The cohesive energy of superheavy element copernicium determined from accurate relativistic coupled-cluster theory.

The cohesive energy of bulk copernicium is accurately determined using the incremental method within a relativistic coupled-cluster approach. For the lowest energy structure of hexagonal close-packed (hcp) symmetry, we obtain a cohesive energy of -36.3 kJ mol-1 (inclusion of uncertainties leads to a lower bound of -39.6 kJ mol-1), in excellent agreement with the experimentally estimated sublimation enthalpy of -38 kJ mol-1 [R. Eichler et al., Angew. Chem. Int. Ed., 2008, 47, 3262]. At the coupled-cluster singles, doubles and perturbative triples level of theory, we find that the hcp structure is energetically quasi-degenerate with both face-centred and body-centred cubic structures. These results provide a basis for testing various density-functionals, of which the PBEsol functional yields a cohesive energy of -34.1 kJ mol-1 in good agreement with our coupled-cluster value.

ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation.

Organ transplantation from ABO blood group-incompatible (ABOi) donors requires accurate detection, effective removal and subsequent surveillance of antidonor antibodies. Because ABH antigen subtypes are expressed differently in various cells and organs, measurement of antibodies specific for the antigen subtypes in the graft is essential. Erythrocyte agglutination, the century-old assay used clinically, does not discriminate subtype-specific ABO antibodies and provides limited information on antibody isotypes. We designed and created an ABO-glycan microarray and demonstrated the precise assessment of both the presence and, importantly, the absence of donor-specific antibodies in an international study of pediatric heart transplant patients. Specific IgM, IgG, and IgA isotype antibodies to nonself ABH subtypes were detected in control participants and recipients of ABO-compatible transplants. Conversely, in children who received ABOi transplants, antibodies specific for A subtype II and/or B subtype II antigens-the only ABH antigen subtypes expressed in heart tissue-were absent, demonstrating the fine specificity of B cell tolerance to donor/graft blood group antigens. In contrast to the hemagglutination assay, the ABO-glycan microarray allows detailed characterization of donor-specific antibodies necessary for effective transplant management, representing a major step forward in precise ABO antibody detection.

A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

The value of angiography in the follow-up of coronary involvement in mucocutaneous lymph node syndrome (Kawasaki disease).

From September 1976 to August 1988, 205 patients with mucocutaneous lymph node syndrome (Kawasaki disease) were evaluated; 29 were suspected of having coronary artery abnormalities because of either abnormalities on echocardiography (n = 21), congestive heart failure (n = 3), prolonged fever (n = 3) or cardiac arrest (n = 2). All 29 underwent cardiac catheterization and 22 were found to have coronary artery abnormalities. An additional 4 patients were diagnosed solely by autopsy; therefore, 26 patients (12%) in this series had coronary artery abnormalities. The clearance of contrast medium from the coronary arteries after aortography was significantly prolonged in patients with coronary artery aneurysms as compared with that in a control group (p less than 0.001). All patients exhibited delayed clearance of contrast medium on the initial aortogram as compared with that on follow-up studies (p less than 0.01). Of the 22 patients with angiographically documented coronary artery abnormalities, 19 had right and 20 had left coronary artery involvement; the majority had diffuse involvement of both vessels. In 15 patients who underwent follow-up catheterization 6 months to 7 years after initial study, complete resolution was observed in only 37% of affected coronary artery segments. In four patients, three of whom were asymptomatic, severely stenotic or occluded coronary artery segments were found on late catheterization. Coronary artery bypass surgery was performed in two of these patients. Echocardiography did not detect any of these stenoses. Although echocardiography is important for initial diagnosis and serial evaluation, angiography is essential to fully define the nature and extent of coronary artery lesions, particularly if stenosis is present.

Role of endomyocardial biopsy in rejection surveillance after heart transplantation in neonates and children.

OBJECTIVES: The aim of this study was to retrospectively evaluate the sensitivity of noninvasive surveillance (physical examination, echocardiography) of rejection in accurately predicting histologically documented rejection episodes. Additionally, the usefulness of routine scheduled biopsy and its safety in pediatric patients was explored. BACKGROUND: Endomyocardial biopsy has been utilized as the standard for rejection surveillance after heart transplantation in adults, but its role in documenting clinically suspected rejection and in routine surveillance of pediatric patients has not been agreed upon. METHODS: Heart transplantation was performed in 14 neonates and 21 children. The immunosuppressive regimen consisted of cyclosporine, azathioprine and prednisone. All patients underwent routine noninvasive rejection surveillance that included clinical examination and echocardiography. In the neonates, biopsy was performed quarterly beginning 6 months after transplantation, after cessation of prednisone therapy. In the children, biopsy was performed 15 times in the 1st year. A minimum of five biopsy samples were interpreted using the Working Formulation for Heart Transplant Rejection. RESULTS: In the neonates, 37 biopsies were performed. Evidence of rejection was present in only three biopsy samples obtained during eight episodes (38%) of clinically suspected rejection. In 29 biopsies performed when rejection was not clinically suspected, each biopsy was free of cellular infiltrate. In the children, 291 biopsies were performed. Evidence of rejection was present in only seven biopsies (41%) from 17 episodes of clinically suspected rejection. Cellular rejection was discovered during routine rejection surveillance biopsies in asymptomatic patients in 23 (8.4%) of 274 biopsies. CONCLUSIONS: In neonates with clinically suspected rejection, endomyocardial biopsy identified which patients did not require rejection therapy. Endomyocardial biopsy surveillance did not detect any unsuspected cases of rejection. In children, noninvasive rejection surveillance was less reliable even in asymptomatic patients, suggesting that periodic endomyocardial biopsy should be utilized.

Echocardiographic assessment of cardiac function during respiratory syncytial virus infection.

Respiratory syncytial virus infection has been associated with increased morbidity and mortality in infants with underlying cardiac and pulmonary disease. To understand better the cardiopulmonary interaction in patients with acute respiratory syncytial virus bronchiolitis, we performed M-mode echocardiograms and pulsed Doppler assessment of pulmonary arterial flow in 19 patients with structurally normal hearts during acute illness. Studies were repeated in 11 of these patients following complete recovery. Based on severity of respiratory compromise, patients were grouped into those with severe illness (ten patients) or mild illness (nine patients). Left ventricular dimensions and shortening fraction were used to assess left ventricular function. Right ventricular systolic time intervals and specific Doppler flow velocity measurements were used to assess right ventricular function and elevation of pulmonary artery pressure. Comparisons were made between patients with severe and mild illness and between acute and follow-up studies. No statistically significant differences in left ventricular function, right ventricular systolic time intervals, or Doppler flow measurements were observed. We conclude that in patients with structurally normal hearts, respiratory syncytial virus bronchiolitis is not associated with significant depression of cardiac performance or elevation in pulmonary resistance.

Reversal of severe late left ventricular failure after pediatric heart transplantation and possible role of plasmapheresis.

Late acute cardiac graft failure carries a high mortality in adults. Vascular mediators and factors other than classic T-cell-mediated rejection may play a role in this process, and aggressive multimodality therapy may improve survival. We report experience with plasmapheresis in treating late severe acute left ventricular dysfunction in a group of pediatric heart transplant recipients. We retrospectively reviewed clinical records, echocardiograms, hemodynamics, coronary angiograms, biopsy specimens, and treatment regimens for 5 patients with 7 episodes of late-onset severe graft failure who recovered. Plasmapheresis was applied in all cases, in addition to methylprednisolone, cyclophosphamide, lympholytic agents, and aggressive supportive care including mechanical ventilation and hemofiltration. All patients presented with acute severe left ventricular dysfunction 1.4 to 7.9 years (mean 3.6) after orthotopic heart transplantation. Mean shortening fraction at presentation was 13 to 23% (mean 16), initial endomyocardial biopsy specimens were grade 0 to 3B, and immunofluorescence studies were negative. Treatment included plasmapheresis, cyclophosphamide, mechanical ventilation, hemofiltration, and inotropes. Clinical recovery was slow, with 4 to 8 weeks until left ventricular function normalized, and 2.2 to 9.4 (mean 4.6) weeks to hospital discharge. At follow-up (50 to 38 months, mean 24), all are alive. Two patients are well, whereas coronary vasculopathy developed in 3. Thus, survival may improve in patients with late graft failure with low biopsy score and plasmapheresis combined with multimodality therapy.

Expanding indications for pediatric coronary artery bypass.

Pediatric coronary artery bypass has been done mostly for ischemic complications of Kawasaki disease. We reviewed our clinical experience between 1987 and 1994 with internal thoracic artery-coronary artery bypass in one infant and five children for varying indications. Indications for coronary bypass included Kawasaki disease (2), congenital left main coronary ostial stenosis, iatrogenic coronary cameral fistula, anomalous origin of the left coronary artery from the pulmonary artery, and single coronary artery traversing between the great arteries in a patient after cardiac transplantation. An additional cohort of 34 control patients of various ages and weights (1 day to 16.1 years, 2.6 kg to 62 kg) had angiographic measurements of the right coronary, left coronary, and left internal thoracic arteries with respect to the feasibility of performing coronary artery bypass. All six patients survived internal thoracic artery-left anterior descending coronary artery bypass without evidence of perioperative myocardial infarction. Postoperative angiographic studies in five and color Doppler echocardiography in one showed graft patency. Retrospective angiographic measurements in the 34 control patients showed that internal thoracic and coronary arteries are proportionately quite large in neonates and infants compared with those in older children and adolescents. Internal thoracic artery-coronary artery bypass should be considered for the expanding indications presented herein and when emergency intraoperative life-threatening situations present themselves. Long-term patency and reoperation rates have yet to be determined.

Long-term results of survivors of surgical valvotomy for severe aortic stenosis in early infancy.

Long-term morbidity and mortality were evaluated in the 21 survivors of a cohort of 51 consecutive infants with severe aortic valve stenosis who underwent surgical treatment in the first 3 months of life during the period from 1958 to 1988. The 21 early survivors have been followed up from 3 to 27 years (median 7.5 years). There have been two late deaths: one at age 13 year from bacterial endocarditis and the other at age 14 years after dislodgment of a prosthetic valve. The calculated 10-year actuarial survival for this group is 100%, with a 15-year actuarial survival of 75% (standard error 15%). Seven repeat operations have been performed in six patients: Three had persistent stenosis and a repeat valvotomy was performed in two of them, aged 2 years and 15 years. The other underwent placement of a conduit from the left ventricle to the descending aorta at 2 years of age. Replacement of the aortic valve has been performed in four patients because of severe valvular insufficiency 13 to 27 years after the initial operation. One of these had required a repeat valvotomy at the age of 15 years. The calculated actuarial freedom from reoperation at 10 years is 90% (standard error 6%) and at 15 years, 67% (standard error 15%). Aortic insufficiency was progressive throughout the period of follow-up. No patient had more than moderate aortic insufficiency 3 to 5 years after the initial valvotomy, whereas aortic insufficiency was severe in five of the eight patients followed up for 11 or more years. Progression of aortic insufficiency and the need for reoperation were not related to the age at initial valvotomy. Survivors of surgical aortic valvotomy in early infancy have a relatively good long-term prognosis and a high freedom from reoperation in the period leading to adolescence. Aortic insufficiency in these patients is progressive, and valve replacement eventually may be required.

Occult restrictive hemodynamics after pediatric heart transplantation.

BACKGROUND: Although resting hemodynamics after pediatric heart transplantation are generally within normal limits, we hypothesized that occult restrictive hemodynamics suggesting diastolic dysfunction may be unmasked by acute volume loading (fluid challenge) during cardiac catheterization. We wished to determine the incidence of diastolic dysfunction and to assess whether it progressed over time. METHODS: From 1988 through 1993, a total of 100 fluid challenges were performed at the time of surveillance endomyocardial biopsy in 31 survivors of orthotopic heart transplantation. Cyclosporine-based immunosuppression was used in 16 patients, and FK506 was used in 15 patients. Right heart hemodynamics and cardiac output (thermodilution) were obtained at baseline and after a fluid challenge with 10 ml/kg of normal saline solution. The data were analyzed to determine whether type of immunosuppression or time elapsed since transplantation predicted the response to fluid challenge. RESULTS: Baseline hemodynamics were normal; however, a marked increase in atrial filling pressures occurred after fluid challenge (p < 0.001). Findings were similar in cyclosporine- and FK506-treated patients. Hemodynamic response to fluid challenge was not related to duration of time since transplantation, including studies on patients surviving more than 4 years. CONCLUSIONS: Diastolic dysfunction after heart transplantation is common; however, the abnormalities do not progress in severity, suggesting stable long-term graft function.

Pharmacologic reduction of pretransplantation pulmonary vascular resistance predicts outcome after pediatric heart transplantation.

Pulmonary hypertension leading to donor right ventricular dysfunction remains a major risk factor associated with poor outcome after heart transplantation. This study evaluated a pretransplantation protocol to assess pulmonary vascular resistance index and its response to pharmacologic modulation. Cardiac catheterization was performed in 25 patients (mean age, 8.6 years [range, 1 to 17 years]; mean weight, 27.3 kg [range, 8.1 to 54 kg]) with end-stage heart failure. Mean pulmonary artery and capillary wedge pressures and cardiac index were measured in the baseline state and during administration of 100% oxygen, dobutamine at 10 micrograms/kg/min, and nitroprusside at 1 to 4 micrograms/kg/min. Transpulmonary pressure gradient and pulmonary vascular resistance index were calculated. In 22 survivors, hemodynamics were reassessed 1 and 4 weeks after transplantation. The mean cardiac index significantly increased (2.2 to 3.2 L/min/m2); transpulmonary pressure gradient (12.7 to 9.6 mm Hg) and pulmonary vascular resistance index (6.2 to 3.0 units/m2) decreased during the drug study. In 12 patients with a baseline pulmonary vascular resistance index of more than 6 units/m2, 10 survived heart transplantation. This study shows that pharmacologic reduction of the pulmonary vascular resistance index in the pretransplantation protocol predicts reduced pulmonary vascular resistance index and a favorable outcome after heart transplantation.

Diltiazem preserves direct vasodilator response but fails to suppress intimal proliferation in rat allograft coronary artery disease.

BACKGROUND: We investigated the effect of diltiazem on transplant coronary artery disease in rat cardiac allografts both with standard histologic techniques and by measuring coronary vascular resistance and vasodilator response of the coronary arteries. METHODS: Hearts from Lewis rats were transplanted into Fischer 344 rats in an abdominal position without immunosuppression as a chronic rejection model. The rats were randomly divided into two groups: (1) no drug intervention (control; n = 36) and (2) diltiazem in drinking water (n = 33). Syngeneic transplants, Lewis donor to Lewis recipient, were used for isograft comparison (n = 17). Rat allografts were observed for length of survival, and at 4 months the surviving allografts were transferred to Langendorff perfusion, where coronary vascular resistance and its response to acetylcholine and nitroglycerin were examined. Allografts were also examined histologically and assigned transplant coronary artery disease and cellular rejection grades. RESULTS: Graft survival at 4 months was 43%, 38%, and 100% in control, diltiazem, and isograft groups, respectively. In the control group baseline coronary vascular resistance was much higher than in isografts (243 +/- 52 versus 35.3 +/- 6.2 cm H2O center dot gm center dot min/ml, p < 0.05) and the response to acetylcholine and nitroglycerin was significantly lower than that in the isografts (acetylcholine 6.2% +/- 4.8% versus 16.4% +/- 3.3%, p < 0.05; nitroglycerin 5.6% +/- 4.7% versus 12.6% +/- 5.7%, p < 0.05). In the diltiazem group baseline coronary vascular resistance (191 +/- 72 cm H2O center dot gm center dot min/ml) and the response to acetylcholine (7.3% +/- 2.9%) were similar to those in the control group (p = not significant); however, the response to nitroglycerin was better than that in the control group and in fact similar to that in the isograft group (13.6% +/- 7.0%; p < 0.05 versus control group, p = not significant versus isograft group). Histologic examination showed no coronary artery disease in isografts but equivalent marked transplant coronary artery disease and inflammation in both the control (transplant coronary artery disease grade 2.9 +/- 0.6, cellular rejection grade 3.6 +/- 0.7) and diltiazem (transplant coronary artery disease grade 3.0 +/- 0.8, cellular rejection grade 4.3 +/- 0.9) groups. CONCLUSION: In this transplant coronary artery disease model, diltiazem did not suppress the development of coronary intimal proliferation, but it did help preserve the vasodilative properties of the allograft coronary arteries in response to nitroglycerin, a direct vasodilator.

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.

Dobutamine stress echocardiography: experience in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary arteriopathy causes late death and is difficult to detect noninvasively. Dobutamine stress echocardiography is being used for risk stratification in adult recipients at some transplant centers, thus we investigated its role in a pediatric population. METHODS: We performed 46 stress echo studies (mean age = 11.8 years; mean years post transplantation = 4.3). An atropine/dobutamine protocol (5-40 mcg/kg/min) was used to attain a predicted target heart rate. Serial echocardiographic images were acquired at baseline and at each increment of dobutamine and recovery, and were digitized online. Data were correlated with endomyocardial biopsy (n = 23), coronary angiography (n = 26) or autopsy (n = 6). All studies were well tolerated. RESULTS: Target heart rate was achieved in 41/46 (89%) studies. The mean heart rate significantly increased from 95 to 169 beats/min and mean systolic blood pressure from 123 to 153 mm Hg (p<.05). The mean peak pressure-rate product was 23,041 beats-mm Hg/min. Coronary arteriopathy was confirmed in 5 patients by angiography (n = 3) explanted heart (n = 1) or autopsy (n = 4). In this group, abnormalities included a new reversible wall motion abnormality (n = 2), left ventricular cavity dilation with stress (n = 3), ischemia (n = 2), increased mitral insufficiency (n = 1) and marked diastolic dysfunction (n = 1). A positive study predicted death or graft failure (p< .0005). CONCLUSIONS: Echocardiographic abnormalities during stress correlated with coronary arteriopathy in this small cohort of patients; however, larger multi-center studies are warranted to assess the utility of dobutamine stress echocardiography for risk stratification for coronary disease in pediatric transplant recipients.

Induction immunotherapy in pediatric heart transplant recipients: a multicenter study.

BACKGROUND: The efficacy and safety of induction immunotherapy with antithymocyte antibody preparations (IND) in pediatric heart transplantation is controversial. Experimentally, recipient age is an important determinant of immune responses. The effects on induction immunotherapy were determined by an analysis of outcomes of 465 pediatric (age <18 years) heart recipients that either did or did not receive IND in the first week post-transplant. METHODS: The outcomes of 2 groups who received either OKT3 (n = 101) or rabbit polyclonal antithymocyte serum (N/R-ATS, n = 105) were compared with 255 recipients who did not receive antithymocyte antibodies. The study population were all heart recipients enrolled in the Pediatric Heart Transplant Study Group (PHTS) between January 1993 and December 1995 and followed up to 36 months. RESULTS: Overall mortality and death due to rejection were lowest with N/R-ATS IND (8/105 and 1/105, respectively) compared with the no-induction group (58/255 and 8/ 255, respectively) or the OKT3 group (22/101 and 7/101, respectively) with significance of p = 0.001 and 0.06 respectively. Late mortality beyond 30 days after transplant was lowest with N/R-ATS IND compared with the OKT3 and no IND (p = 0.01). Induction did not affect cumulative infections, deaths due to infection, or the frequency of malignancies. Patients excluded from N/R-ATS induction had the highest mortality (18/ 43), suggesting that the protocol's exclusion criteria identified a high-risk group. To minimize potential effect(s) of exclusion bias, patients transplanted at centers participating in the N/R-ATS induction trial were reanalyzed with a post hoc intent-to-treat analysis assigning patients by center (IND or no IND) irrespective of actual treatment. With this analysis overall mortality was 18% for N/R-ATS centers, 21% for OKT3 centers, and 26% for centers not using IND (p = 0.3). The mortalities of recipients <6 months old at transplant were lowest at centers using N/R-ATS and OKT3 IND compared to centers not using IND (p = 0.04). Cumulative rejection (0.8 vs 1.2 rejection/pt/year, p = 0.01) and freedom from rejection death (99% vs. 93% at year 1, p = 0.02) of the N/R-ATS centers were lower compared to OKT3 centers but were not different from centers not using IND. CONCLUSION: Following orthotopic transplantation, induction immunotherapy can exert the enduring benefit of reducing late deaths, a possible surrogate for rejection severity, in recipients less than 6 months of age, while not being associated with higher rates of infectious or malignant complications. Since polyclonal anti-T cell antibody preparations appears superior to OKT3 induction in pediatric recipients, the efficacy of ATS induction should be further evaluated in a randomized prospective study in pediatric heart recipients.

Death after rejection with severe hemodynamic compromise in pediatric heart transplant recipients: a multi-institutional study.

BACKGROUND: Rejection with severe hemodynamic compromise results in high mortality in adult transplant patients. This study determines the incidence, outcome and risk factors for rejection with severe hemodynamic compromise in a multi-institutional study of pediatric heart transplant recipients. METHODS: Data from 847 patients transplanted between 1/1/93 and 12/31/98 at 18 centers in the Pediatric Heart Transplant Study were analyzed. Rejection with severe hemodynamic compromise was defined as a clinical event occurring beyond 1 week postoperatively, which led to augmentation of immunosuppression and use of inotropic therapy. Actuarial freedom from such rejection and death after rejection were determined and risk factors sought. RESULTS: Among 1,033 rejection episodes in 532 patients, 113 (11%) episodes were associated with severe hemodynamic compromise in 95 patients. The highest risk for severe rejection was in the first year. Risk factors were older recipient age (p >.05) and non-white race (p >.001). Survival after an episode was poor (60%), and biopsy score did not affect outcome. Deaths were due to rejection (n = 14), other cardiac causes (n = 17), infection (n = 5), lymphoma (n = 2), pulmonary causes (n = 2), and thrombosis (n = 1). CONCLUSIONS: Rejection with severe hemodynamic compromise occurs in 11% of pediatric patients, irrespective of age, sex or biopsy score, and mortality is high. Non-white race and older recipient age are independent risk factors for rejection with severe hemodynamic compromise. Aggressive treatment and close surveillance should be crucial components of protocols aimed at reducing the high mortality.

Coarctation and hypoplasia of the aortic arch: will the arch grow?

Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25.

Pediatric coronary artery bypass for Kawasaki congenital, post arterial switch, and iatrogenic lesions.

BACKGROUND: Pediatric coronary artery bypass (PCAB) has been recently employed for expanding indications to treat acquired, congenital, post arterial switch, and other iatrogenic pediatric coronary artery problems. METHODS: Between 1987 and 1998, 3 infants and 13 children (n = 16, mean age 6.1 years, range 2 months-18 years) underwent one or more internal thoracic artery (ITA) to coronary artery (CA) bypass grafts for Kawasaki disease (n = 4), congenital lesions (n = 3), post arterial switch (n = 4), and other iatrogenic obstructions (n = 5). Proximal left main CA arterioplasty was performed concurrently with ITA-CA bypass in 4 patients. RESULTS: Survival is 93.8%. All bypass grafts in surviving patients are patent 2 months-11 years postoperation. The 11 elective patients are well (NYHA I-II). The 5 emergent operations were performed in 2 infants and 3 adolescents who had poor ventricular function prior to ITA-CA bypass due to iatrogenic injuries in 3, congenital critical left main stenosis in 1, and intraoperative iatrogenic coronary injury in 1. The 3 adolescents fared worse, resulting in death in the first, cardiac transplantation in the second, and full recovery in the third. The 2 infants have steadily improving ventricular function. CONCLUSIONS: ITA-CA bypass can be successfully performed in infants and children for expanding elective and life-saving indications with excellent results. Poor preoperative ventricular function often persists, especially in those older children with iatrogenic injuries, and may result in death or cardiac transplantation.

Left ventricular growth in selected hypoplastic left ventricles: outcome after repair of coarctation of aorta.

BACKGROUND: Models that predict survival in neonates with left ventricular hypoplasia and critical aortic stenosis may not be applicable to neonates with left ventricular hypoplasia and coarctation. METHODS AND RESULTS: We report 8 infants with severe aortic coarctation and left ventricular hypoplasia. Mean age was 18 days (range 1-48 days), and mean weight was 3.5 kg (range 2.7-4.3 kg). Associated diagnoses included mild aortic stenosis (4), ventricular septal defect (2), and venous anomalies (2). All had coarctation repair as a primary procedure (3 of these had concomitant intracardiac procedures); 7 had subsequent operations. All are alive and well 1.1-6.7 years (mean 3.1 years) after the first surgery. Progressive increases were observed in aortic and mitral diameters, and in left ventricular dimensions, areas, and volumes when the preoperative, earliest postoperative, and most recent echocardiograms were compared. CONCLUSIONS: Despite severe left ventricular hypoplasia, a two-ventricle repair is possible in selected cases. The prognostic criteria for left ventricular hypoplasia in critical aortic stenosis may not be applicable to infant coarctation. Relief of coarctation may result in the growth of the very small left ventricle, especially when the aortic root and mitral diameters are satisfactory.

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children.

Size limitations and technical barriers prohibit the use of many conventional mechanical circulatory support systems for postcardiotomy ventricular dysfunction in pediatric populations. Extracorporeal membrane oxygenation (ECMO), frequently used to treat neonatal respiratory failure, can provide cardiac support and is effective treatment of postoperative myocardial failure in children. From 1981 to 1987, 10 patients aged 2 days to 5 years were maintained on ECMO for 15 to 144 hours (mean duration, 92 +/- 16 hours) after cardiotomy. Operative procedures included repair of tetralogy of Fallot (2 patients), closure of a ventricular septal defect (2), the Senning procedure for transposition of the great arteries (1 patient), repair of interrupted aortic arch with closure of a ventricular septal defect (1), repair of a partial atrioventricular septal defect (2), closure of a ventricular septal defect with excision of an anomalous muscle bundle (1), and the Fontan procedure (1). Venoarterial ECMO was established in all 10 children. Six patients underwent transthoracic right atrium-ascending aorta cannulation, 3 had right internal jugular vein-right common carotid artery cannulation through a cervical incision, and 1 had right internal jugular vein-left axillary artery cannulation. Eight of the 10 patients were successfully weaned from ECMO, and 7 are long-term survivors. There were 3 deaths; 1 was caused by cardiac and acute renal failure complicated by sepsis two days after decannulation, another occurred 19 days after atrioventricular septal defect repair, and 1 was caused by massive pulmonary hemorrhage. Major hemorrhage developed in 3 patients while on ECMO; 2 required premature decannulation for mediastinal bleeding from operative sites and ultimately survived, and 1 died of respiratory failure as a result of endobronchial bleeding. We conclude that the use of ECMO in pediatric populations for transient postoperative ventricular dysfunction improves survival with limited overall morbidity.