Prospective evaluation of echocardiography for primary rejection surveillance after infant heart transplantation: comparison with endomyocardial biopsy.

Rejection surveillance is critical to successful heart transplantation, and infant recipients have necessitated the use of noninvasive measures. The survival, incidence of rejection, and accuracy of echocardiography in predicting treatable rejection, as detected on right ventricular endomyocardial biopsy, were prospectively studied in infants. The survival rate (82%) and rejection rate (1.4 rejection episodes per 100 patient days) of infants who underwent transplantation during the study were comparable to other studies that used heart biopsy only. Echocardiography was 98% accurate at predicting biopsy results. The sensitivity of echocardiography was 92%, and the specificity was 98%. We conclude that echocardiography can be used successfully for primary rejection surveillance in infants and that right ventricular biopsy is infrequently required.

Donor shortage: use of the dysfunctional donor heart.

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, LVSF > 28%). 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.

Serial echocardiographic evaluation of cardiac graft rejection after infant heart transplantation.

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 (p < 0.01). 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 (p < 0.05) 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, p < 0.05) 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, p < 0.05). The utility of these echocardiographic measurements to predict rejection has not been prospectively compared with the endomyocardial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in left ventricular mass with rejection after heart transplantation in infants.

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.

Cardiac transplantation in infancy: donors and recipients. Loma Linda University Pediatric Heart Transplant Group.

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.

Late hemodynamic results after orthotopic heart transplantation in early infancy.

To study the late hemodynamic results after infant orthotopic heart transplantation, five late survivors, as of October 1988, underwent right and left cardiac catheterization and endomyocardial biopsy. Mean age at transplantation was 1.4 +/- 1.5 months. Mean post-transplantation period was 17 +/- 5.6 months. All patients were on maintenance immunotherapy. The systemic and mixed venous saturations were normal, with no intracardiac shunt. The atrial and pulmonary artery anastomoses were widely patent. Three patients had coarctation of the aorta with a respective gradient of 24, 26, and 30 mm Hg; two were successfully treated by balloon angioplasty. The right-side hemodynamics were normal in all patients. Left ventricular pressures were elevated only in the patients with coarctation. The ventricular ejection fraction was normal. The right ventricular endomyocardial biopsy revealed no evidence of rejection. The mean cardiac index was 4.7 liter/min/m2 (range, 3.68-5.9). These data indicate excellent hemodynamic results and support orthotopic heart transplantation as therapy for selected neonates and infants with incurable heart disease.

Orthotopic transplantation during early infancy as therapy for incurable congenital heart disease.

Since November 1985, 14 neonates and young infants have undergone orthotopic heart transplantation at Loma Linda University Medical Center (LLUMC) as therapy for hypoplastic aortic tract complex. Eleven (78%) survived surgery and are living and well today. Three perioperative deaths resulted: one due to perforated peptic ulcer, one due to necrotizing pneumonitis, and one due to graft failure unrelated to rejection. No late deaths occurred in the 1-29 months of follow-up, during which time noninvasive surveillance techniques were used. Immunosuppression was accomplished using cyclosporine and azathioprine. Steroids and antithymocyte globulin were used for identified rejection episodes only. Ordinary childhood infections were tolerated well. All survivors were normotensive. There was no late renal dysfunction. Although inadequate donor resources remain a significant limiting factor for transplantation therapy during early life, these results suggest that cardiac transplantation is effective therapy for selected neonates and young infants with incurable congenital heart disease.