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Sick sinus syndrome 4(SSS4)

MedGen UID:
1794159
•Concept ID:
C5561949
•
Disease or Syndrome
Synonym: SSS4
 
Gene (location): GNB2 (7q22.1)
 
Monarch Initiative: MONDO:0859173
OMIM®: 619464

Definition

Sick sinus syndrome-4 (SSS4) is characterized by early and progressive sinus node and atrioventricular conduction dysfunction. Patients show bradycardia and chronotropic incompetence, and may experience syncope. Atrioventricular conduction block ranges from mild to severe, and some patients also have intermittent atrial fibrillation. Many require implantation of a pacemaker, but sudden cardiac death has not been reported (Stallmeyer et al., 2017). For a general phenotypic description and discussion of genetic heterogeneity of sick sinus syndrome, see SSS1 (608567). [from OMIM]

Clinical features

From HPO
Atrioventricular block
MedGen UID:
13956
•Concept ID:
C0004245
•
Disease or Syndrome
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
See: Feature record | Search on this feature
Sinoatrial block
MedGen UID:
19984
•Concept ID:
C0037188
•
Disease or Syndrome
Disturbance in the atrial activation that is caused by transient failure of impulse conduction from the sinoatrial node to the cardiac atria.
See: Feature record | Search on this feature
Syncope
MedGen UID:
21443
•Concept ID:
C0039070
•
Sign or Symptom
Syncope refers to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.
See: Feature record | Search on this feature
Sinus bradycardia
MedGen UID:
39316
•Concept ID:
C0085610
•
Pathologic Function
Bradycardia related to a mean resting sinus rate of less than 50 beats per minute.
See: Feature record | Search on this feature
Paroxysmal atrial fibrillation
MedGen UID:
115990
•Concept ID:
C0235480
•
Disease or Syndrome
Episodes of atrial fibrillation that typically last for several hours up to one day and terminate spontaneously.
See: Feature record | Search on this feature
Chronotropic incompetence
MedGen UID:
745001
•Concept ID:
C1997984
•
Finding
Inability of the heart to increase its rate commensurate with increased activity or demand.
See: Feature record | Search on this feature
Abnormal QRS complex
MedGen UID:
1370423
•Concept ID:
C4476580
•
Finding
An anomaly of the complex formed by the Q, R, and S waves, which occur in rapid succession on the electrocardiogram.
See: Feature record | Search on this feature
Abnormal QT interval
MedGen UID:
1620328
•Concept ID:
C4531051
•
Finding
Any anomaly of the time interval between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).
See: Feature record | Search on this feature
Abnormal PR interval
MedGen UID:
1634800
•Concept ID:
C4703431
•
Finding
An anomaly of the PR interval, which is the portion of the ECG from the onset of the P wave to the beginning of the QRS complex. A normal PR interval in adults is 0.12-0.2 seconds.
See: Feature record | Search on this feature

Professional guidelines

PubMed

The prevalence of diabetes mellitus and other risk factors of atherosclerosis in bradycardia requiring pacemaker treatment.
Podlaha R, Falk A
Horm Metab Res Suppl 1992;26:84-7. PMID: 1490698

Recent clinical studies

Etiology

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.
Müller J, Nentwich K, Berkovitz A, Ene E, Sonne K, Chakarov I, Barth S, Waechter C, Lüsebrink U, Behnes M, Akin I, Deneke T
J Cardiovasc Electrophysiol 2022 Jul;33(7):1425-1434. Epub 2022 May 6 doi: 10.1111/jce.15504. PMID: 35441414
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 36282123
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 33580673Free PMC Article
Pacemaker exteriorization.
Dupont J, Koch A, Vonck A, Sarens T
Acta Cardiol 2020 Aug;75(4):375-376. Epub 2019 Mar 20 doi: 10.1080/00015385.2019.1587139. PMID: 30893006
Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy.
Wilde AAM, Amin AS
JACC Clin Electrophysiol 2018 May;4(5):569-579. Epub 2018 May 2 doi: 10.1016/j.jacep.2018.03.006. PMID: 29798782

Diagnosis

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.
Müller J, Nentwich K, Berkovitz A, Ene E, Sonne K, Chakarov I, Barth S, Waechter C, Lüsebrink U, Behnes M, Akin I, Deneke T
J Cardiovasc Electrophysiol 2022 Jul;33(7):1425-1434. Epub 2022 May 6 doi: 10.1111/jce.15504. PMID: 35441414
Sinus Node Dysfunction.
Sathnur N, Ebin E, Benditt DG
Card Electrophysiol Clin 2021 Dec;13(4):641-659. Epub 2021 Sep 23 doi: 10.1016/j.ccep.2021.06.006. PMID: 34689892
Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy.
Wilde AAM, Amin AS
JACC Clin Electrophysiol 2018 May;4(5):569-579. Epub 2018 May 2 doi: 10.1016/j.jacep.2018.03.006. PMID: 29798782
Sick Sinus Syndrome.
Walsh-Irwin C, Hannibal GB
AACN Adv Crit Care 2015 Oct-Dec;26(4):376-80. doi: 10.1097/NCI.0000000000000099. PMID: 26485000
Sick sinus syndrome.
Br Med J 1977 Jan 1;1(6052):4-5. PMID: 831979Free PMC Article

Therapy

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.
Müller J, Nentwich K, Berkovitz A, Ene E, Sonne K, Chakarov I, Barth S, Waechter C, Lüsebrink U, Behnes M, Akin I, Deneke T
J Cardiovasc Electrophysiol 2022 Jul;33(7):1425-1434. Epub 2022 May 6 doi: 10.1111/jce.15504. PMID: 35441414
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 36282123
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 33580673Free PMC Article
Pacemaker exteriorization.
Dupont J, Koch A, Vonck A, Sarens T
Acta Cardiol 2020 Aug;75(4):375-376. Epub 2019 Mar 20 doi: 10.1080/00015385.2019.1587139. PMID: 30893006
Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction.
Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA; MOde Selection Trial Investigators
Circulation 2003 Jun 17;107(23):2932-7. Epub 2003 Jun 2 doi: 10.1161/01.CIR.0000072769.17295.B1. PMID: 12782566

Prognosis

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.
Müller J, Nentwich K, Berkovitz A, Ene E, Sonne K, Chakarov I, Barth S, Waechter C, Lüsebrink U, Behnes M, Akin I, Deneke T
J Cardiovasc Electrophysiol 2022 Jul;33(7):1425-1434. Epub 2022 May 6 doi: 10.1111/jce.15504. PMID: 35441414
Pacemaker exteriorization.
Dupont J, Koch A, Vonck A, Sarens T
Acta Cardiol 2020 Aug;75(4):375-376. Epub 2019 Mar 20 doi: 10.1080/00015385.2019.1587139. PMID: 30893006
Sick Sinus Syndrome After the Maze Procedure Performed Concomitantly With Mitral Valve Surgery.
Cho MS, Heo R, Jin X, Lee JB, Lee S, Kim DH, Kim JB, Kim J, Jung SH, Choo SJ, Song JM, Nam GB, Choi KJ, Kang DH, Chung CH, Lee JW, Kim YH, Song JK
J Am Heart Assoc 2018 Oct 2;7(19):e009629. doi: 10.1161/JAHA.118.009629. PMID: 30371317Free PMC Article
Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.
Abe K, Machida T, Sumitomo N, Yamamoto H, Ohkubo K, Watanabe I, Makiyama T, Fukae S, Kohno M, Harrell DT, Ishikawa T, Tsuji Y, Nogami A, Watabe T, Oginosawa Y, Abe H, Maemura K, Motomura H, Makita N
Circ Arrhythm Electrophysiol 2014 Jun;7(3):511-7. Epub 2014 Apr 24 doi: 10.1161/CIRCEP.113.001340. PMID: 24762805
Pharmacological testing in the diagnosis of arrhythmias.
Brembilla-Perrot B
Minerva Cardioangiol 2010 Aug;58(4):505-17. PMID: 20938414

Clinical prediction guides

Efficacy and safety of high-power short duration atrial fibrillation ablation in elderly patients.
Müller J, Nentwich K, Berkovitz A, Ene E, Sonne K, Chakarov I, Barth S, Waechter C, Lüsebrink U, Behnes M, Akin I, Deneke T
J Cardiovasc Electrophysiol 2022 Jul;33(7):1425-1434. Epub 2022 May 6 doi: 10.1111/jce.15504. PMID: 35441414
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 36282123
Genetic insight into sick sinus syndrome.
Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K; DBDS Genomic Consortium
Eur Heart J 2021 May 21;42(20):1959-1971. doi: 10.1093/eurheartj/ehaa1108. PMID: 33580673Free PMC Article
The expanding phenotypes of cohesinopathies: one ring to rule them all!
Piché J, Van Vliet PP, Pucéat M, Andelfinger G
Cell Cycle 2019 Nov;18(21):2828-2848. Epub 2019 Sep 13 doi: 10.1080/15384101.2019.1658476. PMID: 31516082Free PMC Article
Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction.
Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA; MOde Selection Trial Investigators
Circulation 2003 Jun 17;107(23):2932-7. Epub 2003 Jun 2 doi: 10.1161/01.CIR.0000072769.17295.B1. PMID: 12782566

Recent systematic reviews

Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.
Nagamine T, Randhawa S, Nishimura Y, Huang R, Leesutipornchai T, Benavente K, Yoshimura S, Zhang J, Kanitsorphan C
Pacing Clin Electrophysiol 2022 Apr;45(4):556-566. Epub 2022 Mar 3 doi: 10.1111/pace.14466. PMID: 35182433Free PMC Article
Tricuspid regurgitation associated with implantable electrical device insertion: A systematic review and meta-analysis.
Tatum R, Maynes EJ, Wood CT, Deb AK, Austin MA, O'Malley TJ, Choi JH, Massey HT, Morris RJ, Pavri BB, Tchantchaleishvili V
Pacing Clin Electrophysiol 2021 Aug;44(8):1297-1302. Epub 2021 Jul 1 doi: 10.1111/pace.14287. PMID: 34081789
Comparison of survival for cardiac resynchronization therapy in atrial fibrillation patients with or without atrio-ventricular junction ablation and patients in sinus rhythm: a systematic review and network meta-analysis.
Xue Y, Wang J, Wang J, Thapa S, Huang K, Peng Y, Qian L, Li J, Ji K
Heart Fail Rev 2019 May;24(3):335-342. doi: 10.1007/s10741-018-9761-5. PMID: 30610455
Chronic Arrhythmias in the Setting of Heterotaxy: Differences between Right and Left Isomerism.
Loomba RS, Willes RJ, Kovach JR, Anderson RH
Congenit Heart Dis 2016 Jan-Feb;11(1):7-18. Epub 2015 Jul 29 doi: 10.1111/chd.12288. PMID: 26219620

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