Robert E. Shaddy

Comparison of angioplasty and surgery for unoperated coarctation of the aorta.

BackgroundThe use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion. Methods and ResultsThirty-six patients were prospectively randomized to either angioplasty (20 patients) or surgery (16 patients). Immediate results and patient follow-up, including physical examination, angiograms, and magnetic resonance imaging, were compared between groups. Reduction in peak systolic pressure gradient across the coarctation was similar (86%) immediately after both balloon coarctation angioplasty and surgery. On follow-up, aneurysms were seen only in the angioplasty group (20%) and not in the surgery group (0%o). No aneurysms have shown progression or required surgery. The incidence of other complications was similar in both groups, although two patients experienced neurological complications after surgery. Although not statistically different, the incidence of restenosis (peak systolic pressure gradient 220 mm Hg) tended to be greater in the angioplasty group (25%) than in the surgery group (6%). Restenosis after angioplasty occurred more frequently in patients with an aortic isthmus/descending aorta diameter ratio <0.65 and was associated with an immediate catheterization residual peak systolic pressure gradient across the coarctation 212 mm Hg. ConclusionsImmediate gradient reduction is similar after balloon coarctation angioplasty and surgical treatment of unoperated coarctation of the aorta. The risks of aneurysm formation and possibly restenosis after angioplasty are higher than after surgery, although the risks of other complications are similar. Balloon coarctation angioplasty may provide an effective initial alternative to surgical repair of unoperated coarctation of the aorta in children beyond infancy, particularly in patients with a well-developed isthmus. Further follow-up is necessary to determine the long-term risks of postangioplasty aneurysms.

Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations

The proper ethical conduct of studies to evaluate drugs in children is of paramount importance to all those involved in these types of studies. This report is an updated revision to the previously published guidelines from the American Academy of Pediatrics in 1995. Since the previous publication, there have been great strides made in the science and ethics of studying drugs in children. There have also been numerous legislative and regulatory advancements that have promoted the study of drugs in children while simultaneously allowing for the protection of this particularly vulnerable group. This report summarizes these changes and advances and provides a framework from which to guide and monitor the ethical conduct of studies to evaluate drugs in children.

Long-Term, Randomized Comparison of Balloon Angioplasty and Surgery for Native Coarctation of the Aorta in Childhood

Background—The purpose of this study was to compare the long-term outcomes of children randomized to surgery or balloon angioplasty (BA) for native coarctation (CoA). A prior randomized, short-term comparison of BA and surgery for native CoA in 36 children demonstrated equivalent relief of obstruction. The risk of aneurysm formation and possibly restenosis was higher among patients treated with BA. Methods and Results—Blood pressure, residual aortic obstruction, and exercise performance were evaluated. Need for repeat intervention was reviewed. Aortic arch anatomy was assessed with magnetic resonance angiography. For subjects who were not available to return for evaluation, the most recent clinical record was utilized. Among the 36 subjects initially randomized, 21 returned for evaluation (11 BA, 10 surgery). The average time since initial intervention to evaluation for all subjects was 10.6±4.7 years for BA subjects and 11.3±3.7 years for surgical subjects. Resting blood pressure, CoA gradient, exercise performance, MRI analysis of the aortic arch, and need for repeat interventions were not different for the 2 treatment strategies. There was a higher incidence of aneurysm formation (35% versus 0%) and a greater difference in blood pressure between the right and left legs with exercise among BA subjects. Some aneurysms developed late, first being detected more than 5 years after the initial intervention. Only 50% of BA subjects remained free of both aneurysm formation and repeat intervention compared with 87.5% of surgical subjects (P=0.03). Conclusions—BA for the treatment of childhood CoA is associated with a higher incidence of aneurysm formation and iliofemoral artery injury than surgery. These differences should be considered when undertaking treatment for native CoA during childhood.

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.

B-Type Natriuretic Peptide Levels in Congenital Heart Disease

The objective of this study was to evaluate the potential role of B-type natriuretic peptide (BNP) levels in children with congenital heart disease undergoing cardiac catheterization. Measurement of plasma BNP concentration has been shown to be useful in the diagnosis, risk stratification, and management of adult patients with congestive heart failure, but little is known about the role of BNP in children with structural congenital heart disease. We measured plasma BNP levels using the Triage BNP test in patients with congenital heart disease referred for diagnostic or interventional cardiac catheterization. Plasma BNP concentration was measured in 96 children and 11 adults ≥19 years old (7.9 ± 8.3 years) undergoing heart catheterization for underlying congenital heart disease. BNP levels ranged from <5 to >1300 pg/ml, with a median BNP concentration of 19.0 pg/ml. Baseline BNP concentrations were >100.0 pg/ml on 19 occasions in 17 patients. The pressure difference between the left ventricle and ascending aorta was 10–110 mmHg in 21 patients. BNP concentrations for this cohort ranged from <5.0 to 1060.0 pg/ml and correlated with the degree of left ventricular outflow obstruction (correlation coefficient, 0.661; p = 0.001). This study suggests that with additional research, BNP concentration may prove to be a useful clinical tool in managing children and adults with congenital heart disease.

Beta-blocker treatment of dilated cardiomyopathy with congestive heart failure in children: a multi-institutional experience

BACKGROUND Dilated cardiomyopathy is the primary indication for heart transplantation in children beyond infancy. Although beta-blockers improve symptoms, ejection fraction, and survival in adults with congestive heart failure, little is known of their effects in children. METHODS This study reviews our pediatric experience with the beta-blocker, metoprolol, at 3 institutions. We gave metoprolol to 15 children, age 8.6 +/- 1.3 years (range 2.5 to 15 years), with idiopathic dilated cardiomyopathy (n = 9), anthracycline cardiomyopathy (n = 3), and Duchenne muscular dystrophy cardiomyopathy, postmyocarditis cardiomyopathy, and post-surgical cardiomyopathy (n = 1 each). All had been treated with conventional medications (digoxin, diuretics, and ACE inhibitors) for 22.5 +/- 9 months before starting metoprolol. Metoprolol was started at 0.1 to 0.2 mg/kg/ dose given twice daily and slowly increased over a period of weeks to a dose of 1.1 +/- 0.1 mg/kg/day (range 0.5 to 2.3 mg/kg/day). RESULTS Between the time point of stabilization on conventional medications and the initiation of metoprolol therapy, there was no significant change in fractional shortening (13.1 +/- 1.2% vs 15.0 +/- 1.2%) or ejection fraction (25.6 +/- 2.1% vs 27.0 +/- 3.4%). However, after metoprolol therapy for 23.2 +/- 7 months, there was a significant increase in fractional shortening(23.3 +/- 2.6%) and ejection fraction (41.1 +/- 4.3%) (p < 0.05). CONCLUSIONS Metoprolol improves ventricular function in some children with dilated cardiomyopathy and congestive heart failure. Further study is warranted to better define which children may benefit most from beta-blocker therapy and which beta-blockers are most efficacious.

Allosensitization and outcomes in pediatric heart transplantation

BACKGROUND Allosensitization among children being considered for heart transplantation remains a great challenge. Controversy exists as to the best approach for those with elevated panel-reactive antibody (PRA) titers. We sought to define the association between elevated PRA and outcomes using data from the multi-institutional Pediatric Heart Transplant Study Group. METHODS Between January 1993 and December 2008, 3,016 patients (>1 month of age) were listed for heart transplantation. PRA data at listing were available for 2,500 (83%) patients, and 2,237 underwent transplantation with PRA data being available for 1,904 (85%). Because various PRA assays were employed (e.g., cell-based and solid phase) we entered the highest value regardless of methodology. RESULTS Among the factors associated with high PRA at transplant were Status 1 at listing, previous sternotomy and prior Norwood procedure. An elevated PRA at listing was associated with higher risk of death while waiting. Of subjects with PRA ≥ 50% only 57% were transplanted by 1 year on the waitlist, as compared with 76% of those with PRA <10%. Waitlist mortality for the highly allosensitized subjects (≥ PRA 50%) was 19% by 12 months. Survival at 1 year after transplantation was significantly lower in those with PRA ≥ 50% versus those with PRA <10% (73% vs 90%, respectively, p < 0.0001). Those with elevated PRA who had a negative prospective crossmatch had no difference in survival compared with those without allosensitization. There was no significant association between PRA levels and time to first rejection or development of coronary allograft vasculopathy. CONCLUSIONS Significant allosensitization is associated with more than a 2-fold increased risk of death within the first transplant year. Although prospective crossmatching abrogates the risk of post-transplant mortality, it may contribute to higher pre-transplant attrition due to longer waitlist times. There is a critical need for strategies to minimize the impact of allosensitization and antibody-mediated rejection immediately after transplantation.

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.

The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary

From the Freeman Hospital, Newcastle upon Tyne, United Kingdom; Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Stanford University, Stanford, California; Columbia University Medical Center, New York, New York; Great Ormond Street Hospital, London, United Kingdom; Joe DiMaggio Children’s Hospital, Hollywood, Florida; Primary Children’s Medical Center, Salt Lake City, Utah; C.S. Mott Children’s Hospital, Ann Arbor, Michigan; Children’s Hospital, Denver, Colorado; Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Ann & Robert H Lurie Children’s Hospital, Chicago, Illinois; Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and the Royal Melbourne Children’s Hospital, Melbourne, Victoria, Australia.

Cardiovascular Monitoring of Children and Adolescents Receiving Psychotropic Drugs: A Statement for Healthcare Professionals From the Committee on Congenital Cardiac Defects, Council on Cardiovascular Disease in the Young, American Heart Association

Reports of sudden deaths of children and adolescents treated with psychotropic medications have raised concerns regarding the appropriateness of this therapy, as well as the advisability of baseline and periodic electrocardiographic (ECG) monitoring of such patients.1 2 3 4 What follows is a review of the drug effects on the ECG, cardiovascular effects of the commonly used psychotropic medications in children and adolescents, a summary of potentially dangerous drug interactions, and recommendations for cardiovascular monitoring. Although medications can potentially cause sudden, unexpected death by a variety of mechanisms (eg, seizures, central nervous system depression, or coronary artery spasm), cardiac arrhythmias are the most frequent cause. In particular, a unique form of ventricular tachycardia termed torsade de pointes has been recognized as the arrhythmia responsible for the so-called proarrhythmic effect of several antiarrhythmia drugs, and recent evidence has pointed to a similar mechanism in syncope and deaths related to other medications5 and in the familial long-QT syndromes.6 The common feature of these conditions is delayed repolarization of the myocardium (related to abnormal sodium or potassium currents) with resultant prolongation of the QT interval of the ECG. This appears to leave the myocardium vulnerable to ventricular tachycardia, primarily in the setting of bradycardia but occasionally in association with exercise. Other ECG abnormalities, such as sinus node depression, …