Frank A. Pigula

Pulmonary Valve Replacement in Tetralogy of Fallot Impact on Survival and Ventricular Tachycardia

Background— Pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (TOF) reduces pulmonary regurgitation and decreases right ventricular (RV) dilation, but its long-term impact on ventricular tachycardia (VT) and mortality is unknown. This study aimed to determine the incidence of death and VT in TOF after PVR and to test the hypothesis that PVR leads to improvement in these outcomes. Methods and Results— A total of 98 patients with TOF and late PVR for RV dilation were identified. Matched control subjects were identified for 77 of these patients; control subjects had TOF with RV dilation but no PVR. Matching was done by age (±2 years) and baseline QRS duration (±30 ms). No significant differences were found in age, QRS duration, type or decade of initial repair, age at TOF repair, or presence of pre-PVR VT between the 2 groups; limited echocardiographic and magnetic resonance imaging data showed no difference in left ventricular function but more RV dilation among PVR patients than control subjects. In the PVR group, 13 events occurred over 272 patient-years. No significant change in QRS duration was seen for any group. Overall 5- and 10-year freedom from death, VT, or both was 80% and 41%, respectively. In the matched comparison, no significant differences were seen in VT, death, or combined VT and/or death (P=0.32, P=0.06 [nearly favoring controls], and P=0.21). Conclusions— This cohort experienced either VT or death every 20 patient-years. In a matched comparison with a similar TOF group, late PVR for symptomatic pulmonary regurgitation/RV dilation did not reduce the incidence of VT or death.

Regional low-flow perfusion provides cerebral circulatory support during neonatal aortic arch reconstruction

OBJECTIVE Because of concerns regarding the effects of deep hypothermia and circulatory arrest on the neonatal brain, we have developed a technique of regional low-flow perfusion that provides cerebral circulatory support during neonatal aortic arch reconstruction. METHODS We studied the effects of regional low-flow perfusion on cerebral oxygen saturation and blood volume as measured by near-infrared spectroscopy in 6 neonates who underwent aortic arch reconstruction and compared these effects with 6 children who underwent cardiac repair with deep hypothermia and circulatory arrest. RESULTS All the children survived with no observed neurologic sequelae. Near-infrared spectroscopy documented significant decreases in both cerebral blood volume and oxygen saturations in children who underwent repair with deep hypothermia and circulatory arrest as compared with children with regional low-flow perfusion. Reacquisition of baseline cerebral blood volume and cerebral oxygen saturations were accomplished with a regional low-flow perfusion rate of 20 mL x kg(-1) x min(-1). CONCLUSIONS Regional low-flow perfusion is a safe and simple bypass management technique that provides cerebral circulatory support during neonatal aortic arch reconstruction. The reduction of deep hypothermia and circulatory arrest time required may reduce the risk of cognitive and psychomotor deficits.

Real-Time Continuous Glucose Monitoring in Pediatric Patients During and After Cardiac Surgery

OBJECTIVES. Given the demonstrated benefit of euglycemia in critically ill patients as well as the risk for hypoglycemia during insulin infusion in children, we sought to validate a subcutaneous sensor for real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. METHODS. Children up to 36 months of age who were undergoing cardiac bypass surgery were recruited. After anesthetic induction, a continuous glucose-monitoring system sensor (CGMS, Medtronic Minimed, Northridge, CA) was inserted subcutaneously. Sensors remained in place for up to 72 hours. Arterial blood glucose was measured intermittently in the central laboratory (Bayer Rapidlab 860, Tarrytown, NY). Sensor data, after prospective calibration with 6-hourly laboratory values using the proprietary Medtronic Minimed Guardian RT algorithm, were compared with all laboratory glucose values. Statistical analysis was performed to test whether sensor performance was affected by body temperature, inotrope dose, or body-wall edema. RESULTS. Twenty patients were enrolled in the study for a total of 40 study days and 246 paired sensor and laboratory glucose values. Consensus error grid analysis demonstrated that 72.0% of sensor value comparisons were within zone A (no effect on clinical action), and 27.6% of comparisons were within zone B (altered clinical action of little or no effect on outcome), with a mean absolute relative deviation of 17.6% for all comparisons. One comparison (0.4%) was in zone C (altered clinical action likely to affect outcome). No significant correlations were found between sensor performance and body temperature, inotrope dose, or body-wall edema. All patients tolerated the sensors well without bleeding or tissue reaction. CONCLUSIONS. Guardian RT real-time subcutaneous blood glucose measurement is safe and potentially useful for continuous glucose monitoring in critically ill children. Subcutaneous sensors performed well in the setting of hypothermia, inotrope use, and edema. These sensors facilitate identifying and following the effects of interventions to control blood glucose.

Acute and chronic morbidity differences between muscle-sparing and standard lateral thoracotomies ☆ ☆☆ ★ ★★ ♢

INTRODUCTION Opinions differ regarding differences between totally muscle-sparing thoracotomy and standard lateral thoracotomy approaches to pulmonary resection with respect to operative time, postoperative pain and morbidity, and occurrence of chronic postthoracotomy pain syndromes and subjective shoulder dysfunction. METHODS Three hundred thirty-five consecutive patients undergoing muscle-sparing thoracotomy (n = 148) or lateral thoracotomy (n = 187) to accomplish lobectomy for stage I lung cancer during a 40-month period were evaluated. Local rib resection was not employed, and two chest tubes were routinely used after operation in both thoracotomy groups. Epidural analgesia use was similar after operation in the two groups (muscle-sparing thoracotomy 38%, lateral thoracotomy 38%). The postoperative hospital courses and patient functional statuses at 1 year were examined. RESULTS Demographic analyses demonstrated no differences between groups in age, sex, or association of significant comorbid medical illness. Although the operative time required for muscle-sparing thoracotomy was shorter, there were no differences between thoracotomy approaches in any of the other primary acute postoperative variables analyzed (chest tube duration, length of hospital stay, postoperative narcotic requirements, and postoperative mortality). The frequencies of chronic pain and shoulder dysfunction assessed 1 year after operation were also similar between thoracotomy groups. CONCLUSIONS The relative efficacies and rates of occurrence of acute or chronic morbidity are equivalent after muscle-sparing thoracotomy and standard lateral thoracotomy. Although muscle-sparing thoracotomy may possibly be performed more expediently, it appears that the singular advantage of muscle-sparing thoracotomy over standard lateral thoracotomy involves the preservation of chest wall musculature in case rotational muscle flaps should be needed later.

Relationship of Intraoperative Cerebral Oxygen Saturation to Neurodevelopmental Outcome and Brain Magnetic Resonance Imaging at 1 Year of Age in Infants Undergoing Biventricular Repair

Background— Near-infrared spectroscopy monitoring of cerebral oxygen saturation (rSo2) has become routine in many centers, but no studies have reported the relationship of intraoperative near-infrared spectroscopy to long-term neurodevelopmental outcomes after cardiac surgery. Methods and Results— Of 104 infants undergoing biventricular repair without aortic arch reconstruction, 89 (86%) returned for neurodevelopmental testing at 1 year of age. The primary near-infrared spectroscopy variable was the integrated rSo2 (area under the curve) for rSo2 ≤45%; secondary variables were the average and minimum rSo2 by perfusion phase and at specific time points. Psychomotor and mental development indexes of the Bayley scales, head circumference, neurological examination, and abnormalities on brain magnetic resonance imaging did not differ between subjects according to a threshold level for rSo2 of 45%. Lower Psychomotor Development Index scores were modestly associated with lower average (r=0.23, P=0.03) and minimum (r=0.22, P=0.04) rSo2 during the 60-minute period after cardiopulmonary bypass but not with other perfusion phases. Hemosiderin foci on brain magnetic resonance imaging were associated with lower average rSo2 from postinduction to 60 minutes post cardiopulmonary bypass (71±10% versus 78±6%, P=0.01) and with lower average rSO2 during the rewarming phase (72±12% versus 83±9%, P=.003) and during the 60-minute period following cardiopulmonary bypass (65±11% versus 75±10%, P=0.009). In regression analyses that adjusted for age ≤30 days, Psychomotor Development Index score (P=0.02) and brain hemosiderin (P=0.04) remained significantly associated with rSo2 during the 60-minute period following cardiopulmonary bypass. Conclusions— Perioperative periods of diminished cerebral oxygen delivery, as indicated by rSo2, are associated with 1-year Psychomotor Development Index and brain magnetic resonance imaging abnormalities among infants undergoing reparative heart surgery. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00006183.

Interim mortality in infants with systemic-to-pulmonary artery shunts.

BACKGROUND This retrospective review examines the risks and causes of death in infants with aortopulmonary shunts between the time of hospital discharge and planned reintervention. METHODS From January 1991 through December 2000, a total of 146 infants aged 60 days or less underwent placement of systemic-to-pulmonary artery shunts and were discharged from the hospital alive. Inpatient, outpatient, and autopsy records were reviewed. RESULTS Indications for surgery were single-ventricle anatomy in 90 cases and complex double-ventricle anatomy in 56. Of the patients, 21 (14%) died after discharge and before further planned surgery. Of these 21 infants, 17 (81%) were clinically doing well before sudden death. Autopsies were obtained in 15 cases and attributed the cause of death to shunt thrombosis in 5 infants (33%), myocardial infarction in 2 (13%), and pneumonia or lung disease in 3. Five autopsies were nondiagnostic. The mortality of patients discharged on aspirin (11.1%) was almost identical to that of patients discharged on no anticoagulation (12.3%). Four infants with sudden death had been notably irritable for 24 to 48 hours before death. CONCLUSIONS There is a significant incidence of sudden death among infants who have undergone shunting. Death may be preceded by unexplained irritability, and such symptoms should therefore be carefully evaluated. Autopsy-proven shunt thrombosis is one of the leading causes of interim sudden death, and aspirin therapy may not be helpful. Options to reduce interim mortality include alternative regimens of anticoagulation (such as low-molecular weight heparin), alternative conduit material, and earlier reoperation.

Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery

OBJECTIVES We previously reported that postoperative hemodynamics and developmental outcomes were better among infants randomized to a higher hematocrit value during hypothermic cardiopulmonary bypass. However, worse outcomes were concentrated in patients with hematocrit values of 20% or below, and the benefits of hematocrit values higher than 25% were uncertain. METHODS We compared perioperative hemodynamics and, at 1 year, developmental outcome and brain magnetic resonance imaging in a single-center, randomized trial of hemodilution to a hematocrit value of 25% versus 35% during hypothermic radiopulmonary bypass for reparative heart surgery in infants undergoing 2-ventricle repairs without aortic arch obstruction. RESULTS Among 124 subjects, 56 were assigned to the lower-hematocrit strategy (24.8% +/- 3.1%, mean +/- SD) and 68 to the higher-hematocrit strategy (32.6% +/- 3.5%). Infants randomized to the 25% strategy, compared with the 35% strategy, had a more positive intraoperative fluid balance (P = .007) and lower regional cerebral oxygen saturation at 10 minutes after cooling (P = .04) and onset of low flow (P = .03). Infants with dextro-transposition of the great arteries in the 25% group had significantly longer hospital stay. Other postoperative outcomes, blood product usage, and adverse events were similar in the treatment groups. At age 1 year (n = 106), the treatment groups had similar scores on the Psychomotor and Mental Development Indexes of the Bayley Scales; both groups scored significantly worse than population norms. CONCLUSIONS Hemodilution to hematocrit levels of 35% compared with those of 25% had no major benefits or risks overall among infants undergoing 2-ventricle repair. Developmental outcomes at age 1 year in both randomized groups were below those in the normative population.

Blood Transfusion After Pediatric Cardiac Surgery Is Associated With Prolonged Hospital Stay

BACKGROUND Red blood cell transfusion is associated with morbidity and mortality among adults undergoing cardiac surgery. We aimed to evaluate the association of transfusion with morbidity among pediatric cardiac surgical patients. METHODS Patients discharged after cardiac surgery in 2003 were retrospectively reviewed. The red blood cell volume administered during the first 48 postoperative hours was used to classify patients into nonexposure, low exposure (≤15 mL/kg), or high exposure (>15 mL/kg) groups. Cox proportional hazards modeling was used to evaluate the association of red blood cell exposure to length of hospital stay (LOS). RESULTS Of 802 discharges, 371 patients (46.2%) required blood transfusion. Demographic differences between the transfusion exposure groups included age, weight, prematurity, and noncardiac structural abnormalities (all p<0.001). Distribution of Risk Adjusted Classification for Congenital Heart Surgery, version 1 (RACHS-1) categories, intraoperative support times, and postoperative Pediatric Risk of Mortality Score, Version III (PRISM-III) scores varied among the exposure groups (p<0.001). Median duration of mechanical ventilation (34 hours [0 to 493] versus 27 hours [0 to 621] versus 16 hours [0 to 375]), incidence of infection (21 [14%] versus 29 [13%] versus 17 [4%]), and acute kidney injury (25 [17%] versus 29 [13%] versus 34 [8%]) were highest in the high transfusion exposure group when compared with the low or nontransfusion groups (all p<0.001). In a multivariable Cox proportional hazards model, both the low transfusion group (adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI]: 0.66 to 0.97, p=0.02) and high transfusion group (adjusted HR 0.66, 95% CI: 0.53 to 0.82, p<0.001) were associated with increased LOS. In subgroup analyses, both low transfusion (adjusted HR 0.81, 95% CI: 0.65 to 1.00, p=0.05) and high transfusion (adjusted HR 0.65, 95% CI: 0.49 to 0.87, p=0.004) in the biventricular group but not in the single ventricle group was associated with increased LOS. CONCLUSIONS Blood transfusion is associated with prolonged hospitalization of children after cardiac surgery, with biventricular patients at highest risk for increased LOS. Future studies are necessary to explore this association and refine transfusion practices.

The effect of cytokine gene polymorphisms on pediatric heart allograft outcome

BACKGROUND Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation. METHODS We performed cytokine genotyping using polymerase chain reaction-sequence specific primers in 93 pediatric heart transplant recipients and 29 heart donors for the following functional polymorphisms: tumor necrosis factor-alpha (TNF-alpha) (-308), interleukin (IL)-10 (-1082, -819, and -592), TGF-beta1 (codon 10 and 25), IL-6 (-174), and interferon-gamma (INF-gamma) (+874). The distribution of polymorphisms in this population did not differ from published controls. The patients were classified as either non-rejecters (0 or 1 episode) or rejecters (> 1 episode) based on the number of biopsy proven rejection episodes in the first year after transplantation. RESULTS Forty-two of the 69 TNF-alpha patients (61%) in the low producer group were non-rejecters, while 9 of the 24 (37.5%) with high TNF-alpha were non-rejecters (p = 0.047). In contrast, IL-10 genotype showed the opposite finding. Forty-two of the 66 patients (64%) in the high and intermediate IL-10 group were non-rejecters, while 9 of the 26 (35%) in the low IL-10 group were non-rejecters (p = 0.011). The combination of low TNF-alpha with a high or intermediate IL-10 genotype was associated with the lowest risk of rejection (34/49 or 69% non-rejecters). Neither the distribution of the IL-6, INF-gamma, and TGF-beta1 genotype in recipients nor the donor genotype showed any association with acute rejection. CONCLUSION Genetic polymorphisms that have been associated with low TNF-alpha and high IL-10 production are associated with a lower number of acute rejection episodes after pediatric heart transplantation.

A bioinspired soft actuated material.

A class of soft actuated materials that can achieve lifelike motion is presented. By embedding pneumatic actuators in a soft material inspired by a biological muscle fibril architecture, and developing a simple finite element simulation of the same, tunable biomimetic motion can be achieved with fully soft structures, exemplified here by an active left ventricle simulator.