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Investigative methods of congenital complete heart block
R M Hamilton1, M Lee-Poy, K Kruger
1Department of Pediatrics and Research Institute, The Hospital for Sick Children, Faculty of Medicine, University of Toronto, Ontario, Canada.
Insights
Maternal autoimmune disease can cause congenital heart block (CHB) in infants. Researchers developed a rabbit model using maternal serum to study CHB mechanisms, identifying a potential link to autoimmune factors.
Area of Science:
- Cardiology
- Immunology
- Fetal Medicine
Background:
- Congenital heart block (CHB) is a known complication linked to maternal autoimmune diseases, yet its underlying mechanisms remain poorly understood.
- Current methods for diagnosing fetal heart block rely on ultrasound to detect mechanical events, with fetal electrocardiography being explored for earlier detection.
Purpose of the Study:
- To investigate the pathophysiology of congenital heart block (CHB) by developing and applying advanced electrophysiological techniques.
- To establish a reliable animal model for studying CHB mechanisms in a controlled laboratory setting.
Main Methods:
- Utilized sequential composite digital recordings from maternal abdomens to enhance fetal electrocardiography signals.
- Developed a Langendorff rabbit model, perfusing rabbit hearts with human serum from mothers at risk for CHB.
- Analyzed the effects of human serum on Wenckebach second-degree atrioventricular block cycle length in the rabbit model.
Main Results:
- Successfully enhanced fetal electrocardiography signals, producing a fetal QRS complex trigger for 3D fetal echocardiography.
- The Langendorff rabbit model demonstrated that human serum from mothers with CHB prolonged the Wenckebach second-degree atrioventricular block cycle length.
- This effect was observed in seven out of eight CHB mothers' serum samples, but not in control mothers' serum.
Conclusions:
- The study provides crucial insights into the pathophysiology of congenital heart block, suggesting a significant role for maternal autoimmune factors.
- The developed rabbit model serves as a valuable tool for further research into CHB mechanisms and potential therapeutic strategies.
- Findings support the hypothesis that maternal autoantibodies contribute to the development of fetal heart block.
Abstract:
Congenital heart block (CHB) has been described for a century and related to the presence of maternal autoimmune disease for three decades, but little is understood about its mechanism. To explore the pathophysiology of CHB, technologies in both basic and clinical electrophysiology are being developed and applied. Human fetal rhythm is currently inferred from cardiac mechanical events by using fetal ultrasound, allowing for the detection of second and third-degree heart block. Fetal electrocardiography is being explored to assess its feasibility as a clinical tool to detect fetal first-degree block in the mid trimester. Sequential composite digital recordings from the maternal abdomen are made every 4 weeks from pregnancies at risk for congenital heart block. Filtering and averaging techniques are used to enhance the fetal signal. So far, these techniques have produced a fetal QRS complex trigger signal for use in three-dimensional fetal echocardiography. Because the human fetus cannot be studied directly, a Langendorff rabbit model of CHB has been developed. With 5-10 mL of human serum in 150-300 mL of Krebs solution, prolongation of the Wenckebach second-degree atrioventricular block cycle length occurred. This was reproduced by using serum from seven of eight CHB mothers as compared with none of six controls mothers.