Letters to the Editor
431
Sympathetic stimulation affects atrial vulnerability in paroxysmal supraventricular tachycardia patients with atrial fibrillation Zhen-xing Xu, Jing-quan Zhong ⁎, Wei Zhang, Xin Yue, Bing Rong, Qing Zhu, Zhaotong Zheng, Yun Zhang Key Laboratory of cardiovascular remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, PR China Department of Cardiology, Qilu Hospital of Shandong University, PR China
a r t i c l e
i n f o
Article history: Received 13 March 2014 Accepted 2 April 2014 Available online 16 April 2014 Keywords: Atrial fibrillation (AF) Ablation Atrial vulnerability Paroxysmal supraventricular tachycardia Sympathetic stimulation
Atrial fibrillation (AF) occurs more frequently in paroxysmal supraventricular tachycardia (PSVT) patients compared with the general population. Even after successful treatment of the arrhythmia, the AF recurrence rate for the PSVT patients is still high (6–10% for atrioventricular reentrant tachycardia, AVRT and 28% for atrioventricular nodal reentrant tachycardia, AVNRT patients) [1,2]. Consequently, the accessory pathways (AP) and the slow pathway of the atrioventricular node may not be the only factors that influence atrial vulnerability, which was defined as the occurrence of spontaneous and inducible AF and maintenance and perpetuation of the arrhythmia in atrial tissues according to the electrophysiological mechanisms underlying AF [3,4], in PSVT patients. Programmed atrial stimulation with and without isoprenaline infusion, which can induce AF on occasion, is widely used to evaluate the effectiveness of the radiofrequency catheter ablation (RFCA) in PSVT patients [5]. In the present study, it was speculated that patients with inducible AF under isoprenaline infusion would be sensitive to sympathetic nerve stimulation (defined as the heart rate at 30% above the basic rate after isoprenaline was titrated), so as to determine whether the AF that occurred in PSVT patients was associated with sympathetic stimulation. In this study, 768 PSVT patients were included (15 were excluded) who were diagnosed as WPW syndrome, AVNRT or AVRT and treated with RFCA. All antiarrhythmic medications that had an effect on cardiac electrophysiological properties were withdrawn for N5 half-lives prior to operation. Exclusion criteria included diabetes mellitus, BMI ≥25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine), hypertension, valvular heart disease and atrial tachycardia. Atrial conduction delay and dispersion of atrial refractoriness (dERP), the primary indexes of atrial vulnerability, were measured before and after the ablation respectively as described previously [6,7]. Briefly, interatrial conduction delay was the interval from beginning of the late diastolic wave of the lateral mitral annulus to the beginning of the late diastolic wave of the tricuspid annulus, intra-atrial conduction delay was the interval from the beginning of the late diastolic wave of the septal mitral annulus to the beginning of the late diastolic wave of the tricuspid annulus. The dERP was defined as the longest atrial effective refractory period (AERP) minus the shortest AERP that was determined at each of the four atrial recording sites, HRA, LRA, distal and proximal CS (respectively CS1-2 and CS9-10 bipoles). ⁎ Corresponding author at: Department of Cardiology, Qilu Hospital of Shandong University, Wen Hua Xi Lu, Jinan 250012, Shandong Province, PR China. Tel.: + 86 531 8216 9339; fax: + 86 531 8692 7544. E-mail address: [email protected] (J. Zhong).
Programmed atrial stimulation (including the burst stimulation) with and without isoprenaline infusion was performed on each patient during the evaluation procedure of the ablation. Patients were divided into 3 groups according to the occurrence of AF in these procedures. Group A (n = 41): AF was induced under the isoprenaline infusion but not induced using the programmed atrial stimulation alone. Group B (n = 73): AF was induced by the programmed atrial stimulation without isoprenaline infusion. Group C (n = 639): AF was not induced. All patients were evaluated at 1, 3, 6, 12, 18 months, or when they presented with palpitations or other cardiovascular symptoms. Study end point was determined as any type of AF with ECG or 24 h Holter evidence. Statistical analysis was performed using SPSS 13.0 software. P b 0.05 was considered statistically significant. The baseline characteristics of these patients were shown in Table 1. The age of group A was significantly lower than groups B and C (41.51 ± 14.68 vs 61.11 ± 10.24 and 41.51 ± 14.68 vs 53.96 ±11.39, P b 0.05 respectively). The dERP in group A was lower than in group B but higher than in group C (43.90 ± 7.26 vs. 72.10 ± 7.40 msec, P b 0.001 and 43.90 ± 7.26 vs. 33.26 ± 6.50 msec, P =0.002). The intra- and interatrial conductions delay in group A were shorter than in group B (4.60 ± 0.45 vs. 5.10 ± 0.47 msec and 20.89 ± 1.77 vs. 25.02 ± 1.85 msec, P b 0.001 respectively). The prevalence of AF was higher in group A than in group B after 18 months follow-up (26.83%, 11/41 vs. 10.96%, 8/73, P b 0.05, Fig. 1). Logistic regression analysis showed age, right and left atrial dimension and sympathetic stimulation (Table 2) were the significant influencing factors for AF. The main finding of this study is that heart sympathetic stimulation was important for the origin of the residual atrial vulnerability in addition to AP and the slow pathway of atrioventricular node in PSVT patients. Stimulation of the heart sympathetic nerve can increase calcium entry and the spontaneous release of calcium from the sarcoplasmic reticulum [8]. All of these factors may promote the occurrence of AF. The atrial vulnerability in group A was lower than in group B, these results are in accordance with the fact that AF could only be induced under programmed atrial stimulation with isoprenaline infusion in group A while it did without isoprenaline in group B.
Table 1 Baseline characteristics of the patients. Group A
Group B
Group C
N
41
73
639
Age SBP (mmHg) DBP (mmHg) TC (mmol/L) TG (mmol/L) HDL-C (mmol/L) LDL-C (mmol/L) GLU (mmol/L) LA (mm) RA (mm)
41.51 ± 14.68⁎,# 118.71 ± 24.14 78.56 ± 9.05 4.01 ± 0.56 1.14 ± 0.46 1.14 ± 0.25 2.81 ± 0.38 4.73 ± 0.49 38.17 ± 8.14 40.34 ± 7.06
61.11 ± 10.24⁎ 117.96 ± 23.54 79.69 ± 8.52 3.98 ± 0.57 1.08 ± 0.39 1.22 ± 0.35 2.73 ± 0.29 4.63 ± 0.37 39.42 ± 5.72 39.86 ± 7.70
53.96 ± 11.39 117.33 ± 23.40 80.21 ± 9.36 4.05 ± 0.58 1.10 ± 0.42 1.19 ± 0.31 2.75 ± 0.31 4.66 ± 0.42 38.48 ± 5.77 39.57 ± 5.34
SBP = systolic blood pressure; DBP = diastolic blood pressure; TC = total cholesterol; TG = triglyceride; LDL-C = low density lipoprotein; HDL-C = high density lipoprotein; GLU = fasting blood-glucose; LA = left atrium dimension; and RA = right atrium dimension. # Compared with group B, P b 0.05. ⁎ Compared with group C, P b 0.05.
432
Letters to the Editor Table 2 Logistic regression analysis of the factors associated with AF.
Age TG LDL-C GLU Gender# LA RA sympathetic stimulation#
Odds ratio
95% CI
P value⁎
1.168 0.526 0.857 0.937 0.952 1.209 1.177 57.977
1.116–1.223 0.234–1.183 0.318–2.313 0.464–1.893 0.483–1.877 1.141–1.281 1.004–1.256 14.761–227.721
0.000 0.120 0.761 0.937 0.888 0.000 0.000 0.000
# Categorical variable; dERP = dispersion of atrial refractoriness; intra = Intra-atrial conduction delay; inter = Interatrial conduction delay; TG = triglyceride; LDLC = low density lipoprotein; GLU = fasting blood-glucose; LA = left atrium dimension; and RA = right atrium dimension. ⁎ P value b 0.05 was considered statistically significant. Fig. 1. Broken line graph for the relationship between the time and the morbidity for the AF.*P b 0.05 vs. group B.
It has been shown that the prevalence of AF increases with age, from b0.5% at 40–50 years to 5–15% at 80 years of age [9]. The mechanism by which age influences the induction of AF is currently unknown. Brembilla-Perrot et al reported that the AERP increased with age after 70 years old, but the increase of AERP was a protective factor against AF [10]. Animal study demonstrated that the increased density of muscarinic type 2 receptor in left atrial free wall enhanced age-related AF vulnerability [11]. The current study found that the ages of the patients in group A were lower than patients in B and C. This finding indicates that the heart sympathetic nerves stimulation could also be used to explain the difference. In conclusion, the age and sympathetic stimulation are important factors of atrial vulnerability and initiation of AF. Further studies will be required to evaluate the potential of targeted anti-adrenergic therapy, such as beta-blockers, for the prevention and treatment of AF in PSVT patients. The detection of AF in all patients by 24 h but not 7 days Holter monitoring and measurement protocol of AERP only at four atrium sites were the primary limitation of the study. This study was sponsored by the Natural Science Foundation of China (81270238) and the Scientific Research Foundation for Doctoral Degree, State Education Ministry of China (20130131110065). http://dx.doi.org/10.1016/j.ijcard.2014.04.030 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
References [1] Centurión OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial fibrillation in the Wolff–Parkinson–White syndrome: intrinsic atrial muscle vulnerability vs. electrophysiological properties of the accessory pathway. Europace 10:294-302. [2] Amasyali B, Kose S, Aytemir K, Kilic A et al. Atrioventricular nodal reentrant tachycardia with paroxysmal atrial fibrillation: clinical and electrophysiological features and predictors of atrial fibrillation recurrence following elimination of atrioventricular nodal reentrant tachycardia. J Interv Card Electrophysiol. 13:195-201. [3] Providência R, Barra S, Paiva L. Atrial fibrillation, elevated troponin, ischemic stroke and adverse outcomes: understanding the connection. Clin Res Cardiol 102:701–711. [4] Gitt AK, Smolka W, Michailov G, Bernhardt A, Pittrow D, Lewalter T. Types and outcomes of cardioversion in patients admitted to hospital for atrial fibrillation: results of the German RHYTHM-AF Study. Clin Res Cardiol 102:713-723. [5] Lampe B, Hammerstingl C, Schwab JO, et al. Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block. Clin Res Cardiol 101:829-836. [6] Yagmur J, Cansel M, Acikgoz N, Ermis N, et al. Assessment of atrial electromechanical delay by tissue Doppler echocardiography in obese subjects. Obesity 19:779-783. [7] Oliveira M, da Silva MN, Timoteo AT, Feliciano J, et al. Inducibility of atrial fibrillation during electrophysiologic evaluation is associated with increased dispersion of atrial refractoriness. Int J Cardiol 136:130-135. [8] Ter Keurs HE, Boyden PA. Calcium and arrhythmogenesis. Physiol Rev 87:457-506. [9] Sharma AD, Klein GJ, Guiraudon GM, Milstein S Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: incidence after surgical ablation of the accessory pathway. Circulation. 72:161-169. [10] Brembilla-Perrot B, Burger G, Beurrier D, et al. Influence of age on atrial fibrillation inducibility. Pacing Clin Electrophysiol 27:287-292. [11] Yang YH, Zheng QS, Li J, et al. Age-related changes in the atrial muscarinic type 2 receptor and their effects on atrial fibrillation vulnerability in rabbits. Experimental Gerontology 44:572–578.
431
Sympathetic stimulation affects atrial vulnerability in paroxysmal supraventricular tachycardia patients with atrial fibrillation Zhen-xing Xu, Jing-quan Zhong ⁎, Wei Zhang, Xin Yue, Bing Rong, Qing Zhu, Zhaotong Zheng, Yun Zhang Key Laboratory of cardiovascular remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, PR China Department of Cardiology, Qilu Hospital of Shandong University, PR China
a r t i c l e
i n f o
Article history: Received 13 March 2014 Accepted 2 April 2014 Available online 16 April 2014 Keywords: Atrial fibrillation (AF) Ablation Atrial vulnerability Paroxysmal supraventricular tachycardia Sympathetic stimulation
Atrial fibrillation (AF) occurs more frequently in paroxysmal supraventricular tachycardia (PSVT) patients compared with the general population. Even after successful treatment of the arrhythmia, the AF recurrence rate for the PSVT patients is still high (6–10% for atrioventricular reentrant tachycardia, AVRT and 28% for atrioventricular nodal reentrant tachycardia, AVNRT patients) [1,2]. Consequently, the accessory pathways (AP) and the slow pathway of the atrioventricular node may not be the only factors that influence atrial vulnerability, which was defined as the occurrence of spontaneous and inducible AF and maintenance and perpetuation of the arrhythmia in atrial tissues according to the electrophysiological mechanisms underlying AF [3,4], in PSVT patients. Programmed atrial stimulation with and without isoprenaline infusion, which can induce AF on occasion, is widely used to evaluate the effectiveness of the radiofrequency catheter ablation (RFCA) in PSVT patients [5]. In the present study, it was speculated that patients with inducible AF under isoprenaline infusion would be sensitive to sympathetic nerve stimulation (defined as the heart rate at 30% above the basic rate after isoprenaline was titrated), so as to determine whether the AF that occurred in PSVT patients was associated with sympathetic stimulation. In this study, 768 PSVT patients were included (15 were excluded) who were diagnosed as WPW syndrome, AVNRT or AVRT and treated with RFCA. All antiarrhythmic medications that had an effect on cardiac electrophysiological properties were withdrawn for N5 half-lives prior to operation. Exclusion criteria included diabetes mellitus, BMI ≥25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine), hypertension, valvular heart disease and atrial tachycardia. Atrial conduction delay and dispersion of atrial refractoriness (dERP), the primary indexes of atrial vulnerability, were measured before and after the ablation respectively as described previously [6,7]. Briefly, interatrial conduction delay was the interval from beginning of the late diastolic wave of the lateral mitral annulus to the beginning of the late diastolic wave of the tricuspid annulus, intra-atrial conduction delay was the interval from the beginning of the late diastolic wave of the septal mitral annulus to the beginning of the late diastolic wave of the tricuspid annulus. The dERP was defined as the longest atrial effective refractory period (AERP) minus the shortest AERP that was determined at each of the four atrial recording sites, HRA, LRA, distal and proximal CS (respectively CS1-2 and CS9-10 bipoles). ⁎ Corresponding author at: Department of Cardiology, Qilu Hospital of Shandong University, Wen Hua Xi Lu, Jinan 250012, Shandong Province, PR China. Tel.: + 86 531 8216 9339; fax: + 86 531 8692 7544. E-mail address: [email protected] (J. Zhong).
Programmed atrial stimulation (including the burst stimulation) with and without isoprenaline infusion was performed on each patient during the evaluation procedure of the ablation. Patients were divided into 3 groups according to the occurrence of AF in these procedures. Group A (n = 41): AF was induced under the isoprenaline infusion but not induced using the programmed atrial stimulation alone. Group B (n = 73): AF was induced by the programmed atrial stimulation without isoprenaline infusion. Group C (n = 639): AF was not induced. All patients were evaluated at 1, 3, 6, 12, 18 months, or when they presented with palpitations or other cardiovascular symptoms. Study end point was determined as any type of AF with ECG or 24 h Holter evidence. Statistical analysis was performed using SPSS 13.0 software. P b 0.05 was considered statistically significant. The baseline characteristics of these patients were shown in Table 1. The age of group A was significantly lower than groups B and C (41.51 ± 14.68 vs 61.11 ± 10.24 and 41.51 ± 14.68 vs 53.96 ±11.39, P b 0.05 respectively). The dERP in group A was lower than in group B but higher than in group C (43.90 ± 7.26 vs. 72.10 ± 7.40 msec, P b 0.001 and 43.90 ± 7.26 vs. 33.26 ± 6.50 msec, P =0.002). The intra- and interatrial conductions delay in group A were shorter than in group B (4.60 ± 0.45 vs. 5.10 ± 0.47 msec and 20.89 ± 1.77 vs. 25.02 ± 1.85 msec, P b 0.001 respectively). The prevalence of AF was higher in group A than in group B after 18 months follow-up (26.83%, 11/41 vs. 10.96%, 8/73, P b 0.05, Fig. 1). Logistic regression analysis showed age, right and left atrial dimension and sympathetic stimulation (Table 2) were the significant influencing factors for AF. The main finding of this study is that heart sympathetic stimulation was important for the origin of the residual atrial vulnerability in addition to AP and the slow pathway of atrioventricular node in PSVT patients. Stimulation of the heart sympathetic nerve can increase calcium entry and the spontaneous release of calcium from the sarcoplasmic reticulum [8]. All of these factors may promote the occurrence of AF. The atrial vulnerability in group A was lower than in group B, these results are in accordance with the fact that AF could only be induced under programmed atrial stimulation with isoprenaline infusion in group A while it did without isoprenaline in group B.
Table 1 Baseline characteristics of the patients. Group A
Group B
Group C
N
41
73
639
Age SBP (mmHg) DBP (mmHg) TC (mmol/L) TG (mmol/L) HDL-C (mmol/L) LDL-C (mmol/L) GLU (mmol/L) LA (mm) RA (mm)
41.51 ± 14.68⁎,# 118.71 ± 24.14 78.56 ± 9.05 4.01 ± 0.56 1.14 ± 0.46 1.14 ± 0.25 2.81 ± 0.38 4.73 ± 0.49 38.17 ± 8.14 40.34 ± 7.06
61.11 ± 10.24⁎ 117.96 ± 23.54 79.69 ± 8.52 3.98 ± 0.57 1.08 ± 0.39 1.22 ± 0.35 2.73 ± 0.29 4.63 ± 0.37 39.42 ± 5.72 39.86 ± 7.70
53.96 ± 11.39 117.33 ± 23.40 80.21 ± 9.36 4.05 ± 0.58 1.10 ± 0.42 1.19 ± 0.31 2.75 ± 0.31 4.66 ± 0.42 38.48 ± 5.77 39.57 ± 5.34
SBP = systolic blood pressure; DBP = diastolic blood pressure; TC = total cholesterol; TG = triglyceride; LDL-C = low density lipoprotein; HDL-C = high density lipoprotein; GLU = fasting blood-glucose; LA = left atrium dimension; and RA = right atrium dimension. # Compared with group B, P b 0.05. ⁎ Compared with group C, P b 0.05.
432
Letters to the Editor Table 2 Logistic regression analysis of the factors associated with AF.
Age TG LDL-C GLU Gender# LA RA sympathetic stimulation#
Odds ratio
95% CI
P value⁎
1.168 0.526 0.857 0.937 0.952 1.209 1.177 57.977
1.116–1.223 0.234–1.183 0.318–2.313 0.464–1.893 0.483–1.877 1.141–1.281 1.004–1.256 14.761–227.721
0.000 0.120 0.761 0.937 0.888 0.000 0.000 0.000
# Categorical variable; dERP = dispersion of atrial refractoriness; intra = Intra-atrial conduction delay; inter = Interatrial conduction delay; TG = triglyceride; LDLC = low density lipoprotein; GLU = fasting blood-glucose; LA = left atrium dimension; and RA = right atrium dimension. ⁎ P value b 0.05 was considered statistically significant. Fig. 1. Broken line graph for the relationship between the time and the morbidity for the AF.*P b 0.05 vs. group B.
It has been shown that the prevalence of AF increases with age, from b0.5% at 40–50 years to 5–15% at 80 years of age [9]. The mechanism by which age influences the induction of AF is currently unknown. Brembilla-Perrot et al reported that the AERP increased with age after 70 years old, but the increase of AERP was a protective factor against AF [10]. Animal study demonstrated that the increased density of muscarinic type 2 receptor in left atrial free wall enhanced age-related AF vulnerability [11]. The current study found that the ages of the patients in group A were lower than patients in B and C. This finding indicates that the heart sympathetic nerves stimulation could also be used to explain the difference. In conclusion, the age and sympathetic stimulation are important factors of atrial vulnerability and initiation of AF. Further studies will be required to evaluate the potential of targeted anti-adrenergic therapy, such as beta-blockers, for the prevention and treatment of AF in PSVT patients. The detection of AF in all patients by 24 h but not 7 days Holter monitoring and measurement protocol of AERP only at four atrium sites were the primary limitation of the study. This study was sponsored by the Natural Science Foundation of China (81270238) and the Scientific Research Foundation for Doctoral Degree, State Education Ministry of China (20130131110065). http://dx.doi.org/10.1016/j.ijcard.2014.04.030 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
References [1] Centurión OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial fibrillation in the Wolff–Parkinson–White syndrome: intrinsic atrial muscle vulnerability vs. electrophysiological properties of the accessory pathway. Europace 10:294-302. [2] Amasyali B, Kose S, Aytemir K, Kilic A et al. Atrioventricular nodal reentrant tachycardia with paroxysmal atrial fibrillation: clinical and electrophysiological features and predictors of atrial fibrillation recurrence following elimination of atrioventricular nodal reentrant tachycardia. J Interv Card Electrophysiol. 13:195-201. [3] Providência R, Barra S, Paiva L. Atrial fibrillation, elevated troponin, ischemic stroke and adverse outcomes: understanding the connection. Clin Res Cardiol 102:701–711. [4] Gitt AK, Smolka W, Michailov G, Bernhardt A, Pittrow D, Lewalter T. Types and outcomes of cardioversion in patients admitted to hospital for atrial fibrillation: results of the German RHYTHM-AF Study. Clin Res Cardiol 102:713-723. [5] Lampe B, Hammerstingl C, Schwab JO, et al. Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block. Clin Res Cardiol 101:829-836. [6] Yagmur J, Cansel M, Acikgoz N, Ermis N, et al. Assessment of atrial electromechanical delay by tissue Doppler echocardiography in obese subjects. Obesity 19:779-783. [7] Oliveira M, da Silva MN, Timoteo AT, Feliciano J, et al. Inducibility of atrial fibrillation during electrophysiologic evaluation is associated with increased dispersion of atrial refractoriness. Int J Cardiol 136:130-135. [8] Ter Keurs HE, Boyden PA. Calcium and arrhythmogenesis. Physiol Rev 87:457-506. [9] Sharma AD, Klein GJ, Guiraudon GM, Milstein S Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: incidence after surgical ablation of the accessory pathway. Circulation. 72:161-169. [10] Brembilla-Perrot B, Burger G, Beurrier D, et al. Influence of age on atrial fibrillation inducibility. Pacing Clin Electrophysiol 27:287-292. [11] Yang YH, Zheng QS, Li J, et al. Age-related changes in the atrial muscarinic type 2 receptor and their effects on atrial fibrillation vulnerability in rabbits. Experimental Gerontology 44:572–578.
