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AV nodal reentrant tachycardia or AV reentrant tachycardia using a concealed bypass tract-related adverse events
International Journal of Cardiology 199 (2015) 84–89
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AV nodal reentrant tachycardia or AV reentrant tachycardia using a concealed bypass tract-related adverse events Béatrice Brembilla-Perrot a,⁎, Maxime Bénichou a, Alice Brembilla b, Erwan Bozec c, Sarah Dorlet a, Jean Marc Sellal a, Arnaud Olivier a, Vladimir Manenti a, Thibaut Villemin a, Daniel Beurrier a, Anne Moulin-Zinsch a, Christian De Chillou a, Nicolas Girerd c a b c
Department of Cardiology, University Hospital of Brabois, Vandoeuvre, France Epidemiology, CHU de Besançon, France INSERM, Centre d'Investigations Cliniques 9501, Université de Lorraine, Institut Lorrain du cœur et des vaisseaux, CHU de Nancy, Nancy, France
a r t i c l e
i n f o
Article history: Received 13 April 2015 Received in revised form 26 May 2015 Accepted 10 July 2015 Available online xxxx Keywords: Supraventricular tachycardia Adverse events Antiarrhythmic drug Ablation
a b s t r a c t Objectives: To jointly study paroxysmal supraventricular tachycardia (SVT)-related adverse events (AE) and ablation-related complications, with specific emphasis on the predictors of SVT-related AE as well as their significance by investigating their association with long-term mortality. Methods: 1770 patients were included, aged 6 to 97, with either atrioventricular nodal reentrant tachycardia (AVNRT) or orthodromic atrioventricular reciprocal tachycardia (AVRT) mediated by concealed accessory pathway, consecutively referred for SVT work-up in a tertiary care center. Results: SVT-related AE were identified in 339 patients (19%). Major AEs were identified in 23 patients (1%; 15 cardiac arrests or ventricular arrhythmias requiring cardioversion and 8 hemodynamic collapses). Other AE were related to syncope (n = 236), acute coronary syndrome (n = 57) and heart failure/rhythmic cardiomyopathy (n = 21). In multivariable analysis, higher age, heart disease and requirement of isoproterenol to induce SVT were independently associated with a higher risk for SVT-related AE. During follow-up (2.8 ± 3.0 years), death occurred more frequently in patients with SVT-related AE, especially in patients with major adverse events (p b 0.001). In multivariable analysis, major SVT-related AE remained significantly associated with occurrence of death (HR = 6.72, IC = (2.58–17.52), p b 0.001) independently of age and presence of underlying heart disease. Major SVT-related AE in the whole population referred for SVT were more frequent than immediate major ablation complications in patients undergoing SVT ablation (5/1186 vs. 23/1770, p = 0.02). Conclusions: SVT-related AE are independent predictors of mortality and are more frequent than immediate major ablation complications in patients undergoing SVT ablation. The present findings support systematically performing SVT ablation in patients with SVT-related adverse events. © 2015 Published by Elsevier Ireland Ltd.
What's new? − Supraventricular tachycardia-related adverse events were found to occur in 19% of patients with atrioventricular tachycardia. − Life-threatening adverse events related to supraventricular tachycardia are rare (1%). Yet, our study demonstrates for the first time that major adverse-events are associated with a six-fold increase in the risk for long-term mortality. This higher risk of death suggests that a specific watchful follow-up is needed in these patients, even after successful ablation. − The prevalence of immediate major ablation-related complications is lower than the prevalence of major adverse events related to
⁎ Corresponding author at: CHU of Brabois, 54500 Vandoeuvre Les Nancy, France. E-mail address: [email protected] (B. Brembilla-Perrot).
http://dx.doi.org/10.1016/j.ijcard.2015.07.048 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
supraventricular tachycardia. This novel finding further establishes the favorable benefit-risk ratio of ablation for SVT.
1. Introduction Paroxysmal supraventricular tachycardia (SVT) is a common form of tachycardia [1]. There are approximately 89,000 new cases/year and 570,000 persons with a history of SVT in the United States. SVT is considered to be benign and ablation is required only in symptomatic patients [2]. However, a more conservative approach has been suggested based on the long-term follow-up of a large cohort of atrioventricular nodal reentrant tachycardia (AVNRT) patients who became asymptomatic, none of which had undergone ablation [3]. This approach is also supported by the risk of ablation-related complications.
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Nevertheless, adverse events related to SVT are a relatively frequent cause for emergency department admission [4]. During SVT episodes, symptoms suggestive of myocardial ischemia, including chest pain (31%), ST-segment depression (61%) and elevated troponin levels (12%), are frequently recorded [5]. Major adverse events can also occur, although far less commonly [6,7]. As a result of the risk for SVT-related adverse events and the risk of ablation-related complications, risk to benefit ratio should therefore to be considered when choosing treatment strategy for a patient with SVT. The purpose of the present analysis was to jointly study SVT-related adverse events and ablation-related complications in patients presenting with either AVNRT or orthodromic atrioventricular reciprocal tachycardia (AVRT). The study also aimed to identify the predictors of SVT-related adverse events as well as their clinical significance in comparison with ablation-related complications. 2. Methods 2.1. Study population The present is a retrospective observational study of patients consecutively referred for a regular paroxysmal SVT in a tertiary care center between January 1990 and January 2014. Patients with preexcitation syndrome on ECG and patients with antidromic AV reciprocating tachycardia (AVRT) due anterograde conduction through an accessory pathway were excluded (n = 480). Among these last patients 55 of them had a normal ECG in sinus rhythm and the diagnosis of anterograde conduction over accessory pathway was made at electrophysiological study. Patients in whom atrial arrhythmia was identified during the work-up were also excluded (n = 182). A total of 1770 patients with either AVNRT (N = 1460) or orthodromic AVRT mediated by a concealed accessory pathway (N = 310) were ultimately included. Among these patients, 85 old patients with an initial diagnosis of atrial tachycardia were shown as having AVNRT or orthodromic AVRT mediated by a concealed accessory pathway after an electrophysiologic study. 2.2. Data extraction Clinical data were retrospectively extracted from the patients' medical records. As part of the systematic work-up performed for SVT, patients underwent a standardized clinical evaluation including the accurate determination of prior adverse events. The study was approved by the Commission nationale de l'informatique et des libertés (CNIL). Under French law, no formal IRB approval is required for data extraction from patients' medical records. The prescription of beta-blockers, verapamil and class I antiarrhythmic drugs was not systematically collected in patients without prior SVT-related adverse events during SVT work-up. 2.3. Adverse event definition Adverse events collected during the SVT work-up, i.e. adverse events that occurred prior to or during the work-up, were classified as major (requiring resuscitation) or minor (management changes). Major events were defined as cardiac arrest or documented life-threatening hemodynamically nontolerated arrhythmia, with collapses or syncope and requiring emergency treatment, generally cardioversion. All major adverse events were witnessed and SVT was confirmed as the cause of the major adverse event after careful adjudication. Minor adverse events were defined as events that required patient hospitalization. These included syncope, ischemic coronary event, acute heart failure or other poorly-tolerated event directly related to an SVT episode. These SVT episodes ended spontaneously or after infusion of either verapamil or adenosine triphosphate. Of note, an isolated increase in troponin level was not considered as an adverse event.
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2.4. Electrophysiology laboratory protocol All patients underwent an electrophysiological study as part of the systematic work-up performed for SVT. Electrophysiological studies were performed after signing the clinical informed consent form endorsed by the French Society of Cardiology (Societé Française de Cardiologie). All antiarrhythmic drugs were discontinued at least five half-lives prior to the study. Details of the protocol have been previously described [8–10]. Briefly, atrial pacing and programmed atrial stimulation were systematically performed during sinus rhythm with atrial pacing conducted at two cycle lengths, 600 and 400 ms. Premature stimuli (S2) were delivered after every eighth paced atrial complex with 10 ms decrements until atrial refractoriness was reached. When a supraventricular tachycardia was induced, the protocol was halted. In the absence of tachycardia induction, isoproterenol (0.02 to 1 μg.min−1) was alternatively infused to increase the sinus rate to at least 130 bpm. Atrial pacing was repeated and programmed atrial stimulation was performed at a cycle length of 400 ms. Diagnosis of SVT was confirmed by the electrophysiological study. The mechanism of SVT was determined according to the method of induction, the relation of atrial and ventricular activation at the onset of tachycardia and during tachycardia, the sequence of retrograde atrial activation and, if necessary, the effect of premature extra-stimulus during SVT. The SVT was classified as typical AV nodal reentry within the atrioventricular node (AVNRT) or atypical AVNRT or reentry within a concealed accessory atrioventricular connection (AVRT). In instances of adverse events occurrence or in the case of abnormal clinical examination, echocardiography was systematically performed. Ablation of SVT was performed in most patients, either immediately after the identification of SVT mechanism during the electrophysiological study or during a second procedure. A 7F deflectable catheter with a 4 mm tip electrode was used to perform AVNRT or accessory pathway ablation. In the case of AVNRT, the slow pathway potential was identified, and a radiofrequency current was applied at this level with an energy limit of 40 watts and a temperature limit of 65 °C. Radiofrequency current was immediately halted if junctional rhythm did not appear within 15 s, otherwise it was continued for 60 s. The absence of AVNRT induction after ablation was verified. If still present, application of the radiofrequency current was repeated, a new application of radiofrequency current was performed. When AVNRT remained inducible, anatomically-guided ablation was used. Slow pathway block or singleAV nodal echo beat represented a procedural endpoint. Isoproterenol infusion was systematically used and the protocol repeated to verify the absence of AVNRT re-induction. In the case of AVRT via a concealed accessory pathway, ablation was performed at the earliest atrial retrograde activation either during ventricular pacing or during AVRT. For both AVNRT and AVRT ablation, catheters were removed 20 min after the disappearance of the anterograde conduction over the slow pathway or of the retrograde conduction over the accessory pathway. Ablation-related complications were defined as major if they were life-threatening and required the admission of the patient in intensive care unit or as minor if they regressed without the need of monitoring in intensive care. Complications considered as major were mostly pericardial tamponade requiring emergency drainage, complete AV block requiring pacemaker implantation and death. Complications considered as minor were local bleeding, vagal syncope at femoral puncture, minor pericardial suffusion, transient traumatic or radiofrequency-related second or complete AV block and transient sinus bradycardia. As a general rule, patients with recurrent tachycardias who refused ablation were discharged with beta-blockers.
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2.5. Other tests performed within the SVT work-up An exercise test was performed in patients with exercise-related symptoms and in instances of chest pain, ST-segment depression or elevated troponin levels during SVT. Other invasive studies such as coronary angiography were indicated in the case of a major adverse event. 2.6. Follow-up Patients treated by SVT ablation were discharged without antiarrhythmic medication and were systematically examined by a cardiologist at least one month after ablation. No treatment was indicated for one or 2 episodes of well-tolerated tachycardia. Medical treatment (initially beta-blockers) was only indicated for recurrent tachycardia's when the patient refused the ablation or when the patient was too young for this treatment. The study enabled access to a mean of 2.75 ± 2.7 years of follow-up performed by the referring cardiologist and/or general practitioner. This follow-up was available from medical correspondence contained in the patient's medical record. In addition, information was also collected from patient telephone interviews from 2010 onward, as part of the usual clinical follow-up after SVT ablation. General physicians, patients and occasionally other hospitals were contacted to identify clinical outcome. ECG and 24-hour Holter recordings were performed if the patient reported palpitations or symptoms suspected to be the consequence of SVT occurrence/recurrence. 2.7. Statistical methods Continuous variables are expressed as mean ± SD and were compared using t tests for independent samples. Differences in proportion were compared using a Chi2 test. Logistic regression with presence of adverse events and absence of adverse events were used as outcome variables. Gender and all variables associated with a p-value b 0.20 on univariable logistic regression analysis were entered in the multivariable models. Similar regression was performed with presence of ablation-related complications as dependent variables. Cox models were used to study the factors associated with death during the follow-up. For both logistic and Cox multivariable analysis, backward selection of variables was performed when the number of events was insufficient to enable the introduction of all candidate variables within the models. A p value b 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS package for Windows (version 21, IBM Corp., Armonk, NY, USA). 3. Results Patients were aged from 6 to 97 years (mean age 48 ± 19 years), 59% of whom were women. 3.1. Prevalence and description of SVT-related adverse events Adverse events related to SVT untreated by ablation were identified in 339 patients (19%) during SVT workup. Major adverse events were identified in 23 patients (1%): 15 patients had a cardiac arrest or ventricular arrhythmia requiring cardioversion while 8 patients suffered hemodynamic collapse. Ten patients presented resuscitated cardiac arrest following torsade de pointes complicated by ventricular fibrillation, all of whom were on antiarrhythmic drugs (sotalol, verapamil, disopyramide, digoxin, amiodarone). One patient had a coronary spasm with beta-blockers complicated by ventricular fibrillation. Two patients with underlying cardiopathy (one patient with coronary heart disease and one patient with hypertrophic
cardiomyopathy) had ventricular fibrillation following SVT, thus attributed to SVT. A 16-year-old girl who had only presented one episode of SVT died from asystole after infusion of verapamil followed by digoxin. One 55-year-old patient with respiratory failure refused SVT ablation and died after a prolonged SVT. Hemodynamic collapses occurred in 7 other patients, one being related to verapamil injection in a patient with Wegener's disease. Remaining patients were admitted for SVTrelated cardiogenic shock. In this latter case, cardiogenic shock was attributed to SVT because it occurred several hours after SVT initiation and required emergency treatment (cardioversion in 5 patients and atrial pacing in 2 patients). Three hundred and sixteen patients (18%) had minor SVT adverse events as defined by SVT episodes that required hospitalization in an emergency unit. Minor SVT adverse events were mainly syncope in 236 patients (15%), acute coronary syndrome in 57 patients (3%) which triggered an admission in the intensive coronary care unit, tachycardiomyopathy (n = 12) or stage IV heart failure (n = 9) in 21 patients, inappropriate shock at implantable cardiac defibrillator in one patient and major antiarrhythmic drug-related bradycardia (b30 bpm) in one patient. Within the study population, 230 had increased troponin levels prior to their SVT work-up, of which 44 had a known coronary heart disease. Only 57 of these patients were hospitalized and considered as having an SVT-related adverse event. 3.2. Factors associated with adverse events In univariable analysis, patients with adverse events were older, and were more likely to be female or to have diabetes than patients without adverse events (Table 1). The rate of tachycardia and the prevalence of atrial fibrillation (AF) history did not differ between patients with and without adverse events. SVT mechanism was similar in patients with and without adverse events. Infusion of isoproterenol during the electrophysiological study was more frequently required to induce SVT in patients with adverse events than in patients without adverse events. In multivariable analysis, higher age, heart disease and requirement of isoproterenol infusion during the electrophysiological study to induce SVT during were independently associated with a higher risk for SVT-related adverse events (Table 2). In contrast, the presence of heart disease was the only factor retained when solely considering major SVT-related adverse events (OR = 6.50, CI = (2.83–14.91), p b 0.001). 3.3. Ablation complications SVT ablation was performed in 1186 patients, more frequently in patients without adverse events than in those with adverse events. Most patients with adverse events who did not undergo ablation had refused ablation (N = 31). The indication of ablation was not dependent on the mechanism of SVT (AVNRT or AVRT). Most accessory pathways were left sided comparatively to only an occasional right posteroseptal location. Only one case involved a parahisian location. Ablation complications were as frequent in patients with or without SVT-related adverse events (Table 3). In patients with a history of SVT-related adverse events, two major ablation complications were recorded (Table 3). A 44 year-old male had sudden death 16 days after ablation of a concealed left lateral accessory pathway. This patient had radial artery thrombosis after a coronary angiography performed after a SVT-related coronary syndrome. A second patient underwent pacemaker implantation one year after ablation. Other than these major complications, two other patients had spontaneous infrahisian conduction abnormalities requiring pacemaker implantation. In patients without adverse events, major complications were as follows: 2 deaths occurred 1 to 3 days after ablation in older women referred for recurrent SVTs. One death was due to disseminated
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Table 1 Characteristics of the study population according to the presence or absence of SVT-related adverse events. AE: adverse event, AF: atrial fibrillation; SVT: supraventricular tachycardia; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia. Comparisons were performed with patients without adverse events.
Age (years) Male gender Heart disease Diabetes AF history SVT rate (bpm) AVNRT Typical AVNRT Atypical AVNRT AVRT Isoproterenol required to induce SVT
No AE
Total AE
Major AE
Minor AE
(N = 1431)
(N = 339)
(N = 23)
(N = 316)
47 ± 19 565 (39.5%) 125 (9%) 20 (1%) 51 (3.5%) 187.5 ± 35 1182 (82.5%) 1018 (71%) 164 (11%) 249 (17%) 454 (32%)
53 ± 21⁎⁎⁎ 157 (46%)⁎ 102 (30%)⁎⁎⁎ 13 (4%)⁎⁎
58 ± 20⁎⁎ 9 (39%) 11 (48%)⁎⁎⁎
53 ± 21⁎⁎⁎ 148 (47%)⁎ 91 (29%)⁎⁎⁎ 12 (4%)⁎⁎
11 (3%) 194 ± 134 278 (82%) 245 (72%) 33 (10%) 61 (18%) 141 (42%)⁎⁎⁎
1 (4%) 2 (9%) 183 ± 32 19 (83%) 18 (78%) 1 (4%) 4 (17%) 11 (49%)
9 (3%) 195 ± 138 259 (82%) 227 (72%) 32 (10%) 57 (18%) 130 (41%)⁎⁎
⁎⁎⁎ p b 0.0001. ⁎⁎ p b 0.01. ⁎ p b 0.05.
intravascular coagulation after local bleeding while the other was related to a fatal collapse induced by vasodepressor syncope. Tamponade occurred during the ablation of a concealed left lateral accessory pathway in one woman. Two pacemaker implantations were required after SVT ablation while 2 other implantations were respectively required 6 months and 1 year later in patients without adverse event. A pacemaker was implanted in 5 older patients several years after the ablation although correlation with ablation per se was uncertain. Major SVT-related adverse events in the whole population referred for SVT work-up was more frequent than immediate major ablation complications in patients undergoing SVT ablation (5/1186 vs. 23/ 1770, p = 0.02). The difference was not significant when both immediate and delayed major ablation complications were considered (9/1186 vs. 23/1770, p = 0.15). In multivariable analysis (Table 4), only higher age (OR per one year increase in age = 1.02, CI = (1.01–1.04), p = 0.003) was independently associated with a higher risk of ablation complication. 3.4. Events during follow-up Death occurred in 42 patients during follow-up (Table 3). Death occurred more frequently in patients with SVT-related adverse events, especially in patients with a major adverse event (p b 0.001). The occurrence of AF during follow-up was similar in patients with and without adverse events. In multivariable analysis (Table 5), major SVT-related adverse events remained significantly associated with the occurrence of death (HR = 6.72, IC = (2.58–17.52), p b 0.001), independently of age and presence of underlying heart disease. Ablation did change the risk of death in the entire cohort (HR = 0.99, IC = (0.53–1.83), p = 0.97). This association between ablation and the risk of death was similar in patients with and without SVT-related adverse events (p for interaction = 0.94).
4. Discussion In the current large cohort of patients referred for a SVT work-up, SVT-related adverse events occurred in 19% of patients. Advanced age and the presence of heart disease were the main factors independently associated with SVT-related adverse events. Major SVT-related adverse events were independently associated with a higher rate of death during follow-up. Therefore, given the possible underlying arrhythmic mechanism of this increased risk of death, patients with SVT-related adverse events might greatly beneficiate from a curative treatment of SVT by ablation. However, as we identified a significant association between SVT-related adverse events and death in this cohort despite the use of ablation, these patients should be carefully followed after the initial workup. Major SVT-related adverse events have previously been reported in these patients [6,7]. Of these, life-threatening arrhythmias were found to be rare (less than 1% of all patients referred for SVT work-up) and most were drug-related. The role of drugs as a cause of adverse event has indeed been previously reported by several authors. Chang [11] reported one major adverse event that occurred in a procainamide-toamiodarone crossover patient who had profound bradycardia and hypotension after receiving a large amiodarone dose. There was also 1 death in a patient receiving amiodarone, although this was attributed to sepsis and progressive deterioration of the patient's primary cardiac disease. Hypotension and bradycardia were the most common minor adverse events among amiodarone recipients. In a sense, these findings should also promote SVT ablation which, unlike antiarrhythmic drugs, has no proarrhythmic effect. The cardiac side effects of all antiarrhythmic drugs represent an exaggeration of their intrinsic electrophysiological and hemodynamic effects. Thus, hemodynamic decompensation and bradyarrhythmias resulting from either sinus nodal, AV nodal, or infranodal dysfunction are of major concern. Side effects of adenosine compounds are
Table 2 Multivariable analysis of SVT-related adverse events.
Age (per one year increase) Male gender Heart disease Diabetes Isoproterenol required to induce SVT a b
All SVT-related adverse events (N = 339)a
SVT-related major adverse events (N = 23)b
OR (CI)
p value
OR (CI)
p value
1.01 (1.01–1.02) 0.86 (0.67–1.10) 3.74 (2.72–5.13) 1.15 (0.55–2.43) 1.54 (0.55–2.43)
0.001 0.24 b0.001 0.71 0.001
/ / 6.50 (2.83–14.91) / /
/ / b0.001 / /
For all SVT-related adverse events, variables were forced in the multivariable logistic model. Given the number of SVT-related major adverse events, a backward selection procedure was used.
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Table 3 Ablation, complications of ablation and events during follow-up.
Ablation Total Ablation of AVNRT Ablation of AVRT Complications of ablation Total complications of ablation Total major complications Immediate major complications Deaths AF occurrence
No AE
Total AE
Major AE
Minor AE
(N = 1431)
(N = 339)
(N = 23)
(N = 316)
984 (68.8%) 815/1182 (69%) * 169/249 (67.8%)
202 (59.6%)** 166/278 (59.7%) ** 36/61 (59%)
12 (52%) 10/19 (52.6%) 2/4 (50%)
189 (60%)* 156/259 (60%) 34/57 (59.6%)
87 (6%) 7 (0.7%) 5 (0.5%) 23 (2%) 83 (6%)
18 (5%) 2 (0.1%) 0 19 (6%)*** 18 (5%)
0 0 0 6 (26%)*** 1 (4%)
18 (9.5%) 2 (0.6%) 0 13 (4%) 17 (5%)
See Table 1 for abbreviations.
extremely common although very short lasting. Verapamil is both highly effective and safe, except in very specific circumstances [12] where several major complications have been reported, predominantly in children [12]. Several other drugs have also been reported as a cause of sudden cardiac arrest [13]. In addition to drug-related adverse events, several mechanisms could account for sudden cardiac arrest. Cardiovascular collapse in patients with hypertrophic cardiomyopathy or patients with advanced heart disease can occur as well as tachycardia-induced cardiomyopathy. Coronary ischemia can also be observed in patients with coronary stenosis or in patients with normal coronary arteries but with an extremely rapid heart rate during supraventricular tachyarrhythmia. Even in patients without underlying heart disease, SVT episodes can degenerate into ventricular tachycardia or fibrillation [6,7]. While heart failure and sudden death in patients with tachycardiainduced cardiomyopathy and recurrent tachycardia have been documented [14], the latter have mainly been described in pediatric patients [15]. SVT was reported as a potentially lethal arrhythmia in children with tachycardia-induced cardiomyopathy, although spontaneous resolution of tachycardia was not uncommon and antiarrhythmic treatment often effective [15]. Radiofrequency ablation was recommended in older children or when rate was not controlled, especially in patients with persistent left ventricular dysfunction [16]. These results confirm that control of incessant tachycardia leads to a regression of symptoms and signs of cardiomyopathy as well as a progressive normalization of the dimensions of the heart [16]. SVT-related syncope has also been reported by our group [17] as well as by several other authors [18]. The causes are various and include rapid heart rate, associated spontaneous AV, sino- or atrioventricular disturbances, advanced heart disease or carotid stenosis-associated SVT as well as enhanced vagal reaction at the end of SVT. SVT ablation is a common procedure and has been performed for many years [17,18]: outcome is generally excellent although complications such as tamponade, complete AV block or hemorrhagic events have been reported [19,20]. However the risk of major complications is small, with major complication rates ranging between 0.8% and 6.0% depending on the ablation procedure performed [21,22]. Moreover, as Table 4 Multivariable analysis of ablation complications.
witnessed in the present study, ablation complications do not occur more frequently in patients with SVT-related adverse events. In addition, in the present series, immediate major complications related to ablation were less frequent than major SVT-related adverse events. Of importance, major SVT-related adverse events were found to be independently associated with subsequent death, independently of age and underlying heart disease. Taken together, these findings strongly support performing SVT ablation systematically in patients with major SVT-related adverse events in the absence of contraindication such as heavy comorbid condition.
5. Limitations of the study The present analysis focuses on patients referred for SVT work-up in one tertiary center. As a result, given this selection bias inherent to the mono-center nature of this study performed in a tertiary care environment, the reported prevalence of SVT-related adverse events in our cohort cannot be extrapolated to the whole population of patients with SVT. Yet, the mono-center nature of our study probably translated in a steep decrease in heterogeneity of patients and SVT medical management. In addition, the adverse events have been systematically recorded in a standardized way for more than 20 years partly thanks to the monocenter nature of the study. Given the observational nature of our study, we cannot assess the impact of ablation of the risk of subsequent death in patients with adverse events. Yet, it is unlikely that a formal randomized clinical trial will eventually assess this effect. Secondly, detailed information regarding antiarrhythmic drugs (class and number) given to those patients without adverse events could not be obtained. Indeed, the prescription of beta-blockers or verapamil or class I antiarrhythmic drugs was not systematically collected except in patients with adverse events. Given the number of resuscitated patients on antiarrhythmic drugs, this information may be of crucial importance. The threshold between major and minor adverse event could be debated in some patients, in particular those with syncope. Radiofrequency (RF) catheter ablation of SVTs began in the early nineties resulting in a learning curve in the ablation procedure both in terms of success as well as in outcome and complications. This fact
Ablation complications
Age (per one year increase) Male gender Heart disease Diabetes Isoproterenol required to induce SVT SVT-related adverse event
OR (CI)
p value
1.02 (1.01–1.04) 0.84 (0.50–1.39) 1.00 (0.46–2.15) 1.70 (0.46–6.21) 1.23 (0.72–2.11) 0.78 (0.39–1.57)
0.003 0.49 0.99 0.43 0.45 0.49
For ablation complications, variables were forced in the multivariable logistic model. Only patients who underwent ablation were considered in this model.
Table 5 Multivariable analysis of deaths during follow-up.
Age (per one year increase) Heart disease Minor SVT-related adverse event Major SVT-related adverse event
HR (CI)
p value
1.05 (1.03–1.08) 4.35 (2.21–8.55) 1.07 (0.52–2.20) 6.72 (2.58–17.52)
b0.001 b0.001 0.870 b0.001
Given the number of deaths during follow-up, a backward selection procedure was used within the Cox model. SVT-related adverse events were forced in the model.
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could have influenced the selection of patients who underwent RF ablation procedure during follow-up. Finally, patient follow-up was somewhat limited due to the design of the study, which is purely based on data obtained during routine clinical care. One might expect that the adverse effects in the SVT group would increase with longer follow-up and hence with increasing age of the patient. 6. Conclusion In the present patient cohort, SVT-related adverse events occurred in 19% of patients with either atrioventricular nodal reentrant tachycardia (AVNRT) or orthodromic atrioventricular reciprocal tachycardia. However, life-threatening arrhythmias were rare and represented less than 1% of patients referred for SVT in our center. Presence of heart disease and higher age were independently associated with a higher risk for SVT-related adverse events. The risk of SVT ablation complications was not increased in patients with SVT-related adverse events, and immediate major complications related to ablation were less frequent than major SVT-related adverse events. The association between adverse events prior to SVT work-up and survival should probably favor performing ablation given the possible underlying arrhythmic mechanism of this increased risk of death. Taken together, these findings strongly support performing SVT ablation systematically in patients with major SVT-related adverse events in the absence of contraindication such as heavy comorbid condition. However, watchful long-term follow-up of patients presenting with SVT-related major adverse events appears adequate despite ablation. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments We wish to thank Pierre Pothier for the editing and proofreading of the article. References [1] L.A. Orejarena, H. Vidaillet, F. De Stefano, D.L. Nordstrom, R.A. Vierkant, P.N. Smith, et al., Paroxysmal supraventricular tachycardia in general population, J. Am. Coll. Cardiol. 31 (1998) 150–157. [2] C. Blomström-Lundqvist, M.M. Scheinman, E.M. Aliot, J.S. Alpert, H. Calkins, A.J. Camm, et al., European Society of Cardiology Committee, NASPE-Heart Rhythm Society. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias–executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society, J. Am. Coll. Cardiol. 42 (Oct 15 2003) 1493–1531.
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[3] D. D'Este, F. Zoppo, E. Bertaglia, F. Zerbo, A. Picciolo, V. Scarabeo, A. Pascotto, et al., Long-term outcome of patients with atrioventricular node reentrant tachycardia, Int. J. Cardiol. 115 (2007) 350–353. [4] S. Luber, W.J. Brady, T. Joyce, A.D. Perron, Paroxysmal supraventricular tachycardia: outcome after ED care, Am. J. Emerg. Med. 19 (2001) 40–42. [5] R.N. Bukkapatnam, M. Robinson, S. Turnipseed, D. Tancredi, E. Amsterdam, U.N. Srivatsa, Relationship of myocardial ischemia and injury to coronary artery disease in patients with supraventricular tachycardia, Am. J. Cardiol. 106 (2010) 374–377. [6] Y.S. Wang, M.M. Scheiman, W.W. Chien, T.J. Cohen, M.D. Lesh, J.C. Griffin, Patients with supraventricular tachycardia presenting with aborted sudden death: incidence, mechanism and long-term follow-up, J. Am. Coll. Cardiol. 18 (1991) 1711–1719. [7] B. Brembilla-Perrot, O. Marçon, F. Chometon, J. Bertrand, A. Terrier de la Chaise, P. Louis, et al., Supraventricular tachyarrhythmia as a cause of sudden cardiac arrest, J. Interv. Card. Electrophysiol. 16 (2006) 97–104. [8] B. Brembilla-Perrot, J. Delobelle, Prevalence of stroke among patients with paroxysmal supraventricular tachycardia, Pacing Clin. Electrophysiol. 36 (2013) 180–186. [9] H. Khachab, B. Brembilla-Perrot, Prevalence of atrial fibrillation in patients with history of paroxysmal supraventricular tachycardia, Int. J. Cardiol. 166 (2013) 221–224. [10] B. Brembilla-Perrot, J.M. Sellal, A. Olivier, V. Manenti, D. Beurrier, C. de Chillou, T. Villemin, N. Girerd, Recurrences of symptoms after AV node re-entrant tachycardia ablation: a clinical arrhythmia risk score to assess putative underlying cause, Int. J. Cardiol. 179 (2015) 292–296. [11] P.M. Chang, M.J. Silka, D.Y. Moromisato, Y. Bar-Cohen, Amiodarone versus procainamide for the acute treatment of recurrent supraventricular tachycardia in pediatric patients, Circ. Arrhythm. Electrophysiol. 3 (2010) 134–140. [12] S. Viskin, B. Belhassen, Acute management of paroxysmal atrioventricular junctional reentrant supraventricular tachycardia: pharmacologic strategies, Am. Heart J. 120 (1990) 180–188. [13] B. Brembilla-Perrot, J.M. Sellal, P.Y. Zinzius, J. Schwartz, H. Blangy, N. Sadoul, Influence of the time on the prevalence of drug-related resuscitated sudden death during these past 20 years, Int. J. Cardiol. 167 (2013) 491–494. [14] P. Nerheim, S. Birger-Botkin, L. Piracha, B. Olshansky, Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia, Circulation 110 (2004) 247–252. [15] G. Vaksmann, C. D'Hoinne, V. Lucet, S. Guillaumont, J.M. Lupoglazoff, A. Chantepie, et al., Permanent junctional reciprocating tachycardia in children: a multicentre study on clinical profile and outcome, Heart 92 (2006) 101–104. [16] F.E. Cruz, E.C. Cheriex, J.L. Smeets, J. Atié, A.K. Peres, O.C. Penn, et al., Reversibility of tachycardia-induced cardiomyopathy after cure of incessant supraventricular tachycardia, J. Am. Coll. Cardiol. 16 (1990) 739–744. [17] B. Brembilla-Perrot, D. Beurrier, P. Houriez, O. Claudon, J. Wertheimer, Incidence and mechanism of presyncope and/or syncope associated with paroxysmal junctional tachycardia, Am. J. Cardiol. 88 (2001) 134–138. [18] F. Drago, A. Turchetta, A. Calzolari, U. Giordano, V. Di Ciommo, A. Santilli, et al., Reciprocating supraventricular tachycardia in children: low rate at rest as a major factor related to propensity to syncope during exercise, Am. Heart J. 132 (1996) 280–285. [19] M. Haissaguerre, F. Gaita, B. Fischer, D. Commenges, P. Montserrat, C. d'Ivernois, P. Lemetayer, J.F. Warin, Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy, Circulation 85 (1992) 2162–2175. [20] W.M. Jackman, K.J. Beckman, J.H. McClelland, X. Wang, K.J. Friday, C.A. Roman, et al., Treatment of supraventricular tachycardia due to atrioventricular nodal reentry, by radiofrequency catheter ablation of slow-pathway conduction, N. Engl. J. Med. 327 (1992) 313–318. [21] G. Hindricks, on behalf of the Multicentre European Radiofrequency Survey (MERFS) investigators of the working group on arrhythmias of the European Society of Cardiology, The multicentre European Radiofrequency Survey (MERFS): complications of radiofrequency catheter ablation of arrhythmias, Eur. Heart J. 14 (1993) 1644–1653. [22] M. Bohnen, W.G. Stevenson, U.B. Tedrow, G.F. Michaud, R.M. John, L.M. Epstein, et al., Incidence and predictors of major complications from contemporary catheter ablation to treat cardiac arrhythmias, Heart Rhythm. 8 (2011) 1661–1666.
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
AV nodal reentrant tachycardia or AV reentrant tachycardia using a concealed bypass tract-related adverse events Béatrice Brembilla-Perrot a,⁎, Maxime Bénichou a, Alice Brembilla b, Erwan Bozec c, Sarah Dorlet a, Jean Marc Sellal a, Arnaud Olivier a, Vladimir Manenti a, Thibaut Villemin a, Daniel Beurrier a, Anne Moulin-Zinsch a, Christian De Chillou a, Nicolas Girerd c a b c
Department of Cardiology, University Hospital of Brabois, Vandoeuvre, France Epidemiology, CHU de Besançon, France INSERM, Centre d'Investigations Cliniques 9501, Université de Lorraine, Institut Lorrain du cœur et des vaisseaux, CHU de Nancy, Nancy, France
a r t i c l e
i n f o
Article history: Received 13 April 2015 Received in revised form 26 May 2015 Accepted 10 July 2015 Available online xxxx Keywords: Supraventricular tachycardia Adverse events Antiarrhythmic drug Ablation
a b s t r a c t Objectives: To jointly study paroxysmal supraventricular tachycardia (SVT)-related adverse events (AE) and ablation-related complications, with specific emphasis on the predictors of SVT-related AE as well as their significance by investigating their association with long-term mortality. Methods: 1770 patients were included, aged 6 to 97, with either atrioventricular nodal reentrant tachycardia (AVNRT) or orthodromic atrioventricular reciprocal tachycardia (AVRT) mediated by concealed accessory pathway, consecutively referred for SVT work-up in a tertiary care center. Results: SVT-related AE were identified in 339 patients (19%). Major AEs were identified in 23 patients (1%; 15 cardiac arrests or ventricular arrhythmias requiring cardioversion and 8 hemodynamic collapses). Other AE were related to syncope (n = 236), acute coronary syndrome (n = 57) and heart failure/rhythmic cardiomyopathy (n = 21). In multivariable analysis, higher age, heart disease and requirement of isoproterenol to induce SVT were independently associated with a higher risk for SVT-related AE. During follow-up (2.8 ± 3.0 years), death occurred more frequently in patients with SVT-related AE, especially in patients with major adverse events (p b 0.001). In multivariable analysis, major SVT-related AE remained significantly associated with occurrence of death (HR = 6.72, IC = (2.58–17.52), p b 0.001) independently of age and presence of underlying heart disease. Major SVT-related AE in the whole population referred for SVT were more frequent than immediate major ablation complications in patients undergoing SVT ablation (5/1186 vs. 23/1770, p = 0.02). Conclusions: SVT-related AE are independent predictors of mortality and are more frequent than immediate major ablation complications in patients undergoing SVT ablation. The present findings support systematically performing SVT ablation in patients with SVT-related adverse events. © 2015 Published by Elsevier Ireland Ltd.
What's new? − Supraventricular tachycardia-related adverse events were found to occur in 19% of patients with atrioventricular tachycardia. − Life-threatening adverse events related to supraventricular tachycardia are rare (1%). Yet, our study demonstrates for the first time that major adverse-events are associated with a six-fold increase in the risk for long-term mortality. This higher risk of death suggests that a specific watchful follow-up is needed in these patients, even after successful ablation. − The prevalence of immediate major ablation-related complications is lower than the prevalence of major adverse events related to
⁎ Corresponding author at: CHU of Brabois, 54500 Vandoeuvre Les Nancy, France. E-mail address: [email protected] (B. Brembilla-Perrot).
http://dx.doi.org/10.1016/j.ijcard.2015.07.048 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
supraventricular tachycardia. This novel finding further establishes the favorable benefit-risk ratio of ablation for SVT.
1. Introduction Paroxysmal supraventricular tachycardia (SVT) is a common form of tachycardia [1]. There are approximately 89,000 new cases/year and 570,000 persons with a history of SVT in the United States. SVT is considered to be benign and ablation is required only in symptomatic patients [2]. However, a more conservative approach has been suggested based on the long-term follow-up of a large cohort of atrioventricular nodal reentrant tachycardia (AVNRT) patients who became asymptomatic, none of which had undergone ablation [3]. This approach is also supported by the risk of ablation-related complications.
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Nevertheless, adverse events related to SVT are a relatively frequent cause for emergency department admission [4]. During SVT episodes, symptoms suggestive of myocardial ischemia, including chest pain (31%), ST-segment depression (61%) and elevated troponin levels (12%), are frequently recorded [5]. Major adverse events can also occur, although far less commonly [6,7]. As a result of the risk for SVT-related adverse events and the risk of ablation-related complications, risk to benefit ratio should therefore to be considered when choosing treatment strategy for a patient with SVT. The purpose of the present analysis was to jointly study SVT-related adverse events and ablation-related complications in patients presenting with either AVNRT or orthodromic atrioventricular reciprocal tachycardia (AVRT). The study also aimed to identify the predictors of SVT-related adverse events as well as their clinical significance in comparison with ablation-related complications. 2. Methods 2.1. Study population The present is a retrospective observational study of patients consecutively referred for a regular paroxysmal SVT in a tertiary care center between January 1990 and January 2014. Patients with preexcitation syndrome on ECG and patients with antidromic AV reciprocating tachycardia (AVRT) due anterograde conduction through an accessory pathway were excluded (n = 480). Among these last patients 55 of them had a normal ECG in sinus rhythm and the diagnosis of anterograde conduction over accessory pathway was made at electrophysiological study. Patients in whom atrial arrhythmia was identified during the work-up were also excluded (n = 182). A total of 1770 patients with either AVNRT (N = 1460) or orthodromic AVRT mediated by a concealed accessory pathway (N = 310) were ultimately included. Among these patients, 85 old patients with an initial diagnosis of atrial tachycardia were shown as having AVNRT or orthodromic AVRT mediated by a concealed accessory pathway after an electrophysiologic study. 2.2. Data extraction Clinical data were retrospectively extracted from the patients' medical records. As part of the systematic work-up performed for SVT, patients underwent a standardized clinical evaluation including the accurate determination of prior adverse events. The study was approved by the Commission nationale de l'informatique et des libertés (CNIL). Under French law, no formal IRB approval is required for data extraction from patients' medical records. The prescription of beta-blockers, verapamil and class I antiarrhythmic drugs was not systematically collected in patients without prior SVT-related adverse events during SVT work-up. 2.3. Adverse event definition Adverse events collected during the SVT work-up, i.e. adverse events that occurred prior to or during the work-up, were classified as major (requiring resuscitation) or minor (management changes). Major events were defined as cardiac arrest or documented life-threatening hemodynamically nontolerated arrhythmia, with collapses or syncope and requiring emergency treatment, generally cardioversion. All major adverse events were witnessed and SVT was confirmed as the cause of the major adverse event after careful adjudication. Minor adverse events were defined as events that required patient hospitalization. These included syncope, ischemic coronary event, acute heart failure or other poorly-tolerated event directly related to an SVT episode. These SVT episodes ended spontaneously or after infusion of either verapamil or adenosine triphosphate. Of note, an isolated increase in troponin level was not considered as an adverse event.
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2.4. Electrophysiology laboratory protocol All patients underwent an electrophysiological study as part of the systematic work-up performed for SVT. Electrophysiological studies were performed after signing the clinical informed consent form endorsed by the French Society of Cardiology (Societé Française de Cardiologie). All antiarrhythmic drugs were discontinued at least five half-lives prior to the study. Details of the protocol have been previously described [8–10]. Briefly, atrial pacing and programmed atrial stimulation were systematically performed during sinus rhythm with atrial pacing conducted at two cycle lengths, 600 and 400 ms. Premature stimuli (S2) were delivered after every eighth paced atrial complex with 10 ms decrements until atrial refractoriness was reached. When a supraventricular tachycardia was induced, the protocol was halted. In the absence of tachycardia induction, isoproterenol (0.02 to 1 μg.min−1) was alternatively infused to increase the sinus rate to at least 130 bpm. Atrial pacing was repeated and programmed atrial stimulation was performed at a cycle length of 400 ms. Diagnosis of SVT was confirmed by the electrophysiological study. The mechanism of SVT was determined according to the method of induction, the relation of atrial and ventricular activation at the onset of tachycardia and during tachycardia, the sequence of retrograde atrial activation and, if necessary, the effect of premature extra-stimulus during SVT. The SVT was classified as typical AV nodal reentry within the atrioventricular node (AVNRT) or atypical AVNRT or reentry within a concealed accessory atrioventricular connection (AVRT). In instances of adverse events occurrence or in the case of abnormal clinical examination, echocardiography was systematically performed. Ablation of SVT was performed in most patients, either immediately after the identification of SVT mechanism during the electrophysiological study or during a second procedure. A 7F deflectable catheter with a 4 mm tip electrode was used to perform AVNRT or accessory pathway ablation. In the case of AVNRT, the slow pathway potential was identified, and a radiofrequency current was applied at this level with an energy limit of 40 watts and a temperature limit of 65 °C. Radiofrequency current was immediately halted if junctional rhythm did not appear within 15 s, otherwise it was continued for 60 s. The absence of AVNRT induction after ablation was verified. If still present, application of the radiofrequency current was repeated, a new application of radiofrequency current was performed. When AVNRT remained inducible, anatomically-guided ablation was used. Slow pathway block or singleAV nodal echo beat represented a procedural endpoint. Isoproterenol infusion was systematically used and the protocol repeated to verify the absence of AVNRT re-induction. In the case of AVRT via a concealed accessory pathway, ablation was performed at the earliest atrial retrograde activation either during ventricular pacing or during AVRT. For both AVNRT and AVRT ablation, catheters were removed 20 min after the disappearance of the anterograde conduction over the slow pathway or of the retrograde conduction over the accessory pathway. Ablation-related complications were defined as major if they were life-threatening and required the admission of the patient in intensive care unit or as minor if they regressed without the need of monitoring in intensive care. Complications considered as major were mostly pericardial tamponade requiring emergency drainage, complete AV block requiring pacemaker implantation and death. Complications considered as minor were local bleeding, vagal syncope at femoral puncture, minor pericardial suffusion, transient traumatic or radiofrequency-related second or complete AV block and transient sinus bradycardia. As a general rule, patients with recurrent tachycardias who refused ablation were discharged with beta-blockers.
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2.5. Other tests performed within the SVT work-up An exercise test was performed in patients with exercise-related symptoms and in instances of chest pain, ST-segment depression or elevated troponin levels during SVT. Other invasive studies such as coronary angiography were indicated in the case of a major adverse event. 2.6. Follow-up Patients treated by SVT ablation were discharged without antiarrhythmic medication and were systematically examined by a cardiologist at least one month after ablation. No treatment was indicated for one or 2 episodes of well-tolerated tachycardia. Medical treatment (initially beta-blockers) was only indicated for recurrent tachycardia's when the patient refused the ablation or when the patient was too young for this treatment. The study enabled access to a mean of 2.75 ± 2.7 years of follow-up performed by the referring cardiologist and/or general practitioner. This follow-up was available from medical correspondence contained in the patient's medical record. In addition, information was also collected from patient telephone interviews from 2010 onward, as part of the usual clinical follow-up after SVT ablation. General physicians, patients and occasionally other hospitals were contacted to identify clinical outcome. ECG and 24-hour Holter recordings were performed if the patient reported palpitations or symptoms suspected to be the consequence of SVT occurrence/recurrence. 2.7. Statistical methods Continuous variables are expressed as mean ± SD and were compared using t tests for independent samples. Differences in proportion were compared using a Chi2 test. Logistic regression with presence of adverse events and absence of adverse events were used as outcome variables. Gender and all variables associated with a p-value b 0.20 on univariable logistic regression analysis were entered in the multivariable models. Similar regression was performed with presence of ablation-related complications as dependent variables. Cox models were used to study the factors associated with death during the follow-up. For both logistic and Cox multivariable analysis, backward selection of variables was performed when the number of events was insufficient to enable the introduction of all candidate variables within the models. A p value b 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS package for Windows (version 21, IBM Corp., Armonk, NY, USA). 3. Results Patients were aged from 6 to 97 years (mean age 48 ± 19 years), 59% of whom were women. 3.1. Prevalence and description of SVT-related adverse events Adverse events related to SVT untreated by ablation were identified in 339 patients (19%) during SVT workup. Major adverse events were identified in 23 patients (1%): 15 patients had a cardiac arrest or ventricular arrhythmia requiring cardioversion while 8 patients suffered hemodynamic collapse. Ten patients presented resuscitated cardiac arrest following torsade de pointes complicated by ventricular fibrillation, all of whom were on antiarrhythmic drugs (sotalol, verapamil, disopyramide, digoxin, amiodarone). One patient had a coronary spasm with beta-blockers complicated by ventricular fibrillation. Two patients with underlying cardiopathy (one patient with coronary heart disease and one patient with hypertrophic
cardiomyopathy) had ventricular fibrillation following SVT, thus attributed to SVT. A 16-year-old girl who had only presented one episode of SVT died from asystole after infusion of verapamil followed by digoxin. One 55-year-old patient with respiratory failure refused SVT ablation and died after a prolonged SVT. Hemodynamic collapses occurred in 7 other patients, one being related to verapamil injection in a patient with Wegener's disease. Remaining patients were admitted for SVTrelated cardiogenic shock. In this latter case, cardiogenic shock was attributed to SVT because it occurred several hours after SVT initiation and required emergency treatment (cardioversion in 5 patients and atrial pacing in 2 patients). Three hundred and sixteen patients (18%) had minor SVT adverse events as defined by SVT episodes that required hospitalization in an emergency unit. Minor SVT adverse events were mainly syncope in 236 patients (15%), acute coronary syndrome in 57 patients (3%) which triggered an admission in the intensive coronary care unit, tachycardiomyopathy (n = 12) or stage IV heart failure (n = 9) in 21 patients, inappropriate shock at implantable cardiac defibrillator in one patient and major antiarrhythmic drug-related bradycardia (b30 bpm) in one patient. Within the study population, 230 had increased troponin levels prior to their SVT work-up, of which 44 had a known coronary heart disease. Only 57 of these patients were hospitalized and considered as having an SVT-related adverse event. 3.2. Factors associated with adverse events In univariable analysis, patients with adverse events were older, and were more likely to be female or to have diabetes than patients without adverse events (Table 1). The rate of tachycardia and the prevalence of atrial fibrillation (AF) history did not differ between patients with and without adverse events. SVT mechanism was similar in patients with and without adverse events. Infusion of isoproterenol during the electrophysiological study was more frequently required to induce SVT in patients with adverse events than in patients without adverse events. In multivariable analysis, higher age, heart disease and requirement of isoproterenol infusion during the electrophysiological study to induce SVT during were independently associated with a higher risk for SVT-related adverse events (Table 2). In contrast, the presence of heart disease was the only factor retained when solely considering major SVT-related adverse events (OR = 6.50, CI = (2.83–14.91), p b 0.001). 3.3. Ablation complications SVT ablation was performed in 1186 patients, more frequently in patients without adverse events than in those with adverse events. Most patients with adverse events who did not undergo ablation had refused ablation (N = 31). The indication of ablation was not dependent on the mechanism of SVT (AVNRT or AVRT). Most accessory pathways were left sided comparatively to only an occasional right posteroseptal location. Only one case involved a parahisian location. Ablation complications were as frequent in patients with or without SVT-related adverse events (Table 3). In patients with a history of SVT-related adverse events, two major ablation complications were recorded (Table 3). A 44 year-old male had sudden death 16 days after ablation of a concealed left lateral accessory pathway. This patient had radial artery thrombosis after a coronary angiography performed after a SVT-related coronary syndrome. A second patient underwent pacemaker implantation one year after ablation. Other than these major complications, two other patients had spontaneous infrahisian conduction abnormalities requiring pacemaker implantation. In patients without adverse events, major complications were as follows: 2 deaths occurred 1 to 3 days after ablation in older women referred for recurrent SVTs. One death was due to disseminated
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Table 1 Characteristics of the study population according to the presence or absence of SVT-related adverse events. AE: adverse event, AF: atrial fibrillation; SVT: supraventricular tachycardia; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia. Comparisons were performed with patients without adverse events.
Age (years) Male gender Heart disease Diabetes AF history SVT rate (bpm) AVNRT Typical AVNRT Atypical AVNRT AVRT Isoproterenol required to induce SVT
No AE
Total AE
Major AE
Minor AE
(N = 1431)
(N = 339)
(N = 23)
(N = 316)
47 ± 19 565 (39.5%) 125 (9%) 20 (1%) 51 (3.5%) 187.5 ± 35 1182 (82.5%) 1018 (71%) 164 (11%) 249 (17%) 454 (32%)
53 ± 21⁎⁎⁎ 157 (46%)⁎ 102 (30%)⁎⁎⁎ 13 (4%)⁎⁎
58 ± 20⁎⁎ 9 (39%) 11 (48%)⁎⁎⁎
53 ± 21⁎⁎⁎ 148 (47%)⁎ 91 (29%)⁎⁎⁎ 12 (4%)⁎⁎
11 (3%) 194 ± 134 278 (82%) 245 (72%) 33 (10%) 61 (18%) 141 (42%)⁎⁎⁎
1 (4%) 2 (9%) 183 ± 32 19 (83%) 18 (78%) 1 (4%) 4 (17%) 11 (49%)
9 (3%) 195 ± 138 259 (82%) 227 (72%) 32 (10%) 57 (18%) 130 (41%)⁎⁎
⁎⁎⁎ p b 0.0001. ⁎⁎ p b 0.01. ⁎ p b 0.05.
intravascular coagulation after local bleeding while the other was related to a fatal collapse induced by vasodepressor syncope. Tamponade occurred during the ablation of a concealed left lateral accessory pathway in one woman. Two pacemaker implantations were required after SVT ablation while 2 other implantations were respectively required 6 months and 1 year later in patients without adverse event. A pacemaker was implanted in 5 older patients several years after the ablation although correlation with ablation per se was uncertain. Major SVT-related adverse events in the whole population referred for SVT work-up was more frequent than immediate major ablation complications in patients undergoing SVT ablation (5/1186 vs. 23/ 1770, p = 0.02). The difference was not significant when both immediate and delayed major ablation complications were considered (9/1186 vs. 23/1770, p = 0.15). In multivariable analysis (Table 4), only higher age (OR per one year increase in age = 1.02, CI = (1.01–1.04), p = 0.003) was independently associated with a higher risk of ablation complication. 3.4. Events during follow-up Death occurred in 42 patients during follow-up (Table 3). Death occurred more frequently in patients with SVT-related adverse events, especially in patients with a major adverse event (p b 0.001). The occurrence of AF during follow-up was similar in patients with and without adverse events. In multivariable analysis (Table 5), major SVT-related adverse events remained significantly associated with the occurrence of death (HR = 6.72, IC = (2.58–17.52), p b 0.001), independently of age and presence of underlying heart disease. Ablation did change the risk of death in the entire cohort (HR = 0.99, IC = (0.53–1.83), p = 0.97). This association between ablation and the risk of death was similar in patients with and without SVT-related adverse events (p for interaction = 0.94).
4. Discussion In the current large cohort of patients referred for a SVT work-up, SVT-related adverse events occurred in 19% of patients. Advanced age and the presence of heart disease were the main factors independently associated with SVT-related adverse events. Major SVT-related adverse events were independently associated with a higher rate of death during follow-up. Therefore, given the possible underlying arrhythmic mechanism of this increased risk of death, patients with SVT-related adverse events might greatly beneficiate from a curative treatment of SVT by ablation. However, as we identified a significant association between SVT-related adverse events and death in this cohort despite the use of ablation, these patients should be carefully followed after the initial workup. Major SVT-related adverse events have previously been reported in these patients [6,7]. Of these, life-threatening arrhythmias were found to be rare (less than 1% of all patients referred for SVT work-up) and most were drug-related. The role of drugs as a cause of adverse event has indeed been previously reported by several authors. Chang [11] reported one major adverse event that occurred in a procainamide-toamiodarone crossover patient who had profound bradycardia and hypotension after receiving a large amiodarone dose. There was also 1 death in a patient receiving amiodarone, although this was attributed to sepsis and progressive deterioration of the patient's primary cardiac disease. Hypotension and bradycardia were the most common minor adverse events among amiodarone recipients. In a sense, these findings should also promote SVT ablation which, unlike antiarrhythmic drugs, has no proarrhythmic effect. The cardiac side effects of all antiarrhythmic drugs represent an exaggeration of their intrinsic electrophysiological and hemodynamic effects. Thus, hemodynamic decompensation and bradyarrhythmias resulting from either sinus nodal, AV nodal, or infranodal dysfunction are of major concern. Side effects of adenosine compounds are
Table 2 Multivariable analysis of SVT-related adverse events.
Age (per one year increase) Male gender Heart disease Diabetes Isoproterenol required to induce SVT a b
All SVT-related adverse events (N = 339)a
SVT-related major adverse events (N = 23)b
OR (CI)
p value
OR (CI)
p value
1.01 (1.01–1.02) 0.86 (0.67–1.10) 3.74 (2.72–5.13) 1.15 (0.55–2.43) 1.54 (0.55–2.43)
0.001 0.24 b0.001 0.71 0.001
/ / 6.50 (2.83–14.91) / /
/ / b0.001 / /
For all SVT-related adverse events, variables were forced in the multivariable logistic model. Given the number of SVT-related major adverse events, a backward selection procedure was used.
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Table 3 Ablation, complications of ablation and events during follow-up.
Ablation Total Ablation of AVNRT Ablation of AVRT Complications of ablation Total complications of ablation Total major complications Immediate major complications Deaths AF occurrence
No AE
Total AE
Major AE
Minor AE
(N = 1431)
(N = 339)
(N = 23)
(N = 316)
984 (68.8%) 815/1182 (69%) * 169/249 (67.8%)
202 (59.6%)** 166/278 (59.7%) ** 36/61 (59%)
12 (52%) 10/19 (52.6%) 2/4 (50%)
189 (60%)* 156/259 (60%) 34/57 (59.6%)
87 (6%) 7 (0.7%) 5 (0.5%) 23 (2%) 83 (6%)
18 (5%) 2 (0.1%) 0 19 (6%)*** 18 (5%)
0 0 0 6 (26%)*** 1 (4%)
18 (9.5%) 2 (0.6%) 0 13 (4%) 17 (5%)
See Table 1 for abbreviations.
extremely common although very short lasting. Verapamil is both highly effective and safe, except in very specific circumstances [12] where several major complications have been reported, predominantly in children [12]. Several other drugs have also been reported as a cause of sudden cardiac arrest [13]. In addition to drug-related adverse events, several mechanisms could account for sudden cardiac arrest. Cardiovascular collapse in patients with hypertrophic cardiomyopathy or patients with advanced heart disease can occur as well as tachycardia-induced cardiomyopathy. Coronary ischemia can also be observed in patients with coronary stenosis or in patients with normal coronary arteries but with an extremely rapid heart rate during supraventricular tachyarrhythmia. Even in patients without underlying heart disease, SVT episodes can degenerate into ventricular tachycardia or fibrillation [6,7]. While heart failure and sudden death in patients with tachycardiainduced cardiomyopathy and recurrent tachycardia have been documented [14], the latter have mainly been described in pediatric patients [15]. SVT was reported as a potentially lethal arrhythmia in children with tachycardia-induced cardiomyopathy, although spontaneous resolution of tachycardia was not uncommon and antiarrhythmic treatment often effective [15]. Radiofrequency ablation was recommended in older children or when rate was not controlled, especially in patients with persistent left ventricular dysfunction [16]. These results confirm that control of incessant tachycardia leads to a regression of symptoms and signs of cardiomyopathy as well as a progressive normalization of the dimensions of the heart [16]. SVT-related syncope has also been reported by our group [17] as well as by several other authors [18]. The causes are various and include rapid heart rate, associated spontaneous AV, sino- or atrioventricular disturbances, advanced heart disease or carotid stenosis-associated SVT as well as enhanced vagal reaction at the end of SVT. SVT ablation is a common procedure and has been performed for many years [17,18]: outcome is generally excellent although complications such as tamponade, complete AV block or hemorrhagic events have been reported [19,20]. However the risk of major complications is small, with major complication rates ranging between 0.8% and 6.0% depending on the ablation procedure performed [21,22]. Moreover, as Table 4 Multivariable analysis of ablation complications.
witnessed in the present study, ablation complications do not occur more frequently in patients with SVT-related adverse events. In addition, in the present series, immediate major complications related to ablation were less frequent than major SVT-related adverse events. Of importance, major SVT-related adverse events were found to be independently associated with subsequent death, independently of age and underlying heart disease. Taken together, these findings strongly support performing SVT ablation systematically in patients with major SVT-related adverse events in the absence of contraindication such as heavy comorbid condition.
5. Limitations of the study The present analysis focuses on patients referred for SVT work-up in one tertiary center. As a result, given this selection bias inherent to the mono-center nature of this study performed in a tertiary care environment, the reported prevalence of SVT-related adverse events in our cohort cannot be extrapolated to the whole population of patients with SVT. Yet, the mono-center nature of our study probably translated in a steep decrease in heterogeneity of patients and SVT medical management. In addition, the adverse events have been systematically recorded in a standardized way for more than 20 years partly thanks to the monocenter nature of the study. Given the observational nature of our study, we cannot assess the impact of ablation of the risk of subsequent death in patients with adverse events. Yet, it is unlikely that a formal randomized clinical trial will eventually assess this effect. Secondly, detailed information regarding antiarrhythmic drugs (class and number) given to those patients without adverse events could not be obtained. Indeed, the prescription of beta-blockers or verapamil or class I antiarrhythmic drugs was not systematically collected except in patients with adverse events. Given the number of resuscitated patients on antiarrhythmic drugs, this information may be of crucial importance. The threshold between major and minor adverse event could be debated in some patients, in particular those with syncope. Radiofrequency (RF) catheter ablation of SVTs began in the early nineties resulting in a learning curve in the ablation procedure both in terms of success as well as in outcome and complications. This fact
Ablation complications
Age (per one year increase) Male gender Heart disease Diabetes Isoproterenol required to induce SVT SVT-related adverse event
OR (CI)
p value
1.02 (1.01–1.04) 0.84 (0.50–1.39) 1.00 (0.46–2.15) 1.70 (0.46–6.21) 1.23 (0.72–2.11) 0.78 (0.39–1.57)
0.003 0.49 0.99 0.43 0.45 0.49
For ablation complications, variables were forced in the multivariable logistic model. Only patients who underwent ablation were considered in this model.
Table 5 Multivariable analysis of deaths during follow-up.
Age (per one year increase) Heart disease Minor SVT-related adverse event Major SVT-related adverse event
HR (CI)
p value
1.05 (1.03–1.08) 4.35 (2.21–8.55) 1.07 (0.52–2.20) 6.72 (2.58–17.52)
b0.001 b0.001 0.870 b0.001
Given the number of deaths during follow-up, a backward selection procedure was used within the Cox model. SVT-related adverse events were forced in the model.
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could have influenced the selection of patients who underwent RF ablation procedure during follow-up. Finally, patient follow-up was somewhat limited due to the design of the study, which is purely based on data obtained during routine clinical care. One might expect that the adverse effects in the SVT group would increase with longer follow-up and hence with increasing age of the patient. 6. Conclusion In the present patient cohort, SVT-related adverse events occurred in 19% of patients with either atrioventricular nodal reentrant tachycardia (AVNRT) or orthodromic atrioventricular reciprocal tachycardia. However, life-threatening arrhythmias were rare and represented less than 1% of patients referred for SVT in our center. Presence of heart disease and higher age were independently associated with a higher risk for SVT-related adverse events. The risk of SVT ablation complications was not increased in patients with SVT-related adverse events, and immediate major complications related to ablation were less frequent than major SVT-related adverse events. The association between adverse events prior to SVT work-up and survival should probably favor performing ablation given the possible underlying arrhythmic mechanism of this increased risk of death. Taken together, these findings strongly support performing SVT ablation systematically in patients with major SVT-related adverse events in the absence of contraindication such as heavy comorbid condition. However, watchful long-term follow-up of patients presenting with SVT-related major adverse events appears adequate despite ablation. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments We wish to thank Pierre Pothier for the editing and proofreading of the article. References [1] L.A. Orejarena, H. Vidaillet, F. De Stefano, D.L. Nordstrom, R.A. Vierkant, P.N. Smith, et al., Paroxysmal supraventricular tachycardia in general population, J. Am. Coll. Cardiol. 31 (1998) 150–157. [2] C. Blomström-Lundqvist, M.M. Scheinman, E.M. Aliot, J.S. Alpert, H. Calkins, A.J. Camm, et al., European Society of Cardiology Committee, NASPE-Heart Rhythm Society. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias–executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society, J. Am. Coll. Cardiol. 42 (Oct 15 2003) 1493–1531.
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[3] D. D'Este, F. Zoppo, E. Bertaglia, F. Zerbo, A. Picciolo, V. Scarabeo, A. Pascotto, et al., Long-term outcome of patients with atrioventricular node reentrant tachycardia, Int. J. Cardiol. 115 (2007) 350–353. [4] S. Luber, W.J. Brady, T. Joyce, A.D. Perron, Paroxysmal supraventricular tachycardia: outcome after ED care, Am. J. Emerg. Med. 19 (2001) 40–42. [5] R.N. Bukkapatnam, M. Robinson, S. Turnipseed, D. Tancredi, E. Amsterdam, U.N. Srivatsa, Relationship of myocardial ischemia and injury to coronary artery disease in patients with supraventricular tachycardia, Am. J. Cardiol. 106 (2010) 374–377. [6] Y.S. Wang, M.M. Scheiman, W.W. Chien, T.J. Cohen, M.D. Lesh, J.C. Griffin, Patients with supraventricular tachycardia presenting with aborted sudden death: incidence, mechanism and long-term follow-up, J. Am. Coll. Cardiol. 18 (1991) 1711–1719. [7] B. Brembilla-Perrot, O. Marçon, F. Chometon, J. Bertrand, A. Terrier de la Chaise, P. Louis, et al., Supraventricular tachyarrhythmia as a cause of sudden cardiac arrest, J. Interv. Card. Electrophysiol. 16 (2006) 97–104. [8] B. Brembilla-Perrot, J. Delobelle, Prevalence of stroke among patients with paroxysmal supraventricular tachycardia, Pacing Clin. Electrophysiol. 36 (2013) 180–186. [9] H. Khachab, B. Brembilla-Perrot, Prevalence of atrial fibrillation in patients with history of paroxysmal supraventricular tachycardia, Int. J. Cardiol. 166 (2013) 221–224. [10] B. Brembilla-Perrot, J.M. Sellal, A. Olivier, V. Manenti, D. Beurrier, C. de Chillou, T. Villemin, N. Girerd, Recurrences of symptoms after AV node re-entrant tachycardia ablation: a clinical arrhythmia risk score to assess putative underlying cause, Int. J. Cardiol. 179 (2015) 292–296. [11] P.M. Chang, M.J. Silka, D.Y. Moromisato, Y. Bar-Cohen, Amiodarone versus procainamide for the acute treatment of recurrent supraventricular tachycardia in pediatric patients, Circ. Arrhythm. Electrophysiol. 3 (2010) 134–140. [12] S. Viskin, B. Belhassen, Acute management of paroxysmal atrioventricular junctional reentrant supraventricular tachycardia: pharmacologic strategies, Am. Heart J. 120 (1990) 180–188. [13] B. Brembilla-Perrot, J.M. Sellal, P.Y. Zinzius, J. Schwartz, H. Blangy, N. Sadoul, Influence of the time on the prevalence of drug-related resuscitated sudden death during these past 20 years, Int. J. Cardiol. 167 (2013) 491–494. [14] P. Nerheim, S. Birger-Botkin, L. Piracha, B. Olshansky, Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia, Circulation 110 (2004) 247–252. [15] G. Vaksmann, C. D'Hoinne, V. Lucet, S. Guillaumont, J.M. Lupoglazoff, A. Chantepie, et al., Permanent junctional reciprocating tachycardia in children: a multicentre study on clinical profile and outcome, Heart 92 (2006) 101–104. [16] F.E. Cruz, E.C. Cheriex, J.L. Smeets, J. Atié, A.K. Peres, O.C. Penn, et al., Reversibility of tachycardia-induced cardiomyopathy after cure of incessant supraventricular tachycardia, J. Am. Coll. Cardiol. 16 (1990) 739–744. [17] B. Brembilla-Perrot, D. Beurrier, P. Houriez, O. Claudon, J. Wertheimer, Incidence and mechanism of presyncope and/or syncope associated with paroxysmal junctional tachycardia, Am. J. Cardiol. 88 (2001) 134–138. [18] F. Drago, A. Turchetta, A. Calzolari, U. Giordano, V. Di Ciommo, A. Santilli, et al., Reciprocating supraventricular tachycardia in children: low rate at rest as a major factor related to propensity to syncope during exercise, Am. Heart J. 132 (1996) 280–285. [19] M. Haissaguerre, F. Gaita, B. Fischer, D. Commenges, P. Montserrat, C. d'Ivernois, P. Lemetayer, J.F. Warin, Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy, Circulation 85 (1992) 2162–2175. [20] W.M. Jackman, K.J. Beckman, J.H. McClelland, X. Wang, K.J. Friday, C.A. Roman, et al., Treatment of supraventricular tachycardia due to atrioventricular nodal reentry, by radiofrequency catheter ablation of slow-pathway conduction, N. Engl. J. Med. 327 (1992) 313–318. [21] G. Hindricks, on behalf of the Multicentre European Radiofrequency Survey (MERFS) investigators of the working group on arrhythmias of the European Society of Cardiology, The multicentre European Radiofrequency Survey (MERFS): complications of radiofrequency catheter ablation of arrhythmias, Eur. Heart J. 14 (1993) 1644–1653. [22] M. Bohnen, W.G. Stevenson, U.B. Tedrow, G.F. Michaud, R.M. John, L.M. Epstein, et al., Incidence and predictors of major complications from contemporary catheter ablation to treat cardiac arrhythmias, Heart Rhythm. 8 (2011) 1661–1666.