Sick sinus syndrome pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]


Sick sinus syndrome occurs as an improperly propagated signal from the sinoatrial (SA) node. Age-dependent progressive fibrosis of the sinus nodal tissue and Remodeling of sinuatrial node are the potential mechanisms of this abnormally formed signal propagation. MYH6 gene may also be involved in the pathogenesis of this condition.


Anatomy & Physiology

The SA node is a right atrium structure, responsible for the generation and propagation of electric signals throughout the heart. This structure is located at the junction of the crista terminalis at the superior cavoatrial junction. The mechanisms underlying AS node pacemaker remain incompletely understood. However, heart rate is regulated through control of SA nodal automaticity by the autonomic nervous system.[1][2]


  • Sick sinus syndrome occurs as the result of age-dependent progressive fibrosis of the sinus nodal tissue and atrial myocardium. This leads to abnormal formation and propagation of atrial impulse and the resultant bradycardic or pause-related syndromes.[3][4]
  • Studies on familial and congenital presentations of sick sinus syndrome have also revealed genetic contributions to dysfunctional ion channels.[5]
  • Remodeling of sinuatrial node as a result of heart failure and atrial fibrillation can also be causes of increased sinus node recovery time, abnormal propagation of the action potential from the node and changes in nodal sensitivity.[6][7]


Sick sinus syndrome occurs sporadically in the majority of cases, however it may also occur as a result of genetic mutations.

Associated Conditions

Conditions associated with sick sinus syndrome include:[4][12]


  1. Opthof, Tobias (1988). "The mammalian sinoatrial node". Cardiovascular Drugs and Therapy. 1 (6): 573–597. doi:10.1007/BF02125744. ISSN 0920-3206.
  2. Anderson, Jeffrey B.; Benson, D. Woodrow (2010). "Genetics of Sick Sinus Syndrome". Cardiac Electrophysiology Clinics. 2 (4): 499–507. doi:10.1016/j.ccep.2010.09.001. ISSN 1877-9182.
  3. Lev, M. (1954). "Aging Changes in the Human Sinoatrial Node". Journal of Gerontology. 9 (1): 1–9. doi:10.1093/geronj/9.1.1. ISSN 0022-1422.
  4. 4.0 4.1 Semelka M, Gera J, Usman S (2013). "Sick sinus syndrome: a review". Am Fam Physician. 87 (10): 691–6. PMID 23939447.
  5. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ; et al. (2003). "Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)". J Clin Invest. 112 (7): 1019–28. doi:10.1172/JCI18062. PMC 198523. PMID 14523039.
  6. Elvan A, Wylie K, Zipes DP (1996). "Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling". Circulation. 94 (11): 2953–60. PMID 8941126.
  7. Dobrzynski H, Boyett MR, Anderson RH (2007). "New insights into pacemaker activity: promoting understanding of sick sinus syndrome". Circulation. 115 (14): 1921–32. doi:10.1161/CIRCULATIONAHA.106.616011. PMID 17420362.
  8. Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C; et al. (2011). "A rare variant in MYH6 is associated with high risk of sick sinus syndrome". Nat Genet. 43 (4): 316–20. doi:10.1038/ng.781. PMC 3066272. PMID 21378987.
  9. Ishikawa T, Jou CJ, Nogami A, Kowase S, Arrington CB, Barnett SM, Harrell DT, Arimura T, Tsuji Y, Kimura A, Makita N (April 2015). "Novel mutation in the α-myosin heavy chain gene is associated with sick sinus syndrome". Circ Arrhythm Electrophysiol. 8 (2): 400–8. doi:10.1161/CIRCEP.114.002534. PMID 25717017.
  10. Ishikawa, Taisuke; Ohno, Seiko; Murakami, Takashi; Yoshida, Kentaro; Mishima, Hiroyuki; Fukuoka, Tetsuya; Kimoto, Hiroki; Sakamoto, Risa; Ohkusa, Takafumi; Aiba, Takeshi; Nogami, Akihiko; Sumitomo, Naokata; Shimizu, Wataru; Yoshiura, Koh-ichiro; Horigome, Hitoshi; Horie, Minoru; Makita, Naomasa (2017). "Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction". Heart Rhythm. 14 (5): 717–724. doi:10.1016/j.hrthm.2017.01.020. ISSN 1547-5271.
  11. Raucci, Frank J.; Shoemaker, M. Benjamin; Knollmann, Bjorn C. (2017). "Clinical phenotype of HCN4-related sick sinus syndrome". Heart Rhythm. 14 (5): 725–726. doi:10.1016/j.hrthm.2017.02.006. ISSN 1547-5271.
  12. Alboni P, Baggioni GF, Scarfò S, Cappato R, Percoco GF, Paparella N; et al. (1991). "Role of sinus node artery disease in sick sinus syndrome in inferior wall acute myocardial infarction". Am J Cardiol. 67 (15): 1180–4. PMID 2035437.