Lisa M. Montenegro

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.

Arterial and venous contributions to near-infrared cerebral oximetry.

BackgroundCerebral oximetry is a noninvasive bedside technology using near-infrared light to monitor cerebral oxygen saturation (Sco2) in an uncertain mixture of arteries, capillaries, and veins. The present study used frequency domain near-infrared spectroscopy to determine the ratio of arterial and venous blood monitored by cerebral oximetry during normoxia, hypoxia, and hypocapnia. MethodsTwenty anesthetized children aged < 8 yr with congenital heart disease of varying arterial oxygen saturation (Sao2) were studied during cardiac catheterization. Sco2, Sao2, and jugular bulb oxygen saturation (Sjo2) were measured by frequency domain near-infrared spectroscopy and blood oximetry at normocapnia room air, normocapnia 100% inspired O2, and hypocapnia room air. ResultsAmong subject conditions, Sao2 ranged from 68% to 100%, Sjo2 from 27% to 96%, and Sco2 from 29% to 92%. Sco2 was significantly related to Sao2 (y = 0.85 × −17, r = 0.47), Sjo2 (y = 0.77 × +13, r = 0.70), and the combination (Sco2 = 0.46 Sao2 + 0.56 Sjo2 − 17, R = 0.71). The arterial and venous contribution to cerebral oximetry was 16 ± 21% and 84 ± 21%, respectively (where Sco2 = &agr; Sao2 + &bgr; Sjo2 with &agr; and &bgr; being arterial and venous contributions). The contribution was similar among conditions but differed significantly among subjects (range, ≈ 40:60 to ≈ 0:100, arterial:venous). ConclusionsCerebral oximetry monitors an arterial/venous ratio of 16:84, similar in normoxia, hypoxia, and hypocapnia. Because of biologic variation in cerebral arterial/venous ratios, use of a fixed ratio is not a good method to validate the technology.

Preoperative Brain Injury in Transposition of the Great Arteries Is Associated With Oxygenation and Time to Surgery, Not Balloon Atrial Septostomy

Background— Preoperative brain injury is an increasingly recognized phenomenon in neonates with complex congenital heart disease. Recently, reports have been published that associate preoperative brain injury in neonates with transposition of the great arteries with the performance of balloon atrial septostomy (BAS), a procedure that improves systemic oxygenation preoperatively. It is unclear whether BAS is the cause of brain injury or is a confounder, because neonates who require BAS are typically more hypoxemic. We sought to determine the relationship between preoperative brain injury in neonates with transposition of the great arteries and the performance of BAS. We hypothesized that brain injury results from hypoxic injury, not from the BAS itself. Methods and Results— Infants with transposition of the great arteries (n=26) were retrospectively included from a larger cohort of infants with congenital heart disease who underwent preoperative brain MRI as part of 2 separate prospective studies. Data collected included all preoperative pulse oximetry recordings, all values from preoperative arterial blood gas measurements, and BAS procedure data. MRI scans were performed on the day of surgery, before the surgical repair. Of the 26 neonates, 14 underwent BAS. No stroke was seen in the entire cohort, whereas 10 (38%) of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. Periventricular leukomalacia was not associated with BAS; however, neonates with periventricular leukomalacia had lower preoperative oxygenation (P=0.026) and a longer time to surgery (P=0.028) than those without periventricular leukomalacia. Conclusions— Preoperative brain injury in neonates with transposition of the great arteries is associated with hypoxemia and longer time to surgery. We found no association between BAS and brain injury.

Cerebral oxygen saturation before congenital heart surgery

BACKGROUND In congenital heart disease (CHD), neurologic abnormalities suggestive of hypoxia-ischemia are often apparent before cardiac surgery. To evaluate preoperative cerebral oxygenation, this study determined cerebral O2 saturation (ScO2) in CHD and healthy children. METHODS Ninety-one CHD and 19 healthy children aged less than 7 years were studied before surgical or radiologic procedures. Arterial saturation (SaO2) and ScO2 were measured by pulse-oximetry and near infrared cerebral oximetry. Cerebral O2 extraction (CEO2) was calculated (SaO2-ScO2). SaO2, ScO2, and CEO2 were compared among diagnoses. Multivariable regression was performed between ScO2 and clinical variables. RESULTS In healthy subjects, ScO2 (68%+/-10%) and CEO2 (30%+/-11%) were similar to patients with ventricular septal defect, aortic coarctation, and single ventricle after Fontan operation. ScO2 was significantly decreased in patients with patent ductus arteriosus (53%+/-8%), tetralogy of Fallot (57%+/-12%), hypoplastic left heart syndrome (46%+/-8%), pulmonary atresia (38%+/-6%), and single ventricle after aortopulmonary shunt (50%+/-7%), or bidirectional Glenn operation (43%+/-6%). CEO2 was significantly different only in patent ductus arteriosus (46%+/-8%) and hypoplastic left heart syndrome (38%+/-12%). In multivariable regression, only SaO2 was related to ScO2 (R = 0.63, p < 0.001). CONCLUSIONS Cerebral oxygenation in CHD varies with anatomy and arterial saturation, and in some patients, it is very low compared with healthy subjects.

Perioperative Stroke in Infants Undergoing Open Heart Operations for Congenital Heart Disease

BACKGROUND The prevalence of perioperative stroke in infants undergoing operations for congenital heart disease has not been well described. The objectives of this study were to determine the prevalence of stroke as assessed by postoperative brain magnetic resonance imaging (MRI), characterize the neuroanatomic features of focal ischemic injury, and identify risk factors for its development. METHODS Brain MRI was performed in 122 infants 3 to 14 days after cardiac operation with cardiopulmonary bypass, with or without deep hypothermic circulatory arrest. Preoperative, intraoperative, and postoperative data were collected. Risk factors were tested by logistic regression for univariate and multivariate associations with stroke. RESULTS Stroke was identified in 12 of 122 patients (10%). Strokes were preoperative in 6 patients and possibly intraoperative or postoperative in the other 6 patients, and were clinically silent except in 1 patient who had clinical seizures. Arterial-occlusive and watershed infarcts were identified with equal distribution in both hemispheres. Multivariate analysis identified lower birth weight, preoperative intubation, lower intraoperative hematocrit, and higher blood pressure at admission to the cardiac intensive care unit postoperatively as significant factors associated with stroke. Prematurity, younger age at operation, duration of cardiopulmonary bypass, and use of deep hypothermic circulatory arrest were not significantly associated with stroke. CONCLUSIONS The prevalence of stroke in infants undergoing operations for congenital heart disease was 10%, half of which occurred preoperatively. Most were clinically silent and undetected without neuroimaging. Mechanisms included thromboembolism and hypoperfusion, with patient-specific, procedure-specific, and postoperative contributions to increased risk.

Effects of Inspired Hypoxic and Hypercapnic Gas Mixtures on Cerebral Oxygen Saturation in Neonates with Univentricular Heart Defects

Background Neonates with functional single ventricle often require hypoxic or hypercapnic inspired gas mixtures to reduce pulmonary overcirculation and improve systemic perfusion. Although the impact of these treatments on arterial oxygen saturation has been described, the effects on cerebral oxygenation remain uncertain. This study examined the effect of these treatments on cerebral oxygen saturation and systemic hemodynamics. Methods Neonates with single ventricle mechanically ventilated with room air were enrolled in a randomized crossover trial of 17% inspired oxygen or 3% inspired carbon dioxide. Each treatment lasted 10 min, followed by a 10–20-min washout period. Cerebral and arterial oxygen saturation were measured by cerebral and pulse oximetry, respectively. Cerebral oxygen saturation, arterial oxygen saturation, and other physiologic data were continuously recorded. Results Three percent inspired carbon dioxide increased cerebral oxygen saturation (56 ± 13 to 68 ± 13%;P < 0.01), whereas 17% inspired oxygen had no effect (53 ± 13 to 53 ± 14%;P = 0.8). Three percent inspired carbon dioxide increased the mean arterial pressure (45 ± 8 to 50 ± 9 mmHg;P < 0.01), whereas 17% inspired oxygen had no effect. And 3% inspired carbon dioxide decreased arterial p H and increased arterial carbon dioxide and oxygen tensions. Conclusions Inspired 3% carbon dioxide improved cerebral oxygenation and mean arterial pressure. Treatment with 17% inspired oxygen had no effect on either.

Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics.

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO2) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (SvO2) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO2 in physiologic units. In addition, microvascular tissue oxygenation (StO2) and indices of microvascular CBF (BFI) and CMRO2 (CMRO2i) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O2/minute per 100 g, respectively. These CBF and CMRO2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global SvO2, CBF, and CMRO2 with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R2=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

Successful Use of the Total Artificial Heart in the Failing Fontan Circulation

Typical left ventricular assist devices are often ineffective for the failing Fontan circulation. We report the first successful use of a total artificial heart as a bridge to transplant in a patient who had previously undergone a Fontan operation.

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome

OBJECTIVE Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. METHODS Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. RESULTS A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). CONCLUSIONS A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury.

Critical heart disease in the neonate: Presentation and outcome at a tertiary care center

Objective: To define the modes of presentation, incidence of major organ dysfunction, predictors of hospital mortality, and adverse outcomes in neonates with critical heart disease admitted to a tertiary care center. Design: Retrospective chart review. Setting: A tertiary care pediatric cardiac intensive care unit and neonatal intensive care unit. Patients: The medical records for all neonates (≤30 days of age) with heart disease admitted to the cardiac intensive care unit or neonatal intensive care unit between October 1, 2002, and September 30, 2003, were reviewed. Interventions: None. Measurements and Main Results: A total of 190 neonates met inclusion criteria during this 1-yr period, of which 146 (77%) had at least one surgical procedure. Single ventricle heart disease was present in 42%. The most common mode of presentation was following a prenatal diagnosis (53%), followed by diagnosis in the newborn nursery (38%) and diagnosis after newborn hospital discharge (8%). The most common presenting findings in the newborn nursery were isolated murmur (38%) or cyanosis (32%), while circulatory collapse (38%) was the most common presentation after discharge. For the entire study cohort, 13% had a known genetic syndrome, 23% had a major noncardiac congenital anomaly, and 16% weighed <2.5 kg. The hospital mortality for the entire cohort was 7.4%. Risk factors associated with an increased risk of hospital mortality included younger age at admission, higher number of cardiopulmonary bypass runs, and need for postoperative cardiopulmonary resuscitation. Total hospital length of stay was >1 month in 17% of neonates. Conclusions: In patients with complex congenital heart disease, including nearly half with single ventricle heart disease, neonatal hospital mortality was 7%. These patients have a high frequency of multiple congenital anomalies, genetic syndromes, low birth weight, and prolonged length of stay.