Transcatheter occlusion of a large pulmonary arteriovenous malformation using the Amplatzer vascular plug.

Pulmonary arteriovenous malformation (AVM) is a rare entity with well-described signs, symptoms, and complications. Pulmonary AVMs can be congenital or acquired. They have been described in the setting of severe liver disease and after palliation with a Glenn shunt in which the hepatic venous blood flow has been excluded from the pulmonary blood flow. A variety of surgical and transcatheter interventions have been used to occlude AVMs. We report the use of the Amplatzer vascular plug to successfully occlude a pulmonary AVM in a 12-year-old patient.

Resolution of right heart enlargement after closure of secundum atrial septal defect with transcatheter technique.

OBJECTIVES: The purpose of this study was to prospectively characterize the reduction in right atrial (RA) area and right ventricular (RV) volume after transcatheter closure of atrial septal defect (ASD) and to investigate factors that may predict magnitude of resolution in right heart enlargement. BACKGROUND: Secundum ASD can cause volume overload of the right side of the heart with the potential for development of late complications. Little is known about reduction in right heart size after closure of ASD. METHODS: Transthoracic echocardiography was performed in 38 patients undergoing transcatheter closure of ASD. The RA area and RV volume were measured prior (n = 38), within 24 hours (n = 37), at 3 to 6 months (n = 24), at 12 months (n = 20) and at 24 months (n = 10) after closure of ASD. Change over time within the study group was assessed and the study group was compared to a control group of 19 patients with structurally normal hearts. RESULTS: Indexed RA area decreased from baseline to 3- to 6-month follow-up (p = 0.004) as did indexed RV volume (p < 0.0001). Indexed RV volume was similar to that in the control group at 24 months (p = 0.3); however, indexed RA area remained greater than in the control group (p = 0.006). Decrease in indexed RA area over the first 12 months of follow-up was related to young age at time of closure by regression analysis (r = 0.55, p = 0.013). CONCLUSION: Closure of secundum ASD results in decreased indexed RV volume comparable to that in control subjects at 24 months following closure. Indexed RA area remains increased compared to that in control subjects but does decrease over time. Decrease in RA area is inversely proportional to age at time of ASD closure. Long-term follow-up is required to evaluate the clinical impact of persistently increased RA size.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation.

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart-lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.

Repair of anomalous left main coronary artery arising from the pulmonary artery in infants: long-term impact on the mitral valve.

BACKGROUND: Infants presenting with anomalous left coronary artery off the pulmonary artery (ALCAPA) are generally in heart failure and often have significant mitral valve regurgitation (MR). Although establishing a dual coronary circulation is the procedure of choice, there remains controversy as to how the mitral valve is handled. METHODS: We reviewed our experience with this lesion at St. Louis Children's Hospital. Over the past 15 years, 17 infants under 18 months of age have undergone repair, with all but one being treated with reimplantation of the left coronary artery into the aorta; the other underwent the Takeuchi procedure (intrapulmonary artery baffle) and was excluded from this evaluation. The average age and weight at operation were 0.5 +/- 0.3 years and 6.1 +/- 1.9 kg, respectively. All presented with varying degrees of heart failure and 9 patients also had either moderate or severe MR. RESULTS: There was one early and no late deaths after reimplantation of the left coronary artery. The left ventricular function postrepair improved from a preoperative shortening fraction of 0.19 +/- 0.09 to 0.34 +/- 0.08 (p < 0.01). Moderate or severe MR was present in 2 patients postoperatively, and both developed significant obstruction in the left coronary artery postoperatively as well. Both underwent mitral valve repair and revascularization of the left coronary artery. CONCLUSIONS: Excellent results can be obtained in the treatment of this very high-risk group of patients. Mitral valve repair is not generally necessary at the time of the initial operation. However, should MR recur or persist late, it may herald the presence of a coexistent, significant coronary stenosis. Cardiac catheterization should be performed to assess the patency of the left coronary artery before performing mitral valve surgery.

Echocardiographic prediction of left-to-right shunt with atrial septal defects.

We investigated the ability of transthoracic echocardiography to predict a ratio of pulmonary to systemic flow (Qp/Qs) > or = 1.5 in patients with secundum atrial septal defects. The 44 study patients included 31 patients undergoing catheterization for device closure of atrial septal defects and 13 additional control patients with normal echocardiograms (median age 7.8 years, mean age 15.9 years, range 1.5 to 69 years). Right atrial end-systolic area, right ventricular end-diastolic volume, and the ratio of pulmonary annulus diameter to aortic annulus diameter were determined from standard transthoracic echocardiographic views. The 26 subjects in the shunt group had Qp/Qs between 1.5 and 3.0. The control subjects included the 5 catheterization patients with Qp/Qs between 0.9 and 1.2 and the 13 patients that did not undergo catheterization with assumed Qp/Qs = 1. The shunt patients had significantly increased median-indexed right atrial area (13.8 versus 8.5 cm(2)/M(2), P <. 0001), median-indexed right ventricular volume (85 versus 39 mL/M(2), P <.0001), and median ratio of pulmonary valve annulus to aortic valve annulus (1.26 versus 1.13, P =.008) compared with controls. Indexed right ventricular volume was the best predictor of significant shunt. A combination of right ventricular volume and right atrial area identified subjects with Qp/Qs >1.5 with 96% sensitivity, 94% specificity, and 96% positive and 94% negative predictive value. We conclude that quantitative transthoracic echocardiography can be used to screen for a significant shunt in patients with atrial septal defects.

Selective coronary angiography in pediatric patients.

Selective coronary angiography (SCA) is an important diagnostic tool in pediatric cardiology; however, there are few reports on its feasibility and safety in young patients. We reviewed our experience with SCA from July 1, 1993 to December 31, 1997. There were 158 cardiac catheterizations that included SCA in patients whose ages ranged from 2 days to 46 years (median, 5.3 years). The most common indication was surveillance for coronary vasculopathy after heart transplantation. A retrograde approach was used in all patients through the femoral artery (n = 157) or umbilical artery (n = 1). Preformed coronary catheters were used and the Judkins left (JL) and Judkins right (JR) were the most common catheters, with the catheter curve size correlating with patient height (R(2) =.76 for JL, R(2) =. 673 for JR). Complications during SCA included brief ST-T wave changes (11%), bradycardia (2.5%), and ventricular fibrillation (0. 6%). Complications of vascular access were transient pulse loss (6%), hematoma (5%), and rebleeding (0.6%). Only one case of femoral artery occlusion was encountered on subsequent cath. In conclusion, complications of SCA were infrequent and serious complications were rare. SCA can be safely performed in pediatric patients at any age including neonates.

Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients.

OBJECTIVES: This study analyzed the relationship of variability in routine trough cyclosporine (CSA) levels to morbidity after pediatric cardiac transplantation. BACKGROUND: Due to high interindividual variation between dosage and blood concentrations, trough surveillance CSA levels are routinely performed after cardiac transplantation to adjust dosages. In addition, trough CSA levels have been used as a measure of patient compliance in transplant recipients. Recent investigations have demonstrated a relationship between late rejection and mistimed CSA dosing intervals, which could also lead to CSA levels that are incorrectly presumed to be trough levels. METHODS: Trough surveillance whole-blood CSA levels were retrospectively reviewed in 49 pediatric heart transplant recipients who had a median follow-up of 42 months (range 6 to 138 months). All patients received the same immunosuppression regimen (CSA, azathioprine, and steroids), the same CSA-level surveillance protocol, and the same stabilization of CSA dose and level in the therapeutic range (150 to 300 ng/ml) prior to hospital discharge. CSA levels drawn because of coexisting phenomena (drug interaction, gastroenteritis) that could cause CSA-level fluctuation were excluded from analysis. Cyclosporine variability was measured as the percentage of CSA levels that were considered sub-therapeutic (< or = 100 ng/ml), toxic (> or = 450 ng/ml), or both. Cyclosporine-level variability was then analyzed in respect to demographic and outcome variables. RESULTS: For the group, the median percentage of sub-therapeutic levels was 3% (range, 0% to 16%); the median percentage of toxic levels was 5% (range, 0% to 36%); the median of the combination of sub-therapeutic and toxic levels was 10% (0% to 38%). Eight of the 49 patients (16%) has a high (>20%) percentage of sub-therapeutic + toxic levels or high CSA variability. High CSA variability was significantly associated with recipients > 12 months of age (p = 0.028), and recipients with a history of non-compliance (p < 0.001). Patients with high CSA variability had a significantly higher median number of hospitalized days per year of follow-up (p = 0.036), higher rate of recurrent rejection (> or = 2 episodes; p = 0.0003), and higher death rate more than 6 months after transplant (p = 0.01). CONCLUSIONS: Although this study could not determine cause, high variability in trough CSA levels was a marker for pediatric heart transplant recipients at greater risk for recurrent rejection and hospitalization after transplantation.

Transplant coronary artery disease in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary artery disease (TxCAD) contributes to a large percentage of late morbidity and mortality among adult heart transplant recipients. Intracoronary ultrasound (ICUS) is a sensitive tool in the diagnosis of TxCAD in adult patients and has allowed analysis of factors contributing to disease development. Experience with ICUS in pediatrics, however, has been limited. By using ICUS we sought to determine the overall prevalence of TxCAD in pediatrics and to characterize factors associated with its development in this population. METHODS: Eighty-six studies were performed in 51 pediatric patients a median of 3.4 years after heart transplantation. Evaluation included angiography and ICUS in 83 and angiography alone in 3 studies. Donor and recipient characteristics were obtained. The ICUS images were analyzed for intimal thickening and compared with coronary angiograms. The presence of any intimal thickening on ICUS was considered TxCAD. An intimal index and point of maximal intimal thickening (MIT) were measured. Vessel disease was graded 0 to 4 based on these results. Four patients had evidence of vasculopathy by angiography, whereas 32 patients (63%) had evidence of intimal proliferation by ICUS. Grade 2 or greater disease was present in 19 (37%) patients. A positive correlation was found when comparing time from transplant with intimal index and MIT (p < 0.001). No other factors were found to predict the development of disease. The overall prevalence of disease was 74% in patients studied at least 5 years after transplant. Intracoronary ultrasound can be performed safely in pediatric patients. Transplant coronary artery disease is common in infants and children after heart transplantation, although its prevalence appears to be less than in adult recipients at similar time intervals. We found no factor other than time from transplant was associated with development of disease.

Rejection with heart failure after pediatric cardiac transplantation.

BACKGROUND: Rejection associated with heart failure or death occurs after pediatric cardiac transplantation but has had limited analysis. METHODS: We analyzed the records of 96 consecutive pediatric cardiac transplant recipients who survived to hospital discharge. RESULTS: Eighteen patients (19%) experienced 23 episodes of heart failure or death associated with rejection. Univariate analysis demonstrated black race (p = 0.041), transplantation after 12 months of age (p = 0.032), later time after transplantation (p = 0.037), rejection episode in the first year after transplantation (p = 0.001), and history of two or more rejection episodes (p < 0.001) were significantly associated with rejection seen with heart failure. A multivariate regression analysis identified two or more rejection episodes to be the only independent risk factor for the development of rejection with heart failure (odds ratio 20; 95% confidence limits, 4-104; p < 0.0001). CONCLUSIONS: This study identified pediatric heart transplant recipients with a history of previous rejection episodes to be at a higher risk for symptomatic or fatal rejection. Further studies are needed to determine if intensification of maintenance immunosuppression, long-term rejection surveillance, or both in patients with multiple rejection episodes could reduce morbidity and mortality from rejection.

Lung retransplantation in children.

BACKGROUND: Early primary graft failure due to reperfusion injury may occur in up to 10% of all patients undergoing lung transplantation. Late graft failure in the form of bronchiolitis obliterans progressively increases in frequency as posttransplantation follow-up increases. In both situations, the degree of pulmonary dysfunction may worsen and result in the death of the recipient. The only treatment in many instances is retransplantation. The results in adults are reasonably well established. METHODS: We reviewed our experience in children. Of the 136 transplant procedures performed to date in children, 14 have been retransplantations. Six patients required retransplantation for early primary graft failure and 8 underwent retransplantation for bronchiolitis obliterans. RESULTS: There were three early and three late deaths. The actuarial survival at 2 years is 58%. The retransplant procedures were more complex than the primary transplant operations as evidenced by the longer time on cardiopulmonary bypass (199 +/- 71 versus 150 +/- 41 minutes; p < 0.01) and the greater volume of blood transfused (1,303 +/- 936 versus 570 +/- 300 mL; p < 0.01). Two of the long-term survivors who received transplants for bronchiolitis obliterans have subsequently had development of this same condition and 1 died secondary to this. In four instances living related donors were used for the retransplant procedure. The most striking difference in these procedures compared with those transplantations performed with cadaveric donors was the shorter donor lung ischemic times (99.5 and 123.3 minutes for the two lungs for living related donors and 251 and 293 minutes for the first and second lung for the cadaveric donors; p < 0.01). CONCLUSIONS: We believe that lung retransplantation in children is a reasonable therapy to offer in the circumstance of severe graft dysfunction. In the older child, the option of living donor transplantation offers advantages that might offset of the overall higher risk of this procedure.

Patterns and potential value of cardiac troponin I elevations after pediatric cardiac operations.

BACKGROUND: Perioperative myocardial injury is a major determinant of postoperative cardiac dysfunction for congenital heart disease, but its assessment during this period is difficult. The objective of this study was to determine the suitability of using postoperative serum concentrations of cardiac troponin I (cTnI) for this purpose. METHODS: Cardiac troponin I levels were measured serially in the serum of patients undergoing uncomplicated repairs of atrial septal defect (n = 23), ventricular septal defect (n = 16) or tetralogy of Fallot (n = 16). The concentrations were correlated with intraoperative parameters (cardiopulmonary bypass time, aortic cross-clamp time, and cardiac bypass temperature), and postoperative parameters (magnitude of inotropic support, duration of intubation, and postoperative intensive care and hospital stay). RESULTS: Postoperative absolute cTnI levels were lesion specific, with a pattern of increase and decrease similar for each lesion. For the total cohort, significant correlations between postoperative cTnI levels at all times (r = 0.43 to 0.83, p < 0.05) until 72 hours were noted for all parameters, except for cardiac bypass temperature. When evaluated as individual procedure groups, no significant relationships were noted in the atrial septal defect group, whereas postoperative cTnI levels were more strongly correlated with all intraoperative and postoperative parameters in the ventricular septal defect group than in the tetralogy of Fallot group. CONCLUSIONS: This study suggests that cTnI values immediately after operation reflect the extent of myocardial damage from both incisional injury and intraoperative factors. Cardiac tropinin I levels in the first hours after operation for congenital heart disease are a potentially useful prognostic indicator for difficulty of recovery.

Clinical effects of benzyl benzoate in the prevention of house-dust-mite allergy. Results of a prospective, double-blind, multicenter study.

The efficacy of the acaricide benzyl benzoate as an additive to a chemically and technically defined cleaning substance (Acarosan) was tested in a multicentric, prospective, randomized, controlled study on 118 outpatients with bronchial asthma due to house-dust-mite allergy. Subjective reports from patients and doctors revealed an improvement in clinical complaints in more than 50%, with only small differences between the verum and the placebo group. Objective parameters such as titrated skin tests, RAST, and bronchial challenge tests with histamine and Dermatophagoides pteronyssinus (D. pt.) did not reveal any significant changes either during the year of testing or between the two groups. A clinical improvement as observed in either group could not be assessed by objective parameters. Additional questions as to the merits of the possible prophylactic use of benzyl benzoate over more than 1 year remain unanswered.

Pediatric lung transplantation at St. Louis Children's Hospital, 1990-1995.

Although accepted therapy in adults, lung transplantation in children is less well established. Reports from the few existing pediatric centers have involved relatively small patient number. Seventy-nine patients underwent 88 lung transplant procedures at St. Louis Children's Hospital between June 1990 and August 1995. Twenty-one transplants (24%) were done in 19 infants and children under the age of 3 yr. Twelve-, 24-, and 48-mo actuarial survival for the primary transplants was 69%, 67%, and 60%, respectively. Survival improved over the course of the program: 12-mo survival for patients transplanted during the first 18 mo was 42% compared with 78% for those transplanted after December 1991. Survival of children transplanted at younger than 3 yr of age was comparable to older children and adults. However, younger children had a lower incidence of acute rejection; none developed bronchiolitis obliterans. Both graft growth and linear growth occurred. Risk factors for early mortality included presence of aortopulmonary collateral vessels and prior thoracic surgery. Risk factors for survival duration included requiring assisted ventilation at the time of transplant, continuous supplemental oxygen requirement, and presence of aortopulmonary collateral vessels. The major late complication was bronchiolitis obliterans, which occurred in 27% of patients and played a role in 64% of late deaths. Investigation of the lower incidence of acute rejection and bronchiolitis obliterans in younger versus older children may reveal important information about the etiology of this disease. The ultimate long-term success of lung transplantation will depend on identification and treatment of the mechanisms responsible. A multicenter data registry would facilitate further clinical studies of pediatric lung transplantation.

Utility of surveillance biopsies in infant heart transplant recipients.

BACKGROUND: Endomyocardial biopsy remains the primary means of rejection surveillance after orthotopic heart transplantation in adults. Perpetual surveillance endomyocardial biopsy has been questioned, however, because of low yield beyond the early posttransplantation period. This issue has not been adequately studied in the pediatric population. The objectives of this study were to define the rate of rejection in infants undergoing orthotopic heart transplantation, correlate rejection with signs and symptoms, and evaluate the utility of surveillance endomyocardial biopsy. METHODS: Records of all patients 24 months of age or younger undergoing orthotopic heart transplantation were reviewed; 38 patients underwent 42 transplantation; 256 endomyocardial biopsies were performed for surveillance, cardiac symptoms, noncardiac symptoms, or lowered immunosuppression. RESULTS: There were 22 rejection episodes International Society for Heart and Lung transplantation grade 1B or higher, half of which occurred in neonates 30 days of age or younger. Linearized rejection rates and actuarial freedom from rejection were not different between neonates and older infants. Linearized rejection rates reached a plateau 3 months after orthotopic heart transplantation of 0.07 episodes/100 patient days. No positive surveillance endomyocardial biopsies were obtained beyond 6 months after orthotopic heart transplantation. The probability of a positive biopsy (International Society for Heart and Lung Transplantation grade 1B or higher) was 20% or more for any other indication (odds ratios for rejection were 12.9 for cardiac symptoms, 3.3 for noncardiac symptoms, and 10.8 for lowered immunosuppression as determined by logistic regression more than 6 months after orthotopic heart transplantation). CONCLUSIONS: Rejection rates are not different between neonatal and older infants, and endomyocardial biopsies done solely for surveillance beyond 6 months after orthotopic heart transplantation rarely yield positive results.

Essential motifs of relaxase (TraI) and TraG proteins involved in conjugative transfer of plasmid RP4.

Two essential transfer genes of the conjugative plasmid RP4 were altered by site-directed mutagenesis: traG of the primase operon and traI of the relaxase operon. To evaluate effects on the transfer phenotype of the point mutations, we have reconstituted the RP4 transfer system by fusion of the transfer regions Tra1 and Tra2 to the small multicopy replicon ColD. Deletions in traG or traI served to determine the Tra phenotype of mutant plasmids by trans complementation. Two motifs of TraG which are highly conserved among TraG-like proteins in several other conjugative DNA transfer systems were found to be essential for TraG function. One of the motifs resembles that of a nucleotide binding fold of type B. The relaxase (TraI) catalyzes the specific cleaving-joining reaction at the transfer origin needed to initiate and terminate conjugative DNA transfer (W. Pansegrau, W. Schröder, and E. Lanka, Proc. Natl. Acad. Sci. USA 90:2925-2929, 1993). Phenotypes of mutations in three motifs that belong to the active center of the relaxase confirmed previously obtained biochemical evidence for the contributions of the motifs to the catalytic activity of TraI. Expression of the relaxase operon is greatly increased in the absence of an intact TraI protein. This finding suggests that the relaxosome which assembles only in the presence of the TraI in addition to its enzymatic activity plays a role in gene regulation.

The mating pair formation system of plasmid RP4 defined by RSF1010 mobilization and donor-specific phage propagation.

Transfer functions of the conjugative plasmid RP4 (IncP alpha) are distributed among distinct regions of the genome, designated Tra1 and Tra2. By deletion analyses, we determined the limits of the Tra1 region, essential for intraspecific Escherichia coli matings. The Tra1 core region encompasses approximately 5.8 kb, including the genes traF, -G, -H, -I, -J, and -K as well as the origin of transfer. The traM gene product, however, is not absolutely required for conjugation but significantly increases transfer efficiency. To determine the transfer phenotype of genes encoded by the Tra2 core region, we generated a series of defined Tra2 mutants. This revealed that at least trbB, -C, -E, -G, and -L are essential for RP4 conjugation. To classify these transfer functions as components of the DNA transfer and replication (Dtr) or of the mating pair formation (Mpf) system, we analyzed the corresponding derivatives with respect to mobilization of IncQ plasmids and donor-specific phage propagation. We found that all of the Tra2 genes listed above and the traG and traF genes of Tra1 are required for RSF1010 mobilization. Expression of traF from Tra1 in conjunction with the Tra2 core was sufficient for phage propagation. This implies that the TraG protein is not directly involved in pilus formation and potentially connects the relaxosome with proteins enabling the membrane passage of the DNA. The proposed roles of the RP4 transfer gene products are discussed in the context of virulence functions encoded by the evolutionarily related Ti T-DNA transfer system of agrobacteria.

Pediatric endomyocardial biopsy performed solely with echocardiographic guidance.

Endomyocardial biopsy has had limited utilization for the diagnosis of myocardial disease in the pediatric population. Through the use of echocardiography for guidance, we attempted 155 consecutive biopsies in 33 patients. A successful biopsy was performed 151 times, including 48 (31%) in infants less than 6 months of age. Biopsies were performed with a right internal jugular approach using 3F, 5F, and 7F bioptomes. A combination of apical four-chamber and parasternal short-axis views could visualize the passage of the bioptome into the ventricle and the action of the jaws. There was no case of ventricular perforation. After biopsy one transplant recipient was left with an increase in the amount of preexisting tricuspid regurgitation by color flow mapping echocardiography. These results demonstrate that echocardiographically guided endomyocardial biopsies may be safely performed over a wide range of patient sizes. The increased portability, lack of radiation exposure, and the simultaneous visualization of the bioptome and chamber wall combined with these results indicate that echocardiographically guided endomyocardial biopsies should be considered the technique of choice for the pediatric population.