Steven M. Schwartz

Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion

OBJECTIVES Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the impact of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion. METHODS Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury. RESULTS Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029). CONCLUSIONS Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgery. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional impact of these lesions.

Combined Steroid Treatment for Congenital Heart Surgery Improves Oxygen Delivery and Reduces Postbypass Inflammatory Mediator Expression

Background—Steroid administration during cardiopulmonary bypass is thought to improve cardiopulmonary function by modulating bypass-related inflammation. This study was designed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome. Methods and Results—Twenty-nine pediatric patients undergoing bypass procedures were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg 4 hours before bypass and in bypass prime, n=14) or intraoperative MP only (30 mg/kg, n=15). Myocardial inflammatory mediator mRNA expression was determined in paired atrial biopsies (before and after bypass) by ribonuclease protection. Before and after bypass, serum IL-6 and IL-10 were measured by ELISA. Postoperative outcome was assessed by intubation time, CICU length of stay, fluid balance, arterio-venous O2 difference (&Dgr;A−Vo2), and inotrope requirements. Compared with intraoperative MP alone, combined preoperative and intraoperative MP was associated with reduced myocardial mRNA expression for IL-6, MCP-1, and ICAM-1 both before and after bypass (P <0.05). Patients who received combined steroids had lower serum IL-6 and increased IL-10 at end-bypass (P <0.05), although differences were negligible by 24 hours. Combined MP treatment was associated with reduced fluid requirements, lower body temperature, and lower &Dgr;A−Vo2 for the first 24 hours after surgery (P <0.05), along with trends toward improvement in other clinical outcomes. Conclusions—Compared with intraoperative steroid treatment, combined preoperative and intraoperative steroid administration attenuates inflammatory mediator expression more effectively and is associated with improved indexes of O2 delivery in the first 24 hours after congenital heart surgery. These findings need to be confirmed in a larger multicenter trial.

Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease

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Emotional distress in chronic hepatitis C patients not receiving antiviral therapy

BACKGROUND/AIMS The aim of our study was to determine the prevalence, type, and severity of emotional distress in a large group of consecutive chronic hepatitis C (CHC) patients not receiving anti-viral therapy. METHODS The brief symptom inventory and a 67-item questionnaire with the SF-36 embedded within it were used to study 220 outpatients with compensated CHC. RESULTS Seventy-seven (35%) participants reported significantly elevated global severity index (GSI) T-scores compared to an expected frequency of 10% in population controls. In addition, significantly elevated depression, anxiety, somatization, psychoticism, and obsessive-compulsive subscale T-scores were reported in 28-40% of subjects. Subjects with an active psychiatric co-morbidity had significantly higher GSI and subscale T-scores compared to subjects with active medical co-morbidities and subjects without medical or psychiatric co-morbidities (P<0.01). However, patients with CHC alone also had a higher frequency of elevated GSI T-scores compared to population controls (20 versus 10%). GSI and subscale T-scores were strongly associated with SF-36 summary scores (P<0.001). CONCLUSIONS Clinically significant emotional distress was reported in 35% of CHC patients not receiving antiviral therapy. In addition to depression, a broad array of psychological symptoms were observed. Further investigation into the etiopathogenesis and treatment of emotional distress in CHC patients is warranted.

Why men should be included in research on binge eating: Results from a comparison of psychosocial impairment in men and women

OBJECTIVE Prevalence of binge eating has been shown to be as common in men as in women, yet few studies have included men. Men are especially underrepresented in treatment studies, raising the question of whether men who binge eat experience less distress or impairment than women. This study compared demographic and clinical correlates of binge eating in a large employee sample of men and women. METHOD Cross-sectional data from 21,743 men and 24,608 women who participated in a health risk self assessment screening were used. Group differences in obesity, hypertension, dyslipidemia, Type 2 diabetes, depression, stress, sleep, sick days, work impairment, and nonwork activity impairment were tested using chi-square tests (categorical variables) and independent sample t-tests (continuous variables). RESULTS Effect size estimates indicate that men (n = 1,630) and women (n = 2,754) who binge eat experience comparable levels of clinical impairment. They also report substantially greater impairment when compared with men and women who do not binge eat. DISCUSSION The underrepresentation of men in treatment-seeking samples does not appear to reflect lower levels of impairment in men versus women. Efforts are needed to raise awareness of the clinical significance of binge eating in men so that this group can receive appropriate screening and treatment services.

Risk, Clinical Features, and Outcomes of Thrombosis Associated With Pediatric Cardiac Surgery

Background— Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. Methods and Results— We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/109 cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. Conclusions— Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Proinflammatory consequences of transgenic fas ligand expression in the heart.

Expression of Fas ligand (FasL) renders certain tissues immune privileged, but its expression in other tissues can result in severe neutrophil infiltration and tissue destruction. The consequences of enforced FasL expression in striated muscle is particularly controversial. To create a stable reproducible pattern of cardiomyocyte-specific FasL expression, transgenic (Tg) mice were generated that express murine FasL specifically in the heart, where it is not normally expressed. Tg animals are healthy and indistinguishable from nontransgenic littermates. FasL expression in the heart does result in mild leukocyte infiltration, but despite coexpression of Fas and FasL in Tg hearts, neither myocardial tissue apoptosis nor necrosis accompanies the leukocyte infiltration. Instead of tissue destruction, FasL Tg hearts develop mild interstitial fibrosis, functional changes, and cardiac hypertrophy, with corresponding molecular changes in gene expression. Induced expression of the cytokines TNF-alpha, IL-1beta, IL-6, and TGF-beta accompanies these proinflammatory changes. The histologic, functional, and molecular proinflammatory consequences of cardiac FasL expression are transgene-dose dependent. Thus, coexpression of Fas and FasL in the heart results in leukocyte infiltration and hypertrophy, but without the severe tissue destruction observed in other examples of FasL-directed proinflammation. The data suggest that the FasL expression level and other tissue-specific microenvironmental factors can modulate the proinflammatory consequences of FasL.

Evaluation of left ventricular mass in children with left-sided congenital diaphragmatic hernia

To evaluate left ventricular (LV) mass in children with left-sided congenital diaphragmatic hernia (CDH), we retrospectively examined the echocardiographic data available on all newborn infants with a diagnosis of CDH between April 1989 and May 1993. Adequate data for evaluation were available for 20 of 31 patients with left-sided CDH and no significant congenital heart disease. Left ventricular mass was determined from two-dimensional echocardiograms by an area-length method. Findings were compared with a control group that consisted of neonates with other causes of pulmonary hypertension. Patients with left-sided CDH had a significantly lower indexed LV mass than control subjects (1.96 gm/kg +/- 0.59 vs 2.84 gm/kg +/- 0.41; p = 0.0001). Additionally, children with left-sided CDH who required extracorporeal membrane oxygenation before repair (n = 7) had a significantly lower indexed LV mass than those patients who did not require extracorporeal membrane oxygenation before repair (1.53 gm/kg +/- 0.50 vs 2.20 gm/kg +/- 0.52; (p = 0.007). Infants who survived (n = 13) had an indexed LV mass of 2.09 gm/kg +/- 0.58 vs 1.64 gm/kg +/- 0.58 in those who died (p = 0.07). We conclude that the LV mass index in children with left-sided CDH is significantly lower than in children with other causes of pulmonary hypertension in the newborn period. Evaluation of LV mass in neonates with left-sided CDH may help predict the need for extracorporeal support before surgical repair, and may help indicate overall prognosis.

Critical aortic stenosis in the neonate: A comparison of balloon valvuloplasty and transventricular dilation

The optimal treatment of critical aortic stenosis in the neonate and infant remains controversial. We compared transventricular dilation using normothermic cardiopulmonary bypass and percutaneous balloon aortic valvuloplasty with respect to early and late survival, relief of aortic stenosis, degree of aortic insufficiency, left ventricular function, and freedom from reintervention. Between July 1987 and July 1993, 30 neonates and infants underwent transventricular dilation or balloon aortic valvuloplasty for critical aortic stenosis. The patients in the transventricular dilation group (n = 21) ranged in age from 1 to 59 days (mean age 18.0 days +/- 19.1 days) and the balloon aortic valvuloplasty group (n = 9) from 1 to 31 days (mean age 10.0 days +/- 9.0 days). There were no significant differences in weight, body surface area, or aortic anulus diameter between the two groups (p = 1.0). Associated cardiovascular anomalies were more common in the transventricular dilation group (48%) than in the balloon aortic valvuloplasty group (11%). After intervention, the degree of residual aortic stenosis and insufficiency was equivalent in the two groups as assessed by postprocedural Doppler echocardiography. Ejection fraction improved within both groups (transventricular dilation 39% +/- 20.2% versus 47% +/- 22.0%; balloon aortic valvuloplasty 51% +/- 16.1% versus 62% +/- 8.4%), and there was no significant difference between groups. The left ventricular mass/volume ratio increased within both groups (p < 0.05) but with no significant difference between groups (transventricular dilation 1.4 +/- 0.5 gm/ml versus 1.8 +/- 0.6 gm/ml; balloon aortic valvuloplasty 1.1 +/- 0.6 gm/ml versus 1.7 +/- 0.4 gm/ml). Early mortality in the transventricular dilation group was 9.5% and in the balloon aortic valvuloplasty group, 11.1%. There was one late death in the transventricular dilation group. Four patients from the transventricular dilation group (19%) and two patients from the balloon aortic valvuloplasty group (22%) required reintervention for further relief of aortic stenosis. We conclude that both transventricular dilation and balloon aortic valvuloplasty provide adequate and equivalent relief of critical aortic stenosis. The treatment strategy adopted should depend on other factors, including associated cardiovascular anomalies, vascular access, preoperative condition, and the technical expertise available at each institution.

Inhaled nitric oxide increases endothelin-1 levels: a potential cause of rebound pulmonary hypertension.

Objective Inhaled nitric oxide (iNO) is front-line therapy for pulmonary hypertension after repair of congenital heart disease. However, little clinical data exists regarding the effects of iNO on regulators of pulmonary vascular resistance. An imbalance between primary vasodilators, such as NO, and vasoconstrictors, such as endothelin-1 (ET-1), has been implicated in rebound pulmonary hypertension upon iNO withdrawal. The objective of this study was to determine whether iNO therapy alters plasma ET-1 levels. Design This is a prospective study involving pediatric and adult patients at risk for pulmonary hypertension. Setting Pediatric patients were in the cardiac intensive care unit and adult patients were in a tertiary-care hospital. Patients Group 1 included children with congenital heart disease requiring iNO for treatment of pulmonary hypertension after cardiopulmonary bypass (n = 15), group 2 was adults receiving iNO (n = 10), and group 3 included children at risk for pulmonary hypertension after bypass that did not require iNO (n = 8). Interventions Dosages of iNO were 2–60 ppm. The duration of therapy ranged from 23 to 188 hrs in group 1 and 29 to 108 hrs in group 2. Measurements and Main Results Arterial blood was obtained for the measurement of ET-1 levels before and during iNO therapy and 24 hrs after iNO withdrawal. Group 1 mean ET-1 levels increased to 127% of baseline by 12 hrs of iNO, remained elevated at 48 hrs (p < .05), then decreased to 71% of iNO levels 24 hrs after withdrawal (p < .01). Group 2 ET-1 levels increased to 147%, and 137% of baseline at 12 and 24 hrs of iNO therapy, then fell to 68% of baseline within 24 hrs of discontinuing iNO. ET-1 levels in group 3 decreased after surgery (p < .05). Conclusions These data suggest that iNO increased plasma ET-1 levels, which subsequently decreased when iNO was discontinued. Increased circulating ET-1 levels might contribute to rebound pulmonary hypertension upon iNO withdrawal.