Louis I. Bezold

Clinical Characterization of Left Ventricular Noncompaction in Children A Relatively Common Form of Cardiomyopathy

Background—Left ventricular noncompaction (LVNC) is a reportedly uncommon genetic disorder of endocardial morphogenesis with a reportedly high mortality rate. The purpose of this study was to identify the clinical characteristics of children with LVNC. Methods and Results—We retrospectively reviewed 36 children with LVNC evaluated at Texas Children’s Hospital (TCH) from January 1997 to December 2002. Five children had associated cardiac lesions. There were 16 girls and 20 boys. The median age at presentation was 90 days (range, 1 day to 17 years). The median duration of follow-up was 3.2 years (range, 0.5 to 12 years). Twenty-seven patients (75%) had ECG abnormalities, most commonly biventricular hypertrophy (10 patients, 28%). Both ventricles were involved in 8 patients (22%) and only the left ventricle in 28 patients (78%). Left ventricular systolic function was depressed in 30 patients (83%), with a median ejection fraction of 30% (range, 15% to 66%) at diagnosis. Nine patients presenting in the first year of life with depressed left ventricular contractility had a transient recovery of function; however, ejection fraction deteriorated later in life, at a median interval of 6.3years (range, 3 to 12 years). Two patients had an “undulating” phenotype from dilated to hypertrophic cardiomyopathy. Two patients (6%) were identified with an underlying G4.5 gene mutation. Five patients (14%) died during the study. Conclusions—LVNC does not have an invariably fatal course when diagnosed in the neonatal period. A significant number of patients have transient recovery of function followed by later deterioration, which may account for many patients presenting as adults, some manifesting an “undulating” phenotype.

Characterization of Left Ventricular Diastolic Function by Tissue Doppler Imaging and Clinical Status in Children With Hypertrophic Cardiomyopathy

Background—Conventional transmitral Doppler indices are unreliable in assessing clinical status in patients with hypertrophic cardiomyopathy (HCM) because they are affected by loading conditions. This study sought to determine whether tissue Doppler velocities are predictive of adverse clinical outcomes including death, cardiac arrest, ventricular tachycardia (VT), significant cardiac symptoms, and exercise capacity in children with HCM. Methods and Results—We studied 80 consecutive children (median age 12 years, median follow-up 26 months) evaluated at 1 hospital from January 1999 to August 2003 compared with 80 age- and gender-matched controls. Patients underwent echocardiography, ambulatory Holter monitoring, and upright exercise testing. Children with HCM had significantly decreased early diastolic tissue Doppler velocities at the lateral mitral (13.2 versus 19.3 cm/s), tricuspid (13.3 versus 16.3 cm/s), and septal (9.4 versus 13.5 cm/s) annuli compared with controls (P <0.001 for each comparison). By forward stepwise regression analysis, early transmitral left ventricular filling velocity (E)/septal Ea ratio predicted death, cardiac arrest, or VT (r =0.610, R2 =0.37, P <0.001). Peak oxygen consumption (&OV0312;O2) was most predictive of children who developed symptoms (r =0.427, R2 =0.182, P <0.001). Peak &OV0312;O2 correlated inversely with E/Ea septal ratio (r =−0.740, P <0.01). Conclusions—Transmitral E/septal Ea ratio predicts children with HCM who are at risk of adverse clinical outcomes including death, cardiac arrest, VT, and significant cardiac symptoms. Peak &OV0312;O2 correlated with peak exercise capacity in HCM patients.

Outcome of 121 Patients with Congenitally Corrected Transpositionof the Great Arteries

Congenitally corrected transposition of the great arteries (ccTGA) is a rare disorder with reduced survival that is influenced by the presence of associated anomalies, tricuspid regurgitation (TR), and right ventricular (RV) function. The double switch procedure has been proposed as an aggressive surgical approach in selected patients. We sought to review our experience with conventional repair to determine if a change in surgical strategy was warranted. Clinical records of 121 patients with ccTGA and two adequate-sized ventricles were retrospectively reviewed. Median length of follow-up was 9.3 years; 5-, 10-, and 20-year survival rates were 92%, 91%, and 75%, respectively. Surgery was performed in 86 patients, including conventional biventricular repair in 47 patients. Risk factors for mortality by univariate analysis included age at biventricular repair (p = 0.04), complete atrioventricular (AV) canal defect (p = 0.02), dextrocardia (p = 0.05), moderate or severe TR (p = 0.05), and poor RV function (p = 0.001). By multivariate analysis, complete AV canal defect (p = 0.006) and poor RV function (p = 0.002) remained significant as risk factors for mortality. Risk factors for the development of significant TR included conventional biventricular repair (p = 0.03) and complete AV block (p = 0.04). Risk factors for progressive RV dysfunction included conventional biventricular repair (p = 0.02), complete AV block (p = 0.001), and moderate or severe TR (p < 0.001). This is the largest nonselected cohort of patients with ccTGA followed at a single center. Our results confirm that significant TR and poor RV function are risk factors for poor outcome and provide convincing evidence that patients undergoing conventional biventricular repair are at higher risk for deterioration of tricuspid valve and right ventricular function compared to palliated or unoperated patients. We support a move toward an alternative surgical approach (double switch procedure) in carefully selected patients.

Echocardiographic predictors of adverse clinical events in children with dilated cardiomyopathy: a prospective clinical study

Objectives: To compare tissue Doppler (TD) velocities between patients with dilated cardiomyopathy (DCM) and normal controls and to determine whether TD velocities, Tei index, right ventricular fractional area change, and left ventricular ejection fraction (LVEF) predict adverse clinical outcomes in children with DCM. Methods: Prospective evaluation of children with DCM. Results: 54 children with DCM and 54 age and sex matched control group participants were studied. Mitral inflow velocities were similar for both groups except for decreased mitral deceleration time in patients with DCM. Systolic and diastolic TD velocities at the mitral annulus (septal and lateral sides) and tricuspid annulus were significantly reduced in children with DCM compared with controls (p < 0.001 for each). By multivariate analysis, after adjustment for Tei index and right ventricular fractional area change, decreased LVEF and tricuspid velocity during early diastole (Ea) were predictors of the primary end point (PEP), a composite end point consisting of need for hospitalisation or the outcome transplantation or death. Tricuspid Ea velocity < 8.5 cm/s had 87% specificity and 60% sensitivity for reaching the PEP. LVEF < 30% had 68% specificity and 74% sensitivity for the PEP. Combined LVEF < 30% and tricuspid Ea < 11.5 cm/s had 100% specificity and 44% sensitivity for the PEP. Conclusions: Children with DCM have significantly lower TD velocities than normal controls. In such cases, lower LVEF (< 30%) is more sensitive but less specific than lower tricuspid Ea velocities (< 8.5 cm/s) in predicting which patients are at risk of hospitalisation, transplantation, or death.

Echocardiographic Evaluation of Asymptomatic Parental and Sibling Cardiovascular Anomalies Associated With Congenital Left Ventricular Outflow Tract Lesions

Objective. Left ventricular outflow tract obstructive (LVOTO) malformations are a leading cause of infant mortality from birth defects. Genetic mechanisms are likely, and there may be a higher rate of asymptomatic LVOTO anomalies in relatives of affected children. This study sought to define the incidence of cardiac anomalies in first-degree relatives of children with congenital aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS). Methods. A total of 113 probands with a nonsyndromic LVOTO malformation of AVS (n = 25), BAV (n = 3), CoA (n = 52), HLHS (n = 30), and aortic hypoplasia with mitral valve atresia (n = 2) were ascertained through chart review or enrolled at the time of diagnosis. Echocardiography was performed on 282 asymptomatic first-degree relatives. Results. Four studies had poor acoustic windows, leaving 278 studies for analysis. BAV were found in 13 (4.68%) first-degree relatives. The relative risk of BAV in the relatives was 5.05 (95% confidence interval: 2.2–11.7), and the broad sense heritability was 0.49, based on a general population frequency of 0.9%. BAV was more common in multiplex families compared with sporadic cases. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve. Conclusions. The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk.

A controlled study of transesophageal echocardiography to guide central venous catheter placement in congenital heart surgery patients.

UNLABELLED Transesophageal echocardiography (TEE) and central venous catheter (CVC) placement are often used during congenital cardiac surgery. Complications of CVC placement include cardiac perforation, inadvertent arterial placement, and erroneous hemodynamic data from unrecognized malposition. In this study, we used a prospective, randomized, controlled design to evaluate the use of TEE to guide depth of insertion and confirm superior vena cava cannulation, and to improve the percentage of correctly placed CVCs and reduce complications of CVC placement. One hundred forty-five patients were studied. Eighty patients were randomized to have subclavian vein insertion, 64 to have internal jugular insertion, and 1 to have external jugular insertion of CVC. TEE-guided CVC placement resulted in 100% correct placement when assessed by preoperative TEE, versus 86% in the control group (72 of 72 vs. 63 of 73; P = 0.01). There was no difference in correct placement between the two groups when assessed by postoperative chest radiograph (81.9% TEE versus 75.3% control; P = not significant). One significant complication, a superior vena cava perforation, occurred in the control group. Time to placement was 9.6 min in the TEE group versus 8.0 min in the control group (P = 0.015). IMPLICATIONS Transesophageal echocardiography can be used to guide central venous catheter placement in congenital heart surgery. Central venous catheters that seem to be located high in the right atrium by chest radiograph in these patients are often actually in the superior vena cava and pose little risk of cardiac perforation.

Cardiac Effects of Antiretroviral Therapy in HIV-Negative Infants Born to HIV-Positive Mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children Cohort Study)

OBJECTIVES The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children. BACKGROUND ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals. METHODS Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-). RESULTS Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference. CONCLUSIONS Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.

Diagnosis of Pentalogy of Cantrell in the Fetus Using Magnetic Resonance Imaging and Ultrasound

We report two cases of pentalogy of Cantrell diagnosed in utero using a combination of fetal echocardiography and magnetic resonance imaging. The cardiac component consisted of tetralogy of Fallot in the first fetus and ventricular septal defect in the second fetus. Whereas fetal echocardiography allowed accurate delineation of the cardiac anatomy, prenatal magnetic resonance imaging allowed clearer delineation of the extent of the thoracic and abdominal wall defects. Fetal magnetic resonance imaging in conjunction with prenatal echocardiography allows optimal assessment of the fetus with ectopia cordis, which has significant implications from the standpoint of preoperative planning and providing prognostic information. This report represents the first description of applying magnetic resonance imaging in combination with echocardiography toward a better understanding of this clinical entity in the fetus.

Outcome of pregnancy following intervention for coarctation of the aorta

There are limited data regarding the outcome of pregnancy in women after intervention for coarctation of the aorta (CoA). The Texas Childrens Hospital Cardiac Database was used to identify female patients with CoA born before 1980 who had undergone balloon angioplasty or surgery. Patients with Turners syndrome and cyanotic congenital heart disease were excluded. A chart review and telephone interview were performed. Data collected included age at intervention, type of intervention, the need for reintervention, functional status, number of pregnancies, and pregnancy outcomes. Seventy-four patients met our criteria and we were able to contact 52. Eighteen patients (39%) were pregnant a total of 36 times. There were 3 spontaneous and 4 elective abortions. Preeclampsia complicated 4 pregnancies in 3 women (17% of primigravidas). One patient had systemic hypertension. Eleven infants were delivered by Cesarean section. There were 29 births, with an average weight of 3.0 kg. There were 5 preterm births, 4 to a teenage mother. Only 1 child (3%) had a congenital heart defect. Thus, in women with an arm-to-leg blood pressure gradient of <20 mm Hg after CoA repair, pregnancy is successful. The occurrence of congenital heart disease in the offspring was 3%. Preeclampsia was similar to that in the general population.

Myocardial Performance Index with Sevoflurane–Pancuronium versus Fentanyl–Midazolam–Pancuronium in Infants with a Functional Single Ventricle

Background:Patients with congenital heart disease characterized by a functional single ventricle make up an increasing number of patients presenting for cardiac or noncardiac surgery. Conventional echocardiographic methods to measure left ventricular function, i.e., ejection fraction, are invalid in these patients because of altered ventricular geometry. Two recently described Doppler echocardiographic modalities, the myocardial performance index and Doppler tissue imaging, can be applied to single-ventricle patients because they are independent of ventricular geometry. This study assessed the changes in myocardial performance index and Doppler tissue imaging in response to two anesthetic regimens, fentanyl–midazolam–pancuronium and sevoflurane–pancuronium. Methods:Thirty patients aged 4–12 months with a functional single ventricle were randomized to receive fentanyl–midazolam or sevoflurane. Myocardial performance index and Doppler tissue imaging were measured by transthoracic echocardiography at baseline and two clinically relevant dose levels. Results:Sixteen patients receiving sevoflurane and 14 receiving fentanyl–midazolam were studied. Myocardial performance index was unchanged from baseline with either agent (fentanyl–midazolam: 0.50 ± 15 baseline vs. 0.51 ± 0.15 at dose 2; sevoflurane: 0.42 ± 0.14 baseline vs. 0.46 ± 0.09 at dose 2). Doppler tissue imaging S (systolic)– and E (early diastolic)–wave velocities in the lateral ventricular walls at the level of the atrioventricular valve annulus were unchanged in the sevoflurane group; however, both Doppler tissue imaging S- and E-wave velocities were decreased significantly from baseline at dose 1 and dose 2 with fentanyl–midazolam, consistent with decreased longitudinal systolic and diastolic ventricular function. Conclusions:Myocardial performance index, a global measurement of combined systolic and diastolic ventricular function, is not affected by commonly used doses of fentanyl–midazolam or sevoflurane in infants with a functional single ventricle.