Study population
Nineteen (26%) of the 72 pAF patients experienced AF recurrence, whereas 53 (74%) patients did not experience postoperative recurrence. Characteristics of patients were stratified by recurrence and nonrecurrence of AF. Age, sex, AF duration, CHADS-VASC score, concomitant diseases, biochemical index, and echocardiographic parameters (LAD, LVEF, and LAVI) were not significantly different between the AF recurrence and AF nonrecurrence groups. However, the early recurrence rates were significantly higher in the AF recurrence group than in the AF nonrecurrence group (P = 0.001). The results were consistent after bootstrapping (1000 times; Table 1).
Table 1
Comparison of clinical and basic information of paroxysmal atrial fibrillation patients of the two groups
| All patients | Nonrecurrence | Recurrence | P-value |
| (N = 72) | (N = 53) | (N = 19) | after boostrapping |
Clinical characteristics | | | | |
Age (yrs) | 61.5 ± 8.8 | 61.6 ± 8.9 | 61.2 ± 8.8 | 0.84 |
Female [n (%)] | 21 (29%) | 16 (30%) | 5 (26%) | 1.00 |
AF period (months) | 61.5 ± 67.5 | 60.3 ± 62.6 | 64.9 ± 81.2 | 0.95 |
CHA2DS2-VASc score | 2.00 ± 1.50 | 1.98 ± 1.52 | 1.76 ± 1.25 | 0.31 |
Hypertension [n (%)] | 32 (48%) | 27 (51%) | 5 (26%) | 0.11 |
Diabetes mellites [n (%)] | 10 (14%) | 8 (15%) | 2 (11%) | 1.00 |
Peripheral arterial disease [n (%)] | 14 (20%) | 11 (21%) | 3 (16%) | 0.75 |
Fasting blood glucose (mmol/L) | 5.41 ± 1.48 | 5.40 ± 0.96 | 5.44 ± 2.45 | 0.92 |
Total cholesterol (mmol/L) | 3.74 ± 1.01 | 3.66 ± 1.02 | 3.97 ± 1.00 | 0.26 |
LDL-cholesterol (mmol/L) | 2.15 ± 1.02 | 2.23 ± 1.04 | 2.07 ± 0.98 | 0.92 |
HDL-cholesterol (mmol/L) | 2.42 ± 1.73 | 2.33 ± 1.72 | 2.40 ± 1.68 | 0.67 |
Triglycerides (mmol/L) | 1.62 ± 0.83 | 1.56 ± 0.68 | 1.84 ± 1.19 | 0.64 |
Uric acid (umol/L) | 296.22 ± 83.71 | 302.25 ± 85.69 | 279.11 ± 77.53 | 0.32 |
Creatinine (umol/L) | 67.71 ± 13.15 | 67.22 ± 12.87 | 65.28 ± 14.18 | 0.59 |
ERAF [n (%)] | 16 (22%) | 6 (11%) | 10 (53%) | 0.001 |
Echocardiographic parameters | | | | |
Left atrial diameter (mm) | 39.65 ± 5.06 | 40.15 ± 4.90 | 38.48 ± 5.70 | 0.24 |
Left atrial volume index (mL/m2) | 33.42 ± 10.18 | 34.19 ± 10.49 | 31.04 ± 9.04 | 0.56 |
Left ventricular ejection fraction (%) | 62.70 ± 4.37 | 63.23 ± 4.59 | 61.65 ± 3.62 | 0.15 |
The values shown are mean ± SD or percentages.
Abbreviation: LDL, low-density lipoprotein; HDL, high-density lipoprotein.
Early recurrence refers the episode of symptomatic or asymptomatic documented atrial tachyarrhythmia > 30 seconds in the blanking period.
Laboratory test
The results revealed that no obvious differences existed between the two groups for the preoperative hs-CRP (hs-CRPpre) and HMGB1pre levels. The levels of hs-CRP and HMGB1 in the left atrium were significantly elevated after ablation. Moreover, the HMGB1post levels were obviously higher in the AF recurrence group than in the AF nonrecurrence group (298.51 µg/L vs. 278.17 µg/L; P = 0.03). However, the postoperative hs-CRP (hs-CRPpost) levels did differ between the two groups (Table 2).
Further, because two types of ablation procedures (RFA and CBA) were performed, we compared the association of HMGB1 between the two groups (RFA group and CBA group). The results revealed that in the RFA group, the HMGB1pre and HMGB1post levels did not differ between the AF recurrence and AF nonrecurrence groups (213.90 µg/L vs. 218.21 µg/L, P = 0.83 and 284.26 µg/L vs.260.28 µg/L, P = 0.15, respectively). Similarly, in the CBA group, no significant differences in the HMGB1pre and HMGB1post levels were noted (281.82 µg/L vs. 242.87 µg/L, P = 0.43 and 295.22 µg/L vs. 271.23 µg/L; P = 0.52, respectively) between the AF recurrence and AF nonrecurrence groups (Table 2).
Table 2
Comparison of high-sensitivity C-reactive protein and high-mobility group box-1 from the left atrial serum between the two groups
| All subjects | Nonrecurrence | Recurrence | P-value |
| (N = 72) | (N = 53) | (N = 19) | |
Pre-operation | | | | |
hs-CRPpre (mg/L) | 4.47 (3.79–5.15) | 4.36 (3.74–5.08) | 4.80 (3.74–8.03) | 0.71 |
HMGB1pre (ug/L) | 221.73 (191.18–250.50) | 221.15 (193.35-246.98) | 239.15 (189.63–360.70) | 0.37 |
Post-operation | | | | |
hs-CRPpost (mg/L) | 41.96 (36.48–50.13) * | 43.17 (36.10-50.24) * | 40.39 (36.97–69.60) * | 0.63 |
HMGB1post (ug/L) | 268.78 (244.24-298.79) * | 260.28 (239.14-295.39) * | 289.73 (270.29-365.42) * | 0.03 |
RFA | | | | |
HMGB1pre (ug/L) | 217.04(190.32-243.36) | 218.21(192.47-245.12) | 213.90(186.21-240.91) | 0.83 |
HMGB1post (ug/L) | 264.06(244.43-295.02) | 260.28(241.41-295.39) | 284.26(258.49-310.87) | 0.15 |
CBA | | | | |
HMGB1pre (ug/L) | 245.42(237.20-375.77) | 242.87(232.50-346.02) | 281.82(240.13-360.69) | 0.43 |
HMGB1post (ug/L) | 293.86(259.85-357.11) | 271.23(228.57-527.95) | 295.22(275.39-357.12) | 0.52 |
The values shown are percentiles.
Abbreviation: hs-CRP, high sensitivity c-reactive protein; HMGB1, high mobility group 1 protein; RAF, radiofrequency ablation; CBA, cryoballoon ablation.
* P < 0.05 vs. pre-operation
Univariate logistic regression analysis revealed that serum HMGB1post released from the left atrium was an independent predictor of AF recurrence (odds ratio [OR]: 3.90 [1.16–13.08], P = 0.03). After adjusting for common clinical risk factors for AF recurrence, such as age, female sex, AF period, CHADS2-VASc score, hypertension, diabetes mellitus, peripheral arterial diseases, left atrial diameter, LAVI, and LVEF, multiple logistic regression analysis confirmed that a high left atrial serum HMGB1post level was a significant prognostic predictor of AF recurrence(OR: 3.62 [1.02–12.77], P = 0.04; Table 3). ROC analysis revealed that serum HMGB1post released from the left atrium (AUC: 0.68; sensitivity: 72%; specificity: 68%) had a moderate predictive power for AF recurrence and the cutoff value of serum HMGB1post was calculated to be 279.35 µg/L (Fig. 1). Kaplan–Meier survival curves for AF recurrence using the HMGB1post values revealed that the 1-year AF-free survival was significantly lower in patients with a high serum HMGB1post level (HMGB1post: ≥279.35 µg/L) than in those with a low HMGB1post level (HMGB1post: <279.35 µg/L) (HR: 3.81 [1.49–9.75], P = 0.005; Fig. 2).
Table 3
Prediction of paroxysmal atrial fibrillation recurrence
| Univariate | | Multivariate | |
| OR [95%CI] | P-value | OR [95%CI] | P-value |
Age (yrs) | 1.00 [0.94–1.06] | 0.87 | 0.96 [0.88–1.06] | 0.45 |
Female (%) | 0.83 [0.25–2.68] | 0.75 | 1.18 [0.26–5.46] | 0.83 |
AF period (months) | 1.00 [0.99–1.01] | 0.80 | 1.00 [0.99–1.01] | 0.64 |
CHA2DS2-VASc score | 0.86 [0.60–1.23] | 0.41 | 0.91 [0.44–1.87] | 0.79 |
Hypertension (%) | 0.34 [0.11–1.09] | 0.07 | 0.71 [0.17–2.99] | 0.64 |
Diabetes mellitus (%) | 0.66 [0.13–3.44] | 0.62 | 1.65 [0.19–14.43] | 0.65 |
Peripheral arterial diseases (%) | 0.72 [0.18–2.90] | 0.64 | 1.64 [0.19–14.84] | 0.66 |
Left atrial diameter (mm) | 0.93 [0.84–1.04] | 0.23 | 0.90 [0.76–1.07] | 0.22 |
Left atrial volume index (mL/m2) | 0.98 [0.93–1.04] | 0.48 | 1.02 [0.93–1.11] | 0.69 |
Left ventricular ejection fraction (%) | 0.91 [0.80–1.04] | 0.15 | 0.88 [0.74–1.09] | 0.27 |
HMGB1post (ug/L) | 3.90 [1.16–13.08] | 0.03 | 5.29 [1.17–23.92] | 0.04 |
Abbreviation: HMGB1, high mobility group 1 protein.