Gil Wernovsky

Developmental and Neurologic Status of Children after Heart Surgery with Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

Background Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants. We compared the developmental and neurologic sequelae of these two strategies one year after surgery. Methods Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass. Developmental and neurologic evaluations and magnetic resonance imaging (MRI) were performed at one year of age. Results Of the 171 patients enrolled in the study, 155 were evaluated. After adjustment for the presence or absence of a ventricular septal defect, the infants assigned to circulatory arrest, as compared with those assigned to low-flow bypass, had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development (a 6.5-point deficit, P = 0.01) and a hig...

Postoperative Course and Hemodynamic Profile After the Arterial Switch Operation in Neonates and Infants A Comparison of Low-Flow Cardiopulmonary Bypass and Circulatory Arrest

BACKGROUND The neurological morbidity associated with prolonged periods of circulatory arrest has led some cardiac surgical teams to promote continuous low-flow cardiopulmonary bypass as an alternative strategy. The nonneurological postoperative effects of both techniques have been previously studied only in a limited fashion. METHODS AND RESULTS We compared the hemodynamic profile (cardiac index and systemic and pulmonary vascular resistances), intraoperative and postoperative fluid balance, and perioperative course after deep hypothermia and support consisting predominantly of total circulatory arrest or low-flow cardiopulmonary bypass in a randomized, single-center trial. Eligibility criteria included a diagnosis of transposition of the great arteries and a planned arterial switch operation before the age of 3 months. Of the 171 patients, 129 (66 assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had an associated ventricular septal defect. There were 3 (1.8%) hospital deaths. Patients assigned to low-flow bypass had significantly greater weight gain and positive fluid balance compared with patients assigned to circulatory arrest. Despite the increased weight gain in the infants assigned to low-flow bypass, the duration of mechanical ventilation, stay in the intensive care unit, and hospital stay were similar in both groups. Hemodynamic measurements were made in 122 patients. During the first postoperative night, the cardiac index decreased (32.1 +/- 15.4%, mean +/- SD), while pulmonary and systemic vascular resistance increased. The measured cardiac index was < 2.0 L.min-1.m-2 in 23.8% of the patients, with the lowest measurement typically occurring 9 to 12 hours after surgery. Perfusion strategy assignment was not associated with postoperative hemodynamics or other nonneurological postoperative events. CONCLUSIONS After heart surgery in neonates and infants, both low-flow bypass and circulatory arrest perfusion strategies have comparable effects on the nonneurological postoperative course and hemodynamic profile.

Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease

Background—Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results—The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-&mgr;g/kg bolus over 60 minutes followed by a 0.25-&mgr;g/kg per min infusion for 35 hours; high dose, 75-&mgr;g/kg bolus followed by a 0.75-&mgr;g/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P =0.023) in 238 treated patients and 64% (P =0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P =0.049). Conclusions—The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

Fontan operation in five hundred consecutive patients: Factors influencing early and late outcome ☆ ☆☆ ★ ★★ ♢ ♢♢ ♦

OBJECTIVES The purpose of this study was to review a large, evolving, single-center experience with the Fontan operation and to determine risk factors influencing early and late outcome. METHODS The first 500 patients undergoing modifications of the Fontan operation at our institution were identified. Perioperative variables were recorded and a cross-sectional review of survivors was undertaken. RESULTS The incidence of early failure decreased from 27.1% in the first quartile of the experience to 7.5% in the last quartile. In a multivariate model, the following variables were associated with an increased probability of early failure: a mean preoperative pulmonary artery pressure of 19 mm Hg or more (p < 0.001), younger age at operation (p = 0.001), heterotaxy syndrome (p = 0.03), a right-sided tricuspid valve as the only systemic atrioventricular valve (p = 0.001), pulmonary artery distortion (p = 0.04), an atriopulmonary connection originating at the right atrial body or appendage (p = 0.001), the absence of a baffle fenestration (p = 0.002), and longer cardiopulmonary bypass time (p = 0.001). An increased probability of late failure was associated with the presence of a pacemaker before the Fontan operation (p < 0.001). A morphologically left ventricle with normally related great arteries or a single right ventricle (excluding heterotaxy syndrome and hypoplastic left heart syndrome) were associated with a decreased probability of late failure (p = 0.003). CONCLUSIONS These analyses indicate that early failure has declined over the study period and that this decline is related in part to procedural modifications. A continuing late hazard phase is associated with few patient-related variables and does not appear related to procedural variables.

Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: The Boston Circulatory Arrest Trial

OBJECTIVES Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery, total circulatory arrest and low-flow cardiopulmonary bypass, results in better neurodevelopmental outcomes at school age. METHODS In a single-center trial, infants with dextrotransposition of the great arteries underwent the arterial switch operation after random assignment to either total circulatory arrest or low-flow cardiopulmonary bypass. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%). RESULTS Treatment groups did not differ in terms of most outcomes, including neurologic status, Full-Scale or Performance IQ score, academic achievement, memory, problem solving, and visual-motor integration. Children assigned to total circulatory arrest performed worse on tests of motor function including manual dexterity with the nondominant hand (P =.003), apraxia of speech (P =.01), visual-motor tracking (P =.01), and phonologic awareness (P =.003). Assignment to low-flow cardiopulmonary bypass was associated with a more impulsive response style on a continuous performance test of vigilance (P <.01) and worse behavior as rated by teachers (P =.05). Although mean scores on most outcomes were within normal limits, neurodevelopmental status in the cohort as a whole was below expectation in many respects, including academic achievement, fine motor function, visual-spatial skills, working memory, hypothesis generating and testing, sustained attention, and higher-order language skills. CONCLUSIONS Use of total circulatory arrest to support vital organs during heart surgery in infancy is generally associated with greater functional deficits than is use of low-flow cardiopulmonary bypass, although both strategies are associated with increased risk of neurodevelopmental vulnerabilities.

Developmental and Neurological Status of Children at 4 Years of Age After Heart Surgery With Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

BACKGROUND It is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest (CA) or low-flow cardiopulmonary bypass. METHODS AND RESULTS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass. Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children (97%). Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA. The CA group scored lower on tests of motor function (gross motor, P=0.01; fine motor, P=0.03) and had more severe speech abnormalities (oromotor apraxia, P=0.007). Seizures in the perioperative period, detected either clinically or by continuous electroencephalographic monitoring, were associated with lower mean IQ scores (12.6 and 7.7 points, respectively) and increased risk of neurological abnormalities (odds ratios, 8.4 and 5.6, respectively). The performance of the full cohort was below expectations in several domains, including IQ, expressive language, visual-motor integration, motor function, and oromotor control. CONCLUSIONS Use of CA to support vital organs during open heart surgery in infancy is associated, at the age of 4 years, with worse motor coordination and planning but not with lower IQ or with worse overall neurological status.

Brain maturation is delayed in infants with complex congenital heart defects.

OBJECTIVE Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. This study tests the hypothesis that congenital heart defects delay in utero structural brain development. METHODS Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue. RESULTS The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 +/- 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 +/- 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development. CONCLUSION Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.

Factors influencing early and late outcome of the arterial switch operation for transposition of the great arteries

Between January 1983 and January 1992, 470 patients underwent an arterial switch operation at our institution. An intact (or virtually intact) ventricular septum was present in 278 of 470 (59%); a ventricular septal defect was closed in the remaining 192. Survivals at 1 month and 1, 5, and 8 years among the 470 patients were 93%, 92%, 91%, and 91%, respectively. The hazard function for death (at any time) had a rapidly declining single phase that approached zero by one year after the operation. Risk factors for death included coronary artery patterns with a retropulmonary course of the left coronary artery (two types) and a pattern in which the right coronary artery and left anterior descending arose from the anterior sinus with a posterior course of the circumflex coronary. The only procedural risk factor identified was augmentation of the aortic arch; longer duration of circulatory arrest was also a risk factor for death. Earlier date of operation was a risk factor for death, but only in the case of the senior surgeon. Reinterventions were performed to relieve right ventricular and/or pulmonary artery stenoses alone in 28 patients. The hazard function for reintervention for pulmonary artery or valve stenosis revealed an early phase that peaked at 9 months after the operation and a constant phase for the duration of follow-up. Incremental risk factors for the early phase included multiple ventricular septal defects, the rapid two-stage arterial switch, and a coronary pattern with a single ostium supplying the right coronary and left anterior descending, with a retropulmonary course of the circumflex. The need for reintervention has decreased with time. The arterial switch operation can currently be performed early in life with a low mortality risk (< 5%) and a low incidence of reintervention (< 10%) for supravalvular pulmonary stenosis. The analyses indicate that both the mortality and reintervention risks are lower in patients with less complex anatomy.

Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes.

Objective. Necrotizing enterocolitis (NEC) is primarily a disease of the premature infant. Among children born at term, however, congenital heart disease may be an important predisposing factor for this condition. To determine risk factors for NEC in patients with congenital heart disease, we conducted a case–control study of neonates with cardiac disease admitted to the cardiac intensive care unit at our center during the 4-year period from January 1995 to December 1998. Methods. Cardiac diagnosis and age at admission were analyzed for association with NEC among the 643-patient inception cohort. Demographic, preoperative, and operative variables were recorded retrospectively in 21 neonates with congenital heart disease who developed NEC and 70 control neonates matched by diagnosis and age at admission. Using parametric and nonparametric analysis, cases and controls were compared with respect to previously identified risk factors for NEC. Results. Among the entire cohort of 643 neonates with heart disease admitted to the cardiac intensive care unit, diagnoses of hypoplastic left heart syndrome (odds ratio [OR] = 3.8 [1.6–9.1]) and truncus arteriosus or aortopulmonary window (OR = 6.3 [1.7–23.6]) were independently associated with development of NEC by multivariable analysis. In the case–control analysis, earlier gestational age at birth (36.7 ± 2.7 weeks vs 38.1 ± 2.3 weeks), prematurity (OR = 3.9 [1.2–12.5]), highest dose of prostaglandin >0.05 μg/kg/minute (OR = 3.9 [1.2–12.5]), and episodes of low cardiac output (meeting specific laboratory criteria) or clinical shock (OR = 6.5 [1.8–23.5]) correlated with the development of NEC. Earlier gestational age and episodes of low output were the only factors that remained significantly associated with NEC by multivariable analysis. Although there was no difference in hospital mortality between patients with and without NEC, mean hospital stay was significantly longer in those who developed NEC (36 ± 22 days vs 19 ± 14 days). Conclusions. The risk of NEC in neonates with congenital heart disease is substantial. Factors associated with an elevated risk of NEC in infants with heart disease include premature birth, hypoplastic left heart syndrome, truncus arteriosus, and episodes of poor systemic perfusion or shock. Heightened suspicion is warranted in newborns with these risk factors.

Factors that influence the development of atrial flutter after the fontan operation

OBJECTIVES Atrial flutter is a frequent, potentially fatal complication of the Fontan operation, but risk factors for its development are ill defined. We evaluated clinical features that might predict the development of atrial flutter in patients who had a Fontan operation. METHODS We evaluated 334 early survivors of a Fontan operation done between April 1973 and July 1991 (mean follow-up, 5.0 +/- 3.8 years). Evaluation included electrocardiography, Holter monitor recordings, and chart review. Modifications of the Fontan operation included an extracardiac conduit (n = 43), an atriopulmonary anastomosis (n = 117), or a total cavopulmonary anastomosis (n = 174). Patient, time, and procedure-related variables were analyzed with respect to the development of atrial flutter. RESULTS Atrial flutter was identified in 54 (16%) patients at a mean of 5.3 +/- 4.7 years (range 0 to 19.7 years) after Fontan operation. Atrial flutter developed sooner and was more likely to occur in patients who were older at the time of Fontan operation (12.4 +/- 7.6 vs 6.3 +/- 5.2 years; p < 0.001), had a longer follow-up interval (8.7 +/- 3.9 vs 4.4 +/- 3.4 years; p < 0.001), had a prior atrial septectomy or pulmonary artery reconstruction (p < 0.01), and had worse New York Heart Association class symptoms (p < 0.02). The presence of sinus node dysfunction was associated with a higher incidence of atrial flutter (p < 0.001). Although there was a lower prevalence of atrial flutter in those patients with a total cavopulmonary anastomosis, the follow-up for this group was shorter. Anatomic diagnoses, perioperative hemodynamics, and other previous palliative operations were not associated with an increased incidence of atrial flutter. Multivariate analysis identified age at operation, duration of follow-up, extensive atrial baffling, and type of repair as factors associated with the development of atrial flutter after Fontan operation. CONCLUSION Atrial flutter continues to develop with time after the Fontan operation. Further follow-up is necessary to determine whether a total cavopulmonary anastomosis reduces the incidence of atrial flutter.