Support with extracorporeal membrane oxygenation for over 1 year duration as a bridge to cardiac transplantation: a case report and review of the literature.

We present the case of a 13-year-old male with a complex congenital cardiac history who was supported with extracorporeal membrane oxygenation for 394 days while awaiting cardiac transplantation. The patient underwent successful cardiac transplantation after 394 days of support with veno-arterial extracorporeal membrane oxygenation and is currently alive 2 years after cardiac transplantation. We believe that this case represents the longest period of time that a patient has been supported with extracorporeal membrane oxygenation as a bridge to cardiac transplantation.We also review the literature associated with prolonged support with extracorporeal membrane oxygenation. This case report documents many of the challenges associated with prolonged support with extracorporeal membrane oxygenation, including polymicrobial bacterial and fungal infections, as well as renal dysfunction. It is possible to successfully bridge a patient to cardiac transplantation with prolonged support with extracorporeal membrane oxygenation of over 1 year; however, multidisciplinary collaboration is critical.

Double-outlet right ventricle revisited.

OBJECTIVES: Double-outlet right ventricle is a form of ventriculoarterial connection. The definition formulated by the International Society for Nomenclature of Paediatric and Congenital Heart Disease is based on hearts with both arterial trunks supported in their greater part by a morphologically right ventricle. Bilateral infundibula and ventricular septal defects are highly debated criteria. This study examines the anatomic controversies surrounding double-outlet right ventricle. We show that hearts with double-outlet right ventricle can have atrioventricular-to-arterial valvular continuity. We emphasize the difference between the interventricular communication and the zone of deficient ventricular septation. METHODS: The hearts examined were from the University of Florida in Gainesville; Johns Hopkins All Children's Hospital, St Petersburg, Fla; and Lurie Children's Hospital, Chicago, Ill. Each specimen had at least 75% of both arterial roots supported by the morphologically right ventricle, with a total of 100 hearts examined. The morphologic method was used to assess anatomic features, including arterial-atrioventricular valvular continuity, subarterial infundibular musculature, and the location of the hole between the ventricles. RESULTS: Most hearts had fibrous continuity between one of the arterial valves and an atrioventricular valve, with bilateral infundibula in 23%, and intact ventricular septum in 5%. CONCLUSIONS: Bilateral infundibula are not a defining feature of double-outlet right ventricle, representing only 23% of the specimens in our sample. The interventricular communication can have a posteroinferior muscular rim or extend to become perimembranous (58%). Double-outlet right ventricle can exist with an intact ventricular septum.

Elevated pre-transplant pulmonary vascular resistance is not associated with mortality in children without congenital heart disease: a multicenter study.

BACKGROUND: Traditionally, an elevated pulmonary vascular resistance index (PVRI) has been a relative contraindication to pediatric orthotopic heart transplantation. This study examined the risk of elevated pre-transplant PVRI on early (30-day) and intermediate-term mortality in pediatric heart transplant recipients without congenital heart disease (CHD). METHODS: A review of the prospective multicenter Pediatric Heart Transplant Study registry identified all patients without CHD in whom a pre-transplant PVRI was recorded. Of 35 participating centers, 29 reported heart transplants in children with a markedly elevated PVRI (> 5 WU × m(2), corresponding to the highest quartile). Multiphase parametric analysis was performed, adjusting for potential risk factors to assess the association of PVRI with early and intermediate-term mortality. RESULTS: Between 1993 and 2011, 1,909 children without CHD underwent heart transplantation at a median age of 9.7 years (range, 1.6 months-18 years). Of those, 795 (42%) had a recorded or calculable pre-transplant PVRI, and PVRI > 5 WU × m(2) was present in 193 patients (24%). For all recipients, median pre-transplant PVRI was 3.15 WU × m(2) (range, 0.4-23 WU × m(2)); 2.8 WU × m(2) in infants < 1 year, 3.5 WU × m(2) in patients aged 1 to 10 years, and 3.0 WU × m(2) in patients aged > 10 years (p = 0.03). Multivariable hazard analysis controlling for graft ischemic time and pre-transplant ventilation showed no association of elevated PVRI with early mortality (relative risk, 1.2; p = 0.66), nor with intermediate mortality when controlled for year of transplant, age, race, and pre-sensitization (relative risk, 0.7; p = 0.27). CONCLUSIONS: Elevation of PVRI did not affect post-transplant survival in this large, multicenter cohort of pediatric heart transplant recipients without CHD, suggesting that the barrier of elevated PVRI can be successfully overcome in this population.

Ventricular septal defect.

BACKGROUND: Ventricular septal defects are the commonest congenital cardiac malformations. They can exist in isolation, but are also found as integral components of other cardiac anomalies, such as tetralogy of Fallot, double outlet right ventricle, or common arterial trunk. As yet, there is no agreement on how best to classify such defects, nor even on the curved surface that is taken to represent the defect. METHODS: Based on our previous pathological and clinical experiences, we have reviewed the history of classification of holes between the ventricles. We proposed that the defects are best defined as representing the area of deficient ventricular septation. This then permits the recognition of clinically significant variants according to the anatomic borders, and the way the curved surface representing the area of deficient septation opens into the morphologically right ventricle. RESULTS: Clinical manifestation depends on the size of the defect, and on the relationship between systemic and pulmonary vascular resistances. Symptoms include failure to thrive, along with the manifestations of the increase in flow of blood to the lungs. Diagnosis can be made by physical examination, but is confirmed by echocardiographic interrogation, which delineates the precise anatomy, and also provides the physiologic information required for optimal clinical decision-making. Cardiac catheterization offers additional information regarding hemodynamics, particularly if there is a concern regarding an increase in pulmonary vascular resistance. Hemodynamic assessment is rarely necessary to make decisions regarding management, although it can be helpful if assessing symptomatic adults with hemodynamically restrictive defects. In infants with defects producing large shunts, surgical closure is now recommended in most instances as soon as symptoms manifest. Only in rare cases is palliative banding of the pulmonary trunk now recommended. Closure with devices inserted on catheters is now the preferred approach for many patients with muscular defects, often using a hybrid procedure. Therapeutic closure should now be anticipated with virtually zero mortality, and with excellent anticipated long-term survival. CONCLUSION: Ventricular septal defects are best defined as representing the borders of the area of deficient ventricular septation. An approach on this basis permits recognition of the clinically significant phenotypic variants.

Increased myocardial performance index correlates with biopsy-proven rejection in pediatric heart transplant recipients.

BACKGROUND: To date, cardiac catheterization and endomyocardial biopsy have been considered the "gold standard" for rejection surveillance after heart transplantation. Factors such as patient size (i.e., infant transplantation), loss of vascular access after repeated catheterizations, and anesthesia requirements all present unique problems and risks related to pediatric rejection surveillance. Therefore, additional methods to monitor for rejection in a non-invasive, reliable and frequent manner have been sought. We studied the utility of echocardiographic measurement of the left ventricular myocardial performance index (LVMPI), a reproducible measure of combined systolic and diastolic performance, in pediatric heart transplant recipients as a method of identifying acute rejection. METHODS: Two-dimensional/Doppler echocardiographic studies (n = 36) were performed on 21 cardiac transplant patients (ages 6.2 to 21.9 years) at the time of endomyocardial biopsy. The LVMPI, the sum of the isovolumic contraction time and isovolumic relaxation time divided by aortic ejection time, was determined at each study, as well as other echocardiographic measures of systolic and diastolic function. Patients were grouped by concurrent histologic rejection grade and the results compared between groups. RESULTS: Significant differences in LVMPI (p < 0.001) were noted between patients with no rejection (Grade 0; n = 23) and those with moderate to severe rejection (Grade 3; n = 5), as well as between those with no rejection and those with focal moderate (Grade 2; n = 8) rejection (p < 0.05). The LVMPI was 0.42 +/- 0.03 (mean +/- SEM) for the group without rejection, 0.57 +/- 0.06 for those with Grade 2 rejection and 0.73 +/- 0.05 for those with Grade 3 rejection. Although 9 of the 23 studies in the non-rejection group had LVMPI values exceeding 0.44 (upper threshold value), 12 of 13 patients in the rejection groups exceeded this threshold. LVMPI >or= 0.64 was associated with significant rejection in all cases in this study (n = 7). No significant differences were noted between groups for left ventricular ejection fraction or shortening fraction, percent septal or posterior wall thickening, left ventricular mass index or mitral valve deceleration time. In addition, for those individual patients with multiple studies, the LVMPI consistently increased with higher rejection grades and decreased after therapy. CONCLUSIONS: In this series, increased LVMPI correlated with biopsy-proven rejection, and frequent serial assessments using this technique may provide a relatively sensitive non-invasive means of rejection surveillance after pediatric cardiac transplantation. False positive results may be encountered, likely due to alterations in diastolic function that have been previously observed in transplant recipients.

Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are an important cause of morbidity and mortality after organ transplantation. We sought to better define the prevalence, pathology, current therapeutic approaches, and outcomes of PTLD in a large group of children who had received heart transplants. METHODS: We assessed data on patients followed up at 19 centres in the Pediatric Heart Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTLD was assessed along with details of presentation, pathology, treatment, and outcomes. Risk factors for survival and event-free survival were investigated. FINDINGS: Of 1184 primary transplant recipients, 56 (5%) developed PTLD. Probability of freedom from PTLD was 98% at 1 year, 94% at 3 years, and 92% at 5 years. Mean time to PTLD was 23.8 months. Most common sites of disease were gastrointestinal tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polymorphic in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39 of 45 (87%) were Epstein-Barr virus positive. Probability of survival was 75% at 1 year, 68% at 3 years, and 67% at 5 years after diagnosis. Death from graft loss was as frequent as death from PTLD. INTERPRETATION: About 5% of paediatric heart-transplant recipients develop PTLD, almost always of B-cell lineage and driven by Epstein-Barr virus. Although many achieve satisfactory outcomes, mortality remains substantial with death due to progressive disease and allograft loss. Advances in management should focus on strategies to protect the allograft as well as improved therapies for PTLD.

An institutional review of the value of computed tomographic angiography in the diagnosis of congenital cardiac malformations.

The ultra-fast, thin-cut computerised tomographic angiogram is an efficient method to diagnose extracardiac lesions associated with congenital cardiac disease. For the purposes of this review, we evaluated various facets of the technique as used in 30 patients who were referred for diagnosis of congenital cardiac disease. The technique had high diagnostic accuracy, with a sensitivity of 93 percent in 15 of these patients referred for either interventional catheterisation or surgery. There were no immediate side-effects associated with the scanning procedure. The scan was also found to be more cost-effective as compared to an alternative noninvasive modality for imaging modality, namely magnetic resonance imaging. The angiographic technique, however, does expose the child to between 2 and 2.5 rems of radiation, despite the short period of scanning, of 10 plus or minus 2 seconds.

Toxic serum trough concentrations after administration of nebulized tobramycin.

The goal of administering nebulized antibiotics is to provide patients with a high concentration of drug at the infection site with minimal systemic effects. In two studies in which nebulized tobramycin 300 mg twice/day was administered, systemic peak concentrations were below 0.2 and 3.62 microg/ml, and trough concentrations were undetectable, making toxicity from this route of administration negligible. A 19-year-old woman who received a heart transplant was administered tobramycin inhalation solution for Acinetobacter baumanii pneumonia; her serum trough concentrations were found to be toxic (> 2.0 microg/ml). Her risk factors for experiencing these toxic concentrations were renal failure and administration of the drug by positive pressure ventilation. Although nebulized tobramycin is safe under routine circumstances, clinicians must be aware of its potential for toxicity in patients with renal dysfunction or in those receiving positive pressure ventilation.