Europace (2008) 10, 513527 doi:10.

1093/europace/eun104

Consensus document on antithrombotic therapy in the setting of electrophysiological procedures

Jean Jacques Blanc, (Chair; Brest, FR)*, Jesus Almendral, (Co-chair; Madrid, SP), Michele Brignole, (Lavagna, IT), Marjaneh Fatemi, (Brest, FR), Knut Gjesdal, (Oslo, N), Esteban Gonzalez-Torrecilla, (Madrid, SP), Piotr Kulakowski, (Warsaw, PL), Gregory Y.H. Lip, (Birmingham, UK), Dipen Shah, (Geneva, CH), and Christian Wolpert, (Mannheim, DE), on behalf of the Scientic Initiatives Committee of the European Heart Rhythm Association
Received 28 March 2008; accepted after revision 28 March 2008

Preamble
Guidelines and Expert Consensus documents are proposed to help physicians to select the best possible diagnostic or therapeutic strategies for an individual patient with a specic disease. Recommendations issued from these documents are based on an extensive review of the literature and on discussions among experts when hard data are incomplete or missing. It has been shown that patient outcomes improve when guidelines recommendations are applied in clinical practice. Publication and promotion of these guidelines is one of the most important tasks of scientic societies. The recently created European Heart Rhythm Association (EHRA) wants to meet this commitment in its specic eld of competence and one assignment of the scientic committee of EHRA is to propose and promote Guidelines in the management of heart rhythm disturbances not already covered by the European Society of Cardiology (ESC).

Introduction
Electrophysiological studies (EPSs), whether or not associated with therapeutic procedures (ablation using different sources of energy or reduction of tachycardia), show the percutaneous introduction of one or multiple catheters to record the electrical activity of the heart or to pace its different cavities. The introduction and manipulation of these catheters in arteries, veins, or cardiac cavities have multiple pathophysiological consequences and one of the most evident is to activate the coagulation cascade with the risk to induce new clots or to mobilize pre-existing ones. Furthermore, withdrawal of catheters induces
* Corresponding author. Jean Jacques, Department of Cardiology, Hopital de la Cavale Blanche, Bd Tanguy Prigent, Brest 29200, France. Tel: 33 2 98 34 73 92; fax: 33 2 98 34 78 03. E-mail address: jean-jacques.blanc@univ-breast.fr

haemorrhage usually limited by the compression of the site of venous or arterial puncture. There is also a close relationship between EPS and thrombus formation (thrombogenesis) and thus, rhythmologists need to balance the risks between thrombo-embolism and bleeding. There are no guidelines on the use of antithrombotic therapies in the setting (before, during, and after) of EPS. Generally, different laboratories have their own approaches to this clinical problem. The aim of the present document is to propose consensus recommendations written according to the Guidelines for guidelines published by the Guidelines committee of the ESC. It should be stressed that this topic has been poorly studied in clinical trials and that very few well-designed studies are at our disposal to guide evidence-based management. This is a major limitation to give hard recommendations and explains why the level of recommendation in most instances is Grade C (expert opinion). The present document has been divided into ve main sections: the rst three deals with the general risks of thrombo-embolism or bleeding, whereas the fourth section relates more to the risks of venous or arterial access and the last section relates to some special situations. The division between low-, intermediate-, and high-risk procedures for thrombo-embolism or bleeding is partly arbitrary, as a low-risk intervention in a high-risk patient becomes an intermediate-risk procedure. Even with these limitations, such a division could be helpful for readers. It is the hope of the task force that this document will prompt well-designed trials that would hopefully strengthen the impact of the following recommendations.

Epidemiology
Radiofrequency (RF) catheter ablation, because of its curative nature and high success and low complication rates, has become the treatment of choice for a wide variety of

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

514

J.J. Blanc et al.

arrhythmias. Indications have recently expanded to include even complex arrhythmias such as atrial brillation (AF), atrial utter (AFL), and ventricular tachycardia (VT) associated with structural heart disease. A recent review indicates an overall low incidence of 0.6% of reported thrombo-embolic complications; the risk was increased when an ablation procedure was performed in the left heart (1.62.8%).13 In an earlier survey,2 the reported procedure-related complications of RF ablation occur in 5.1%. The risk is also high when the ablation procedure is performed in the left heart (1.82%) and for VT (2.8%).3

Atrial utter
Radiofrequency catheter ablation of isthmus-dependent AFL is considered the therapeutic strategy of choice. Gronefeld et al.12 reported a case series of 201 patients with AFL: 62 were not on therapeutic anticoagulation, and had a relative risk for thrombo-embolism of 12.5 [95% condence interval (CI): 355, P , 0.001].

Pathophysiology
Mechanisms of thrombo-embolism in electrophysiological procedures
The mechanisms of thrombo-embolism peri-ablation have been open to much speculation.13 About 150 years ago, Virchow proposed a triad of abnormalities that predispose to thrombus formationow abnormalities, abnormalities of the vessel wall, and abnormal blood constituents. The pathophysiology of thrombo-embolism is therefore multifactorial, but increasing evidence points to the fullment of Virchows triad in the context of an electrophysiological procedure leading to a prothrombotic or hypercoagulable state.13 In the setting of complex catheter ablation procedures, thrombo-embolic complications result most commonly from the embolization of thrombi of cardiogenic origin. As an illustrative example, in AF ablation, possibilities include a reduction in the LA function, endocardial/tissue damage leading to a prothrombotic surface on the endocardium, activation per se of coagulation and platelets, and so on. However, this may be an over-simplication, as atheroembolic plaques from major arteries, calcic debris from systemic valves, and paradoxical emboli generated in the right side of the circulation have all been shown to give rise to embolic complications. Bubbles of air are frequently sucked into long sheaths during catheter withdrawal and can be embolized into the systemic circulation by ushing or catheter re-introduction. Thrombi formed in situ within the long sheaths may embolize with an improper ushing technique. Rarely, catheter debris or broken off bits may also be embolized. Theoretically, insufciently anchored thrombus can be launched into the circulating bloodstream by a vigorous contractione.g. by a post-cardio version beat (and supplemented in variable measure by the shock of electrical cardio version) or by catheter manipulation or as pointed outushing, or catheter reintroduction within long sheaths. In the clinical setting where multiple factors usually coexist, a multi-pronged approach is therefore appropriate to minimize or prevent these complications. Abnormal blood ow During medium-term follow-up, restoration of sinus rhythm by LA ablation results in partial return of LA function in patients with chronic AF, whereas in patients with paroxysmal AF, LA catheter ablation results in decreased LA function.14 Also, ablation of AFL has been associated with signicant LA stunning and the development of spontaneous echo contrast,15 perhaps indicating more stasis within the left atrium. Atrial stunning is dened by transient atrial mechanical dysfunction that follows conversion of AF to normal sinus rhythm. It has been reported with all modes of conversion

Atrial brillation
Non-pharmacological measures play an increasing role in AF management and, in many instances, offer the possibility of a cure.4 However, AF recurrence rates with catheter ablation techniques are signicant. For example, only 54 and 82% of the patients remained free of arrhythmia-related symptoms at the 6-month follow-up period, after circumferential pulmonary vein ablation and segmental pulmonary vein ablation for AF, respectively.5 Also, asymptomatic AF episodes can occur and may be increased after catheter ablation, especially among previously symptomatic patients.6 In a real world survey of the methods, efcacy, and safety of catheter ablation for AF, there was a clear relation of procedural success and complications to centre expertise and follow-up duration.7 Major complications did occur in 5.9%, and for procedures involving left atrial (LA) ablation, the prevalence of stroke was 0.28% and that of transient ischaemic attack was 0.66%. This needs to be put in context of other complications, including mortality (0.05%) and tamponade (1.22%). Clearly, practice from individual centre series varies from registry data.811 During a follow-up of 33.6 months, Gasparini et al.9 reported that thrombo-embolic events were observed in 17 patients (3%); the actuarial occurrence rates of thrombo-embolism were 1.1, 3, 4.2, and 7.4% after 1, 3, 5, and 7 years, respectively. In the multivariate analysis, the only predictor of embolic events during follow-up was the presence of chronic AF. There was a relatively low incidence (1.04% per year) of thrombo-embolic events after AV node ablation and pacing for drug refractory, high rate AF. Oral et al.10 recently reported a study of percutaneous LA RF ablation in 755 consecutive patients with paroxysmal (n 490) or chronic (n 265) AF, of which 411 (56%) had one or more risk factors for stroke. All patients were anticoagulated with warfarin for 3 months after LA RF ablation. Thrombo-embolism occurred in seven patients (0.9%) within 2 weeks of LA RF ablation, whereas late thrombo-embolism occurred 610 months after ablation in two patients (0.2%), one of whom still had AF, despite therapeutic anticoagulation in both. None of the patients in whom anticoagulation was discontinued had a thrombo-embolic event during 25 months of followup. They concluded that the risk of thrombo-embolism after LA RF ablation is 1.1%, with most events occurring within 2 weeks after the procedure. Indeed, thromboembolism may still occur, despite the appearance of sinus rhythm maintenance.11

Consensus document on antithrombotic therapy

515

of AF, including RF ablation. Atrial stunning results in paradoxical reduction of LA and LA appendage blood ow velocities. There is strong evidence to suggest that this condition is responsible for an increased risk of thrombo-embolism for hours to weeks after conversion of AF in to sinus rhythm and results in a ve-fold increase in the risk of stroke.16 The time delay for atrial function to recover is dependent on the duration of the arrhythmia, the atrial size, and underlying heart disease. Left atrial mechanical dysfunction induced by ablation may contribute to abnormal ow and thrombogenesis. As extensive lesions in the left atrium are required to achieve complete pulmonary vein disconnection, one might speculate that AF ablation results in signicant atrial dysfunction. In contrast, maintenance of sinus rhythm following ablation should result in reverse atrial remodelling and recovery of atrial function. In a study by Beukema et al.,17 patients who remain free of AF recurrence after ablation demonstrate signicant decrease in LA cavity size, whereas in those with recurrent AF, LA dimension increased compared with baseline. In another study in which LA function was determined by measuring LA ejection fraction, in patients with paroxysmal AF, ablation resulted in more depressed LA function when compared with baseline. In patients with chronic AF, there was partial recovery of LA function. In both the cases, LA ejection fraction was lower than that in control subjects.18 Whether the impairment of the left atrium is severe enough to predispose to thrombus formation despite elimination of AF remains to be determined. Abnormal vessel wall The heating of tissue and/or blood during RF current delivery, or debrillation energy with an atrioverter, may leave a damaged endocardial/endothelial surface that activates the coagulation system.19 Tissue overheating during current delivery may even result in gas formation, with audible popping. The type of sheath used, given the nature of the foreign substance within the blood, as well as the procedure duration, would have implications for thrombogenesis. In one study in which thrombus formation was documented by intracardiac echocardiography19 during pulmonary vein isolation, 50% of the thrombi developed before RF application and after transseptal catheterization, and in the remaining patients, it developed after RF delivery. In both groups, thrombi were attached either to the sheath or to the lasso catheter and never to the ablation catheter. Interestingly, no mural or mobile thrombus attached to RF lesion was observed. In one of the rare studies20 to look at clinical thrombo embolic events (TEE) during LA ablations (including both AF and left AFL), the authors observed a high incidence with a strategy of low ow (3 cc/h) heparinized perfusion of the long LA sheath. When they changed to a high ow (180 cc/h) perfusion of the long sheath placed into the left atrium, they observed no more TEE in 54 subsequent similar cases. Although limited by its retrospective nature, this observational study highlights an important mechanism of thrombus generation and embolization: stasis within the long sheath (low ow perfusion) leads to the formation of a thrombus, which is then pushed into the left atrium by resumption of an interrupted ushing perfusion or another

catheter. The lamentous shape of many intracardiac thrombi and their attachment to the sheath tip clearly corroborate this mechanism. Therefore, a proper technique should be applied. Withdrawal of 23 cc of blood content from short sheaths and more from long ones with use of a separate syringe should precede regular ushing with the use of clean heparized saline, thus ensuring avoidance of introducing thrombi already formed within the sheath; this should be repeated periodically unless a high ow perfusion technique is employed and also every time a new catheter is inserted into the sheath. Finally, a catheter should be introduced if blood cannot be freely withdrawn and proper ushing can not be completed. The type of ablation procedure may itself inuence thrombogenesis and may reect the extent of tissue injury. Pulmonary vein disconnection with or without additional lesion lines is required to cure AF. Radiofrequency energy application results in a spherical-shaped area of necrosis surrounded by a haemorrhagic zone because of resistive heating of the tissue. Pathological studies in animals have shown thrombus formation on the lesion.21 In contrast, if tissue temperature exceeds 1008C during RF application, thrombus develops at the tip of the ablation catheter. Thrombus formation decreases the efcacy of RF application and is also a potential source of embolization.22 Air can also be sucked in through the non-return valve (which is designed primarily to prevent blood from leaking out) when a catheter is rapidly pulled out of the long LA sheath and then embolizes out into the left atrium. Fortunately, the commonest clinical manifestation is transient ST-elevation, typically in a right coronary distribution with accompanying angina. Aspirating the sheath side arm with a nger or thumb over the sheath valve (to prevent further air aspiration) or simply letting the side-arm bleed passively (with a few taps on the valve to dislodge trapped bubbles) after each catheter withdrawal and before resuming sheath perfusion may signicantly reduce this complication. Abnormal blood constituents Abnormalities of procoagulant blood constituents are well recognized in relation to ablation procedures. Thrombus formation can represent predominantly brinrich clot (red clot) or predominantly platelet-rich thrombus (white clot). In AF, thrombus is mainly brin-rich and is reected by immunohistological data23 and by the dramatic reduction of stroke with anticoagulation therapy when compared with antiplatelet therapy.24 Reduction of stroke with aspirin in AF is similar to the 22% odds reduction of vascular events by antiplatelet therapy in high-risk vascular disease patients, in whom aspirin 75325 mg daily is commonly prescribed.25 In atherosclerotic vascular disease, thrombus formation is mainly platelet-rich, and thus, antiplatelet therapy is benecial. This is evident in the setting of coronary artery disease.26 Evidence supporting increased platelet activation in AF has been provided by numerous studies,27 but the platelet activation in AF is not beyond that which would be expected from associated vascular disease. Following ablation, there is some evidence of signicant haemostatic activation.28 For example, Manolis et al.29 reported increased brin D-dimer levels, an index of

516

J.J. Blanc et al.

intravascular thrombogenesis post-ablation, irrespective of heparin therapy usage. In another study, Michelucci et al.30 found that coagulation system and platelets were activated immediately after electrophysiological and ablation procedures, but this returned to normal by 24 h post-procedure. In a study conducted on 37 patients,31 brin D-dimer and thrombinantithrombin levels (as indices of thrombogenesis) were measured at baseline, after sheath insertion, after electrophysiological study but before ablation, at the completion of the procedure, and at 24 h post-procedure. D-dimer levels increased signicantly from baseline values after sheath insertion. There was a further signicant increase after electrophysiological study was performed and a slight but not signicant increase was observed after ablation. D-dimer levels remained elevated at 24 h. Procedure duration was the only predictor of increased thrombogenicity. Different modalities of ablation may result in the differential activation of platelets and coagulation activity. For example, an RF procedure induces signicantly more platelet activation and haemostasis than the conventional cryo-application procedure.32 Given that thrombin is one of the most potent stimulants of platelets, anticoagulation therapy will still remain the cornerstone of antithrombotic management per-ablation, but the role of antiplatelet therapy as monotherapy, combination therapy (e.g. aspirin clopidogrel or aspirinticlopidine) or co-administered with warfarin remains uncertain given the lack of large clinical trials addressing this issue. In summary, electrophysiological interventions may confer a prothrombotic state by the fullment of various components of Virchows triad for thrombogenesis.13

practice reports or case series. In a single-centre study,35 for example, intravenous heparin was administered with an initial bolus of 5000 U followed by 1000 U/h for the duration of the procedure in 376 patients undergoing right- and left-sided ablation. Neither warfarin nor aspirin was given after ablation. No embolic complication occurred, and deep vein thrombosis was observed in three patients (0.8%).

Prolonged anticoagulant therapy in high-risk patients

Most physicians recommend continued anticoagulant therapy following RF ablation. However, the optimal duration of this therapy has not been clearly established. When RF is performed during AF, atrial stunning following conversion to sinus rhythm (SR) favours thrombo-embolic complications and, therefore, anticoagulation should at least be maintained until recovery of atrial functionthe latter is a function of LA size, duration of AF and the underlying heart disease.36 However, owing to the risk of relapse, current guidelines recommend that anticoagulation should be continued long-term in subjects with stroke risk factors and those at high risk of AF recurrence.34 Some assurance that there is no arrhythmia recurrence before discontinuation of anticoagulation can be considered. In a series of 755 patients undergoing AF ablation,10 1.1% had thrombo-embolic complications. In 0.9% of the patients, thrombo-embolism occurred within 2 weeks of the procedure, and in 0.2% (two patients), late thromboembolism was observed at 610 months, despite therapeutic anticoagulation level. Among patients who remained in SR and had no risk factor, anticoagulation was discontinued in 79% at a median of 4 months. Among those who remained in sinus rhythm and had one or more risk factors, anticoagulation was discontinued in 68% of the patients at a median of 5 months. In patients who had AF recurrence (233 patients), anticoagulation was discontinued in 6% of the patients. None of the patients who were taken off anticoagulants had late thrombo-embolism during the 25 months of follow-up. Patients older than 65 years or with a history of stroke were more likely to remain anticoagulated despite successful outcome of AF ablation. On the basis of the results of this study, it is probably safe to discontinue anticoagulant therapy after 45 months in patients with successful ablation of AF and no risk factor or with risk factors other than age .65 years and history of stroke. There are insufcient data to support discontinuation of anticoagulation in patients older than 65 years or with a history of stroke. In another large-scale non-randomized study in which pulmonary vein isolation was compared no early with anti-arrhythmic drug therapy,35 thrombo-embolism was observed following ablation. Late thrombo-embolism was observed in 2.5% of the patients in the ablation group and 10% of the patients in the medically treated group; 54 and 49% of ablated and medically managed patients, respectively, had thrombo-embolism while receiving inadequate anticoagulation. Thromboembolic complications were signicantly more frequent among patients who had AF recurrence suggesting the continuation of anticoagulation in patients with unsuccessful outcome of ablation.

Associated comorbid conditions

Although several factors have been identied to increase the thrombo-embolic risk of AF, not all of them have been studied during AF ablation. Given the interest into stroke and thrombo-embolism following a rhythm control strategy compared with a rate control strategy, it is clear that anticoagulation is an independent predictor of survival.33 Thus, current recommendations for anticoagulation emphasize the need for continuation of anticoagulation therapy beyond 4 weeks postcardioversion where there is a high risk of AF recurrence and/ or stroke risk factors are present.34 Thrombus formation during AF ablation as determined by intracardiac echocardiography could be related to increased LA size, spontaneous echo contrast, and persistent AF. The most important determinant of thrombus formation was the presence of spontaneous echo contrast, as nearly as 70% of the patients with this condition develop LA thrombus. In contrast, LA size and ischaemic heart disease are associated with increased incidence of atrial stunning, which also favours thrombus formation.

Measures to minimize thrombo-embolic complications

The adjunctive administration of specic inhibitors of platelet activation, application of intraprocedural intracardiac echocardiography, irrigated RF ablation, and cryoablation catheter systems could all potentially reduce the risk of thrombo-embolism during ablation.1 Randomized trials are lacking and much of the evidence is based on clinical

Consensus document on antithrombotic therapy

517

Intravenous heparin
Intravenous heparin is extensively used to prevent thrombo-embolic complications of RF ablations performed in left-side cavities. Although thrombus formation is not completely eliminated by heparin infusion, increased intensity of anticoagulation may reduce the risk of embolic events during AF ablation. Wazni et al.37 performed a study on 785 patients who underwent AF ablation. Patients who had activated coagulation time (ACT) maintained between 350 and 400 ms were less likely to develop char or have TEE than those in whom the ACT was between 250 and 300 ms. Similarly, Ren et al.38 reported reduced risk of LA thrombus in patients with spontaneous echo contrast by maintaining the ACT .300 ms. The use of platelet inhibition with eptibatide did not have incremental benecial effect.

patients with AF, the use of irrigated-tip catheter was demonstrated to be safe with low complication rates and a reasonable medium-term success rate: 81% of the patients were in sinus rhythm, 33% of whom required additional antiarrhythmic therapy. At the end of the ablation procedure, no signs of coagulum formation were present around the tip of the catheter.45

Alternative energy sources for tissue ablation

In an animal study,46 the use of cryoenergy resulted in less thrombus formation than RF (30.1 vs. 75.8%). Cryoablation was also associated with smaller thrombi (0.8 vs. 5.4 mm3). However, human studies are lacking to conrm safety and efcacy of this method in the ablation of human AF. Other alternative energy sources such as microwave, laser, or ultrasound energy all result in tissue heating; although clinical data are lacking, there is no reason to anticipate any reduction in thrombo-embolic potential.

Aspirin and ticlopidine or clopidogrel

Limited data are available on the role of dual antiplatelet therapy as thromboprophylaxis in electrophysiological interventions. As discussed later (see Special situations section) many patients undergoing ablation may have had associated coronary disease and/or stents, which require the use of such drugs, and bleeding complications may be an issue.26 Combination therapy may have some potential to reduce the propensity to thrombogenesis when compared with monotherapy. In a study conducted on 59 patients undergoing RF ablation,39 pre-treatment with aspirin or ticlopidine alone did not decrease the thrombogenic potential of RF ablation, although combined therapy with aspirin and ticlopidine had a favourable effect, as reected by the lower degree of D-dimer elevation when compared with baseline. Nonetheless, these are data based on surrogate endpoints and should be considered in context of other data in relation to the lack of benet of aspirinclopidogrel in reducing thrombogenesis in AF40 and clinical trials that show superiority of warfarin over aspirinclopidogrel combination therapy.41

Other measures
Limited data exist on other therapeutic strategies for dealing with catheter-related thrombus during electrophysiological interventions. Thrombus dissolution should be possible with brinolytic therapy, and such agents are used in the management of acute myocardial infarction and acute shunt thrombosis. Concern remains on the feasibility of local delivery of such agents, as well as embolism of thrombus fragments during (partial) dissolution.

The role of echocardiography

Intracardiac echocardiography
Intracardiac echocardiography monitoring during RF applications allows early detection of LA thrombi that can be removed by withdrawal of the sheath and catheter into the right atrium. However, the clinical signicance of these thrombi is not clear. Ren et al.19 reported a 10% incidence of thrombus formation as identied by intracardiac echocardiography imaging. In most series of AF ablation the incidence of clinical thrombo-embolism is much less than this value. In contrast, patients with spontaneous echo contrast are more likely to develop thrombus during RF procedure. Identication of these patients by intracardiac echocardiography imaging is, therefore, important. In another study,38 increased intensity of anticoagulation may reduce risk of thrombus during AF ablation in patients with spontaneous echo contrast that is when ACT was .300 ms, LA thrombus was observed in only 4.6% of the patients, whereas when ACT was between 250 and 300 ms, the risk of thrombus was 44.9%. Intracardiac echocardiography imaging has also been used to monitor micro-bubble formation during RF delivery, considered to reect tissue heating. Marrouche et al.47 showed that RF power reduction prompted by an increase in the micro-bubble formation was associated with the lowest incidence of complications, including thrombo-embolism and pulmonary vein stenoses.

Temperature control during radiofrequency ablation

For irreversible injury to occur during RF application, a tissue temperature of at least 508C must be achieved. As temperature increases, lesion size also increases. However, if temperature exceeds 1008C, coagulation (or thrombus?) develops.22 Temperature monitoring with closed-loop control of power during RF application minimizes the likelihood of developing coagulum while ensuring maximum lesion formation. It has been demonstrated that below an electrode temperature of 708C, thrombus was observed in 0% of RF applications vs. 7% of applications when the target temperature was 858C.42

Irrigated-tip catheter
Irrigation of the ablation electrode has been demonstrated to reduce the risk of thrombus formation at the tip of the electrode.43 A direct comparison in vitro between an externally irrigated (shower tip) catheter and a closed circuit internally irrigated ablation catheter clearly showed that coagulum generation correlated very well with elevated electrodetissue interface temperature and that little or no coagulum was observed with an externally irrigated catheter.44 In a single-centre study conducted on 52 consecutive

Transoesophageal echocardiography
Transoesophageal echocardiography (TOE) is useful to identify spontaneous echo contrast, which is associated with an

518

J.J. Blanc et al.

increased incidence of thrombus formation during RF, and to detect LA thrombus which contraindicates ablation. After conversion to sinus rhythm following ablation, TOE might be helpful to assess the severity of LA stunning by measuring LA appendage velocities48,49 and emptying fraction.47

Risk stratication
Low-risk procedures: right-side interventions (atrial tachycardias, kent bundle, and junctional and ventricular tachycardia) except those performed during atrial utter
Thrombo-embolic vs. bleeding complications In the MERFS retrospective registry,2 among 1715 patients who performed right-sided ablation (AV node re-entrant tachycardia or AV junction ablation), there were 1 case of cerebral embolism (0.06%), 4 cases of pulmonary embolism (0.23%), and 18 cases of venous thrombosis (1.04%). Conversely, there were three cases of pericardial tamponade (0.17%), seven cases of pericardial effusion (0.41%), and two cases of major bleeding/haematoma (0.11%). In the 1998 NASPE prospective catheter ablation registry,50 among 2142 patients with right-sided ablation (AV node re-entrant tachycardia, AV junction ablation, rightsided accessory pathway or atrial tachycardia) there were three cases (0.14%) of thrombo-embolism (pulmonary or venous), two cases (0.09%) of pericardial tamponade, and six cases (0.28%) of major bleeding/haematoma. In the Atakr prospective multicentre registry performed in 11 centres,51 embolic complications were rare after RF ablation in patients without other risk factors for systemic embolization, occurring in 4 of 558 right-sided procedures (0.7%) and in 3 of 272 left-sided procedures (1.1%). Moreover, three of these involved systemic venous thrombosis and were presumably unrelated to catheter manipulation within the heart. Conversely, in the same study,42 there were 6 cases of pericardial tamponade (0.6%), 20 cases of pericardial effusion (1.9%), and 32 cases of major bleeding/haematoma (3.05%). In a single-centre study,52 intravenous heparin was administered with an initial bolus of 5000 U followed by 1000 U/h for the duration of the procedure in 376 patients undergoing right- and left-sided ablation. Neither warfarin nor aspirin was given after ablation. No embolic complication occurred, and deep vein thrombosis was observed in three patients (0.8%). However, cardiac tamponade occurred in three patients (0.8%) and one of them died. Pericardial effusion occurred in other three patients (0.8%). Anticoagulation vs. no anticoagulation In the Atakr prospective registry performed in 11 centres,51 anticoagulation protocols differed among centres for rightsided procedures: seven centres gave intravenous heparin during procedures, three did not, and one gave oral aspirin. Outpatient and post-procedure anticoagulation protocols also differed: ve centres discharged patients on oral aspirin and six on nothing. Embolic complications could not be attributed to the use of anticoagulation either during or after the procedure, because a wide range of both inpatient and outpatient anticoagulation protocols were utilized and no single protocol was associated with a higher incidence of thrombo-embolic complications.51 Thakur et al.53

observed that embolic complications occurred despite both intraoperative and post-procedure anticoagulation. In the 1998 NASPE prospective catheter ablation registry,50 post-procedure anticoagulation was prescribed in 22%, aspirin in 42%, and no specic therapy in 35%. The incidence of thrombo-embolism or bleeding complications was generally low, and there were no signicant differences in these complications among groups (Table 1). In summary, no rm relationship has been proved between low-risk procedures with thrombo-embolic complications and the anticoagulation protocol, procedure time, or number of RF lesions.
Recommendations for low-risk procedures Right-sided procedures (except AFL) are at low risk of thrombo-embolism during and after the procedure. Conversely, the risk of bleeding seems to be higher with anticoagulation. Therefore, anticoagulation therapy is not necessary for right-sided procedures (before, during, and after the procedure) unless other risk factors for systemic embolism are present.

Intermediate risk procedures

Atrial utter Ablation for persistent common atrial utter: ablation during utter. Patients with persistent AFL are at increased risk for embolic events, although this risk seems to be lower than that in patients with AF.5458 Observational studies of patients undergoing electrical cardioversion with sub-therapeutic anticoagulation suggest that this risk seems to be particularly high in relation to restoration of sinus rhythm.5965 Additional information reinforcing the nature of this risk comes from echocardiographic studies analysing the presence of atrial thrombi, echo contrast, and LA appendage function.6670 This risk extends over a period of time after the restoration of sinus rhythm, probably because electrical stunning of atrial myocardium during persistent AFL does not recover immediately after sinus rhythm restoration.66,71 Only a few studies have dealt specically with these phenomena in the context of sinus rhythm restoration with catheter ablation, but similar observations were made in these studies.7274 In contrast, an ablation procedure by itself is not expected to carry a signicant risk for systemic embolism, because both lesions and catheter manipulation are produced in the right atrium. Thus, the embolic risk of the

Table 1 Incidence of thrombotic or bleeding complications vs. type of anticoagulant therapy used after ablation in 3388 patients at low risk50 Complications Warfarin (n 767) 0.52% 0.26% Aspirin (n 1437) 1.04% 0.39% None (n 1184) 0.42% 0.08%

Bleeding/ haematoma Thrombotic events*

*Thrombotic events were considered: cerebral, deep vein thrombosis, and pulmonary.

Consensus document on antithrombotic therapy

519

procedure per se can be considered equal to that of the low-risk procedures, as discussed previously. In summary, as ablation in a patient with persistent common AFL presumably implies the restoration of sinus rhythm, there is a risk for procedure-related systemic embolism, not because of the procedure per se, but because of the underlying arrhythmic process, and that this risk extends for a period of time after the procedure. Ablation for paroxysmal occasional common atrial utter: ablation during sinus rhythm. If AFL is paroxysmal, the thrombo-embolic risk secondary to persistent AFL is not expected to be present at the time of the ablation procedure. Furthermore, no subsequent embolic risk is expected after the procedure, as there is no sinus rhythm recovery. As in the case of persistent AFL, the ablation procedure in itself is not expected to carry a signicant risk for systemic embolism. Thus, the full ablation procedure can be considered equal to the low-risk procedures, as discussed previously. Left-sided interventions excluding atrial brillation and patients with overt structural heart disease Several studies have shown that RF catheter ablation procedures carry some thrombo-embolic risk, despite the use of temperature feedback and different levels of prophylactic anticoagulation. A 10-year systematic review of the literature found a three-fold increase in the incidence of thrombo-embolic complications of left-sided RF ablation procedures (1.82%) when compared with an overall rate of only 0.6% when all ablation procedures are considered.1 Embolic events after LA ablation procedures were not included in this review. The underlying mechanisms of a higher incidence in leftsided interventions are not clear. On the risk of systemic embolism associated with RF catheter ablation in the left heart, Hindricks2 reported an incidence of 0.46%, including cerebral embolism (0.4%) and peripheral arterial embolism (0.06%). In the particular case of RF procedures in left-sided accessory pathways, Thakur et al.53 reported the three late embolic complications in 153 patients (2%), despite the use of heparin during the procedure (activating clotting time .300 ms) and aspirin for 3 months after the ablation. In the Atakr registry study,42 two patients had a stroke (0.2%); one after the ablation of a left-sided accessory pathway with a transseptal approach and the other after the ablation of the AV junction with a retrograde aortic approach. Moreover, under the diagnosis of thrombus/ embolic event four more patients (0.4%) were included as major complications. Finally, the 1998 NASPE Prospective Catheter Ablation Registry reports no embolic events after the ablation of left free-wall accessory pathways in 418 patients.50 The differing anticoagulation protocols reported in these registries limit their conclusions and possible management recommendations. The incidence of embolic events after ablation procedures in patients with idiopathic left-sided VTs is unknown. The absence of signicant structural heart disease in these patients suggests a lower incidence of events when compared with those with left ventricular dysfunction42 and similar to that observed in left-sided accessory pathway procedures. Other energy sources such

as cryoenergy have showed the lower incidence of thrombus formation.46 At the current time, there is no scientic evidence that anticoagulant therapies prevent TEE in patients undergoing RF ablation procedures. Therefore, our recommendations are based on the experience of previous observational studies. However, systemic embolization consequences can be so devastating as to demand an antithrombotic therapy to decrease its risk, even if the rate of the embolic events is very low, as long as the haemorrhagic risk does not become prohibitive. In contrast, there is no clear relation between anticoagulation protocol and the incidence of bleeding complications in these procedures. However, an incidence of bleeding ranging from 2 to 3%42,50 brings us to consider anticoagulation protocols of intermediate intensity.
Recommendations for intermediate risk Ablation for persistent common atrial utter: ablation during utter In agreement with the previous discussion, with the ACC/AHA/ ESC 2006 Guidelines for the management of patients with AF, and with the ACC/AHA/ESC Guidelines for the management of patients with supraventricular arrhythmias, we recommend that antithrombotic therapy is undertaken before, during, and after the ablation procedure. The following protocol is proposed: Effective anti-vitamin K anticoagulation for 3 weeks or TOE screening prior to the ablation procedure. Stop anti-vitamin K for 25 days before the ablation procedure. Bridging therapy with heparin until the day before the ablation procedure is recommended. Sodium heparin during (or immediately after) the ablation procedure, at doses of a bolus of 5000 and 1000 U/h is recommended, although evidence for this practice is lacking. Re-start effective anticoagulation for 4 weeks after the ablation procedure. Minimize the window of ineffective anticoagulation. Ablation for paroxysmal occasional common atrial utter: ablation during sinus rhythm In patients without a conventional indication for anticoagulation, follow previous recommendations for low-risk procedures. Left-sided interventions excluding atrial brillation and patients with overt structural heart disease Anticoagulation therapy prior to the intervention is not advised in this clinical setting. Intravenous sodium heparin is recommended during the ablation procedure, immediately after arterial access at doses of a bolus of 5000 U followed by 1000 U/h during the procedure. Other more aggressive anticoagulation regimens may also be considered in the individual cases such as those undergoing complex, long procedures, and extensive RF applications.

High-risk procedures
Atrial brillation ablation Thrombo-embolic complications reported that incidence is higher when the RF ablation is performed in systemic chambers (1.82%).1 The ablation of AF bears a risk of thrombo-embolic complication that is inherent to the procedure and has been reported in up to 5% of the patients.8 In a worldwide survey on efcacy and safety of the RF ablation for human AF,7 including 8745 patients, 4 early deaths were reported in which 2 of them resulting from massive

520

J.J. Blanc et al.

cerebral thrombo-embolism. The reported risk of non-fatal stroke was 0.28%, and transient ischaemic attacks were observed in 0.66% of the patients. In another large series of AF ablation,10 thrombo-embolism occurred in 1.1% of the patients, 0.9% of which were observed within 2 weeks of the procedure, despite the use of low-molecular-weight heparin in half of these patients. In all patients, INR levels were sub-therapeutic. Late thrombo-embolism occurred in 0.2% of the patients 610 months after the procedure, despite therapeutic INR. Half of these patients had recurrence of AF. In a large non-randomized study comparing RF ablation of AF with anti-arrhythmic drug therapy,35 no thrombo-embolic complication was observed in the peri-procedure period. Late thrombo-embolism occurred more frequently in medically treated patients (10 vs. 2.5% in the ablated patients) and was associated with a higher recurrence of AF (58 vs. 20%). Thus, these results seem to underestimate the true incidence of thrombus formation that might result in subclinical events. Results of a study performed with intracardiac echocardiography seem to report thrombus formation in more than 10% of the patients.19 In 90% of the patients, the thrombus could be withdrawn into the right atrium by pulling back the sheath and the mapping catheter. In the remaining patients, the thrombus was wedged in the inter-atrial septum and was incompletely withdrawn in the right atrium or was only recognized on post-procedure review of intracardiac images. None of these patients had any neurological complaint following the procedure. In the absence of prospective and multicentre evidence, it is not possible to formulate precise recommendations. Nevertheless, a cohort of basic recommendations are summarized below, based on pathophysiological considerations, single-centre experiences, and consensus.

Minimize or eliminate the generation of thrombi during the procedure Intravenous heparin administration, an adjunctive continuous heparinized ush, and correct technique to aspirate and ush sheaths placed on the systemic side of the circulation are the bare minimum measures necessary during the procedure. Additionally, intracardiac echocardiography monitors the development of thrombi (and perhaps micro-bubble formation) and may help reduce the thromb-oembolic complication rate, particularly if an external irrigated-tip catheter is not used for ablation. Maintaining electrode temperatures as low as possible, preferably with external irrigation, helps reduce the formation of soft coagulum and char. Simple measures such as ensuring a continuous (100200 cc/h) heparinized ush through the side-arm of all systemic sheaths (to be maintained despite catheter exchange), withdrawing the sheath into the right atrium after introducing the ablation or circular pulmonary veins mapping catheter into the left atrium, and minimizing the procedure and ablation times should be widely adopted. Unresolved issues remain such as the appropriate intensity of heparin anticoagulation during the procedure, which has varied from one laboratory to anotherranging from an ACT target of 200 to 400 s and even to no ACT monitoring. A related issue is the timing of institution of heparin therapy, indeed; although most physicians administer heparin after the conrmation of the LA access, there are advocates of administration even before transseptal puncture.

Minimize or eliminate the possibility of pre-existing left atrial thrombi Effective continuous pre-procedure anticoagulation (target INR 23) for a minimum of 46 consecutive weeks leading up to the intervention is important, perhaps supplemented by a TOE before the intervention (ie, on the same or previous day). Effective oral anticoagulation is expected to minimize the development of intracardiac thrombus or to encourage endothelialization. Transoesophageal echocardiography screening is an additional measure that should be able to detect all but the smallest LA thrombi. Intuitively, it appears to be important to avoid windows of ineffective (or sub-therapeutic) anticoagulation, particularly in patients at high or higher risk of atrial thrombi formation (e.g. patients with a previous history of thrombo-embolic events, those with prosthetic valves, or with LA smoke), and fractionated or unfractionated heparin is frequently used to provide effective anticoagulation during the interval between cessation of oral anticoagulation and 412 h before the procedure. This interval is required to ensure that the INR declines sufciently to diminish the risk of uncontrolled bleeding or tamponade and depending upon the half-life of the anti-vitamin K used, it ranges from 48 h to 5 days. Although no data are available, most interventionalists believe that an RF ablation can be safely performed if the INR is below 1.8.

Minimize or eliminate thrombus generation following the procedure The aim of anticoagulation management during this phase is to permit a smooth transition, which allows uncomplicated free sheath removal while at the same time ensures minimal interruption of effective anticoagulation. Although published details are limited, heparin is usually withheld for a xed period (14 h) or till the ACT declines to 150 s and sheaths are removed. Although the risk of haemorrhagic complicationslocal and delayed tamponadeis elevated during the rst 1224 h post-procedure, intravenous heparin is preferred to fractionated heparin during this period in view of unfractionated heparins shorter half-life, ability to monitor its effect rapidly with bedside ACT or prothrombin time (PTT), and ability to antagonize with protamine. Haemostasis after arterial sheath removal requires careful attention to anticoagulation intensity, and some physicians get around this problem by either avoiding arterial puncture or by placing a thin gauge cannula only sufcient for pressure monitoring. The practice of protamine reversal should be discouraged, although there may not be much choice in the rare event of tamponade. Therapeutically effective levels of anticoagulation are maintained with intravenous heparin till the following day and then replaced with fractionated heparin. Oral anticoagulation is started on the evening of the procedure, and weight-adjusted fractionated heparin continued till an INR . 2 is achieved.

Consensus document on antithrombotic therapy

521

Ventricular tachycardia ablation associated with structural heart disease Radiofrequency ablation can be applied in the treatment of VT in patients with left ventricular dysfunction because of prior myocardial infarction,7577 dilated cardiomyopathy,78,79 bundle branch re-entry,80,81 and various forms of idiopathic VT.82 Although the risk of thrombo-embolic complications associated with left-sided ablations can be as high as 2.8%,1 there are no recommendations with regard to anticoagulation in left-sided VT. In most studies of VT ablation, heparin infusion of 1000 U/h is administered after the insertion of sheath preceded by a bolus of at least 5000 U, with no ACT monitoring during the procedure.76,8385 Other authors performed ACT monitoring during the procedure with the target values of 200250 s.77,86 Although manyif not allconsiderations offered for ablation of AF hold true for left-sided VT, the access route is usually arterial with retrograde crossing of the aortic valve with a bare catheter into a high pressure LV in contrast to a transseptal access into the low pressure LA through a long sheath. As a result, a sheath is used only for a transseptal, transmitral access to the LV and then it would be wise to use the same precautions as for AF procedures. Echocardiographic screening is necessary to rule out the presence of intracardiac thrombus, particularly within the LV. Transoesophageal echocardiography generally provides sub-optimal images of the LV, particularly its apical region.
Recommendations for catheter ablation of atrial brillation Warfarin for at least 4 weeks prior to the ablation procedure. Stop warfarin 45 days before the ablation procedure. Bridging therapy with heparin (either low-molecular-weight heparin or unfractionated heparin) until the day before the ablation procedure. Peri-procedure anticoagulation After sheath insertion and transseptal puncture, administration of a bolus of IV heparin (bolus dose empirically 500010 000 U or 50100 U/kg) followed by continuous infusion of 1000 1500 U/h in order to achieve ACT at least in excess of 300 s is checked every 3045 min. At the completion of the procedure, IV heparin is discontinued and sheaths removed when the ACT is sub-therapeutic (,160 s). IV heparin to be resumed for 1224 h at a maintenance dose of 1000 U/h without a bolus that will maintain a PTT at 6080 s or at least twice the baseline level. Oral anticoagulation to be resumed the day of the procedure. Replace IV heparin with subcutaneous low-molecular-weight heparin after 1224 h. Stop low-molecular-weight heparin when the target INR2,3 is reached. Continue therapeutic warfarin for a minimum of 12 weeks after the ablation procedure. Recommendations for catheter ablation of ventricular tachycardia with overt heart disease In the presence of prior anticoagulation with warfarin, stop anticoagulation with therapeutic warfarin 45 days before the ablation procedure. Bridging therapy may be administered with heparin (either low-molecular-weight heparin or unfractionated heparin) until the day before the ablation procedure. Peri-procedure anticoagulation After sheath insertion, administration of a bolus of IV heparin (bolus dose empirically 500010 000 U or 50100 U/kg) followed by continuous infusion of 10001500 U/h in order to maintain the ACT level of 300 s.

At the completion of the procedure, IV heparin is discontinued and sheaths removed when the ACT is sub-therapeutic (,160 s). IV heparin may be administered for 1224 h, particularly in case of prior indication for anticoagulation in which case oral anticoagulation to be resumed the day of the procedure. Replace IV heparin with subcutaneous low-molecular-weight heparin after 1224 h. Stop low-molecular-weight heparin when the target INR 2,3 is reached. Continue therapeutic warfarin as per original indication (but at least for 1 month). In the absence of prior indication for warfarin, peri-procedure anticoagulation as above followed by fractionated heparin or IV heparin for 1224 h and aspirin thereafter (80325 mg/day) for at least 1 month.

Table 2 shows venous thrombosis and complications associated with vascular access. Although complications because of vascular access are inevitably associated with invasive electrophysiological procedures, no randomized study comparing the effects of various anticoagulation regimens or local approach with the catheterization site has, to the best of our knowledge, been published. The clinical practice has evolved with little scientic evidence. Complications reported from a few studies are summarized in Table 3. The overall rate of vascular access-related complications ranges from 0.01 to 4%.50,51,8790 A signicantly higher complication rate has been reported in the elderly (.65 years old) than in young patients undergoing electrophysiological study (2.2 vs. 0.5%, P 0.0002) or RF ablation (6.1 vs. 2.0%, P 0.00 015).89 The incidence of vascular complications depends on several factors: type of vascular access (arterial, venous, or both), site of vascular access (i.e. femoral vs. subclavian or jugular), number of introduced catheters, length of the procedure, patients prole (i.e. obesity and baseline coagulation parameters), type of anticoagulation used, management of catheterization site during the procedure (i.e. ush) and afterwards (immediate vs. delayed catheter removal, duration and strength of compression, and use of protamine), and operator experience.

Venous haematoma and thrombosis

The most frequent complications associated with venous access are signicant haematoma and venous thrombosis (18 of 11 258 procedures, Table 1). Despite the lack of supporting data, the introduction of two sheaths through one puncture site probably increases the risk of haematoma, as does the use of wide-calibre sheaths for several simultaneous catheters. In children, the rate of femoral vein occlusion may be high, reaching 22% as documented by magnetic resonance angiography, despite the administration of intravenous heparin. However, all the cases were asymptomatic.91 Also, detailed ultrasonography revealed a surprisingly high rate of non-occlusive deep vein thrombosis in adults (18%), which resolved in all but one patient within 1 week after the procedure.92 This study also showed that the local complication rate was not associated with the number of introduced catheters or such clinical variables as age,

522

J.J. Blanc et al.

Deep vein thrombosis with pulmonary embolism (n 1) and groin haematoma (n 3) Pneumothorax (n 6); arterial haematoma (n 3); venous thrombosis (n 8); femoral pseudoaneurysm (n 1); arterio-venous stula (n 1); and infection (n 1) Pseudoaneurysm (n 2) and arterio-venous stula (n 1) Aortic dissection (n 2); femoral artery thrombosis (n 3); deep vein thrombosis (n 1); signicant haematoma (n 2)

Table 3 Major complications following catheter ablation for atrial brillation Complication type No. of patients Percentage of patients

Two pneumothorax and one pseudoaneurysm

Venous thrombosis (n 3)

For all types of procedures (n 8745 patients) Periprocedural death 4 0.05 Tamponade 107 1.22 Sepsis, abscesses, or 1 0.01 endocarditis Pneumothorax 2 0.02 Haemothorax 14 0.16 Permanent diaphragmatic 10 0.11 paralysis Femoral pseudoaneurysm 47 0.53 Arterovenous stulae 37 0.42 Valve damage 1 0.01 Aortic dissection 3 0.03 For procedures involving left atrial ablation (n 7154 patients) Stroke 20 0.28 Transient ischaemic attack 47 0.66 Pulmonary vein stenosis No. with ,50% stenosis Acute 23 0.32 Chronic 94 1.31 No. with closure Acute 2 0.03 Chronic 15 0.21 Patients with symptoms Acute 3 0.04 Chronic 41 0.57 Patients undergoing intervention Percutaneous 51 0.71 Surgical 2 0.03 Grand total 524 5.9

Table 2 Data from the literature on vascular complications associated with catheterization site (11 258 procedures in 9813 patients)

Overall complication rate

Details

3 (4%) 12 (0.4%)

3 (0.04%)

19 (0.3%)

4 (1.4%)

Heparin infusion to achieve ACT . 350 s Left-sided: heparin bolus 5000 U, then 1000 U/h, reversed by protamine at the end. Right-sided: no heparin Various

Heparin bolus 2500 U, then 1000 U/h

0.01%

Anti-coagulation protocol

gender, height, body weight, procedure time, femoral vein diameter, or heparinization. Despite the high incidence of silent occlusion of a punctured femoral vein, clinical pulmonary embolism is infrequent (1 of 11 258 procedures, Table 1). However, there may be a great number of sub-clinical emboli, the consequences of which are unknown.
Various

Various

Complications due to arterial puncture

The most frequent complication associated with arterial access is haematoma, followed by pseudoaneurysm and arterio-venous stula. Dangas et al.93 reported an incidence of 5.1% vascular complications after percutaneous coronary interventions with standard femoral compression. In a systematic literature search, arterial puncture closing devices appeared to be effective in terms of reducing time to haemostasis; however, when looking at the studies with a higher methodological quality, complications such as haematoma and pseudoaneurysm formation occurred more often when devices were used.94 Pseudoaneurysm occurs in 0.82.2% of the patients after interventional procedures.95 Ultrasound-guided compression has replaced the need for surgical repair of femoral artery pseudoaneurysms in some cases. Also, thrombin injections can close the aneurysm.96 Arterio-venous stulation (2 of

Population studied

Cheema et al.89 Chen et al.90

Arch Mal Coeur Vaiss88

Epstein et al.51

Study

Scheinman and Huang50

Kihel et al.87

64 patientsAF ablation 2593 patients3966 various ablation or diagnostic EP procedures 758 patients830 procedures (WPW or AVNRT/a-v nodal ablations) 3357 procedures

276 elderlyAVNRT ablation

2765 patientsvarious ablation procedures

Consensus document on antithrombotic therapy

523

11 258 procedures, Table 1) and dissection of large arteries (2 of 11 258 procedures, Table 1) are infrequent and usually caused by poor technique.

Other complications
Infection has been reported in 3 of 9813 patients (Table 1). Nerve injury is very infrequent. Pneumothorax is an infrequent complication when the subclavian vein is punctured and very rare after jugular vein puncture.

Anticoagulation may also be considered on an individual basis, particularly for long procedures. Reversal of anticoagulation before catheter removal has been suggested in some reports, but no randomized study was performed to clarify this issue.

Recommendations Prevention of venous thrombosis: the use of intravenous heparin can be individualized as discussed elsewhere in the document; however, in patients with a history of distal venous thrombosis (DVT), heparin is indicated; only light compression at the puncture site and rapid patients mobilization (46 h); ushing of sheaths with heparin; draining back blood through sheaths before sheaths withdrawal in order to prevent thrombus migration from sheath to the femoral vein; limiting the number of femoral vein or artery sheaths on the same side. Prevention of arterial complications: bleedingproper compression or angioseal as after coronary angiography and avoidance of excessive anticoagulation; prevention of false aneurysm or arterio-venous stulaproper puncture technique and proper compression after sheath removal.

Prevention of venous thrombosis and embolism

We lack large randomized trials with clinical endpoints for the effects of aspirin and other platelet inhibitors, as well as for heparin. There is a time-dependent activation of platelets, coagulation, and brinolysis due to puncture and to the presence of sheaths and catheters.28 Charng et al.97 found the same pattern in left- and right-sided procedures. Saline irrigation of the venous sheaths did not prevent this, but intravenous heparin administered immediately after the introduction of the venous sheaths decreased haemostatic activation signicantly.98 Heparin also reduces the platelet activation.99 Several studies have examined the effects of preventive measures upon surrogate endpoints, i.e. activation of coagulation that occurs after catheter introduction. Wang et al.100 suggested that pre-treatment with platelet inhibitors could reduce the incidence of thrombo-embolic events. In another study, aspirin and ticlopidin had to be combined to prevent the rise of D-dimer during the procedure;39 however, no bleeding or thrombo-embolic complications were noted in the treated or untreated groups. Thus, clinical benets of such an approach could not be documented. Aspirin only modestly reduces the risk of deep vein thrombosis in high-risk medical and surgical patients,101 and there are no studies on aspirin use after invasive electrophysiological procedures, although in some centres, aspirin is prescribed for 13 months after the RF ablation. Finally, clinical observations suggest that late post-procedural deep vein thrombosis is so infrequent that even if it were effective would hardly be indicated.53 Heparin and low-molecular-weight heparin are effective agents in preventing deep venous thrombosis.102 Clinical practice varies from laboratories that always use heparin for right-sided procedures than those who never do so. The most frequently reported regimen is the administration of heparin during left-sided procedures (5000 U in bolus and 1000 U/h), whereas patients undergoing right-sided procedures usually do not receive heparin, unless there are other indications for heparin use, or the procedure is lengthy and with numerous RF applications. However, no study has prospectively and in a randomized manner studied the effects of heparin usage on the rate of complications associated with vascular access during invasive electrophysiological procedures. The higher rate of complications (4%) in patients undergoing ablation of AF suggests that aggressive heparin treatment may be associated with an increased risk of local complications.89 The NASPE Guidelines103 state that for procedures involving the right heart, anticoagulation should be strongly considered if an intracardiac defect that could allow paradoxical embolism is present, or when mapping or ablation devices that increase the risk of thrombus formation are used.

Special situations
Electrophysiological study and ablation in infants and children
Invasive EPS and catheter ablation in infants or children are rare, but increasing in number and anticoagulation regimen needs to be addressed. The problem with this population is that among infants and children, there is a large heterogeneity with respect to underlying heart disease, body weight, and size. There are different aspects regarding anticoagulation such as risk of cardiac perforation, bleeding, and risk of thrombo-embolism. Furthermore, when compared with adults there is an increasing risk of arterial occlusion or venous thrombosis because of the discordance between smaller vessel diameter and catheter size. There are data from the Pediatric RF Catheter Ablation Registry that provide an overview on the general risk of complications, although there is no information on the anticoagulation protocol used. The risk of emboli or thrombi was 6/3187 for ablation of supra-VT in the new era. Unfortunately, the risk of bleeding was not mentioned.104106 In the Report of the Seventh ACCP Conference on Antithrombotic and thrombolytic therapy, published in 2004, the following recommendations for thromboprophylaxis in diagnostic cardiac catheterization in neonates and children are given107: For neonates and children requiring cardiac catheterization via an artery, IV heparin prophylaxis is recommended (Grade 1A). It is suggested to use heparin doses of 100150 U/kg as a bolus. Further doses may be required in prolonged procedures (both Grade 2B).

524

J.J. Blanc et al.

In this report, it is referred to neonates as infants from birth to 28 days of age corrected for gestational age and to children as from 28 days of age to 16 years. When a left-sided ablation is performed, the administration of heparin is weight-adjusted and targeted at an effective anticoagulation as in adults to avoid thrombo-embolism. Differences in heparin effects depending on the age have to been taken into account. It can be summarized that in contrast to adults or adolescents, the risk of arterial occlusion or venous thrombosis has to be considered because of vessel/sheath and electrode-mismatch in children and infants.

Recommendations For neonates and children requiring diagnostic cardiac catheterization via an artery intravenous heparin prophylaxis is recommended. It is suggested to use heparin at 100150 U/kg as a bolus. Further doses may be required in prolonged procedures. When a left-sided ablation is performed, the administration of heparin is weight-adjusted and targeted at an effective level as in adults to avoid thrombo-embolism. For exclusively transvenous approaches, no specic recommendations are given.

Electrophysiological study and ablation in patients requiring permanent anticoagulation

Electrophysiological study and/or catheter ablation in patients with the need for permanent anticoagulation is a relevant and frequent setting in every day practice. All patients with mechanical heart valves, AF and relevant additional risk factors, and LA or left ventricular thrombus will need effective anticoagulation before and after the procedure. The thrombo-embolic risk for interventions on the right side such as AFL, atrial, or junctional tachycardias is very low (discussed earlier). However, there are no specic data on patients who require permanent anticoagulation.

cardiac tamponade are different when the patient is on both drugs. For the introduction and manoeuvring of the sheaths and catheters, the risk of peripheral bleeding or complications when using aspirin and clopidogrel is low. In a large prospective trial on the use of clopidogrel and aspirin for the prevention of stent thrombosis after coronary intervention, the risk of major bleeding was 0.6% and the risk of vascular complication was 0.5%.108,109 In all these interventions, additional use of effective unfractionated heparin was present and presumably adds to the risk of bleeding so that the risk in electrophysiology or approaches without heparin is probably lower. Thus, the risk for left-sided electrophysiological interventions should be no larger than this. In reality, the general risk of vascular complications during or after ablation in the Spanish EP registry is 0.37% in 6162 ablations.110 On the basis of these data, regarding vascular complications, the use of clopidogrel should not be a relevant issue. With respect to the left-sided approaches, the bleeding risk should be comparable with coronary interventions, because usually only one femoral arterial sheath with 68 Fr diameter is used when compared with coronary interventions. The other problem may be the management of cardiac tamponade or pericardial effusion because of perforation when the patient is on aspirin and clopidogrel. Again, there are no relevant data in the literature on this specic question and therefore no denite answer can be given. However, the risk of perforation in right-sided catheter ablation is certainly extremely low and for left-sided interventions also (except in the ablation of AF which carries higher incidences of tamponade). It can be assumed that bleeding is more severe and more difcult to be managed when the patient is on aspirin and clopidogrel.

Recommendations Right-sided procedures and uncomplicated left-sided procedures, such as ablation of accessory pathways, can be performed with a low risk. Ablation of AF should not be performed in patients on aspirin and clopidogrel because of an increased risk of major bleeding secondary to cardiac tamponade. In these cases, ablation should be postponed to a time when aspirin and clopidogrel can be safely discontinued.

Recommendations For anticoagulation management in patients requiring permanent effective anticoagulation, the 2006 Guidelines for the management of patients with valvular heart diseases or the guidelines for the management of patients with AF could be applied. For the specic recommendations for anticoagulation regimen, see section on Anticoagulation in high-risk patients.

Conict of interest: none declared.

References
Electrophysiological study and ablation in patients with clopidogrel and aspirin
With the increasing use of intracoronary stents and especially drug-eluting stents, the issue of anticoagulation and invasive electrophysiological study and catheter ablation is certainly increasing. There are two different problems: the risk of peripheral bleeding and the risk of cardiac tamponade due to cardiac perforation. Although both agents cannot be adequately antagonized, a question of whether the risk of bleeding and the outcome of
1. Zhou L, Keane D, Reed G, Ruskin J. Thromboembolic complications of cardiac RF catheter ablation: a review of the reported incidence, pathogenesis and current research directions. J Cardiovasc Electrophysiol 1999;10:61120. 2. Hindricks G. The Multicentre European RF Survey (MERFS): complications of RF catheter ablation of arrhythmias. The Multicentre European RF Survey (MERFS) investigators of the Working Group on Arrhythmias of the European Society of Cardiology. Eur Heart J 1993; 14:164453. 3. Greene TO, Huang SK, Wagshal AB, Mittleman RS, Pires LA, Mazzola F et al. Cardiovascular complications after RF catheter ablation of supraventricular tachyarrhythmias. Am J Cardiol 1994;74:6157.

Consensus document on antithrombotic therapy

4. Lip GY, Tello-Montoliu A. Management of AF. Heart 2006;92:117782. 5. Karch MR, Zrenner B, Deisenhofer I, Schreieck J, Ndrepepa G, Dong J et al. Freedom from atrial tachyarrhythmias after catheter ablation of AF: a randomized comparison between 2 current ablation strategies. Circulation 2005;111:287580. 6. Hindricks G, Piorkowski C, Tanner H, Kobza R, Gerds-Li JH, Carbucicchio C et al. Perception of AF before and after RF catheter ablation: relevance of asymptomatic arrhythmia recurrence. Circulation 2005;112:30713. 7. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J et al. Worldwide survey on the methods, efcacy, and safety of catheter ablation for human AF. Circulation 2005;111:11005. 8. Kok LC, Mangrum JM, Haines DE, Mounsey JP. Cerebrovascular complication associated with pulmonary vein ablation. J Cardiovasc Electrophysiol 2002;13:7647. 9. Gasparini M, Mantica M, Brignole M, Gianfranchi L, Menozzi C, Pizzetti F et al. Thromboembolism after AV node ablation and pacing: long term follow up. Heart 1999;82:4948. 10. Oral H, Chugh A, Ozaydin M, Good E, Fortino J, Sankaran S et al. Risk of TEE after percutaneous LA radiofrequency ablation of AF. Circulation 2006;114:75965. 11. Thibault B, Talajic M, Dubuc M, Guerra P, Gagne P, Roy D et al. Canadian Trial of AF. Thromboembolic events occur despite sinus rhythm maintenance in patients treated for AF: the Canadian Trial of AF experience. Can J Cardiol 2004;20:1959. 12. Gronefeld GC, Wegener F, Israel CW, Teupe C, Hohnloser SH. Thromboembolic risk of patients referred for RF catheter ablation of typical AFL without prior appropriate anticoagulation therapy. Pacing Clin Electrophysiol 2003;26:3237. 13. Lip GY, Kamath S. Do electrophysiological interventions confer a prothrombotic state? Pacing Clin Electrophysiol 2001;24:14. 14. Lemola K, Desjardins B, Sneider M, Case I, Chugh A, Good E et al. Effect of LA circumferential ablation for AF on left atrial transport function. Heart Rhythm 2005;2:9238. 15. Sparks PB, Jayaprakash S, Vohra JK, Mond HG et al. LA stunning following RF catheter ablation of chronic atrial utter. J Am Coll Cardiol 1998; 32:46875. 16. Missault L, Jordaens L, Gheeraert P, Adang L, Clement D. Embolic stroke after unanticoagulated cardioversion despite prior exclusion of atrial thrombi by transoesophageal echocardiography. Eur Heart J 1994;15: 127980. 17. Beukema WP, Elvan A, Sie HT, Misier AR, Wellens HJ. Successful radiofrequency ablation in patients with previous atrial brillation results in a signicant decrease in left atrial size. Circulation 2005;112:208995. 18. Dorbala S, Cohen AJ, Hutchinson LA, Menchavez-Tan E, Steinberg JS. Does RF ablation induce a prothrombotic state? Analysis of coagulation system activation and comparison to electrophysiologic study. J Cardiovasc Electrophysiol 1998;9:115260. 19. Ren JF, Marchlinsli F, Callans DJ. Left atrial thrombus associated with ablation of atrial brillation: identication with intracardiac echocardiography. J Am Coll Cardiol 2004;43:18617. 20. Cauchemez B, Extramiana F, Cauchemez S, Cosson S, Zouzou H, Meddane M et al. High-ow perfusion of sheaths for prevention of thromboembolic complications during complex catheter ablation in the left atrium. J Cardiovasc Electrophysiol 2004;15:27683. 21. Huang SK, Graham AR, Hoyt RH, Odell RC. Transcatheter dessication on the canine left ventricle using radiofrequency energy-a pilot study. Am Heart J 1987;114:428. 22. Haines DE, Verow AF. Observations on electrode-tissue interface temperature and effect on electrical impedance during radiofrequency ablation of the ventricular myocardium. Circulation 1990;82:10348. 23. Wysokinski WE, Owen WG, Fass DN, Patrzalek DD, Murphy L, McBane RD 2nd. Atrial brillation and thrombosis: immunohistochemical differences between in situ and embolized thrombi. J Thromb Haemost 2004;2:163744. 24. Lip GYH, Edwards SJ. Stroke prevention with aspirin, warfarin and xilmelagatran in patients with non-valvular AF: a systematic review and meta-analysis. Thromb Res 2006;118:32133. 25. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:7186. 26. Lip GY, Karpha M. Anticoagulant and antiplatelet therapy use in patients with AF undergoing percutaneous coronary intervention: the need for consensus and a management guideline. Chest 2006;130:18237.

525
27. Choudhury A, Chung I, Blann AD, Lip GY. Elevated platelet microparticle levels in nonvalvular atrial brillation: relationship to p-selectin and antithrombotic therapy. Chest 2007;131:80915. 28. Annsen OG, Gjesdal K, Brosstad F, Orning OM, Amlie JP. The activation of platelet function, coagulation, and brinolysis during RF catheter ablation in heparinized patients. J Cardiovasc Electrophysiol 1999;10: 50312. 29. Manolis AS, Melita-Manolis H, Vassilikos V, Maounis T, Chilidakis J, Christopoulan-Cokkinou V et al. Thrombogenecity of RF lesions: results with serial D-dimer determinations. J Am Coll Cardiol 1996;28:12576. 30. Michelucci A, Antonuci E, Conti AA, Alessandrello Liotta A, Fedi S, Padeletti L et al. Electrophysiologic procedures and activation of the hemostatic system. Am Heart J 1999;138:12832. 31. Lee DS, Dorian P, Downar E, Burns M, Yeo EL, Gold WL et al. Thrombogenicity of radiofrequency ablation procedures: what factors inuence thrombus generation? Europace 2001;3:195200. 32. Van Oeveren W, Crijns HJ, Korteling BJ, Wegereef EW, Haan J, Tigchelaar E et al. Blood damage, platelet and clotting activation during application of RF or cryoablation catheters: a comparative in vitro study. J Med Eng Technol 1999;23:205. 33. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL et al. AFFIRM Investigators. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004;109:150913. 34. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial brillation: 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 Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006;48: e149e246. 35. Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial brillation. J Am Coll Cardiol 2003;42: 18597. 36. Khan IA. Atrial stunning: basics and clinical considerations. Int J Cardiol 2003;92:11328. 37. Wazni OM, Rossillo A, Marrouche NF, Saad EB, Martin DO, Bhargava M et al. Embolic events and char formation during pulmonary vein isolation in patients with atrial brillation: impact of different anticoagulation regimens and importance of intracardiac echo imaging. J Cardiovasc Electrophysiol 2005;16:57681. 38. Ren JF, Marchlinski FE, Callans DJ, Gerstenfeld EP, Dixit S, Lin D et al. Increased intensity of anticoaguoation may reduce risk of thrombus during atrial brillation ablation procedures in patients with spontaneous echo contrast. J Cardiovasc Electrophysiol 2005;16:4747. 39. Manolis AS, Maounis T, Vassilikos V, Melita-Manolis H, Psarros L, Terzoglou G et al. Pretreatment with antithrombotic agents during radiofrequency catheter ablation: a randomized comparison of aspirin versus ticlopidine. J Cardiovasc Electrophysiol 1998;9:114451. 40. Kamath S, Blann AD, Chin BS, Lip GY. A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in AF. J Am Coll Cardiol 2002;40:48490. 41. ACTIVE Writing Group on behalf of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S et al. Clopidogrel plus aspirin versus oral anticoagulation for AF in the AF Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:190312. 42. Calkins H, Prystowsky E, Carlson M, Klein LS, Saul JP, Gillette P et al. Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Circulation 1994;90:127986. 43. Weiss C, Antz M, Thuneke F, Meinertz T, Kuck KH, Willems S. Radiofrequency catheter ablation using long coiled electrodes: impact of irrigation on lesion dimensions and incidence of coagulum formation. Pacing Clin Electrophysiol 2001;24:9338. 44. Yokoyama K, Nakagawa H, Wittkampf FH, Pitha JV, Lazzara R, Jackman WM. Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop. Circulation 2006;113:119. 45. Horlitz M, Schely P, Shing D, Ghouzi A, Muller M, Sause A et al. Circumferentail pulmonary vein ablation for treatment of atrial brillation using an irrigated-tip catheter. Am J Cardiol 2004;94:9457.

526
46. Khairy P, Chauvet P, Lehmann J, Lambert J, Macle L, Tanguay JE et al. Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 2003;107:204550. 47. Marrouche NF, Martin DO, Wazni O, Gillinov AM, Klein A, Bhargave M et al. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial brillation: impact on outcome and complications. Circulation 2003;107:27106. 48. Kortz RA, Delemarre BJ, van Dantzig JM, Bot HK, Visser CA. Left atrial appendage blood ow determined by transoesophageal echocardiography in health subjects. Am J Cardiol 1993;71:97681. 49. Tabata T, Oki T, Fukuda N, Iuchi A, Manabe K, Kaggi Y et al. Inuence of aging on left atrial appendage ow velocity patterns in normal subjects. J Am Soc Echocardiogr 1996;9:27480. 50. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. PACE 2000;23:10208. 51. Epstein M, Knapp L, Martindill M, Lulu J, Triedman J, Calkins H et al. Embolic complications associated with RF catheter ablation. Am J Cardiol 1996;77:6558. 52. Greene T, Huang S, Wagshal A, Mittleman R, Pires L, Mazzola F et al. Cardiovascular complications after RF catheter ablation of supraventricualr tachyarrhythmias. Am J Cardiol 1994;74:6157. 53. Thakur RK, Klein GJ, Yee R, Zardini M. Embolic complications after RF catheter ablation. Am J Cardiol 1994;74:2789. 54. Wood KA, Eisenberg SJ, Kalman JM, Drew BJ, Saxon LA, Lee RJ et al. Risk of thromboembolism in chronic atrial utter. Am J Cardiol 1997;79: 10437. 55. Seidl K, Hauer B, Schwick NG, Zellner D, Zahn R, Senges J. Risk of TEE in patients with atrial utter. Am J Cardiol 1998;82:5803. 56. Biblo LA, Yuan Z, Quan KJ, Mackall JA, Rimm AA. Risk of stroke in patients with atrial utter. Am J Cardiol 2001;87:3469, A9. 57. Halligan SC, Gersh BJ, Brown RD Jr, Rosales AG, Munger TM, Shen WK et al. The natural history of lone atrial utter. Ann Intern Med 2004; 140:2658. 58. Ghali WA, Wasil BI, Brant R, Exner DV, Cornuz J. AFL and the risk of thromboembolism: a systematic review and meta-analysis. Am J Med 2005;118:1017. 59. Mehta D, Baruch L. Thromboembolism following cardioversion of common atrial utter. Risk factors and limitations of transesophageal echocardiography. Chest 1996;110:10013. 60. Lanzarotti CJ, Olshansky B. Thromboembolism in chronic atrial utter: is the risk underestimated? J Am Coll Cardiol 1997;30:150611. 61. Liaudet L, Kehtari R, Enrico JF. Cerebral thromboembolism after direct current cardioversion for pure atrial utter. Intensive Care Med 1997; 23:1967. 62. Bertaglia E, DEste D, Franceschi M, Pascotto P. Cardioversion of persistent AFLin non-anticoagulated patients at low risk for thromboembolism. Ital Heart J 2000;1:34953. 63. Corrado G, Sgalambro A, Mantero A, Gentile F, Gasparini M, Bufalino R et al. Thromboembolic risk in atrial utter. The FLASIEC (FLutter Atriale Societa Italiana di Ecograa Cardiovascolare) multicentre study. Eur Heart J 2001;22:104251. 64. Elhendy A, Gentile F, Khandheria BK, Gersh BJ, Bailey KR, Montgomery SC et al. Thromboembolic complications after electrical cardioversion in patients with atrial utter. Am J Med 2001;111:4338. 65. Hernandez Madrid A, Pena Perez G, Gonzalez Rebollo JM, Gomez Bueno M, Marin Marin I, Bernal Morell E et al. Systemic embolism after reversion to sinusal rhythm of persistent atrial utter. Rev Clin Esp 2003;203:2305. 66. Bikkina M, Alpert MA, Mulekar M, Shakoor A, Massey CV, Covin FA. Prevalence of intraatrial thrombus in patients with atrial utter. Am J Cardiol 1995;76:1869. 67. Irani WN, Grayburn PA, Afridi I. Prevalence of thrombus, spontaneous echo contrast, and atrial stunning in patients undergoing cardioversion of atrial utter. A prospective study using transesophageal echocardiography. Circulation 1997;95:9626. 68. Omran H, Jung W, Rabahieh R, MacCarter D, Illien S, Rang B et al. Left atrial appendage function in patients with atrial utter. Heart 1997;78: 2504. 69. Thumala A, Parra C, Maragano P, Puelma A, Florenzano F. Thromboembolic risk factors in atrial utter. Transesophageal echocardiographic study. Rev Med Chil 2000;128:132734. 70. Schmidt H, von der Recke G, Illien S, Lewalter T, Schimpf R, Wolpert C et al. Prevalence of left atrial chamber and appendage thrombi in patients with AFL and its clinical signicance. J Am Coll Cardiol 2001; 38:77884.

J.J. Blanc et al.

71. Weiss R, Marcovitz P, Knight BP, Bahu M, Souza JJ, Zivin A et al. Acute changes in spontaneous echo contrast and atrial function after cardioversion of persistent atrial utter. Am J Cardiol 1998;82:10525. 72. Sparks PB, Jayaprakash S, Vohra JK, Mond HG, Yapanis AG, Grigg LE et al. Left atrial stunning following RF catheter ablation of chronic atrial utter. J Am Coll Cardiol 1998;32:46875. 73. Gronefeld GC, Wegener F, Israel CW, Teupe C, Hohnloser SH. Thromboembolic risk of patients referred for RF catheter ablation of typical AFL without prior appropriate anticoagulation therapy. Pacing Clin Electrophysiol 2003;26:3237. 74. Takami M, Suzuki M, Sugi K, Ikeda T. Time course for resolution of left atrial appendage stunning after catheter ablation of chronic atrial utter. J Am Coll Cardiol 2003;41:220711. 75. Stevension WG, Friedman PL, Kocovic D, Sager PT, Saxon LA, Pavri B. Radiofrequency ablation of ventricular tachycardia after myocardial infarction. Circulation 1998;98:30814. 76. De Chilloux C, Lacroix D, Klug D, Magnin-Poull I, Marquie C, Messier M et al. Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction. Circulation 2002;105:72631. 77. Bogun F, Krishnan S, Siddiqui M, Marine JE, Schuger C, Oral H et al. Electrogram characteristics in postinfarction ventricular tachycardia. J Am Coll Cardiol 2005;46:66774. 78. Arenal A, Glez Torrecilla E, Ortiz M, Villacastin F, Fdez-Portales J, Sausa E et al. Ablation of electrograms with an isolated delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease. J Am Coll Cardiol 2003; 41:8192. 79. Delacatraz E, Stevenson WG, Ellison K, Marisel WH, Friedman PL. Mapping and radiofrequency catheter ablation of the three types of sustained monomorphic ventricular tachycardia in non ischemic heart disease. J Cardiovasc Electrophysiol 2000;11:117. 80. Tchou P, Jazayeri M, Denker S, Dongas J, Caceres J, Ahktar M et al. Transcatheter electrical ablation of right bundle branch. A method of treating macroreentrant ventricular tachycardia attributed to bundle branch reentry. Circulation 1988;78:24657. 81. Caceres J, Jazayeri M, McKinnie J, Avitall B, Denker ST, Tchou P et al. Sustained bundle branch reentry as a mechanism of clinical tachycardia. Circulation 1989;79:25670. 82. Simons GR, Klein GJ, Natale A. Ventricular tachycardia: pathophysiology and radiofrequency catheter ablation. Pacing Clin Electrophysiol 1997; 20:53451. 83. El-Shalakany A, Hadjis T, Papageorgiou P, Monahan K, Epstein L, Josephon ME. Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radiofrequency lesion in patients with coronary artery disease. Circulation 1999;99:22839. 84. Harada T, Stevenson WG, Kocovic DZ, Friedman PL. Catheter ablation of ventricular tachycardia after myocardial infarction: relation to endocardial sinus rhythm late potentials to the reentry circuit. J Am Coll Cardio 1997;30:101523. 85. Morady F, Harvey M, Kalbeisch SJ, El-Atassi R, Calkins H, Langberg JJ. Radiofrequency catheter ablation of ventricular tachycardia in patients with coronary artery disease. Circulation 1993;87:36372. 86. Della-Bella P, De Ponti R, Uriarte JAS, Tondo J, Klersy C, Carbucicchio C et al. Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia. Eur Heart J 2002;23: 41424. 87. Kihel J, Da Costa A, Kihel A, Romeyer-Bouchard C, Thevenin J, Gonthier R et al. Long-term efcacy and safety of RF ablation in elderly patients with AV nodal re-entrant tachycardia. Europace 2006; 8:41620. 88. Anonymous. Complications of RF ablation: a French experience. Le Groupe de Rythmologie de la Societe Francaise de Cardiologie. Arch Mal Coeur Vaiss 1996;12:1599605. 89. Cheema A, Dong J, Dalal D, Vasamreddy CR, Marine JE, Henrikson CA et al. Long-term safety and efcacy of circumferential ablation with pulmonary vein isolation. J Cardiovasc Electrophysiol 2006;17:10805. 90. Chen SA, Chiang CE, Tai CT, Cheng CC, Chiou CW, Lee SH et al. Complications of diagnostic electrophysiologic studies and RF catheter ablation in patients with tachyarrhythmias: an eight-year survey of 3,966 consecutive procedures in a tertiary referral center. Am J Cardiol 1996; 77:416. 91. Miga DE, McKellar LF, Denslow S, Wiles HB, Case CL, Gillette PC. Incidence of femoral vein occlusion after catheter ablation in children: evaluation with magnetic resonance angiography. Pediatr Cardiol 1997;18:2047.

Consensus document on antithrombotic therapy

92. Chen JY, Chang KC, Lin YC, Chou HT, Hung JS. Safety and outcomes of short-term multiple femoral venous sheath placement in cardiac electrophysiological study and RF catheter ablation. Jpn Heart J 2004;45: 25764. 93. Dangas G, Mehran R, Kokolis S, Feldman D, Satler LF, Pichard AD et al. Vascular complications after percutaneous coronary interventions following hemostasis with manual compression versus arterial puncture closing devices. J Am Coll Cardiol 2001;38:63841. 94. Koreny M, Riedmuller E, Nikfardjam M, Siostrzonek P, Mullner M. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis. JAMA 2004;291:3507. 95. Lenartova M, Tak T. Iatrogenic pseudoaneurysm of femoral artery: case report and literature review. Clin Med Res 2003;1:2437. 96. Kang SS, Labropoulos N, Mansour MA, Baker WH. Percutaneous ultrasound guided thrombin injection: a new method for treating postcatheterization femoral pseudoaneurysms. J Vasc Surg 1998;27:10328. 97. Charng MJ, Lin YJ, Chiu TY, Cheng CM, Ding PYA. Comparison of hemostatic activation created by right- and left-heart RF catheter ablation. Clin Cardiol 2004;27:916. 98. Annsen OG, Gjesdal K, Aass H, Brosstad F, Orning OM, Amlie JP. When should heparin preferably be administered during RF catheter ablation? Pacing Clin Electrophysiol 2001;24:512. 99. Wang LH, Jin ZM, Chen JZ, Zhu JH, Zheng LR, Tao QM et al. Effect of heparin on activation of platelet function in patients during RF catheter ablation. Clin Exp Pharmacol Physiol 2006;33:667. 100. Wang TL, Lin JL, Hwang JJ, Tseng CD, Lo HM, Lien WP et al. The evolution of platelet aggregability in patients undergoing catheter ablation for supraVT with RF energy: the role of antiplatelet therapy. Pacing Clin Electrophysiol 1995;18:198090. 101. Antiplatelet Trialists Collaboration. Collaborative overview of randomised trials of antiplatelet therapy III. Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994;308:23546. 102. Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D et al. Prevention of venous thromboembolism in

527
internal medicine with unfractionated heparin or low-molecular weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000;83:149. Scheinman M, Calkins H, Gillette P, Klein R, Lerman BB, Morady F et al. NASPE policy statement on catheter ablation: personnel, policy, procedures, and therapeutic recommendations. Pacing Clin Electrophysiol 2003;26:78999. Blaufox AD, Felix GL, Philip Saul J Participating Members of the Pediatric Catheter Ablation Registry*. RF catheter ablation in infants ,18 months old when is it done and how do they fare? Short-term data from the pediatric ablation registry. Circulation 2001;104:28038. Grady M, Eisenberg PR, Bridges ND. Rational approach to use of heparin during cardiac catheterization in children. J Am Coll Cardiol 1995;25: 7259. Kugler JD, Danford DA, Houston KA, Felix G The other participating members of the Pediatric RF Ablation Registry of the Pediatric Electrophysiology Society. Pediatric RF catheter ablation registry success, uoroscopy time, and complication rate for supraventricular tachycardia: comparison of early and recent eras. J Cardiovasc Electrophysiol 2002;13:33641. Monagle P, Chan A, Massicotte P, Chalmers A, Michelson AD. Antithrombotic therapy in children*: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:64587. Fox KA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ et al. Benets and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for nonST-elevation acute coronary syndrome: the clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) Trial. Circulation 2004;110:12028. Lee S, Park M, Hong Y, Kim B, Lee J, Song K et al. Triple versus dual antiplatelet therapy after coronary stenting impact on stent thrombosis. J Am Coll Cardiol 2005;46:18337. Alvarez-Lopez M, Rodr guez-Font E, Garc a-Alberola A. Registro Espanol de Ablacion con Cateter.V Informe Ocial de la Seccion de Electrosio log y Arritmias de la Sociedad Espanola de Cardiolog (2005) Rev Esp a a. Cardiol 2006;59:116574.

103.

104.

105.

106.

107.

108.

109.

110.