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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).
See: Feature record | Search on this feature
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 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.
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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
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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

Baroreflex Sensitivity in Patients With Atrial Fibrillation.
Miyoshi M, Kondo H, Ishii Y, Shinohara T, Yonezu K, Harada T, Sato H, Yano Y, Yoshimura S, Abe I, Shuto T, Akioka H, Teshima Y, Wada T, Yufu K, Nakagawa M, Anai H, Miyamoto S, Takahashi N
J Am Heart Assoc 2020 Dec 15;9(24):e018019. Epub 2020 Dec 2 doi: 10.1161/JAHA.120.018019. PMID: 33263265Free 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
An uncommon cause of syncope.
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
The genetics of cardiac arrhythmias.
Beery TT
Biol Res Nurs 2005 Apr;6(4):249-61. doi: 10.1177/1099800404273840. PMID: 15788734
Survival in patients with permanent pacemakers.
Rosenqvist M, Nordlander R
Cardiol Clin 1992 Nov;10(4):691-703. PMID: 1423381

Diagnosis

Potential consequences of cardioneuroablation for vasovagal syncope: A call for appropriately designed, sham-controlled clinical trials.
Chakraborty P, Chen PS, Gollob MH, Olshansky B, Po SS
Heart Rhythm 2024 Apr;21(4):464-470. Epub 2023 Dec 16 doi: 10.1016/j.hrthm.2023.12.004. PMID: 38104955
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
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
An uncommon cause of syncope.
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
The genetics of cardiac arrhythmias.
Beery TT
Biol Res Nurs 2005 Apr;6(4):249-61. doi: 10.1177/1099800404273840. PMID: 15788734

Therapy

The culprit was inside myocardium.
Marinho AV, Ferreira MJ, Silva R, Elvas L, Gonçalves L
J Nucl Cardiol 2021 Aug;28(4):1785-1787. Epub 2020 Apr 29 doi: 10.1007/s12350-020-02060-0. PMID: 32350766
Baroreflex Sensitivity in Patients With Atrial Fibrillation.
Miyoshi M, Kondo H, Ishii Y, Shinohara T, Yonezu K, Harada T, Sato H, Yano Y, Yoshimura S, Abe I, Shuto T, Akioka H, Teshima Y, Wada T, Yufu K, Nakagawa M, Anai H, Miyamoto S, Takahashi N
J Am Heart Assoc 2020 Dec 15;9(24):e018019. Epub 2020 Dec 2 doi: 10.1161/JAHA.120.018019. PMID: 33263265Free 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
Evidence-based pharmacological treatment of geriatric bipolar disorder.
Young RC
Psychiatr Clin North Am 2005 Dec;28(4):837-69, viii. doi: 10.1016/j.psc.2005.09.011. PMID: 16325732
Cardiac pacing: atrial fibrillation may go unrecognised.
Corea F, Tambasco N
Lancet Neurol 2005 May;4(5):265. doi: 10.1016/S1474-4422(05)70051-X. PMID: 15847834

Prognosis

Baroreflex Sensitivity in Patients With Atrial Fibrillation.
Miyoshi M, Kondo H, Ishii Y, Shinohara T, Yonezu K, Harada T, Sato H, Yano Y, Yoshimura S, Abe I, Shuto T, Akioka H, Teshima Y, Wada T, Yufu K, Nakagawa M, Anai H, Miyamoto S, Takahashi N
J Am Heart Assoc 2020 Dec 15;9(24):e018019. Epub 2020 Dec 2 doi: 10.1161/JAHA.120.018019. PMID: 33263265Free 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 features, predictors, and long-term prognosis of pacing-induced cardiomyopathy.
Cho SW, Gwag HB, Hwang JK, Chun KJ, Park KM, On YK, Kim JS, Park SJ
Eur J Heart Fail 2019 May;21(5):643-651. Epub 2019 Feb 8 doi: 10.1002/ejhf.1427. PMID: 30734436
An uncommon cause of syncope.
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
Survival in patients with permanent pacemakers.
Rosenqvist M, Nordlander R
Cardiol Clin 1992 Nov;10(4):691-703. PMID: 1423381

Clinical prediction guides

Interesting phenomena during threshold testing of conduction system pacing: What is the mechanism?
Shen J, Jiang L, Wu H, Pan L
Pacing Clin Electrophysiol 2023 Apr;46(4):319-322. Epub 2022 Oct 10 doi: 10.1111/pace.14600. PMID: 36193871
Permanent pacemaker implantation rates following cardiac surgery in the modern era.
Kho J, Ioannou A, O'Sullivan KE, Jones M
Ir J Med Sci 2020 Nov;189(4):1289-1294. Epub 2020 May 22 doi: 10.1007/s11845-020-02254-y. PMID: 32445118Free 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
Clinical features, predictors, and long-term prognosis of pacing-induced cardiomyopathy.
Cho SW, Gwag HB, Hwang JK, Chun KJ, Park KM, On YK, Kim JS, Park SJ
Eur J Heart Fail 2019 May;21(5):643-651. Epub 2019 Feb 8 doi: 10.1002/ejhf.1427. PMID: 30734436
Predictors of future arrhythmic events in patients with unexplained syncope.
Prochnau D, Lambert T, Sigusch H, Surber R, Schulze PC
Acta Cardiol 2017 Oct;72(5):530-535. Epub 2017 Jul 6 doi: 10.1080/00015385.2017.1306389. PMID: 28682147

Recent systematic reviews

Epicardial Versus Endocardial Pacing in Paediatric Patients with Atrioventricular Block or Sinus Node Dysfunction: A Systematic Review and Meta-analysis.
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
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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