The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation.

Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.

The use of oral sildenafil for management of right ventricular dysfunction after pediatric heart transplantation.

High pulmonary vascular resistance index (PVRI) can lead to right ventricular dysfunction and failure of the donor heart early after pediatric heart transplantation. Oral pulmonary vasodilators such as sildenafil have been shown to be effective modifiers of pulmonary vascular tone. We performed a retrospective, observational study comparing patients treated with sildenafil ("sildenafil group") to those not treated with sildenafil ("nonsildenafil group") after heart transplantation from 2007 to 2012. Pre- and posttransplant data were obtained, including hemodynamic data from right heart catheterizations. Twenty-four of 97 (25%) transplant recipients were transitioned to sildenafil from other systemic vasodilators. Pretransplant PVRI was higher in the sildenafil group (6.8 ± 3.9 indexed Woods units [WU]) as compared to the nonsildenafil group (2.5 ± 1.7 WU, p=0.002). In the sildenafil group posttransplant, there were significant decreases in systolic pulmonary artery pressure, mean pulmonary artery pressure, transpulmonary gradient and PVRI (4.7 ± 2.9 WU before sildenafil initiation to 2.7 ± 1 WU on sildenafil, p=0.0007). While intubation time, length of inotrope use and time to hospital discharge were longer in the sildenafil group, survival was similar between both groups. Oral sildenafil was associated with a significant improvement in right ventricular dysfunction and invasive hemodynamic measurements in pediatric heart transplant recipients with high PVRI early after transplant.

Pediatric cardiac transplantation using hearts previously refused for quality: a single center experience.

Pediatric donor hearts are regularly refused for donor quality with limited evidence as to which donor parameters are predictive of poor outcomes. We compare outcomes of recipients receiving hearts previously refused by other institutions for quality with the outcomes of recipients of primarily offered hearts. Data for recipients aged ≤18 and their donors were obtained. Specific UNOS refusal codes were used to place recipients into refusal and nonrefusal groups; demographics, morbidity and mortality were compared. Kaplan-Meier analysis with log-rank test was used to determine differences in graft survival. A multivariable Cox proportional hazards model was constructed to determine independent risk factors for postoperative mortality. From July 1, 2000 to April 30, 2011, 182 recipients were transplanted and included for analysis. One hundred thirty received a primarily offered heart; 52 received a refused heart. No difference in postoperative complications or graft survival between the two groups (p = 0.190) was found. Prior refusal was not an independent risk factor for recipient mortality. Analysis of this large pediatric cohort examining outcomes with quality-refused hearts shows that in-hospital morbidity and long-term mortality for recipients of quality-refused hearts are no different than recipients of primarily offered hearts, suggesting that donor hearts previously refused for quality are not necessarily unsuitable for transplant and often show excellent outcomes.

Unusual presentation of propionic acidaemia as isolated cardiomyopathy.

Propionic acidaemia (PA) is an autosomal recessive disease that results from deficiency of propionyl-CoA carboxylase (PCC). In the majority of reported cases, the phenotype includes metabolic acidosis and/or neurological deficits. We report on a 14-year-old Asian-American male with PA who presented with isolated cardiomyopathy without any documented episodes of metabolic acidosis or evidence of any neurocognitive deficits. On routine metabolic screening, the patient was found to have urine organic acids suggestive of PA. Biochemical and genetic characterization confirmed a PCC deficiency with two novel mutations in PCCB: IVS7 + 2 T > G (c.763 + 2 T > G) and p.R410Q (c.1229 G > A). Residual enzyme activity likely explains our patient's mild phenotype. Splicing mutations tend to result in a milder phenotype as these mutations may still produce small amounts of normal enzyme. In addition, the similar p.R410W mutation has been shown to have partial residual activity. Moreover, this case illustrates that a thorough metabolic evaluation should be performed in both paediatric and adult patients with cardiomyopathy. Such an evaluation has important implications for clinical management and genetic counselling.

Twenty-year experience with heart transplantation for infants and children with restrictive cardiomyopathy: 1986-2006.

Idiopathic restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children notable for severe diastolic dysfunction and progressive elevation of pulmonary vascular resistance (PVR). Traditionally, those with pulmonary vascular resistance indices (PVRI) >6 W.U. x m(2) have been precluded from heart transplantation (HTX). The clinical course of all patients transplanted for RCM between 1986 and 2006 were reviewed. Preoperative, intraoperative and postoperative variables were evaluated. A total of 23 patients underwent HTX for RCM, with a mean age of 8.8 +/- 5.6 years and a mean time from listing to HTX of 43 +/- 60 days. Preoperative and postoperative (114 +/- 40 days) PVRI were 5.9 +/- 4.4 and 2.9 +/- 1.5 W.U. x m(2), respectively. At time of most recent follow-up (mean = 5.7 +/- 4.6 years), the mean PVRI was 2.0 +/- 1.0 W.U. x m(2). Increasing preoperative mean pulmonary artery pressure (PA) pressure (p = 0.04) and PVRI > 6 W.U. x m(2) (chi(2)= 7.4, p < 0.01) were associated with the requirement of ECMO postoperatively. Neither PVRI nor mean PA pressure was associated with posttransplant mortality; 30-day and 1-year actuarial survivals were 96% and 86%, respectively. Five of the seven patients with preoperative PVRI > 6 W.U. x m(2) survived the first postoperative year. We report excellent survival for patients undergoing HTX for RCM despite the high proportion of high-risk patients.

Outcome of listing for cardiac transplantation for failed Fontan: a multi-institutional study.

BACKGROUND: The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients. METHODS AND RESULTS: A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation. CONCLUSIONS: Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.

Acute pulmonary embolism in pediatric patients awaiting heart transplantation.

Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation.

Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts.

OBJECTIVES: The objective of the study was to evaluate nitric oxide (NO) mediated regulation of mitochondrial respiration after implantation of a mechanical assist device in end-stage heart failure. BACKGROUND: Ventricular unloading using a left ventricular assist device (LVAD) can improve mitochondrial function in end-stage heart failure. Nitric oxide modulates the activity of the mitochondrial electron transport chain to regulate myocardial oxygen consumption (MVO2). METHODS: Myocardial oxygen consumption was measured polarographically using a Clark-type oxygen electrode in isolated left ventricular myocardium from 26 explanted failing human hearts obtained at the time of heart transplantation. RESULTS: The rate of decrease in oxygen concentration was expressed as a percentage of baseline. Results of the highest dose of drug are shown. Decrease in MVO2 was greater in LVAD hearts (n = 8) compared with heart failure controls (n = 18) in response to the following drugs: bradykinin (-34+/-3% vs. -24+/-5%), enalaprilat (-37+/-5% vs. -23+/-5%) and amlodipine (-43+/-13% vs. -16+/-5%; p<0.05 from controls). The decrease in MVO2 in LVAD hearts was not significantly different from controls in response to diltiazem (-22+/-5% in both groups) and exogenous NO donor, nitroglycerin (-33+/-7% vs. -30+/-3%). N(w)-nitro-L-arginine methyl ester, inhibitor of NO synthase, attenuated the response to bradykinin, enalaprilat and amlodipine. Reductions in MVO2 in response to diltiazem and nitroglycerin were not altered by inhibiting NO. CONCLUSIONS: Chronic LVAD support potentiates endogenous NO-mediated regulation of mitochondrial respiration. Use of medical or surgical interventions that augment NO bioavailability may promote myocardial recovery in end-stage heart failure.

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Pediatric heart transplantation after operations involving the pulmonary arteries.

A prohibitive perioperative mortality has been previously ascribed to pediatric heart transplantation after palliative operations for congenital heart disease involving the pulmonary arteries. Of 46 children who have undergone heart transplantation at our institution between June 1984 and February 1990, 7 (15%; mean age 8 +/- 3 years; range 1 to 18 years) have previously undergone such operations: right ventricle to pulmonary artery conduit/homograft for levo-transposition of the great arteries (2), Waterston shunt for tricuspid and pulmonary atresia (1), pulmonary artery banding for single ventricle (1), Fontan procedure for single ventricle (1), first-stage Norwood procedure for hypoplastic left heart syndrome (1), and classic right Blalock-Taussig shunt for atrioventricular canal with pulmonic stenosis (1). Three categories of pulmonary artery anatomy that require different approaches to reconstruction at the time of transplantation are recognized: abnormalities of position, pulmonary outflow obstruction, and previous systemic- or atrial-pulmonary connections. At operation, individualized pulmonary arterial reconstruction was employed, including use of previously created right ventricular-pulmonary artery conduits/homografts and angioplasty (with and without pericardial patches). Transplantation was successful in all patients. Posttransplant right ventricular-pulmonary artery pressure gradients and pulmonary vascular resistance indices were acceptable, with a tendency to decrease with time. Two patients had critical right ventricular failure postoperatively; one of them required support with extracorporeal membrane oxygenation. There was no perioperative mortality, with three deaths occurring from 5 to 39 months after transplantation. All surviving patients are in New York Heart Association functional class I. Techniques borrowed from the repair of congenital cardiac lesions can be applied to subgroups of children undergoing heart transplantation. Additional length of donor aorta and pulmonary artery should be harvested for possible use in designing pulmonary artery connections. Previous palliative operations involving the pulmonary arteries with associated complex pulmonary artery anatomy are not of themselves an insurmountable obstacle to successful heart transplantation.

Arrhythmias in pediatric heart transplant recipients: prevalence and association with death, coronary artery disease, and rejection.

To ascertain the prevalence and types of arrhythmias occurring after heart transplantation in children, all available 24-hour ambulatory ECGs (mean, 1.5/patient), and 12-lead surface ECGs (mean, 27/patient) obtained from 59 orthotopic pediatric heart transplant recipients (mean age, 9.7 +/- 5.9 years) were examined. Correlation of the appearance of arrhythmias with the occurrence of rejection, coronary artery disease, or death was investigated. Of the 59 patients, 24 (41%) were found to have arrhythmias including chronic sinus tachycardia (eight patients), sinus bradycardia (four patients), supraventricular tachyarrhythmias (nine patients), significant ventricular premature depolarization (seven patients), and nonsustained ventricular tachyarrhythmias (seven patients). The occurrence of arrhythmias was not significantly associated with the number of rejections per patient month of survival. However, a significant proportion of patients with supraventricular (seven of nine patients; p = 0.006) and ventricular (six of seven patients; p = 0.02) tachyarrhythmias experienced a rejection episode in association with the onset of the rhythm abnormality. The presence of coronary artery disease was significantly associated with the presence of ventricular tachyarrhythmias (p = 0.03). Graft survival was significantly lower in those patients with arrhythmias as compared with the arrhythmia-free group (58% versus 86%, p = 0.02). The results suggest that the appearance of arrhythmias in a pediatric heart transplant recipient should prompt a search for the presence of rejection and/or coronary artery disease.

Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group.

BACKGROUND: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population. METHODS: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group. RESULTS: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients. CONCLUSIONS: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.

Implantable left ventricular assist devices can successfully bridge adolescent patients to transplant.

BACKGROUND: Left ventricular assist devices (LVAD) have been used successfully as a life-sustaining bridge to transplantation in adults with end-stage heart failure. Long-term implantable cardiac assist devices for smaller adolescent patients are not yet available in the United States. METHODS: This study reviews the experience with patients less than 21 years old that received HeartMate LVADs (TCI) at our institution. Twelve patients were implanted with 13 LVADs. The patients ranged in age from 11 to 20 years (mean 16 years). Body surface area ranged from 1.4 to 2.2 m2 (mean 1.8 m2). Patients were selected for LVAD placement based on eligibility for heart transplant and evidence of end-organ dysfunction. Device placement in small patients was facilitated with prosthetic graft abdominal wall closure. No patient received systemic anticoagulation. RESULTS: The duration of LVAD support ranged from 0 to 397 days (mean 123 days). Seven of the 8 patients eligible for discharge from the hospital with a vented-electric LVAD were supported at home while awaiting transplantation. Outcomes of LVAD support were: LVAD explantation in 2 cases (15%), expiration with LVAD in place in 3 cases (23%), and successful transplantation in 8 cases (62%). Complications included 4 patients with systemic infection, 3 re-operations for hemorrhage, 1 embolic event, and 1 intraoperative air embolus that proved fatal. One explanted patient required a subsequent LVAD and the other expired 4 months after explantation. Six of the 8 transplanted patients are alive and well with follow-up ranging from 8 to 43 months. CONCLUSIONS: Adolescent patients with heart failure can be successfully supported on a long-term basis to heart transplantation with the HeartMate LVAD. The wearable device allows for discharge home while awaiting transplantation. Device explantation without subsequent transplantation can be unpredictable. The incidence of thromboembolism remains low despite the absence of systemic anticoagulation. The technique of prosthetic graft closure of the abdominal wall facilitates the use of this device in smaller patients.

Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients.

BACKGROUND: The objective of this study was to assess the relationship between Epstein-Barr virus (EBV) infection and posttransplantation lymphoproliferative disease (PTLD) in pediatric heart transplant recipients. EBV is implicated in the development of PTLD. However, the relationship between primary EBV infection and PTLD is not well understood. METHODS: Serial EBV titers were determined prospectively in 50 children before and after heart transplantation. Results were correlated with the development of PTLD. The clinical presentation, management, and outcome of PTLD were characterized. RESULTS: Before transplantation, EBV titers were positive in 19 and negative in 31 patients. After transplantation, all EBV-positive patients remained positive; 1 developed PTLD. Among EBV-negative patients, 12 of 31 remained negative; none developed PTLD. Nineteen patients demonstrated serologic evidence of primary EBV infection after heart transplantation; 12 developed PTLD. Mean follow-up after heart transplantation was 3.3 years (range 0.4 to 8.4 years). Mean time from heart transplantation to histologic confirmation of PTLD was 29 months (range 3 to 72 months). Survival with PTLD was 92%. CONCLUSIONS: Twelve of 13 pediatric heart transplant recipients who developed PTLD had evidence of primary EBV infection. Serial monitoring of EBV titers may lead to earlier identification and improved treatment of PTLD.

Biventricular assist device as a bridge to transplantation in a pediatric patient.

A 5 1/2-year-old boy with idiopathic cardiomyopathy and rapidly worsening hemodynamic parameters underwent placement of a biventricular assist device as a bridge to transplantation. Direct anastomoses to both the aorta and pulmonary artery with Dacron grafts attached to Carmeda-coated tubing facilitated the support period. Inflow was provided by right atrial appendage and left ventricular apex cannulas. A centrifugal pump provided support for 2 days until a suitable donor was identified. The technique is simple, reproducible, and effective for patients with small body surface areas.

Experience with right ventricular assist devices for perioperative right-sided circulatory failure.

BACKGROUND: Right-sided circulatory failure remains a significant source of morbidity and mortality for both cardiac transplant and left ventricular assist device recipients. METHODS: We reviewed our experience with 11 patients who required a right ventricular assist device (RVAD) after either orthotopic heart transplantation or left ventricular assist device implantation. Variables analyzed included total time of RVAD support, hemodynamic and hematologic parameters, and parameters of end-organ perfusion. These were assessed at five time points: (1) at least 2 weeks before RVAD implantation, (2) intraoperatively just before RVAD insertion, (3) while on RVAD support, and, for those who survived, (4) just before RVAD explantation, and (5) off RVAD support. Survival was assessed as the ability to be weaned successfully from RVAD support. Urine output and serum transaminase levels were recorded throughout the period of RVAD support. RESULTS: Five patients received an ABIOMED 5000 BVS RVAD, and 6 received a Bio-Medicus centrifugal pump. Nine patients in the study underwent orthotopic heart transplantation and had development of right-sided circulatory failure from 0 to 96 hours after donor organ insertion, and 2 patients underwent left ventricular assist device implantation 12 to 48 hours before RVAD support. The mean time of RVAD support for survivors was 133.6 +/- 33.6 hours (range, 107 to 190 hours). Six patients were successfully separated from RVAD support, and 5 patients died while on RVAD support. Causes of death included sepsis (2), biventricular failure (2), and coagulopathy (1). Continuous arteriovenous hemodialysis was employed in 3 of 6 survivors and 1 of 5 nonsurvivors. CONCLUSIONS: Right ventricular assist devices work most effectively if implanted early enough to avoid significant, potentially irreversible end-organ injury. We liberally employ continuous arteriovenous hemodialysis, minimize the use of heparin immediately postoperatively, keep patients sedated, and continue RVAD support until the patient displays signs of hemodynamic and end-organ recovery as heralded by (1) a decrease in central venous pressure and, more importantly, a decrease in pulmonary artery diastolic pressure, (2) an increase in urine output, and (3) a decrease in serum transaminase levels.

Management of lymphoproliferative disorders after cardiac transplantation.

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.

Left ventricular assist device options in pediatric patients.

Left ventricular assist devices can be successfully used in the pediatric population if currently available devices are used appropriately. To highlight their management strategies, the authors' experience with pediatric left ventricular assist devices is reviewed, with case studies documenting options for device use. A retrospective study was conducted for all patients supported at the authors' institutions. Nine pediatric patients received devices during this time, with ages ranging from 12 days to 15 years. There was considerable size differences in our patients, with weights ranging between 2.5 and 73 kg. Either the Abiomed BVS 5000 (Abiomed Cardiovascular, Inc, Danvers, MA) or the Biomedicus centrifugal pump (Bio-Medicus, Inc, Eden Prairie, MN) were used for all patients. Patients were supported for an average of 5 days (range 1-11 days). Eight patients were successfully weaned from the device, with four undergoing transplant. Four patients were discharged and are long-term survivors, and one is still recovering post transplant. Neurologic sequelae were the most common complications in these patients, with four patients having events. Pediatric ventricular assist devices are limited because of size considerations, although current devices can be successfully used for bridging to recovery or transplantation. New devices are needed to meet the flow and size characteristics for pediatric patients. Successful use of assist devices, as has been recognized in adults, is possible in pediatric patients if these requirements are met.