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Published on: December 22, 2023
Inherited bradyarrhythmia: A diverse genetic background
Taisuke Ishikawa1, Yukiomi Tsuji1, Naomasa Makita1
1Department of Molecular Physiology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Abstract:
Bradyarrhythmia is a common heart rhythm abnormality comprising number of diseases and is associated with decreased heart rate due to the failure of action potential generation and propagation at the sinus node. Permanent pacemaker implantation is often used therapeutically to compensate for decreased heart rate and cardiac output. The vast majority of bradyarrhythmia cases are attributable either to aging or to structural abnormalities of the cardiac conduction system, caused by underlying structural heart disease. However, there is a subset of bradyarrhythmia primarily caused by genetic defects in the absence of aging or underlying structural heart disease. These include several genes that play principal roles in cardiac electrophysiology, heart development, cardioprotection, and the structural integrity of the membrane and sarcomere. Recent advances in the functional analysis of mutations using a heterologous expression system and genetically engineered animal models have provided significant insights into the underlying molecular mechanisms responsible for inherited arrhythmia. In this review, current understandings of the genetic and molecular basis of inherited bradyarrhythmia are presented.
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