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Diagnostic and Prognostic Value of Electrophysiologic Study in Patients With Nondocumented Palpitations
Diagnostic and Prognostic Value of Electrophysiologic Study in Patients With Nondocumented Palpitations Ermengol Vallès, MD*, Julio Martí-Almor, MD, PhD, Victor Bazan, MD, PhD, Fabiola Suarez, MD, Debora Cian, MD, Laura Portillo, MD, and Jordi Bruguera-Cortada, MD The 12-lead electrocardiogram helps to define the arrhythmic mechanism in patients with palpitations. However, in the setting of nondocumented palpitations the value of the electrophysiologic study (EPS) needs additional investigation. We investigated the utility of the EPS in patients with nondocumented palpitations. A total of 172 patients with normal electrocardiographic findings and nondocumented palpitations underwent an EPS. The clinical and electrophysiologic characteristics were assessed. The symptoms were longlasting (>5 minutes) in 56%. Sudden onset was present in 99%, and termination was rapid in 65%. Neck palpitations were reported in 36%. The EPS findings were normal in 86 patients (50%); atrioventricular nodal reentrant tachycardia was induced in 43, orthodromic reentrant tachycardia in 9, and nonsustained atrial tachycardia/fibrillation (AT/AF) in 34. Long-lasting episodes, sudden termination, and neck palpitations predicted positive EPS findings and were associated with reentrant supraventricular tachycardia (p <0.001). The induction of AT/AF was associated with age >50 years and structural heart disease (p <0.001). After 53 ⴞ 36 months of follow-up, 92% of patients with negative EPS findings were symptom free. Only 32% of patients with induced AT/AF remained free of symptoms (p <0.001). The recurrence of palpitations was more prevalent among patients with structural heart disease and aged >50 years (p <0.001). In conclusion, 50% of patients with nondocumented palpitations had positive EPS findings. A long duration, sudden termination, and neck palpitations, together with structural heart disease and age >50 years, predicted tachycardia inducibility and recurrence and could help in selecting patients suitable for EPS and ablation. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1333–1337) The long-term prognosis of patients with nondocumented palpitations has not been widely assessed. Both the clinical baseline characteristics and the results of the electrophysiologic study (EPS) can predict the long-term outcome of this population. The identification of clinical and/or EPS predictors of palpitation recurrence would help improve the treatment of these patients by improving their quality of life and, in some cases, survival. The purpose of the present study was to search for clinical pretest predictors of tachycardia induction during the EPS and to identify the clinical and EPS predictors of long-term recurrence. Methods Patients undergoing an EPS for nondocumented palpitations were considered for inclusion in the present prospective study. All patients provided written informed consent in accordance with institutional guidelines of the Hospital del Mar in Barcelona, Spain.
From the Electrophysiology Division, Department of Cardiology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain. Manuscript received November 9, 2010; manuscript received and accepted December 31, 2010. *Corresponding author: Tel: (⫹34) 66-643-7038; fax: (⫹34) 93-2483489. E-mail address: [email protected] (E. Vallès). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.12.047
From January 2000 to December 2009, 172 consecutive patients with normal baseline electrocardiographic findings who had presented with sustained palpitations in the emergency room were referred to the Electrophysiology Unit. The patients were considered candidates for a comprehensive EPS if they had ⱖ2 of the 4 following clinical criteria: long-lasting palpitations (⬎5 minutes), sudden onset, sudden termination, and neck palpitations. In all patients, the documentation of the tachycardia was not obtained in the emergency room, nor after a systematic and extensive noninvasive evaluation, including 24-hour Holter monitoring in all patients, stress testing in 40%, and, in some cases, 7-day Holter monitoring. If sustained tachycardia was observed during noninvasive testing, the patient was excluded from the present study and underwent EPS/ablation if considered appropriate. All patients included had presented with palpitations of ⱖ5 seconds in duration (not suggesting isolate premature depolarizations) and were submitted to a specific questionnaire in the search for the clinical characteristics of the palpitations. Transthoracic echocardiography was performed in all patients to identify the presence of underlying structural heart disease (SHD). A comprehensive EPS was performed using standard techniques. Quadripolar electrode catheters were positioned in the high right atrium for registration and atrial stimulation and in the right ventricular septum for His registration and ventricular/para-hisian stimulation.1 An octopolar electrode catheter was positioned into the coronary sinus for left atrial registration, if deemed necessary. At least 3 electrocardiowww.ajconline.org
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graphic leads and intracardiac electrograms were recorded and stored on the Bard (C.R. Bard, Lowell, Massachusetts) recording system. Bipolar intracardiac electrograms were filtered at 30 to 500 kHz and recorded from each electrode pair at a speed of 100 mm/s. The study protocol included programmed atrial stimulation with ⱕ3 extrastimuli and burst pacing. If tachycardia was not induced under basal conditions, the protocol was repeated after infusion of isoproterenol to ⱕ3 g/kg/min. Patients with SHD also underwent programmed ventricular stimulation with ⱕ3 extrastimuli. The diagnosis of orthodromic reentrant tachycardia using a retrograde accessory pathway and typical atrioventricular nodal reentrant tachycardia (AVNRT) were made according to the VA interval, tachycardia entrainment maneuvers from the right ventricle/His catheter,1,2 and the response to premature ventricular depolarization occurring when the His bundle was refractory.3 The diagnosis of atypical AVNRT was made according to the VA interval, earliest retrograde atrial activation site, VA linking, and response to entrainment of the tachycardia from the right ventricle/His catheter. The diagnosis of atrial tachycardia was made when a “VAAV” response to ventricular stimulation during tachycardia4 or the lack of VA linking was demonstrated. Induced runs of nonsustained atypical atrial flutter were considered in the group of induced nonsustained atrial tachycardia/fibrillation (AT/AF). The results of the EPS were considered positive on the induction of sustained supraventricular tachycardia (SVT), including AVNRT, orthodromic reentrant tachycardia, AT/ AF, and ventricular tachycardia or fibrillation. The EPS findings were also considered positive on the induction of short runs of nonsustained (⬎3 beats, ⬍30 seconds) tachycardia if the patients identified those runs as their clinical palpitations. Patients with induced sustained arrhythmias were proposed for catheter ablative therapy. For the patients with induced AT/AF and those with induced nonsustained tachycardia, ablation was not indicated, because pharmacologic therapy had not yet been attempted. This was independent of whether the patients had identified tachycardia as their clinical palpitations. The patients were followed up for the assessment of clinical recurrences. Clinical assessments were made by direct or telephone interviews at 3 and 6 months and subsequently every 12 months in all patients. This was independent of the EPS results. The following clinical and electrophysiologic characteristics were included and analyzed as predictors for positive EPS findings and/or clinical recurrences of the palpitations during follow-up: age, gender, sudden onset and termination of tachycardia, tachycardia duration of ⱖ5 minutes, neck palpitations, presence of SHD, previous attempt at ablation of any tachycardia, and type of arrhythmia induced during the EPS. The categorical variables were compared using a chisquare test. Continuous variables (expressed as the mean ⫾ SD) were compared using an unpaired Student’s t test (normal distribution). The predictors found during follow-up were evaluated using a Kaplan-Meier analysis. p Values ⱕ0.05 were considered statistically significant.
Table 1 Population characteristics (n ⫽ 172) Characteristic Age (years) Gender Male Female Heart disease Previous ablation Palpitation duration (min) ⬍1 1–5 ⬎5 Sudden onset Sudden termination Neck palpitations
Value 46 ⫾ 18 132 (77%) 40 (23%) 21 (12%) 10 (6%) 17 (10%) 58 (34%) 97 (56%) 171 (99%) 112 (65%) 61 (35%)
Data are presented as mean ⫾ SD or n (%).
Results A total of 172 patients fitting the inclusion criteria underwent a comprehensive EPS. The baseline main clinical characteristics of the population are listed in Table 1. None of the patients with a previous ablation procedure (AVNRT in 5 patients, orthodromic reentrant tachycardia in 4 patients, and typical atrial flutter in 1 patient) had the index arrhythmia reinduced during the EPS. Of the 21 patients with SHD, 11 had hypertensive cardiomyopathy, 6 had ischemic cardiomyopathy, 2 had valvular disease, and 2 had idiopathic cardiomyopathy. Only 1 of the 21 patients with SHD had a diminished left ventricular ejection fraction (left ventricular ejection fraction ⬍50%). A total of 86 patients (50%) had normal EPS findings and 86 patients (50%) had inducible SVT. AVNRT was induced in 43 patients (25%). Orthodromic reentrant tachycardia using a concealed accessory pathway was induced in 9 patients (5%). Nonsustained runs of AT/AF identified by the patient as their clinical palpitations were observed in 34 patients (20%). Nonsustained runs of ventricular tachycardia or fibrillation (maximum of 6 beats) were observed in 14 patients; however, none associated it with their clinical symptoms. No complications related to the procedure were seen in our series. The analysis of the clinical and palpitation characteristics predicting positive EPS findings is summarized in Table 2. The duration of episodes of ⱖ5 minutes predicted positive EPS findings with a sensitivity of 77% and specificity of 71% (p ⬍0.001) and also predicted the induction of reentrant SVT (AVNRT or orthodromic reentrant tachycardia) with a sensitivity of 92% and specificity of 60%. Sudden onset was not associated with tachycardia induction. In contrast, sudden termination predicted positive EPS findings with a sensitivity of 79% and specificity of 55% (p ⬍0.001) and the induction of reentrant SVT with a sensitivity of 96% and specificity of 48%. Neck palpitations were associated with positive EPS findings, with a sensitivity of 44% and specificity of 77% (p ⬍0.001) and with reentrant SVT induction with a sensitivity of 71% and specificity of 79%. To improve the accuracy of the statistically significant predictors for reentrant SVT induction, we considered the association of the best 2 individual predictors for both AVNRT and
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Table 2 Predictors for tachycardia induction Variable Age (years) Gender Male Female Duration (min) ⬍5 ⬎5 Sudden onset Sudden termination Neck palpitations Structural heart disease Previous ablation
Total (n ⫽ 172)
No Induction (n ⫽ 86)
Reentrant SVT (n ⫽ 52)
AT/AF (n ⫽ 34)
p Value
46 ⫾ 18
44 ⫾ 17
38 ⫾ 15
62 ⫾ 14
⬍0.001* 0.17
23% 77%
29% 71%
19% 81%
15% 85%
44% 56% 99% 65% 35% 12% 6%
66% 34% 99% 47% 23% 4% 8%
8% 92% 100% 96% 71% 4% 2%
41% 59% 100% 65% 12% 47% 6%
⬍0.001† — ⬍0.001† ⬍0.001† ⬍0.001* 0.38
* Predictor for AT/AF induction. † Predictor for SVT induction.
SVT plus ablation No inducible Induction of AT/AF
%
months
Age <50 years Age >50 years
%
months
SHD No SHD
%
months
Figure 1. Predictors for clinical recurrence. Kaplan-Meier analysis of freedom for recurrence in relation to (Top) results of EPS, (Middle) patient age, and (Bottom) presence of SHD. Induction of AT/AF during EPS, age ⬎50 years, and presence of SHD were associated with increased risk of recurrence during long-term follow up.
orthodromic reentrant tachycardia. The combination of sudden termination of tachycardia and the presence of longlasting palpitations increased the accuracy for predicting reentrant SVT, with a sensitivity of 90% and specificity of 76%. Neither age nor gender predicted tachycardia inducibility during the EPS. However, when considering specific tachycardias individually, age ⬎50 years was associated with induction of AT/AF, with a sensitivity of 73% and specificity of 67% (p ⬍0.001). The presence of SHD was
not associated with positive EPS findings but did predict the induction of AT/AF, with a sensitivity of 48% and specificity of 96% (p ⬍0.001). The patients were followed up for 53 ⫾ 36 months. Among the 86 patients with negative EPS results, 79 (92%) remained symptom free. Significant differences were observed when comparing these patients with those with AT/AF induction during the EPS, only 32% of whom remained symptom free during the follow-up period (p ⬍0.001).
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None of the differences with the other subgroups were statistically significant. The patients with induced nonsustained runs of AT/AF were not considered suitable for ablative therapy owing to the short duration of the arrhythmia and the absence of previous antiarrhythmic drug therapy. Antiarrhythmic drugs (amiodarone or flecainide in ⬎95% of cases) and antithrombotic therapy for the prevention of eventual arrhythmic relapses and potential embolic events were initiated instead. All 52 patients with induced reentrant SVT (30%) underwent radiofrequency ablation. Two patients with AVNRT had relapses after the procedure, requiring a second ablation. Ultimately, radiofrequency ablation was successful in 100% of cases without any clinical recurrences at long-term follow-up. Figure 1 shows the Kaplan-Meier analysis identifying the predictors of recurrence. Age ⬎50 years and the presence of SHD remained as independent predictors on multivariate analysis. Discussion The relation between certain clinical variables and the presence of specific arrhythmias5 is well known. The results from the present study have demonstrated that the EPS is a feasible and safe alternative for the treatment of patients with nondocumented palpitations and normal electrocardiographic findings at baseline. The clinical predictors of tachycardia inducibility during EPS are easily identifiable, including a duration of palpitations ⬎5 minutes, sudden termination, and neck palpitations. These results suggest that the EPS is especially indicated when sudden termination and long-lasting palpitations are present together. When merging these 2 predictors, excellent sensitivity (ⱖ90%) and good specificity (ⱖ75%) for predicting reentrant SVT induction was observed. When considering each of the predictors individually, limited specificity was obtained. The presence of neck palpitations showed good accuracy for predicting reentrant SVT, likely because of to its strong association with AVNRT, which was much more frequent than orthodromic reentrant tachycardia in our population. Both age ⬎50 years and the presence of underlying SHD were predictors of AT/AF induction during the EPS. These results suggest that in this subset of patients, the EPS might indicate the need for antiarrhythmic drugs and antithrombotic therapy for the prevention of eventual arrhythmic relapses and potential embolic events. Implanting loop-recording systems were introduced by Babikar et al6 and, overall, had a diagnostic yield in ⬍35% of the patients. Giada et al7 reported better results but needed an average of 279 days to reach the diagnosis, which could have been overestimated because the implanting loop-recording systems reported both clinical and nonclinical events. Brembilla-Perrot et al8 highlighted the utility of the transesophageal EPS for stimulation to induce the arrhythmia. We recommend the EPS in patients fulfilling ⱖ2 of the 4 clinical criteria we reported, even when no arrhythmias have been reported by previous tests. We believe the finding of a 50% tachycardia inducibility during the EPS justifies such an approach in this selected population. Furthermore, 30% of patients had reentrant SVT induced and underwent successful ablative therapy. Also, 20% of patients had
AT/AF induced, and, in many cases, pharmacologic management was initiated according to the EPS results. The remaining 50% of patients had negative EPS findings, allowing rapid hospital discharge. During the long-term follow-up period, all patients with induced reentrant SVT remained symptom free after ablation. Furthermore, the vast majority (92%) of patients with negative EPS findings had no additional palpitation recurrences, some of them with -blocker treatment. There are several possible explanations for this phenomenon. First, a possible “placebo effect” of the EPS itself can not be ruled out. Second, for those patients in whom sinus tachycardia was established as the suspected cause of the patient’s palpitations, the potential use of a  blocker after negative EPS findings (which was indicated in an undetermined percentage of this subpopulation) also might have influenced this outcome. Finally, and mainly for those patients with sudden onset palpitations, the educational role of demonstrating atrial rapid pacing during the EPS as reproducing the clinical symptoms from likely nonsustained runs of AT might have been helpful to reduce the patients’ anxiety. Only 32% of patients with AT/AF induced were free of long-term recurrences, suggesting that this group should undergo close follow-up because antiarrhythmic and, especially, anticoagulant management are of special concern. The decision for eventual ablative therapy in these patients should be undertaken on the basis of the observation of sustained AT/AF during follow-up. We have concluded that the EPS effectively and safely differentiates a population with nondocumented palpitations into 2 groups: any EPS result, with the exception of AT/AF induction, will be an excellent predictor of a good prognosis with 95% symptom free during long-term follow-up. In contrast, AT/AF induction is a predictor of recurrent symptoms, with a 68% relapse rate during long-term follow-up. We found that the presence of SHD and age ⬎50 years were also predictors of recurrence, independent of the EPS results. Our results suggest that young patients (⬍50 years old) without SHD, who present with nondocumented palpitations and with ⱖ2/3 of the described clinical criteria favoring positive EPS findings, will be inducible in most of the cases, with high probabilities of having AVNRT or orthodromic reentrant tachycardia. Also, young patients (⬍50 years old) without SHD and without ⱖ2/3 of the described criteria and patients ⬎50 years old and/or with SHD might be suitable for a conservative approach and close follow-up, with long-term electrocardiographic monitoring techniques, when considered necessary. In these cases, the EPS and, when indicated ablative therapy, should be used as a backup technique. We had pre-established several inclusion criteria suggesting SVT. We also included a population with no or mild SHD in the present study. This might have led to an increase in proportion of positive EPS results (especially of SVT) compared to the total population with palpitations. Ablative therapy was only performed in patients with reentrant SVT induced during the EPS. The rest of the patients with positive EPS findings had nonsustained runs of AT/AF induced and were not considered for ablative therapy. It is unknown whether this conservative approach precluded an additional benefit of ablative therapy in these patients; however, we
Arrhythmias and Conduction Disturbances/Invasive Study in Nondocumented Palpitations
undertook therapeutic approaches in these cases in concordance with current recommendations. Acknowledgment: We express our appreciation for the editing assistance of Roger Fan, MD. 1. Pérez-Rodon J, Bazan V, Bruguera-Cortada J, Mojal-García S, Manresa-Domínguez JM, Martí-Almor J. Entrainment from the para-Hisian region for differentiating atrioventricular node reentrant tachycardia from orthodromic atrioventricular reentrant tachycardia. Europace 2008;10:1205–1211. 2. Michaud GF, Tada H, Chough S, Baker R, Wasmer K, Sticherling C, Oral H, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Differentiation of atypical atrioventricular node re-entrant tachycardia from orthodromic reciprocating tachycardia using a septal accessory pathway by the response to ventricular pacing. J Am Coll Cardiol 2001;38:1163–1167. 3. Miles WM, Yee R, Klein GJ, Zipes DP, Prystowsky EN. The preexcitation index: an aid in determining the mechanism of supraventricular tachycardia and localizing accessory pathways. Circulation 1986;74: 493–500.
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4. Knight BP, Zivin A, Souza J, Flemming M, Pelosi F, Goyal R, Man C, Strickberger SA, Morady F. A technique for the rapid diagnosis of atrial tachycardia in the electrophysiology laboratory. J Am Coll Cardiol 1999;33:775–781. 5. González-Torrecilla E, Almendral J, Arenal A, Atienza F, Atea L, Del Castillo S, Fernández-Avilés F. Combined evaluation of bedside clinical variables and the electrocardiogram for the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation. J Am Coll Cardiol 2009;53:2353–2358. 6. Babikar A, Hynes B, Ward N, Oslizok P, Walsh K, Keane D. A retrospective study of the clinical experience of the implantable loop recorder in a paediatric setting. Int J Clin Pract 2008;62:1520 –1525. 7. Giada F, Gulizia M, Francese M, Croci F, Santangelo L, Santomauro M, Occhetta E, Menozzi C, Raviele A. Recurrent unexplained palpitations (RUP) study comparison of implantable loop recorder versus conventional diagnostic strategy. J Am Coll Cardiol 2007;49:1951–1956. 8. Brembilla-Perrot B, Groben L, Chometon F, Lethor JP, Admant P, Cloez JL, Popescu I, Marchal C, Cedano J, Abdelaal A, Huttin O, Tatar C, Benzaghou N, Azman B, Terrier De La Chaise A, Marçon F. Rapid and low-cost method to prove the nature of no documented tachycardia in children and teenagers without pre-excitation syndrome. Europace 2009;11:1083–1089.
From the Electrophysiology Division, Department of Cardiology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain. Manuscript received November 9, 2010; manuscript received and accepted December 31, 2010. *Corresponding author: Tel: (⫹34) 66-643-7038; fax: (⫹34) 93-2483489. E-mail address: [email protected] (E. Vallès). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.12.047
From January 2000 to December 2009, 172 consecutive patients with normal baseline electrocardiographic findings who had presented with sustained palpitations in the emergency room were referred to the Electrophysiology Unit. The patients were considered candidates for a comprehensive EPS if they had ⱖ2 of the 4 following clinical criteria: long-lasting palpitations (⬎5 minutes), sudden onset, sudden termination, and neck palpitations. In all patients, the documentation of the tachycardia was not obtained in the emergency room, nor after a systematic and extensive noninvasive evaluation, including 24-hour Holter monitoring in all patients, stress testing in 40%, and, in some cases, 7-day Holter monitoring. If sustained tachycardia was observed during noninvasive testing, the patient was excluded from the present study and underwent EPS/ablation if considered appropriate. All patients included had presented with palpitations of ⱖ5 seconds in duration (not suggesting isolate premature depolarizations) and were submitted to a specific questionnaire in the search for the clinical characteristics of the palpitations. Transthoracic echocardiography was performed in all patients to identify the presence of underlying structural heart disease (SHD). A comprehensive EPS was performed using standard techniques. Quadripolar electrode catheters were positioned in the high right atrium for registration and atrial stimulation and in the right ventricular septum for His registration and ventricular/para-hisian stimulation.1 An octopolar electrode catheter was positioned into the coronary sinus for left atrial registration, if deemed necessary. At least 3 electrocardiowww.ajconline.org
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graphic leads and intracardiac electrograms were recorded and stored on the Bard (C.R. Bard, Lowell, Massachusetts) recording system. Bipolar intracardiac electrograms were filtered at 30 to 500 kHz and recorded from each electrode pair at a speed of 100 mm/s. The study protocol included programmed atrial stimulation with ⱕ3 extrastimuli and burst pacing. If tachycardia was not induced under basal conditions, the protocol was repeated after infusion of isoproterenol to ⱕ3 g/kg/min. Patients with SHD also underwent programmed ventricular stimulation with ⱕ3 extrastimuli. The diagnosis of orthodromic reentrant tachycardia using a retrograde accessory pathway and typical atrioventricular nodal reentrant tachycardia (AVNRT) were made according to the VA interval, tachycardia entrainment maneuvers from the right ventricle/His catheter,1,2 and the response to premature ventricular depolarization occurring when the His bundle was refractory.3 The diagnosis of atypical AVNRT was made according to the VA interval, earliest retrograde atrial activation site, VA linking, and response to entrainment of the tachycardia from the right ventricle/His catheter. The diagnosis of atrial tachycardia was made when a “VAAV” response to ventricular stimulation during tachycardia4 or the lack of VA linking was demonstrated. Induced runs of nonsustained atypical atrial flutter were considered in the group of induced nonsustained atrial tachycardia/fibrillation (AT/AF). The results of the EPS were considered positive on the induction of sustained supraventricular tachycardia (SVT), including AVNRT, orthodromic reentrant tachycardia, AT/ AF, and ventricular tachycardia or fibrillation. The EPS findings were also considered positive on the induction of short runs of nonsustained (⬎3 beats, ⬍30 seconds) tachycardia if the patients identified those runs as their clinical palpitations. Patients with induced sustained arrhythmias were proposed for catheter ablative therapy. For the patients with induced AT/AF and those with induced nonsustained tachycardia, ablation was not indicated, because pharmacologic therapy had not yet been attempted. This was independent of whether the patients had identified tachycardia as their clinical palpitations. The patients were followed up for the assessment of clinical recurrences. Clinical assessments were made by direct or telephone interviews at 3 and 6 months and subsequently every 12 months in all patients. This was independent of the EPS results. The following clinical and electrophysiologic characteristics were included and analyzed as predictors for positive EPS findings and/or clinical recurrences of the palpitations during follow-up: age, gender, sudden onset and termination of tachycardia, tachycardia duration of ⱖ5 minutes, neck palpitations, presence of SHD, previous attempt at ablation of any tachycardia, and type of arrhythmia induced during the EPS. The categorical variables were compared using a chisquare test. Continuous variables (expressed as the mean ⫾ SD) were compared using an unpaired Student’s t test (normal distribution). The predictors found during follow-up were evaluated using a Kaplan-Meier analysis. p Values ⱕ0.05 were considered statistically significant.
Table 1 Population characteristics (n ⫽ 172) Characteristic Age (years) Gender Male Female Heart disease Previous ablation Palpitation duration (min) ⬍1 1–5 ⬎5 Sudden onset Sudden termination Neck palpitations
Value 46 ⫾ 18 132 (77%) 40 (23%) 21 (12%) 10 (6%) 17 (10%) 58 (34%) 97 (56%) 171 (99%) 112 (65%) 61 (35%)
Data are presented as mean ⫾ SD or n (%).
Results A total of 172 patients fitting the inclusion criteria underwent a comprehensive EPS. The baseline main clinical characteristics of the population are listed in Table 1. None of the patients with a previous ablation procedure (AVNRT in 5 patients, orthodromic reentrant tachycardia in 4 patients, and typical atrial flutter in 1 patient) had the index arrhythmia reinduced during the EPS. Of the 21 patients with SHD, 11 had hypertensive cardiomyopathy, 6 had ischemic cardiomyopathy, 2 had valvular disease, and 2 had idiopathic cardiomyopathy. Only 1 of the 21 patients with SHD had a diminished left ventricular ejection fraction (left ventricular ejection fraction ⬍50%). A total of 86 patients (50%) had normal EPS findings and 86 patients (50%) had inducible SVT. AVNRT was induced in 43 patients (25%). Orthodromic reentrant tachycardia using a concealed accessory pathway was induced in 9 patients (5%). Nonsustained runs of AT/AF identified by the patient as their clinical palpitations were observed in 34 patients (20%). Nonsustained runs of ventricular tachycardia or fibrillation (maximum of 6 beats) were observed in 14 patients; however, none associated it with their clinical symptoms. No complications related to the procedure were seen in our series. The analysis of the clinical and palpitation characteristics predicting positive EPS findings is summarized in Table 2. The duration of episodes of ⱖ5 minutes predicted positive EPS findings with a sensitivity of 77% and specificity of 71% (p ⬍0.001) and also predicted the induction of reentrant SVT (AVNRT or orthodromic reentrant tachycardia) with a sensitivity of 92% and specificity of 60%. Sudden onset was not associated with tachycardia induction. In contrast, sudden termination predicted positive EPS findings with a sensitivity of 79% and specificity of 55% (p ⬍0.001) and the induction of reentrant SVT with a sensitivity of 96% and specificity of 48%. Neck palpitations were associated with positive EPS findings, with a sensitivity of 44% and specificity of 77% (p ⬍0.001) and with reentrant SVT induction with a sensitivity of 71% and specificity of 79%. To improve the accuracy of the statistically significant predictors for reentrant SVT induction, we considered the association of the best 2 individual predictors for both AVNRT and
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Table 2 Predictors for tachycardia induction Variable Age (years) Gender Male Female Duration (min) ⬍5 ⬎5 Sudden onset Sudden termination Neck palpitations Structural heart disease Previous ablation
Total (n ⫽ 172)
No Induction (n ⫽ 86)
Reentrant SVT (n ⫽ 52)
AT/AF (n ⫽ 34)
p Value
46 ⫾ 18
44 ⫾ 17
38 ⫾ 15
62 ⫾ 14
⬍0.001* 0.17
23% 77%
29% 71%
19% 81%
15% 85%
44% 56% 99% 65% 35% 12% 6%
66% 34% 99% 47% 23% 4% 8%
8% 92% 100% 96% 71% 4% 2%
41% 59% 100% 65% 12% 47% 6%
⬍0.001† — ⬍0.001† ⬍0.001† ⬍0.001* 0.38
* Predictor for AT/AF induction. † Predictor for SVT induction.
SVT plus ablation No inducible Induction of AT/AF
%
months
Age <50 years Age >50 years
%
months
SHD No SHD
%
months
Figure 1. Predictors for clinical recurrence. Kaplan-Meier analysis of freedom for recurrence in relation to (Top) results of EPS, (Middle) patient age, and (Bottom) presence of SHD. Induction of AT/AF during EPS, age ⬎50 years, and presence of SHD were associated with increased risk of recurrence during long-term follow up.
orthodromic reentrant tachycardia. The combination of sudden termination of tachycardia and the presence of longlasting palpitations increased the accuracy for predicting reentrant SVT, with a sensitivity of 90% and specificity of 76%. Neither age nor gender predicted tachycardia inducibility during the EPS. However, when considering specific tachycardias individually, age ⬎50 years was associated with induction of AT/AF, with a sensitivity of 73% and specificity of 67% (p ⬍0.001). The presence of SHD was
not associated with positive EPS findings but did predict the induction of AT/AF, with a sensitivity of 48% and specificity of 96% (p ⬍0.001). The patients were followed up for 53 ⫾ 36 months. Among the 86 patients with negative EPS results, 79 (92%) remained symptom free. Significant differences were observed when comparing these patients with those with AT/AF induction during the EPS, only 32% of whom remained symptom free during the follow-up period (p ⬍0.001).
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None of the differences with the other subgroups were statistically significant. The patients with induced nonsustained runs of AT/AF were not considered suitable for ablative therapy owing to the short duration of the arrhythmia and the absence of previous antiarrhythmic drug therapy. Antiarrhythmic drugs (amiodarone or flecainide in ⬎95% of cases) and antithrombotic therapy for the prevention of eventual arrhythmic relapses and potential embolic events were initiated instead. All 52 patients with induced reentrant SVT (30%) underwent radiofrequency ablation. Two patients with AVNRT had relapses after the procedure, requiring a second ablation. Ultimately, radiofrequency ablation was successful in 100% of cases without any clinical recurrences at long-term follow-up. Figure 1 shows the Kaplan-Meier analysis identifying the predictors of recurrence. Age ⬎50 years and the presence of SHD remained as independent predictors on multivariate analysis. Discussion The relation between certain clinical variables and the presence of specific arrhythmias5 is well known. The results from the present study have demonstrated that the EPS is a feasible and safe alternative for the treatment of patients with nondocumented palpitations and normal electrocardiographic findings at baseline. The clinical predictors of tachycardia inducibility during EPS are easily identifiable, including a duration of palpitations ⬎5 minutes, sudden termination, and neck palpitations. These results suggest that the EPS is especially indicated when sudden termination and long-lasting palpitations are present together. When merging these 2 predictors, excellent sensitivity (ⱖ90%) and good specificity (ⱖ75%) for predicting reentrant SVT induction was observed. When considering each of the predictors individually, limited specificity was obtained. The presence of neck palpitations showed good accuracy for predicting reentrant SVT, likely because of to its strong association with AVNRT, which was much more frequent than orthodromic reentrant tachycardia in our population. Both age ⬎50 years and the presence of underlying SHD were predictors of AT/AF induction during the EPS. These results suggest that in this subset of patients, the EPS might indicate the need for antiarrhythmic drugs and antithrombotic therapy for the prevention of eventual arrhythmic relapses and potential embolic events. Implanting loop-recording systems were introduced by Babikar et al6 and, overall, had a diagnostic yield in ⬍35% of the patients. Giada et al7 reported better results but needed an average of 279 days to reach the diagnosis, which could have been overestimated because the implanting loop-recording systems reported both clinical and nonclinical events. Brembilla-Perrot et al8 highlighted the utility of the transesophageal EPS for stimulation to induce the arrhythmia. We recommend the EPS in patients fulfilling ⱖ2 of the 4 clinical criteria we reported, even when no arrhythmias have been reported by previous tests. We believe the finding of a 50% tachycardia inducibility during the EPS justifies such an approach in this selected population. Furthermore, 30% of patients had reentrant SVT induced and underwent successful ablative therapy. Also, 20% of patients had
AT/AF induced, and, in many cases, pharmacologic management was initiated according to the EPS results. The remaining 50% of patients had negative EPS findings, allowing rapid hospital discharge. During the long-term follow-up period, all patients with induced reentrant SVT remained symptom free after ablation. Furthermore, the vast majority (92%) of patients with negative EPS findings had no additional palpitation recurrences, some of them with -blocker treatment. There are several possible explanations for this phenomenon. First, a possible “placebo effect” of the EPS itself can not be ruled out. Second, for those patients in whom sinus tachycardia was established as the suspected cause of the patient’s palpitations, the potential use of a  blocker after negative EPS findings (which was indicated in an undetermined percentage of this subpopulation) also might have influenced this outcome. Finally, and mainly for those patients with sudden onset palpitations, the educational role of demonstrating atrial rapid pacing during the EPS as reproducing the clinical symptoms from likely nonsustained runs of AT might have been helpful to reduce the patients’ anxiety. Only 32% of patients with AT/AF induced were free of long-term recurrences, suggesting that this group should undergo close follow-up because antiarrhythmic and, especially, anticoagulant management are of special concern. The decision for eventual ablative therapy in these patients should be undertaken on the basis of the observation of sustained AT/AF during follow-up. We have concluded that the EPS effectively and safely differentiates a population with nondocumented palpitations into 2 groups: any EPS result, with the exception of AT/AF induction, will be an excellent predictor of a good prognosis with 95% symptom free during long-term follow-up. In contrast, AT/AF induction is a predictor of recurrent symptoms, with a 68% relapse rate during long-term follow-up. We found that the presence of SHD and age ⬎50 years were also predictors of recurrence, independent of the EPS results. Our results suggest that young patients (⬍50 years old) without SHD, who present with nondocumented palpitations and with ⱖ2/3 of the described clinical criteria favoring positive EPS findings, will be inducible in most of the cases, with high probabilities of having AVNRT or orthodromic reentrant tachycardia. Also, young patients (⬍50 years old) without SHD and without ⱖ2/3 of the described criteria and patients ⬎50 years old and/or with SHD might be suitable for a conservative approach and close follow-up, with long-term electrocardiographic monitoring techniques, when considered necessary. In these cases, the EPS and, when indicated ablative therapy, should be used as a backup technique. We had pre-established several inclusion criteria suggesting SVT. We also included a population with no or mild SHD in the present study. This might have led to an increase in proportion of positive EPS results (especially of SVT) compared to the total population with palpitations. Ablative therapy was only performed in patients with reentrant SVT induced during the EPS. The rest of the patients with positive EPS findings had nonsustained runs of AT/AF induced and were not considered for ablative therapy. It is unknown whether this conservative approach precluded an additional benefit of ablative therapy in these patients; however, we
Arrhythmias and Conduction Disturbances/Invasive Study in Nondocumented Palpitations
undertook therapeutic approaches in these cases in concordance with current recommendations. Acknowledgment: We express our appreciation for the editing assistance of Roger Fan, MD. 1. Pérez-Rodon J, Bazan V, Bruguera-Cortada J, Mojal-García S, Manresa-Domínguez JM, Martí-Almor J. Entrainment from the para-Hisian region for differentiating atrioventricular node reentrant tachycardia from orthodromic atrioventricular reentrant tachycardia. Europace 2008;10:1205–1211. 2. Michaud GF, Tada H, Chough S, Baker R, Wasmer K, Sticherling C, Oral H, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Differentiation of atypical atrioventricular node re-entrant tachycardia from orthodromic reciprocating tachycardia using a septal accessory pathway by the response to ventricular pacing. J Am Coll Cardiol 2001;38:1163–1167. 3. Miles WM, Yee R, Klein GJ, Zipes DP, Prystowsky EN. The preexcitation index: an aid in determining the mechanism of supraventricular tachycardia and localizing accessory pathways. Circulation 1986;74: 493–500.
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4. Knight BP, Zivin A, Souza J, Flemming M, Pelosi F, Goyal R, Man C, Strickberger SA, Morady F. A technique for the rapid diagnosis of atrial tachycardia in the electrophysiology laboratory. J Am Coll Cardiol 1999;33:775–781. 5. González-Torrecilla E, Almendral J, Arenal A, Atienza F, Atea L, Del Castillo S, Fernández-Avilés F. Combined evaluation of bedside clinical variables and the electrocardiogram for the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation. J Am Coll Cardiol 2009;53:2353–2358. 6. Babikar A, Hynes B, Ward N, Oslizok P, Walsh K, Keane D. A retrospective study of the clinical experience of the implantable loop recorder in a paediatric setting. Int J Clin Pract 2008;62:1520 –1525. 7. Giada F, Gulizia M, Francese M, Croci F, Santangelo L, Santomauro M, Occhetta E, Menozzi C, Raviele A. Recurrent unexplained palpitations (RUP) study comparison of implantable loop recorder versus conventional diagnostic strategy. J Am Coll Cardiol 2007;49:1951–1956. 8. Brembilla-Perrot B, Groben L, Chometon F, Lethor JP, Admant P, Cloez JL, Popescu I, Marchal C, Cedano J, Abdelaal A, Huttin O, Tatar C, Benzaghou N, Azman B, Terrier De La Chaise A, Marçon F. Rapid and low-cost method to prove the nature of no documented tachycardia in children and teenagers without pre-excitation syndrome. Europace 2009;11:1083–1089.