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.

Lung transplantation in infants and toddlers from 1990 to 2004 at St. Louis Children's Hospital.

In a retrospective, single-center cohort study, outcomes of infants and toddlers undergoing lung transplant at St. Louis Children's Hospital between 1990 and 2004 were compared to older children. Patients with cystic fibrosis (exclusively older children) and those who underwent heart-lung, liver-lung, single lung or a second transplantation were excluded from comparisons. One hundred nine lung transplants were compared. Thirty-six were in infants <1 year old, 26 in toddlers 1-3 years old and 47 in children >3 years old. Graft survival was similar for infants and toddlers (p = 0.35 and p = 0.3, respectively) compared to children over 3 years old at 1 and 3 years after transplant. Significantly more infants (p < 0.0001 and p = 0.003) and toddlers (p = 0.002 and p = 0.03) were free from acute rejection and bronchiolitis obliterans compared to older patients. While most infants and toddlers had only minimal lung function impairment, and achieved normal to mildly delayed developmental scores, somatic growth remained depressed 5 years after transplant. Lung transplantation in infants and young children carries similar survival rates to older children and adults. Further insights into the unique immunologic aspects of this group of patients may elucidate strategies to prevent acute and chronic rejection in all age groups.

The failing Fontan: options for surgical therapy.

The Fontan procedure has been a significant contribution to the therapeutic armamentarium of congenital heart surgeons for the treatment of single ventricle anomalies. However, it has its limitations. Patients may have failure of the Fontan circulation acutely postoperatively or late during the long-term follow-up. Early failure is often related to an intraoperative myocardial injury or unsuspected elevated pulmonary vascular resistance; this has a very high mortality. Late failure of the Fontan procedure may present with symptoms typical for heart failure. However, protein-losing enteropathy is another condition related to late failure of the Fontan operation. Late failure may be related to a number of different factors, many of which are amenable to reoperation. Every effort should be made to identify which hemodynamic factors are responsible for late failures. However, cardiac transplantation will likely be necessary for the majority of patients.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation.

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart-lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.

Lung transplantation in infants.

Lung transplantation is an accepted mode of therapy for patients with end-stage pulmonary vascular or parenchymal diseases. To date, application to the pediatric age population in general, and the infantile group in particular, has been limited both in terms of number of transplants and follow-up thereafter. We performed our first transplant in an infant in 1993 and have performed 30 lung transplants in children under 1 year of age subsequent to that. This chapter will review the experience to date including indications for transplantation, post-transplant management, complications, and long-term follow-up.

Repair of anomalous left main coronary artery arising from the pulmonary artery in infants: long-term impact on the mitral valve.

BACKGROUND: Infants presenting with anomalous left coronary artery off the pulmonary artery (ALCAPA) are generally in heart failure and often have significant mitral valve regurgitation (MR). Although establishing a dual coronary circulation is the procedure of choice, there remains controversy as to how the mitral valve is handled. METHODS: We reviewed our experience with this lesion at St. Louis Children's Hospital. Over the past 15 years, 17 infants under 18 months of age have undergone repair, with all but one being treated with reimplantation of the left coronary artery into the aorta; the other underwent the Takeuchi procedure (intrapulmonary artery baffle) and was excluded from this evaluation. The average age and weight at operation were 0.5 +/- 0.3 years and 6.1 +/- 1.9 kg, respectively. All presented with varying degrees of heart failure and 9 patients also had either moderate or severe MR. RESULTS: There was one early and no late deaths after reimplantation of the left coronary artery. The left ventricular function postrepair improved from a preoperative shortening fraction of 0.19 +/- 0.09 to 0.34 +/- 0.08 (p < 0.01). Moderate or severe MR was present in 2 patients postoperatively, and both developed significant obstruction in the left coronary artery postoperatively as well. Both underwent mitral valve repair and revascularization of the left coronary artery. CONCLUSIONS: Excellent results can be obtained in the treatment of this very high-risk group of patients. Mitral valve repair is not generally necessary at the time of the initial operation. However, should MR recur or persist late, it may herald the presence of a coexistent, significant coronary stenosis. Cardiac catheterization should be performed to assess the patency of the left coronary artery before performing mitral valve surgery.

Does the extent of proximal or distal resection influence outcome for type A dissections?

BACKGROUND: The extent of proximal and distal aortic resection that should be performed for acute type A aortic dissections remains controversial. METHODS: From 1984 to 1999, 119 patients underwent repair of an acute type A dissection. Distal resection was to the ascending aorta in 78 (66%) and hemiarch in 41 (34%) patients. Proximally, the aortic valve was preserved in 69 (58%) patients, 40 (34%) underwent composite valve grafting, and 10 (8%) underwent separate graft and valve replacement. RESULTS: Operative mortality was higher for separate graft and valve (50%+/-16%) than for valve preservation (16%+/-5%) or composite grafts (20%+/-7%) (p < 0.05). Hemiarch replacement did not increase operative risk compared to distal reconstruction to the ascending aorta (17%+/-6% versus 22%+/-5%, p > 0.71). At 10 years, freedom from reoperation was 81%+/-7% and long-term survival was 60%+/-8%, but neither was related to the proximal or distal surgical technique (p > 0.15). Risk factors for late reoperation included a nonresected primary tear and Marfan syndrome (p < 0.05). CONCLUSIONS: An aggressive surgical approach, including a full root or hemiarch replacement, is not associated with increased operative risk and should be considered when type A dissections extensively involve the valve, sinuses, or arch.

Quality of life after aortic valve replacement at the age of >80 years.

BACKGROUND: The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival. METHODS AND RESULTS: We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84+/-3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old. CONCLUSIONS: Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

High incidence of posttransplant lymphoproliferative disease in pediatric patients with cystic fibrosis.

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.

Heart and lung preservation for transplantation.

Since the beginning of transplantation the search for optimal means of organ preservation has been ongoing. One of the major causes of death early following heart or lung transplantation is graft failure. Factors that play a role in this problem include recipient and donor issues, but clearly procurement techniques and preservation solutions are important. This article summarizes the history, current clinical practice, and research devoted to heart and lung preservation for transplantation.

Intestinal obstruction after lung transplantation in children with cystic fibrosis.

BACKGROUND/PURPOSE: Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. METHODS: Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). RESULTS: After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). CONCLUSIONS: (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.

Lung transplantation in very young infants.

INTRODUCTION: Established successes with adult lung transplantation have laid the foundation for extension of this therapeutic modality to infants and children dying of end-stage pulmonary disease. The purpose of this report is to convey our experience with 19 infants undergoing lung transplantation before the age of 6 months. METHODS: Six patients with predominantly pulmonary vascular disease and 13 patients with primarily pulmonary parenchymal disease have undergone bilateral sequential lung transplantation at our institution since 1990. Mean age at transplant was 104 +/- 44 days, and mean weight was 4.9 +/- 1.6 kg. RESULTS: Although early mortality (32%, 6/19) was higher than that previously reported for older pediatric age groups, long-term survival was similar (44% at a maximum follow-up of 6 years). Although anastomotic complications and infections occurred at a rate approximating that seen in older pediatric age groups, episodes of acute rejection appear to occur with decreased frequency. Similarly, at a mean follow-up of 3 years, only 2 (15%) of 13 long-term survivors have evidence of bronchiolitis obliterans. The functional residual capacity, as measured on infant pulmonary function tests, has gradually increased as the children have grown, suggesting that lung growth is occurring. CONCLUSIONS: Bilateral lung transplantation is a viable alternative in infants dying of end-stage pulmonary disease. Efforts directed toward avoiding the complications that lead to early posttransplant mortality combined with the seemingly lower incidence of early and late rejection may provide long-term results better than those in other age groups.

Rejection with heart failure after pediatric cardiac transplantation.

BACKGROUND: Rejection associated with heart failure or death occurs after pediatric cardiac transplantation but has had limited analysis. METHODS: We analyzed the records of 96 consecutive pediatric cardiac transplant recipients who survived to hospital discharge. RESULTS: Eighteen patients (19%) experienced 23 episodes of heart failure or death associated with rejection. Univariate analysis demonstrated black race (p = 0.041), transplantation after 12 months of age (p = 0.032), later time after transplantation (p = 0.037), rejection episode in the first year after transplantation (p = 0.001), and history of two or more rejection episodes (p < 0.001) were significantly associated with rejection seen with heart failure. A multivariate regression analysis identified two or more rejection episodes to be the only independent risk factor for the development of rejection with heart failure (odds ratio 20; 95% confidence limits, 4-104; p < 0.0001). CONCLUSIONS: This study identified pediatric heart transplant recipients with a history of previous rejection episodes to be at a higher risk for symptomatic or fatal rejection. Further studies are needed to determine if intensification of maintenance immunosuppression, long-term rejection surveillance, or both in patients with multiple rejection episodes could reduce morbidity and mortality from rejection.

Combined lung and liver transplantation in a girl with cystic fibrosis.

PURPOSE: To describe the anesthetic considerations of a combined lung and liver transplant in a 14-yr-old girl with cystic fibrosis. CLINICAL FEATURES: A 14 yr-old girl with cystic fibrosis presented for combined liver and lung transplantation. Anesthetic management was complex in that the pulmonary, hemodynamic, and hematological changes after cardiopulmonary bypass and lung transplantation made the management of the subsequent liver transplant unique. We used a moderate dose fentanyl and isoflurane anesthetic with invasive monitoring including a pulmonary artery catheter. Upon reperfusion of the new liver our patient exhibited severe pulmonary hypertension that was associated with a decrease in cardiac output and systemic hypotension. Utilizing a pulmonary artery catheter, this episode was treated with an increase of prostaglandin E1 (PGE1) infusion to 0.025 microg x kg(-1) x min(-1) and the initiation of 3 microg x kg(-1) x min(-1) dobutamine. The pulmonary hypertension resolved and the cardiac output and blood pressure returned to baseline levels. CONCLUSION: The anesthetic considerations for a combined lung and liver transplant are complex because of the interactions and alterations in cardiovascular, pulmonary and hemostatic systems. The use of a pulmonary artery catheter was critical to the management of our patient because it allowed us to accurately treat an episode of hypotension occurring during liver transplantation. This episode was secondary to acute pulmonary hypertension which is common after pulmonary transplantation but unusual during liver transplantation. It is also critical that a team approach is used to consider all of the concerns of the multiple services managing these complex patients.