Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

A systematic approach to transplanting non-resident, non-citizens in an established US pediatric lung transplant program.

Introduction: The Texas Children's Hospital Lung Transplant Program undertook consideration of its first non-resident, non-citizen for lung transplantation in 2011. Methods: Four referrals from the Royal Embassy of Saudi Arabia were received, and two patients were evaluated from 2011 to 2013. Results: After a suitable candidate and family was identified, the program adopted a systematic approach to ensure that all the necessary elements of pre-transplant care, informed consent, and post-transplant care could be effectively delivered. Conclusion: The use of hospital translation services and the development of a strong professional relationship with a well-trained pediatric respirologist in Saudi Arabia combined with an excellent early post-transplant clinical course provide lessons that may be of help to other transplant programs considering international patients as candidates for solid organ transplantation.

Clostridium difficile colitis in children following lung transplantation.

Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.

Mycobacterium abscessus in cystic fibrosis lung transplant recipients: report of 2 cases and risk for recurrence.

Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.

Ex vivo characterization of human anti-porcine hyperacute cardiac rejection.

Hyperacute rejection (HAR) currently precludes the use of discordant organs for human transplantation. In order to comprehensively evaluate HAR in a clinically applicable species combination, we have developed an ex vivo perfusion model utilizing a neonatal extracorporeal membrane oxygenator circuit; this model allows for functional and sequential biopsy studies of working piglet hearts sustained by human, single donor AB+ type blood. A detailed description of the methods employed is included. Hearts perfused by allogeneic pig blood sustained normal function throughout the study period, while those perfused with human blood lost organized ventricular contraction in 25-34 min with markedly attenuated function. Compared with biopsies from piglet hearts perfused with allogeneic blood and biopsies taken prior to human blood perfusion (t = 0), biopsies of hearts perfused with human blood at t = 15 and 30 min demonstrated significant inflammatory changes involving vessels (endothelial and myointimal swelling and reaction) as well as myocardium (injury and necrosis). By immunohistology, significant vascular deposition of IgM, IgG, fibrinogen, C3, and C1q was seen, along with infiltrates of human leukocytes consisting predominantly of neutrophils, macrophages, and T cells, with occasional B cells and NK cells. Sequential studies of circulating blood demonstrated the progressive consumption of human leukocytes and human anti-porcine antibodies, but no decrease in complement activity as measured by CH50. These findings indicate that the rapid loss of function seen in human anti-porcine cardiac HAR is associated with deposition of IgM and IgG xenoreactive antibody and early complement components and that extensive infiltration by inflammatory cells occurs within 15-30 min. This model provides a useful system for the study of human anti-porcine HAR.

The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.

Early extubation after cardiac operations in neonates and young infants.

OBJECTIVE: This study was undertaken to determine the feasibility of early extubation of the neonate and young infant after surgical repair of congenital heart lesions. METHODS: The records of all patients less than 90 days of age who had cardiac operations over a 1-year period were reviewed. During this time, all patients were managed as potential candidates for early extubation. Fifty-six patients are included with a mean age of 32 +/- 31 days and a mean weight of 3.7 +/- 0.9 kg. RESULTS: Twenty-eight patients (50%) were extubated in the operating room or within 3 hours after arriving in the intensive care unit. This included 38% of patients less than 7 days of age, 50% of patients 8 to 30 days of age, 44% of patients 31 to 60 days of age, and 69% of patients 61 to 90 days of age. Three patients (11%) extubated early required reintubation. No deaths were related to early extubation. Only one patient was negatively affected by early extubation. Patients extubated early had shorter stays in the intensive care unit (3.3 +/- 3.9 vs 6.7 +/- 2.9 days) and shorter postoperative hospital stays (5.9 +/- 3.3 vs 13.5 +/- 9.7 days), as well as lower intensive care unit ($5,851 +/- $7,225 vs $12,064 +/- $4,419) and total hospital ($21,108 +/- $14,941 vs $31,608 +/- $9,861) costs than patients who were ventilated. CONCLUSIONS: Early extubation can be accomplished safely in many neonates and young infants undergoing cardiac operations for repair of congenital heart defects and can shorten hospital stay and reduce costs.

Myocardial function is normal after rapid cooling of the in vivo neonatal heart.

Rapid cooling (RC) on cardiopulmonary bypass (CPB) has been reported to be injurious to the neonatal myocardium when compared with slow cooling (SC). However, previous studies have been performed on isolated heart preparations using asanguineous perfusates and may not represent clinically valid conclusions. In this study, the effect of RC versus SC on post-CPB cardiac function in an in vivo neonatal heart model using a blood perfusate was investigated. Thirteen neonatal piglets underwent median sternotomy. Left ventricular ultrasonic dimension transducers were placed in the minor and major axis diameters, and an intraventricular micromanometer was placed. Baseline left ventricular pressure-dimension data were obtained during transient vena caval occlusion. Animals were then placed on CPB (blood prime; mean hematocrit, 25%) with the prime temperature at either 18 degrees C (RC) or 37 degrees C (SC) and perfusion cooled either quickly (RC) or gradually (SC) such that within 2 minutes of cooling the average myocardial temperature was 23.5 degrees C in the RC group versus 33.8 degrees C in the SC group (p = 0.0001). Animals were cooled to 20 degrees C, rewarmed to 37 degrees C, and then weaned from CPB. Left ventricular pressure-dimension data were obtained 30 minutes after CPB and compared with baseline. The slope (MW) and x-intercept (Vo) of the linear stroke work-end-diastolic volume relationship were used as load-insensitive indices of left ventricular function at baseline and after CPB. There was no statistically significant difference in baseline versus postbypass MW or Vo in the RC or SC groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral metabolism and circulatory arrest: effects of duration and strategies for protection.

Hypothermic total circulatory arrest (CA) is commonly used to facilitate repair of complex congenital heart defects. However, the "safe" period of CA remains to be defined. Extended periods of hypothermic total circulatory arrest may impair cerebral metabolism and cause ischemic brain injury. This study defines the relationship between increasing durations of CA at 18 degrees C and cerebral metabolism, and examines the protective value of topical cooling of the head or continuous "trickle" flow (5 to 10 mL.kg-1.min-1). Thirty-three 1-week-old piglets were randomized to six experimental groups: control; 15, 30, or 60 minutes of CA; 60 minutes of CA with topical cooling of the head; and 60 minutes of trickle flow. Animals were placed on cardiopulmonary bypass (CPB) at 100 mL.kg-1.min-1 and cooled to 18 degrees C. After the experimental period of CA or trickle flow (or 60 minutes of CPB at normal flow for the control group), animals were rewarmed to 37 degrees C and weaned from CPB. Data were obtained before and immediately after CPB at 37 degrees C, and before and immediately after the experimental period at 18 degrees C. Parameters measured included cerebral blood flow by xenon 133 clearance, arterial and sagittal sinus blood gases, and cerebral metabolism. Hypothermic total circulatory arrest caused an impairment of cerebral metabolism that was directly proportional to CA duration (r2 = 0.73; p = 0.0001), and recovery of metabolic function after 60 minutes of CA improved more than 50% if the head was packed in ice.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral metabolic effects of sequential periods of hypothermic circulatory arrest.

During repair of congenital heart defects, extended periods of hypothermic circulatory arrest (CA) have been shown to cause short-term cerebral metabolic and flow abnormalities as well as long-term neuropsychologic dysfunction. Occasionally, a second period of CA is required during the same operative setting to revise a complicated repair. However, the metabolic effects of two consecutive periods of CA on the brain are unclear. In this study, we compared the recovery of cerebral metabolism after 60 minutes of CA with that after two sequential 30-minute periods of CA separated by a brief period of rewarming (30'SEQ). Fifteen neonatal piglets (2 to 3 kg) were placed on cardiopulmonary bypass at 100 mL.kg-1 x min-1 and cooled to 18 degrees C. Each animal then underwent either 60 minutes of uninterrupted cardiopulmonary bypass at 18 degrees C, 60 minutes of CA, or two 30-minute periods of CA separated by a brief period of rewarming. After these experimental periods, animals were rewarmed to 37 degrees C and weaned from cardiopulmonary bypass. Data were obtained before cardiopulmonary bypass and after cardiopulmonary bypass at 37 degrees C and included measurements of cerebral blood flow by xenon 133 clearance, arterial and sagittal sinus blood gases, and cerebral metabolism (mL O2.100 g-1 x min-1). Our results demonstrated that acute recovery of cerebral metabolism was significantly impaired after 60 minutes of CA and that recovery of cerebral metabolism after two sequential 30-minute periods of CA was significantly better than after 60 minutes of continuous CA.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced cardiac preservation with oxygenated University of Wisconsin solution.

The purpose of this study was to determine if oxygen delivery to rabbit cardiac allografts arrested and stored in University of Wisconsin solution (UWS) at 4 degrees C would affect preservation. Nineteen isolated rabbit hearts were rapidly excised and perfused at 80 mm Hg on an isovolumic modified Langendorff apparatus. A micromanometer was placed within a balloon and inserted into the left ventricle through the mitral valve orifice. Digitized pressure waveforms were collected at 11 known balloon volumes from 0.8 to 1.2 ml. Baseline data were obtained for all hearts while perfused with Krebs-Henseleit solution equilibrated with 95% O2:5% CO2 at 37 degrees C. All hearts were arrested with 30 ml of UWS (290 mOsm). The control group (N = 10) was stored in UWS at 4 degrees C for 8 hr, and the experimental group (N = 9) was perfused with oxygenated UWS (O2 content = 5.6 ml O2) at 4 degrees C for 8 hr at a pressure of 60 mm Hg (5-10 ml/min). Both groups were then reperfused with Krebs-Henseleit buffer at 80 mm Hg for 15 min at for postpreservation data acquisition. Left ventricular developed pressures over a physiologic range (pressure-volume area) and maximum positive and negative dP/dt were calculated. Recovery of left ventricular parameters as a percentage of the baseline values was determined. Mean pressure-volume area recovery in the nonperfused group was 40 +/- 7.9% versus the perfused group (71 +/- 7.0%, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)