Ultrasound in Med. & Biol., Vol. 40, No. 6, pp. 1133–1137, 2014 Copyright Ó 2014 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/$ - see front matter
http://dx.doi.org/10.1016/j.ultrasmedbio.2014.01.006
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Original Contribution ATRIAL CONDUCTION DELAY PREDICTS ATRIAL FIBRILLATION IN PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA PATIENTS AFTER RADIOFREQUENCY CATHETER ABLATION ZHEN-XING XU, JING-QUAN ZHONG, WEI ZHANG, XIN YUE, BING RONG, QING ZHU, ZHAOTONG ZHENG, and YUN ZHANG Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, China (Received 13 July 2013; revised 23 December 2013; in final form 6 January 2014)
Abstract—This study aimed to assess whether intra- and inter-atrial conduction delay could predict atrial fibrillation (AF) for paroxysmal supraventricular tachycardia (PSVT) patients after successful treatment by radiofrequency catheter ablation (RFCA). Echocardiography examination was performed on 524 consecutive PSVT patients (15 patients were excluded). Left atrial dimension, right atrial diameter and intra- and interatrial conduction delay were measured before ablation. Patients were divided into group A (n 5 32): occurrence of AF after the ablation and group B (n 5 477): remained in sinus rhythm during follow-up. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of intra- and inter-atrial conduction delay. Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 ± 0.30 msec vs. 4.56 ± 0.32 msec; 21.98 ± 1.32 msec vs. 20.01 ± 1.33; p , 0.05). Binary logistic regression analysis showed that intra- and inter-atrial conduction were significant influential factors for the occurrence of AF (odds ratio [OR] 5 13.577, 95% confidence interval [CI], 3.469–48.914; OR 5 2.569, 95% CI, 1.90923.459, p , 0.05). The ROC cure analysis revealed that intra-atrial conduction delay $ 4.45 msec and inter-atrial conduction delay $ 20.65 were the most optimal cut-off value for predicting AF in PSVT patients after RFCA. In conclusion, this is the first study to show that the intra- and inter-atrial conduction delay could effectively predict AF in post-ablation PSVT patients. (E-mail: gilman_zhong@hotmail. com) Ó 2014 World Federation for Ultrasound in Medicine & Biology. Key Words: Atrial conduction delay, Atrial fibrillation, Ablation, Atrial vulnerability, Paroxysmal supraventricular tachycardia.
lar events, especially thromboembolic stroke, increases cardiovascular morbidity and mortality (Friberg et al. 2010; Knecht et al. 2008). Intra- and inter-atrial conduction delay has been widely assessed by determining the time from the onset of the P-wave to the beginning of atrial contraction using electrocardiogram (ECG) and M-mode or Doppler echocardiography (Akturk et al. 2012; Pytkowski et al. 2008). The prolongation of this conduction delay provides an electrophysiologic substrate for multiple re-entry wavelets by reducing the wavelength of atrial tissue and subsequently promotes the occurring of AF (Cui et al. 2008; Daubert et al. 2004; Pytkowski et al. 2008; Sengul et al. 2011). Therefore, in this prospective study we aimed to assess whether intra- and inter-atrial conduction delay could serve as the predictor of AF for PSVT patients who are successfully treated by RFCA.
INTRODUCTION Atrial fibrillation (AF) occurs more frequently in paroxysmal supraventricular tachycardia (PSVT) patients than in general population. Even after the arrhythmia are successfully cured by radiofrequency catheter ablation (RFCA), the morbidity of AF is still high for PSVT patients: 6%–10% in atrioventricular re-entrant tachycardia (AVRT) and 28% in atrioventricular nodal reentrant tachycardia (AVNRT) (Amasyali et al. 2005; Centuri on et al. 2008; Haissaguerre et al. 1992; Hurwitz et al. 1990; Sharma et al. 1985). AF-related cardiovascu-
Address correspondence to: Jing-quan Zhong, Department of Cardiology, Qilu Hospital of Shandong University, Wen Hua Xi Lu, Jinan 250012, Shandong Province, China. E-mail: gilman_zhong@hotmail. com 1133
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METHODS Study population Five hundred and twenty-four consecutive PSVT patients undergoing electrophysiology examination at Qilu Hospital between January 2007 and October 2009 were enrolled in this study. All patients provided written informed consent and the protocol was approved by Ethics Committee of Qilu Hospital. All anti-arrhythmic medications, digoxin and other drugs that affected cardiac electrophysiologic indexes were withdrawn for .5 half-lives before operation. RFCA was performed after the arrhythmia was diagnosed by the electrophysiology. Before RFCA, intra- and inter-atrial conduction delay were measured. Exclusion criteria were diabetes mellitus, body mass index $ 25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine) and any type of AF with ECG or 24-h Holter (Quntian Inc, Shanhai, China) evidence and hypertension. Patients who developed any type of AF during the study period were grouped into group A, while patients who remained in sinus rhythm were grouped into group B. To compare the atrial conduction delay between PSVT patients with AF and the AF patients without PSVT, 49 AF patients with successful RFCA during the study period were enrolled in this study and defined as group C. Intra- and inter-atrial conduction delay were measured before successful RFCA. Transthoracic echocardiography and atrial electromechanical coupling interval measurement Before the RFCA, echocardiography examination was carried out by a cardiologist (dr W) who was blinded to the clinical details and the other examination information with a 2.5–3.5 MHz phased array transducer (Vivid 7; GE Vingemed Ultrasound, Horten, Norway). Left atrial diameter (LA, the largest diameter on the parasternal long axis view), right atrial diameter (RA, the largest diameter on the four-chamber views) and mitral and tricuspid annulus inflow velocities E-wave and A-wave were measured. All of the echocardiography indices were recorded on super video home system videotape. All measurements were carried out and analyzed of $3 cardiac cycles. One ECG monitor channel was displayed on the screen of the machine. The atrial conduction delay of the atrium were measured at three time intervals based on the information recorded on the videotape, and three measurements were performed at each time interval for average: T1: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the lateral mitral annulus. T2: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the septal mitral annulus.
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T3: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the tricuspid annulus (Sakabe et al. 2010; Sengul et al. 2011). Inter-atrial conduction delay was the interval from T3 to T1, expressed as T1-T3. Intra-atrial conduction delay was the interval from T3 to T2, expressed as T2-T3. Follow-up All patients were followed-up at the outpatient clinic 1, 3, 6, 12, 18, 24, 30, and 36 mo after the operation and whenever the patients complained of palpitations or other symptoms. A 24-h Holter recording was performed during the follow-up and whenever the patients had symptoms such as palpitations, dizziness and syncope. Study endpoint was the occurrence of any type of AF with ECG or 24-h Holter evidence. Thirteen patients were lost during follow-up, one patient died because of strokes and one patient died because of myocardial infarctions, respectively. These 15 patients were excluded from the study, and they did not manifest any evidence of AF before being lost to follow-up or dying. Statistical analysis Statistical analysis was performed using SPSS 13.0 software (SPSS Inc, Chicago, IL, USA). Continuous variables were reported as means 6 SD and analyzed by student’s t test. Categorical variables were compared using c2 test. A binary logistic regression analysis was used to identify signification predictor of the initiation of AF. Occurrence of AF was selected as the dependent variable for the logistic regression model. Factors such as age, gender (in the regression equation, male was coded as ‘‘0’’ and female was coded as ‘‘1’’), total cholesterol (TC), low-density lipoprotein (LDL-C), fasting bloodglucose (GLU), systolic pressure (SBP), LA and RA were selected as co-variates for the binary logistic regression analysis. The optimal cut-off levels of intra-atrial and inter-atrial conduction delay for the prediction of AF were evaluated by receiver operating characteristic (ROC) curve analysis. The discrimination of intra-atrial and inter-atrial conduction delay was determined by measuring the area under the ROC curve. Correlation between variables was assessed by Pearson correlation coefficients. p , 0.05 was considered statistically significant. RESULTS Baseline characteristics A total of 509 patients completed this study, their age ranged from 9–79 y (mean age 53.65 6 11.96 y). The baseline characteristics of these patients are shown in Table 1.
Atrial conduction delay predicts AF in PSVT patients d Z.-X. XU et al.
Table 1. Baseline characteristics of the patients in groups A, B and C Group A
Group B
Group C
n 32/509 477/509 49 Age 56.09 6 15.66 53.48 6 11.68 54.38 6 13.68 SBP (mmHg) 119.68 6 24.32 117.65 6 23.69 121.23 6 26.25 DBP (mmHg) 77.56 6 10.35 79.39 6 9.85 81.21 6 11.35 HR (beats/min) 68.9 65.2 72.3 6 4.8 71.7 6 6.3 TC (mmol/L) 4.03 6 0.67 3.97 6 0.59 3.96 6 0.63 TG (mmol/L) 1.17 6 0.47 1.09 6 0.42 1.16 6 0.35 HDL-C (mmol/L) 1.16 6 0.24 1.18 6 0.32 1.14 6 0.26 LDL-C (mmol/L) 2.77 6 0.42 2.76 6 0.31 2.74 6 0.38 GLU (mmol/L) 4.73 6 0.73 4.67 6 0.42 4.62 6 0.65 LA (mm) 37.03 6 8.18 38.48 6 5.52 38.12 6 6.78 RA (mm) 39.78 6 6.24 39.18 6 5.51 39.57 6 7.56 Gender (male) 15/32 242/477 26/49 Group A 5 PSVT patients with AF after ablation; Group B 5 PSVT patients remained in sinus rhythm after ablation; Group C 5 AF patients without PSVT; SBP 5 systolic pressure; DBP 5 diastolic pressure; HR 5 heart rate; TC 5 total cholesterol; TG 5 triglyceride; HDL-C 5 high-density lipoprotein; LDL-C 5 low-density lipoprotein; GLU 5 fasting blood-glucose; LA 5 left atrium dimension; RA 5 right atrium dimension. All the above variables showed no statistical significance between group A, B and C (p . 0.05).
Intra- and inter-atrial conduction delay and the correlations with atrial diameter Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 6 0.30 msec vs. 4.56 6 0.32 msec; 21.98 6 1.32 msec vs. 20.01 6 1.33, p , 0.05, respectively, Table 2), but there were no significant differences in intra- and inter-atrial conduction delay between group A and group C (4.79 6 0.30 msec vs. 4.82 6 0.28 msec; 21.98 6 1.32 msec vs. 22.15 6 1.45 msec, p , 0.05, respectively, Table 2). No correlation was found between atrial conduction delay and LA (r 5 0.040, p 5 0.365, r 5 20.026, p 5 0.561 for intra- and inter-atrial conduction, respectively). Inter-atrial conduction delay also showed no correlations with RA (r 5 0.009, p 5 0.836), but there was a weak positive correlation between intra-atrial conduction delay and RA (r 5 0.103, p 5 0.020). Binary logistic regression analysis showed that intra- and inter-atrial conduction were the significant
Table 2. Atrial conduction delay in groups A, B and C Group A
Group B
Group C
Inter-atrial 21.98 6 1.32 (p 5 0.002)* 20.01 6 1.33 22.15 6 1.45 (msec) Intra-atrial 4.79 6 0.30 (p 5 0.003)* 4.56 6 0.32 4.82 6 0.28 (msec) Group A 5 PSVT patients with AF after ablation; Group B 5 PSVT patients remained in sinus rhythm after ablation; Group C 5 AF patients without PSVT; Inter-atrial 5 inter-atrial conduction delay; Intraatrial 5 intra-atrial conduction delay. * Compared with Group B.
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influential factors for the occurrence of AF (odds ratio [OR] 5 13.577, 95% confidence interval (CI), 3.469– 48.914; OR 5 2.569, 95% CI, 1.909–3.459, p , 0.05, respectively, Table 3). Intra- and inter-atrial conduction delay predicts the risk of AF in PSVT patients after RFCA Receiver operator characteristic cure analysis revealed that intra- and inter-atrial conduction delay significantly discriminated PSVT patients who developed any type of AF and those who remained in sinus rhythm, with an area under the curve of 0.708 and 0.874, respectively (95% CI, 0.632–0.785 and 0.788–0.909, p , 0.05, respectively, Fig. 1). The intra-atrial conduction delay of 4.450 msec and inter-atrial conduction delay of 20.650 msec could effectively predict AF in post-ablation PSVT patients with the sensitivity of 91% and 81%, and specificity of 42% and 80%, respectively (p , 0.05, Fig. 1). DISCUSSION Several clinical studies suggested that increased risk of AF was associated with AVNRT (Amasyali et al. 2005; Hurwitz et al. 1990) and AVRT (Centurion et al. 2008; Haissaguerre et al. 1992; Sharma et al. 1985) involving accessory pathways. Even after successful ablation of accessory pathways and slow pathway of atrioventricular node, a high risk of AF recurrence has been reported, especially for elderly patients (Centurion et al. 2008). In our study, high morbidity of AF (recurrence plus first diagnosed) was found at the end of a 3-y follow-up period (32/ 509, 6.27%). However, the difference in the age of the patients with or without AF after the operation was not statistically significant, suggested that age may not be the independent predictor of AF for post-ablation PSVT patients. In addition, factors associated with aging Table 3. Binary logistic regression analysis for the risk factors of AF
Age Inter-atrial Intra-atrial TG LDL-C GLU Gender* LA RA
Odds ratio
95% CI
p value
1.019 2.569 13.577 1.321 1.351 1.357 0.993 0.954 1.058
0.986–1.053 1.909–3.459 3.769–48.914 0.458–3.811 0.374–4.873 0.515–3.576 0.429–2.299 0.884–1.010 0.978–1.144
0.266 0.000 0.000 0.606 0.646 0.537 0.987 0.094 0.159
Inter-atrial 5 inter-atrial conduction delay; Intra-atrial 5 intra-atrial conduction delay; TG 5 triglyceride; LDL-C 5 low-density lipoprotein; GLU 5 fasting blood-glucose; LA 5 left atrium dimension; RA 5 right atrium dimension. * In the regression equation, male was coded as ‘‘0’’ and female was coded as ‘‘1’’.
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Fig. 1. The ROC curve analysis revealed that the area under the curve of 0.708 for intra-atrial conduction delay and 0.874 for inter-atrial conduction delay (95% CI, 0.632–0.785 and 0.788–0.909, p , 0.05, respectively).
especially diabetes mellitus and hypertension was excluded in the present study. Furthermore, PSVT itself could influence the presence of AF. All of these might contribute to the low correlation between age and AF in our study. Most PSVT patients present abnormally prolonged and fractionated atrial electrograms that are recorded with atrial endocardial mapping (Centurion et al. 2005). The electrophysiologic disorder may attribute to the electrophysiologic properties of the accessory pathway (Hsieh et al. 2004) and the intrinsic atrial muscle vulnerability due to the presence of an underlying atrial disease (Fujimura et al. 1990). The prolongation of intra-atrial and inter-atrial conduction delay, which can be assessed by Doppler echocardiography, provides a substrate for multiple re-entry wavelets by generating heterogeneous intra-atrial and inter-atrial conduction (Daubert et al. 2004), subsequently promoting the occurrence of AF (Cui et al. 2008; Pytkowski et al. 2008; Sengul et al. 2011). In fact, the increasing intra-atrial and inter-atrial conduction delay has been suggested as a predictor of increased atrial vulnerability (Pytkowski et al. 2008; Sakabe et al. 2010). Consistent with previous studies, our study demonstrated that the atrial conduction delay for PSVT patients with post-ablation AF was higher than the patients who remained in sinus rhythm. Ermis
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et al (2011) reported that LA diameter was correlated with atrial eletromechanical conduction interval. However, a weak correlation between the large range of conduction delay and a given left size was reported (Markides et al. 2003). In the present study, we found no correlation between atrial conduction delay and LA diameter (r 5 0.040, p 5 0.365; r 5 20.026, p 5 0.561 for intraand inter-atrial conduction, respectively). This may be due to that the atrium size and cardiac conduction system are independent (Daubert et al. 2004). To our knowledge, this is the first study to evaluate the predictive value of intra- and inter-atrial conduction delay for the occurrence of AF (recurrence plus first diagnosed) in post-ablation PSVT patients. ROC curve analysis demonstrated that intra-atrial conduction delay $ 4.450 msec (with the sensitivity and specificity of 91% and 42%, respectively) and inter-atrial conduction delay $ 20.650 msec (with the sensitivity and specificity of 81% and 80%, respectively) were the most powerful predictive factor of AF (together with recurrence and first diagnosed, p , 0.05). After excluding factors such as diabetes mellitus, body mass index $ 25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine) and hypertension, the binary logistic regression analysis showed that intra- and inter-atrial conduction delay were the significant predictors for the occurrence of AF (OR 5 13.577, 95% CI, 3.469–48.914; OR 5 2.569, 95% CI, 1.909–3.459, p , 0.05, respectively). Thus atrial conduction delay can be regarded as a clinical predictor of AF for post-ablation PSVT patients who are at high risk of AF. PSVT patients with high atrial conduction delay, which can be detected by the pre-ablation echocardiography examination, should be paid great attention. A 24-h Holter recording should be taken regularly and routinely to improve the detection of AF. Anti-atrial remodeling measures, such as angiotensin-converting enzyme inhibitors, aldosterone antagonists, statins and Omega-3 fatty acid, should be taken for the prevention and treatment of AF with high prevalence after successful PSVT ablation and reducing AF related cardiovascular morbidity and mortality. Study limitations There are several limitations of this study. First, all patients were evaluated by 24-h Holter monitoring. Inevitable initiation of paroxysmal AF may have been underestimated. Second, the measurements for intra- and inter-atrial conduction delay in this study were done manually with commonly less reliability and repeatability, although three measurements were performed at each time interval to reduce errors. Third, the protocol did not include measurements of atrium volumes, atrial area and dimensions indexed by body surface area. Therefore, it was not sufficient to explain the relationship
Atrial conduction delay predicts AF in PSVT patients d Z.-X. XU et al.
between the atrial conduction delay and the shape of atrium. Finally, AVRT and AVNRT patients were considered together in this study, but the effects of atrial remodeling and atrial vulnerability may differ (Chang et al. 2008). CONCLUSION The intra-atrial conduction delay $4.45 and interatrial conduction delay $20.65 could effectively predict AF in post-ablation PSVT patients. Acknowledgments—This study was sponsored by the Natural Science Foundation of China (81270238) and the Scientific Research Foundation for the Doctoral Degree, State Education Ministry of China (20100131110059).
REFERENCES Akturk E, Ya gmur J, Ac¸ıkg€oz N, Ermis¸ N, Cansel M, Karakus¸ Y, Tas¸olar H, Eyupkoca F, Pekdemir H. Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in smokers. J Interv Card Electrophysiol 2012;34:247–253. Amasyali B, Kose S, Aytemir K, Kilic A, Heper G, Kursaklioglu H, Iyisoy A, Celik T, Kaya EB, Isik E. 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 2005;13:195–201. Centuri on OA, Shimizu A, Isomoto S, Konoe A, Kaibara M, Hayano M, Yano K. Influence of advancing age on fractionated right atrial endocardial electrograms. Am J Cardiol 2005;96:239–242. Centuri on 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 2008; 10:294–302. Chang SL, Tai CT, Lin YJ, Lo LW, Tuan TC, Udyavar AR, Tsao HM, Hsieh MH, Hu YF, Chiang SJ, Chen YJ, Wongcharoen W, Ueng KC, Chen SA. Electrophysiological characteristics and catheter ablation in patients with paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2008;19: 367–373. Cui QQ, Zhang W, Wang H, Sun X, Wang R, Yang HY, Meng XQ, Zhang Y, Wang H. Assessment of atrial electromechanical coupling and influential factors in nonrheumatic paroxysmal atrial fibrillation. Clin Cardiol 2008;31:74–78.
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Daubert JC, Pavin D, Jauvert G, Mabo P. Intra- and interatrial conduction delay: Implications for cardiac pacing. Pacing Clin Electrophysiol 2004;27:507–525. Ermis N, Acikgoz N, Cuglan B, Cansel M, Yagmur J, Tasolar H, Barutcu I, Pekdemir H, Ozdemir R. Comparison of atrial electromechanical coupling interval and P-wave dispersion in non-dipper versus dipper hypertensive subjects. Blood Press 2011;20:60–66. Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial fibrillation: Report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart J 2010;31:967–975. Fujimura O, Klein GJ, Yee R, Sharma AD. Mode of onset of atrial fibrillation in the Wolff-Parkinson-White syndrome: How important is the accessory pathway? J Am Coll Cardiol 1990;15:1082–1086. Haissaguerre M, Fischer B, Labbe T, Lemetayer P, Montserrat P, d’Ivernois C, Dartigues JF, Warin JF. Frequency of recurrent atrial fibrillation after catheter ablation of overt accessory pathway. Am J Cardiol 1992;69:493–497. Hsieh MH, Tai CT, Chiang CE, Tsai CF, Chen YJ, Chan P, Kuo YC, Lee SH, Ueng KC, Chen SA. Double atrial potentials recorded in the coronary sinus in patients with Wolff-Parkinson-White syndrome: A possible mechanism of induced atrial fibrillation. J Interv Card Electrophysiol 2004;11:97–103. Hurwitz JL, German LD, Packer DL, Wharton JM, McCarthy EA, Wilkinson WE, Prystowsky EN, Pritchett EL. Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry. Pacing Clin Electrophysiol 1990;13:705–710. Knecht S, Oelschl€ager C, Duning T, Lohmann H, Albers J, Stehling C, Heindel W, Breithardt G, Berger K, Ringelstein EB, Kirchhof P, Wersching H. Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy. Eur Heart J 2008;29:2125–2132. Markides V, Schilling RJ, Ho SY, Chow AW, Davies DW, Peters NS. Characterization of left atrial activation in the intact human heart. Circulation 2003;107:733–739. Pytkowski M, Jankowska A, Maciag A, Kowalik I, Sterlinski M, Szwed H, Saumarez RC. Paroxysmal atrial fibrillation is associated with increased intra-atrial conduction delay. Europace 2008;10: 1415–1420. Sakabe K, Fukuda N, Fukuda Y, Morishita S, Shinohara H, Tamura Y. Relation of gender and interatrial dyssynchrony on tissue Doppler imaging to the prediction of the progression to chronic atrial fibrillation in patients with nonvalvular paroxysmal atrial fibrillation. Heart Vessels 2010;25:410–416. Sengul C, Cevik C, Ozveren O, Sunbul A, Kilicarslan F, Oduncu V, Can M, Semiz E, Dindar I. Assessment of Atrial Conduction Time in Patients with Coronary Artery Ectasia. Pacing Clin Electrophysiol 2011;34:1468–1474. 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 1985;72: 161–169.
http://dx.doi.org/10.1016/j.ultrasmedbio.2014.01.006
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Original Contribution ATRIAL CONDUCTION DELAY PREDICTS ATRIAL FIBRILLATION IN PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA PATIENTS AFTER RADIOFREQUENCY CATHETER ABLATION ZHEN-XING XU, JING-QUAN ZHONG, WEI ZHANG, XIN YUE, BING RONG, QING ZHU, ZHAOTONG ZHENG, and YUN ZHANG Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, China (Received 13 July 2013; revised 23 December 2013; in final form 6 January 2014)
Abstract—This study aimed to assess whether intra- and inter-atrial conduction delay could predict atrial fibrillation (AF) for paroxysmal supraventricular tachycardia (PSVT) patients after successful treatment by radiofrequency catheter ablation (RFCA). Echocardiography examination was performed on 524 consecutive PSVT patients (15 patients were excluded). Left atrial dimension, right atrial diameter and intra- and interatrial conduction delay were measured before ablation. Patients were divided into group A (n 5 32): occurrence of AF after the ablation and group B (n 5 477): remained in sinus rhythm during follow-up. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of intra- and inter-atrial conduction delay. Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 ± 0.30 msec vs. 4.56 ± 0.32 msec; 21.98 ± 1.32 msec vs. 20.01 ± 1.33; p , 0.05). Binary logistic regression analysis showed that intra- and inter-atrial conduction were significant influential factors for the occurrence of AF (odds ratio [OR] 5 13.577, 95% confidence interval [CI], 3.469–48.914; OR 5 2.569, 95% CI, 1.90923.459, p , 0.05). The ROC cure analysis revealed that intra-atrial conduction delay $ 4.45 msec and inter-atrial conduction delay $ 20.65 were the most optimal cut-off value for predicting AF in PSVT patients after RFCA. In conclusion, this is the first study to show that the intra- and inter-atrial conduction delay could effectively predict AF in post-ablation PSVT patients. (E-mail: gilman_zhong@hotmail. com) Ó 2014 World Federation for Ultrasound in Medicine & Biology. Key Words: Atrial conduction delay, Atrial fibrillation, Ablation, Atrial vulnerability, Paroxysmal supraventricular tachycardia.
lar events, especially thromboembolic stroke, increases cardiovascular morbidity and mortality (Friberg et al. 2010; Knecht et al. 2008). Intra- and inter-atrial conduction delay has been widely assessed by determining the time from the onset of the P-wave to the beginning of atrial contraction using electrocardiogram (ECG) and M-mode or Doppler echocardiography (Akturk et al. 2012; Pytkowski et al. 2008). The prolongation of this conduction delay provides an electrophysiologic substrate for multiple re-entry wavelets by reducing the wavelength of atrial tissue and subsequently promotes the occurring of AF (Cui et al. 2008; Daubert et al. 2004; Pytkowski et al. 2008; Sengul et al. 2011). Therefore, in this prospective study we aimed to assess whether intra- and inter-atrial conduction delay could serve as the predictor of AF for PSVT patients who are successfully treated by RFCA.
INTRODUCTION Atrial fibrillation (AF) occurs more frequently in paroxysmal supraventricular tachycardia (PSVT) patients than in general population. Even after the arrhythmia are successfully cured by radiofrequency catheter ablation (RFCA), the morbidity of AF is still high for PSVT patients: 6%–10% in atrioventricular re-entrant tachycardia (AVRT) and 28% in atrioventricular nodal reentrant tachycardia (AVNRT) (Amasyali et al. 2005; Centuri on et al. 2008; Haissaguerre et al. 1992; Hurwitz et al. 1990; Sharma et al. 1985). AF-related cardiovascu-
Address correspondence to: Jing-quan Zhong, Department of Cardiology, Qilu Hospital of Shandong University, Wen Hua Xi Lu, Jinan 250012, Shandong Province, China. E-mail: gilman_zhong@hotmail. com 1133
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METHODS Study population Five hundred and twenty-four consecutive PSVT patients undergoing electrophysiology examination at Qilu Hospital between January 2007 and October 2009 were enrolled in this study. All patients provided written informed consent and the protocol was approved by Ethics Committee of Qilu Hospital. All anti-arrhythmic medications, digoxin and other drugs that affected cardiac electrophysiologic indexes were withdrawn for .5 half-lives before operation. RFCA was performed after the arrhythmia was diagnosed by the electrophysiology. Before RFCA, intra- and inter-atrial conduction delay were measured. Exclusion criteria were diabetes mellitus, body mass index $ 25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine) and any type of AF with ECG or 24-h Holter (Quntian Inc, Shanhai, China) evidence and hypertension. Patients who developed any type of AF during the study period were grouped into group A, while patients who remained in sinus rhythm were grouped into group B. To compare the atrial conduction delay between PSVT patients with AF and the AF patients without PSVT, 49 AF patients with successful RFCA during the study period were enrolled in this study and defined as group C. Intra- and inter-atrial conduction delay were measured before successful RFCA. Transthoracic echocardiography and atrial electromechanical coupling interval measurement Before the RFCA, echocardiography examination was carried out by a cardiologist (dr W) who was blinded to the clinical details and the other examination information with a 2.5–3.5 MHz phased array transducer (Vivid 7; GE Vingemed Ultrasound, Horten, Norway). Left atrial diameter (LA, the largest diameter on the parasternal long axis view), right atrial diameter (RA, the largest diameter on the four-chamber views) and mitral and tricuspid annulus inflow velocities E-wave and A-wave were measured. All of the echocardiography indices were recorded on super video home system videotape. All measurements were carried out and analyzed of $3 cardiac cycles. One ECG monitor channel was displayed on the screen of the machine. The atrial conduction delay of the atrium were measured at three time intervals based on the information recorded on the videotape, and three measurements were performed at each time interval for average: T1: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the lateral mitral annulus. T2: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the septal mitral annulus.
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T3: time interval from the beginning of P-wave on surface ECG to the beginning of the late diastolic wave of the tricuspid annulus (Sakabe et al. 2010; Sengul et al. 2011). Inter-atrial conduction delay was the interval from T3 to T1, expressed as T1-T3. Intra-atrial conduction delay was the interval from T3 to T2, expressed as T2-T3. Follow-up All patients were followed-up at the outpatient clinic 1, 3, 6, 12, 18, 24, 30, and 36 mo after the operation and whenever the patients complained of palpitations or other symptoms. A 24-h Holter recording was performed during the follow-up and whenever the patients had symptoms such as palpitations, dizziness and syncope. Study endpoint was the occurrence of any type of AF with ECG or 24-h Holter evidence. Thirteen patients were lost during follow-up, one patient died because of strokes and one patient died because of myocardial infarctions, respectively. These 15 patients were excluded from the study, and they did not manifest any evidence of AF before being lost to follow-up or dying. Statistical analysis Statistical analysis was performed using SPSS 13.0 software (SPSS Inc, Chicago, IL, USA). Continuous variables were reported as means 6 SD and analyzed by student’s t test. Categorical variables were compared using c2 test. A binary logistic regression analysis was used to identify signification predictor of the initiation of AF. Occurrence of AF was selected as the dependent variable for the logistic regression model. Factors such as age, gender (in the regression equation, male was coded as ‘‘0’’ and female was coded as ‘‘1’’), total cholesterol (TC), low-density lipoprotein (LDL-C), fasting bloodglucose (GLU), systolic pressure (SBP), LA and RA were selected as co-variates for the binary logistic regression analysis. The optimal cut-off levels of intra-atrial and inter-atrial conduction delay for the prediction of AF were evaluated by receiver operating characteristic (ROC) curve analysis. The discrimination of intra-atrial and inter-atrial conduction delay was determined by measuring the area under the ROC curve. Correlation between variables was assessed by Pearson correlation coefficients. p , 0.05 was considered statistically significant. RESULTS Baseline characteristics A total of 509 patients completed this study, their age ranged from 9–79 y (mean age 53.65 6 11.96 y). The baseline characteristics of these patients are shown in Table 1.
Atrial conduction delay predicts AF in PSVT patients d Z.-X. XU et al.
Table 1. Baseline characteristics of the patients in groups A, B and C Group A
Group B
Group C
n 32/509 477/509 49 Age 56.09 6 15.66 53.48 6 11.68 54.38 6 13.68 SBP (mmHg) 119.68 6 24.32 117.65 6 23.69 121.23 6 26.25 DBP (mmHg) 77.56 6 10.35 79.39 6 9.85 81.21 6 11.35 HR (beats/min) 68.9 65.2 72.3 6 4.8 71.7 6 6.3 TC (mmol/L) 4.03 6 0.67 3.97 6 0.59 3.96 6 0.63 TG (mmol/L) 1.17 6 0.47 1.09 6 0.42 1.16 6 0.35 HDL-C (mmol/L) 1.16 6 0.24 1.18 6 0.32 1.14 6 0.26 LDL-C (mmol/L) 2.77 6 0.42 2.76 6 0.31 2.74 6 0.38 GLU (mmol/L) 4.73 6 0.73 4.67 6 0.42 4.62 6 0.65 LA (mm) 37.03 6 8.18 38.48 6 5.52 38.12 6 6.78 RA (mm) 39.78 6 6.24 39.18 6 5.51 39.57 6 7.56 Gender (male) 15/32 242/477 26/49 Group A 5 PSVT patients with AF after ablation; Group B 5 PSVT patients remained in sinus rhythm after ablation; Group C 5 AF patients without PSVT; SBP 5 systolic pressure; DBP 5 diastolic pressure; HR 5 heart rate; TC 5 total cholesterol; TG 5 triglyceride; HDL-C 5 high-density lipoprotein; LDL-C 5 low-density lipoprotein; GLU 5 fasting blood-glucose; LA 5 left atrium dimension; RA 5 right atrium dimension. All the above variables showed no statistical significance between group A, B and C (p . 0.05).
Intra- and inter-atrial conduction delay and the correlations with atrial diameter Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 6 0.30 msec vs. 4.56 6 0.32 msec; 21.98 6 1.32 msec vs. 20.01 6 1.33, p , 0.05, respectively, Table 2), but there were no significant differences in intra- and inter-atrial conduction delay between group A and group C (4.79 6 0.30 msec vs. 4.82 6 0.28 msec; 21.98 6 1.32 msec vs. 22.15 6 1.45 msec, p , 0.05, respectively, Table 2). No correlation was found between atrial conduction delay and LA (r 5 0.040, p 5 0.365, r 5 20.026, p 5 0.561 for intra- and inter-atrial conduction, respectively). Inter-atrial conduction delay also showed no correlations with RA (r 5 0.009, p 5 0.836), but there was a weak positive correlation between intra-atrial conduction delay and RA (r 5 0.103, p 5 0.020). Binary logistic regression analysis showed that intra- and inter-atrial conduction were the significant
Table 2. Atrial conduction delay in groups A, B and C Group A
Group B
Group C
Inter-atrial 21.98 6 1.32 (p 5 0.002)* 20.01 6 1.33 22.15 6 1.45 (msec) Intra-atrial 4.79 6 0.30 (p 5 0.003)* 4.56 6 0.32 4.82 6 0.28 (msec) Group A 5 PSVT patients with AF after ablation; Group B 5 PSVT patients remained in sinus rhythm after ablation; Group C 5 AF patients without PSVT; Inter-atrial 5 inter-atrial conduction delay; Intraatrial 5 intra-atrial conduction delay. * Compared with Group B.
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influential factors for the occurrence of AF (odds ratio [OR] 5 13.577, 95% confidence interval (CI), 3.469– 48.914; OR 5 2.569, 95% CI, 1.909–3.459, p , 0.05, respectively, Table 3). Intra- and inter-atrial conduction delay predicts the risk of AF in PSVT patients after RFCA Receiver operator characteristic cure analysis revealed that intra- and inter-atrial conduction delay significantly discriminated PSVT patients who developed any type of AF and those who remained in sinus rhythm, with an area under the curve of 0.708 and 0.874, respectively (95% CI, 0.632–0.785 and 0.788–0.909, p , 0.05, respectively, Fig. 1). The intra-atrial conduction delay of 4.450 msec and inter-atrial conduction delay of 20.650 msec could effectively predict AF in post-ablation PSVT patients with the sensitivity of 91% and 81%, and specificity of 42% and 80%, respectively (p , 0.05, Fig. 1). DISCUSSION Several clinical studies suggested that increased risk of AF was associated with AVNRT (Amasyali et al. 2005; Hurwitz et al. 1990) and AVRT (Centurion et al. 2008; Haissaguerre et al. 1992; Sharma et al. 1985) involving accessory pathways. Even after successful ablation of accessory pathways and slow pathway of atrioventricular node, a high risk of AF recurrence has been reported, especially for elderly patients (Centurion et al. 2008). In our study, high morbidity of AF (recurrence plus first diagnosed) was found at the end of a 3-y follow-up period (32/ 509, 6.27%). However, the difference in the age of the patients with or without AF after the operation was not statistically significant, suggested that age may not be the independent predictor of AF for post-ablation PSVT patients. In addition, factors associated with aging Table 3. Binary logistic regression analysis for the risk factors of AF
Age Inter-atrial Intra-atrial TG LDL-C GLU Gender* LA RA
Odds ratio
95% CI
p value
1.019 2.569 13.577 1.321 1.351 1.357 0.993 0.954 1.058
0.986–1.053 1.909–3.459 3.769–48.914 0.458–3.811 0.374–4.873 0.515–3.576 0.429–2.299 0.884–1.010 0.978–1.144
0.266 0.000 0.000 0.606 0.646 0.537 0.987 0.094 0.159
Inter-atrial 5 inter-atrial conduction delay; Intra-atrial 5 intra-atrial conduction delay; TG 5 triglyceride; LDL-C 5 low-density lipoprotein; GLU 5 fasting blood-glucose; LA 5 left atrium dimension; RA 5 right atrium dimension. * In the regression equation, male was coded as ‘‘0’’ and female was coded as ‘‘1’’.
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Fig. 1. The ROC curve analysis revealed that the area under the curve of 0.708 for intra-atrial conduction delay and 0.874 for inter-atrial conduction delay (95% CI, 0.632–0.785 and 0.788–0.909, p , 0.05, respectively).
especially diabetes mellitus and hypertension was excluded in the present study. Furthermore, PSVT itself could influence the presence of AF. All of these might contribute to the low correlation between age and AF in our study. Most PSVT patients present abnormally prolonged and fractionated atrial electrograms that are recorded with atrial endocardial mapping (Centurion et al. 2005). The electrophysiologic disorder may attribute to the electrophysiologic properties of the accessory pathway (Hsieh et al. 2004) and the intrinsic atrial muscle vulnerability due to the presence of an underlying atrial disease (Fujimura et al. 1990). The prolongation of intra-atrial and inter-atrial conduction delay, which can be assessed by Doppler echocardiography, provides a substrate for multiple re-entry wavelets by generating heterogeneous intra-atrial and inter-atrial conduction (Daubert et al. 2004), subsequently promoting the occurrence of AF (Cui et al. 2008; Pytkowski et al. 2008; Sengul et al. 2011). In fact, the increasing intra-atrial and inter-atrial conduction delay has been suggested as a predictor of increased atrial vulnerability (Pytkowski et al. 2008; Sakabe et al. 2010). Consistent with previous studies, our study demonstrated that the atrial conduction delay for PSVT patients with post-ablation AF was higher than the patients who remained in sinus rhythm. Ermis
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et al (2011) reported that LA diameter was correlated with atrial eletromechanical conduction interval. However, a weak correlation between the large range of conduction delay and a given left size was reported (Markides et al. 2003). In the present study, we found no correlation between atrial conduction delay and LA diameter (r 5 0.040, p 5 0.365; r 5 20.026, p 5 0.561 for intraand inter-atrial conduction, respectively). This may be due to that the atrium size and cardiac conduction system are independent (Daubert et al. 2004). To our knowledge, this is the first study to evaluate the predictive value of intra- and inter-atrial conduction delay for the occurrence of AF (recurrence plus first diagnosed) in post-ablation PSVT patients. ROC curve analysis demonstrated that intra-atrial conduction delay $ 4.450 msec (with the sensitivity and specificity of 91% and 42%, respectively) and inter-atrial conduction delay $ 20.650 msec (with the sensitivity and specificity of 81% and 80%, respectively) were the most powerful predictive factor of AF (together with recurrence and first diagnosed, p , 0.05). After excluding factors such as diabetes mellitus, body mass index $ 25 kg/m, thyroid dysfunction, toxic abuse (alcohol, caffeine and nicotine) and hypertension, the binary logistic regression analysis showed that intra- and inter-atrial conduction delay were the significant predictors for the occurrence of AF (OR 5 13.577, 95% CI, 3.469–48.914; OR 5 2.569, 95% CI, 1.909–3.459, p , 0.05, respectively). Thus atrial conduction delay can be regarded as a clinical predictor of AF for post-ablation PSVT patients who are at high risk of AF. PSVT patients with high atrial conduction delay, which can be detected by the pre-ablation echocardiography examination, should be paid great attention. A 24-h Holter recording should be taken regularly and routinely to improve the detection of AF. Anti-atrial remodeling measures, such as angiotensin-converting enzyme inhibitors, aldosterone antagonists, statins and Omega-3 fatty acid, should be taken for the prevention and treatment of AF with high prevalence after successful PSVT ablation and reducing AF related cardiovascular morbidity and mortality. Study limitations There are several limitations of this study. First, all patients were evaluated by 24-h Holter monitoring. Inevitable initiation of paroxysmal AF may have been underestimated. Second, the measurements for intra- and inter-atrial conduction delay in this study were done manually with commonly less reliability and repeatability, although three measurements were performed at each time interval to reduce errors. Third, the protocol did not include measurements of atrium volumes, atrial area and dimensions indexed by body surface area. Therefore, it was not sufficient to explain the relationship
Atrial conduction delay predicts AF in PSVT patients d Z.-X. XU et al.
between the atrial conduction delay and the shape of atrium. Finally, AVRT and AVNRT patients were considered together in this study, but the effects of atrial remodeling and atrial vulnerability may differ (Chang et al. 2008). CONCLUSION The intra-atrial conduction delay $4.45 and interatrial conduction delay $20.65 could effectively predict AF in post-ablation PSVT patients. Acknowledgments—This study was sponsored by the Natural Science Foundation of China (81270238) and the Scientific Research Foundation for the Doctoral Degree, State Education Ministry of China (20100131110059).
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