Initial transcatheter palliation of hypoplastic left heart syndrome.

Initial percutaneous transcatheter palliation of hypoplastic left heart syndrome is now feasible. The primary procedures for palliation include stenting of the ductus arteriosus with a self expanding nitinol stent to secure an adequate systemic blood flow, placement of an internal pulmonary arterial band to protect the pulmonary vascular bed and to prevent pulmonary overcirculation, and widening of the interatrial communication by blade and balloon septostomy or static balloon dilation to decompress the left atrium. Anatomic variations of the ductus arteriosus have important implications for technical success with ductal stenting. Patients who have undergone complete transcatheter palliation with the internal pulmonary band appear to have less immediate morbidity at the time of transplant, with preserved integrity and growth of the branch pulmonary arteries at one year follow-up.

Exercise capacity in pediatric heart transplant candidates: is there any role for the 14 ml/kg/min guideline?

A peak oxygen consumption (VO2) of < 14 ml/kg/min has been identified as a predictor of l-year mortality in adults with congestive heart failure (CHF) and is used as a criterion for listing for cardiac transplantation (OHT). The role of VO2 measurement in children awaiting OHT has not been thoroughly evaluated. We sought to assess the degree of exercise impairment and the clinical applicability of the 14 ml/kg/min rule in children awaiting OHT. Cardiopulmonary exercise test (CPT) and cardiac catheterization data in all patients listed for OHT during the period of 1995-2003 were reviewed. Fourteen patients with a mean age of 15.5 +/- 2.9 years underwent CPT with no serious adverse events at an interval of 6.6 +/- 5.1 months prior to OHT. The etiology of CHF was multifactorial. Patients had impaired aerobic capacity with a mean peak VO2 of 20.4 +/- 6.8 ml/kg/min. Eleven of 14 patients (79%) had a peak VO2 higher than the adult cutoff value of 14 ml/kg/min. Pediatric ambulatory patients with CHF can safely undergo CPT. Because of age-related differences in oxygen consumption and varied etiologies of CHF a peak VO2 of < 14 ml/kg/min is not a useful criterion for listing for OHT in this population.

Fate of infants with hypoplastic left heart syndrome listed for cardiac transplantation: a multicenter study.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) commonly undergo cardiac transplantation as primary management. METHODS: We examined outcomes of primary transplantation for unpalliated HLHS. We analyzed data from the 20 institutions of the Pediatric Heart Transplant Study Group, from January 1, 1993, through December 31, 1998, using actuarial and parametric survival analysis and competing outcomes analysis. RESULTS: During the 6 years studied, 1,234 patients were listed for cardiac transplantation; 262 patients (21.2%) had unpalliated HLHS. The number (and percentage) of patients with HLHS decreased from 58 (27% of patients listed) in 1993 to 30 (14%) in 1998. Overall, 25% of infants with HLHS died while waiting; primary cause of death was cardiac failure (50%). Of the remaining patients awaiting transplantation, 23 (9%) underwent Norwood/Fontan-type surgeries as interim palliation: 52% died. Ultimately, 175 patients underwent cardiac transplantation (67%); 50% received organs by 2 months after listing. Post-transplant actuarial survival was 72% at 5 years, with 76% of deaths (35/46) occurring within 3 months; early mortality was caused primarily by graft failure within the first 30 days after transplantation (in 54%). Among 1-month survivors, survival at 1 and at 5 years was 92% and 85%, respectively. Of the 262 patients listed with unpalliated HLHS, overall survival, taking into account mortality after listing and after transplantation, was 68% at 3 months and 54% at 5 years. CONCLUSIONS: Cardiac transplantation offers good intermediate survival for infants with unpalliated HLHS.

Ductal anatomy: a determinant of successful stenting in hypoplastic left heart syndrome.

Interventional palliation for hypoplastic left heart syndrome (HLHS) could reduce the current morbidity and mortality. Stenting of the arterial duct is the critical interventional step for HLHS. We reviewed our experience with 40 consecutive patients with HLHS referred for stenting of the ductus arterious (DA). Thirty-nine of 40 (97%) infants had suitable anatomy and were successfully stented. The infants were grouped by orientation of the ductus in the frontal plane. Type 1 DA anatomy had a leftward loop at a mean orientation of 18 degrees from the vertical plane. Type 2 ductal anatomy was mesoverted, with a mean orientation of 7.1 degrees from the vertical plane. Type 3 ductal anatomy displayed a rightward axis, with a mean of -4 degrees rightward. Orientation of the DA was significantly related to length of the ductus, number of stents required for complete coverage, and technical and procedural complications. Type 1 DA occurred in 65% of patients, and there was 100% technical success, no mortality, and only an 8% incidence of complications. Type 2 anatomy occurred in 27% of patients and there was 100% success. However, the technical and procedural complications increased to approximately 50%. Type 3 ductal anatomy was seen in only 3 patients, 2 of whom were successfully stented. There was no procedural-related mortality, and all stented patients were weaned from prostaglandin. There were only two late complications (coarctation). We conclude that ductal stenting using self-expanding nitinol stents is successful in more than 95% of infants with HLHS. Patients with HLHS and favorable ductal anatomy should be considered for primary ductal stenting.

Improved pretransplant management of infants with hypoplastic left heart syndrome enables discharge to home while waiting for transplantation.

For infants whose families select primary transplantation for hypoplastic left heart syndrome (HLHS), the waiting time averages 3 months. Given the relative shortage of organs, the morbidity and mortality of these patients have been high. Therefore, pretransplant management is critical to improve the number of patients who survive to transplantation. This series shows our evolving management for these children, with an emphasis on nonintensive care. Fifty-two infants with HLHS were listed for primary transplantation at our institution during a 6-year period. The management was aimed at manipulating the pulmonary and systemic blood flows by low-dose continuous infusion of prostaglandin E1 (PGE1), early use of inhaled nitrogen, delayed opening of the atrial septum, and discharge to home with PGE1 infusion for continuing care when the child was on room air and growing. Almost all of the children (46/ 52) required nitrogen therapy with initial FiO2 of 0.16-0.17. Patients were weaned off nitrogen by 5 to 6 weeks of age. One fourth of the children needed atrial septal opening, typically at 2 or 3 months of age. Seventeen (32.7%) of the infants were able to spend at least some of their waiting time at home. Forty-five of the 52 children (86.5%) survived to receipt of a donor heart. Newborns with HLHS whose families select primary transplantation as their surgical option can be managed with a minimally invasive approach until receipt of a donor heart with an improvement in mortality rate.

Mycophenolic acid levels in pediatric heart transplant recipients receiving mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive agent that has shown promise in adult patients who have undergone heart transplantation. There have been a number of studies of the pharmacokinetics of MMF in adult solid organ transplant recipients, but there is very little information in the pediatric population. The purpose of this study was to review our experience with MMF dosing and the role of mycophenolic acid (MPA) levels for therapeutic drug monitoring in a population of pediatric heart transplant recipients. METHODS: Data were obtained by review of the pediatric heart transplant database between November 1, 1997 and October 15, 1998. The data included all serum trough MPA levels, patient age, weight, height, indication for and dose of MMF, other medications, and details of all episodes of graft rejection. RESULTS: Forty-four patients (27 males) had a total of 128 serum trough MPA levels. Median age at transplant was 2.7 years (7 days to 18.4 years), and at time of review was 6.3 years (29 days to 23.5 years). MMF treatment was used for induction in 18 patients, induction and rejection in 23 patients and graft vasculopathy in 3 patients. Dosing by body surface area (mg/m(2)), age and interval from transplantation were all independently associated with MPA level. There was a trend toward requiring higher doses to achieve desired levels (>3 ng/ml) in younger patients. The average dose to achieve desired levels was higher in the immediate post-transplant period. There was a trend that MPA levels for a given dose were higher in patients on concurrent tacrolimus therapy. CONCLUSIONS: (1) There is marked individual variation in pharmacokinetics of MMF in pediatric patients; (2) dosing by body surface area may be advantageous; (3) higher MMF doses may be required at younger ages and in the early period after transplantation; (4) lower MMF doses may be required with concurrent tacrolimus therapy; and (5) serum trough MPA levels may relate to efficacy. Therefore, therapeutic drug monitoring of serum trough MPA levels may be required for individualized MMF dosing in pediatric cases.

An improved echocardiographic rejection-surveillance strategy following pediatric heart transplantation.

BACKGROUND: The unique demands of cardiac transplantation in infancy have led to non-invasive rejection-surveillance strategies. ECHO-A is a multiparametric, two-dimensionally guided, M-mode analysis algorithm that assigns an empirically derived score for deviations of recipient parameters to age-adjusted, population-based normal values. A cumulative ECHO-A score > or =4 is highly predictive of endomyocardial biopsy Grade > or =3 and of cellular rejection. METHODS: This study determined whether modifying ECHO-A to score for deviations of recipient parameters from the recipient's baseline would improve the predictive power of ECHO-A. We reanalyzed 701 consecutive echocardiograms of 18 pediatric cardiac transplant recipients (median age at transplantation, 142 days) and based scoring on significant (Z score > or =1) deviation from the patients' baseline means (ECHO-B). RESULTS: Eight episodes of treated rejection occurred during the first year after transplantation (median, 1.4 years). Approximately 10% (72) of the analyses had ECHO-A scores > or =4 that were not associated with treated rejection and were considered false positives. We identified parameters that contributed to the false-positive evaluations and calculated patient-specific baseline mean +/- standard deviation. The ECHO-B, in comparison with ECHO-A, decreased the number of false positives from 72 to 10, increased specificity from 90% to 99%, and increased the positive predictive value about 4-fold (10% to 44%). With treated rejection episodes, ECHO-B increased ECHO-A scores in 7 of 8 recipients and increased the mean score from 6 to 8. CONCLUSIONS: analysis algorithm based on change from baseline improved the positive predictive power without reducing the negative predictive value of multiparametric quantitative analyses of echocardiograms following pediatric heart transplantation.

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.

Infant heart transplantation: improved intermediate results.

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.