Clinical and hemodynamic characteristics of the pediatric failing Fontan.

AIM: To describe the clinical and hemodynamic characteristics of Fontan failure in children listed for heart transplant. METHODS: In a nested study of the Pediatric Heart Transplant Society, 16 centers contributed information on Fontan patients listed for heart transplant between 2005and 2013. Patients were classified into four mutually exclusive phenotypes: Fontan with abnormal lymphatics (FAL), Fontan with reduced systolic function (FRF), Fontan with preserved systolic function (FPF), and Fontan with "normal" hearts (FNH). Primary outcome was waitlist and post-transplant mortality. RESULTS: 177 children listed for transplant were followed over a median 13 (IQR 4-31) months, 84 (47%) were FAL, 57 (32%) FRF, 22 (12%) FNH, and 14 (8%) FPF. Hemodynamic characteristics differed between the 4 groups: Fontan pressure (FP) was most elevated with FPF (median 22, IQR 18-23, mmHg) and lowest with FAL (16, 14-20, mmHg); cardiac index (CI) was lowest with FRF (2.8, 2.3-3.4, L/min/m2). In the entire cohort, 66% had FP >15 mmHg, 21% had FP >20 mmHg, and 10% had CI <2.2 L/min/m2. FRF had the highest risk of waitlist mortality (21%) and FNH had the highest risk of post-transplant mortality (36%). CONCLUSIONS: Elevated Fontan pressure is more common than low cardiac output in pediatric failing Fontan patients listed for transplant. Subtle hemodynamic differences exist between the various phenotypes of pediatric Fontan failure. Waitlist and post-transplant mortality risks differ by phenotype.

Outcomes of fetal listed patients awaiting heart transplantation.

HTx in neonates is mainstay therapy for those with severe cardiomyopathies and congenital heart disease. Fetal listing for HTx has been proposed as a way to increase the potential window for a donor with outcomes predicted to be similar to the neonatal population. Data from the PHTS, a prospective multicenter study, were used to examine the outcomes of fetuses listed between 1993 and 2009. Four thousand three hundred and sixty-five children were listed for HTx during this period. Fetuses comprised 1% and neonates 19.8% of listed patients. In those patients listed as fetus and transplanted, the median wait time from listing to HTx was 55 days (range 4-255), with a median of 25 days (range 0-233) after birth. By six months post-listing, a higher proportion of fetal listed patients had undergone HTx with a lower waitlist mortality when compared with neonate. There was no significant difference in survival following HTx between the two group (p = 0.4). While the results of this study may be less applicable to current practice due to changes in referrals for fetal listing, they do indicate that fetal listing can be a reasonable option. These results are of particular interest at the present time given the ongoing public discourse on the proposed elimination of fetal listing within UNOS.

Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation.

BACKGROUND: Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population. METHODS: A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups. RESULTS: VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups. CONCLUSIONS: VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT.

Prevalence and risk factors for tricuspid valve regurgitation after pediatric heart transplantation.

BACKGROUND: Risk factors for tricuspid regurgitation (TR) after adult orthotopic heart transplantation (OHT) have been reported, although there are no pediatric data. METHODS: This study was a single-center retrospective analysis of patients

Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group.

BACKGROUND: Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure. METHODS AND RESULTS: A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed. CONCLUSIONS: This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

Longitudinal assessment of cardiovascular exercise performance after pediatric heart transplantation.

BACKGROUND: No existing longitudinal data document exercise performance after pediatric heart transplantation. We report the exercise performance findings from the longitudinal study of pediatric heart transplantation patients and the association of aerobic capacity with echocardiographic measures of graft function. METHODS: We performed a retrospective analysis of 28 children after heart transplantation who underwent 87 exercise tests and echocardiograms. Subjects exercised using graded cycle or treadmill protocols. Maximal oxygen consumption (VO2), physical working capacity, peak heart rate, and anaerobic threshold were evaluated. To measure systolic and diastolic function, shortening fraction and mitral valve pressure half-time (PHT) respectively, were obtained by echocardiography. RESULTS: The average age at transplantation was 10.9 +/- 5.6 years, at initial exercise test was 13.8 +/- 5.0 years, and at final exercise test was 15.8 +/- 5.2 years. Percent-predicted values at the initial exercise test were VO2, 59.3%; physical working capacity, 60.2%; and peak heart rate, 75.8%; these remained similarly decreased at the final exercise test. Shortening fraction and PHT were within normal limits, but PHT was significantly greater at final test (p < 0.05). The relationship of VO2% with time was statistically significant, described by a quadratic equation that included initial VO2% and time from heart transplantation. This relationship remained significant when the shortening fraction (p < .05) but not PHT was added as a covariate in the equation. CONCLUSIONS: Exercise performance after pediatric heart transplantation is impaired and, despite an initial improvement, declines over time. This can be explained by increasing diastolic dysfunction independent of donor graft age. If confirmed, these findings point the direction to further research aimed at limiting this aerobic capacity decline after heart transplantation.

Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation.

Idiopathic infantile arterial calcification (IIAC) is a rare, but important, cause of rapidly progressive ischemic heart disease in children. In this paper, we report two recent cases of IIAC seen at tertiary referral hospitals. Both cases presented in infancy with signs of heart failure and, ultimately, died with the diagnosis of IIAC confirmed at postmortem examination. A thorough review of the literature reveals approximately 160 reported cases of IIAC. The clinical outcomes, radiographic findings and pathologic details are summarized. Proposed etiologic mechanisms are reviewed, including promising research into the role of inorganic pyrophosphate as a regulatory factor in the development of IIAC. Because of the typically fatal outcome of IIAC and the lack of proven therapies, the potential role for cardiac transplantation is discussed.

Cardiac transplantation for hypoplastic left heart syndrome.

Future improvements can be expected in cardiac transplantation in children. We continue to advance our understanding of the immune system, and to develop more specific immunosuppressive agents. Ultimately, the future for recipients may be improved by strategies such as induction therapy or donor-derived chimeric destined transfusions, designed to enhance the tolerance of the host to a human leukocyte antigen incompatible graft. Improvements in tolerance of the host would allow for reduction or elimination of many, if not all, of the immunosuppressive agents, and for longevity extending well into the adulthood. Survival, particularly for infants, has improved dramatically in the last decade. The most recent results from the registry of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing show that recipients less than one year old at transplantation, who survive the first year, have greater than a 95% survival to four years (Fig. 1). As late outcomes continue to improve, transplantation will provide a better quality and duration of life for infants with hypoplastic left heart syndrome. It is possible, nonetheless, that some infants will require retransplantation, since the half life of a transplanted heart in children has been about 12 years. The alternative is conventional surgery with multiple palliative operations, and the need for later transplantation as end-stage cardiac function is reached. Efforts to increase potential donors and donor utilization can be supported by innovative schemes, such as ABO incompatible transplants. Additional efforts are made more urgent when the current data indicate excellent outcomes after transplantation, but a high mortality while waiting for transplantation.

Idiopathic colitis following cardiac transplantation: three pediatric cases.

Colitis can cause significant morbidity in pediatric solid organ transplant recipients. In many cases, despite intensive evaluation, a specific infectious, inflammatory, or immunologic etiology is not identified, and idiopathic colitis may be the ultimate diagnosis. We defined idiopathic colitis as the presence of gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) with inflammatory changes seen on intestinal biopsy in the absence of identifiable bowel disease. We describe three cases of idiopathic colitis following cardiac transplantation. In each case, the post-transplant course was complicated by persistent abdominal pain, diarrhea, and in two cases, vomiting. All three patients' post-transplant courses were marked by multiple graft rejection episodes, and all received intensified immune therapy in addition to usual maintenance immunosuppression. Differential diagnosis of the patients' gastrointestinal symptoms included drug side effect, indolent opportunistic infections, inflammatory bowel disease, post-transplant lymphoproliferative disease, and microvascular ischemic colitis. Continued symptoms led these patients to extensive evaluation including imaging studies, endoscopy and tissue biopsy, and stool, blood and tissue cultures for viral, bacterial and parasitic pathogens. Definitive differentiation presented significant diagnostic challenge, and once identifiable etiologies were excluded, the diagnosis of idiopathic colitis was assigned. We conclude that idiopathic colitis following pediatric cardiac transplantation can be a cause of significant morbidity. Endoscopic evaluation of patients who present with gastrointestinal symptoms after transplant is warranted to identify the presence of idiopathic colitis once common causes are ruled out. Further study is needed to identify its incidence, etiology, therapeutic options and prognosis.

Outcome of idiopathic restrictive cardiomyopathy in children.

Eighteen children with idiopathic restrictive cardiomyopathy (IRC) were studied in an attempt to identify potential predictors of poor outcome. Four patients presented with low cardiac output (CO) syndrome. Fourteen remaining patients were minimally symptomatic at presentation but developed a low CO syndrome at a mean of 2.8 +/- 2.3 years after diagnosis. At the time of development of low CO in the 18 patients, mean left ventricular end-diastolic pressure was 27 mm Hg, right ventricular end-diastolic pressure was 18 mm Hg, cardiac index was 2.5 L/min/m(2), and pulmonary vascular resistance index (PVRI) was 8.8 U-m(2). Eleven of the 18 patients underwent cardiac transplantation. One died perioperatively from donor right-sided cardiac failure and 10 survived. Six were not transplanted and died, including 3 in whom transplantation was precluded secondary to extremely elevated PVRI. One patient is alive with right-sided cardiac failure. Ten of our 18 patients had pulmonary hypertension (PVRI >6 U-m(2)) at the time of referral for cardiac transplant and/or development of low CO syndrome. In comparison, children with dilated cardiomyopathy who were referred for heart transplant during the same time period had a PVRI that was significantly lower (5.2 U-m(2)). Elevated PVRI was associated with death (p <0.01) and 40% of our children with pulmonary hypertension were precluded from receiving an orthotopic heart transplant because their pulmonary hypertension was so severe. No risk factors for the development of pulmonary hypertension were identified; therefore, all children with IRC should undergo serial monitoring of their PVRI, and any increase should prompt a transplant evaluation.