A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

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.

Fate of infants with hypoplastic left heart syndrome listed for cardiac transplantation: a multicenter study.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) commonly undergo cardiac transplantation as primary management. METHODS: We examined outcomes of primary transplantation for unpalliated HLHS. We analyzed data from the 20 institutions of the Pediatric Heart Transplant Study Group, from January 1, 1993, through December 31, 1998, using actuarial and parametric survival analysis and competing outcomes analysis. RESULTS: During the 6 years studied, 1,234 patients were listed for cardiac transplantation; 262 patients (21.2%) had unpalliated HLHS. The number (and percentage) of patients with HLHS decreased from 58 (27% of patients listed) in 1993 to 30 (14%) in 1998. Overall, 25% of infants with HLHS died while waiting; primary cause of death was cardiac failure (50%). Of the remaining patients awaiting transplantation, 23 (9%) underwent Norwood/Fontan-type surgeries as interim palliation: 52% died. Ultimately, 175 patients underwent cardiac transplantation (67%); 50% received organs by 2 months after listing. Post-transplant actuarial survival was 72% at 5 years, with 76% of deaths (35/46) occurring within 3 months; early mortality was caused primarily by graft failure within the first 30 days after transplantation (in 54%). Among 1-month survivors, survival at 1 and at 5 years was 92% and 85%, respectively. Of the 262 patients listed with unpalliated HLHS, overall survival, taking into account mortality after listing and after transplantation, was 68% at 3 months and 54% at 5 years. CONCLUSIONS: Cardiac transplantation offers good intermediate survival for infants with unpalliated HLHS.

Invasive pneumococcal infections in pediatric cardiac transplant patients.

BACKGROUND: Bacterial infections cause significant morbidity and mortality in cardiac transplant patients. Because Streptococcus pneumoniae is the most prominent bacterial pathogen of childhood, the objective of this study was to define the role of S. pneumoniae as a pathogen in the cardiac transplant population. METHODS: Medical records of cardiac transplant patients from March, 1990, through November, 2000, were reviewed to identify invasive pneumococcal infections after transplantation. Demographic, clinical and microbiologic data were reviewed. RESULTS: Nine (11%) of 80 patients had 12 episodes of pneumococcal bacteremia for an incidence rate of 39 cases/1,000 patient years. Patients who were African-American, transplanted before 2 years of age and transplanted because of idiopathic dilated cardiomyopathy were at increased risk of invasive pneumococcal disease (P < 0.05). Six patients were eligible for the 23-valent pneumococcal polysaccharide vaccine before their first invasive infection, but only 1 had received it at the recommended age. Most isolates (82%) were penicillin-susceptible, and no single serotype predominated. There were 2 deaths in the study group, but each was unrelated to infection. Three patients (33%) had recurrent invasive disease with a second serotype an average of 12 months after the first infection. CONCLUSIONS: The incidence of pneumococcal bacteremia in cardiac transplant patients is higher than in the general pediatric population. Risks for infection were being African-American, being younger than 2 years at the time of transplant and being transplanted because of idiopathic cardiomyopathy. It is plausible that pneumococcal vaccine would decrease this risk.

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.

Exercise capacity in children with hypertrophic cardiomyopathy and its relation to diastolic left ventricular function.

Left ventricular diastolic impairment is often seen in children with hypertrophic cardiomyopathy regardless of left ventricular outflow tract obstruction. Such impairment in diastolic filling is related to the presence of symptoms and exercise impairment.

Cardiomyopathy and heart transplantation in children.

Cardiomyopathy is one of the most common causes of death in children with heart disease. Increasingly, dilated cardiomyopathy is recognized to be familial, and specific gene products related to the myocyte cytoskeleton and contractile proteins have been identified. Other associations with metabolic disease, dysmorphic syndromes, and neuromuscular disease are important to establish, particularly in pediatric patients, to guide therapy and patient selection for transplantation. Survival in children with dilated cardiomyopathy depends on accurate diagnosis and aggressive therapy. Patients may respond to conventional treatment for heart failure or may deteriorate, requiring mechanical support. Extracorporeal membrane oxygenation has been used effectively for mechanical support in children until improvement occurs or as a bridge to transplantation. For those who are listed, the mortality rate while waiting for a donor organ averages approximately 20%. Survival after transplantation is good, with an intermediate survival rate of approximately 70%. Late survival remains to be determined in the current cyclosporin era but may in fact be improving. However, increased organ donation or strategies to increase the size of the organ donor pool, such as xenotransplantation, are needed to significantly reduce the rate of mortality while waiting.

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.

Safety and efficacy of intravenous adenosine for pharmacologic stress testing in children with aortic valve disease or Kawasaki disease.

This study assessed the safety and efficacy of intravenous adenosine used as a coronary vasodilator in 18 pediatric patients with aortic valve disease or Kawasaki disease. Adenosine infusion effectively produced coronary vasodilation and was well tolerated.

Development of superior vena cava to pulmonary vein fistulae following modified Fontan operation: case report of a rare anomaly and embolization therapy.

A patient with double inlet single ventricle, L-transposition of the great arteries, and atrioventricular valve regurgitation developed progressive heart failure necessitating modified Fontan operation at 16 months of age. The procedure included replacement of the atrioventricular valve and pacemaker insertion. Eight years following the operation, the patient developed progressive cyanosis. Catheterization confirmed the presence of fistulae from the superior vena cava and innominate vein to the pulmonary veins as the cause of cyanosis. Coil embolization of several fistulae was performed successfully at catheterization. Contributing factors for fistula formation in Fontan patients are discussed, and therapy is reviewed.

Myocardial flow reserve in long-term survivors of repair of anomalous left coronary artery from pulmonary artery.

OBJECTIVES: This study sought to evaluate regional myocardial flow reserve in long-term survivors of repair of anomalous left coronary artery from pulmonary artery (ALCAPA) and to relate the flow abnormalities to the patients' exercise performance. BACKGROUND: Patients with ALCAPA usually present during infancy with severe ischemic cardiomyopathy. The left ventricular function recovers after surgical repair. However, the extent of recovery of myocardial blood flow (MBF) and its potential physiologic significance in long-term survivors are unknown. METHODS: We evaluated MBF (ml/g per min) at baseline and during maximal coronary vasodilation by adenosine in 11 patients after ALCAPA repair (median age 17 years, range 7 to 22) using nitrogen-13 ammonia and dynamic positron emission tomographic imaging. Patients also underwent an incremental exercise test with metabolic monitoring. In each patient, MBF was quantified in the three major vascular territories: the left anterior descending and left circumflex coronary artery territories and the right coronary artery (control region) territory. RESULTS: Basal MBF was mildly reduced in the left coronary territories versus the control region (0.79 +/- 0.14 vs. 0.85 +/- 0.19, p = 0.05). During hyperemia, flow in the left coronary territories was significantly lower than that in the control region (2.1 +/- 0.5 vs. 2.6 +/- 0.5, p < 0.001). As a result, myocardial flow reserve was lower in the left coronary territories than in the control region (2.6 +/- 0.7 vs. 3.2 +/- 0.7, p < 0.001). Exercise performance was impaired in patients when compared with age-matched control subjects. Maximal oxygen consumption correlated linearly with maximal hyperemic flows in the left coronary artery territories (r = 0.73, p = 0.03). CONCLUSIONS: Long-term survivors of ALCAPA repair demonstrate regional impairment of myocardial flow reserve. This may contribute to impaired exercise performance by limiting cardiac output reserve.

Arch growth after staged repair of interrupted aortic arch using carotid artery interposition.

BACKGROUND: Between 1980 and 1990, our practice was to perform carotid artery interposition as part of a staged repair of interrupted aortic arch with various associated cardiac defects. METHODS: This procedure was used in 16 patients with IAA type B. The median age at operation was 4.5 days and the median weight, 3.2 kg. Ten of the patients had an associated ventricular septal defect. Six more had complex anatomy. There were two death at carotid interposition, two interim deaths, and two deaths after intracardiac repair. Preoperative echocardiographic and angiographic studies were compared with postoperative studies in 11 survivors of arch repair to assess sequential growth of the interposed carotid artery. Measurements of the carotid artery were normalized to the descending aorta. RESULTS: Preoperatively, the left carotid artery had a median diameter of 3.7 mm and was 42.9% of the descending aortic diameter. Postoperative studies performed at a median age of 5.7 months disclosed that the interposed carotid artery had grown to a median diameter of 7.0 mm and was 69.6% of the diameter of the descending aorta (normal > or = 81%). On follow-up at a median time of 4 years, 6 of 9 patients have no gradient by blood pressure measurements or echocardiographic Doppler studies, and 3 have modest gradients. No patient has required revision of the arch repair. CONCLUSIONS: Survival is good after carotid artery interposition for interrupted aortic arch and growth of the carotid artery approaches that of a normal arch. Carotid artery interposition is a viable alternative for repair of this lesion should primary definitive repair not be feasible.

Predicting outcome after listing for heart transplantation in children: comparison of Kaplan-Meier and parametric competing risk analysis. Pediatric Heart Transplant Study Group.

After listing for pediatric heart transplantation, at any point in time one of the following possibilities could have occurred; death, transplantation, removal from the list because of clinical improvement, or continuing to wait. In the setting of those competing outcomes, the Kaplan-Meier estimate portrays the time-relatedness of an event while ignoring the effect of the other possible outcomes. The competing outcomes method, however, depicts the time relatedness of an event while solving for all possible events simultaneously. The competing outcomes method may potentially provide more accurate information regarding the actual proportion of patients experience an outcome after listing.

Coil occlusion versus conventional surgical closure of patent ductus arteriosus.

This retrospective cohort study evaluated the clinical outcome and cost-effectiveness of 2 treatment strategies for children with an isolated restrictive patent ductus arteriosus. Results indicate a superior cost-effectiveness of transcatheter coil occlusion compared with conventional surgery for these patients.

Reduced radiation during cardiac catheterization of infants using acquisition zoom technology.

The new digital technology of obtaining images in an AZ mode effectively reduces the radiation dose to infants undergoing cardiac catheterization. Future software advances in this technique should enhance the image quality and potentially broaden its application to older patients.

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.

Outcome of listing for heart transplantation in infants younger than six months: predictors of death and interval to transplantation. The Pediatric Heart Transplantation Study Group.

BACKGROUND: The major limiting factor to successful heart transplantation in infants is the limited supply of donors. To examine the impact of donor limitations on survival after listing, a multiinstitutional study was designed to identify risk factors for death while waiting and for longer interval to transplantation. METHODS: Between January 1 and December 31, 1993, 118 infants 6 months of age or younger (86 younger than 29 days) were listed for heart transplantation from 21 institutions. The primary diagnosis was hypoplastic left-sided heart syndrome (HLHS) in 70 (59%), other congenital defects in 32 (27%), cardiomyopathy or myocarditis in 13 (11%), and other diagnoses in 3. Among the 48 patients without HLHS, 32 (67%) required inotropic, mechanical, or prostaglandin support, whereas 16 (33%) did not. RESULTS: At 6 months after listing, only 6% remained on the list awaiting transplantation, 59% underwent transplantation. 31% died while waiting, and 4% were removed from the list. The greatest mortality rate before transplantation was among patients with HLHS in whom the actuarial mortality rate if they were unable to receive a transplant was 77% at 6 months, compared with 52% in patients without HLHS and without inotropic or mechanical support (p = 0.05). By multivariable analysis, risk factors for death while waiting included inotropic support (p = 0.02), smaller size (p = 0.0007), and blood type O (p = 0.003). Surgical procedures before listing did not significantly influence pretransplantation mortality rates. The interval from listing to transplantation increased with young age (p = 0.01) in patients without HLHS and smaller size (p = 0.001) and blood group O (p = 0.0006) for patients with HLHS. The effect of blood type O on mortality rates and longer interval to transplantation was due to the distribution of type O donor hearts to non-type O recipients. Palliative operations after listing did not favorably influence survival; nine patients underwent first-stage Norwood while waiting, and six died before transplantation. CONCLUSIONS: The mortality rate is unacceptably high among infants awaiting transplantation, particularly in patients with HLHS. Infants receiving intravenous inotropes or mechanical support at listing are at high risk of early death while waiting. The distribution of blood group O donors to non-blood group O recipients results in higher mortality rates among blood group O recipients. Greater emphasis should be placed on medical strategies to improve survival while waiting and on expanding existing graft resources.

Acute results of balloon angioplasty of native coarctation versus recurrent aortic obstruction are equivalent. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry Investigators.

OBJECTIVES: This study sought to compare the immediate results and risk factors for suboptimal outcomes of percutaneous balloon angioplasty for native versus recurrent aortic obstruction. BACKGROUND: Some cardiology centers have been reluctant to adopt balloon angioplasty for treatment of native aortic coarctation, while advocating balloon angioplasty over an operation for treatment of postsurgical or recurrent aortic obstruction. METHODS: Acute results were analyzed from 970 procedures (422 native and 548 recurrent lesions) performed between 1982 and 1995 in 907 patients from 25 centers. An acute suboptimal outcome was defined as one or more of the following: residual systolic pressure gradient > or = 20 mm Hg, residual proximal to distal systolic pressure ration > or = 1.33 or a major complication (death, aortic transmural tear, stroke). RESULTS: Bal loon angioplasty significantly (p = 0.0001) increased lesion diameter fo r both native (mean [+/= SD] 128 +/= 94%) and recurrent aortic obstruction (97 +/= 87%), with a significantly greater increase in the native group (p = 0.0001). A reduction in systolic pressure gradients was significant in both groups (p = 0.0001), but slightly higher (p = 0.01) for native (-74 +/- 24%) versus recurrent obstruction (-70 +/- 31%). Death associated with angioplasty was reported in 0.7% of patients with native and in 0.7% of patients with recurrent lesions (p = 1.00). An acute suboptimal outcome was noted with angioplasty in 19% of native and in 25% of recurrent lesions (p = 0.04). Significant independent risk factors included higher preangioplasty systolic gradient (odds ratio [OR] 1.39/10-mm Hg increment; 95% confidence interval [CI] 1.28 to 1.50, p = 0.0001), earlier study date (OR 0.92/1-year increment, 95% CI 1.02 to 1.26, p = 0.02) and recurrent obstruction (OR 1.39 vs. native lesions, 95% CI 1.00 to 1.94, p = 0.05). CONCLUSIONS: Acute results and complications of balloon angioplasty of native coarctation appear to be equivalent or slightly superior to those of recurrent aortic obstructions.