Elizabeth A. Frazier

Blade and balloon atrial septostomy for left heart decompression in patients with severe ventricular dysfunction on extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is used as circulatory support or bridge to transplantation in patients with severe left ventricular (LV) dysfunction. Left heart decompression is needed to reduce pulmonary edema, prevent pulmonary hemorrhage, and reduce ventricular distention that may aid in recovery of function. We reviewed our experience from November 1993 to December 1997 with 10 patients having severe LV dysfunction (7 myocarditis, 3 dilated cardiomyopathy) who required circulatory support with ECMO and who underwent left heart decompression with blade and balloon atrial septostomy (BBAS). Patients ranged in age from 1 to 24 years (median, 3 years). Indications for BBAS included left atrial/left ventricular distension (10), pulmonary edema/hemorrhage (9), or severe mitral regurgitation (2). BBAS was performed electively in eight patients and urgently in two patients. BBAS was performed while on ECMO in seven patients and pre‐ECMO in three. A femoral venous approach was used in all patients. ECMO patients were fully heparinized. Transseptal puncture was required in nine patients while one patient had a patent foramen ovale. Blade septostomy was performed in all patients. Enlargement of the defect was then performed by stationary balloon dilation in nine and Rashkind balloon atrial septostomy in one. Balloon diameters ranged from 10 to 20 mm. Sequential balloon inflations were performed in some patients. Adequacy of the atrial septal defect (ASD) was confirmed by pressure measurement and echocardiography. Adequate left heart decompression was achieved in all patients. Pulmonary edema improved in nine of nine patients. Left atrial mean pressure fell from a mean of 30.5 mm Hg, (range, 12–50 mm Hg) to 16 mm Hg (range, 9–24 mm Hg). Left atrial to right atrial pressure gradient fell from a mean of 20 mm Hg pre‐BBAS to 3 mm Hg post‐BBAS. ASDs ranged in size from 2.5 to 8 mm (mean, 5.9 mm). Complications included needle perforation of the left atrium without hemodynamic compromise (one), ventricular fibrillation requiring defibrillation (one), and hypotension following BBAS which responded to volume infusion (two). Duration of ECMO ranged from 41 hr to 704 hr (mean, 294 hr). Seven patients survived and four patients had recovery of normal LV function. Of those who recovered, two had no ASD at follow‐up while two ASDs are patent 14 days and 3 months post‐BBAS. Three patients underwent successful cardiac transplantation. Three patients died, all of whom had multisystem organ failure with or without sepsis. A patent ASD was noted at transplant (three) or autopsy (two). No patient required a second BBAS. BBAS alleviates severe left atrial hypertension and pulmonary edema. In addition, BBAS avoids the potential bleeding complications of surgical left heart decompression. Stationary balloon dilation of the atrial septum is an effective alternative to Rashkind balloon septostomy in older patients. BBAS achieves left heart decompression that may permit recovery of LV function or allow extended ECMO support as a bridge to transplant. Cathet. Cardiovasc. Intervent. 46:179–186, 1999.

Survival and risk factors for death after cardiac transplantation in infants: A multi-institutional study

BACKGROUND Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood. METHODS AND RESULTS To examine early survival and risk factors for death in infants (< 1 year of age) undergoing cardiac transplantation, 141 infants (36 < 1 months of age) underwent primary cardiac transplantation between January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%), other congenital heart disease (17%), cardiomyopathy (14%), and other (3%). Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1 year, and 69% at 2 years, with the greatest hazard for death within the first 3 months. The principal cause of death was early graft failure in 20 patients (52% of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the basis of multivariate analysis, risk factors for early mortality were history of previous sternotomy (P = .0003), nonidentical blood type donor (P = .01), recipient non-blood group A (P = .02), and donor cause of death other than closed head trauma (P = .04). Diagnosis at listing, waiting time (mean, 1.3 months), graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient ventilatory or inotropic support at listing were not predictive for mortality after transplant. CONCLUSIONS The higher mortality rate observed with infant heart transplantation is due to a higher mortality within the first month after transplantation as a result of early graft failure. Strategies to improve donor heart function at implantation would have the greatest impact on survival after infant cardiac transplantation.

Pediatric arteriovenous extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation

BACKGROUND Since 1990, extracorporeal membrane oxygenation (ECMO) has been used as a bridge to cardiac transplantation in 47 patients. METHODS A review of the ECMO database, approved by the Arkansas Childrens Hospital institutional review board, forms the basis of this report. We made statistical comparison using Fishers exact probability testing. The ECMO circuitry was a roller occlusion pump with computer-assisted perfusion system technology. RESULTS Thirty-two (68%) patients underwent transcatheter septostomy for cardiac decompression. Diagnosis at presentation was either congenital heart disease (CHD, n = 15) or cardiomyopathy (n = 32). Ages ranged from 1 day to 22 years old (median, 18 months old), and weight ranged from 2.9 to 100 kg (median, 10 kg). The average duration of support was 242 hours (range, 22-1078 hours). Overall long-term survival was 47%, with 16 (34%) patients successfully bridged to cardiac transplantation (of which 9 [56%] survived) and 13 (28%) successfully weaned from ECMO. Patients undergoing ECMO after cardiotomy had 31% survival. Survival was improved significantly (p < 0.02) in patients with cardiomyopathy (59%) vs those with CHD (20%). Patients with cardiomyopathy underwent 8 transplantations with 7 survivors (88%), whereas in the CHD group, there were 8 transplantations with only 2 survivors (25%), p < 0.05. Sub-analysis of the cardiomyopathy group revealed that patients with acute cardiomyopathy in association with documented viral illness had a 75% chance of being weaned from ECMO without undergoing transplantation. Complications during ECMO occurred in 45% of survivors and were more frequent in non-survivors. Infectious complications were most frequent, followed by neurologic complications, technical ECMO problems, and renal insufficiency. CONCLUSIONS Patients with cardiomyopathy has a better prognosis than did those with CHD when using ECMO as a bridge to transplantation or survival. Complications are significant and increase with the duration of support. Extracorporeal membrane oxygenation for salvage and subsequent transplantation in this high-risk group of patients requires critical review. Alternative support options must be developed in the pediatric population that will allow improved outcomes, comparable with outcomes achieved in the adult population.

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.

Extracorporeal Membrane Oxygenation for Cardiac Failure After Congenital Heart Operation

Despite continuing improvement in myocardial protection and surgical technique, the repair of complex congenital heart lesions can result in cardiopulmonary compromise refractory to conventional therapy. In a 29-month period, 24 patients (aged 14 hours to 6 years) were treated with extracorporeal membrane oxygenation (ECMO) 28 times for profound cardiopulmonary failure. Four patients required ECMO after each of two cardiopulmonary bypass procedures. Seventeen patients required ECMO to be initiated in the operating room: 12 (71%) were weaned successfully from ECMO, and 8 (47%) survived. Seven patients had ECMO initiated in the intensive care unit: 6 (86%) were weaned, and 5 (71%) survived. Serial echocardiograms demonstrated substantial recovery of cardiac function in 18 of 21 instances (86%) of ventricular failure from myocardial dysfunction. Overall, 18 of 24 patients (75%) were successfully weaned from ECMO including all 4 who underwent 2 ECMO treatments. We conclude that ECMO can successfully salvage children who have serious cardiopulmonary failure immediately after a congenital heart operation and that long-term survival is possible after two ECMO treatments.

Bridge to Cardiac Transplant in Children: Berlin Heart versus Extracorporeal Membrane Oxygenation

BACKGROUND For small children requiring mechanical circulatory support as a bridge to transplantation (BTT), extracorporeal membrane oxygenation (ECMO) has been the only option until the recent introduction of the Berlin Heart EXCOR ventricular assist device (Berlin Heart AG, Berlin, Germany). We reviewed our recent experience with these two technologies with particular focus on early outcomes. METHODS Data for 55 consecutive children undergoing BTT between 2001 and 2008 were abstracted from an institutional database. The analysis excluded 13 patients because EXCOR was not used for acute postcardiotomy BTT. Patients were divided into ECMO (n = 21) and EXCOR groups (n = 21). Specific end points included survival to transplant, overall survival, and bridge to recovery. Incidences of adverse events and the duration of support were determined. RESULTS Groups were similar in weight, age, and etiologies of heart failure. Likewise, the incidences of stroke and multisystem organ failure were similar. Survival to transplant, recovery, or continued support was 57% in ECMO and 86% in EXCOR (p = 0.040). EXCOR patients had overall significantly better survival (p = 0.049). Two ECMO patients and 1 EXOR patient were bridged to recovery. The mean duration of support was 15 +/- 12 days in the ECMO group and 42 +/- 43 days in the EXCOR group (p < 0.001). CONCLUSIONS In children requiring BTT, EXCOR provided substantially longer support times than ECMO, without significant increase in the rates of stroke or multisystem organ failure. Survival to transplant and long-term survival was higher with EXCOR.

Preliminary single center North American experience with the Berlin Heart pediatric EXCOR device.

For children requiring mechanical circulatory support as a bridge to cardiac transplantation in North America, options previously were limited to extracorporeal membrane oxygenation (ECMO) or centrifugal pump ventricular assist, both of which were suitable for only very short term application and were associated with significant complications and limitations. The Berlin Heart EXCOR ventricular assist device (VAD) was recently introduced into practice in North America to address this deficiency. We report a preliminary single center experience with the EXCOR in 17 children, 13 who received only a left-sided pump and four who required biventricular support. Before EXCOR placement, six patients were on ECMO, and one was on a centrifugal VAD. Eleven children were bridged to transplantation, one was bridged to recovery, and one remains on support. Three children died during support and one died after explantation. There was one late death nearly 2 years after transplant. Complications included stroke in seven patients, two of which were ultimately fatal. Five patients required re-operations for bleeding or evacuation of hematoma. Despite a disappointing rate of neurologic morbidity, our preliminary experience with the EXCOR has been very encouraging.

Rapid reduction in donor-specific anti-human leukocyte antigen antibodies and reversal of antibody-mediated rejection with bortezomib in pediatric heart transplant patients.

Background. High titer donor-specific antibodies (DSA) and positive crossmatch in cardiac transplant recipients is associated with increased mortality from antibody-mediated rejection (AMR). Although treatment to reduce anti-human leukocyte antigen antibodies using plasmapheresis, intravenous immunoglobulin, and rituximab has been reported to be beneficial, in practice these are often ineffective. Moreover, these interventions do not affect the mature antibody producing plasma cell. Bortezomib, a proteasome inhibitor active against plasma cells, has been shown to reduce DSA in renal transplant patients with AMR. We report here the first use of bortezomib for cardiac transplant recipients in four pediatric heart recipients with biopsy-proven AMR, hemodynamic compromise, positive crossmatch, and high titer class I DSA. Methods. Patients received four intravenous dose of bortezomib (1.3 mg/m2) over 2 weeks with plasmapheresis and rituximab. DSA specificity and strength (mean fluorescence intensity) was determined with Luminex. All had received previous treatment with plasmapheresis, intravenous immunoglobulin, and rituximab that was ineffective. Results. AMR resolved in all patients treated with bortezomib with improvement in systolic function, conversion of biopsy to C4d negative in three patients and IgG negative in one patient, and a prompt, precipitous reduction in DSAs. In three patients who received plasmapheresis before bortezomib, plasmapheresis failed to reduce DSA. In one case, DSA increased after bortezomib but decreased after retreatment. Conclusions. Bortezomib reduces DSA and may be an important adjunct to treatment of AMR in cardiac transplant recipients. Bortezomib may also be useful in desensitization protocols and in prevention of AMR in sensitized patients with positive crossmatch and elevated DSA.

Noninvasive Cerebral Oximeter as a Surrogate for Mixed Venous Saturation in Children

We evaluated the relationship between regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS) cerebral oximeter with superior vena cava (SVC), inferior vena cava (IVC), right atrium (RA), and pulmonary artery (PA) saturation measured on room air and 100% inspired oxygen administered via a non-rebreather mask (NRB) in children. Twenty nine pediatric post-orthotopic heart transplant patients undergoing an annual myocardial biopsy were studied. We found a statistically significant correlation between rSO2 and SVC saturations at room air and 100% inspired oxygen concentration via NRB (r = 0.67, p = 0.0002 on room air; r = 0.44, p = 0.02 on NRB), RA saturation (r = 0.56, p = 0.002; r = 0.56, p = 0.002), and PA saturation (r = 0.67, p < 0.001; r = 0.4, p = 0.03). A significant correlation also existed between rSO2 and measured cardiac index (r = 0.45, p = 0.01) and hemoglobin levels (r = 0.41, p = 0.02). The concordance correlations were fair to moderate. Bias and precision of rSO2 compared to PA saturations on room air were −0.8 and 13.9%, and they were 2.1 and 15.6% on NRB. A stepwise linear regression analysis showed that rSO2 saturations were the best predictor of PA saturations on both room air (p = 0.0001) and NRB (p = 0.012). In children with biventricular anatomy, rSO2 readings do correlate with mixed venous saturation.

Survival after listing for cardiac transplantation in children

Despite improvement in surgical and medical management of children with congenital and acquired heart disease, cardiac transplantation remains an important therapeutic option for infants and children with end-stage heart disease. Ultimate survival in patients who are listed for transplantation is a function of both mortality while awaiting transplantation and survival after transplantation. Survival of heart transplantation is affected by the severity of illness before transplantation, the unique pathophysiology of certain defects, and the availability of donor hearts. Outcome following listing for transplantation is best studied with the use of recent modifications in statistical methods of competing outcomes analysis. By this analysis a predicted mortality while waiting among all pediatric patients is 20% at 1 year, with 67% undergoing transplantation, 10% still on the list awaiting transplant, and 3% removed from the list. Among infants, most of them with hypoplastic left heart syndrome, 60% will have transplantation by 6 months after listing, with 27% of patients dying while waiting. In infants the major risk factors for death while waiting are the need for inotropic support at listing, smaller size, and recipient blood type. In older children risk factors for death while waiting are Status 1 at listing and a need for mechanical ventilation. Intermediate-term survival after transplant is excellent in all age groups with 86% alive at 6 months, 84% at 1 year, and 73% at 5 years. Survival after transplant in infants is comparable to survival in older children, although the early mortality after transplantation is greater. Infants who have recently undergone sternotomy or received organs from donors who did not die of closed head trauma are more likely to die early after transplant. Among older children risk factors for death after transplantation include the need for a mechanical support device or a younger age in patients greater than 1 year of age. Death following transplantation is primarily related to early graft failure in infants, whereas rejection, infection, and sudden death account for the majority of deaths in older children. Although improved immunosuppressive agents promise to lead to even better survival rates after transplantation, greater access to donors is essential if overall survival is to be improved.