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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
Sudden cardiac death
MedGen UID:
38841
Concept ID:
C0085298
Pathologic Function
The heart suddenly and unexpectedly stops beating resulting in death within a short time period (generally within 1 h of symptom onset).
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.
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.
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads 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.
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.
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.
Chronotropic incompetence
MedGen UID:
745001
Concept ID:
C1997984
Finding
Inability of the heart to increase its rate commensurate with increased activity or demand.
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.
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).
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.

Professional guidelines

Recent clinical studies

Etiology

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
Yang PS, Kim D, Jang E, Yu HT, Kim TH, Sung JH, Pak HN, Lee MH, Joung B
J Cardiovasc Electrophysiol 2021 Oct;32(10):2704-2714. Epub 2021 Aug 16 doi: 10.1111/jce.15202. PMID: 34379851
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
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
Campagna D, Amaradio MD, Battaglia E, Demma S, Russo C, Polosa R
Intern Emerg Med 2016 Apr;11(3):425-9. Epub 2015 Sep 25 doi: 10.1007/s11739-015-1317-2. PMID: 26407606

Diagnosis

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
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
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
Walsh-Irwin C, Hannibal GB
AACN Adv Crit Care 2015 Oct-Dec;26(4):376-80. doi: 10.1097/NCI.0000000000000099. PMID: 26485000
Br Med J 1977 Jan 1;1(6052):4-5. PMID: 831979Free PMC Article

Therapy

Mehta NA, Saqi B, Sabzwari SRA, Gupta R, Vyas A, Gordon J, Cossu S, Nazir T, Freudenberger R, Bozorgnia B
J Cardiovasc Electrophysiol 2022 Jul;33(7):1529-1536. Epub 2022 May 26 doi: 10.1111/jce.15545. PMID: 35586896
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
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
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
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

Prognosis

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
Liang E, Wu L, Fan S, Li X, Hu F, Zheng L, Fan X, Chen G, Ding L, Yao Y
Am J Cardiol 2019 May 15;123(10):1690-1695. Epub 2019 Feb 23 doi: 10.1016/j.amjcard.2019.02.032. PMID: 30885416
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
Campagna D, Amaradio MD, Battaglia E, Demma S, Russo C, Polosa R
Intern Emerg Med 2016 Apr;11(3):425-9. Epub 2015 Sep 25 doi: 10.1007/s11739-015-1317-2. PMID: 26407606
Brembilla-Perrot B
Minerva Cardioangiol 2010 Aug;58(4):505-17. PMID: 20938414

Clinical prediction guides

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
Yang PS, Kim D, Jang E, Yu HT, Kim TH, Sung JH, Pak HN, Lee MH, Joung B
J Cardiovasc Electrophysiol 2021 Oct;32(10):2704-2714. Epub 2021 Aug 16 doi: 10.1111/jce.15202. PMID: 34379851
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
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
Sutton R, Kenny RA
Pacing Clin Electrophysiol 1986 Nov;9(6):1110-4. doi: 10.1111/j.1540-8159.1986.tb06678.x. PMID: 2432517

Recent systematic reviews

Patsiou V, Haidich AB, Baroutidou A, Giannopoulos A, Giannakoulas G
Pediatr Cardiol 2023 Dec;44(8):1641-1648. Epub 2023 Jul 22 doi: 10.1007/s00246-023-03213-x. PMID: 37480376Free PMC Article
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
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
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
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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