Andrew J. Lodge

Cardiac surgery in infants with low birth weight is associated with increased mortality: Analysis of the Society of Thoracic Surgeons Congenital Heart Database

OBJECTIVE The evaluation of operative mortality risk for cardiac surgery in infants with low weight is limited. To determine whether low weight is a risk factor for increased mortality, we reviewed the experience within the Society of Thoracic Surgeons Congenital Heart Surgery Database of infants who have undergone surgical correction or palliation for congenital heart disease. METHODS We analyzed mortality in 3022 infants ages 0 to 90 days weighing 1 to 2.5 kg (n = 517) and greater than 2.5 to 4 kg (n = 2505) who underwent cardiac surgery from 2002 through 2004 at 32 participating centers. Patients were grouped according to the primary procedure performed and analyzed according to their weight at the time of surgical intervention. Patients were also analyzed according to Risk Adjustment for Congenital Heart Surgery-1 and Aristotle Basic Complexity scores. RESULTS Compared with infants weighing 2.5 to 4 kg, infants weighing less than 2.5 kg had a significantly higher mortality for the following operations: repair of coarctation of the aorta, total anomalous pulmonary venous connection repair, arterial switch procedure, systemic to pulmonary artery shunt, and the Norwood procedure. Lower infant weight remained strongly associated with mortality risk after stratifying the population by Risk Adjustment for Congenital Heart Surgery-1 levels 2 through 6 and Aristotle Basic Complexity levels 2 through 4. CONCLUSIONS Low weight at the time of surgical intervention is associated with increased mortality in patients undergoing several types of cardiovascular procedures. These data do not allow assessment of specific risks or benefits of any particular treatment strategy. However, they do support the need for prospective analysis of specific treatment strategies for these high-risk patients.

Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important.

INTRODUCTION Cardiopulmonary bypass produces an inflammatory response that can cause significant postoperative pulmonary dysfunction and total body edema. This study evaluates the efficacy of preoperative methylprednisolone administration in limiting this injury in neonates and compares the effect of giving methylprednisolone 8 hours before an operation to the common practice of adding methylprednisolone to the cardiopulmonary bypass circuit prime. METHODS A control group of neonatal pigs (control; n = 6) received no preoperative medication. One experimental group (n = 6) received methylprednisolone sodium succinate (30 mg/kg) both 8 and 1.5 hours before the operation. A second experimental group received no preoperative treatment, but methylprednisolone (30 mg/kg) was added to the cardiopulmonary bypass circuit prime. All animals underwent cardiopulmonary bypass and 45 minutes of deep hypothermic circulatory arrest. Hemodynamic and pulmonary function data were acquired before cardiopulmonary bypass and at 30 and 60 minutes after bypass. RESULTS In the control group, pulmonary compliance, alveolar-arterial gradient, and pulmonary vascular resistance were significantly impaired after bypass (P <.01 for each by analysis of variance). In the group that received methylprednisolone, compliance (P =.02), alveolar-arterial gradient (P =.0003), pulmonary vascular resistance (P =.007), and extracellular fluid accumulation (P =.003) were significantly better after bypass when compared with the control group. Results for the group that received no preoperative treatment fell between the control group and the group that received methylprednisolone. CONCLUSIONS When given 8 hours and immediately before the operation, methylprednisolone improves pulmonary compliance after bypass, alveolar-arterial gradient, and pulmonary vascular resistance compared with no treatment. The addition of methylprednisolone to the cardiopulmonary bypass circuit prime is beneficial but inferior to preoperative administration.

Marginal Cardiac Allografts Do Not Have Increased Primary Graft Dysfunction in Alternate List Transplantation

Background— Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.1 The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.2 The objective of this study was to determine the incidence of and predictors for PGD. Methods and Results— A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine ≥0.07 &mgr;g/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group.2 The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (≥4.5hours) were independent predictors of PGD. Conclusion— Select marginal donor hearts used in AL HT do not have an increased incidence of PGD. Pre-transplant VAD and prolonged ischemic times are more important determinants of PGD. These data support continued aggressive utilization of marginal donor hearts in AL HT.

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass

BACKGROUND Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Corticosteroids and Outcome in Children Undergoing Congenital Heart Surgery Analysis of the Pediatric Health Information Systems Database

Background— Children undergoing congenital heart surgery often receive corticosteroids with the aim of reducing the inflammatory response after cardiopulmonary bypass; however, the value of this approach is unclear. Methods and Results— The Pediatric Health Information Systems Database was used to evaluate outcomes associated with corticosteroids in children (0 to 18 years of age) undergoing congenital heart surgery at 38 US centers from 2003 to 2008. Propensity scores were constructed to account for potential confounders: age, sex, race, prematurity, genetic syndrome, type of surgery (Risk Adjustment in Congenital Heart Surgery [RACHS-1] category), center, and center volume. Multivariable analysis, adjusting for propensity score and individual covariates, was performed to evaluate in-hospital mortality, postoperative length of stay, duration of ventilation, infection, and use of insulin. A total of 46 730 children were included; 54% received corticosteroids. In multivariable analysis, there was no difference in mortality among corticosteroid recipients and nonrecipients (odds ratio, 1.13; 95% confidence interval, 0.98 to 1.30). Corticosteroids were associated with longer length of stay (least square mean difference, 2.18 days; 95% confidence interval, 1.62 to 2.74 days), greater infection (odds ratio, 1.27; 95% confidence interval, 1.10 to 1.46), and greater use of insulin (odds ratio, 2.45; 95% confidence interval, 2.24 to 2.67). There was no difference in duration of ventilation. In analysis stratified by RACHS-1 category, no significant benefit was seen in any group, and the association of corticosteroids with increased morbidity was most prominent in RACHS-1 categories 1 through 3. Conclusion— In this observational analysis of children undergoing congenital heart surgery, we were unable to demonstrate a significant benefit associated with corticosteroids and found that corticosteroids may be associated with increased morbidity, particularly in lower-risk patients. # Clinical Perspective {#article-title-43}Background— Children undergoing congenital heart surgery often receive corticosteroids with the aim of reducing the inflammatory response after cardiopulmonary bypass; however, the value of this approach is unclear. Methods and Results— The Pediatric Health Information Systems Database was used to evaluate outcomes associated with corticosteroids in children (0 to 18 years of age) undergoing congenital heart surgery at 38 US centers from 2003 to 2008. Propensity scores were constructed to account for potential confounders: age, sex, race, prematurity, genetic syndrome, type of surgery (Risk Adjustment in Congenital Heart Surgery [RACHS-1] category), center, and center volume. Multivariable analysis, adjusting for propensity score and individual covariates, was performed to evaluate in-hospital mortality, postoperative length of stay, duration of ventilation, infection, and use of insulin. A total of 46 730 children were included; 54% received corticosteroids. In multivariable analysis, there was no difference in mortality among corticosteroid recipients and nonrecipients (odds ratio, 1.13; 95% confidence interval, 0.98 to 1.30). Corticosteroids were associated with longer length of stay (least square mean difference, 2.18 days; 95% confidence interval, 1.62 to 2.74 days), greater infection (odds ratio, 1.27; 95% confidence interval, 1.10 to 1.46), and greater use of insulin (odds ratio, 2.45; 95% confidence interval, 2.24 to 2.67). There was no difference in duration of ventilation. In analysis stratified by RACHS-1 category, no significant benefit was seen in any group, and the association of corticosteroids with increased morbidity was most prominent in RACHS-1 categories 1 through 3. Conclusion— In this observational analysis of children undergoing congenital heart surgery, we were unable to demonstrate a significant benefit associated with corticosteroids and found that corticosteroids may be associated with increased morbidity, particularly in lower-risk patients.

Intermittent perfusion protects the brain during deep hypothermic circulatory arrest

BACKGROUND Deep hypothermic circulatory arrest (DHCA) has been shown to cause impairment in recovery of cerebral blood flow (CBF) and cerebral metabolism (CMRO2) proportional to the duration of the DHCA period. This effect on CMRO2 may be a marker for brain injury, because CMRO2 recovers normally after cardiopulmonary bypass (CPB) when DHCA is not used. The aim of this study was to investigate the effects of intermittent perfusion during DHCA on the recovery of CMRO2 after CPB and to correlate these findings with electron microscopy (EM) of the cerebral microcirculatory bed. METHODS Fifteen neonatal piglets were placed on CPB and cooled to 18 degrees C. Each animal then underwent either: (1) 60 minute continuous CPB (control), (2) 60 minute uninterrupted DHCA (UI-DHCA), or (3) 60 minute DHCA with intermittent perfusion (1 minute every 15 minutes) (I-DHCA). All animals were then rewarmed and weaned from CPB. Measurements of CBF and CMRO2 were taken before and after CPB. A further 9 animals underwent CPB without DHCA (2 animals) or with DHCA (7 animals), under various conditions of arterial blood gas management, intermittent perfusion, and reperfusion time. RESULTS UI-DHCA resulted in significant impairment to recovery of CMRO2 after CPB (p < 0.05). Regardless of the blood gas strategy used, the EM after UI-DHCA revealed extensive damage characterized by perivascular intracellular and organelle edema, and vascular collapse. I-DHCA, on the other hand, produced a pattern of normal CMRO2 recovery identical to controls, and the EM was normal for both these groups. CONCLUSIONS Intermittent perfusion during DHCA is clinically practical and results in normal cerebral metabolic and ultrastructural recovery. Furthermore, the correlation between brain structure and CMRO2 suggests that monitoring CMRO2 during the operation may be an outstanding way to investigate new strategies for neuroprotection designed to reduce cerebral damage in children undergoing correction of congenital cardiac defects.

Total respiratory support from swine lungs in primate recipients

UNLABELLED The use of nonhuman lung donors, such as swine, has the potential to provide an unlimited supply of organs. However, hyperacute rejection has prevented pulmonary xenotransplantation. OBJECTIVE Our aim was to test the hypothesis that immunodepletion by pretransplantation swine lung perfusion will prevent hyperacute swine-to-primate pulmonary xenograft rejection and allow for a functional swine pulmonary xenograft. METHODS Seven baboons underwent left pneumonectomy followed by orthotopic transplantation of the swine left lung. Four baboons received immunodepletion by perfusion with swine lungs before transplantation, and three received no treatment before transplantation. RESULTS After transplantation, pulmonary xenografts from immunodepleted baboons had a low pulmonary vascular resistance and a high pulmonary blood flow compared with control animals, which had a high pulmonary vascular resistance and a low pulmonary blood flow. After 60 minutes of reperfusion, three of four immunodepleted animals also tolerated complete occlusion of the right pulmonary artery, with the baboon relying completely on the swine pulmonary xenograft for respiratory function for 11 hours. Pathologic analysis of peripheral lung biopsy specimens taken from control lungs displayed alveolar disruption and hemorrhage within small vessels, whereas swine lungs transplanted into immunodepleted baboons displayed little histologic evidence of injury. Furthermore, pulmonary xenografts transplanted into immunodepleted baboons demonstrated excellent respiratory function and adequate hemodynamics during occlusion of the right pulmonary artery. CONCLUSION Hyperacute pulmonary xenograft rejection can be prevented by pretransplantation swine lung perfusion. Swine pulmonary xenografts can provide complete respiratory support in primates when rejection is prevented.

Left Ventricular Assist Device Destination Therapy Versus Extended Criteria Cardiac Transplant

BACKGROUND End-stage heart failure is a growing problem associated with a high mortality using conventional medical care. Although cardiac transplantation is an excellent treatment option, it is a limited resource and most patients are ineligible for cardiac transplantation using standard listing criteria. Increasingly, newer surgical options for these patients include the usage of marginal donor organs in an extended criteria-alternate list heart transplant program (EC-AL), or left ventricular assist devices as destination therapy (DT-LVAD). The purpose of this study was to compare baseline characteristics and outcomes after EC-AL versus DT-LVAD. METHODS From March 2000 to August 2008, 153 consecutive patients who had been turned down for standard heart transplantation underwent either EC-AL or DT-LVAD. The most common reasons for standard heart transplant ineligibility for both groups were advanced age, diabetes mellitus with end-organ dysfunction, and significant renal insufficiency. Patients in the alternate list program received a donor organ that had been turned down by all other centers for standard list recipients. The most common reasons for donor heart refusal were decreased left ventricular function, left ventricle hypertrophy, or coronary artery disease. Outcomes for both groups were retrospectively reviewed after Institutional Review Board permission was obtained. Comparisons were also made between patients that had been matched by propensity score analysis. RESULTS In all, 93 patients underwent EC-AL, and 60 underwent DT-LVAD. Baseline preoperative characteristics of both groups were similar except that 87% of DT-LVAD patients (52 of 60) required preoperative mechanical or inotropic support whereas only 51% of EC-AL patients (47 of 93) required support (p<0.0001). Thirty-day operative mortality and 1-year survival were 2.5% and 82.2% for EC-AL and 6.7% and 77.5% DT-LVAD, respectively (p=0.2411 and p=0.5036). Overall survival at 3 years was better for EC-AL versus DT-LVAD. The DT-LVAD patients had improved survival compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial DT-LVAD cohort, a historical control. These findings were corroborated in the analysis of propensity-matched patients. CONCLUSIONS Preoperatively, the DT-LVAD cohort was more unstable, with greater need for inotropes or mechanical support. Despite this, perioperative and 1-year mortality was similar for the two groups. Three-year survival was better for EC-AL. The DT-LVAD patient survival was better than that of the REMATCH DT-LVAD cohort.

Center Variation in Hospital Costs for Patients Undergoing Congenital Heart Surgery

Background— Congenital heart disease consumes significant health care resources; however, there are limited data regarding factors affecting resource utilization. The purpose of this study was to evaluate variation between centers in total hospital costs for 4 congenital heart operations of varying complexity and associated factors. Methods and Results— The Premier Database was used to evaluate total cost in children undergoing isolated atrial septal defect (ASD) repair, ventricular septal defect (VSD) repair, tetralogy of Fallot (TOF) repair, or arterial switch operation (ASO) from 2001 to 2007. Mixed models were used to evaluate the impact of center on total hospital costs adjusting for patient and center characteristics and length of stay. A total of 2124 patients were included: 719 ASD (19 centers), 792 VSD (20 centers), 420 TOF (17 centers), and 193 ASO (13 centers). Total cost increased with complexity of operation from median

Mini-circuit cardiopulmonary bypass with vacuum assisted venous drainage: feasibility of an asanguineous prime in the neonate

12 761 (ASD repair) to