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Frontiers in genetics
2021;12 654925.

Genetic Complexity of Sinoatrial Node Dysfunction.

Michael J Wallace, Mona El Refaey, Pietro Mesirca, Thomas J Hund, Matteo E Mangoni, Peter J Mohler
Author Information
  1. Michael J Wallace: Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
  2. Mona El Refaey: Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
  3. Pietro Mesirca: CNRS, INSERM, Institut de Génomique Fonctionnelle, Université de Montpellier, Montpellier, France.
  4. Thomas J Hund: Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
  5. Matteo E Mangoni: CNRS, INSERM, Institut de Génomique Fonctionnelle, Université de Montpellier, Montpellier, France.
  6. Peter J Mohler: Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
PMID: 33868385 DOI: 10.3389/fgene.2021.654925

Abstract

The pacemaker cells of the cardiac sinoatrial node (SAN) are essential for normal cardiac automaticity. Dysfunction in cardiac pacemaking results in human sinoatrial node dysfunction (SND). SND more generally occurs in the elderly population and is associated with impaired pacemaker function causing abnormal heart rhythm. Individuals with SND have a variety of symptoms including sinus bradycardia, sinus arrest, SAN block, bradycardia/tachycardia syndrome, and syncope. Importantly, individuals with SND report chronotropic incompetence in response to stress and/or exercise. SND may be genetic or secondary to systemic or cardiovascular conditions. Current management of patients with SND is limited to the relief of arrhythmia symptoms and pacemaker implantation if indicated. Lack of effective therapeutic measures that target the underlying causes of SND renders management of these patients challenging due to its progressive nature and has highlighted a critical need to improve our understanding of its underlying mechanistic basis of SND. This review focuses on current information on the genetics underlying SND, followed by future implications of this knowledge in the management of individuals with SND.

Keywords

GIRK4 HCN4 Nav1.5 atrial fibrillation calsequestrin-2 genetics sick sinus syndrome sinoatrial node dysfunction

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  4. K99 HL146969/NHLBI NIH HHS
  5. R01 HL135096/NHLBI NIH HHS
  6. R01 HL134824/NHLBI NIH HHS
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