Supplementary material – RESPIRE
Supplementary Table 1. Baseline characteristics in the full analysis set (FAS) and modified intention-to-treat (mITT) populations (n=553 and n=1024, respectively)
Data are presented as mean ± standard deviation, median [interquartile range], or number (percentage).
Baseline characteristics FAS n=553
mITT n=1024
Age (years) 75.2±9.5 75.5±10.4
<65 years 70 (12.7%) 132 (12.9%)
≥65 to <85 years 399 (72.2%) 712 (69.5%)
≥85 years 79 (14.3%) 173 (16.9%)
Male 340 (61.5%) 588 (57.4%)
SBP (mm Hg) 141±23 141±22
DBP (mm Hg) 73±12 74±12
Heart rate (bpm) 64±16 65±17
BMI (kg/m2) 26.6 [24.0; 29.9] 26.7 [24.0; 30.1]
Cardiovascular history
CAD 65 (11.8%) 121 (11.8%)
Angina 26 (4.7%) 33 (3.2%)
Cardiomyopathy 26 (4.7%) 48 (4.7%)
Myocardial infarction 30 (5.4%) 56 (5.5%)
Heart failure 18 (3.3%) 46 (4.5%)
Cardiac surgery 36 (6.5%) 63 (6.2%)
Stroke history 32 (5.8%) 57 (5.6%)
TIA 10 (1.8%) 19 (1.9%)
Renal failure 20 (3.6%) 42 (4.1%)
Implant indication
Sinus dysfunction 122 (22.1%) 235 (22.9%)
AV block 264 (47.7%) 469 (45.8%)
Syncope 50 (9.0%) 96 (9.4%)
Carotid sinus syndrome 6 (1.1%) 11 (1.1%)
Brady-tachy syndrome 57 (10.3%) 122 (11.9%)
Other 50 (9.0%) 83 (8.1%)
Unknown 4 (0.7%) 8 (0.8%)
History of rhythm disorders
Atrial fibrillation 132 (23.9%) 248 (24.2%)
Paroxysmal 111 (20.1%) 219 (21.4%)
Permanent 3 (0.5%) 5 (0.5%)
Persistent 16 (2.9%) 21 (2.1%)
Unknown 2 (0.4%) 3 (0.3%)
Atrial flutter 26 (4.7%) 52 (5.1%)
Atrial extrasystole >10/minute 5 (0.9%) 8 (0.8%) Ventricular extrasystole >10/minute 9 (1.6%) 15 (1.5%)
Long QT syndrome 3 (0.5%) 4 (0.4%)
Ventricular tachycardia 6 (1.1%) 13 (1.3%)
Sleep apnea 44 (8.0%) 73 (7.1%)
Light (5≤ AHI <15) 2 (0.4%) 3 (0.3%)
Moderate (15≤ AHI <30) 3 (0.5%) 6 (0.6%)
Severe (AHI ≥30) 18 (3.3%) 35 (3.4%)
AHI unknown 21 (3.8%) 29 (2.8%)
Comorbidities
COPD 19 (3.4%) 30 (2.9%)
Diabetes 97 (17.5%) 171 (16.7%)
Smoking status
Non-smoker 354 (64.0%) 677 (66.1%)
Baseline characteristics FAS n=553
mITT n=1024
Unknown 39 (7.1%) 79 (7.7%)
Medication Antiarrhythmic
Amiodarone 49 (8.9%) 114 (11.1%)
Beta-blocker 134 (24.2%) 264 (25.8%)
Digoxin 4 (0.7%) 10 (1.0%)
Disopyramide 2 (0.4%) 2 (0.2%)
Dronedarone 2 (0.4%) 2 (0.2%)
Flecainide 14 (2.5%) 25 (2.4%)
Propafenone 3 (0.5%) 5 (0.5%)
Sotalol 8 (1.4%) 24 (2.3%)
Other antiarrhythmic 19 (3.4%) 35 (3.4%)
Anticoagulant
Antivitamin Ka 80 (14.5%) 168 (16.4%)
NOACb 47 (8.5%) 80 (7.8%)
Other anticoagulant 23 (4.2%) 42 (4.1%)
Antiplatelet drug 131 (23.7%) 243 (23.7%)
aeg, coumadin, warfarin, acenocumarol. beg, dabidatran, rivaroxavan, apixaban, edoxaban.
Abbreviations: AHI, apnea-hypopnea index; AV, atrioventricular; BMI, body mass index; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; NOAC, non-vitamin K oral anticoagulant; SBP, systolic blood pressure; TIA, transient ischemic attack.
Supplementary Table 2. Baseline characteristics in the modified intention-to-treat (mITT) population (n=1024) according to severity of sleep apnea (SA)
Data are presented as mean ± standard deviation or number (percentage).
Baseline characteristics Severe SA n=321
Non-severe SA n=698
P-value
Age (years) 77.9±9.5 74.4±10.6 <0.001
<65 years 28 (8.7%) 104 (14.9%)
<0.001
≥65 to <85 years 214 (66.7%) 494 (70.8%)
≥85 years 77 (24.0%) 95 (13.6%)
Male 211 (65.7%) 374 (53.6%) <0.001
SBP (mm Hg) 141±21 141±22 0.99
DBP (mm Hg) 74±12 74±12 0.66
Heart rate (bpm) 65±16 65±17 0.57
BMI (kg/m2) 28.7±5.9 26.9±4.5 0.007
Cardiovascular history
CAD 51 (15.9%) 70 (10.0%) 0.009
Angina 12 (3.7%) 21 (3.0%) 0.57
Cardiomyopathy 25 (7.8%) 23 (3.3%) 0.002
Myocardial infarction 25 (7.8%) 31 (4.4%) 0.038
Heart failure 19 (5.9%) 27 (3.9%) 0.15
Cardiac surgery 30 (9.3%) 33 (4.7%) 0.007
Stroke history 22 (6.9%) 35 (5.0%) 0.24
TIA 8 (2.5%) 11 (1.6%) 0.33
Renal failure 15 (4.7%) 27 (3.9%) 0.61
Implant indication
Sinus dysfunction 63 (19.6%) 170 (24.4%)
0.030
AV block 149 (46.4%) 318 (45.6%)
Syncope 31 (9.7%) 65 (9.3%)
Carotid sinus syndrome 5 (1.6%) 6 (0.9%)
Brady-tachy syndrome 34 (10.6%) 87 (12.5%)
Other 37 (11.5%) 43 (6.2%)
Unknown 1 (0.3%) 7 (1.0%)
History of rhythm disorders
Atrial fibrillation 89 (27.7%) 157 (22.5%) 0.08
Paroxysmal 75 (23.4%) 142 (20.3%)
Permanent 4 (1.2%) 1 (0.1%)
Persistent 9 (2.8%) 12 (1.7%)
Unknown 1 (0.3%) 2 (0.3%)
Atrial flutter 23 (7.2%) 29 (4.2%) 0.047
Atrial extrasystole
>10/minute
3 (0.9%) 5 (0.7%)
0.71 Ventricular extrasystole
>10/minute
5 (1.6%) 8 (1.1%)
0.56
Long QT syndrome 1 (0.3%) 3 (0.4%) 1
Ventricular tachycardia 2 (0.6%) 10 (1.4%) 0.36
Sleep apnea 20 (6.2%) 53 (7.6%) 0.51
Light (5≤ AHI <15) - 3 (0.4%)
Moderate (15≤ AHI <30) 1 (0.3%) 5 (0.7%)
Severe (AHI ≥30) 9 (2.8%) 26 (3.7%)
AHI unknown 10 (3.1%) 19 (2.7%)
Comorbidities
COPD 13 (4.0%) 17 (2.4%) 0.17
Diabetes 70 (21.8%) 101 (14.5%) 0.005
Smoking status
Non-smoker 202 (62.9%) 472 (67.6%)
Smoker 20 (6.2%) 47 (6.7%) 0.17
Ex-smoker 72 (22.4%) 115 (16.5%)
Baseline characteristics Severe SA n=321
Non-severe SA n=698
P-value
Amiodarone 41 (4.0%) 72 (7.0%) 0.28
Beta-blocker 103 (10.1%) 160 (15.6%) 0.003
Digoxin 7 (0.7%) 3 (0.3%) 0.014
Disopyramide 1 (0.1%) 1 (0.1%) 0.53
Dronedarone 1 (0.1%) 1 (0.1%) 0.53
Flecainide 5 (0.5%) 20 (2.0%) 0.28
Propafenone 0 (0%) 5 (0.5%) 0.33
Sotalol 9 (0.9%) 14 (1.4%) 0.50
Other antiarrhythmic 10 (1.0%) 25 (2.4%) 0.85
Anticoagulant
Antivitamin Ka 60 (5.9%) 107 (10.4%) 0.20
NOACb 32 (3.1%) 47 (4.6%) 0.078
Other anticoagulant 15 (1.5%) 27 (2.6%) 0.61
Antiplatelet drug 93 (9.1%) 149 (14.6%) 0.009
aeg, coumadin, warfarin, acenocumarol. beg, dabidatran, rivaroxavan, apixaban, edoxaban.
Abbreviations: AHI, apnea-hypopnea index; AV, atrioventricular; BMI, body mass index; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; NOAC, non-vitamin K oral anticoagulant; SBP, systolic blood pressure; TIA, transient ischemic attack.
Supplementary Table 3. Association between different burdens of atrial fibrillation (AF) and sleep apnea (SA) in the mITT population (n=1024)
1 month 6 months 12 months 18 months
Evaluable patients 826 (80.7%) 679 (66.3%) 553 (54%) 430 (42%)
Severe SA (RDI ≥20) 301 (36.4%) 230 (33.9%) 172 (31.1%) 118 (27.4%)
FMS <6 m in 1 d 209 (69.4%) 127 (55.2%) 81 (47.1%) 44 (37.3%)
6 m ≤FMS <6 h in 1 d 43 (14.3%) 35 (15.2%) 26 (15.1%) 23 (19.5%)
6 h ≤FMS <24 h in 1 d 11 (3.7%) 22 (9.6%) 20 (11.6%) 13 (11.0%)
24 h ≤FMS <7 d in 7 d 18 (6.0%) 17 (7.4%) 16 (9.3%) 12 (10.2%)
FMS over 7 d 20 (6.6%) 29 (12.6%) 29 (16.9%) 26 (22.0%)
Non-severe SA (RDI <20) 525 (63.6%) 449 (66.1%) 381 (68.9%) 312 (72.6%)
FMS <6 m in 1 d 400 (76.2%) 285 (63.5%) 208 (54.6%) 161 (51.6%)
6 m ≤FMS <6 h in 1 d 59 (11.2%) 81 (18.0%) 79 (20.7%) 63 (20.2%)
6 h ≤FMS <24 h in 1 d 19 (3.6%) 23 (5.1%) 35 (9.2%) 30 (9.6%)
24 h ≤FMS <7 d in 7 d 32 (6.1%) 40 (8.9%) 31 (8.1%) 31 (9.9%)
FMS over 7 d 15 (2.9%) 20 (4.5%) 28 (7.3%) 27 (8.7%)
Δ severe vs non-severe SA (% [95% CI])
FMS <6 m in 1 d -6.8% [-14.0; 0.5] -8.3% [-17.2; 0.7] -7.5% [-17.8; 2.8] -14.3% [-26.1; -2.5]
6 m ≤FMS <6 h in 1 d 3.1% [-2.4; 8.5] -2.8% [-9.5; 3.9] -5.6% [-13.3; 2.1] -0.7% [-10.3; 8.9]
6 h ≤FMS <24 h in 1 d 0.04% [-3.0; 3.1] 4.4% [-0.5; 9.4] 2.4% [-4.0; 8.9] 1.4% [-6.1; 8.9]
24 h ≤FMS <7 d in 7 d -0.1% [-4.0; 3.7] -1.5% [-6.4; 3.4] 1.2% [-4.7; 7.0] 0.2% [-7.1; 7.5]
FMS over 7 d 3.8% [0.2; 7.4] 8.2% [2.8; 13.5] 9.5% [2.5; 16.6] 13.4% [4.1; 22.7]
Abbreviations: CI, confidence interval; FMS, fallback mode switch; mITT, modified intention-to-treat; RDI, respiratory disturbance index; SA, sleep apnea
SupplementaryTable 4. Sleep apnea (SA) referrals, examinations and treatment in an unselected pacemaker population Patients with
severe SA N=313
Patients without severe SA N=706 Referred to sleep specialist at 12 months N=77 (24.6%) N=74 (10.5%)
Pneumologist 69 (22.0%) 67 (9.5%)
Neurologist 5 (1.6%) 1 (0.1%)
Ear Nose Throat specialist 0 (0%) 4 (0.6%)
Cardiologist 1 (0.3%) 2 (0.3%)
Other 5 (1.6%) 5 (0.7%)
Referred for a sleep apnea exam at 12 months N=68 (21.7%) N=65 (9.2%)
Polysomnography 55 (17.6%) 46 (6.5%)
Polygraphy 12 (3.8%) 17 (2.4%)
Other 5 (1.6%) 4 (0.6%)
Treated for sleep apnea at 12 months N=48 (15.3%) N=62 (8.8%)
