Joseph R. Cava

Home surveillance program prevents interstage mortality after the Norwood procedure

OBJECTIVE To determine whether early identification of physiologic variances associated with interstage death would reduce mortality, we developed a home surveillance program. METHODS Patients discharged before initiation of home surveillance (group A, n = 63) were compared with patients discharged with an infant scale and pulse oximeter (group B, n = 24). Parents maintained a daily log of weight and arterial oxygen saturation according to pulse oximetry and were instructed to contact their physician in case of an arterial oxygen saturation less than 70% according to pulse oximetry, an acute weight loss of more than 30 g in 24 hours, or failure to gain at least 20 g during a 3-day period. RESULTS Interstage mortality among infants surviving to discharge was 15.8% (n = 9/57) in group A and 0% (n = 0/24) in group B (P =.039). Surveillance criteria were breached for 13 of 24 group B patients: 12 patients with decreased arterial oxygen saturation according to pulse oximetry with or without poor weight gain and 1 patient with poor weight gain alone. These 13 patients underwent bidirectional superior cavopulmonary connection (stage 2 palliation) at an earlier age, 3.7 +/- 1.1 months of age versus 5.2 +/- 2.0 months for patients with an uncomplicated interstage course (P =.028). A growth curve was generated and showed reduced growth velocity between 4 and 5 months of age, with a plateau in growth beyond 5 months of age. CONCLUSION Daily home surveillance of arterial oxygen saturation according to pulse oximetry and weight selected patients at increased risk of interstage death, permitting timely intervention, primarily with early stage 2 palliation, and was associated with improved interstage survival. Diminished growth identified 4 to 5 months after the Norwood procedure brings into question the value of delaying stage 2 palliation beyond 5 months of age.

Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging: a multicenter experience.

OBJECTIVES The aim of this study was to report the results of an international multicenter experience of cardiac magnetic resonance imaging (MRI) evaluation of cardiac tumors in children, each with histology correlation or a diagnosis of tuberous sclerosis, and to determine which characteristics are predictive of tumor type. BACKGROUND Individual centers have relatively little experience with diagnostic imaging of cardiac tumors in children, because of their low prevalence. The accuracy of cardiac MRI diagnosis on the basis of a pre-defined set of criteria has not been tested. METHODS An international group of pediatric cardiac imaging centers was solicited for case contribution. Inclusion criteria comprised: 1) age at diagnosis ≤18 years; 2) cardiac MRI evaluation of cardiac tumor; and 3) histologic diagnosis or diagnosis of tuberous sclerosis. Data from the cardiac MRI images were analyzed for mass characteristics. On the basis of pre-defined cardiac MRI criteria derived from published data, 3 blinded investigators determined tumor type, and their consensus diagnoses were compared with histologic diagnoses. RESULTS Cases (n = 78) submitted from 15 centers in 4 countries had the following diagnoses: fibroma (n = 30), rhabdomyoma (n = 14), malignant tumor (n = 12), hemangioma (n = 9), thrombus (n = 4), myxoma (n = 3), teratoma (n = 2), and paraganglioma, pericardial cyst, Purkinje cell tumor, and papillary fibroelastoma (n = 1, each). Reviewers who were blinded to the histologic diagnoses correctly diagnosed 97% of the cases but included a differential diagnosis in 42%. Better image quality grade and more complete examination were associated with higher diagnostic accuracy. CONCLUSIONS Cardiac MRI can predict the likely tumor type in the majority of children with a cardiac mass. A comprehensive imaging protocol is essential for accurate diagnosis. However, histologic diagnosis remains the gold standard, and in some cases malignancy cannot be definitively excluded on the basis of cardiac MRI images alone.

Near-infrared spectroscopy in neonates before palliation of hypoplastic left heart syndrome.

BACKGROUND Neonates with hypoplastic left heart syndrome have circulatory vulnerability that results in shock and high risk of mortality without intervention. High arterial saturation (SaO(2)) is often used as a proxy for inadequate systemic oxygen delivery and triggers the use of invasive therapies to restore circulatory balance. We hypothesized that preoperative use of near-infrared spectroscopy (NIRS) would reduce the need for invasive therapies, including controlled ventilation and inspired gas manipulation. METHODS A Human Research Review Board-approved retrospective review of patients who had stage 1 palliation from January 2000 to January 2006 was conducted. Preoperative patient characteristics, cardiorespiratory support, and monitored data were collected for all patients. Cerebral and somatic tissue oxyhemoglobin saturations were recorded for patients with preoperative NIRS monitoring. RESULTS The studied cohort included 92 patients, 47 without and 45 with preoperative NIRS. Patient characteristics were similar between groups. Differences were observed in preoperative respiratory support. Controlled ventilation was less common in the NIRS group (51% versus 79%, p = 0.005) as was the use of inspired nitrogen (16% versus 70%, p = 0.001). The NIRS patients had higher mean SaO(2) (92% versus 88%, p = 0.001). Age at surgery was similar between groups (5.7 +/- 3.2 versus 6.5 +/- 5.2 days, p = 0.3). Early survival was 96% in each group. CONCLUSIONS Near-infrared spectroscopy monitoring of patients with hypoplastic left heart syndrome awaiting palliation provides noninvasive assessment of oxygen delivery and simplified management, with reduced use of controlled ventilation and inspired gas. Higher SaO(2) in the NIRS group was not associated with impaired systemic oxygen delivery, and did not lead to earlier palliation or postoperative mortality.

COMPUTATIONAL SIMULATIONS DEMONSTRATE ALTERED WALL SHEAR STRESS IN AORTIC COARCTATION PATIENTS TREATED BY RESECTION WITH END-TO-END ANASTOMOSIS

BACKGROUND Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. METHODS Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. RESULTS The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. CONCLUSIONS Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies.

Rhizobial purine and pyrimidine auxotrophs: nutrient supplementation, genetic analysis, and the symbiotic requirement for the novo purine biosynthesis

Previously described Rhizobium leguminosarum bv. phaseoli mutants elicit nodules on bean without infection thread formation. These mutants were shown to be purine or, in one case, pyrimidine auxotrophs. Each of the seven purine auxotrophs grew normally when supplied the penultimate precursor of inosine, 5-aminoimidazole-4-carboxamide riboside. Four seemed blocked early in the purine pathway, because they were also thiamine auxotrophs. Reversion analysis and genetic complementation using cloned wild-type DNA showed that in each mutant a single mutation was responsible for both the symbiotic defect and purine or pyrimidine auxotrophy. The mutations were mapped to five dispersed chromosomal locations. The previously reported weak Calcofluor staining of these mutants on minimal agar appeared to be caused by partial growth on contaminating nutrients in the agar, rather than deficient exopolysaccharide production. Nodulation by the mutants was not enhanced by supplying purine or pyrimidine compounds exogenously. Furthermore, with or without added purine, the purine auxotrophs grew in the root environment as well as the wild type. However, nodulation by the purine auxotrophs was enhanced greatly in the presence of 5-aminoimidazole-4-carboxamide riboside. The results suggest that undiminished metabolic flow through de novo purine biosynthesis, or a particular intermediate in the pathway, is essential in early symbiotic interactions.

Perioperative monitoring in high-risk infants after stage 1 palliation of univentricular congenital heart disease

OBJECTIVE Survival of high-risk patients with univentricular heart disease after Norwood palliation is reduced. We hypothesized that early goal-directed monitoring with venous oximetry and near-infrared spectroscopy would offset their increased vulnerability and improve survival. METHODS A prospective database of patients undergoing stage 1 palliation was used to assess differences in outcomes across risk groups in the setting of a comprehensive, goal-directed monitoring program. High-risk criteria included gestational age 35 weeks or less, birth weight less than 2.5 kg, and additional cardiac or extracardiac anomalies. Outcomes included survival to defined end points and measures of postoperative support. RESULTS From September 2000 to September 2008, 162 patients underwent stage 1 palliation: 28% (45/162) high-risk and 72% (117/162) standard-risk patients. Lesions other than hypoplastic left heart syndrome were more common among high-risk patients (38%, 17/45, vs 15%, 18/117, P = .003). Operative survival was not statistically different(87%, 39/45, high risk vs 95%, 111/117, standard risk, P = .1). High-risk patients were more likely to receive inpatient treatment until stage 2 palliation (24%, 11/45, vs 10%, 12/117, P = .001) and had lower 1-year survival (78% vs 93%, P = .01) and survival to date (71% vs 92%, P = .001). CONCLUSIONS Intensive monitoring partially offset biologic vulnerability of high-risk patients, helping attain comparable early outcomes. Vulnerability persisted throughout the interstage period, however, and increased mortality beyond cavopulmonary shunt was seen only among high-risk patients. Although enhanced monitoring reduced early mortality, high resource use and attrition after stage 2 palliation suggest an ongoing need to evaluate our current palliative strategy for this subset of patients.

Near infrared spectroscopy monitoring during pediatric aortic coarctation repair

Background:  Near infrared spectroscopy (NIRS) measures regional tissue oxygenation continuously and noninvasively and may allow assessment of changes in regional perfusion in real time.

Mapping of complementation groups within a Rhizobium leguminosarum CFN42 chromosomal region required for lipopolysaccharide synthesis

SummaryA major genetic region specifying portions of the carbohydrate structure of Rhizobium leguminosarum CFN42 lipopolysaccharide was analyzed by Tn5 mutagenesis, constructing deletions in cloned DNA, restriction mapping, and complementation analysis. Mutations affecting lipopolysaccharide synthesis were arranged in nine complementation groups spanning 18 kb of DNA. One mutation resulted in O-polysaccharide-containing lipopolysaccharide having a slightly increased mobility in gel electrophoresis. This mutation did not affect the symbiosis with bean plants. The other mutations eliminated the 0-polysaccharide-containing lipopolysaccharide and resulted in strains defective in eliciting bean nodule development.

INCLUDING AORTIC VALVE MORPHOLOGY IN COMPUTATIONAL FLUID DYNAMICS SIMULATIONS: INITIAL FINDINGS AND APPLICATION TO AORTIC COARCTATION

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality.

Droperidol for perioperative sedation causes a transient prolongation of the QTc time in children under volatile anesthesia1

Background : Droperidol is useful for postoperative sedation in infants and children after cardiac surgery because it provides sedation and akinesia with minimal respiratory depression. However, droperidol has been associated with QT prolongation and ventricular arrhythmias. We investigated, if neuroleptanalgesic doses of droperidol led to QT prolongation and cardiac arrhythmias in children undergoing cardiac surgery.