coronary artery bypass (PCAB) has been recently employed for expanding indications to treat acquired, congenital, post arterial switch, and other iatrogenic pediatric coronary artery problems. METHODS Between 1987 and 1998, 3 infants and 13 children (n = 16, mean age 6.1 years, range 2 months-18 years) underwent one or more internal thoracic artery (ITA) to coronary artery (CA) bypass grafts for Kawasaki disease (n = 4), congenital lesions (n = 3), post arterial switch (n = 4), and other iatrogenic obstructions (n = 5). Proximal left main CA arterioplasty was performed concurrently with ITA-CA bypass in 4 patients. RESULTS Survival is 93.8%. All bypass grafts in surviving patients are patent 2 months-11 years postoperation. The 11 elective patients are well (NYHA I-II). The 5 emergent operations were performed in 2 infants and 3 adolescents who had poor ventricular function prior to ITA-CA bypass due to iatrogenic injuries in 3, congenital critical left main stenosis in 1, and intraoperative iatrogenic coronary injury in 1. The 3 adolescents fared worse, resulting in death in the first, cardiac transplantation in the second, and full recovery in the third. The 2 infants have steadily improving ventricular function. CONCLUSIONS ITA-CA bypass can be successfully performed in infants and children for expanding elective and life-saving indications with excellent results. Poor preoperative ventricular function often persists, especially in those older children with iatrogenic injuries, and may result in death or cardiac transplantation.

Prevention of giant coronary artery aneurysms in Kawasaki disease by intravenous gamma globulin therapy.

Previous studies have demonstrated the efficacy of intravenous gamma globulin in the prevention of coronary artery abnormalities in Kawasaki disease. We retrospectively reviewed our single-hospital experience with patients in whom Kawasaki disease was diagnosed from January 1979 to July 1987. Only 3 of 68 (4%) patients treated with intravenous gamma globulin in the first 10 days of illness developed coronary artery abnormalities (one of the three had abnormalities before gamma globulin therapy), in comparison with 39 of 119 (33%) patients not treated with gamma globulin (p less than 0.001). Giant coronary artery aneurysms, which are associated with the greatest morbidity and mortality rates in Kawasaki disease, developed in none of the 68 patients treated with gamma globulin but in 7 of 119 patients (6%) not treated with gamma globulin (p = 0.04). Intravenous gamma globulin appears to be effective not only in reducing the overall prevalence of coronary artery abnormalities in Kawasaki disease but, more important, in preventing the formation of giant aneurysms, the most serious form of coronary abnormality after this illness.

Valve Replacement in Children: Guidelines for Selection of Prosthesis and Timing of Surgical Intervention

One hundred fifty-nine patients ranging from 3 months to 18 years old (mean, 8.1 +/- 3.7 years) underwent 162 primary valve implantations. A porcine valve was used in 104 patients, a St. Jude Medical valve in 40, and a Björk-Shiley valve in 18. The valve replaced was the aortic in 25 patients, the mitral (systemic atrioventricular [AV] valve) in 43, the pulmonary in 71, and the tricuspid (pulmonary AV valve) in 23. Hospital mortality was 6%. Patients with a Björk-Shiley valve received warfarin sodium anticoagulation, and those with a St. Jude Medical valve were given salicylates and dipyridamole. Follow-up is available on all patients 0.6 to 12 years postoperatively (mean, 6.3 +/- 2.6 years). New York Heart Association Functional Class improved in 62% and remained unchanged in 38% of the patients. Thromboembolic complications occurred in only 8 (57%) of 14 patients with a St. Jude Medical valve in the right (pulmonary) side and in 3 (12%) of 26 with the valve in the left (systemic) side of the circulation. Bacterial endocarditis developed in 3 patients, all with porcine valves. Early valve replacement, less than 2 years after detection of hemodynamic deterioration, resulted in improvement in the ventricular ejection fraction in 25 of 29 patients (from 81 +/- 14% to 90 +/- 12% of normal; p less than 0.05). In contrast, the ejection fraction remained abnormal in all 22 patients with delayed valve insertion (more than 2 years) (81 +/- 16% of normal preoperatively and 80 +/- 10% of normal following operation; p = not significant).

Supraarterial decompression myotomy for myocardial bridging in a child

A 10-year-old boy presented with a history of exertional chest pain. An electrocardiogram demonstrated an inferior apical myocardial infarction. Cardiac catheterization revealed myocardial bridging of the left anterior descending coronary artery with evidence of intramyocardial obstruction during systole. The patient underwent successful treatment with supraarterial decompression myotomy and remains symptom free at 1 year.

Mucocutaneous lymph node syndrome (Kawasaki disease): Delayed aortic and mitral insufficiency secondary to active valvulitis

A 2 8/12 year old girl with acute mucocutaneous lymph node syndrome (Kawasaki disease), presented 17 months later with a new onset of mitral and aortic insufficiency. Congestive heart failure rapidly developed and double valve replacement was performed. Pathologic study of the excised valve tissue disclosed active valvulitis. This is the first report of late onset aortic and mitral valvulitis associated with Kawasaki disease.

Does banding the pulmonary artery affect pulmonary valve function after the Damus-Kaye-Stansel operation?

BACKGROUND The Damus-Kaye-Stansel (DKS) operation can be an effective palliation in patients who have single-ventricle physiology and systemic outflow obstruction. Pulmonary artery banding (PAB) may be used as a preliminary procedure in these patients to limit overperfusion of the pulmonary circulation. In some series, the DKS operation has been associated with pulmonary insufficiency (PI). We retrospectively analyzed medical records of our patients who had PAB and later DKS to determine the incidence of PI in these patients. METHODS Between 1982 and 1996, 15 patients underwent PAB before DKS. Median age at PAB placement was 7 days and median duration of PAB was 7 months. Echocardiograms obtained before PAB, before DKS, and at the most recent post-DKS follow-up were reviewed. RESULTS Follow-up ranged from 1 to 15 years (mean follow-up, 7.5 years). One patient had trivial PI before PAB, which progressed to moderate PI at the last follow-up. Only 1 other patient had mild PI, but only at the last follow-up after DKS. CONCLUSIONS These findings suggest that prior PAB does not appear to cause significant PI in patients slated for DKS, and the incidence of significant PI after the DKS operation is relatively low.

Usefulness of echocardiographic evidence of pericardial effusion and mitral regurgitation during the acute stage in predicting development of coronary arterial aneurysms in the late stage of kawasaki disease

In 28 patients with Kawasaki disease, the relation of specific echocardiographic findings identified during the acute study of the illness, including valvular regurgitation, to development of coronary aneurysms was evaluated. Initial studies were performed at the time of clinical presentation, 5 to 10 days after the onset of fever, and follow-up studies were performed 1 to 2 months later. Patients in whom coronary aneurysms developed were more likely to have pericardial effusion (p = 0.0006) or mitral regurgitation (MR) (p = 0.014) at initial echocardiographic study than those without aneurysms. Presence of either mitral regurgitation (MR) or pericardial effusion had a positive predictive value of 0.84 for aneurysm development. Twenty-three percent of patients had MR, and it was associated with mild LV dilatation (35 +/- 3 vs 32 +/- 5 mm, p less than 0.05). Insufficiency of other valves was rare. Thus, MR and pericardial effusion on acute phase echocardiographic examination may predict development of coronary aneurysms in Kawasaki disease. Mild MR occurs frequently in acute Kawasaki disease and is associated with mild LV dilation.