Atrial fibrillation burden and the risk of stroke: A systematic review and dose-response meta-analysis

Table 1 Characteristics of the included 16 studies, all except 1 were randomized controlled trial studies

Ref.1	Study type	Significant AF burden definition	Adverse outcomes	Sample size	Follow-up period	AF monitoring	Age (male/female)	Nation	Population
Glotzer et al[19], 2003, Ancillary MOST	Secondary analysis of multicenter RCT	AF rate > 220 bpm, AF burden ≥ 5 min	Stroke/systematic embolism	312	Median: 27 mo	PM	74 yr (141/171)	United States	Patients with sinus node disease who required PM for bradycardia and a history of AF
Capucci et al[7], 2005, Italian AT 500 Registry	Prospective, observational study	AF rate > 174 bpm, AF burden ≥ 5 min or ≥ 1 d	Thromboembolic event	725	Median: 22 mo	PM	72 yr (360/365)	Italy	Patients with symptomatic atrial tachyarrhythmias and a history of AF. Permanent AF were excluded
Botto et al[20], 2009, NA	Prospective, observational study	AF rate > 174 bpm, AF burden ≥ 5 min or ≥ 1 d	Stroke/systematic embolism	568	Mean: 1 yr	PM	70 yr (NA)	Italy	Patients with a class I or II American College of Cardiology/American Heart Association indication for dual-chamber PM, symptomatic atrial tachyarrhythmias and a history of AF. Permanent AF were excluded
Glotzer et al[21], 2009, TRENDS	Prospective, observational study	AF rate > 175 bpm, AF burden ≥ 20 s	Ischemic stroke, TIA, and systemic embolism	2486	Mean: 1.4 yr	PM, ICD or CRT	70 yr (1650/836)	International	Patients with an established class I/II indication for an ICD or stroke risk factor and a history of AF. Permanent AF were excluded
Healey et al[8], 2012, ASSERT ClinicalTrials	Prospective, observational study	AF rate > 190 bpm, AF burden＞6 min	Ischemic stroke or systemic embolism	2580	Mean: 2.5 yr	PM or ICD	77 yr (1506/1074)	International	Patients who had a history of hypertension, but no AF
Shanmugam et al[22], 2012, Home Monitor CRT	Prospective, observational study	AF rate > 180 bpm, AF burden > 14 min	Thromboembolic event	560	Median: 370 d	PM or ICD	66 yr (434/136)	Europe	Patients with a heart failure, CRT and a history of AF. Permanent AF were excluded
Gonzalez et al[23], 2014, NA	Retrospective, observational study	AF rate > 178 bpm, AF burden ≥ 5 min	Stroke and all-cause mortality	224	Median: 6.6 yr	PM	74 yr (118/106)	United States	Consecutive patients with no history of AF who underwent dual-chamber PM implantation
Boriani et al[24], 2014, SOS AF project (PANORAMA, TRENDS, ClinicalService)	Prospective studies	AF rate > 175 bpm, AF burden > 5 min	Ischemic stroke or TIA events	10016	Median: 2 yr	PM or ICD	70 yr (6859/3157)	International	Patients who had at least months of follow-up and with a history of AF. Permanent AF were excluded
Turakhia et al[25], 2015, NA	Case-Crossover	AF burden > 5.5 h in a day during a defined 30-d period	Ischemic Stroke	9850	Case period: 1-30 d Control period: 91-120 d	PM or ICD	NA	United States	Patients with CIEDs remotely monitored in the Veterans Administration Health Care System and a history of AF
Witt et al[26], 2015, NA	Retrospective, observational study	AF burden > 6 min	Thromboembolic events	394	Median: 4.2 yr	CRT	67 yr (290/104)	Denmark	Patients with a CRT device, and no history of AF
Benezet-Mazuecos et al[27], 2015, NA	Prospective, observational study	AF rate > 225 bpm, AF burden ≥ 5 min	Silent ischemic brain lesions	109	Median: 2 yr	PM, ICD or CRT	74 yr (61/48)	Europe	Patients with PMs, ICDs, and CRT capable of atrial activity monitoring, and with no history of AF
Van Gelder et al[28], 2017, ASSERT ClinicalTrials	Prospective, observational study	AF rate > 190 bpm, AF burden > 6 min	Ischemic stroke or systemic embolism	2455	Mean: 2.5 yr	PM or ICD	NA	International	Patients with hypertension but no prior AF requiring medical therapy
Chu et al[29], 2020, NA	Retrospective, observational study	AF rate > 250 bpm, AF burden > 6 min	Ischemic stroke, transient ischemic attack, or systemic embolism	152	Median: 67 mo	PM	73.2 yr (86/66)	China	Patients who were with a dual-chamber PM and a history of AF
Kaplan et al[30], 2019, NA	Retrospective, observational study	AF burden > 6 min	Ischemic Stroke and systemic embolism	21768	NA	PM, ICD or CRT	68.6 yr (13611/8157)	United States	Patients who had a cardiovascular diagnosis code or had a cardiovascular related procedure performed during the data collection period and with a history of AF
Li et al[31], 2019, The West Birmingham Atrial Fibrillation Project	Prospective, observational study	AF rate > 175 bpm, AF burden > 5 min	Thromboembolic event	594	Median: 4.2 yr	PM, ICD or CRT	69 yr (360/234)	United Kingdom	Patients receiving a PM, ICD, or CRT between Januar1999 and January 2017
Nakano et al[32], 2019, NA	Retrospective, observational study	AF rate > 200 bpm	Embolic stroke	348	Median: 65 mo	PM or ICD	70 yr (224/124)	Japan	Patients receiving PMs and ICDs between May 1980 and May 2016

¹Healey et al[8], 2012 and Van Gelder et al[28], 2017 were both from ASSERT clinical Trials and were used for analysis the association between atrial fibrillation burden > 5 min and future stroke, the dose-response association, respectively. PM: Pacemaker; ICD: Implantable cardioverter-defibrillator; CRT: Cardiac-resynchronization device; NA: Not applicable; AF: Atrial fibrillation.