Population characteristics
Between 2016 and 2019, 70 patients (79% male, 78.54 ± 10.87 years) with high risk to develop AF and no history of AF were included: 48 patients (85% male, 76.11 ± 10.68 years) were consecutive non-selected patients included after CTI ablation with complete bidirectional block (AFL group) independent of the PACE calculator risk score, and 22 patients (64% male, 80.59 ± 10.74 years) were included based on a high PACE calculator score (PACE group). Overall 60 patients (86%) underwent an ILR implantation during admission, while the remaining 10 patients (14%) had a previously implanted CDAL. There were either no complications related to the ablation procedure or to the ILR implantation. Patients with previous AFL had less comorbidities, including renal failure, hypertension, dyslipidemia, left ventricle hypertrophy, previous stroke, ischemic coronary disease and valvular disease (Table 1). As expected, the PACE calculator score was lower among patients with previous AFL (20.09 ± 19.3 with AFL vs. 47.05 ± 20.77 without AFL; p < 0.001), as the history of AFL was the only reason for them to be enrolled, whereas patients without AFL were selected for their higher PACE calculator score. For the same reason CHA2DS2-VASC score was higher in patients without AFL compared to those with AFL (4.5 ± 1.4 vs 2.7 ± 1.6, respectively; p < 0.001). No differences were observed in terms of ECG, echocardiography, Holter or polysomnography parameters between both groups.
Table 1
Comparison of characteristics in patients who had prior AFL ablation and patients who did not, but had high-risk score for AF
|
Total population (n = 70)
|
Without AFL
(n = 22)
|
With AFL
(n = 48)
|
p-value
|
Clinical variables
|
|
|
|
|
Age (years) mean (SD)
|
78.54 (10.87)
|
80.59 (10.74)
|
76.11 (10.87)
|
0.079
|
BMI (kg/m2) mean (SD)
|
30.10 (5.51)
|
29.92 (4.17)
|
30.18 (5.99)
|
0.885
|
Glom. F (ml/min) mean (SD)
|
65.10 (19.40)
|
55.82 (16.89)
|
69.54 (19.10)
|
0.019
|
Hemoglobin (mg/dL) mean (SD)
|
13.70 (1.95)
|
13.07 (2.11)
|
13.99 (1.82)
|
0.115
|
Hypertension
|
55 (78.5%)
|
21 (95.4%)
|
34 (70.8%)
|
0.026
|
Tobacco use
|
31 (44.3%)
|
7 (31.8%)
|
24 (50%)
|
0.303
|
Diabetes mellitus
|
23 (32.8%)
|
7 (31.8%)
|
16 (33.3%)
|
1.000
|
Dyslipidemia
|
39 (55.7%)
|
17 (77.3%)
|
22 (45.8%)
|
0.020
|
Ischemic disease
|
21 (30%)
|
11 (50%)
|
10 (20.8%)
|
0.023
|
Valvular disease
|
9 (12.8%)
|
7 (31.8%)
|
2 (4.2%)
|
0.003
|
Stroke
|
7 (10%)
|
6 (27.3%)
|
1 (2.1%)
|
0.003
|
CHA2DS2-VASC
|
3.2 (1.8)
|
4.5 (1.4)
|
2.7 (1.6)
|
< 0.001
|
PACE-Calc. mean (SD)
|
28.41 (23.28)
|
47.05 (20.77)
|
20.09 (19.30)
|
< 0.001
|
Polysomnography variables
|
|
|
|
|
Snorer
|
29 (41.4%)
|
8 (27.6%)
|
21 (72.4%)
|
0.610
|
Epworth. mean (SD)
|
8.68 (4.28)
|
8.09 (3.99)
|
8.92 (4.45)
|
0.642
|
IAH. mean (SD)
|
31.95 (19.48)
|
26.00 (16.63)
|
34.60 (20.34)
|
0.157
|
CT90%. mean (SD)
|
17.90 (27.93)
|
12.54 (24.55)
|
20.38 (29.48)
|
0.660
|
Echocardiography variables
|
|
|
|
|
LAD (mm) mean (SD)
|
42.14 (5.97)
|
41.36 (5.59)
|
42.59 (6.21)
|
0.481
|
LAS (cm2) mean (SD)
|
22.33 (4.28)
|
21.59 (4.88)
|
22.87 (3.78)
|
0.379
|
LA dilatation
|
45 (64.3%)
|
18 (81.8%)
|
27 (56.3%)
|
0.059
|
LVEF (%) mean (SD)
|
54.89 (12.52)
|
58.95 (13.13)
|
52.59 (11.71)
|
0.058
|
LVEF < 55%
|
26 (37.1%)
|
8 (36.4%)
|
18 (37.5%)
|
1.000
|
Electrophysiological variables
|
|
|
|
|
AH interval (msec) mean (SD)
|
-
|
-
|
115.59 (32.53)
|
-
|
HV interval (msec) mean (SD)
|
-
|
-
|
51.77 (8.40)
|
-
|
PR interval (msec) mean (SD)
|
194.63 (43.67)
|
205.10 (41.08)
|
190.27 (44.38)
|
0.239
|
QRS duration (msec) mean (SD)
|
113.91 (29.33)
|
117.35 (38.03)
|
112.48 (25.19)
|
0.898
|
SV ectopy > 0.2% at 24h-HM
|
23 (32.8%)
|
10 (45.4%)
|
13 (27%)
|
0.172
|
Atrial Tachycardia at 24h-HM
|
25 (35.7%)
|
9 (40.9%)
|
16 (33.3%)
|
0.597
|
SV ectopy > 0.2% or AT at 24h-HM
|
36 (51.4%)
|
13 (59.1%)
|
23(47.9%)
|
0.446
|
AT at ILR
|
16 (22.8%)
|
4 (18.2%)
|
12 (25%)
|
0.760
|
Bradycardia at ILR
|
15 (21.4%)
|
5 (22.7%)
|
10 (20.8%)
|
1.000
|
AF: atrial fibrillation; AFL: atrial typical flutter; AT: atrial tachycardia; BMI: body mass index; HM: 24h-holter monitoring; ILR: internal loop recorder; LA: left atrium; LAD: left atrium diameter; LAS: left atrium surface; LVEF: left ventricle ejection fraction; LVH: left ventricle hypertrophy; SV: supraventricular. |
Typical atrial flutter is the strongest predictor for new onset AF
When examining the entire cohort, the only two variables associated with new onset AF were the history of previously ablated typical AFL and the presence of SVE. Interestingly CHA2DS2-VASC score was not associated to new onset AF (3.3 ± 1.6 in patients without AF at follow-up vs 3.1 ± 2 in patients with AF at follow-up; p = 0.61). Among patients with AFL, 56.3% developed new onset AF, vs 22.7% of patients without AFL (p = 0.011). Concerning atrial ectopy, among patients with SVE 58.3% developed new onset AF, vs 32.4% of patients without SVE (p = 0.039). Survival analyses demonstrated AFL as the only predictor for new onset AF at median follow-up of 12 months (Q1-Q3: 4–19 months; HR: 3.82; 95% CI: 1.46–10.03; p = 0.006). Multivariate analyses, including PACE calculator score, LA enlargement, and hypertension confirmed AFL as the only predictor (see Table 2).
Table 2
Multivariate analysis of predictors for AF in the entire cohort
|
HR (95% IC
|
p-value
|
PACE calculator
|
1.02 [1.00;1.03]
|
0.076
|
Hypertension
|
1.17 [0.49;2.78]
|
0.728
|
LA dilatation
|
1.44 [0.65;3.21]
|
0.370
|
AFL
|
5.96 [2.01;17.73]
|
0.001
|
AF: atrial fibrillation; AFL: atrial typical flutter; LA: left atrium |
Figure 2 shows the survival curve for freedom from AF incidence in relation to the presence of AFL.
Predictors for new onset AF in patients with previous AFL
Focusing only on patients with previous AFL ablation, Table 3 shows the characteristics of patients with vs without new onset AF at follow-up. Interestingly SVE remains as the only variable associated with AF in this subgroup of patients (73.9% of patients with SVE vs 26.1% without SVE; p = 0.023).
Table 3
Characteristics of patients who underwent AFL ablation who developed new onset AF
|
Total AFL group (n = 48)
|
No AF (n = 21)
|
New onset AF (n = 27)
|
p-value
|
Clinical variables
|
|
|
|
|
BMI (kg/m2) mean (SD)
|
30.18 (5.99)
|
31.84 (5.94)
|
29.04 (5.91)
|
0.300
|
Glom. F (ml/min) mean (SD)
|
69.54 (19.10)
|
70.30 (16.34)
|
68.96 (21.29)
|
0.790
|
Hemoglobin (mg/dL) mean (SD)
|
13.99 (1.82)
|
14.21 (1.94)
|
13.82 (1.74)
|
0.379
|
Hypertension
|
34 (70.8%)
|
14 (66.7%)
|
20 (74.1%)
|
0.750
|
Tobacco use
|
24 (50%)
|
10 (47.6%)
|
14 (51.8%)
|
0.482
|
Diabetes mellitus
|
16 (33.3%)
|
6 (28.6%)
|
10 (37%)
|
0.758
|
Dyslipidemia
|
22 (45.8%)
|
12 (57.1%)
|
10 (37%)
|
0.244
|
Ischemic disease
|
10 (20.8%)
|
3 (14.3%)
|
7 (25.9%)
|
0.478
|
Valvular disease
|
2 (4.2%)
|
1 (4.7%)
|
1 (3.7%)
|
1
|
Stroke
|
1 (2.1%)
|
0 (0%)
|
1 (3.7%)
|
1
|
CHA2DS2-VASC
|
2.7 (1.6)
|
2.7 (1.5)
|
2.7 (1.7)
|
1
|
PACE Calc (% at 3 y) mean (SD)
|
20.09 (19.30)
|
14.73 (14.28)
|
24.41 (21.88)
|
0.104
|
Polysomnography variables
|
|
|
|
|
Snorer
|
21 (43.7%)
|
9 (42.9%)
|
12 (44.4%)
|
1
|
Epworth mean (SD)
|
8.92 (4.45)
|
7.58 (4.12)
|
10.07 (4.55)
|
0.165
|
IAH mean (SD)
|
34.60 (20.34)
|
32.83 (14.89)
|
36.01 (24.28)
|
0.961
|
CT90% mean (SD)
|
20.38 (29.48)
|
33.88 (37.70)
|
8.80 (12.50)
|
0.060
|
Echocardiography variables
|
|
|
|
|
LAD (mm) mean (SD)
|
42.59 (6.21)
|
42.40 (5.96)
|
42.73 (6.50)
|
0.817
|
LAS (cm2) mean (SD)
|
22.87 (3.78)
|
23.17 (4.43)
|
22.67 (3.40)
|
0.933
|
LA dilatation
|
27 (56.2%)
|
10 (47.6%)
|
17 (63%)
|
0.382
|
LVEF (%) mean (SD)
|
52.59 (11.71)
|
52.63 (14.23)
|
52.57 (9.94)
|
0.875
|
LVEF < 55%
|
18 (37.5%)
|
8 (38.1%)
|
10 (37%)
|
1
|
LVH
|
15 (31.2%)
|
7 (33.3%)
|
8 (29.6%)
|
1
|
Electrical variables
|
|
|
|
|
AH interval (msec) mean (SD)
|
115.59 (32.53)
|
112.00 (21.84)
|
117.55 (37.98)
|
1
|
HV interval (msec) mean (SD)
|
51.77 (8.40)
|
48.00 (5.25)
|
54.13 (9.25)
|
0.092
|
PR interval (msec) mean (SD)
|
180.27 (44.38)
|
177.48 (57.02)
|
184.67 (31.39)
|
0.589
|
QRS duration (msec) mean (SD)
|
112.48 (25.19)
|
112.14 (24.93)
|
112.74 (25.86)
|
0.975
|
SV ectopy > 02% at 24h-HM
|
13 (27.1%)
|
5 (23.8%)
|
8 (29.6%)
|
0.750
|
Atrial tachycardia at 24h-HM
|
16 (33.3%)
|
4 (19%)
|
12 (44.4%)
|
0.075
|
SV ectopy > 0,2% or AT at 24h-HM
|
23 (47.9%)
|
6 (28.6%)
|
17 (63%)
|
0.023
|
AF: atrial fibrillation; AFL: atrial typical flutter; AT: atrial tachycardia; BMI: body mass index; HM: 24h-holter monitoring; LA: left atrium; LAD: left atrium diameter; LAS: left atrium surface; LVEF: left ventricle ejection fraction; LVH: left ventricle hypertrophy; SV: supraventricular. |
Univariate analyses demonstrated a clear trend, although not significant, for SVE (HR 2.14, 95% CI: 0.98–4.68; p = 0.057). Among continuous variables the HV interval was the only predictor for new onset AF, with a HR 1.08 (95% CI: 1.01–1.16; p = 0.026). The PACE calculator revealed a trend towards predicting AF, (HR 1.02, 95% CI: 1-1.03; p = 0.1).
Given the fact that SVE is included in the PACE calculator and that SVE and HV interval showed a limited discrimination potential as continuous variables, we carried out a new analysis using the PACE calculator and HV interval as categorical variables (Table 4). Multivariate analyses showed that a PACE calculator score of ≥30% predicted the occurrence of new onset AF at a median follow-up of 12 months (Q1-Q3: 4–19 months), with a HR of 6.9 (95% CI: 1.71–27.91; p = 0.007) and HV interval of ≥55msec predicted the occurrence of new onset AF with a HR of 11.86 (95% CI: 2.57–54.8; p = 0.002). Interestingly LA dilatation did not predict AF incidence in our population. Figure 3shows survival curves for freedom from AF incidence related to the PACE calculator score and HV interval, respectively, in patients with previously ablated AFL.
Table 4
Multivariate analysis of predictors for AF in patients who had AFL ablation
|
HR (95% IC
|
p-value
|
PACE calculator ≥ 30
|
6,9 [1,71;27,91]
|
0.007
|
HV interval > 55
|
11,86 [2,57;54,83]
|
0.002
|
Hypertension
|
2,27 [0,67;7,73]
|
0.191
|
LVH
|
0,66 [0,24;1,82]
|
0.421
|
LA dilatation
|
0,47 [0,14;1,58]
|
0.220
|
Ischemic disease
|
0,43 [0,1;1,89]
|
0.262
|
Glom. F. (ml/min)
|
1,01 [0,99;1,04]
|
0.345
|
QRS duration (msec)
|
0,99 [0,97;1,02]
|
0.535
|
Hemoglobin (mg/dL)
|
0,88 [0,67;1,16]
|
0.371
|
AF: atrial fibrillation; AFL: atrial typical flutter; LA: left atrium; LVH: left ventricle hypertrophy |
Predicting high-risk patients
We analyzed the added value of considering the PACE calculator score and/or HV interval in order to better stratify the risk for new onset AF in patients undergoing an AFL ablation procedure. Concerning the PACE calculator, a score of ≥30% predicted the incidence of new onset AF during follow-up with a specificity of 90.5%, a sensitivity of 38.5%, a positive predictive value (PPV) of 83.3% and a negative predictive value (NPV) of 54.3%. Regarding the HV interval, a value of ≥55 msec predicted the incidence of new onset AF during the follow-up with a specificity of 88.9%, a sensitivity of 62.5%, a positive predictive value (PPV) of 88.2% and a negative predictive value (NPV) of 64%. Therefore if the PACE score was ≥ 30 or the HV was ≥ 55msec, the probability of developing AF at a median of 12 months follow-up was greater than 83% and 88%, respectively. Figure 4 shows area under ROC curve to predict new onset AF in patients with AF with PACE calculator score ≥ 30 or with HV interval ≥ 55msec, respectively. Finally when combining both variables, the NPV of having a PACE calculator score of < 30 and an HV interval of < 55msec was 75% (95% CI: 50.9%-91.3%).