Steven R. Leonard

Myocardial inflammatory activation in children with congenital heart disease

Objective In several cardiac-related diseases, there is a strong association between systemic endotoxemia, myocardial cytokine production, and cardiac failure. Because pre- and postoperative endotoxemia recently was reported in children with congenital heart disease, we sought direct evidence of myocardial inflammatory activation in a cohort of children undergoing congenital heart surgery on cardiopulmonary bypass. Inflammatory activation was prospectively defined as the presence of nuclear factor-&kgr;B nuclear translocation in myocardial tissue samples. Design Prospective observational study. Setting Tertiary care pediatric intensive care unit. Patients Fifteen children with congenital heart disease undergoing operative repair on cardiopulmonary bypass. Interventions All patients underwent operative repair of congenital heart disease on cardiopulmonary bypass and had plasma samples obtained for endotoxin and tumor necrosis factor-&agr;, both pre- and postoperatively. Myocardial tissue samples were obtained intraoperatively, both before and during cardiopulmonary bypass. Measurements and Main Results Elevated plasma endotoxin concentrations were documented in all 15 patients during the study period. In 12 patients, plasma endotoxin was elevated before cardiopulmonary bypass. The median preoperative tumor necrosis factor-&agr; concentration was 16.4 pg/mL, which is higher than concentrations reported in adults with New York Heart Association class III congestive heart failure. Examination of myocardial tissue samples revealed nuclear factor-&kgr;B nuclear translocation (predominantly p50/p65 heterodimers) in nine of 15 patients (60%). Four of these nine patients had nuclear factor-&kgr;B nuclear translocation before initiation of cardiopulmonary bypass, with p50/p50 homodimers present in two of the four. Conclusions These data provide the first evidence of nuclear factor-&kgr;B activation in children with congenital heart disease and the first evidence of myocardial nuclear factor-&kgr;B translocation in human hearts before explant for transplantation. Furthermore, these data suggest that, similar to adults with advanced congestive heart failure, the myocardial inflammatory cascade may contribute to the pathophysiology of congenital heart disease in infants and children.

Two-dimensional and Doppler echocardiography alone can adequately define preoperative anatomy and hemodynamic status before repair of complete atrioventricular septal defect in infants <1 year old

OBJECTIVES We sought to assess the ability of two-dimensional and Doppler echocardiography alone, without cardiac catheterization, to evaluate infants < 1 year of age for complete open heart repair of complete balanced atrioventricular (AV) septal defect. BACKGROUND Two-dimensional echocardiographic-Doppler examinations provide accurate anatomic detail in patients with AV septal defect. Lung biopsy data have shown that patients rarely develop significant inoperable pulmonary vascular disease before 7 months of age. Although calculated pulmonary arteriolar resistance is often elevated in young infants with this heart defect, this elevation rarely reflects significant pulmonary vascular changes in infants < 7 to 12 months of age. METHODS We performed a retrospective review of 34 patients who underwent complete repair of AV septal defect at our institution between January 1, 1988 and September 1, 1992. Some patients had both catheterization and echocardiographic-Doppler studies (group I, n = 16); others had only echocardiographic-Doppler studies (group II, n = 18). RESULTS The groups were comparable with regard to age at echocardiography and operation, days in the hospital, days with ventilatory and inotropic support and occurrence of postoperative pulmonary hypertension. One child (2.9%) died during the early postoperative period, and one child in each group (5.8%) died within the 1st year of life. Preoperative echocardiography allowed better detailing of anatomy, valve commitment and regurgitation than was possible with catheterization alone. Knowledge of preoperative pulmonary resistance did not alter the surgical decision or predict postoperative pulmonary hypertension. There was no apparent difference in mortality between the two groups (0 vs. 5.5%), but the small number of patients in each group provides for a very low power (beta = 0.04) calculation. This mortality rate is not different from that reported in recent studies. CONCLUSIONS Patients with AV septal defect can safely undergo surgical correction of this defect on the basis of echocardiographic-Doppler data alone.

Major intrahepatic venovenous fistulas after a modified Fontan operation

After the Fontan operation, systemic venous hypertension drives transpulmonary blood flow. Owing to this physiology, there is a significant incidence of effusions, splanchnic congestion, and generalized edema. To attentuate the effusive problems, partial exclusion of the hepatic veins has been recently practiced by Jacobs and Norwood. This report concerns a patient we recently treated for profound progressive cyanosis due to an acquired intrahepatic venovenous shunt after a Fontan operation with partial hepatic vein exclusion.

Cerebral near-infrared spectroscopy during cardiopulmonary bypass predicts superior vena cava oxygen saturation

OBJECTIVE Cerebral and flank near-infrared spectroscopy are used to monitor tissue oxygenation during cardiopulmonary bypass in pediatric patients. We sought to validate these noninvasive measurements as predictors of oxygen saturation in the superior and inferior venae cavae during cardiopulmonary bypass. METHODS Eight patients underwent elective repair of congenital heart defects with bicaval cannulation. Ultrasonic flow probes and oximetric catheters were placed in the superior and inferior venae cavae limbs of the perfusion circuit. Cerebral and flank near-infrared spectroscopy and 12 additional variables were recorded each minute on cardiopulmonary bypass. Relationships between these variables and superior and inferior venae cavae oxygen saturation were analyzed by linear mixed modeling. The regression of superior vena cava oxygen saturation by current cerebral near-infrared spectroscopy and 1-minute lag cerebral near-infrared spectroscopy, which are equivalent to the regression of the superior vena cava saturation by the current cerebral near-infrared spectroscopy and the 1-minute change in cerebral near-infrared spectroscopy, were used to assess cerebral near-infrared spectroscopy as a trend monitor. RESULTS The mean number of observation time points per patient was 86 (median 72, range 34-194) for 690 total observations. The root mean square percentage error was 6.39% for the prediction model of superior vena cava saturation by single-factor cerebral near-infrared spectroscopy. The root mean square percentage error was 10.8% for the prediction model of inferior vena cava saturation by single-factor flank near-infrared spectroscopy. CONCLUSIONS Cerebral near-infrared spectroscopy accurately predicts superior vena cava oxygen saturation and changes in superior vena cava oxygen saturation on cardiopulmonary bypass. The relationship between flank near-infrared spectroscopy and inferior vena cava saturation is not as strong.

Ministernotomy for repair of congenital cardiac disease.

We report our experience with repair of a variety of congenital heart defects utilizing a ministernotomy incision. A ministernotomy was used in 79 patients with a variety of congenital heart diseases from November 2004 to August 2007. Patients included 36 males and 43 females with ages ranging from 1 month to 122 months (median age, 22 months). The weight ranged from 3.5 kg to 40 kg (median weight, 10.9 kg). There were no deaths, and one conversion to full median sternotomy (1/79, 1.3%). The median cardiopulmonary bypass time was 59 min, and median aortic cross-clamp time was 38 min. One patient underwent atrial septal defect (ASD) repair with fibrillatory arrest time of 35 min. The operating time ranged from 103 min to 312 min (median operating time, 168 min). The intensive care unit (ICU) stay ranged from 1 to 21 days (median ICU stay, 1 day) and the hospital stay ranged from 2 to 56 days (median hospital stay, 4 days). There were no reinterventions for residual cardiac defects. We demonstrate the safety and efficacy of ministernotomy for the correction of a range of congenital heart defects with improved cosmetic results.

Stent implantation for coarctation of the aorta in a premature infant through carotid cutdown as a bridge to surgical correction

Isolated coarctation of the aorta accounts for 5% to 10% of all congenital heart defects. Neonatal repair is typically surgical at our institution. Stent implantation for coarctation is typically reserved for older children in whom a larger-caliber stent can be used that can potentially be postdilated to adult diameters. We report a case of stent implantation for native coarctation as a bridge to successful surgical repair in an extremely preterm infant. CLINICAL SUMMARY The patient was a male infant born at 25 weeks’ gestation because of preterm labor. Birth weight was 875 g. After delivery, the patient was noted to have a large patent ductus arteriosus (PDA). He underwent PDA ligation on day of life 6 through a left thoracotomy with multiple clips. After PDA ligation, he had significant upper extremity hypertension. Repeat echocardiographic analysis demonstrated severe aortic coarctation with a Doppler-predicted 58 mm Hg gradient. He was transferred to our institution for further care. Echocardiographic analysis at our institution confirmed the diagnosis. The patient remained severely hypertensive, with systolic blood pressures ranging from 97 to 118 mm Hg in the upper extremities and 35 to 47 mm Hg in the lower extremities with evidence of end-organ hypoperfusion. A carotid cutdown was performed in the cardiac catheterization laboratory, and a 4F sheath was placed in the right internal carotid artery. Angiographic analysis revealed a discrete coarctation adjacent to the ductal clips (Figure 1). The transverse aortic arch measured 3.5 mm, narrowing to 1.04 mm in the region of the coarctation. The descending aorta

Echocardiographic Diagnosis of Anomalous Drainage of the Superior Vena Cava Into the Left Atrium

A 1-day-old, 2805 g baby girl who was carried to term was cyanotic shortly after birth. Pulse oximetry documented an oxygen saturation of 65%. The saturation improved to 80% with hyperoxic challenge. Physical examination revealed a grade II/VI long systolic murmur best heard at the base of the heart, and a mid-diastolic rumble at the left lower sternal border. The ECG exhibited left ventricular hypertrophy. Chest roentgenogram demonstrated cardiomegaly with …

Usefulness of external counterpulsation early postoperatively after the Fontan procedure in children

temic venous return, and reduces ventricular afterload. 1‐3 We hypothesized that EC could benefit patients who underwent the Fontan procedure by improving cardiac output in the early postoperative period. EC had not been studied in the postoperative setting, and had never previously performed in the pediatric population. Therefore, this investigation sought to provide preliminary evidence of EC safety and short-term efficacy in children after Fontan surgery. ••• We performed a prospective, within-patient, controlled investigation of EC in children who underwent the Fontan procedure (fenestrated and nonfenestrated) at Children’ s Medical Center, Dallas, from May 1999 to June 2001. Children were considered for participation in the study if they were consecutive pediatric patients for whom parental consent was obtained, if there was an EC machine available, and if EC cuff sizes were deemed appropriate (pediatric-sized cuff straps able to be tightened over a sheepskin barrier to prevent excessive movement and skin irritation during EC). Patients were excluded from study for the following reasons: significant intraoperative surgical complications that may have compromised postoperative neurologic status (defined as 10 minutes of hypotension off bypass with blood pressure less than the fifth percentile for age), extubation before or immediately upon arrival to the cardiac intensive care unit, presence of a cardiac arrhythmia or paced heart rhythm, invasive line(s) in the femoral or lower extremities, peripheral vascular disease, musculoskeletal anomaly involving the lower extremities, significant and prolonged postoperative hemorrhage (3 ml/kg/ hour persisting for 10 hours after arrival to the cardiac intensive care unit), or aortic insuf ficiency. After admission to the cardiac intensive care unit, each patient was assessed for clinical stability. Blood products and/or volume (5% albumin) were administered and inotropes were adjusted at the discretion of the attending physician based on hemodynamic status, chest tube drainage, hemoglobin level, and degree of anticoagulation. Intravenous fluid was administered before the investigation if systemic perfusion was determined to be clinically poor, or if systolic blood pressure decreased below the fifth percentile for age at any time. The study protocol was initiated while patients were sedated and anesthetized with midazolam and fentanyl, before extubation, and after mediastinal blood loss was controlled (3 ml/kg/hour). Inotropes and vasoactive medications were unchanged during the period of investigation. The study protocol was divided into 3 10-minute periods. During the first period, baseline parameters were measured before initiation of EC. This was immediately followed by a 10-minute EC period, and directly thereafter, a postintervention period. The hemodynamic parameters obtained during all 3 periods included cardiac index (CI) by ascending aortic pulse Doppler echocardiography (averaged over 8 cardiac cycles), 4 vital signs (heart rate, blood pressure), and central venous pressure (CVP). Each parameter was measured every minute during the 3 study intervals, except ascending aortic Doppler flow, which was evaluated every 2 minutes. Echocardiographic determinations of CI were made off-line by a single interpreter who was blinded to the period of testing. Blinded interpretation was feasible because EC does not alter ascending aortic Doppler flow patterns.5 Chest tube output and oxygen saturation were recorded throughout the investigation. EC was performed using the Cardiomedics Cardi

Use of the cardioprotectants thymosin β4 and dexrazoxane during congenital heart surgery: proposal for a randomized, double-blind, clinical trial

Neonates and infants undergoing heart surgery with cardioplegic arrest experience both inflammation and myocardial ischemia‐reperfusion (IR) injury. These processes provoke myocardial apoptosis and oxygen‐free radical formation that result in cardiac injury and dysfunction. Thymosin β4 (Tβ4) is a naturally occurring peptide that has cardioprotective and antiapoptotic effects. Similarly, dexrazoxane provides cardioprotection by reduction of toxic reactive oxygen species (ROS) and suppression of apoptosis. We propose a pilot pharmacokinetic/safety trial of Tβ4 and dexrazoxane in children less than one year of age, followed by a randomized, double‐blind, clinical trial of Tβ4 or dexrazoxane versus placebo during congenital heart surgery. We will evaluate postoperative time to resolution of organ failure, development of low cardiac output syndrome, length of cardiac ICU and hospital stays, and echocardiographic indices of cardiac dysfunction. Results could establish the clinical utility of Tβ4 and/or dexrazoxane in ameliorating ischemia‐reperfusion injury during congenital heart surgery.