Bosentan for increased pulmonary vascular resistance in a patient with single ventricle physiology and a bidirectional Glenn shunt.

We present a case of the successful use of bosentan for increased pulmonary vascular resistance (PVR) in a 10-year-old male who underwent late single ventricle surgical palliation for double-inlet left ventricle with pulmonary artery banding and a bidirectional Glenn shunt. The patient was treated with bosentan for 16 weeks, with decreases in mean pulmonary artery pressure from 23 to 16 mmHg on the right and from 31 to 21 mmHg on the left, and a decrease of the transpulmonary gradient by 7-8 mmHg. Cardiopulmonary exercise testing demonstrated an increase in peak oxygen consumption (VO2) by 8% and peak work rate by 10%. Bosentan is a relatively new oral therapy option for increased PVR in patients with single ventricle physiology and bidirectional Glenn shunts.

Predictors of graft longevity in pediatric heart transplantation.

Given the volume of pediatric orthotopic heart transplants (OHTs) at several centers, it is now possible to generate pediatric-specific, single-center OHT survival data. The transplant experience for 152 pediatric OHT patients at our institution was reviewed. The following were noted for each patient: graft survival; immunosuppressant therapy; initial diagnosis; cause of graft failure; clinical status at time of transplant; donor and recipient blood type, sex, weight, and age; ischemic time; previous cardiac surgery; race; and immune status. A series of Kaplan-Meier survival curves were constructed. Univariate comparisons of survival curves were performed with the Breslow test to determine equality of each pair of curves. Only immunosuppression with tacrolimus and an initial diagnosis of noncongenital heart disease positively influenced survival in pediatric OHT patients (p < or = 0.021 and p < or = 0.03, respectively). The more recently transplanted patients, managed with tacrolimus, had less mortality early after OHT (acute rejection) and less mortality during the period 2 or 3 years after OHT. No other factors, including prior cardiothoracic surgery, sex matching, and race matching, significantly influenced survival. Recently transplanted patients managed with tacrolimus-based immunosuppression and patients with noncongenital cardiomyopathy have significantly superior graft survival.

Echocardiographic findings of hypertrophic cardiomyopathy in children after orthotopic liver transplantation.

This study was carried out to compare echocardiographic findings of children taking tacrolimus and cyclosporin A (CsA) after orthotopic liver transplantation (OLT). Echocardiograms of 19 children were reviewed during hospitalizations after OLT, and echocardiograms were performed on 23 children who returned to the clinic for a routine follow-up visit after OLT. Measurements were made of the left ventricle (LV) end-diastolic dimension, and of the thickness of the LV free wall (LVFW) and the inter-ventricular septum (IVS). From these measurements, the LV mass was calculated. LV outflow gradient was measured by using Doppler interrogation. Comparisons were made between patients on CsA and patients on tacrolimus. Children with hypertrophic cardiomyopathy (HCM) were identified. Two patients from the in-patient tacrolimus group were found to have HCM. These two patients had asymmetric septal hypertrophy with dynamic LV outflow obstruction and were successfully treated with propranolol, with or without discontinuing tacrolimus. In the out-patient studies, there was no difference in LVFW and IVS thickness, or LV mass index, between children on CsA and children on tacrolimus. Hence, tacrolimus is associated with the development of HCM in children. The effect of tacrolimus on HCM development may be acute and temporary. More data are needed to determine the incidence of HCM in children on tacrolimus therapy and to establish guidelines for clinicians who follow-up these children.

Diagnosis and treatment of pediatric viral myocarditis.

Acute myocarditis is characterized by the rapid development of life-threatening congestive heart failure and arrhythmias. Although the initial stages of this disorder apparently result from direct cytopathic effects on the atrial and ventricular myocardium, later stages of progressive decompensation may result from immune-mediated myocyte destruction. There has been recent improvement in understanding the role of this immunologic cascade. As a result, treatment now begins earlier in the course of the disease and can target both the virus and the immune response. Our ability to implement mechanical support in children as a bridge to transplant or recovery, even in children presenting in the final stages of their disease, has led to an improved outcome regarding morbidity and mortality.

Use of OKT3 for acute myocarditis in infants and children.

Acute viral myocarditis triggers an autoimmune phenomenon that aggressive immunosuppressive therapy with monoclonal OKT3 may suppress. We treated 5 patients, aged 15 months to 16.5 years, who had acute viral myocarditis and left ventricular ejection fraction (LVEF) of 5% to 20%, with a combination immunosuppressive regimen that included OKT3, intravenous immunoglobulin, methylprednisone, cyclosporine, and azathioprine. Within 2 weeks of therapy, all patients demonstrated normalization of LVEF to 50% to 74%, and on mid-term follow-up, we have found no recurrence of heart failure or progression to dilated cardiomyopathy. In patients with severe acute myocarditis, aggressive immunosuppressive regimen based on OKT3 is safe and may inhibit or reverse the immune response, resulting in dramatic improvement in myocardial function.

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Transplantation for congenital heart disease.

Refinements in surgical technique, donor and recipient myocardial preservation, and immunosuppression have brought pediatric heart transplantation for end-stage heart failure (whatever the cause) from the heyday of clinical experimentation to the realm of a viable therapeutic. Heart transplantation in this subpopulation yields excellent early and midterm survival. Acute rejection remains an important cause of morbidity and mortality after heart transplantation in children. Future improvement in quality of life for these patients calls for newer immunosuppressive strategies to reduce acute rejection episodes and ultimately improve long-term graft survival.

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Three-dimensional helical CT of pulmonary arteries in infants and children with congenital heart disease.

OBJECTIVE: The purpose of our study was to determine the value of three-dimensional reconstructed helical CT in the assessment of the pulmonary arteries in infants and children with complex congenital heart disease. MATERIALS AND METHODS: Twenty patients were examined with contrast-enhanced helical CT. Three-dimensional reconstructions were performed with multiplanar reformations, maximum intensity projection, and shaded-surface display. Correlation was made with 19 echocardiograms and 14 cineangiocardiograms. All imaging studies were reviewed independently for the following parameters: the caliber of the main and branch pulmonary arteries and their confluence, the presence of stenosis, the number and caliber of aortopulmonary collaterals, and the patency of vascular shunts and conduits. Surgical confirmation, which was used as the reference standard, was available in all patients. RESULTS: Helical CT was as accurate as angiocardiography in revealing stenotic and nonconfluent central pulmonary arteries and in revealing aortopulmonary collaterals (overall CT test parameters: sensitivity, 90%; specificity, 100%; accuracy, 93%).Three-dimensional rendition did not improve the accuracy of CT. The patency of shunts was shown equally well with CT as with angiography, but CT showed thrombosis more directly. Echocardiography was the least accurate technique in revealing pulmonary artery anatomy (accuracy, 65%), primarily because a relatively large number of studies were technically unsatisfactory to assess the study parameters. CONCLUSION: Helical CT angiocardiography with three-dimensional reconstruction is superior to echocardiography for the noninvasive assessment of pulmonary artery anatomy in patients with complex congenital heart disease. Helical CT may be used as a complementary technique and occasionally as a substitute for the diagnostic imaging portion of cardiac catheterization with cineangiocardiography.

Bubble contrast echocardiography in detecting pulmonary arteriovenous shunting in children with univentricular heart after cavopulmonary anastomosis.

OBJECTIVES: We sought to compare bubble contrast echocardiography and pulmonary angiography in detecting pulmonary arteriovenous malformation (PAVM) in children with cavopulmonary anastomosis (CPA), and to examine anatomic and physiologic variables associated with the development of PAVM. BACKGROUND: Development of PAVM in patients with CPA may cause profound cyanosis. Pulmonary arteriovenous malformation has been traditionally diagnosed by pulmonary angiography with reported incidence of 20% to 25% in patients with CPA. METHODS: Fourteen patients (age 1.1 to 12.6 years) with any forms of CPA and normal pulmonary venous drainage formed the study population. All patients underwent cardiac catheterization and pulmonary angiography. Bubble contrast echocardiographic studies were performed with injection of 10 ml of agitated saline solution into branch pulmonary arteries. Transthoracic echocardiograms using an apical view were performed to assess the appearance of bubble contrast in the systemic ventricles. We compared the results of pulmonary angiograms and contrast echocardiograms, and findings of contrast echocardiograms between lungs with hepatic venous blood flow and lungs without hepatic venous blood. RESULTS: Ten of the 14 patients (71%) had positive contrast echocardiographic studies, compared with three (21%) detected by pulmonary angiograms (p = 0.01). No difference was found in pulmonary artery pressure, transpulmonary gradient or presence of heterotaxy syndrome between patients with positive contrast echocardiographic studies and patients with negative studies. However, patients with positive contrast echocardiograms tended to have lower oxygen saturation (81%) and higher hemoglobin (16.4 g/dl) compared with patients with negative studies (88% and 14.7 g/dl, p = 0.10 and p = 0.18 respectively). Patients with Glenn shunt or unidirectional Fontan had higher incidence of PAVM (10/11) compared with patients with classic or lateral tunnel Fontan (0/3, p = 0.01). All 12 lungs with no perfusion of hepatic venous blood had positive contrast echocardiographic studies. Lungs with no hepatic venous blood flow were more likely to develop PAVM compared with lungs with hepatic venous blood flow (12/12 and 3/16 respectively, p < 0.01). CONCLUSIONS: Bubble contrast echocardiography is more sensitive in detecting PAVM compared with pulmonary angiography. The prevalence of PAVM in patients with CPA may be much higher than what had been reported previously. Lungs with no hepatic venous blood flow are more likely to develop PAVM than lungs with hepatic venous blood flow.

Minimally invasive mechanical cardiac support without extracorporeal membrane oxygenation in children awaiting heart transplantation.

BACKGROUND: Mechanical cardiac assist for small children (< 30 kg) requiring bridge strategy to orthotopic heart transplantation often requires sternotomy for cannulation access to ensure perfusion to the aortic arch. Extracorporeal membrane oxygenation (ECMO) through neck cannulation is an option in very small (< 10 kg) patients, but the risk of stroke is increased in larger children. Another disadvantage is poor decompression of the left atrium, which can cause persistent pulmonary edema. METHODS: Two cases are used to illustrate two methods of avoiding sternotomy during mechanical assist in children with dilated cardiomyopathy. One of these approaches avoids the need for extracorporeal oxygenation. RESULTS: Decompression of the left-sided chambers with a left atrial cannula decreased pulmonary edema and improved pulmonary function. CONCLUSIONS: Pediatric patients with dilated cardiomyopathy may benefit from a left ventricular assist technique using a centrifugal pump, which avoids the neck vessels and sternotomy, as well as ECMO.

Marked left ventricular hypertrophy in children on tacrolimus (FK506) after orthotopic liver transplantation.

Although the cardiac effects of tacrolimus (FK506) have not been well documented, clinical cases of children on FK506 who developed hypertrophic obstructive cardiomyopathy have been reported. We report 2 cases of marked concentric hypertrophy of the left ventricular myocardium found at autospy in children on FK506.

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.

Effect of late postoperative atrial septal defect closure on hemodynamic function in patients with a Lateral tunnel Fontan procedure.

OBJECTIVES: The aim of this study was to evaluate prospectively the effect of late atrial septal defect closure on cardiac output and oxygen delivery in patients who have undergone the Fontan procedure. BACKGROUND: An adjustable atrial septal defect is incorporated in patients undergoing the Fontan procedure who have increased pulmonary vascular resistance or poor ventricular function, or both. After the Fontan procedure, the atrial septal defect is test occluded. Patients with mean right atrial and pulmonary artery pressures > 15 mm Hg are discharged with the atrial septal defect open. METHODS: Twelve patients (20 months to 12 years old) underwent evaluation and closure of the atrial septal defect at a mean interval of 3.8 months (range 1 to 18) after the Fontan procedure. Each patient underwent full right and left heart catheterization. Cardiac output was obtained using the cine-volume method. The study included six patients with a high transpulmonary gradient or poor ventricular function preoperatively, or both (high risk group) and six who had only borderline increased pulmonary vascular resistance (low risk group). Patients in both groups had a mean right atrial pressure > 15 mm Hg when the atrial defect was test occluded in the first week after the Fontan procedure. RESULTS: All results are given as mean value +/- SD. Ventricular end-diastolic pressure was significantly lower (p = 0.03) with the atrial septal defect open in low risk patients (6 +/- 3 mm Hg) than in high risk patients (10 +/- 3 mm Hg). With the atrial septal defect open, low risk patients had a significantly higher (p = 0.04) cardiac index (4.87 +/- 0.81 liters/min per m2) than the high risk patients (3.96 +/- 0.47 liters/min per m2). There was no significant difference (p = 0.14) in cardiac index between the two groups with occlusion of the atrial septal defect. Oxygen delivery was also significantly higher (p < 0.05) with the atrial septal defect open in low risk patients (836 +/- 99 ml/min per m2) than in high risk patients (704 +/- 106 ml/min per m2). There was no significant difference (p = 0.89) in oxygen delivery between the two groups with occlusion of the atrial septal defect. With the atrial septal defect open, the interatrial gradient was not significantly different in low risk patients (4 +/- 1 mm Hg) from that in high risk patients (4 +/- 1 mm Hg). CONCLUSIONS: These data show that an interatrial communication results in increased postoperative systemic perfusion and oxygen delivery in patients with good diastolic ventricular function after the Fontan procedure.

Anomalous origin of the left main pulmonary artery from the ascending aorta associated with DiGeorge syndrome.

We place on record 2 infants with the DiGeorge syndrome and anomalous origin of the left pulmonary artery from the ascending aorta. We postulate that: (1) embryogenesis of anomalous origin of the left pulmonary artery from the ascending aorta might be due to the persistent fifth aortic arch connecting both arterial systems; (2) an anomalous pulmonary artery arising from the ascending aorta is part of the aortic arch abnormality accompanied by normal conotruncal septation; and (3) in the DiGeorge syndrome, cardiac anomalies that originate from the conotruncus or aortic arch, or both, may have the same embryologic mechanisms.

Factors influencing survival in patients undergoing the bidirectional Glenn anastomosis.

The bidirectional Glenn anastomosis (BGA) has long been used as a surgical intervention for patients with single ventricle physiology. Initially, this procedure was the final stage in palliation and was performed in older children. Eventually, as the Fontan procedure came to be used as a method to separate circulations, the Glenn procedure was performed as an intermediate step. Over time, the BGA was performed as an alternative for patients who were considered to be at high risk with the Fontan procedure. Between January 1, 1988, and January 1, 1994, 129 patients underwent BGA at the University of California-Los Angeles. These patients were reviewed retrospectively, including clinic visits, catheterization, and echocardiographic information. The overall survival rate was 87% (112 of 129 patients). The average length of follow-up was 27 months. This information was then analyzed by univariate and multivariate analysis. Several factors were related to failure in patients who underwent BGA including pulmonary artery pressure, systemic right ventricle, and presence of anomolous pulmonary venous drainage and heterotaxy syndrome.

Conversion of atriopulmonary to cavopulmonary anastomosis in management of late arrhythmias and atrial thrombosis.

The original atriopulmonary connection or "classic" Fontan operation is associated with several late complications such as arrhythmias, right atrial dilatation, and thromboembolism. This report describes our experience with 3 patients who presented with the acute onset of atrial arrhythmias and upon further evaluation were found to have significant hemodynamic lesions. After failing medical management, all 3 patients were treated successfully with surgical conversion of their atriopulmonary connection to a lateral tunnel cavopulmonary Fontan. The postoperative course of these patients was uneventful. However, long-term evaluation is needed to assess the efficacy of this technique in the prevention of postoperative morbidity.