K. Gambetta

Transcription repression and blocks in cell cycle progression in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is characterized by abnormally developed atrial septum and a severe underdevelopment of the left side of the heart. Despite significant advances in its surgical management, little is known about the molecular abnormalities in this syndrome. To gain molecular insights into HLHS, expression profiling by gene-chip microarray (Affymetrix U133 2.0) and by real-time RT-PCR was performed in the atrial septum of patients diagnosed with HLHS and compared with age-matched non-HLHS patients. Hierarchical clustering of all expressed genes with a P < 0.01 of all tissue samples showed two main clusters, one of HLHS and the other of non-HLHS, suggesting different expression patterns by the two groups. Net affix followed by real-time RT-PCR analysis identified the differentially expressed genes to be those involved in chromatin remodeling, cell cycle regulation, and transcriptional regulation. These included remodeling factors, histone deactylase 2 and SET and MYND domain containing 1; transcription factors, FoxP1, and components of the calcineurin-nuclear factor of activated T cells signaling pathway; and cell cycle regulators, cyclin-dependent kinase (CDK)-4, phosphatase and tensin homolog, and p18. Since these factors play essential roles in heart growth and development, the abnormal expression pattern suggests that these molecules may contribute to the pathogenesis of HLHS.

Real-Time Three-Dimensional Echocardiographic Assessment of Left Ventricular Systolic Dyssynchrony in Healthy Children

BACKGROUND The use of resynchronization therapy for the treatment of left ventricular (LV) systolic dysfunction in children has been expanding. Because QRS duration is not a reliable indicator of the presence or severity of dyssynchrony in every case, additional methods of quantitation of dyssynchrony are needed. The purpose of this study was threefold: (1) to define normal values for LV real-time quantitative three-dimensional echocardiographic (3DE) dyssynchrony indices (DIs), (2) to analyze the feasibility and observer variability of 3DE DIs in a wide range of children, and (3) to determine the effects of age, heart rate, body surface area, and LV end-diastolic volume on these parameters. METHODS The two specific parameters studied were the standard deviation of the time to minimum systolic volume for the number of segments analyzed and the time difference between the earliest and latest contracting segments. Both parameters were expressed as a percentage of the cardiac cycle length. RESULTS In 125 normal children aged 1 day to 19 years, adequate dyssynchrony studies were obtained in 102 (81.8%). The mean LV 3DE DIs expressed as the standard deviation of the time to minimum systolic volume for the number of segments analyzed were 1.16 ± 0.58 for 16 segments, 1.01 ± 0.60 for 12 segments, and 0.93 ± 0.68 for 6 segments. The mean LV 3DE DIs expressed as the time difference between the earliest and latest contracting segments were 3.80 ± 1.57 for 16 segments, 2.99 ± 1.42 for 12 segments, and 2.27 ± 1.35 for 6 segments. There were no effects of age, heart rate, body surface area, or LV end-diastolic volume on 3DE DIs. Intraobserver variability was 5.1%, and interobserver variability was 7.6%. CONCLUSION Three-dimensional echocardiographic DI analysis is reproducible and feasible in most children. Three-dimensional echocardiographic DIs are not affected by growth-related parameters in children but are lower than previously reported adult values.

Anomalous Left Coronary Artery from the Right Sinus of Valsalva and Noncompaction of the Left Ventricle

Anomalous origin of the left coronary artery is a well-known cause of sudden death. Noncompaction of the ventricular myocardium is a cardiomyopathy characterized by prominent trabeculae and deep intertrabecular recesses. Both anomalies are rare. We report the case of a child with both anomalous origin of the left coronary artery from the right sinus of Valsalva and noncompaction of the left ventricular myocardium found during an evaluation for Kawasaki’s disease.

Bilateral Coronary Artery Fistulas and Left Ventricle Noncompaction in a Neonate: Diagnosis and Management

This report describes a neonate with heart failure resulting from bilateral coronary artery fistulas and left ventricle noncompaction. The patient underwent successful surgical ligation of the fistulas.