Use of Palmaz stents in a newborn with congenital aneurysms and coarctation of the abdominal aorta.

Anomalies of the abdominal aorta are rare in the pediatric population limiting the reported knowledge base from which management decisions can be made. A 3-week-old male with congenital abdominal aortic coarctation and multiple aneurysms presented with malignant hypertension. We report the safe deployment of overlapping Palmaz stents using a 4-French catheter delivery system with significant relief of the coarctation gradient and restoration of adequate renal perfusion.

Usefulness of routine surveillance biopsies in children more than one year after orthotopic heart transplantation.

This retrospective study examines the usefulness of routine biopsies following the first year after transplant. This study found that routine biopsies detect few episodes of rejection in the first year after transplant and were less useful than nonroutine biopsies.

Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric heart transplant recipients.

BACKGROUND: Few reports document long-term results of pediatric cardiac transplantation in which triple therapy (cyclosporine, azathioprine, and corticosteroids) was the mainstay of immunosuppression. This report details a single center's pediatric transplant experience and analyzes the relative contributions of selected pre/posttransplant risk factors on long-term morbidity and mortality. METHODS: Retrospective data were collected for all non-neonatal pediatric transplant recipients including: presenting diagnosis, cardiac hemodynamics (particularly pulmonary vascular resistance index), donor ischemic time, occurrence of postoperative infections, episodes of allograft rejection, incidence of posttransplant lymphoproliferative disease or coronary artery disease (CAD), and overall survival. Analysis of single variables and a Cox-proportional hazards model were utilized to determine the impact of pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to 1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who had inoperable complex congenital heart disease, underwent cardiac transplantation and received triple-drug immunosuppression. Orthotopic transplantation was performed unless the pulmonary vascular resistance index remained >6 um2 (despite use of pulmonary vasodilator). One patient required heterotopic transplantation. Average donor ischemic time was 217 min. An average of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months). No patient developed posttransplant lymphoproliferative disease, but 22 patients (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10 years, respectively. Of outcome variables analyzed, rejection frequency was significantly increased in patients who subsequently developed CAD, but the presence of CAD was not significantly correlated with mortality. CONCLUSION: Triple-drug-based immunosuppressive maintenance therapy in pediatric heart transplant recipients results in good long-term graft survival.

Cardiac transplantation for pediatric patients. With inoperable congenital heart disease.

Recent studies have reported the expanding use of transplantation as the definitive option for pediatric patients with inoperable congenital heart disease. This study compares perioperative risk factors and outcomes in pediatric patients who received heart transplants for congenital heart disease with those in pediatric patients who received heart transplants for cardiomyopathy. Retrospective data collected on 40 consecutive pediatric patients undergoing cardiac transplantation from 1 January 1990 through 31 January 1995 provided the following results: 26 patients with cardiomyopathy (mean age, 7.6 years) and 14 patients with congenital heart disease (mean age, 7.2 years) underwent heart transplantation. Between groups, no significant difference was detected in waiting time for a donor heart (cardiomyopathy = 85 days, range = 2 to 409; congenital heart disease = 126 days, range = 9 to 396; P = NS); in donor/recipient weight ratio (1.27 +/- 0.34 vs 1.27 +/- 0.28, P = NS); or in ischemic times (209 +/- 92 minutes vs 248 +/- 70 minutes, P = NS). Cardiopulmonary bypass times accounted for the only significant difference (73 +/- 21 minutes vs 102 +/- 29 minutes, P = 0.003). No significant difference was found in the number of infection episodes, total days hospitalized, rejection episodes, or incidence of transplant coronary artery disease. Forty-month actuarial survival was 88% +/- 6% and 92% +/- 7% for cardiomyopathy and congenital heart disease transplant recipients, respectively (P = NS). We conclude that post-transplantation morbidity and mortality in patients with previous congenital heart disease are not significantly different from morbidity and mortality in patients with cardiomyopathy. Transplantation should be considered an acceptable therapeutic option for patients with congenital heart disease when surgical repair of the native heart is not possible.

Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block.

BACKGROUND: Radiographic evidence of cardiomegaly is common in patients with congenital complete atrioventricular block (CCAVB). It has been speculated that left ventricular (LV) remodeling and increased stroke volume counteract the bradycardia, but the effects of slow heart rate and atrioventricular asynchrony on LV dimensions, geometry, wall stress, and function have not been examined in detail. METHODS AND RESULTS: Thirty patients with CCAVB without associated congenital heart disease (mean age, 8.5+/-5.3 years; range, 0.2 to 20 years) were included in a cross-sectional two-institution study. Thirty-five echocardiograms were performed using standard techniques. ECG and 24-hour ECG recordings were reviewed. Seven patients did not receive a pacemaker, whereas 23 patients underwent pacemaker implantation after the echocardiogram. Compared with normal control subjects, LV volume (Z score=1.5+/-1.3) and LV mass (Z=1.2+/-1.5) were significantly increased, whereas LV mass-to-volume ratio (1.1+/-0.3) and geometry (short-axis diameter/length ratio=0.65+/-0.09) were normal. LV end-systolic stress (ESS) (a measure of afterload) was normal (Z score=0.2+/-2.3), whereas shortening fraction (Z=3+/-2.9) and velocity of circumferential fiber shortening (VCF) (Z=3+/-3.1) were increased. The relationship between VCF and ESS (a preload-insensitive and afterload-adjusted index of contractility) was increased (Z=2.2+/-2) with only small increase in preload (Z=1.02+/-1.1). Regression analyses showed no significant change over age in LV mass, volume, geometry, loading conditions, or systolic function. Patients who ultimately met criteria for pacemaker implantation did not differ from those who did not in terms of heart rate or LV function but did have increased LV volume (Z score=1.8+/-1.4 versus 0.4+/-0.9, P=.03) and LV mass (Z score=1.7+/-1.2 versus 0.2+/-1.7, P=.001) compared to the unpaced group. CONCLUSIONS: In most patients with CCAVB, the LV was enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation LV function did not differ from those who remained unpaced, but evidence of a slightly increased load manifested as increased end-diastolic volume and mass.

Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction.

BACKGROUND: Inflammatory diseases of the heart, including myocarditis and cardiac transplant rejection, are important causes of morbidity and mortality in children. Although viral infection may be suspected in either of these clinical conditions, the definitive etiology is often difficult to ascertain. Furthermore, the histology is identical for both disorders. Coxsackievirus has long been considered the most common cause of viral myocarditis; however, we previously demonstrated by polymerase chain reaction (PCR) analysis that many different, and sometimes unexpected, viruses may be responsible for myocarditis and cardiac rejection. In this study, we describe the association of parvovirus genome identified through PCR analysis of cardiac tissue in the clinical setting of myocarditis and cardiac allograft rejection. METHODS AND RESULTS: Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699-base pair PCR product from the VP1 gene region. Samples tested included those obtained from patients with suspected myocarditis (n=360) or transplant rejection (n=200) or control subjects (n=250). Parvoviral genome was identified through PCR in 9 patients (3 myocarditis; 6 transplant) and no control patients. Of the 3 patients with myocarditis, 1 presented with cardiac arrest leading to death, 1 developed dilated cardiomyopathy, and the other gradually improved. Four of the 6 transplant patients had evidence of significant rejection on the basis of endomyocardial biopsy histology. All transplant patients survived the infection. CONCLUSIONS: Parvovirus is associated with myocarditis in a small percentage of children and may be a potential contributor to cardiac transplant rejection. PCR may provide a rapid and sensitive method of diagnosis.

Outcomes among pediatric heart transplant recipients.

Postoperative cytomegalovirus prophylaxis with cytomegalovirus immunoglobulin or ganciclovir has decreased the incidence of cytomegalovirus disease in cytomegalovirus-negative recipients of cytomegalovirus-positive donor organs. In adults, these drugs have also been used to treat recipients who developed symptomatic cytomegalovirus disease. This report describes outcomes of predominantly cytomegalovirus-negative pediatric cardiac transplant recipients of cytomegalovirus-positive donor organs who received cytomegalovirus immunoglobulin plus ganciclovir as cytomegalovirus prophylaxis, as well as results of this combination therapy when used to treat cytomegalovirus disease. We reviewed the records of children who received donor hearts at our institution between 1989 and 1994. Cytomegalovirus-negative patients who received cytomegalovirus-positive donor organs were given prophylaxis consisting of ganciclovir (5 mg/kg every 12 hours for 14 days, followed by maintenance dosage of 5 to 6 mg/kg every day for 14 days) plus 7 scheduled cytomegalovirus immunoglobulin infusions. Cytomegalovirus infection was documented by culture, polymerase chain reaction, and cytomegalovirus immunoglobulin M seroconversion of a 4-fold or greater rise in cytomegalovirus immunoglobulin G titers. After infection, patients were diagnosed with cytomegalovirus disease when they developed clinical symptoms. These episodes were treated with cytomegalovirus immunoglobulin infusions plus ganciclovir (5 mg/kg every 12 hours) until symptoms resolved. Of 40 cardiac transplant recipients, 10 cytomegalovirus-negative and 9 cytomegalovirus-positive patients received cytomegalovirus-positive donor organs. Five patients (3 of whom were seronegative and had received dual-agent prophylaxis) developed cytomegalovirus disease, which resolved with dual-agent therapy. During an average 15-month follow-up period, no significant morbidity or mortality was attributable to cytomegalovirus disease. Post-transplant dual-therapy cytomegalovirus prophylaxis appears to be as safe and effective in children as in adults, when our results are compared with the published results of studies in adults. Dual-agent treatment eradicated symptoms among patients who developed cytomegalovirus disease. This regimen may allow safer use of the cytomegalovirus-positive donor pool for pediatric recipients.

Update on pediatric heart transplantation. Long-term complications.

Despite evolution to "higher-order" immunosuppressive agents that better control cell-mediated allograft rejection and, therefore, short- and intermediate-term survival, allograft vasculopathy and PTLD remain factors that limit extended graft survival. While improved basic science "bench" techniques have enabled investigation of their pathogenesis at the subcellular and molecular levels, each scientific advance leads the way to the next horizon of complex questions. Only through a more complete understanding of the etiology and pathophysiology of these processes will we be able to design strategies to combat these complications.

Restrictive cardiomyopathies in childhood. Etiologies and natural history.

Restrictive cardiomyopathy is rare in childhood and little is known about the causes and outcome. This lack of information results in extrapolation of adult data to the care and management of children, who might require different treatment from that of adults. This study was undertaken retrospectively to evaluate the causes and natural history of restrictive cardiomyopathy in childhood. Twelve cases of restrictive cardiomyopathy were identified by database review of patient records from 1967 to 1994. The cases were selected on the basis of echocardiographic and cardiac catheterization criteria. Charts were reviewed for the following variables: age, sex, cause, right-and left-sided hemodynamics, pulmonary vascular resistance index, shortening fraction, therapy, and outcome. There were 6 males and 6 females with a mean age of 4.6 years at presentation (median, 3.4 yr; range, 0.9 to 12.3 yr). Etiologies included hypertrophic cardiomyopathy in 3 patients, cardiac hypertrophy with restrictive physiology in 3, idiopathic in 2, familial in 2 (twins), "chronic eosinophilia" in 1, and "post inflammatory" with no definitive causes in 1. At presentation the mean shortening fraction was 33% +/- 2% (mean +/- SEM), average right ventricular pressures were 44/13 +/- 3/1, average left ventricular pressures were 88/25 +/- 4/3, and the mean pulmonary vascular resistance index was 3.4 +/- 1.3 U.m2 (n = 9), but increased to 9.9 +/- 3.1 U.m2 (n = 5, p = 0.04) by 1 to 4 years after diagnosis. Four of the 12 patients had embolic events (1, recurrent pulmonary emboli; 1, saddle femoral embolus; 2, cerebrovascular accidents) and 9 of 12 died within 6.3 years despite medical therapies, which included diuretics, verapamil, propranolol, digoxin, and captopril. In conclusion, restrictive cardiomyopathy in childhood is commonly idiopathic or associated with cardiac hypertrophy, and the prognosis is poor. Embolic events occurred in 33% of our patients, and 9 of 12 patients died within 6.3 years. Within 1 to 4 years of diagnosis, patients may develop a markedly elevated pulmonary vascular resistance index; therefore, transplantation should be considered early.

Influence of age on the effect of bidirectional cavopulmonary anastomosis on left ventricular volume, mass and ejection fraction.

OBJECTIVES: We sought to identify age-related differences in the ventricular response of patients after bidirectional cavopulmonary anastomosis (CPA) and to compare changes in the ventricular response among children < 3 years of age who underwent CPA with that of age-matched control subjects who had a systemic to pulmonary artery shunt alone. BACKGROUND: Pre-Fontan CPA has been advocated over a systemic to pulmonary artery shunt alone in patients with a single ventricle to facilitate ventricular volume unloading and minimize risk of the Fontan operation. METHODS: Our study evaluated 23 patients who initially received a systemic to pulmonary artery shunt as an initial procedure before subsequent Fontan palliation. In eight of these patients (group I), bidirectional CPA was performed before age 3 years, and in four (group II), it was performed after age 10 years. The remaining 11 patients (group III, age and weight control group for group I) were maintained with their initial shunt until they underwent Fontan palliation. Serial echocardiographic analysis was used retrospectively to evaluate left ventricular volume and mass and systolic pump function (ejection fraction) before and after bidirectional CPA. RESULTS: Through 10 months of follow-up, group I patients showed significant decreases in indexed end-diastolic volume both after CPA (120 ml/m1.5 body surface area vs. 78 ml/m1.5, p = 0.001) and in comparison with values in patients in group II and III, who showed no changes in end-diastolic volume (p < 0.001). Indexed ventricular mass decreased moderately after bidirectional CPA in group I (from 228 g/m1.5 body surface area to 148 g/m1.5) but remained unchanged in groups II and III. The differences in trends between groups I and III were significant (p = 0.03). Ejection fraction decreased significantly in group II versus group I patients (0.48 to 0.27 vs. 0.51 to 0.52, p < 0.05) after CPA. Oxygen saturation measurements before and after bidirectional CPA revealed a significant increase in group I (73% to 86%, p < 0.001) and a decrease in group II (82% to 73%, p < 0.01). CONCLUSIONS: Bidirectional CPA facilitates ventricular volume unloading and promotes regression of left ventricular mass in younger children (< 3 years) in preparation for a Fontan operation. In contrast, bidirectional CPA is of questionable value in older children as a staging procedure for Fontan palliation.

Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23.

Dilated cardiomyopathy (DCM) is the most common form of primary myocardial disorder, accounting for 60% of all cardiomyopathies. In 20-30% of cases, familial inheritance can be demonstrated; an autosomal dominant transmission is the usual type of inheritance pattern identified. Previously, genetic heterogeneity was demonstrated in familial autosomal dominant dilated cardiomyopathy (FDCM). Gene localization to chromosome 1 (1p1-1q1 and 1q32), chromosome 3 (3p25-3p22), and chromosome 9 (9q13-9q22) has recently been identified. We report one family with 26 members (12 affected) with familial autosomal dominant dilated cardiomyopathy in which linkage to chromosome 10 at the 10q21-q23 locus is identified. Using short tandem repeat polymorphism (STR) markers with heterozygosity > 70%, 169 markers (50% of the genome) were used before linkage was found to markers D10S605 and D10S201 with a pairwise LOD score = 3.91, theta = 0, penetrance = 100% for both markers. Linkage to 1p1-1q1, 1q32, 3p25-3p22, and 9q13-9q22 was excluded. We conclude that a new locus for pure autosomal dominant FDCM exists, and that this gene is localized to a 9 cM region of 10q21-10q23. The search for the disease causing gene and the responsible mutation(s) is ongoing.

Fontan palliation versus heart transplantation: a comparison of charges.

Surgical approaches to single-ventricle physiologic abnormalities have included Fontan palliation or transplantation. No cost expenditures have been published. This study compared expenditures between the Fontan procedure and heart transplantation. Between 1988 and 1992, records of 82 patients who underwent the Fontan procedure and 26 who underwent transplant were retrospectively reviewed. Charges for Fontan or transplant procedures were accrued from the date of surgical admission until discharge or patient death and included hospital, physician, and diagnostic laboratory charges. Additionally, the frequency and cost of postoperative hospital readmissions, outpatient evaluations, and diagnostic procedures were recorded for each patient. Estimated expenditures for each evaluated parameter were based on 1992 to 1993 dollar charges. The total expenditure (surgery plus yearly follow-up) for transplantation exceeded that for the Fontan procedure ($96,475 vs $29,730; p < 0.001). Although both groups had similar follow-up periods and mortality rates, the number of hospital readmissions and postoperative diagnostic tests was higher among transplant recipients. Within 1 postoperative year at least four high-risk patients who had undergone a Fontan procedure required listing for transplantation; the total costs of their combined procedures (approximately $80,000 + $3,000 to $5,000 annual outpatient charges) was markedly greater than the cost of the Fontan procedure alone. Although the expenditure for heart transplantation far exceeds that for the Fontan procedure, Fontan palliation in high-risk patients is ultimately more costly and increases postoperative morbidity. In this subgroup, we recommend heart transplantation as the initial definitive procedure because it may increase long-term survival rates and minimize health care expenditures.

Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction.

BACKGROUND: Viral infections, particularly those caused by cytomegalovirus, are a major cause of postoperative morbidity and mortality in heart transplant recipients. These infections have classically been diagnosed by history, physical examination, peripheral viral cultures, and serologic studies. These methods are often time-consuming and lack sensitivity. Positive viral cultures from the heart are rarely obtained, and viral myocarditis and acute cellular rejection are unable to be differentiated histologically. We have therefore used the polymerse chain reaction to diagnose possible viral infection in pediatric heart transplant recipients with findings consistent with acute unexplained rejection. METHODS: Polymerase chain reaction was used as an aid to diagnose cytomegalovirus infection of cardiac tissue obtained by right ventricular endomyocardial biopsy and follow its long-term course. In addition, polymerase chain reaction was used to diagnose infection of the heart by other viruses in patients with clinical and histologic evidence of rejection, especially those with unexplained late rejection or chronic rejection. Polymerase chain reaction primers were designed to amplify nucleic acid sequences from cytomegalovirus, parvovirus, adenovirus, herpes simplex virus, Epstein-Barr virus, and the RNA viruses of the Enterovirus family. RESULTS: Forty patients underwent serial right ventricular endomyocardial biopsy (129 samples) for rejection surveillance with positive results obtained in 41 samples (32%) from 21 patients. Viral genome amplified included cytomegalovirus in 16 samples, adenovirus in 14, enterovirus in 6, parvovirus in 3, and herpes simplex virus in 2. In 13 of the 21 patients positive for viral genome (62%), endomyocardial biopsy histologic scores were consistent with multifocal moderate to severe rejection (Internal Society for Heart and Lung Transplantation scores of 3A or greater). CONCLUSIONS: Polymerase chain reactions may be used as a rapid and sensitive method to evaluate postoperative viral infections in heart transplant recipients, especially in those with late-onset rejection or chronic rejection. Polymerase chain reaction may also be useful in the serial analysis of cytomegalovirus status in transplant recipients. The use of multiple viral primers improves the diagnostic evaluation of these patients and may lead to a better understanding of the epidemiologic characteristics of posttransplantation viral infections and the cause of late or chronic rejection.

Genetic heterogeneity in familial dilated cardiomyopathy.

Familial dilated cardiomyopathy (FDCM), an inherited primary form of myocardial disease, is a significant cause of morbidity and mortality at all ages and the leading reason for cardiac transplantation worldwide. Although typically inherited as an autosomal dominant disorder, all forms of inheritance have been recognized. FDCM appears to be responsible for approximately 20-30% of all cases of dilated cardiomyopathy, the most common form of cardiomyopathy. Recently, two families having autosomal dominant FDCM were mapped. The first family had conduction abnormalities and FDCM and was mapped to 1p1-1q1, while the second family, which had pure FDCM, was mapped to 9q13-q22. Neither gene has been identified to date. In this report, one family with pure FDCM was analyzed for linkage to the 1p1-1q1 and 9q13-q22 loci using parameteric linkage analysis, with linkage to both regions excluded. This demonstrates that the pure form of FDCM is caused by multiple different genes, i.e., genetic heterogeneity. Identification of large families with FDCM will be required to identify the various genes responsible for this important clinical entity.

Effect of donor-recipient size mismatch on left ventricular remodeling after pediatric orthotopic heart transplantation.

Left ventricular (LV) hypertrophy has been reported after orthotopic heart transplantation. This study was designed to determine the pattern of LV remodeling in the first year after pediatric orthotopic heart transplantation and to elucidate the mechanism responsible for changes in LV dimensions. Serial echocardiograms of 20 children who underwent cardiac transplantation were analyzed off-line, and the following LV parameters were measured and indexed to body surface area (BSA): short-axis diameters, posterior wall thickness, length, mass, and volume in systole and diastole. Mass/volume and short-axis diameter/length ratios and ejection fraction were calculated. In 5 patients, the donor's echocardiogram was also available for analysis. The patient's systemic blood pressure at the time of the echocardiogram, ischemic time of the donor heart, number of rejection episodes, biopsy scores, and body size of the donor and patient were recorded. Patients were assigned to 2 groups based on their donor-recipient weight ratio:group 1, < or = 1.2 (n = 9); and group 2, > 1.2 (n = 11). In group 1, LV mass index remained within normal limits throughout the study period. In group 2, mass index was significantly increased 2 weeks after transplantation (72 +/- 24 vs 133 +/- 37 g/BSA1.5, p = 0.0008). LV volume, geometry, ejection fraction, systemic blood pressure, and number of rejection episodes did not differ significantly between groups. The excess LV mass index in group 2 regressed significantly during the first year after transplantation from 133 +/- 37 to 93 +/- 17 g/BSA1.5 (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent advances in the etiology, diagnosis, and treatment of myocarditis and cardiomyopathies in children.

The cardiomyopathies are usually classified as dilated, hypertrophic, or restrictive. Although clinical presentations vary among these myopathies, systolic or diastolic dysfunction characterizes the principal pathophysiologic features of each. Advances in genetic linkage analysis and mutation screening have recently allowed investigators to establish a genetic basis for several forms of dilated and hypertrophic cardiomyopathy. Although traditional treatment modalities and newer strategies (such as atrioventricular pacing in patients with dilated cardiomyopathy and pacing or amiodarone therapy for patients with hypertrophic cardiomyopathy) may provide short-term relief, cardiac transplantation may be the only intervention that can alter the natural history and poor prognosis for these potentially lethal conditions. Myocarditis, which usually presents as an acute form of dilated cardiomyopathy, may have a broad spectrum of presentation and is currently treated with nonspecific supportive measures. Although the polymerase chain reaction may provide rapid diagnosis of viral etiologies, newer therapies have not yet been developed. Clinical trials with intravenous immunoglobulin, however, are currently in progress. In patients whose symptoms do not resolve, cardiac transplantation may afford the only potential for long-term survival.