Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: Analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database.

OBJECTIVE: Criteria for simultaneous heart-kidney transplant (HKTx) recipients are unclear. We characterized the evolution of combined HKTx in the United States over time compared with isolated heart transplantation (HTx) and determined factors maximizing post-transplant survival. We focused on whether a threshold estimated glomerular filtration rate (eGFR) could be identified that justified combined transplantation. METHODS: A supplemented United Network Organ Sharing Dataset identified HTx and HKTx recipients from 2000 to 2010. eGFR was calculated for HTx and recipients were grouped into eGFR quintiles. Time-related mortality was compared among recipients, with multivariable factors sought using Cox proportional hazard regression models. RESULTS: We identified 26,183 HTx recipients, of whom 593 were HKTx recipients. HTx increased modestly over time (3.6%), whereas prevalence of HKTx increased dramatically (147%). Risk-unadjusted survival was similar among HTx recipients (8.4 ± 0.04 years) and HKTx recipients (7.7 ± 0.2 years) (P = .76). Isolated HTx recipients in the lowest eGFR quintile had decreased survival (P < .001), but those in the third eGFR quintile had superior survival, suggesting a benefit in this subgroup. HTx recipients in the lowest eGFR quintile (eGFR less than mean 37 mL/minute) had worse survival than combined HKTx recipients (7.1 ± 0.07 vs 7.7 ± 0.2; P < .001). Multivariable factors for increased mortality among HTx recipients included lower eGFR, higher recent panel reactive antibody score, older age, African American race, diabetes, longer ischemic time, and certain diagnoses. CONCLUSIONS: Performance of combined HKTx is increasing out of proportion to isolated HTx. eGFR is an important determinant of improved HTx survival. Combined HKTx recovers post-transplant survival in patients with eGFR <37 mL/minute and can be recommended in this subgroup.

Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children.

BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. METHODS AND RESULTS: This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

Increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients.

OBJECTIVE: We sought to examine the relationship between extracorporeal membrane oxygenation center case volume and survival in pediatric patients requiring extracorporeal membrane oxygenation support. METHODS: Pediatric patients (≤ 20 years) undergoing extracorporeal membrane oxygenation cannulation were identified using the Healthcare Cost and Utilization Project Kids' Inpatient Database for 2000 to 2009. Annual hospital extracorporeal membrane oxygenation volume tertiles were <15 patients/year (low volume), 15 to 30 patients/year (medium volume), and >30 patients/year (high volume). Cases of extracorporeal membrane oxygenation were segregated by indication into cardiac and noncardiac groups. Cases of cardiac extracorporeal membrane oxygenation were mapped to Risk Adjustment for Congenital Heart Surgery categories to adjust for case complexity. Weighted multivariable logistic and linear regression models identified determinants of in-hospital mortality. RESULTS: Overall, 3867 cases of extracorporeal membrane oxygenation were identified, yielding a national estimate of 6333 ± 495 cases. Extracorporeal membrane oxygenation was used with nearly equivalent prevalence across volume tertiles for all Risk Adjustment for Congenital Heart Surgery categories, suggesting that patient selection for extracorporeal membrane oxygenation was fairly uniform. A higher annual extracorporeal membrane oxygenation volume tertile was associated with reduced in-hospital mortality (P = .01) within nearly all Risk Adjustment for Congenital Heart Surgery categories. After adjustment for Risk Adjustment for Congenital Heart Surgery category and other patient variables, lower extracorporeal membrane oxygenation volume remained an important determinant of in-hospital death (odds ratio, 1.75; 95% confidence interval, 1.03-2.94; P = .03). CONCLUSIONS: Higher extracorporeal membrane oxygenation case volume is associated with improved hospital survival in pediatric cardiac extracorporeal membrane oxygenation patients. The results of this study may support the paradigm of regionalized centers of excellence for managing pediatric cardiac extracorporeal membrane oxygenation patients.

Prospective trial of a pediatric ventricular assist device.

BACKGROUND: Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS: We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS: Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

Direct optical measurement of intraoperative myocardial oxygenation during congenital heart surgery.

This study demonstrates use of novel technology to measure cellular oxygenation during corrective congenital heart surgery. Cellular oxygenation was measured using a custom-designed optical probe placed on the free wall of the right ventricle. Cellular oxygenation, determined from myoglobin saturation, was calculated using multiwavelength analysis. Timing of bypass, aortic cross-clamp, infusion of cardioplegic solution, and length of intensive care unit (ICU) stay were recorded. Baseline cellular oxygenation was approximately 50% just before aortic cross-clamp and decreased to approximately 20% during cardioplegia. Cellular oxygenation remained low throughout cardioplegia and returned toward baseline after bypass. In four cases, cellular oxygenation did not return as quickly to baseline as in the other three cases. Among the four patients demonstrating slow recovery, the average ICU length of stay was 2.25 days compared with an average stay of 1.33 days for those patients exhibiting rapid cellular oxygenation recovery (p = 0.06). The slow recovery group had an average cross-clamp time of 40.1 ± 28.4 minutes, compared with 26.0 ± 8.5 minutes for the fast recovery group (p = 0.34). This study demonstrates for the first time that myocyte cellular oxygenation can be measured intraoperatively during cardiac surgery. Measurement of cellular oxygenation may be useful for improving myocardial preservation techniques.

Minimizing bleeding associated with mechanical circulatory support following pediatric heart surgery.

OBJECTIVE: The use of extracorporeal membrane oxygenation (ECMO) to support patients with early postcardiotomy heart failure may be associated with catastrophic bleeding, making its use undesirable. However, postcardiotomy mechanical circulatory assistance is necessary in some patients to allow for myocardial recovery. We have assembled a centrifugal pump system (CPS) that does not require early systemic anticoagulation. This study compares postoperative bleeding in pediatric patients placed on standard ECMO versus CPS within 24h of cardiotomy. METHODS: Between November 2002 and February 2007, 25 patients (age 0 days-1.72 years) received postcardiotomy mechanical support. Fourteen patients were placed on ECMO and 11 patients were placed on CPS within 24h of surgical repair. Retrospective analysis was performed of chest-tube drainage at multiple time points following initiation of mechanical support. Additional variables, including Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score, total time on mechanical support, 30-day mortality, activated clotting time, blood-product administration, circuit-related complications, and circuit changes were also analyzed. RESULTS: Patients on ECMO (0.30 ± 0.39 years) and CPS (0.40 ± 0.56 years) were of similar age (p = 0.64). Patients on ECMO (0.3 ± 0.1m(2)) and CPS (0.3 ± 0.1m(2)) had similar body surface areas (p = 0.46). Patients placed on CPS had significantly less chest-tube drainage during the first 4h of support. Activated clotting times appeared to be higher during the first 12h of ECMO versus CPS. There was no statistical difference between ECMO and CPS with respect to the following variables: RACHS-1 score, time on support, 30-day mortality, circuit-related complications, and circuit changes. Blood-product administration at 24h of support was significantly less (p = 0.04) for patients on CPS versus ECMO. CONCLUSIONS: Mechanical circulatory support can be provided without the complication of clinically significant bleeding if a specialized circuit is used. This has important implications for the decision to use mechanical support in the immediate postoperative period in the face of ventricular failure. In addition, early mechanical support can be used with a low incidence of circuit-related complications.

Association of thymectomy with infection following congenital heart surgery.

BACKGROUND: Congenital absence of the thymus can lead to profound immunodeficiency, suggesting that thymic function during fetal development is essential to normal lymphocyte development. How vital the thymus after birth is to human immune competence and regulation is not known. Routine thymectomy, especially at an early age, may influence immunity, and therefore the risk of infection, autoimmunity, or malignancy. METHODS: A retrospective review of cardiac surgery patients followed at Seattle Children's Hospital was performed. The primary outcome was rate of serious infections requiring hospitalization. Secondary analyses included age, type of infection, cardiac diagnosis, surgical procedure, and comorbidities. RESULTS: Patients fell into 2 groups: 60 with complete thymectomy and 35 with partial or no thymectomy. There was no statistical difference between groups in the overall prevalence of serious infections (16.7% vs 17.2%, P = 1.0). There was a nonsignificant trend toward reduced time between surgery and onset of first infection in patients in the total thymectomy group versus those without thymectomy (1.7 years vs 4.6 years, P = .07). Total thymectomy before 6 months of age also tended to increase infection rate, but the effect was not significant (0.09/year vs 0.02, P = .14). Gastroesophageal reflux in patients with total thymectomy increased the risk of infection (P = .013), suggesting a cumulative effect. CONCLUSIONS: Though infections occurred frequently in the childhood cardiac surgery population, total thymectomy was not associated with increased risk of serious infection. Comorbid conditions may be more important contributing factors increasing the risk of infection in this complex and vulnerable population.

Bridging children of all sizes to cardiac transplantation: the initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device.

BACKGROUND: Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation. METHODS: Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available. RESULTS: Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR. CONCLUSIONS: This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

Congenital cardiac surgical complications of the integument, vascular system, vascular-line(s), and wounds: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease.

A complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval. The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrinal systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to a collection of loosely related topics that include the following groups of complications: 1) Complications of the Integument, 2) Complications of the Vascular System, 3) Complications of the Vascular-Line(s), 4) Complications of Wounds. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases. As surgical survival in children with congenital cardiac disease has improved in recent years, focus has necessarily shifted to reducing the morbidity of congenital cardiac malformations and their treatment. A comprehensive list of complications is presented. This list is a component of a systems-based compendium of complications that will standardize terminology and thereby allow the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease will be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.

Superior cardiac function via anaplerotic pyruvate in the immature swine heart after cardiopulmonary bypass and reperfusion.

Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the tricarboxylic acid (TCA) cycle via carboxylation are linked to the stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age: 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2-(13)C]pyruvate (to achieve an estimated final concentration of 8 mM) was given for 35 min, starting either during weaning (group I) and after its discontinuation (group II) or without (control) CPB. Hemodynamic data were collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the TCA cycle via pyruvate carboxylation (PC) to total TCA cycle entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment. Pyruvate infusion starting during the weaning of mechanical circulatory support improved maximum dP/dt (P<0.05) but waiting to start the infusion until after the discontinuation of CPB did not. Glutamate fractional enrichment was confirmed by liquid chromatography-mass spectroscopy as adequate (>5%) to provide signal to noise in the NMR experiment in all groups. The ratio of pyruvate carboxylase to total pyruvate entry into the TCA cycle did not differ between groups (group I: 20+/-4%, group II: 23+/-7%, and control: 27+/-7%). These data show that robust PC operates in the neonatal pig heart and is maintained during reperfusion under conditions that emulate CPB and reperfusion in human infants.

An investigation of Aspergillus cardiac surgical site infections in 3 pediatric patients.

BACKGROUND: Within a 3-month period, 3 pediatric patients at our hospital developed Aspergillus surgical site infections after undergoing cardiac surgery. METHODS: A multidisciplinary team conducted an epidemiologic review of the 3 patients and their infections, operative and postoperative patient care delivery, and routine maintenance of hospital equipment and air-filtration systems and investigated potential environmental exposures within the hospital that may have contributed to the development of these infections. RESULTS: Review of the patients and their infections, operative and postoperative patient care delivery, and routine maintenance did not reveal a source for infection. Inspection of operating room (OR) facilities identified several areas in need of repair. Of the 58 samples of air and equipment exhaust in the ORs and patient care areas, 11 revealed 2 to 4 colony-forming units of various Aspergillus species per cubic meter of air, and the remaining 47 samples were negative for Aspergillus. Eighty-three samples of surfaces and equipment water reservoirs were obtained from the OR and patient care areas. One culture of a soiled liquid nitrogen tank housed between the 2 cardiac ORs revealed 13 colony-forming units of Aspergillus. CONCLUSION: No definitive source was identified, although a soiled liquid nitrogen tank contaminated with Aspergillus and kept near the OR was found and could have been a possible source.

Intraoperative echocardiography for atrioventricular canal: decision-making for surgeons.

Intraoperative echocardiography has become a standard patient management tool in the assessment of the patient undergoing surgical repair of a congenital cardiac defect. Over the past 15 years transesophageal echocardiography has emerged as an integral part of the intraoperative assessment of the congenital cardiac surgery patient. The important role of intraoperative echocardiography is largely because of its ability to define complex anatomy, identify functional abnormalities, and recognize flow disturbances at the time of surgical repair. Intracardiac defects are particularly suited to the strengths of intraoperative transesophageal echocardiography because of the unobstructed windows that can be obtained. This article focuses on how intraoperative echocardiography can guide surgical decision-making in the patient undergoing repair of an atrioventricular canal defect.

Effect of polymer coating (poly 2-methoxyethylacrylate) of the oxygenator on hemostatic markers during cardiopulmonary bypass in children.

OBJECTIVE: Heparin and other oxygenator coatings have been used in attempts to reduce hemostatic activation during cardiopulmonary bypass (CPB). This study evaluated whether an oxygenator coated with poly 2-methoxyethylacrylate (PMEA) (X-coating; Terumo Corporation, Tokyo, Japan) would cause less activation of coagulation and fibrinolytic systems during CPB in children than a noncoated oxygenator. DESIGN: Observational study. SETTING: University-affiliated children's hospital. PATIENTS: Twenty-six patients, 3 months to 5 years old, who underwent congenital heart surgery for repair of a ventricular septal defect, atrial septal defect, or both. INTERVENTIONS: Patients were divided into 2 age-matched groups based on the type of oxygenator used: a noncoated oxygenator (group NC) versus a PMEA-coated oxygenator (group C). MEASUREMENTS AND MAIN RESULTS: Blood samples for coagulation and fibrinolytic markers were compared before, during, and after CPB. Despite increases in thrombin generation markers (F1.2 and TAT) at certain times during CPB in group C compared to group NC, a comparison over all times during CPB were not statistically different between groups. Overall D-dimer concentrations during CPB were elevated in group C compared to group NC (p = 0.02). Active tPA and active PAI-1 were not different between groups during or after CPB. Group C had higher platelet counts (181,000 +/- 29,000) during CPB than group NC (155,000 +/- 57,000, p = 0.04) but not postoperatively. Twelve hours postoperatively, chest tube outputs were 8.8 +/- 3 mL/kg in group C and 19.1 +/- 12 mL/kg in group NC (p = 0.003). The corresponding outputs 24 hours after surgery were 12.4 +/- 3 mL/kg and 24 +/- 11 mL/kg, respectively (p = 0.005). CONCLUSIONS: Except for a somewhat higher platelet count during CPB, there was no indication that PMEA coating resulted in less activation of coagulation and fibrinolytic systems. The lower postoperative chest tube output observed after CPB with PMEA-coated oxygenators needs to be studied further.

Transposition of the great arteries and quadricuspid pulmonary valve: an unusual combination.

Quadricuspid semilunar valves are very rare, especially in association with other congenital cardiac anomalies. A quadricuspid pulmonary valve has never been described in the setting of transposition of the great arteries. In this brief article we describe one such case, and we discuss the operative strategy during the arterial switch operation with particular reference to the technique of coronary translocation.

Percutaneous left ventricular "vent" insertion for left heart decompression during extracorporeal membrane oxygenation.

OBJECTIVE: Description of a novel method of left ventricular decompression by a percutaneous technique under transthoracic echocardiographic guidance. DESIGN: Case report. SETTING: Supraregional cardiac referral center. PATIENT: PATIENT with end-stage cardiomyopathy. INTERVENTIONS: Percutaneous insertion of a modified Mullins transseptal sheath under transthoracic echocardiographic guidance. MEASUREMENTS AND MAIN RESULTS: Successful decompression of the left ventricle and subsequent orthotopic heart transplantation. CONCLUSIONS: In patients at high risk of bleeding, a percutaneous technique may be useful for left ventricular decompression.

Management of complex tracheo-aortic fistula following neonatal tracheal reconstruction.

We describe an unusual case of tracheo-aortic fistula, which occurred after tracheal surgery and tracheal stenting. The management of this complex case and the surgical technique used for repair are discussed and illustrated. Repair of the aortic arch was accomplished using a modified technique of regional low-flow perfusion, similar to that described for neonatal aortic arch reconstruction. This strategy allowed maintenance of cerebral, myocardial, and systemic perfusion during arch repair, thus avoiding total circulatory arrest.