Perinatal and early surgical outcome for the fetus with hypoplastic left heart syndrome: a 5-year single institutional experience.

OBJECTIVES: To review our experience with the prenatal diagnosis of hypoplastic left heart syndrome (HLHS). Our goal was to establish the benchmark for perinatal and early surgical outcome in the current era, from a center with an aggressive surgical approach and a cohort with a high level of intention-to-treat. METHODS: Outcome was assessed in fetuses with HLHS following stratification into high-risk and standard-risk categories. High risk was defined as the presence of any of the following: extracardiac, genetic or chromosomal anomalies; prematurity of < 34 weeks' gestation; additional cardiac findings such as intact or highly restrictive atrial septum, severe degree of tricuspid regurgitation or severe ventricular dysfunction. Standard risk was defined as absence of these risk factors. RESULTS: Of 240 fetuses evaluated over 5 years, 162 (67.5%) were in the standard-risk group and 78 (32.5%) were in the high-risk group. Of the 240 sets of parents, 38 (15.8%) chose termination or non-intervention at birth at initial prenatal counseling and 185 of the neonates (77.1%) underwent first-stage Norwood surgery with 155 surviving and 30 deaths, giving an overall Norwood operative survival of 83.8%. Breakdown by risk class reveals a significant Norwood operative survival advantage for the standard-risk group (92.8%) over the high-risk group (56.5%) (P < 0.001). CONCLUSIONS: Following prenatal diagnosis of HLHS, families should be strongly encouraged to undertake comprehensive prenatal evaluation in order to obtain an accurate prognosis. One-third have additional risk factors that limit survival outcome, however two-thirds do not and have an excellent chance of early survival.

Tricuspid valve dysplasia with severe tricuspid regurgitation: fetal pulmonary artery size predicts lung viability in the presence of small lung volumes.

Congenital tricuspid valve disease (Ebstein's anomaly, tricuspid valve dysplasia) with severe tricuspid regurgitation and cardiomegaly is associated with poor prognosis. Fetal echocardiography can accurately measure right atrial enlargement, which is associated with a poor prognosis in the fetus with tricuspid valve disease. Fetal lung volumetric assessments have been used in an attempt to predict viability of fetuses using ultrasonogram and prenatal MRI. We describe a fetus with tricuspid dysplasia, severe tricuspid regurgitation, right atrial enlargement and markedly reduced lung volumes. The early gestational onset of cardiomegaly with bilateral lung compression raised the possibility of severe lung hypoplasia with decreased broncho-alveolar development. Use of fetal echocardiography with measurement of pulmonary artery size combined with prenatal MRI scanning of lung volumes resulted in an improved understanding of this anomaly and directed the management strategy towards a successful Fontan circulation.

Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution.

BACKGROUND: There are limited data regarding the long-term survival of patients who have undergone reconstructive surgery for hypoplastic left heart syndrome (HLHS). We reviewed the 15-year experience at our institution to examine survival in the context of continued improvements in early operative results. METHODS AND RESULTS: Between 1984 and 1999, 840 patients underwent stage I surgery for HLHS. From review of medical records and direct patient contact, survival status was determined. The 1-, 2-, 5-, 10-, and 15-year survival for the entire cohort was 51%, 43%, 40%, 39%, and 39%, respectively. Late death occurred in 14 of the 291 patients discharged to home after the Fontan procedure, although only 1 patient has died beyond 5 years of age. Heart transplantation after stage I reconstruction was performed in 5 patients. Later era of stage I surgery was associated with significantly improved survival (P:<0.001). Three-year survival for patients undergoing stage I reconstruction from 1995 to 1998 was 66% versus 28% for those patients undergoing surgery from 1984 to 1988. Age >14 days at stage I and weight <2.5 kg at stage I were also associated with higher mortality (P:=0.004 and P:=0.01, respectively). Other variables, including anatomic subtype, heterotaxia, and age at subsequent staging procedures, were not associated with survival. CONCLUSIONS: Over the 15-year course of this study, early- and intermediate-term survival for patients with HLHS undergoing staged palliation increased significantly. Late death and the need for cardiac transplantation were uncommon.

Are outcomes of surgical versus transcatheter balloon valvotomy equivalent in neonatal critical aortic stenosis?

BACKGROUND: For neonates with critical aortic valve stenosis who are selected for biventricular repair, valvotomy can be achieved surgically (SAV) or by transcatheter balloon dilation (BAV). METHODS AND RESULTS: Data regarding 110 neonates with critical aortic valve stenosis were evaluated in a study by the Congenital Heart Surgeons Society from 1994 to 1999. Reduced left ventricular function was present in 46% of neonates. The initial procedure was SAV in 28 patients and BAV in 82 patients. Mean percent reduction in systolic gradient was significantly greater with BAV (65+/-17%) than SAV (41+/-32%; P<0.001). Higher residual median gradients were present in the SAV versus BAV group (36 mm Hg [range, 10 to 85 mm Hg] versus 20 mm Hg [0 to 85 mm Hg], P<0.001). Important aortic regurgitation was more often present after BAV (18%) than SAV (3%; P=0.07). Time-related survival after valvotomy was 82% at 1 month and 72% at 5 years, with no significant difference for SAV versus BAV, even after adjustment for differences in patient and disease characteristics. Independent risk factors for mortality were mechanical ventilation before valvotomy, smaller aortic valve annulus (z score), smaller aortic diameter at the sinotubular junction (z score), and a smaller subaortic region. A second procedure was performed in 46 survivors. Estimates for freedom from reintervention were 91% at 1 month and 48% at 5 years after the initial valvotomy and did not differ significantly between groups. CONCLUSIONS: SAV and BAV for neonatal critical aortic stenosis have similar outcomes. There is a greater likelihood of important aortic regurgitation with BAV and of residual stenosis with SAV.

Impact of inspired gas mixtures on preoperative infants with hypoplastic left heart syndrome during controlled ventilation.

BACKGROUND: Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation. METHODS AND RESULTS: Ten anesthetized and paralyzed preoperative infants with HLHS were evaluated in a prospective, randomized, crossover trial comparing hypoxia (17% FIO(2)) with hypercarbia (2.7% FICO(2)). Each patient was treated in a random order (10 minutes per condition) with a recovery period (15 to 20 minutes) in room air. Arterial (SaO(2)) and superior vena caval (SvO(2)) co-oximetry and cerebral oxygen saturation (ScO(2)) measurements were made at the end of each condition and recovery period. ScO(2) was measured by near infrared spectroscopy. Hypoxia significantly decreased both SaO(2) (-5.2+/-1.1%, P=0.0014) and SvO(2) (-5.6+/-1.7%, P=0.009) compared with baseline, but arteriovenous oxygen saturation (AVO(2)) difference (SaO(2)-SvO(2)) and ScO(2) remained unchanged. Hypercarbia decreased SaO(2) (-2.6+/-0.6%, P=0.002) compared with baseline but increased both ScO(2) (9.6+/-1.8%, P=0.0001) and SvO(2) (6+/-2.2%, P=0.022) and narrowed the AVO(2) difference (-8.5+/-2.3%, P=0.005). Both hypoxia and hypercarbia decreased the balance between pulmonary and systemic blood flow (Qp:Qs) compared with baseline. CONCLUSIONS: In preoperative infants with HLHS, under conditions of anesthesia and paralysis, although Qp:Qs falls in both conditions, oxygen delivery is unchanged during hypoxia and increased during hypercarbia. These data cannot differentiate cerebral from systemic oxygen delivery.

The hypoplastic left heart syndrome with intact atrial septum: atrial morphology, pulmonary vascular histopathology and outcome.

OBJECTIVES: The purpose of this study was to investigate the outcome in infants with hypoplastic left heart syndrome and intact atrial septum and to evaluate the relationship of atrial morphology, left atrial decompression pathway and lung histopathology to outcome. BACKGROUND: In the hypoplastic left heart syndrome, severe restriction at the atrial level results in marked systemic hypoxemia after birth. Infants with intact atrial septum may be at high risk for mortality after Norwood operation. METHODS: Of 316 infants with hypoplastic left heart syndrome seen at our center over a 6.5-year period, 18 (5.7%) had intact atrial septum. Medical records and echocardiograms were reviewed. RESULTS: On echocardiography, three types of intact atrial septal morphology were identified: 1) large left atrium, thick prominent septum secondary with thin septum primary adherent (type A, n = 12); 2) small left atrium with thick, muscular atrial septum (type B, n = 4), and 3) giant left atrium, thin atrial septum with severe mitral regurgitation (type C, n = 2). Seven infants had left atrial decompression pathways that were severely obstructed (3/12 type A, 4/4 type B). Norwood operation was performed in 17 infants; one underwent emergency balloon atrial septostomy and died. Of six early survivors, all with type A atrial morphology and unobstructed decompression pathway, three died after subsequent cavopulmonary surgery. Lung histopathology revealed severely dilated lymphatics and "arterialization" of the pulmonary veins in those with the severest degree of obstruction to left atrial egress (type B atrial morphology). CONCLUSIONS: Despite aggressive intervention, outcome for infants born with hypoplastic left heart syndrome and intact atrial septum is poor. Maldevelopment of the pulmonary vasculature contributes to the high mortality seen. Atrial morphology can be used as a marker for the severity of pulmonary vascular disease.

Dilated cardiomyopathy in infants and children.

The outcome of medical treatment of dilated cardiomyopathy in infants and children was reviewed to develop a predictive index for selection of patients likely to benefit from cardiac transplantation. The clinical findings, laboratory investigations, treatment and outcome of 20 patients (Group 1) less than 2 years of age at presentation and 12 patients (Group 2) greater than 2 years of age at onset were compared. Of 20 Group 1 patients, 5 (25%) died. Available autopsies (four patients) showed endocardial fibroelastosis. Of 15 survivors, 10 showed improvement in cardiac status and 5 remained unchanged. Ninety-three percent of survivors had dilated cardiomyopathy consistent with endocardial fibroelastosis by angiocardiography. All 12 Group 2 patients died. In addition to age at presentation and poor outcome, Group 2 differed from Group 1 in having a higher incidence of other family members with cardiomyopathy, more significant rhythm disturbances at presentation and a more rapid course to death. Risk factors of poor outcome in both groups included persistent cardiomegaly and the development of significant arrhythmias by Holter electrocardiographic monitoring. Cardiac transplantation is recommended for children with dilated cardiomyopathy presenting after age 2 years who survive 1 month. Those patients less than 2 years old at presentation whose condition has not improved after 1 year and who have persistent cardiomegaly or complex ventricular arrhythmias may also benefit from transplantation.

What factors are important to parents making decisions about neonatal research?

BACKGROUND: Although parents of neonates with congenital heart disease are often asked permission for their neonates to participate in research studies, little is known about the factors parents consider when making these decisions. OBJECTIVE: To determine the reasons for parents' decisions about participation in research studies. METHODS: Qualitative analysis of the unsolicited comments of 34 parents regarding reasons for agreeing or declining to participate in research studies. Parents' comments were offered spontaneously during interviews about clinical care decisions for neonates with congenital heart disease. RESULTS: Parents cited five types of reason for or against permitting their newborn to participate in research studies: societal benefit (n = 18), individual benefit for their infant (n = 16), risk of study participation (n = 10), perception that participation posed no harm (n = 9), and anti-experimentation views (n = 4). CONCLUSION: Addressing parental decision making in the light of these reasons could enhance the parental permission process for parents of critically ill neonates.

Successful use of alternate waste nitrogen agents and hemodialysis in a patient with hyperammonemic coma after heart-lung transplantation.

BACKGROUND: Lethal hyperammonemic coma has been reported in 2 adults after lung transplantation. It was associated with a massive elevation of brain glutamine levels, while plasma glutamine levels were normal or only slightly elevated. In liver tissue, glutamine synthetase activity was markedly reduced, and the histologic findings resembled those of Reye syndrome. The adequacy of therapy commonly used for inherited disorders of the urea cycle has not been adequately evaluated in patients with this form of secondary hyperammonemia. OBJECTIVE: To determine whether hemodialysis, in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy, would be efficacious in a patient with hyperammonemic coma after solid-organ transplantation. DESIGN: Case report. SETTING: A children's hospital. PATIENT: A 41-year-old woman with congenital heart disease developed a hyperammonemic coma with brain edema 19 days after undergoing a combined heart and lung transplantation. METHODS: Ammonium was measured in plasma. Amino acids were quantitated in plasma and cerebrospinal fluid by column chromatography. The effectiveness of therapy was assessed by measuring plasma ammonium levels and intracranial pressure and performing sequential neurological examinations. RESULTS: The patient had the anomalous combination of increased cerebrospinal fluid and decreased plasma glutamine levels. To our knowledge, she is the first patient with this complication after solid-organ transplantation to survive after combined therapy with sodium phenylacetate, sodium benzoate, arginine hydrochloride, and hemodialysis. Complications of the acute coma included focal motor seizures, which were controlled with carbamazepine, and difficulty with short-term memory. CONCLUSIONS: The aggressive use of hemodialysis in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy may allow survival in patients after solid-organ transplantation. An acute acquired derangement in extra-central nervous system glutamine metabolism may play a role in the production of hyperammonemia in this illness that resembles Reye syndrome, and, as in other hyperammonemic disorders, the duration and degree of elevation of brain glutamine levels may be the important determining factors in responsiveness to therapy.

Medial calcinosis of Mönckeberg. A review of the problem and a description of a patient with involvement of peripheral, visceral and coronary arteries.

Massive medial calcific deposits (Mönckeberg's calcinosis) are described in the peripheral and visceral arteries, and similar but small-sized deposits in the coronary arteries of a 41 year old woman with diabetes mellitus. Although observed by roentgenogram fairly commonly during life in the muscular arteries of the legs in middle-aged men, medial calcinosis infrequently involves the visceral arteries and has never, to our knowledge, been documented in the coronary arteries. Although it may be associated with intimal atherosclerosis, medial calcinosis, per se, does not obstruct the lumens of the arteries and, therefore, does not lead to symptoms or signs of limb or organ ischemia. The cause of medial calcinosis remains a mystery, but it appears to affect people with diabetes more frequently than those without.

Outcome of children with pulmonary hypertension referred for lung or heart and lung transplantation.

We reviewed our institutional experience with 24 children with pulmonary hypertension, who were referred for lung or heart and lung transplantation. Diagnosis, age, and previously published predictive survival scores calculated at the time of referral were analyzed as predictors of pretransplant death. Among the 24 children, 7 did not meet criteria for listing and 17 were listed for transplantation. Of those listed, eight died waiting, two await transplantation, and seven were transplanted and are alive and well 7-20 months after transplantation. Poor functional status (New York Heart Association class 3 or 4) at the time of referral was significantly associated with death before transplant (P=0.05) in univariate analysis. Analysis of the predictive scores was possible in 21 of 24 patients; lower predictive scores were significantly associated with death before transplantation and shorter duration of survival without transplantation in univariate analysis. Multivariate analysis (Cox regression) confirmed that lower scores were significantly associated with poor survival. We conclude that children with pulmonary hypertension are often referred for transplantation too late in the course of their disease. Early complete hemodynamic evaluation before the onset of severe symptoms, followed by serial evaluations of disease progression and consultation with a transplant center, should result in earlier, more appropriate time of listing and improved survival. A systematic study of pretransplant mortality among all children listed for lung transplantation would provide a basis for clinical decision making and policies affecting organ allocation.

Pediatric lung transplantation--are there surgical contraindications?

Lung transplantation has evolved as a successful treatment for end-stage cardiopulmonary disease in children; however, clear guidelines regarding surgical exclusion criteria for pediatric lung transplant candidates have not been well-established. Since December 1994, we have performed 10 bilateral lung transplants and 1 heart-lung transplant in 10 recipients (mean age, 7 years; range, 3 months to 19 years). Indications for transplantation included pulmonary vascular disease (n=6), bronchiolitis obliterans (n=2), bronchopulmonary dysplasia (n=1), graft failure due to viral pneumonitis (n=1), and cystic fibrosis (n=1). Among the 10 patients, 4 were evaluated elsewhere for lung transplantation; of these, 3 were rejected by 1 or more programs because of "high-risk" characteristics. We considered 8 of the 10 patients to have 1 or more "high-risk" characteristics, as follows: previous chest operations other than open lung biopsy (n=6 patients having 1-4 previous operations), ventilator-dependence with tracheostomy and high-dose corticosteroids (n=4), redo lung transplant (n=2), concomitant intracardiac repair (n=6), portal hypertension (n=1), and the use of extracorporeal membrane oxygenation (ECMO) at the time of transplant (n=1). Our standard operative approach was a bilateral thoracosternotomy. Cardiopulmonary bypass was used for explant of the recipient lungs and implant of the donor lungs, and during repair of coexisting congenital heart defects. Aprotinin and fresh whole blood were administered during the procedure to aid in hemostasis. Concomitant procedures were frequently performed and included repair of an intra-atrial baffle leak (prior Mustard procedure), closure of an atrial septal defect, repair of partial anomalous pulmonary venous return, reconstruction of the pulmonary venous confluence, ECMO decannulation, and splenectomy. There were no operative deaths, and no patient required re-exploration for bleeding. One patient had primary graft failure due to adenovirus infection of the donor lungs, and required prolonged mechanical ventilation and eventually ECMO support until retransplantation was performed. The mean hospital stay after transplant was 25+/-13 days (range, 10-56 days). All patients were discharged with a natural airway. Airway complications consisted of one bronchial anastomotic stricture which required dilation, for a complication rate of 5% per anastomoses at risk. One patient required reoperation for stenosis of the superior vena cava. There have been no late deaths, with a mean follow-up of 7+/-4 months (range, 1-13 months). We attribute this 100% operative and short-term survival in these "high-risk" pediatric lung transplant recipients to our operative methods, a multidisciplinary approach to postoperative management, and the enormous physiologic reserve of pediatric patients. Therefore, the standard exclusion criteria used for adult lung transplantation may not be applicable to the pediatric age group. We hope to use these data to expand the use of lung transplantation in pediatric patients.

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Structural changes in porcine xenografts used as substitute cardiac valves. Gross and histologic observations in 51 glutaraldehyde-preserved Hancock valves in 41 patients.

Gross and histologic changes are described in 51 Hancock glutaraldehyde-preserved porcine heterograft bioprostheses from 41 patients: 33 valves from 25 patients had been in place for less than 2 months ("early") and 18 valves from 17 patients were examined at later periods up to 75 months ("late") after implantation. The major gross changes were thrombosis (five bioprostheses) and degeneration (three bioprotheses) of the cusps. Major histologic changes observed in 44 bioprostheses (26 early and 18 late) examined histologically were: (1) fibrin deposits on inflow and outflow surfaces of the cusps; (2) inflammatory cell infiltrates; (3) histiocyte deposition; (4) giant cell formation, and (5) focal disruption of the fibrocollagenous structure of the cusps. These observations indicate that porcine bioprostheses are not biologically inert in the human circulation. However, valve failure is rare at the implantation periods studied.

Extracorporeal life support in cyanotic congenital heart disease before cardiovascular operation.

From July 1988 to March 1991, extracorporeal membrane oxygenation (ECMO) was used in 8 infants (newborn to 16 months old) with unoperated cyanotic congenital heart disease and cardiopulmonary collapse, associated with hypercyanotic spells (4 infants), pulmonary hypertensive crises (3) and sepsis (1). Indications for ECMO support were arterial saturations less than or equal to 60% accompanied by hypotension and metabolic acidosis unresponsive to mechanical ventilation with 100% oxygen, paralysis and sedation, and pharmacologic support with inotropes or vasodilators, or both. Venoarterial bypass by carotid/jugular cannulation with flow rates of 100 to 840 ml/kg/min (mean 460) stabilized all patients. Duration of ECMO support ranged from 15 to 840 hours and was associated with transient seizures (1 patient) and renal failure (1). Seven patients underwent palliative (3 patients) or corrective (4) surgical procedures while on ECMO or within 48 hours of decannulation, including 1 patient bridged to double-lung transplantation with a long (840 hours) duration of ECMO. There was 1 operative and 2 late (greater than 1 month after decannulation) deaths, for an overall survival rate of 62%. These 5 survivors all have normal growth and development, and patent neck vessels at the site of cannulation. These early results indicate that ECMO can be effective mechanical support in cardiovascular crises untreatable with maximal conventional medical therapy and can be used as a bridge to successful surgical palliation or repair.

Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients.

Scanning and transmission electron microscopic studies were made of (1) 12 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for 2 days to 76 months; (2) 3 unimplanted commercially processed porcine aortic valves; and (3) 1 unprocessed porcine aortic valve. Comparison of unprocessed porcine valves and unimplanted commercially processed valves showed loss of endothelium and acid mucopolysaccharides during preimplantation processing. Short-term (less than 2 months) changes after implantation consisted of insudation of plasma proteins, penetration of erythrocytes into surface crevices, formation of a thin surface layer of fibrin, and deposition of macrophages, giant cells and a few platelets. Longer-term (more than 2 months) changes were proportional to the time interval after implantation and consisted of progressive disruption of collagen, erosion of the valve surfaces, formation of aggregates of platelets and accumulation of lipid. The surfaces of the leaflets did not become covered with endothelium or with a fibrous sheath. Calcific deposits were found in one valve and bacterial organisms in another. Thus, progressive breakdown of collagen appears to be a critical factor in determining the long-term durability of glutaraldehyde-treated porcine valvular heterografts.

Infection of glutaraldehyde-preserved porcine valve heterografts.

Gross, histologic and ultrastructural changes associated with bacterial infection are described in four porcine valve heterografts that had been in place in patients for 6 days to 28 months. In one patient, culture of the aortic tissue tag included in the heterograft container grew Mycobacterium chelonei; however, examination of the heterograft, recovered at necropsy 6 days after implantation, revealed small colonies of bacteria that differed morphologically from mycobacteria. A second heterograft was the site of staphylococcal infection associated with extensive destruction of collagen in the leaflets. Similar destruction was observed in a third heterograft, which was found to have organisms on ultrastructural study even though bacterial cultures of the valve were negative. The fourth heterograft, from a patient who died of coronary embolism secondary to dislodgment of vegetative material, contained structures resembling lysed bacteria. Observations in these 4 patients and review of published reports of infection involving 43 other patients with porcine valve heterografts indicates that infection in these valves: (1) develops in the fibrin layer that covers the cusps, (2) can involve the collagen in the leaflets, and (3) is uncommonly (three patients) associated with valve ring abscesses.

Aortic hypoplasia in homozygous familial hypercholesterolemia.

Diagnosis of hypoplastic aortic root with ultrafast computed tomography provides important clinical information in homozygous familial hypercholesterolemic patients with supravalvular aortic stenosis.

Early results after pediatric cardiac transplantation with triple immunosuppression therapy.

Pediatric heart transplant recipients were previously reported to have higher early mortality and morbidity than do adult patients treated with triple immunosuppression therapy (steroids, azathioprine and cyclosporine). Nineteen patients (11 infants and 8 older children) underwent orthotopic transplantation using triple immunosuppression therapy. Surveillance for cellular rejection and coronary arteriopathy was performed with endomyocardial biopsy and selective coronary angiography in all patients, with continuous monitoring for hypertension and serious infection. Seventeen of 19 patients (89%; 10 infants and 7 older children) are current survivors, with a median follow-up of 29 months (range 17 to 94). There were 5 and 7 episodes of rejection in the first 12 months after transplantation in the infant and older groups, respectively, for actuarial freedom-from-rejection rates of 65% at 3 months and 54% at 12 months. Severe coronary arteriopathy was detected in 1 infant 11 months after transplantation. In the first 12 months after transplantation, there were 3 hospitalizations for infection, and 2 patients needed treatment for hypertension in the infant group, compared with 1 hospitalization for infection, and 4 patients on antihypertensives in the older group. An increased prevalence of noninfectious complications in the infant group led to significantly longer postoperative stays than in the older group (mean 27.3 vs 19.4 days; p < 0.05). The results indicate that cardiac transplantation using triple immunosuppression therapy in infants, children and adolescents is associated with a high survival rate, and low rates of rejection and serious infection.

Deletion within chromosome 22 is common in patients with absent pulmonary valve syndrome.

Interstitial deletions in chromosome 22 and features associated with CATCH-22 syndrome have been reported in patients with conotruncal congenital heart anomalies. Absent pulmonary valve syndrome is characterized by absent or rudimentary pulmonary valve cusps, absent ductus arteriosus, conoventricular septal defect, and massive dilation of the pulmonary arteries. Because absence of the ductus arteriosus is a key element in the pathogenesis of this syndrome and aortic arch malformations are frequently seen in patients with CATCH-22 syndrome, we hypothesized that patients with absent pulmonary valve syndrome would have a high incidence of deletions in the critical region of chromosome 22. Eight patients with absent pulmonary valve syndrome were studied. Metaphase preparations were examined with fluorescent in situ hybridization of the N25 (D22S75) probe to the critical region of chromosome 22q11.2. Deletions were detected in 6 of 8 patients. The presence of deletions in chromosome 22 in most of the patients we have examined with a diagnosis of absent pulmonary valve syndrome supports a specific genetic and embryologic mechanism involving the interaction of the neural crest and the primitive aortic arches as one cause of congenital absence of the pulmonary valve.