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Studies from a number of centers have documented the growth and success of pediatric heart transplantation. The 1st year of life is the period of greatest mortality from congenital heart disease and has now become the single most frequent age of pediatric heart transplantation. Appropriately, congenital heart disease is the most common diagnosis leading to heart transplantation. Early mortality is still greatest in recipients who undergo transplantation during the 1st year of life. The patients at greatest risk are being identified and new maneuvers to lower early mortality are emerging. Long-term follow-up continues to indicate excellent late survival with low morbidity. This review focuses on key advances in knowledge reported in the last year.

Transplant surgeons are reluctant to use hearts that have undergone cardiopulmonary resuscitation for cardiac arrest because of the fear of poor early and late cardiac function. A policy of minimizing contraindications to use of donor hearts has led to the unique opportunity of assessing the effects of donor arrest and successful cardiopulmonary resuscitation on early and late cardiac function in pediatric heart transplantation. A number of 140 infants and children undergoing transplantation from birth to 17 years of age were studied retrospectively and divided into two groups on the basis of cardiopulmonary resuscitation status. Group 1 (72 patients) received donor hearts that were not subjected to cardiopulmonary resuscitation; group 2 (68 patients) received donor hearts that had cardiopulmonary resuscitation for a mean of 18.8 +/- 14.6 minutes, the longest period of time being 60 minutes. Mean ischemic times were almost identical in the two groups: 4.43 +/- 2.0 hours (cardiopulmonary resuscitation) versus 4.5 +/- 2.1 hours (no cardiopulmonary resuscitation). Early cardiac function was assessed on the basis of the number of days the recipient was supported by the ventilator, days receiving dopamine, days receiving isoproterenol, and the amount of inotropic agents required after the operation. The groups did not differ. Parameters of systolic function included fractional shortening, posterior wall thickening, and maximum velocity of change in left ventricular posterior wall dimension during systole. Diastolic function was measured on the basis of left ventricular end-diastolic volume, left ventricular mass, and maximum velocity of change in left ventricular posterior wall dimension during diastole. Both systolic and diastolic function were measured and analyzed from M-mode echocardiography at 1 week, 1 month, 6 months, 1 year, and 2 years after the operation. There were no statistically significant differences in graft function between the two groups in any of the echocardiographic parameters studied, even at 2 years. No group differed from ranges of normal. Our results suggest that hearts undergoing cardiopulmonary resuscitation for periods of up to 60 minutes can be used safely without evidence of deterioration of early or late cardiac function.

The cause of brain death and the physiologic sequelae of brain death may impair heart function. Pharmacologic attempts to maintain donor viability may further jeopardize myocardial performance and could only be justified if dysfunctional donor organs subsequently prove to recover normal function after transplantation. Survival data on heart transplantation with organs donated from infants with sudden infant death syndrome indicate that prolonged ischemia (cardiopulmonary resuscitation up to 60 minutes) and metabolic abnormalities a priori do not increase the risk of graft failure. To provide a donor organ to infants in immediate peril, we have used donor hearts with documented dysfunction (left ventricular shortening fraction [LVSF]28%, wall motion abnormalities, and mitral regurgitation). The results of heart transplantation with use of dysfunctional donor hearts (n = 22, LVSF = 24.5% +/- 3%) were compared with donors with normal left ventricular function (n = 133, LVSF28%). Early death (30 days) was similar for the dysfunctional donor group (14%) and normal function donor group (11%). Postoperative inotropic support was equally frequent in both groups. Graft function on echocardiography was normal at 30 days after transplantation for both types of donor organs. We conclude that donor hearts with decreased left ventricular function (LVSF 15% to 28% and/or asymmetric wall motion), despite massive inotropic support, can function normally in the recipient. Significant donor mitral regurgitation was seen in grafts that ultimately failed after transplantation. Research into the reversible mechanisms of myocardial dysfunction associated with brain death could enlarge the donor pool.

Heart transplantation uniquely offers infants with irreversible myopathies and complex congenital heart disease (CCHD) the potential for survival. Heart transplantation in the first year of life has an actuarial 1-year survival rate of 85%. Controlling for the variables that lead to perioperative death can improve 1-year survival rates to 95%. Mortality is also accrued before transplantation, with 15% to 20% of infants dying before a donor organ is available. Because of this cumulative mortality, an algorithm was developed to maximize pre- and posttransplantation survival and thus increase the likelihood that the limited donor supply would have the greatest impact. The risk factors considered in the algorithm include: (1) hemodynamic stability, (2) central venous access/prostaglandin requirements, (3) need for ventilator support, (4) pulmonary blood flow dependent on a critically restricted atrial septal defect, (5) risk for pulmonary hypertension, (6) anomalous pulmonary venous return, and (7) history of sepsis. Overall, patient survival would be maximized by only using transplantation for patients with CCHD who have moderate or less risk of pre- or posttransplantation death (20%). Donor organ utilization could be maximized by reserving transplantation for patients without options (myopathies) and for patients with CCHD who have a low predicted risk of death (10%). Because the risks of death at transplantation or in the first year after transplantation are low and relatively fixed, changes in risks of palliative surgery or donor availability can be easily used to adjust the decision algorithm.

In patients who have undergone successful orthotopic heart transplantation, echocardiography has the potential to be a noninvasive method for rejection surveillance that would reduce the frequency and guide the timing of endomyocardial biopsies, as well as allow for more frequent monitoring, with less cost and risk to the patient. To determine the applicability of echocardiography to detect moderate to severe rejection in children, 26 two-dimensional-guided M-mode echocardiograms with Doppler/color flow mapping were performed within 24 hours of endomyocardial biopsy. M-mode echocardiograms of the left ventricle were digitized and analyzed with a computer-assisted measurement format for left ventricular size, mass, and wall motion in systole and diastole. These echocardiographic parameters were clustered and analyzed by a unique echocardiographic scoring algorithm blinded to the biopsy interpretation. In eight cases in which findings of biopsies were consistent with moderate to severe rejection, left ventricular mass was increased and indexes of systolic and diastolic function were depressed compared with the remainder of the cases (n = 18), in which findings of biopsies included either no evidence or mild evidence of rejection. The echocardiographic score of the group with moderate to severe rejection was significantly greater than the score of the group that was normal or had mild rejection (5.4 +/- 0.7 vs 2.2 +/- 0.3; p0.001). With rejection prospectively defined as an echocardiographic score of greater than or equal to score 4, echocardiography achieved 88% sensitivity and 83% specificity in detecting moderate to severe rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients who have undergone successful orthotopic heart transplantation, a noninvasive method for rejection surveillance would reduce the frequency of endomyocardial biopsy, guide the timing of biopsies, and allow for more frequent monitoring. This study identified the pattern of change in echocardiographically determined indexes of left ventricular mass, volume, and function that characterized biopsy-positive acute rejection in adult heart transplant patients receiving triple-drug immunosuppressive therapy and describes a simple computer-driven algorithm capable of identifying rejection with high sensitivity and specificity. Two-dimensional and M-mode echocardiography and Doppler color flow analyses were performed within 24 hours of endomyocardial biopsy. M-mode echocardiograms of the left ventricle were digitized and analyzed blinded to the biopsy interpretation, using a computer-assisted measurement format, for size, mass, and wall motion in systole and diastole. Twenty-nine studies were retrospectively analyzed to define the echocardiographic pattern characteristic for rejection. Left ventricular chamber size decreased, and indexes of diastolic function were significantly depressed in patients with biopsy evidence of moderate or severe rejection. However, no single parameter was sufficiently sensitive to detect all episodes of rejection partly because of differences between patients in the echocardiographic manifestations of acute rejection. To accommodate this patient variability, multiple echocardiographic parameters were clustered into a unique scoring algorithm (ECHO score). When applied prospectively to 49 studies, the likelihood that a patient would have an ECHO score not indicative of rejection but with moderate/severe rejection on biopsy was low (less than 3%) or a negative predictive value of 97.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of cardiac graft rejection on infant myocardial function as assessed by echocardiography are largely unknown. To quantitate the myocardial response to rejection, serial echocardiographic studies were prospectively performed on 20 infants (less than 1 year of age at transplantation). Two-dimensional guided-M-mode tracings were digitized and quantified with a computer-assisted format. Rejection was diagnosed by clinical criteria, and 85% were graded as mild, that is without cardiac signs or symptoms. Echocardiographic analysis was blinded to rejection status, with studies available 4.2 +/- 2.9 days before rejection, on the day of rejection diagnosis, and 2.9 +/- 1.5 days after rejection treatment. Left ventricular mass increased acutely from 109% of predicted normal to 129% with rejection and decreased to 110% with therapy (p0.01). Left ventricular volume also tended to fall with rejection and increase with therapy. The left ventricular volume/mass ratio fell from 0.29 +/- 0.10 to 0.25 +/- 0.13 and increased to 0.37 +/- 0.15 (p0.05) with treatment. Systolic function was depressed by rejection as reflected in the posterior wall thickening fraction and velocity of wall thickening. Diastolic dysfunction was reflected in a decreased velocity of posterior wall thinning (-9.7 +/- 3.9 to -7.7 +/- 2.7 and recovery to -10.8 +/- 3.8 (1/second, p0.05) and depressed average velocity of cavity enlargement (41.2 +/- 9.6 to 36.4 +/- 8.9 and recovery to 40.7 +/- 8.6 mm/sec, p0.05). The utility of these echocardiographic measurements to predict rejection has not been prospectively compared with the endomyocardial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Early age at cardiac transplantation may favor successful engrafting with minimal chronic immunosuppression. Fifty-two newborns underwent orthotopic heart transplantation; 47 (90%) survived the operation, and 44 (85%) were late survivors. Actuarial survival was 92% at 1 month, 86% at 1 year, and 84% at 5 years. Forty-four infants who survived 12 weeks and the corresponding 100 rejection episodes were analyzed. Mean follow-up was 2.2 years. The mean number of rejections per year of follow-up was 1.2. No episodes of rejection were identified in six patients. Seven patients had a late rejection episode more than 1 year after transplantation, and only one had a late rejection episode after 2 years. Neonatal cardiac transplantation is effective and durable therapy for uncorrectable heart disease. Intermediate-term results are excellent. Severe rejection is uncommon, and few episodes occur after 1 year of follow-up.

We studied the feasibility of transesophageal echocardiography to guide endomyocardial biopsies in five heart transplant patients and two baboons with heart transplantations. The patients were 1 month to 1.5 years old with weight range of 2.9 to 9.5 kg. The two juvenile baboons weighed 6.6 and 7 kg. Transesophageal echocardiography was performed uneventfully in all cases with the use of sedation and anesthesia, which were necessary for catheterization. The combination of four-chamber and short-axis views easily identified the exact location of the bioptome within the heart, views that fluoroscopic imaging could not provide. Transesophageal echocardiography proved to be a safe and useful tool for guiding the endomyocardial biopsy procedure. With further refinement endomyocardial biopsy with only transesophageal echocardiography guidance could become the routine method for endomyocardial biopsies in infants, particularly when there are abnormalities of heart situs or position.

Thirty-three infants who underwent successful heart transplantation before 6 months of age were studied to evaluate subacute changes in left ventricular mass (LVM) and its correlation to a history of rejection episodes. LVM and left ventricular wall mass (LVWM) and their percentage of predicted normal values were analyzed by means of M-mode echocardiography. LVM (as a percentage of predicted normal for body surface area) at 1 week, 1 month, and 3 months after transplantation was 103.2% +/- 24.5%, 137.3% +/- 36.0%, and 138.6% +/- 32.0%, respectively. Values for the wall mass were 82.1% +/- 23.0%, 111.3% +/- 35.7%, and 104.6% +/- 30.4%. After 1 and 3 months, both LVM and LVWM were significantly (p less than 0.01) increased from the values in the first week. The patients were subdivided on the basis of a history of rejection. There were six patients without a rejection episode within 1 month (group 1), 17 patients with one rejection episode (group 2), and 10 patients with two or more episodes (group 3). LVM at 1 month was 104.5% +/- 27.7% for group 1, 142.5% +/- 27.7% for group 2 (p less than 0.05), and 148.9% +/- 31.3% for group 3 (p less than 0.05). LVWM at 1 month was 83.4% +/- 24.6%, 114.8% +/- 35.3%, and 122.2% +/- 36.2% (groups 1 through 3, respectively). Thus an increase in posttransplant LVM may signify a rejection episode. Heart transplantation in infancy increases LVM and LVWM (septum and posterior wall); the degree of thickening of septum correlates well with rejection episodes.

We examined the early and late results of operations in 29 consecutive neonates with pulmonary atresia and intact ventricular septum treated from 1980 to 1988. Transventricular pulmonary valvotomy and central aorta-pulmonary artery shunting were performed in 19 of 22 infants who had a patent infundibulum. Pulmonary valvotomy alone was performed in 3 of the 22 infants with a patent infundibulum, but 2 of these required subsequent systemic-pulmonary artery shunts. Primary shunting was used to palliate 7 infants who had absent infundibular portions of the right ventricle and a very diminutive right ventricular cavity. Tricuspid valve excision and atrial septectomy were also performed in 5 of these 7 infants to decompress large fistulous communications between the right ventricule and coronary artery. Two early deaths (2/29, 6.9%) occurred overall. Both were in infants who had a very small right ventricle. Definitive operation has been accomplished in 16 patients; 13 have had closure of residual interatrial communications and shunt ligation with no deaths, and 3 have undergone modified Fontan repair with 1 death. Actuarial survival rate for the entire group, including operative deaths, is 86% at 5 years. The technique of transventricular pulmonary valvotomy and systemic-pulmonary artery shunting offers a reliable means of palliating neonates with pulmonary atresia and intact ventricular septum and obtains good late right ventricular growth. Systemic-pulmonary shunting, tricuspid valvectomy, and atrial septectomy may offer a means of reducing or obliterating right ventricular-coronary artery fistulas.

To evaluate the role of orthotopic cardiac transplantation for infants with lethal cardiac disease, we reviewed the results from our first 25 patients. Data on the donors were also reviewed to define the characteristics of a successful cardiac donor. Patients had transplants between November 1985 and November 1988. Several primary cardiac diagnoses were indications for transplantation, including congestive cardiomyopathy, hypoplastic left-heart syndrome, and other types of native and postoperative complex congenital heart diseases. The ages ranged from birth to 7 months. Of 25 patients, 21 are still alive (84% survival rate) with follow-up from 4 to 40 months. No late deaths have occurred. Long-term immunosuppression was accomplished with cyclosporine and azathioprine. Rejection surveillance was performed noninvasively; only one child required an endomyocardial biopsy. Donors died from a variety of traumatic and metabolic causes, including sudden infant death syndrome. The majority (72%) of donors had a history of cardiac arrest requiring cardiopulmonary resuscitation. One third were receiving inotropic support at the time of cardiac evaluation. We conclude that orthotopic cardiac transplantation is an effective therapy for infants with lethal heart disease. A larger donor pool is required, and many dying infants, despite cardiac arrest and resuscitation, would be suitable donors.

We studied the response of the renin-angiotensin system (RAS) to a surgically created ventricular septal defect (VSD) in immature ovines and also the role of angiotensin II in the pathophysiology of VSD in the chronically instrumented ovine. Plasma renin activity (PRA) was increased from 2.39 +/- 1.1 to 3.78 +/- 1.4 ng/ml/hr (p less than 0.05, n = 17) after VSD but not after sham procedure. The change in PRA was positively correlated with the amount of left-to-right shunt through the VSD (r = 0.74, p less than 0.05). Inhibition of angiotensin II effect with saralasin (10 micrograms/kg/min) or angiotensin II production with captopril (2 mg/kg) lowered systemic resistance (Rs) by 14% and 34%, respectively (p less than 0.05), and raised pulmonary resistance (Rp) by 35% and 77%, respectively (p less than 0.05). Thirty minutes following captopril, the ratio of pulmonary to systemic flow (Qp/Qs) decreased from 3.31 +/- 0.18 to 2.15 +/- 0.18 (p less than 0.05) while total pulmonary flow fell from 7.15 +/- 0.38 to 5.92 +/- 0.34 l/min/M2 (p less than 0.05, n = 11). Systemic flow increased from 2.17 +/- 0.14 to 2.86 +/- 0.33 l/min/M2 (p less than 0.05) despite a reduction in left atrial pressure (17.3 +/- 1.0 vs. 13.0 +/- 1.7, p less than 0.01). Reinfusion of angiotensin II (0.02 micrograms/kg/min) into the central aorta after captopril returned the hemodynamics to baseline including a rise in Rs and fall in Rp. Exogenous angiotensin II alone (0.08 micrograms/kg/min) or a threefold stimulation in PRA with furosemide (2 mg/kg) caused little hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

From November 1981 to November 1982, intra-aortic balloon pumping (IABP) was used after surgery in eight patients who were from 6 weeks to 6 years old and who weighed from 4.2 to 16.2 kg. In seven patients, specially constructed intra-aortic balloons with 2.5 and 5.0 ml volumes mounted on No. 5F catheters were used. In the largest and oldest patient, a two-chamber 10 ml balloon was used. The pumping module used was the Datascope System 82. Effective diastolic augmentation of arterial pressure was accomplished in seven of the eight patients and suprasystolic diastolic augmentation was accomplished in four. The two youngest and smallest patients are the only long-term survivors. There were two short-term survivors who died 5 and 10 days after successful IABP. In only one patient was there no appreciable effect of IABP. Miniaturization of the equipment has permitted IABP to be used effectively in pediatric patients.