Brian W. Duncan

Outcomes of Children Bridged to Heart Transplantation With Ventricular Assist Devices A Multi-Institutional Study

Background— Current ventricular assist devices (VADs) in the United States are designed primarily for adult use. Data on VADs as a bridge to transplantation in children are limited. Methods and Results— A multi-institutional, prospectively maintained database of outcomes in children after listing for heart transplantation (n=2375) was used to analyze outcomes of VAD patients (n=99, 4%) listed between January 1993 and December 2003. Median age at VAD implantation was 13.3 years (range, 2 days to 17.9 years); diagnoses were cardiomyopathy (78%) and congenital heart disease (22%). Mean duration of support was 57 days (range, 1 to 465 days). Seventy-three percent were supported with a long-term device, with 39% requiring biventricular support. Seventy-seven patients (77%) survived to transplantation, 5 patients were successfully weaned from support and recovered, and 17 patients (17%) died on support. In the recent era (2000 to 2003), successful bridge to transplantation with VAD was achieved in 86% of patients. Peak hazard for death while waiting was the first 2 weeks after VAD placement. Risk factors for death while awaiting a transplant included earlier era of implantation (P=0.05), female gender (P=0.02), and congenital disease diagnosis (P=0.05). There was no difference in 5-year survival after transplantation for patients on VAD at time of transplantation as compared with those not requiring VAD. Conclusions— VAD support in children successfully bridged 77% of patients to transplantation, with posttransplantation outcomes comparable to those not requiring VAD. These encouraging results emphasize the need to further understand patient selection and to delineate the impact of VAD technology for children.

Studies in Fetal Wound Healing, VI. Second and Early Third Trimester Fetal Wounds Demonstrate Rapid Collagen Deposition Without Scar Formation

The mechanisms that underlie the lack of scarring in fetal wounds are unknown, but probably relate to the control of collagen fibrillogenesis. The role of collagen in the fetal wound matrix is controversial, and several wound implant models have been used to evaluate collagen deposition in fetal wounds. Unfortunately, these models create an artificial wound environment and may thereby affect the results. In order to study fetal wound collagen deposition in linear wounds without artificially altering the wound environment, we applied a highly sensitive immunohistochemical technique that uses antibodies to collagen types I, III, IV, and VI. We found that collagen was deposited in fetal wounds much more rapidly than in adult wounds. Wound collagen deposition occurred in a normal dermal and mesenchymal pattern in second and early third trimester fetal lambs. These findings are consistent with the observation that the fetus heals rapidly and without scar formation. In contrast, wounds in late gestation fetal lambs showed some evidence of scar formation. Further studies may suggest ways to alter the adult wound so that it heals in a fetal manner.

Mechanical circulatory support in children with cardiac disease

OBJECTIVE To review the experience from a single center that uses both extracorporeal membrane oxygenation and ventricular assist devices for children with cardiac disease requiring mechanical circulatory support. METHODS A retrospective chart review was performed for all pediatric patients with cardiac disease who required support with extracorporeal membrane oxygenation or ventricular assist devices. Statistical analysis of the impact of multiple clinical parameters on survival was performed. RESULTS From 1987 through 1996 we provided mechanical circulatory support for children with a primary cardiac diagnosis using extracorporeal membrane oxygenation (67 patients) and ventricular assist devices (29 patients). Twenty-seven of 67 (40.3%) patients supported with extracorporeal membrane oxygenation and 12 of 29 (41.4%) patients supported with ventricular assist devices survived to hospital discharge. Failure of return of ventricular function within 72 hours of the institution of support was an ominous sign in patients supported with either modality. Univariate analysis revealed the serum pH at 24 hours of support, the serum bicarbonate at 24 hours of support, the urine output over the first 24 hours of support, and the development of renal failure to have a statistically significant association with survival in children supported with extracorporeal membrane oxygenation. None of the clinical parameters evaluated by univariate analysis were significantly associated with survival in the patients supported with ventricular assist devices. CONCLUSIONS Extracorporeal membrane oxygenation and ventricular assist devices represent complementary modalities of mechanical circulatory support that can both be used effectively in children with cardiac disease.

Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest.

INTRODUCTION We have recently used extracorporeal membrane oxygenation as a means of rapidly resuscitating pediatric patients with heart disease after cardiopulmonary arrest, in whom conventional resuscitation measures have failed. METHODS We developed a fully portable extracorporeal membrane oxygenation circuit that is maintained vacuum and carbon dioxide-primed at all times. When needed, the circuit is crystalloid-primed and can be ready for use within 15 minutes. Since February 1996, we have used this rapid-deployment circuit to resuscitate 11 pediatric patients in full cardiopulmonary arrest. RESULTS The median age of the 11 patients was 120 days (2 days to 4.6 years). Nine patients had a cardiac arrest after cardiac surgery. One patient had a cardiac arrest during cardiac catheterization and one patient had a cardiac arrest before cardiac surgery. Median duration of cardiopulmonary resuscitation was 55 minutes (range 20 to 103 minutes), with no difference in the duration of cardiopulmonary resuscitation between survivors and nonsurvivors. Ten of 11 patients (91%) were weaned from extracorporeal membrane oxygenation and seven (64%) survived to hospital discharge. Six patients are long-term survivors, five of whom are in New York Heart Association class I; one survivor is in class II. Seven patients resuscitated with extracorporeal membrane oxygenation before the use of this rapid-deployment circuit had a median duration of cardiopulmonary resuscitation of 90 minutes, with two (28.6%) survivors. CONCLUSIONS The use of rapid-deployment extracorporeal membrane oxygenation results in shorter resuscitation times and improved survival in pediatric patients with heart disease after cardiopulmonary arrest.

The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program

Options for the circulatory support of pediatric patients under the age of 5 years are currently limited to short-term extracorporeal devices, the use of which is often complicated by infection, bleeding, and thromboembolism. Recognizing this void, the National Heart, Lung, and Blood Institute solicited proposals for the development of novel circulatory support systems for infants and children from 2 to 25 kg with congenital or acquired cardiovascular disease. Five contracts were awarded to develop a family of devices that includes (1) an implantable mixed-flow ventricular assist device designed specifically for patients up to 2 years of age, (2) another mixed-flow ventricular assist device that can be implanted intravascularly or extravascularly depending on patient size, (3) compact integrated pediatric cardiopulmonary assist systems, (4) apically implanted axial-flow ventricular assist devices, and (5) pulsatile-flow ventricular assist devices. The common objective for these devices is to reliably provide circulatory support for infants and children while minimizing risks related to infection, bleeding, and thromboembolism. The devices are expected to be ready for clinical studies at the conclusion of the awards in 2009.

Is Arrhythmia Detection by Automatic External Defibrillator Accurate for Children? Sensitivity and Specificity of an Automatic External Defibrillator Algorithm in 696 Pediatric Arrhythmias

Background—Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. Methods and Results—Children aged ≤12 years who either developed arrhythmias or were at risk for developing arrhythmias were studied. Two sources were used for the database: children whose rhythms were recorded prospectively via a modified AED and children who had arrhythmias captured on paper and digitized for subsequent analysis. The rhythms were divided into 5-second strips, classified by 3 reviewers, and then assessed by the AED analysis algorithm. A total of 696 five-second rhythm strips from 191 children (81 female and 110 male) aged 1 day to 12 years (median 3.0 years) were analyzed. There was 100% specificity for nonshockable rhythms. Sensitivity for ventricular fibrillation was 96%. Conclusions—There was excellent AED rhythm analysis sensitivity and specificity in all age groups for ventricular fibrillation and nonshockable rhythms. The high specificity and sensitivity indicate that there is a very low risk of an inappropriate shock and that the AED correctly identifies shockable rhythms, making the algorithm both safe and effective for children.

Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid.

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Left ventricular assist device improves survival in children with left ventricular dysfunction after repair of anomalous origin of the left coronary artery from the pulmonary artery.

BACKGROUND Repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in infants carries a high operative risk, particularly in infants with myocardial infarction and poor left ventricular function. The marked recovery of left ventricular function reported late after repair, however, suggests that an aggressive approach to repair should be undertaken. METHODS Of 31 children undergoing primary repair of ALCAPA at our institution from 1987 to 1996, 26 were infants (6 weeks to 9 months old). All but 2 had severe left ventricular dysfunction, and 8 had moderate to severe mitral regurgitation. Seven children were unable to be weaned from cardiopulmonary bypass because of poor left ventricular function and elevated left atrial pressure. These 7 children were placed on mechanical left ventricular support using a centrifugal pump, with support ranging from 2.2 to 70.6 hours. RESULTS One child died shortly after the start of left ventricular assist (2.2 hours), and another died of arrhythmia within 24 hours after successful decannulation. All 5 survivors had significant improvement in left ventricular function, with 2 requiring late mitral valve repair. CONCLUSIONS Infants with ALCAPA who have severe left ventricular dysfunction represent a higher risk group for repair. However, with use of mechanical circulatory support in those unable to be weaned from cardiopulmonary bypass, a high survival rate can be achieved with good long-term recovery. We conclude that an aggressive approach to early repair in all children with ALCAPA is warranted, regardless of the degree of left ventricular dysfunction.

Pulmonary arteriovenous malformations after cavopulmonary anastomosis

Pulmonary arteriovenous malformations (PAVMs) are a cause of progressive cyanosis after cavopulmonary anastomosis in children with single ventricle physiology who are on the pathway leading to a Fontan procedure. Investigations into possible mechanisms for the etiology of PAVMs are ongoing and suggest that the liver might play a key regulatory role in the development of these lesions.

Mechanical Circulatory Support for Infants and Children With Cardiac Disease

Mechanical circulatory support is assuming an expanding role in the practice of congenital cardiac surgery. Extracorporeal membrane oxygenation and centrifugal ventricular assist devices are still the mainstay of mechanical circulatory support for children; however, newly developed pulsatile, paracorporeal ventricular assist devices designed for pediatric applications are achieving increased utilization. In addition, several new, continuous flow devices that are under development as fully implantable systems for adults, ultimately may be useful for pediatric patients.