Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 14, Number 3, June 2023, pages 183-191

Obstructive Sleep Apnea as a Predictor of Inducible Atrial Flutter During Pulmonary Vein Isolation in Patients With Atrial Fibrillation: Clinical Significance and Follow-Up Outcomes

Figure 1. Flow diagram illustrating patient selection. AFL: atrial flutter; PVI: pulmonary vein isolation; Maze: Cox maze procedure.

**Table 1.** Baseline Characteristics of the Patients
Characteristics	All patients (n =192)
Data for continuous variables (Age and BMI) are expressed as median and range. Data for categorical variables is expressed as mean ± standard deviation or proportion (percentages). AF: atrial fibrillation; BMI: body mass index; COPD: chronic obstructive pulmonary disease; OSA: obstructive sleep apnea.
Age (years)	66 (49 -71)
Sex
Male	122 (63.5%)
Female	70 (36.5%)
BMI	32 (28 - 37)
Medical history
OSA	92 (47.9%)
COPD	12 (6.3%)
Asthma	10 (5.2%)
Hypertension	153 (79.7%)
Hyperlipidemia	132 (68.8%)
Diabetes mellitus	50 (26%)
Coronary artery disease	58 (30.2%)
Failed previous antiarrhythmic	86 (44.8%)
Procedural indication
Paroxysmal AF	90 (46.9%)
Persistent AF	102 (53.1%)

Table 1. Baseline Characteristics of the Patients

Characteristics

All patients (n =192)

Data for continuous variables (Age and BMI) are expressed as median and range. Data for categorical variables is expressed as mean ± standard deviation or proportion (percentages). AF: atrial fibrillation; BMI: body mass index; COPD: chronic obstructive pulmonary disease; OSA: obstructive sleep apnea.

Age (years)

66 (49 -71)

Sex

Male

122 (63.5%)

Female

70 (36.5%)

BMI

32 (28 - 37)

Medical history

OSA

92 (47.9%)

COPD

12 (6.3%)

Asthma

10 (5.2%)

Hypertension

153 (79.7%)

Hyperlipidemia

132 (68.8%)

Diabetes mellitus

50 (26%)

Coronary artery disease

58 (30.2%)

Failed previous antiarrhythmic

86 (44.8%)

Procedural indication

Paroxysmal AF

90 (46.9%)

Persistent AF

102 (53.1%)

**Table 2.** Patient Home Medications and Antiarrhythmic Therapy
Drugs	All patients (n = 192)	Any inducible atrial flutter (n = 100)	P value	Typical right atrial flutter (n = 82)	P value	Atypical atrial flutter (n = 18)	P value
Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant. ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor blockers; SGLT2-I: sodium-glucose cotransporter-2 inhibitors; DOAC: direct oral anticoagulants; non-DHP CCB: non-dihydropyridine calcium channel blockers.
Home medications
Beta blocker	103 (53.6%)	63 (63%)	0.01*	52 (63.4%)	0.01*	11 (61.1%)	0.20
Non-DHP CCB	50 (26.0%)	21 (21%)	0.10	16 (19.5%)	0.07	5 (27.8%)	0.75
ACEI	49 (25.5%)	30 (30%)	0.19	27 (32.9%)	0.10	3 (16.7%)	0.76
ARBs	36 (18.8%)	15 (15%)	0.17	13 (15.9%)	0.25	2 (11.1%)	0.26
Sacubitril/valsartan	7 (3.6%)	3 (3%)	0.62	3 (3.7%)	1.0	0 (0%)	1.0
SGLT2-I	3 (1.6%)	0 (0%)	0.11	0 (0%)	0.25	0 (0%)	1.0
Spironolactone	19 (9.9%)	12 (12%)	0.31	12 (14.6%)	0.14	0 (0%)	0.60
Thiazide	19 (9.9%)	11 (11%)	0.58	10 (12.2%)	0.43	1 (5.6%)	1.0
Digoxin	2 (1.0%)	1 (1%)	1.0	1 (1.2%)	1.0	0 (0%)	1.0
Loop diuretic	39 (20.3%)	26 (26%)	0.07	23 (28%)	0.04*	3 (16.7%)	1.0
Statin	101 (52.6%)	56 (56%)	0.41	47 (57.3%)	0.33	9 (50%)	1.0
Aspirin	46 (24%)	22 (22%)	0.41	18 (21.9%)	0.43	4 (22.2%)	0.78
DOAC	162 (84.4%)	86 (86%)	0.66	72 (87.8%)	0.44	14 (77.8%)	0.54
Warfarin	13 (6.8%)	9 (9%)	0.26	5 (6.1%)	0.74	4 (22.2%)	0.02*
Current antiarrhythmic therapy
Amiodarone	105 (54.7%)	59 (59%)	0.53	51 (62.2%)	0.32	8 (44.4%)	0.42
Dronedarone	8 (4.2%)	2 (2%)	0.21	1 (1.2%)	0.19	1 (5.6%)	0.24
Sotalol	6 (3.1%)	3 (3%)	0.75	3 (3.7%)	0.74	0 (0%)	0.71
Dofetilide	5 (2.6%)	1 (1%)	0.34	1 (1.2%)	0.44	0 (0%)	0.60
Flecainide	24 (12.5%)	12 (12%)	0.95	8 (9.8%)	0.79	4 (22.2%)	0.47
Propafenone	2 (1.0%)	2 (2%)	0.09	2 (2.4%)	0.11	0 (0%)	0.59
Previous/failed antiarrhythmic therapy
Amiodarone	20 (10.4%)	10 (10%)	0.53	6 (7.3%)	0.32	4 (22.2%)	0.42
Dronedarone	21 (10.9%)	13 (13%)	0.21	9 (10.9%)	0.19	4 (22.2%)	0.24
Sotalol	20 (10.4%)	12 (12%)	0.75	10 (12.2%)	0.74	2 (11.1%)	0.71
Dofetilide	6 (3.1%)	3 (3%)	0.34	2 (2.4%)	0.44	1 (5.6%)	0.60
Flecainide	35 (18.2%)	19 (19%)	0.95	15 (18.3%)	0.79	4 (22.2%)	0.47
Propafenone	6 (3.1%)	1 (1%)	0.09	1 (1.2%)	0.11	0 (0%)	0.59

Table 2. Patient Home Medications and Antiarrhythmic Therapy

Drugs

All patients (n = 192)

Any inducible atrial flutter (n = 100)

P value

Typical right atrial flutter (n = 82)

P value

Atypical atrial flutter (n = 18)

P value

Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant. ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor blockers; SGLT2-I: sodium-glucose cotransporter-2 inhibitors; DOAC: direct oral anticoagulants; non-DHP CCB: non-dihydropyridine calcium channel blockers.

Home medications

Beta blocker

103 (53.6%)

63 (63%)

0.01*

52 (63.4%)

0.01*

11 (61.1%)

0.20

Non-DHP CCB

50 (26.0%)

21 (21%)

0.10

16 (19.5%)

0.07

5 (27.8%)

0.75

ACEI

49 (25.5%)

30 (30%)

0.19

27 (32.9%)

0.10

3 (16.7%)

0.76

ARBs

36 (18.8%)

15 (15%)

0.17

13 (15.9%)

0.25

2 (11.1%)

0.26

Sacubitril/valsartan

7 (3.6%)

3 (3%)

0.62

3 (3.7%)

1.0

0 (0%)

1.0

SGLT2-I

3 (1.6%)

0 (0%)

0.11

0 (0%)

0.25

0 (0%)

1.0

Spironolactone

19 (9.9%)

12 (12%)

0.31

12 (14.6%)

0.14

0 (0%)

0.60

Thiazide

19 (9.9%)

11 (11%)

0.58

10 (12.2%)

0.43

1 (5.6%)

1.0

Digoxin

2 (1.0%)

1 (1%)

1.0

1 (1.2%)

1.0

0 (0%)

1.0

Loop diuretic

39 (20.3%)

26 (26%)

0.07

23 (28%)

0.04*

3 (16.7%)

1.0

Statin

101 (52.6%)

56 (56%)

0.41

47 (57.3%)

0.33

9 (50%)

1.0

Aspirin

46 (24%)

22 (22%)

0.41

18 (21.9%)

0.43

4 (22.2%)

0.78

DOAC

162 (84.4%)

86 (86%)

0.66

72 (87.8%)

0.44

14 (77.8%)

0.54

Warfarin

13 (6.8%)

9 (9%)

0.26

5 (6.1%)

0.74

4 (22.2%)

0.02*

Current antiarrhythmic therapy

Amiodarone

105 (54.7%)

59 (59%)

0.53

51 (62.2%)

0.32

8 (44.4%)

0.42

Dronedarone

8 (4.2%)

2 (2%)

0.21

1 (1.2%)

0.19

1 (5.6%)

0.24

Sotalol

6 (3.1%)

3 (3%)

0.75

3 (3.7%)

0.74

0 (0%)

0.71

Dofetilide

5 (2.6%)

1 (1%)

0.34

1 (1.2%)

0.44

0 (0%)

0.60

Flecainide

24 (12.5%)

12 (12%)

0.95

8 (9.8%)

0.79

4 (22.2%)

0.47

Propafenone

2 (1.0%)

2 (2%)

0.09

2 (2.4%)

0.11

0 (0%)

0.59

Previous/failed antiarrhythmic therapy

Amiodarone

20 (10.4%)

10 (10%)

0.53

6 (7.3%)

0.32

4 (22.2%)

0.42

Dronedarone

21 (10.9%)

13 (13%)

0.21

9 (10.9%)

0.19

4 (22.2%)

0.24

Sotalol

20 (10.4%)

12 (12%)

0.75

10 (12.2%)

0.74

2 (11.1%)

0.71

Dofetilide

6 (3.1%)

3 (3%)

0.34

2 (2.4%)

0.44

1 (5.6%)

0.60

Flecainide

35 (18.2%)

19 (19%)

0.95

15 (18.3%)

0.79

4 (22.2%)

0.47

Propafenone

6 (3.1%)

1 (1%)

0.09

1 (1.2%)

0.11

0 (0%)

0.59

**Table 3.** Transesophageal Echocardiogram Prior to PVI
Characteristics	All patients (n = 192)
Data for ejection fraction are expressed as median (range). Data for categorical variables are expressed as mean ± standard deviation or proportion (percentages). PVI: pulmonary vein isolation.
Ejection fraction (%)	55 (25 - 75)
Left atrial dilation
Mild	43 (22.4%)
Moderate	19 (9.8%)
Severe	0 (0%)
Right atrial dilation
Mild	17 (8.9%)
Moderate	4 (2.1%)
Severe	0 (0%)
Mitral regurgitation
Mild	150 (78.1%)
Moderate	20 (10.4%)
Severe	0 (0%)
Tricuspid regurgitation
Mild	125 (65.1%)
Moderate	3 (1.6%)
Severe	1 (0.52%)

Table 3. Transesophageal Echocardiogram Prior to PVI

Characteristics

All patients (n = 192)

Data for ejection fraction are expressed as median (range). Data for categorical variables are expressed as mean ± standard deviation or proportion (percentages). PVI: pulmonary vein isolation.

Ejection fraction (%)

55 (25 - 75)

Left atrial dilation

Mild

43 (22.4%)

Moderate

19 (9.8%)

Severe

0 (0%)

Right atrial dilation

Mild

17 (8.9%)

Moderate

4 (2.1%)

Severe

0 (0%)

Mitral regurgitation

Mild

150 (78.1%)

Moderate

20 (10.4%)

Severe

0 (0%)

Tricuspid regurgitation

Mild

125 (65.1%)

Moderate

3 (1.6%)

Severe

1 (0.52%)

**Table 4.** Bivariate Analysis for Outcomes “Any, Typical, and Atypical Atrial Flutter”
Variable	Any inducible atrial flutter	P value	Typical right atrial flutter	P value	Atypical atrial flutter	P value
Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant. AF: atrial fibrillation; COPD: chronic obstructive pulmonary disease; OSA: obstructive sleep apnea.
Female	39 (56%)	0.45	26 (46%)	0.78	13 (30%)	0.002*
Persistent AF	60 (59%)	0.047*	50 (54%)	0.043*	10 (19%)	0.44
OSA	55 (60%)	0.04*	46 (55%)	0.04*	9 (20%)	0.44
COPD	6 (50%)	0.88	5 (46%)	0.91	1 (14%)	0.88
Asthma	5 (50%)	0.89	4 (44%)	0.87	1 (17%)	1.0
Hypertension	84 (55%)	0.12	69 (50%)	0.14	15 (18%)	0.45
Hyperlipidemia	71 (54%)	0.48	60 (50%)	0.33	11 (15%)	0.67
Diabetes mellitus	29 (58%)	0.33	24 (53%)	0.33	5 (19%)	0.65
Coronary artery disease	26 (45%)	0.19	21 (40%)	0.19	5 (14%)	0.57
Failed previous antiarrhythmic	46 (55%)	0.56	36 (49%)	0.78	10 (21%)	0.28

Table 4. Bivariate Analysis for Outcomes “Any, Typical, and Atypical Atrial Flutter”

Variable

Any inducible atrial flutter

P value

Typical right atrial flutter

P value

Atypical atrial flutter

P value

Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant. AF: atrial fibrillation; COPD: chronic obstructive pulmonary disease; OSA: obstructive sleep apnea.

Female

39 (56%)

0.45

26 (46%)

0.78

13 (30%)

0.002*

Persistent AF

60 (59%)

0.047*

50 (54%)

0.043*

10 (19%)

0.44

OSA

55 (60%)

0.04*

46 (55%)

0.04*

9 (20%)

0.44

COPD

6 (50%)

0.88

5 (46%)

0.91

1 (14%)

0.88

Asthma

5 (50%)

0.89

4 (44%)

0.87

1 (17%)

1.0

Hypertension

84 (55%)

0.12

69 (50%)

0.14

15 (18%)

0.45

Hyperlipidemia

71 (54%)

0.48

60 (50%)

0.33

11 (15%)

0.67

Diabetes mellitus

29 (58%)

0.33

24 (53%)

0.33

5 (19%)

0.65

Coronary artery disease

26 (45%)

0.19

21 (40%)

0.19

5 (14%)

0.57

Failed previous antiarrhythmic

46 (55%)

0.56

36 (49%)

0.78

10 (21%)

0.28

**Table 5.** Bivariate Analysis for Outcomes “Any, Typical, and Atypical Atrial Flutter”
Outcome	Variable	Outcome - yes	Outcome - no	P value
Data are expressed as median (interquartile range). *P < 0.05 indicates the difference between the two groups is statistically significant. BMI: body mass index; EF: ejection fraction; MR: mitral regurgitation; TR: tricuspid regurgitation.
Any inducible atrial flutter
	Age	66.0 (61.5 - 72.5)	65.0 (58.5 - 71.0)	0.28
	BMI	33.3 (29.6 - 38.1)	31.4 (28.2 - 34.5)	0.02*
	EF	55.0 (50.0 - 55.0)	55.0 (50.0 - 55.0)	0.97
	Left atrial size	0.0 (0.0 - 1.0)	0.0 (0.0 - 0.5)	0.03*
	Right atrial size	0.0 (0.0 - 0.0)	0.0 (0.0 - 0.0)	0.33
	TR severity	1.0 (0.0 - 1.0)	1.0 (0.0 - 1.0)	0.47
	MR severity	1.0 (1.0 - 1.0)	1.0 (1.0 - 1.0)	0.54
Typical right atrial flutter
	Age	66.0 (62.0 - 70.0)	65.0 (58.5 - 71.0)	0.48
	BMI	33.3 (29.8 - 38.1)	31.4 (28.2 - 34.5)	0.02*
	EF	55.0 (50.0 - 55.0)	55.0 (50.0 - 55.0)	0.54
	Left atrial size	0.0 (0.0 - 1.0)	0.0 (0.0 - 0.5)	0.02*
	Right atrial size	0.0 (0.0 - 0.0)	0.0 (0.0 - 0.0)	0.22
	TR severity	1.0 (0.0 - 1.0)	1.0 (0.0 - 1.0)	0.42
	MR severity	1.0 (1.0 - 1.0)	1.0 (1.0 - 1.0)	0.63
Atypical atrial flutter
	Age	70.0 (61.0 - 73.0)	65.0 (58.5 - 71.0)	0.14
	BMI	32.9 (28.0 - 36.6)	31.4 (28.2 - 34.5)	0.30
	EF	55.0 (50.0 - 55.0)	55.0 (50.0 - 55.0)	0.05
	Left atrial size	0.0 (0.0 - 1.0)	0.0 (0.0 - 0.5)	0.42
	Right atrial size	0.0 (0.0 - 0.0)	0.0 (0.0 - 0.0)	0.70
	TR severity	1.0 (0.0 - 1.0)	1.0 (0.0 - 1.0)	0.95
	MR severity	1.0 (1.0 - 1.0)	1.0 (1.0 - 1.0)	0.53

Table 5. Bivariate Analysis for Outcomes “Any, Typical, and Atypical Atrial Flutter”

Outcome

Variable

Outcome - yes

Outcome - no

P value

Data are expressed as median (interquartile range). *P < 0.05 indicates the difference between the two groups is statistically significant. BMI: body mass index; EF: ejection fraction; MR: mitral regurgitation; TR: tricuspid regurgitation.

Any inducible atrial flutter

Age

66.0 (61.5 - 72.5)

65.0 (58.5 - 71.0)

0.28

BMI

33.3 (29.6 - 38.1)

31.4 (28.2 - 34.5)

0.02*

55.0 (50.0 - 55.0)

0.97

Left atrial size

0.0 (0.0 - 1.0)

0.0 (0.0 - 0.5)

0.03*

Right atrial size

0.0 (0.0 - 0.0)

0.33

TR severity

1.0 (0.0 - 1.0)

0.47

MR severity

1.0 (1.0 - 1.0)

0.54

Typical right atrial flutter

Age

66.0 (62.0 - 70.0)

65.0 (58.5 - 71.0)

0.48

BMI

33.3 (29.8 - 38.1)

31.4 (28.2 - 34.5)

0.02*

55.0 (50.0 - 55.0)

0.54

Left atrial size

0.0 (0.0 - 1.0)

0.0 (0.0 - 0.5)

0.02*

Right atrial size

0.0 (0.0 - 0.0)

0.22

TR severity

1.0 (0.0 - 1.0)

0.42

MR severity

1.0 (1.0 - 1.0)

0.63

Atypical atrial flutter

Age

70.0 (61.0 - 73.0)

65.0 (58.5 - 71.0)

0.14

BMI

32.9 (28.0 - 36.6)

31.4 (28.2 - 34.5)

0.30

55.0 (50.0 - 55.0)

0.05

Left atrial size

0.0 (0.0 - 1.0)

0.0 (0.0 - 0.5)

0.42

Right atrial size

0.0 (0.0 - 0.0)

0.70

TR severity

1.0 (0.0 - 1.0)

0.95

MR severity

1.0 (1.0 - 1.0)

0.53

**Table 6.** Multivariate Analysis for Outcome of “Any Inducible Atrial Flutter”
Parameter	AOR (95% CI)	P value
Values are expressed as AOR (95% CI). *P < 0.05, statistically significant finding. AOR: adjusted odds ratio; CI: confidence interval; BMI: body mass index; MR: mitral regurgitation; OSA: obstructive sleep apnea; TR: tricuspid regurgitation.
Constant	0.75 (-)	0.59
Gender (female)	0.63 (0.33 - 1.21)	0.17
Type of atrial fibrillation (persistent)	1.62 (0.88 - 2.96)	0.12
BMI	1.22 (0.63 - 2.36)	0.55
OSA	1.92 (1.03 - 3.69)	0.049*
Failed at least one antiarrhythmic	0.97 (0.53 - 1.79)	0.92
Left atrial size	1.68 (0.96 - 2.95)	0.07
Right atrial size	1.14 (0.45 - 2.90)	0.78
TR severity	1.22 (0.66 - 2.26)	0.53
MR severity	0.68 (0.35 - 1.34)	0.26

Table 6. Multivariate Analysis for Outcome of “Any Inducible Atrial Flutter”

Parameter

AOR (95% CI)

P value

Values are expressed as AOR (95% CI). *P < 0.05, statistically significant finding. AOR: adjusted odds ratio; CI: confidence interval; BMI: body mass index; MR: mitral regurgitation; OSA: obstructive sleep apnea; TR: tricuspid regurgitation.

Constant

0.75 (-)

0.59

Gender (female)

0.63 (0.33 - 1.21)

0.17

Type of atrial fibrillation (persistent)

1.62 (0.88 - 2.96)

0.12

BMI

1.22 (0.63 - 2.36)

0.55

OSA

1.92 (1.03 - 3.69)

0.049*

Failed at least one antiarrhythmic

0.97 (0.53 - 1.79)

0.92

Left atrial size

1.68 (0.96 - 2.95)

0.07

Right atrial size

1.14 (0.45 - 2.90)

0.78

TR severity

1.22 (0.66 - 2.26)

0.53

MR severity

0.68 (0.35 - 1.34)

0.26

**Table 7.** Recurrence of Atrial Fibrillation and Atrial Flutter at 1 Year
Group	Atrial fibrillation	P value	Atrial flutter	P value	Either	P value
Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant.
Inducible (n = 100)	30 (30%)	0.7	14 (14%)	0.09	40 (40%)	0.46
Inducible + ablated (n = 89)	27 (30%)	0.8	12 (13%)	0.20	36 (40%)	0.43
Inducible + not ablated (n = 11)	3 (27%)	1	2 (18%)	0.32	4 (36%)	1

Table 7. Recurrence of Atrial Fibrillation and Atrial Flutter at 1 Year

Group

Atrial fibrillation

P value

Atrial flutter

P value

Either

P value

Data are expressed as mean ± standard deviation or proportion (percentages). *P < 0.05 indicates the difference between the two groups is statistically significant.

Inducible (n = 100)

30 (30%)

0.7

14 (14%)

0.09

40 (40%)

0.46

Inducible + ablated (n = 89)

27 (30%)

0.8

12 (13%)

0.20

36 (40%)

0.43

Inducible + not ablated (n = 11)

3 (27%)

2 (18%)

0.32

4 (36%)