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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]]. | 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]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
===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]].<ref name="Opthof1988">{{cite journal|last1=Opthof|first1=Tobias|title=The mammalian sinoatrial node|journal=Cardiovascular Drugs and Therapy|volume=1|issue=6|year=1988|pages=573–597|issn=0920-3206|doi=10.1007/BF02125744}}</ref><ref name="AndersonBenson2010">{{cite journal|last1=Anderson|first1=Jeffrey B.|last2=Benson|first2=D. Woodrow|title=Genetics of Sick Sinus Syndrome|journal=Cardiac Electrophysiology Clinics|volume=2|issue=4|year=2010|pages=499–507|issn=18779182|doi=10.1016/j.ccep.2010.09.001}}</ref> | |||
===Pathogenesis=== | |||
*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.<ref name="Lev1954">{{cite journal|last1=Lev|first1=M.|title=Aging Changes in the Human Sinoatrial Node|journal=Journal of Gerontology|volume=9|issue=1|year=1954|pages=1–9|issn=0022-1422|doi=10.1093/geronj/9.1.1}}</ref><ref name="pmid23939447">{{cite journal| author=Semelka M, Gera J, Usman S| title=Sick sinus syndrome: a review. | journal=Am Fam Physician | year= 2013 | volume= 87 | issue= 10 | pages= 691-6 | pmid=23939447 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23939447 }} </ref> | *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.<ref name="Lev1954">{{cite journal|last1=Lev|first1=M.|title=Aging Changes in the Human Sinoatrial Node|journal=Journal of Gerontology|volume=9|issue=1|year=1954|pages=1–9|issn=0022-1422|doi=10.1093/geronj/9.1.1}}</ref><ref name="pmid23939447">{{cite journal| author=Semelka M, Gera J, Usman S| title=Sick sinus syndrome: a review. | journal=Am Fam Physician | year= 2013 | volume= 87 | issue= 10 | pages= 691-6 | pmid=23939447 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23939447 }} </ref> | ||
*Studies on familial and congenital presentations of sick sinus syndrome have also revealed [[genetic]] contributions to dysfunctional [[ion channels]].<ref name="pmid14523039">{{cite journal| author=Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ et al.| title=Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). | journal=J Clin Invest | year= 2003 | volume= 112 | issue= 7 | pages= 1019-28 | pmid=14523039 | doi=10.1172/JCI18062 | pmc=198523 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14523039 }} </ref> | *Studies on familial and congenital presentations of sick sinus syndrome have also revealed [[genetic]] contributions to dysfunctional [[ion channels]].<ref name="pmid14523039">{{cite journal| author=Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ et al.| title=Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). | journal=J Clin Invest | year= 2003 | volume= 112 | issue= 7 | pages= 1019-28 | pmid=14523039 | doi=10.1172/JCI18062 | pmc=198523 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14523039 }} </ref> | ||
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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]
Overview
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.
Pathophysiology
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]
Pathogenesis
- 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]
Genetic
Genes involved in the pathogenesis of sick sinus syndrome include:[8][9]
- MYH6 gene:recent research has shown a higher incidence of SSS in carriers of a rare variant of the MYH6 gene, which encodes the alpha heavy chain subunit of cardiac myosin.
Associated Conditions
Conditions associated with sick sinus syndrome include:[4][10]
References
- ↑ Opthof, Tobias (1988). "The mammalian sinoatrial node". Cardiovascular Drugs and Therapy. 1 (6): 573–597. doi:10.1007/BF02125744. ISSN 0920-3206.
- ↑ 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.
- ↑ 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.
- ↑ 4.0 4.1 Semelka M, Gera J, Usman S (2013). "Sick sinus syndrome: a review". Am Fam Physician. 87 (10): 691–6. PMID 23939447.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.