L. LuAnn Minich

Coronary Artery Involvement in Children With Kawasaki Disease Risk Factors From Analysis of Serial Normalized Measurements

Background— Most studies of coronary artery involvement and associated risk factors in Kawasaki disease have used the Japanese Ministry of Health dichotomous criteria. Analysis of serial normalized artery measurements may reveal a broader continuous spectrum of involvement and different risk factors. Methods and Results— Clinical, laboratory, and echocardiographic measurements obtained at baseline and 1 week and 5 weeks after presentation were examined in 190 Kawasaki disease patients as part of a clinical trial of primary therapy with pulse steroids in addition to standard intravenous immunoglobulin. Maximum coronary artery z score normalized to body surface area was significantly greater than normal at all time points, decreasing significantly over time from baseline. A maximal z score ≥2.5 at any time was noted in 26% of patients. Japanese Ministry of Health dimensional criteria were met by 23% of patients. Significant independent factors associated with greater z score at any time included younger patient age, longer interval from disease onset to treatment with intravenous immunoglobulin, lower serum IgM level at baseline, and lower minimum serum albumin level. z Scores of the proximal right coronary artery were higher than those in the left anterior descending branch. Conclusions— Analyses of serial normalized coronary artery measurements in optimally treated Kawasaki disease patients demonstrated that for most patients, measurements are greatest at baseline and subsequently diminish; baseline measurements appear to be good predictors of involvement during early follow-up. When a more precise assessment is used, risk factors for coronary artery involvement are similar to those defined with arbitrary dichotomous criteria.

Evaluation of Kawasaki Disease Risk-Scoring Systems for Intravenous Immunoglobulin Resistance

OBJECTIVES To assess the performance of 3 risk scores from Japan that were developed to predict, in children with Kawasaki disease, resistance to intravenous immunoglobulin (IVIG) treatment. STUDY DESIGN We used data from a randomized trial of pulsed steroids for primary treatment of Kawasaki disease to assess operating characteristics of the 3 risk scores, and we examined whether steroid therapy lowers the risk of coronary artery abnormalities in patients prospectively classified as IVIG resistant. RESULTS For comparability with published cohorts, we analyzed the data of 99 patients who were not treated with steroids (16% IVIG-retreated) and identified male sex, lower albumin level, and higher aspartate aminotransferase level as independent risk factors for IVIG resistance. The Kobayashi score was similar in IVIG-resistant and -responsive patients, yielding a sensitivity of 33% and specificity of 87%. There was no interaction of high-risk versus low-risk status by treatment received (steroid versus placebo) with any of the 3 risk score algorithms. CONCLUSION Risk-scoring systems from Japan have good specificity but low sensitivity for predicting IVIG resistance in a North American cohort. Primary steroid therapy did not improve coronary outcomes in patients prospectively classified as being at high-risk for IVIG resistance.

Endorsement of Health and Human Services Recommendation for Pulse Oximetry Screening for Critical Congenital Heart Disease

Incorporation of pulse oximetry to the assessment of the newborn infant can enhance detection of critical congenital heart disease (CCHD). Recently, the Secretary of Health and Human Services (HHS) recommended that screening for CCHD be added to the uniform screening panel. The American Academy of Pediatrics (AAP) has been a strong advocate of early detection of CCHD and fully supports the decision of the Secretary of HHS. The AAP has published strategies for the implementation of pulse oximetry screening, which addressed critical issues such as necessary equipment, personnel, and training, and also provided specific recommendations for assessment of saturation by using pulse oximetry as well as appropriate management of a positive screening result. The AAP is committed to the safe and effective implementation of pulse oximetry screening and is working with other advocacy groups and governmental agencies to promote pulse oximetry and to support widespread surveillance for CCHD. Going forward, AAP chapters will partner with state health departments to implement the new screening strategy for CCHD and will work to ensure that there is an adequate system for referral for echocardiographic/pediatric cardiac evaluation after a positive screening result. It is imperative that AAP members engage their respective policy makers in adopting and funding the recommendations made by the Secretary of HHS.

Kawasaki Disease: More Patients Are Being Diagnosed Who Do Not Meet American Heart Association Criteria

Objective. To determine the frequency of Kawasaki disease (KD) diagnosis in patients who did and did not meet American Heart Association (AHA) diagnostic criteria and to examine the clinical findings, the time to treatment, and the outcomes of the two groups. Design. Retrospective review of all patients with a discharge diagnosis of KD at a tertiary care childrens hospital (1991–1997). Results. A total of 127 patients were identified. All received intravenous immune globulin (IVIG) and had complete echocardiographic studies. AHA criteria were met in 81 (63.8%). More patients who did not meet criteria (9 of 46, 20%) had coronary artery abnormalities (CAA), compared with those who had the complete clinical picture (6 of 81, 7%). The 15 patients with CAA received IVIG later (12.4 ± 7.4 days) from onset of symptoms compared with those with no CAA (8.2 ± 4.6). The time period was the same for patients with CAA who met the criteria, (11.8 ± 5.8 days) as for patients who did not meet AHA criteria (12.8 ± 8.6 days). Infants were more likely than were older children to develop CAA, to receive IVIG later, and to be diagnosed with an incomplete clinical picture. Conclusion. Physicians are increasingly likely to diagnose KD in patients who do not meet complete AHA criteria. Despite the potential risks of overdiagnosis and overtreatment, this practice seems justified because the complete criteria are an insensitive indicator of having or developing CAA.

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts.

BACKGROUND Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material. METHODS We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 +/- 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 +/- 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique. RESULTS We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P >.05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 +/- 15 mm Hg at 8 +/- 2.6 months postoperatively as compared to a gradient of 24 +/- 18 mm Hg measured 12 +/- 6 months postoperatively in standard allografts (P =.11). CONCLUSIONS Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.

Quantitative Assessment of Ventricular Function in Children With Single Ventricles Using the Doppler Myocardial Performance Index

Assessment of ventricular function in patients with functionally single ventricles and unusual ventricular geometry is difficult. The Doppler myocardial performance index (MPI) may provide a method of assessing function in these patients. The purposes of this study were to compare the MPI in normal children and in children with a functionally single ventricle, and to compare the MPI in patients with single ventricles before and after bidirectional cavopulmonary anastamosis (BCPA). Echocardiograms of all patients who underwent BCPA between January 1994 and December 1998 were reviewed before and after surgical palliation. Age-matched normal subjects (n = 30) served as controls. The MPI was calculated from Doppler tracings of ventricular inflow and outflow. Of the 60 patients with single ventricles who underwent BCPA, 41 had adequate preoperative Doppler studies to allow calculation of the MPI, and 21 of 41 had adequate studies before and after BCPA. The MPI was higher in patients with single ventricles than in normal controls (0.67 +/- 0.14 vs 0.32 +/- 0.10, p < 0.001). There was no significant difference in the MPI in patients with single ventricles before and after surgery (0.70 +/- 0.16 vs 0.66 +/- 0.15). However, patients who had a BCPA at < 1 year of age had a significant decrease in the MPI after surgery (0.71 +/- 0.10 vs 0.61 +/- 0.11, p = 0.01). Compared with controls, the MPI was significantly higher in patients with single ventricles suggesting an altered hemodynamic state consistent with decreased ventricular function. The MPI decreased in patients who underwent BCPA at < 1 year of age, suggesting an improvement in ventricular function. The MPI provides an objective method of assessing and following ventricular function in patients with single ventricles that is independent of ventricular geometry.

Pulmonary vein stenosis with normal connection: associated cardiac abnormalities and variable outcome

BACKGROUND Pulmonary vein (PV) stenosis with anatomically normal connection is considered rare, unresponsive to treatment, progressive, and usually fatal. METHODS We reviewed the records of 13 children with this diagnosis at our center since 1990. RESULTS The number of stenosed PVs ranged from all PVs (n = 5); three PVs (n = 1); two PVs (n = 5); and one PV (n = 2). All patients had associated congenital cardiac abnormalities. Operation on PV stenosis was attempted in 7 patients (54%), 2 of whom have done well and 5 of whom have not. Two patients underwent heart transplantation for inoperable associated cardiac lesions. Significantly more patients with three or four stenosed PVs died (83%) compared with patients with one or two stenosed PVs (0%). CONCLUSIONS (1) Pulmonary vein stenosis with anatomically normal connection is associated with other congenital cardiac abnormalities, (2) presentation and outcome are contingent on the number of stenosed PVs, (3) surgical palliation may be helpful in some patients, and (4) heart transplantation for inoperable associated cardiac abnormalities may be an option in patients with only one or two stenosed PVs.

Delayed diagnosis of Kawasaki disease: what are the risk factors?

OBJECTIVE. Because late diagnosis of Kawasaki disease increases the risk for coronary artery abnormalities, we explored the prevalence of and possible risk factors for delayed diagnosis by using the database of the Pediatric Heart Network trial of corticosteroid treatment for Kawasaki disease. METHODS. We collected sociodemographic and clinical data at presentation for all patients who were treated for presumed Kawasaki disease at 8 centers (7 in the United States, 1 in Canada). Delayed diagnosis was evaluated by total number of illness days to diagnosis and by the percentage of patients who were treated after day 10 of illness. Independent predictors of delayed diagnosis were identified by using multivariate linear and logistic regression. RESULTS. Of the 589 patients who received intravenous immunoglobulin, 27 were treated before screening for the trial and excluded; 562 patients formed the cohort for analysis. Kawasaki disease was diagnosed at 7.9 ± 3.9 days, 92 (16%) cases after day 10. Centers were similar with respect to patient age and gender. Centers differed in the patient percentage with incomplete Kawasaki disease; clinical criteria of cervical adenopathy, oral changes, and conjunctivitis; and distance of residence from the center. Independent predictors of greater number of illness days at diagnosis included center, age of <6 months, incomplete Kawasaki disease, and greater distance from the center. Independent predictors of diagnosis after day 10 were age of <6 months, incomplete Kawasaki disease, and greater distance). Socioeconomic variables had no association with delayed diagnosis. CONCLUSIONS. Even after adjustment for patient factors, illness duration at diagnosis varies by center. These findings underscore the need to maintain a high index of suspicion of Kawasaki disease in the infant who is younger than 6 months and has prolonged fever even with incomplete criteria. Outreach educational programs may be useful in promoting earlier recognition and treatment of Kawasaki disease.

Aortic valve repair and replacement after balloon aortic valvuloplasty in children

Background. Little is known about the incidence, indications, and results of surgical repair or replacement of the aortic valve afte balloon aortic valvuloplasty (BAV) for congenital aortic stenosis in children. This was study was designed to evaluate patterns of failure requiring operation after BAV for congenital aortic stenosis and to review our experience with successful repair, rather than replacement, of selected aortic valves after BAV. Methods. From March 1986 to June 1995, 60 patients with congenital aortic stenosis aged 1 day to 27 years (mean ± standard deviation, 7.3 ± 6 years) undewent BAV. Twenty-three patients (38%) required operation a mean of 44 ± 37 months (range, 1 to 110 months) after BAV, because of severe aortic insufficiency in 13 patients and recurrent or residual aortic stenosis in 10 patients. Severe aortic insufficiency was invariably due to avulsion of a cusp from the annulus, with resulting cusp prolapse and insufficiency. Operative intervention consisted of valve replacement in 14 patients and valve repair in 9 patients. Repair techniques included reattachment of an avulsed cusp to the aortic annulus, relief of commissural fusion, and ddebridement of thickened cusps. Results. Actuarial freedom from surgical intervention after BAV was 88% ± 4% at 1 year, 70% ± 6% at 5 years, and 51% ± 12% at 9 years. The need for aortic valve operation was unrelated to age at the time of BAV, indication for operation (aortic insufficiency versus aortic stenosis), age at operation, or preoperative gradient. All patients survived aortic valve operation; there was one late death at an average follow-up of 27 ± 20 months (range, 2 to 61 months) after aortic valve operation. Stenosis was well relieved in all patients undergoing valve replacement. The 9 valve repair patients have been followed for 22 ± 14 months (range, 1 to 47 months). Echocardiographic follow-up of the valve repair patients revealed a mean residual aortic stenosis peak instantaneous gradient of 32 mm Hg and mild aortic insufficiency or less in all patients. Conclusions. Aortic valve operation is required in 5% to 7% of patients yearly after BAV. The need for operation appears to be unrelated to age at the time of BAV; aortic insufficiency predominates over aortic stenosis as as indication for operative intervention. Valve repair can be applied in some patients after BAV with good intermediate-term results and may delay the need for aortic valve replacement.

The Pediatric Heart Network: A Primer for the Conduct of Multicenter Studies in Children with Congenital and Acquired Heart Disease

Most contemporary diagnostic and treatment strategies for pediatric patients with cardiovascular disease are not supported by evidence from clinical trials but instead are based on expert opinion, single-institution observational studies, or extrapolated from adult cardiovascular medicine. In response to this concern, the National Heart, Lung, and Blood Institute established the Pediatric Heart Disease Clinical Research Network (PHN) in 2001. The purposes of this article are to describe the initiation, structure, and function of the PHN; to review the ongoing studies; and to address current and future challenges. To date, four randomized clinical trials and two observational studies have been launched. Design and conduct of complex, multicenter studies in children with congenital and acquired heart disease must address numerous challenges, including identification of an appropriate clinically relevant primary endpoint, lack of preliminary data on which to base sample size calculations, and recruitment of an adequate number of subjects. The infrastructure is now well developed and capable of implementing complex, multicenter protocols efficiently and recruiting subjects effectively. The PHN is uniquely positioned to contribute to providing evidence-based medicine for and improving the outcomes of pediatric patients with cardiovascular disease.