Kyung J. Chung

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.

Doppler color flow mapping of simulated in vitro regurgitant jets: Evaluation of the effects of orifice size and hemodynamic variables

The spatial distribution of simulated regurgitant jets imaged by Doppler color flow mapping was evaluated under constant flow and pulsatile flow conditions. Jets were simulated through latex tubings of 3.2, 4.8, 6.35 and 7.9 mm by varying flow rates from 137 to 1,260 cc/min. Color jet area was linearly related to flow rate at each orifice (r = 0.96, SEE = 3.4; r = 0.99, SEE = 1.6; r = 0.97, SEE = 2.3; r = 0.97, SEE = 3.2, respectively), but significantly higher flow rates were required to maintain the same maximal spatial distribution of the jet at the larger regurgitant orifices. Constant flow jets were also simulated through needle orifices of 0.2, 0.5 and 1 mm, with a known total volume (5 cc) injected at varying flow rates and with differing absolute volumes injected at the same flow rate (0.2, 1.0 and 2.0 cc/s, respectively). Again, maximal color jet area was linearly related to flow rate at each orifice (r = 0.97, SEE = 2.3; r = 0.97, SEE = 2.4; r = 0.92, SEE = 3.9, respectively), but was not related to the absolute volume of regurgitation. Color encoding of regurgitant jets on Doppler color flow maps was demonstrated to be highly dependent on velocity and, hence, driving pressure, such that color encoding was obtained from a constant flow jet injected at a velocity of 4 m/s through an orifice of 0.04 mm diameter with flow rates as low as 0.008 cc/s. Mitral regurgitant jets were also simulated in a physiologic in vitro pulsatile flow model through three prosthetic valves with known regurgitant orifice sizes (0.2, 0.6 and 2.0 mm2). For each regurgitant orifice size, color jet area at each was linearly related to a regurgitant pressure drop (r = 0.98, SEE = 0.15; r = 0.97, SEE = 0.20; r = 0.97, SEE = 0.23, respectively), regurgitant stroke volume (r = 0.77, SEE = 0.55; r = 0.94, SEE = 0.30; r = 0.91, SEE = 0.41, respectively) and peak regurgitant flow rate (r = 0.98, SEE = 0.16; r = 0.97, SEE = 0.21; r = 0.93, SEE = 0.37, respectively), but the spatial distribution of the regurgitant jets was most highly dependent on the regurgitant pressure drop. Jet kinetic energy calculated from the summation of the individual pixel intensities integrated over the jet area was closely related to driving pressure (r = 0.84), but integration of the power mode area times pixel intensities provided the best estimation of regurgitant stroke volume (r = 0.80).(ABSTRACT TRUNCATED AT 400 WORDS)

Cine magnetic resonance imaging for evaluation of anatomy and flow relations in infants and children with coarctation of the aorta.

Sixteen cine magnetic resonance imaging (MRI) studies were performed in 14 patients aged 1 week to 17 years (mean age, 46 months), who had coarctation of the aorta confirmed at angiography or surgery. Conventional echocardiographic-gated MRI was first performed in axial and rotated sagittal views and was used to identify the slice locations for cine MRI. Cine MRI was performed by gradient-recalled acquisition in steady state with a 30 degree flip angle, 12-msec echo time, 22-msec pulse repetition time, and a 128 x 256 acquisition matrix. Coarctation anatomy was extremely well defined in all but one patient who had vascular clips at the coarctation repair site. The smallest descending aortic flow diameter on cine MRI showed excellent agreement with angiography (r = 0.90). Lucent jets of high-velocity flow through the site of coarctation were imaged in eight patients, and jet length correlated well with the angiographic severity of coarctation (r = -0.81). Two patients were restudied after surgery, and they exhibited excellent repair and normal flow patterns. Cine MRI provides high-resolution imaging of coarctation anatomy with a dynamic spatial and temporal visualization of flow and with excellent detail of vascular anatomy and flow both proximal and distal to the coarctation.

Real-time Doppler color flow mapping for detection of patent ductus arteriosus.

In this study, ultrasound Doppler color flow mapping systems were utilized to examine flow in the pulmonary artery in 31 premature and term infants (aged 4 hours to 9 months) with patent ductus arteriosus accompanying respiratory distress syndrome, as an isolated lesion, or with patent ductus in association with other cyanotic or acyanotic congenital heart disorders. The flow mapping patterns were compared with those of a control population of 15 infants who did not have patent ductus arteriosus. In unconstricted ductus arteriosus, the flow from the aorta into the pulmonary artery was detected in late systole and early diastole and was distributed along the superior leftward lateral wall of the main pulmonary artery from the origin of the left pulmonary artery back in a proximal direction toward the pulmonary valve. In constricted patent ductus arteriosus, or especially in a ductus in association with cyanotic heart disease, the position of the ductal shunt in the pulmonary artery was more variable, often directed centrally or medially. Waveform spectral Doppler sampling could be performed in specific positions guided by the Doppler flow map to verify the phasic characteristics of the ductal shunt on spectral and audio outputs. Shunts through a very small patent ductus arteriosus were routinely detected in this group of infants, and right to left ductal shunts could also be verified by the Doppler flow mapping technique. This study suggests substantial promise for real-time two-dimensional Doppler echocardiographic flow mapping for evaluation of patent ductus arteriosus in infants.

Color Doppler flow mapping in patients with coarctation of the aorta: new observations and improved evaluation with color flow diameter and proximal acceleration as predictors of severity.

We performed color Doppler flow mapping in 15 patients, 1 week to 17 years old (mean 42 months), with coarctation of the aorta that was confirmed subsequently by angiography and/or surgery. Twelve patients had native coarctation and three had mild recoarctation after surgical repair. Color Doppler flow maps were analyzed with a digital analysis package and a Sony computer system. The diameter in the region of coarctation from the color Doppler flow map (mean = 2.0 +/- 0.8 mm [SD]) correlated well with the coarctation diameter measured at angiography (mean = 1.8 +/- 0.8 mm; r = .83, SEE 0.43 mm) in the 10 patients with native coarctation undergoing angiography, but the coarctation diameter measured by two-dimensional echocardiography (3.9 +/- 1.5 mm) was poorly predictive of the angiographic severity (r = .23). Additionally, spatial acceleration was seen in all patients proximal to the coarctation site, with an aliased and accelerating stream narrowing progressively as it proceeded toward the coarctation site, a pattern that is not seen in healthy subjects. Computer analysis of the color Doppler images provided pseudo three-dimensional and digital velocity maps for blue, red, and green (turbulent) flow velocities to allow an enhanced appreciation of the accelerating stream, easily separating this from normal descending aortic aliasing patterns. The narrowing of the acceleration area in the proximal descending aorta (distal/proximal acceleration zone ratio) was also predictive of the angiographic severity of coarctation (r = .83). The distribution of low-level turbulence seen proximally paralleled the distribution of the proximal accelerating stream.(ABSTRACT TRUNCATED AT 250 WORDS)

Cine magnetic resonance imaging after surgical repair in patients with transposition of the great arteries.

Cine magnetic resonance imaging (MRI) was used for postoperative evaluation of eight patients who underwent intra-atrial baffle procedure for surgical repair of D-transposition of the great arteries (D-TGA). Their ages ranged from 9 months to 8 years. Younger patients were sedated with chloral hydrate (80 to 100 mg/kg) orally. MRI was performed with use of a General Electric Signa system operating at a field strength of 1.5 tesla. A body or head coil was used depending on the size of the patient. Images were obtained by use of a technique of gradient-recalled acquisition in steady state (GRASS) that utilizes a low flip angle and shorter repetition and echo times. Five patients had widely patent venae cavae and three had superior vena caval obstruction at the junction of the right atrium with a dilated azygos vein. There was no evidence of pulmonary venous obstruction in any of the patients. Right ventricular function was assessed in four patients and their ejection fractions ranged from 58% to 81%. Tricuspid and mitral regurgitation were observed in three and two patients, respectively. Both right and left ventricular outflow tracts were well visualized and showed no evidence of obstruction. Cine MRI is an entirely noninvasive, nonionizing, and safe procedure in young patients and appears to be a valuable alternative method for evaluating patients after surgical repair of D-TGA. With advancing technologies and an accumulation of experience with cine MRI, it appears that this new technique will play an important role in patient care for children with congenital heart disease.

Elucidation of the Natural History of Ventricular Septal Defects by Serial Doppler Color Flow Mapping Studies

Two-dimensional echocardiography has provided information to aid in the diagnosis and management of infants with ventricular septal defect, but its inability to resolve very small ventricular septal defects and problems with defining ventricular septal defect orifice size (because of overlying muscle or tricuspid tissue) have made it unsuitable as a standard for defining the natural history of ventricular septal defect. In this study, 114 serial two-dimensional Doppler color flow mapping studies were performed to define ventricular septal defect anatomy, location and color flow diameter as an indicator of shunt size in 66 patients (over a 40 month period). Twenty-five patients first studied at 6 months of age (mean age at most recent study 15.9 months) had congestive heart failure and 41 (mean age 45 months) did not. In the congestive heart failure group, there were 24 perimembranous and 1 muscular ventricular septal defect and aneurysm formation was present in 17. Mean (+/- SD) color flow diameter was 8.2 +/- 1.9 mm and color flow diameter/aortic root diameter ratio was 0.63. In the 30 patients who underwent cardiac catheterization, color flow diameter bore a close relation to angiographic diameter (r = 0.96) and pulmonary/systemic flow ratio (Qp/Qs) (r = 0.88). In the patients with congestive heart failure, 4 of the 25 ventricular septal defects, all with aneurysm present or positioned adjacent to the tricuspid valve, became smaller but none closed. Of the 41 patients without congestive heart failure, 21 had a perimembranous defect (15 with aneurysm), 18 had a muscular ventricular septal defect and 2 had a supracristal ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing the structure and shape of stenotic and regurgitant jets an in vitro investigation using doppler color flow mapping and optical flow visualization

To evaluate factors influencing the structure and shape of stenotic and regurgitant jets, Doppler color flow mapping and optical flow visualization studies were performed with use of a syringe model with a constant rate of ejection to simulate jets of valvular regurgitation and a pulsatile flow model of the right heart chambers to simulate jets of mild, moderate and severe valvular pulmonary stenosis. Ink-(0 to 40%) glycerol-water jets (viscosity 1 to 3.5 centiPoise) were produced by injecting the fluid at a constant rate into a 10 gallon rectangular reservoir of the same still fluid through 1.4 and 3.4 mm needles. The Doppler color flow scanners imaged the laminar jet length within 3 mm of actual jet length (2 to 6 cm) and the jet width within 2 to 3 mm of the actual jet width. Jet flows with Reynolds numbers ranging from 230 to 1,200 injected into still fluid yielded jet length/width ratios that decreased with increasing Reynolds numbers and leveled off to a length/width ratio of 5-6:1 at a Reynolds number near 600. When the fluid reservoir was swirled to better mimic the effect of flow entering the same cardiac chamber from a second source, the jets showed diminution of the jet length/width ratio and a clearly defined zone of turbulence. Studies of the pulsatile flow model were performed at cardiac outputs of 1 to 6 liters/min for the normal and each stenotic valve. Mild stenosis had an orifice area of 2.8 cm2, moderate stenosis an area of 1.0 cm2 and severe stenosis an area of 0.5 cm2. Laminar jet length represented the length of the total jet, which had a symmetric width and was measured from the valve opening to a region where the jet exhibited a spray effect. Laminar jet lengths (0.2 to 1.1 cm) were imaged by Doppler color flow mapping and optical visualization only in the moderate and severely stenotic valves and only at flows less than or equal to 3 liters/min (mean Reynolds numbers less than or equal to 3,470). Beyond this flow rate the jets exhibited a spray effect. Laminar jet length/width ratio approached unity with an increased amount of valvular stenosis and higher flow volumes (cardiac output). Proximal aliasing was present in each valve studied. the length of aliasing (0 to 3.2 cm) proximal to the valve was longer with increased flow rates and increased amounts of stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac and coronary arterial involvement in infants and children from New England with mucocutaneous lymph node syndrome (Kawasaki disease). Angiocardiographic-echocardiographic correlations.

Forty-four patients, aged 6 months to 11 years, meeting the clinical criteria for mucocutaneous lymph node syndrome (Kawasaki disease) were studied from March 1980 to March 1981. A protocol was designed for evaluation of cardiac involvement including electrocardiogram, chest X-ray film, cardiac enzyme determinations and M mode and two dimensional echocardiograms. Aspirin was given during the acute febrile period as an anti-inflammatory agent in a dosage of 100 mg/kg per day; followed by 30 mg/kg per day for 10 weeks or longer if platelet counts were elevated. Angiocardiography was performed in 38 patients. Twenty-one patients (48 percent) showed abnormal M mode echocardiographic findings (flat or greatly decreased ventricular septal motion, pericardial effusion or decreased left ventricular function) during the acute febrile stage. Coronary artery disease developed in seven patients, all of whom had abnormal M mode echocardiographic abnormalities in the acute stage. Five patients had coronary aneurysms and two patients had dilated coronary arteries. Two dimensional echocardiograms identified coronary arterial lesions accurately if present proximally but failed to detect aneurysms beyond 1.5 cm from the aortic root. The study shows that serial M mode and two dimensional echocardiograms provide sufficient information to rule out cardiac involvement in Kawasaki disease. Echocardiograms should be obtained every 3 to 4 days during the acute febrile stage because all patients with coronary artery disease detected with angiography had abnormal echocardiographic findings during that period.