Association between sick sinus syndrome and atrial fibrillation: A systematic review and meta-analysis
Introduction
The sinoatrial node (SAN) located in the right atrium is responsible for generating the regular heart rhythm. Sick sinus syndrome (SSS) is a disorder of the SAN often caused by age-related degeneration, but can also be the result of infiltrative disorders [1,2], congenital heart diseases such as Brugada syndrome [3,4], long QT syndrome [5], catecholaminergic polymorphic ventricular tachycardia [[6], [7], [8]] and early repolarization syndrome [9], or cardiac surgery [10]. Atrial fibrillation (AF) is the most common accompanying arrhythmia in SSS [11], accounting for 40%‐70% [12]. It is also the most common persistent arrhythmia worldwide, which represents a significant burden on patients, doctors and global healthcare systems [13]. In a study with a median follow-up of 17 years, SSS is associated with a four-fold increase in the risk of AF after adjustment for other cardiovascular diseases [14]. Interestingly, the occurrence of AF was not associated with higher resting heart rate (heart rate (HR) > 90 bpm) but with lower resting heart rate (HR < 60 bpm), suggesting that for every 5 bpm decrease in HR, the risk of AF increased by 1.06-fold [15].
The use of antiarrhythmic drugs may aggravate SSS in AF patients with SSS by decreasing heart rate. Therefore, the influence of different interventional strategies on the prognosis of AF patients with SSS has been increasingly studied. Cardiac pacing simulates the generation and conduction of cardiac impulses and a series of electrophysiological functions through a pacing pulse generator, and stimulates the heart to beat by emitting low-energy pulses. Therefore, it is the most effective treatment for SSS. However, with the increasing use of pacemaker therapy, an increasing number of complications have been found, among which, AF is one of the most common complications. Catheter ablation is thought to prevent AF and improve the symptoms. For patients with AF and SSS, catheter ablation reduced the use of arrhythmic drugs and pacemaker implantation [16]. This systematic review and meta-analysis aimed to decipher the precise relationship between SSS and AF, further exploring and comparing different therapy strategies on the occurrence or progression of AF in patients with SSS.
Section snippets
Search strategy
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search was conducted in PubMed, Embase, Cochrane Library and Web of Science until 10th November 2022 by two investigators (Ying Liu and Yi Zheng), independently. We developed search strategies based on medical subject headings (MESH) terms and entry terms of atrial fibrillation and sick sinus syndrome (The detailed search
Study selection and characteristics
A flow diagram of study selection is listed in Fig. 1. A total of 3564 studies were identified from PubMed, Embase, Cochrane Library and Web of Science from an initial search. After excluding 908 duplications and 2546 records from titles and abstracts, 110 studies were eligible for full-text reviews. Subsequently, 75 studies were excluded for the following reasons: 26 articles implemented unrelated inventions, 46 articles reported no outcomes of interest or provided no relevant data, and 3
Discussion
This systematic review and meta-analysis aimed to decipher the precise relationship between SSS and AF, further exploring and comparing different therapy strategies on the occurrence or progression of AF in patients with SSS. The main findings are that i) patients with SSS were associated with higher risks of AF development compared to those without SSS or those with AVB; ii) Catheter ablation was associated with a lower risk of AF recurrence, AF progression, all-cause mortality, stroke and
Limitations
For this meta-analysis, several possible limitations should be noted. First of all, as the fundamental purpose of this paper is to elucidate the relationship between SSS and AF, the studies not elucidated that pacemaker implantation indication is SSS were excluded, resulting in several groups with only two or three studies. The study subjects included in different studies were not homogenized, which may cause high heterogeneity. Secondly, 22 studies included in this meta-analysis were
Conclusion
SSS is associated with a higher risk of AF. For AF patients with SSS, catheter ablation should be considered as it is associated with lower risks of AF recurrence, AF development and adverse outcomes including all-cause mortality, stroke and hospitalization of heart failure. Importantly, this meta-analysis re-emphasizes that high percentage of ventricular pacing should be avoided in patients with SSS in order to decrease AF burden and mortality.
Fundings
The work was funded by grants from National Natural Science Foundation of China (81970270, 82170327 to TL) and Tianjin Key Medical Discipline (Specialty) Construction Project(TJYXZDXK-029A).
Authors' contributions
TL, YL and YZ conceived and designed the paper. YL and YZ drafted the first version of the manuscript. GT, GB, KL, CG, PK and GPL provided crucial intellectual contribution and assisted in the revision of the manuscript. TL is the guarantor. All authors have approved the final version of the manuscript. All listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Declaration of Competing Interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments
We would like to express our sincere gratitude to all participants and thanks to all the peer reviewers for their opinions and suggestions.
References (73)
- et al.
Sick sinus syndrome as a late complication after ventricular septal defect surgery
J. Cardiol. Cases
(2013) - et al.
The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and baseline characteristics of the first 1000 patients
Am. Heart J.
(2000) - et al.
Spatial relationships of complex fractionated atrial Electrograms and continuous electrical activity to focal electrical sources: implications for substrate ablation in human atrial fibrillation
JACC Clin. Electrophysiol.
(2017) - et al.
Sinoatrial node electrical activity modulates pulmonary vein arrhythmogenesis
Int. J. Cardiol.
(2014) - et al.
Sick sinus syndrome and atrial fibrillation in older persons - a view from the sinoatrial nodal myocyte
J. Mol. Cell. Cardiol.
(2015) - et al.
Patterns of left atrial activation and evaluation of atrial dyssynchrony in patients with atrial fibrillation and normal controls: factors beyond the left atrial dimensions
Heart Rhythm.
(2016) - et al.
Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation
Heart Rhythm.
(2012) - et al.
Brugada syndrome: a comprehensive review of pathophysiological mechanisms and risk stratification strategies
Int. J. Cardiol. Heart Vasc.
(2020) - et al.
Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene
Forensic Sci. Int.
(2017) - et al.
Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction
Heart Rhythm.
(2017)
Effects of minimizing ventricular pacing on the incidence of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials
J. Am. Coll. Cardiol.
Association between ventricular pacing and persistent atrial fibrillation in patients indicated to elective pacemaker replacement: results of the Prefer for elective replacement MVP (PreFER MVP) randomized study
Heart Rhythm.
Randomized crossover comparison of right atrial appendage pacing versus interatrial septum pacing for prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia
Am. Heart J.
Secondary cardiac lymphoma presenting as sick sinus syndrome and atrial fibrillation which required leadless pacemaker implantation
Intern. Med.
A case report of sick sinus syndrome as an initial presentation of primary amyloidosis
Cureus.
Territory-wide cohort study of Brugada syndrome in Hong Kong: predictors of long-term outcomes using random survival forests and non-negative matrix factorisation
Open Heart.
Brugada syndrome and sinus node dysfunction
J. Arrhythm.
Paediatric/young versus adult patients with long QT syndrome
Open Heart.
Arrhythmic outcomes in catecholaminergic polymorphic ventricular tachycardia
medRxiv.
Clinical characteristics, genetic findings and arrhythmic outcomes of patients with catecholaminergic polymorphic ventricular tachycardia from China: a systematic review
Life (Basel)
Clinical characteristics, genetic basis and healthcare resource utilisation and costs in patients with catecholaminergic polymorphic ventricular tachycardia: a retrospective cohort study
Rev. Cardiovasc. Med.
Genetic analysis of sick sinus syndrome in a family harboring compound CACNA1C and TTN mutations
Mol. Med. Rep.
Tachycardia-bradycardia syndrome: electrophysiological mechanisms and future therapeutic approaches (review)
Int. J. Mol. Med.
Atrial fibrillation
Nat. Rev. Dis. Primers
Association of sick sinus syndrome with incident cardiovascular disease and mortality: the atherosclerosis risk in communities study and cardiovascular health study
PLoS One
Prevalence of conduction delay of the right atrium in patients with SSS: implications for pacing site selection
J. Cardiovasc. Med. (Hagerstown)
Pacing or ablation: which is better for paroxysmal atrial fibrillation-related tachycardia-bradycardia syndrome?
Pacing Clin. Electrophysiol.
Long-term clinical outcomes of radiofrequency catheter ablation versus permanent pacemaker implantation in patients with tachycardia-bradycardia syndrome
Korean Circ J.
Sinoatrial remodeling caused by persistent atrial fibrillation: what is the relationship between postcardioversion sinus node dysfunction and increased atrial vulnerability?
J. Cardiovasc. Electrophysiol.
Atrial cardiomyopathy: from cell to bedside
ESC Heart Fail.
Electrophysiological and electroanatomic characterization of the atria in sinus node disease: evidence of diffuse atrial remodeling
Circulation.
Atrial size independently correlates with the development of paroxysmal atrial fibrillation in patients with sick sinus syndrome
Chang Gung Med. J.
Clinical and biological determinants of P-wave duration: cross-sectional data from the population-based CoLaus|PsyCoLaus study
BMJ Open
Sinus node and atrial arrhythmias
Circulation.
Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling
Europace.
Atrial fibrillation pathophysiology: implications for management
Circulation.
Cited by (2)
Association of Antiarrhythmic Drug Therapy With Syncope and Pacemaker Implantation in Patients With Atrial Fibrillation
2024, Journal of the American College of CardiologyDoes asymptomatic atrial fibrillation exist?
2024, Journal of Cardiovascular Electrophysiology
- 1
Co-first authors/equal contributions.