Cardiac Septal Defects in Children: Hemodynamics, Clinical Manifestations and Detection

Cardiac septal defect in children is one of the congenital heart defects characterized by atrial septal defects (ASD), ventricular septal defects (VSD) and defects in both atrial and ventricular septum (AVSD). The hemodynamic changes that occur are caused by a left to the right shunt. Differences in location, size of the defect and pulmonary vascular resistance make hemodynamic differences and clinical manifestations between the three types of cardiac septal defects. Detection of cardiac septal defects can be done by clinical examination by listening to the characteristic heart sounds and murmurs for each defect. However, clinical examination alone is often still difficult to determine the type of cardiac septal defect so that several supporting examinations such as photothorax, ECG, echocardiogram and cardiac catheterization need to be done to help establish the diagnosis.

Cardiac Septal Defects in Children: Hemodynamics, Clinical Manifestations and Detection

Cardiac septal defect in children is one of the congenital heart defects characterized by atrial septal defects (ASD), ventricular septal defects (VSD) and defects in both atrial and ventricular septum (AVSD). The hemodynamic changes that occur are caused by a left to the right shunt. Differences in location, size of the defect and pulmonary vascular resistance make hemodynamic differences and clinical manifestations between the three types of cardiac septal defects. Detection of cardiac septal defects can be done by clinical examination by listening to the characteristic heart sounds and murmurs for each defect. However, clinical examination alone is often still difficult to determine the type of cardiac septal defect so that several supporting examinations such as photothorax, ECG, echocardiogram and cardiac catheterization need to be done to help establish the diagnosis.

ANALYSIS OF GENE COPY NUMBER VARIATIONS IN PATIENTS WITH CARDIAC SEPTAL DEFECTS USING MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION

Objective: Cardiac septal defects (CSDs), the most common human congenital heart malformations are complex and heterogeneous. Progress in molecular biology has helped to identify many genes responsible for cardiac morphogenesis. However, etiologic factors in familial as well as isolated syndromes are being identified; the root genetic cause still needs to be resolved and its mechanism is yet to be revealed. The objective of this study is to identify DNA copy number variations (CNVs) and their possible association with septal defects. Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to detect DNA copy number in non-syndromic CSDs using the P311-A1 Kit consisting of probes for the key genes, namely, NKX2-5 (NK2 transcription factor related, locus 5), GATA4 (GATA binding protein 4), TBX5 (T-box transcription factor), bone morphogenetic protein 4, and CRELD1 (cysteine rich with EGF-like domains 1). Results: We studied 124 clinically diagnosed CSD subjects, of which 111 (89.5%) had atrial septal defects and 13 (10.5%) had ventricular septal defects. MLPA assay was carried out in all these patients after a thorough clinical and cytogenetic screening. CNVs were identified in 16 (12.9%) cases, of which heterozygous deletions and heterozygous duplications were detected (8 patients each) with apparent phenotypes. Conclusion: MLPA could be a useful assay for the detection of CNVs and to be adopted as the first line of screening in patients with congenital heart diseases.

Abstract W P190: Contrast Transcranial Doppler Detects More Intra and Extra-Cardiac Right-to-Left Shunts than Trans-Esophageal Echocardiogram

INTRODUCTION/OBJECTIVES: Paradoxical embolism is initially evaluated with a contrast trans-thoracic echocardiogram (cTTE), since the more sensitive method of contrast trans-esophageal echocardiogram (cTEE) is also more invasive. An adequate valsalva is essential to raise intra-thoracic pressures, but since the patient is sedated for the procedure, it is not always possible with cTEE. The amount of RLS through a PFO depends on strain rate and duration of the Valsalva maneuver. CTCD is a non-invasive method of detecting RLS that has been shown to be as good as cTEE. The goal of this study was to evaluate whether or not cTCD could be more effective at detecting RLS. MATERIALS AND METHODS: A review and evaluation of medical records and imaging was done on patients with embolic stroke from 2012-2013 at a university affiliated comprehensive stroke center. Patients had embolic stroke and a cTCD to be included. A subgroup of patients who had cTCD also had a cTEE. Patients who were positive for RLS on cTCD were compared with those who had RLS on cTEE. Statistical analysis was performed to determine significance and potential for future complications. RESULTS: A total of 1,033 patient records were reviewed and of those 130 patients (55% women) had embolic stroke and a cTCD, 35 were positive for a RLS based on the presence of microbubbles in the cerebral circulation, and 95 were negative. Of the 35 patients with positive cTCD, 45% (n=16) also underwent cTEE; however, only 44% (n=7) of those had positive results for RLS. Conversely, 56% (n=9) of the patients who were shown to have RLS on cTCD were missed on cTEE (without cardiac septal defects). Of the 95 patients who had negative cTCD, 19 of them also underwent cTEE and all were negative on cTEE. CONCLUSION: Using cTCD to detect microbubbles in cerebral arteries appears to be more reliable and accurate for discovering RLS of intra or extra-cardiac origin. For embolic ischemic strokes, we recommend using cTCD as a first-line study and suggest it should be the new “gold standard”. Randomized, prospective studies should be conducted to further validate this data.