Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia

Transcription

1 European Heart Journal (2002) 23, doi: /euhj , available online at on Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia Long-term outcome in relation to acute electrophysiological findings P. Della Bella 1, R. De Ponti 2, J. A. S. Uriarte 2, C. Tondo 1, C. Klersy 4, C. Carbucicchio 1, C. Storti 3, S. Riva 1 and M. Longobardi 3 1 Centro Cardiologico Monzino, Institute of Cardiology, University of Milan, Milan, Italy; 2 Institute of Cardiology, Mater Domini Hospital, University of Insubria, Castellanza, Varese, Italy; 3 Institute of Cardiology, Città di Pavia Hospital, University of Pavia, Pavia, Italy; 4 Biometry and Clinical Epidemiology, Research Department, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy Aims Radiofrequency catheter ablation is effective at terminating ventricular tachycardia, but the overall clinical role of the technique in patients with a prior myocardial infarction is still debated, due to the uncertainties of the long-term reliability of the procedure. The purpose of this study was to prospectively investigate the relationship between acute results obtained by catheter ablation and long-term outcome in a homogeneous population of patients with post-myocardial infarction ventricular tachycardia. Methods and Results One hundred and twenty-four consecutive patients with recurrent, drug-refractory, haemodynamically tolerated ventricular tachycardia were included in the study. This population accounted for 30% of the patients with post-myocardial infarction ventricular tachycardia admitted between April 1992 and September 1997 to the investigating centres. The ablation was successful in eliminating sustained ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21 (17%) and failure in 12 (10%). Low dose amiodarone and/or betablockers were maintained in 86% of the patients. Over a median follow-up of 41 5 months (interquartile range months), there were 15 deaths (12%), three of which were sudden (2 4%); the 12 remaining patients died of heart failure. Event-free survival analysis showed a significally lower ventricular tachycardia recurrence rate in patients with a successful procedure as compared to those with failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years, P=0 003). A repeat procedure was performed in 15 patients with early recurrences and was followed in all by long-term success. Of those who submitted to a second procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences. An implantable cardioverter-defibrillator (ICD), following procedure failure, was implanted in 13 patients (11%) of the study population. Conclusions Radiofrequency catheter ablation is effective in a wide population of patients with recurrent tolerated ventricular tachycardia, with very low sudden death and cardiac mortality rates over the long-term. Persistent ventricular tachycardia inducibility after catheter ablation requires an ICD implant and/or repeat ablation. (Eur Heart J 2001, 23: , doi: /euhj ) 2001 The European Society of Cardiology Key Words: Catheter ablation, ventricular tachycardia, myocardial infarction. See page 352, doi: /euhj for the Editorial comment on this article Revision submitted 10 May 2001, accepted 16 May 2001, and published online 24 September Correspondence: Dr Paolo Della Bella, Centro Cardiologico Monzino, Institute of Cardiology, University of Milan, Via Parea 4, Milano, Italy X/02/ $35.00/0 Introduction The role of radiofrequency catheter ablation in the overall clinical management of recurrent post infarction ventricular tachycardia is still debated. Although the technique is effective in achieving arrhythmia 2001 The European Society of Cardiology

2 Post infarction treatment for VT 415 Table 1 Study population (number of patients: 124; mean age: 64 8 years) Number of patients* % Prior myocardial infarction(s) Anterior Inferior Multiple LV ejection fraction 30% <30% Mean ejection fraction 34 10% (range 15 67) Number of diseased coronary arteries < >= Syncope at VT presentation Uneffective AADs (range 0 5) < >= Previous ventricular aneurismectomy/freezing+peeling 15 12% *Total number of patients per variable may not amount to 124 due to the effect of missing information. LV=left ventricular; VT=ventricular tachycardia; AAD=antiarrhythmic drugs. termination and in preventing its subsequent reinduction in a high percentage of cases [1 3], persisting uncertainties of the long-term reliability of catheter ablation in this clinical setting are due to the low number of patients included in the published series and to the different criteria used to define acute success [4 9]. Furthermore, it is not clear whether and when adjunctive forms of treatment, such as antiarrhythmic drugs or implantable cardioverter-defibrillator (ICD), are required. These aspects have been systematically addressed in the present longitudinal prospective study, including the evaluation of acute results of catheter ablation and the relationship to the long-term follow-up in a homogenous population of patients with drug-refractory recurrent ventricular tachycardia, late after myocardial infarction. Homogenous criteria for inclusion of the patients in the study and identical procedure protocols were adopted by the investigating centres. Methods Patients were included in the study if the following criteria were met: Spontaneous occurrence of sustained monomorphic ventricular tachycardia with systolic arterial blood pressure 80 mmhg; the number of documented morphologies of ventricular tachycardia did not affect patient enrollment; Absence of fresh thrombus in the left ventricle detected by echocardiography; Absence of spontaneous or induced myocardial ischaemia: all patients underwent preliminary ECG or echo stress test when not contraindicated; coronary angiography and left ventriculography were performed to guide the correction of resting or stress induced myocardial ischaemia by coronary angioplasty or bypass grafting; in such patients catheter ablation was subsequently undertaken. Study population (Table 1) Recruitment of the patients began in April 1992 and was terminated on 30 September 1997; during this period 124 patients entered the study because of recurrent (at least three documented episodes during the previous year) sustained ventricular tachycardia; 117 of them were males, the mean age being 64 9 years. This number was 30% of the patient population (397 patients) referred to the investigating centres for the treatment of ventricular tachycardia during the study period. The reasons for patient exclusion were the following: (1) untolerated ventricular tachycardia during antiarrhythmic drug treatment (12%); (2) documented cardiac arrest due to fast ventricular tachycardia/ventricular fibrillation (35%); (3) a first onset of ventricular tachycardia in the absence of any antiarrhythmic drug treatment (40%); (4) need for surgical interventions (aneurismectomy) (8%); (5) fresh thrombus (5%); (6) induced untolerated ventricular tachycardias before any ablation attempt in patients with documented tolerated ventricular tachycardia (10%). The interval between myocardial infarction and the first ventricular tachycardia episode ranged from 2 months to 31 years. Ventricular tachycardia occurring

3 416 P. Della Bella et al. in the setting of an acute myocardial infarction was an exclusion criterion. Syncope was the presenting symptom at the time of first ventricular tachycardia occurrence in 30/124 (24%). External DC cardioversion was required to terminate the arrhythmia in 60%. All patients had failed on one to four antiarrhythmic drugs (median two per patient) and all were taking antiarrhythmic drugs (amiodarone in 94% of cases) at the time of the last recurrence. The median number of diseased coronary arteries was two per patient; four (3%) had no significant vessel disease (diagnosis of myocardial infarction based upon standard criteria during the acute phase), 54 (44%) had single vessel, 38 (30%) two-vessel, and 28 (23%) three-vessel disease. The mean left ventricular ejection fraction was 34%; 37 patients (32%) had an ejection fraction below 30%. Eleven (9%) patients had an ICD implanted 3 months to 2 years prior to the procedure. Catheter ablation was required in them because of excessive ICD therapy (2 to 60 shocks per month). Left ventricular aneurismectomy with map guided endocardial resection and/or cryoablation had been previously performed in 10 patients. Study design The procedure was performed in the fasting sedated state after having obtained an informed written consent concerning the details and the possible risks involved in the procedure. Briefly, quadripolar electrode catheters were placed in the high right atrium, the His bundle region and the apex of the right ventricle; a 4 mm tip 7 F steerable electrode catheter (Cordis-Webster, EPT Blazer or Medtronic-Marinr) was introduced in the left ventricle through a retrograde transaortic or transseptal approach. Programmed ventricular stimulation was performed from the right ventricular apex at the basic drive rates of 100, 120 and 140 beats. min 1 with up to three extrastimuli; the stimulation protocol was repeated at multiple left ventricular sites until the induction of clinical ventricular tachycardia; all tolerated ventricular tachycardias that could be induced were mapped and ablated. The procedure was carried out during continuous monitoring of the arterial blood pressure through a radial artery cannula; O 2 saturation was also continuously monitored by infrared plethysmography. Fluid balance was carefully checked throughout the procedure; urinary output was measured using a ureteral catheter. Systemic anticoagulation was achieved by a heparin i.v. bolus (5000 to U) followed by continuous infusion titrated to achieve activated clotting time values, checked every 30 min, of s. Computerized multichannel recordings of all 12 standard ECG leads and bipolar intracardiac tracings were performed. The choice for the ablation site was based upon the following electrophysiological criteria: Recording of fragmented diastolic activity; (70 ms or earlier with respect to the onset of the earliest surface QRS); Recording of isolated diastolic potentials; Concealed entrainment and the demonstration of a post-stimulation cycle equal to the ventricular tachycardia cycle were used to confirm the choice of the ablation site. Radiofrequency current was delivered in the unipolar mode between the electrode tip and a cutaneous electrodispersive patch placed posteriorly in the left infrascapular space; impedance control was performed during constant current delivery (50 to 60 V) until January 1995; a temperature controlled generator was used afterwards, with the catheter tip temperature setting at 65 C. Delivery of radiofrequency current at any given site was discontinued if ventricular tachycardia did not terminate within 10 s; pulse duration was 60 s in the cases of ventricular tachycardia termination during current delivery; additional 60 min radiofrequency current applications were delivered during sinus rhythm at the successful site. Following radiofrequency termination of ventricular tachycardia, repeat programmed ventricular stimulation was undertaken using the same stimulation protocol as in the baseline study. Any type of sustained ventricular tachycardia induced thereafter, that could be haemodynamically tolerated, was mapped, and radiofrequency ablation was attempted in all instances. Overdrive pacing or direct current cardioversion were promptly undertaken in cases of haemodynamic compromise. Failure of ventricular tachycardia ablation required either ICD implant, surgery or a change in the antiarrhythmic drug regimen. An echocardiogram was performed after the procedure and the following day to exclude the possibility of pericardial effusion or aortic valve damage. Patients were kept under telemetric ECG monitoring for 48 h following the procedure. Systemic oral anticoagulation was prescribed at discharge for 2 months. Treatment with beta-blockers and/or low dose ( mg. week 1 ) Amiodarone was maintained for most of the patients, including those with an acute success, as will be described in detail later. After hospital discharge, all patients were seen at the outpatient clinic at 1 month and then at 3 monthly intervals for clinical evaluation, and analysis of the standard and 24 h ECG. Patients with an ICD had the device checked at regular 3 monthly intervals. Patients were asked to promptly notify one of the investigating physicians, in the case of hospital admission due to cardiac events or relevant symptoms. The 12-lead ECG recorded was used to assess the morphology of the recurrent ventricular tachycardia. Where there was ventricular tachycardia recurrence, a repeat ablation was offered as a first choice; the treatment with antiarrhythmic drugs was modified in patients unwilling to undergo a repeat procedure. According to the outcome of the repeat procedure, a decision was taken on whether to implant an ICD. The study was approved by institutional review committee and all subjects gave informed written consent.

4 Post infarction treatment for VT 417 Table 2 Ventricular tachycardia recurrences in relation to acute results Patient groups % Further treatment Full success n: 91 19/91 (21) 13/13 Patients: successful II procedure 2 Patients: ICD implantation 8 Patients: on AADs Partial success n: 21 10/21 (48) 2/2 Patients: successful II procedure 5 Patients: ICD implantation 1 Patient: on AADs Complete failure n: 12 6/12 (50) 2 Patients died of heart failure (incessant VT) 6 Patients: ICD implant, 1 Patient: surgery 3 Patients: no recurrences on AADs ICD=implanted cardioverter defibrillator. See Table 1 for other abbreviations. Definitions According to the results of the post-procedure electrophysiological study, the acute outcome of radiofrequency ablation was defined as follows: Class A: interruption of the index ventricular tachycardia and of all the induced ventricular tachycardias; prevention of induction of any form of sustained ventricular arrhythmia. Class B: interruption of the index and/or other induced ventricular tachycardia, but persistent inducibility of other sustained, haemodynamically stable or unstable, ventricular tachycardia, including ventricular flutter or fibrillation. Class C: failure at terminating the index ventricular tachycardia. Statistics Data are presented as mean and standard deviation (SD) for continuous variables, or median and quartiles if skewed, and as absolute and relative frequencies for categorical variables. The Wilcoxon matched pair test has been used to compare the number of ICD therapies before and after ablation procedure. The following end-points have been considered for the analysis: (a) the acute success of the radiofrequency catheter ablation procedure and the long-term outcome, namely time to first recurrence of ventricular tachycardia or sudden death, whichever the first (main outcome); (b) time to first ICD treatment and analysis of the rate of the treated ventricular tachycardia ((c) time to death from cardiac failure; (d) time to any cardiac event (cardiac death or ventricular tachycardia recurrence, whichever the first). A series of determinants of the acute success of a procedure has been evaluated by means of a uni- and multivariate logistic model. Odds ratios (OR) with their 95%CI have been calculated. Kaplan Meier estimation has been used to calculate and plot the cumulative probabilities of survival and event-free survival. Cox proportional hazard models have been fitted to assess the univariate prognostic value of a series of candidate risk factors: age; sex; site of previous myocardial infarction; left ventricular ejection fraction; number of diseased coronary vessels, number of ventricular tachycardia morphologies, ICD implantation, success of catheter ablation, number of radiofrequency current pulses, cycle length of the induced and ablated ventricular tachycardias. The adequacy of adopting a Cox model has been checked graphically by comparing predicted and observed survival curves. The hazard ratio and its 95% confidence interval (95%CI) is reported for each variable. The likelihood ratio test has been used for calculating the significance of the model. A multivariate Cox model has then been fitted by including all variables showing a P-value <0 2 at univariate analysis. Stata 6.0 (Stata Corp, College Station, TX, U.S.A.) has been used for computation. A P-value <0 05 has been retained for statistical significance. Results Electrophysiological findings At the time of the study, 92/124 patients were on amiodarone, 27 on sotalol and five on no drug. Two hundred and thirty-six morphologies of haemodynamically tolerated sustained ventricular tachycardia were induced and interrupted by radiofrequency ablation. The mean cycle length was ms (range 202 to 666 ms). One type of ventricular tachycardia had been previously documented and could be reinduced in 59 patients, whereas multiple (2 to 7, median 3) morphologies had been documented and/or were induced at electrophysiological studies in 65. Acute results Complete success (Class A) was achieved in 91 patients (73% of the population); a partial success (Class B) in 21 (17%) and failure in the remaining 12 patients (10%) (Table 2). The duration of the procedure ranged from 75

5 418 P. Della Bella et al. to 300 min (mean min) and the fluoro time from 5 to 130 min (mean min); the median number of 1 min radiofrequency pulses per patient was nine, with a range from 1 to 60. One hundred and sixteen out of 236 ventricular tachycardia (49%) were terminated within 10 s of the onset of radiofrequency current delivery, when the ablation was performed on sites with early fractionated activity (range 50 to 205 ms preceeding the onset of the QRS); 85/236 ventricular tachycardia (36%) on sites with isolated diastolic potentials, and 14% when applied at sites with early activation of the local electrogram. Concealed entrainment could be proven in 26% of the ablation sites; the success rate of ablation of sites with concealed entrainment was 35%, this being roughly equivalent to the success rate at sites where the concealed entrainment either could not be proven for technical reasons or was negative. The only determinant of complete acute success of the procedure at univariate logistic regression were an ejection fraction above 30% (OR=0 34; 95%CI: ), and a ventricular tachycardia cycle length 350 ms (OR=3 68; 95%CI: ), with a borderline significance for a number of radiofrequency pulses >8 (OR=2 11; 95%CI: ). At multivariate analysis an ejection fraction above 30% appeared to be the only independent determinant of acute success (OR=0 35; 95%CI: ). Of borderline importance was the year of the procedure (OR=0 53; 95%CI= ). The following complications were observed: one death occurring within 24 h of the procedure due to cardiogenic shock; the patient had had incessant ventricular tachycardia for 2 months and was transferred to one of the investigating centres, after a failed radiofrequency ablation at another institute. The procedure was uneventful and acutely successful in restoring stable sinus rhythm without signs of myocardial ischaemia or pericardial effusion; the patient, however, died the day after because of irreversible cardiogenic shock. Other procedure-related complications were: one transient ischaemic attack with full recovery and no neurological sequelae; two peripheral emboli; one complete atrioventricular block requiring pacemaker implant; rapid ventricular tachycardias requiring DC cardioversion, within 48 h of ablation, in four patients in whom sinus rhythm was achieved by catheter ablation. All four patients had incessant ventricular tachycardia prior to the procedure and presented with overt heart failure. Long-term outcome The analysis of follow-up was performed according to the status as of 31 January The duration of follow-up ranged from 1 to 86 months, median 41 5 months (interquartile range ). Clinical information was available for all 124 enrolled patients, either directly, from the outpatient clinic, or through information obtained by the referring physician. Treatment with antiarrhythmic drug (amiodarone mg. week 1 ) and/or beta-blockers was maintained in 94 patients (86%). There were 15 deaths, three of which were sudden. One sudden death occurred 9 months after a partially successful procedure. Antiarrhythmic treatment with amiodarone had been interrupted 3 months before by the referring physician, without further electrophysiological testing. The second occurred 24 months after a successful procedure and was due to ventricular fibrillation documented upon arrival at the Emergency Room. The third patient died 66 months after the procedure. The remaining 12 deaths were due to cardiac failure. Arrhythmia recurrence related to palpitation was experienced by 23/91 (25%) patients with a fully successful procedure; no syncopal episodes had occurred in these patients. In 11/21 (52%) of those with an intermediate result, the highest recurrence rate related to the incidence of faster ventricular tachycardia not considered amenable to ablation. Six out of 12 (50%) patients experienced complete failure. Treatment modalities following the first ventricular tachycardia recurrence A second radiofrequency ablation was performed in 15 patients who had recurrence of ventricular tachycardia. The second ablation was successful in 13/13 patients who had full success at the first procedure and in 2/2 of those with a prior partial success. There was one recurrence among patients treated with a successful repeat ablation. After the second procedure, 93/124 patients (75%) are free of arrhythmia recurrence. In 13 patients (11%) an ICD was implanted; in eight of them at time of the initial ablation, due to failure or partial result. Five additional patients had an ICD implanted after ventricular tachycardia recurrence. One patient following an unsuccessful ablation underwent mapping guided surgery with endocardial resection and cryoablation of the arrhythmogenic tissue. Radiofrequency ablation in patients with excessive ICD therapy Eleven/124 patients had an ICD previously implanted at the time of the first radiofrequency ablation, and were referred for the control of excessive ICD therapy. In two patients shocks were due to incessant ventricular tachycardia. The number of shocks ranged from 2 to 60 per month. The ICD had been implanted in seven for drug refractory haemodynamically stable recurrent ventricular tachycardia and in four for ventricular fibrillation. The median interval from the time of ICD implant to radiofrequency catheter ablation was 12 months (range 2 months 3 years). In 10/11 patients the ventricular tachycardia was successfully interrupted with complete prevention of ventricular tachycardia induction in 6/11. Death from heart failure occurred in one patient 2 months after a failed procedure due to incessant ventricular tachycardia. The mean number of ICD therapies

6 Post infarction treatment for VT 419 Cumulative proportion surviving P = Follow-up time (months) Figure 1. Event-free survival function according to class (recurrences including sudden death). =class A: complete success; =class B: partial result; =class C: failure. Cumulative proportion surviving P = Follow-up time (months) Figure 2. Event-free survival function according to the number of morphologies (recurrences including sudden death). Number of VT morphologies: =1; =2; =3; =4 or more. decreased in this group of patients from 113 in the 6 months before to 0 9 in the 6 months following the procedure (P>0 05 ). Relation of clinical and electrophysiologic characteristics to long-term outcome Recurrences of ventricular tachycardia (including sudden death) Kaplan Meier estimates showed a rate of recurrence of 26 8% (95%CI: ) at 12 months and of 34 7% (95%CI: ) at 36 months. Univariate event-free survival analysis (Table 3) elicited a statistically significant benefit in patients with successful ablation (Fig. 1); on the other hand, recurrence rates were similar between patients with a partial success and those with failure. The 1-year recurrence rate after the first procedure was 19% (95%CI: 12 28), 55% (95%CI: 34 78), 49% (95%CI: 24 81) for Group A, B and C respectively; the 3-year rate was 27% (95%CI: 19 37), 61% (95%CI: 40 83) and 59% (95%CI: 32 87). Similarly, patients with an implanted ICD had a significantly higher rate of recurrences. The number of presenting or induced ventricular tachycardia morphologies did not affect the long-term outcome, that was similar in patients with only one morphology and in those with two, three and four or more (Fig. 2). At multivariate analysis, the only independent predictors of the absence of recurrence or sudden death remained the acute success of the radiofrequency catheter ablation procedure (hazard ratio= %CI: (class B and C vs A)) and ICD implantation (hazard ratio= %CI: ).

7 420 P. Della Bella et al. Cumulative proportion surviving P = Follow-up time (months) Figure 3. Survival function according to left ventricular ejection fraction (death from heart failure). =ejection fraction 30%; =ejection fraction <30%. Table 3 Potential risk factors for recurrence and sudden death (Univariate Cox regression) Hazard ratio 95% CI P value Age (years) Sex F vs M Site of previous MI (inferior vs. anterior) LV ejection fraction <30% vs 30% No. of diseased coronary vessels No. of VT morphology >2 vs VT cycle ICD implantation* Success of RFCA class B vs A class C vs A No. of RF pulses>8 vs *no patient with ICD experienced sudden death; CI=confidence interval; MI=myocardial infarction; LV=left ventricular; VT=ventricular tachycardia; RFCA=radiofrequency catheter ablation; RF=radiofrequency. Among the patients with an ICD implanted following the procedure, 11/13 (85%) experienced one or more appropriate therapies. In 9/11, analysis of the ventricular tachycardia rate in the stored electrogram at the time of the treatment was compatible with the same ventricular tachycardia that could not be ablated. Death from heart failure Kaplan Meier estimates showed a death rate of 5 6% (95%CI: ) at 12 months and of 9 1% (95%CI: ) at 36 months. At univariate survival analysis older age, anterior myocardial infarction, left ventricular ejection fraction below 30% (Fig. 3), failure of procedure, more than eight radiofrequency pulses and a longer ventricular tachycardia cycle length, all increased the risk of death from heart failure (Table 4). Multivariate analysis showed that older age, ejection fraction below 30% and failure of the procedure were independent predictors of death from heart failure hazard ratio=61 68; 95%CI: , ejection fraction below 30%. hazard ratio=62 5; 95%CI: ) for class B andcvsa. Any cardiac event (recurrence or cardiac death) Altogether, the rate of cardiac events was 31 4% (95%CI: 24 40) at 12 months and 39 7% (95%CI: 32 49) at 36 months, as estimated by the Kaplan Meier method. Cardiac mortality was 6 4% (95%CI: ) and 10 7% (95%CI: ) at 12 and 36 months, respectively. Discussion Main findings In this series of 124 consecutive patients undergoing radiofrequency catheter ablation for recurrent,

8 Post infarction treatment for VT 421 Table 4 Potential risk factors for death from heart failure (Univariate Cox regression) Hazard ratio 95% CI P value Age (years) Sex F vs M Site of previous MI (inferior vs anterior) LV ejection fraction <30% vs 30% No. of diseased coronary vessels No. of VT morphology >2 vs ICD implantation Success of RFCA class B vs A class C vs A No. of RF pulses >8 vs VT cycle (ms) vs vs vs For abbreviations, see Table 3. drug-refractory ventricular tachycardia, a low 1 and 3 year incidence of recurrences as well as a low mortality rate from all causes has been observed. Acute success of the procedure was shown to be predictive of long-term control of ventricular arrhythmias and was associated with a very low incidence of sudden death. Further, poor left ventricular function (left ventricular ejection fraction <30%) and failure of catheter ablation appeared to be predictive of death from heart failure. The results of the present prospective study appear relevant in that they are related to a large patient population, with standard criteria of enrollment, assessment of acute procedure outcome and modalities of adjunctive treatment. Furthermore, the duration of the follow-up is the longest reported among similar clinical studies [4 9]. Clinical characteristics of the study population Patients presenting with haemodynamically stable recurrent ventricular tachycardia following a myocardial infarction represent a group with a low risk for sudden death. In the series published by Sarter et al. [10], the 2 and 3-year rate of sudden death was 3 and 7%, respectively; similar rates have been reported by others [11,12] in patients presenting with recurrent tolerated ventricular tachycardia. The most frequent cause of mortality among the patients presented in this series, as in other similar series, was related to progression of heart failure. This fact is further supported by the threefold mortality from heart failure in patients with an ejection fraction of 30% (Fig. 3). The low incidence of recurrent ischaemic events observed in our study is most likely due to patient selection, since elimination of myocardial ischaemia was required as an enrolment criterion. In this setting, our data suggest that catheter ablation and continued antiarrhythmic treatment are more effective in preventing ventricular tachycardia induction and recurrence than antiarrhythmic drug therapy alone, and at least as effective as antiarrhythmia surgery both acutely and over the long-term, as has been shown by comparing our results to those of the literature [10,13 15]. The very low perioperative morbidity and mortality of catheter ablation resulted in a significant reduction in long-term overall mortality. This was about 10% in this series on a median 41 month follow up, with a mortality rate of four per 1000 person months of observation. One factor that appeared, at univariate analysis, to be a potential risk factor for death from heart failure was the ventricular tachycardia cycle length of more than 405 ms. Although this factor may appear at first parodoxical, it confirms previous observations in patients with ventricular tachycardia following a myocardial infarction. The possibility of a deleterious effect of antiarrhythmic therapy in these patients has been suggested by Sarter et al. [10] ; alternatively, the longer ventricular tachycardia cycle might be related to a more dilated ventricle or to the diffuse presence of diseased and slowly conducting myocardium surrounding the infarcted area. At variance with our data, a higher 3 year mortality (33 6%) has been reported in a retrospective observational study [16] in patients presenting with stable ventricular tachycardia. In spite of its limitations, related to the lack of information on treatment modalities and the causes of death, the study supports the concept of benign clinical presentation. However, tolerated ventricular tachycardia may not necessarily imply a good prognosis. In fact, it is known that multiple morphologies, including untolerated forms, can be induced in patients presenting with tolerated ventricular tachycardias [17]. In this respect, the detailed electrophysiological assessment achieved by the programmed stimulation study performed following catheter ablation in our

9 422 P. Della Bella et al. patients, may have been of great relevance in assessing high risk patients (partial result and failure) in need of an ICD, and this may have contributed to the improved arrhythmia survival observed in our population. Acute procedure outcome as a predictor of long-term results Prevention of the inducibility of any sustained ventricular arrhythmia was taken as a primary procedure endpoint and was achieved in about 75% of the patient population, this figure averaging the success rate of the published series [3,4,6,8,9]. Patients in whom this end-point could be achieved at the end of the procedure had a significantly lower recurrence rate over the follow-up, as compared to those with a partial result (different ventricular tachycardia persistently inducible) or an acute ablation failure. Similar data were published in the studies by Rothman et al. [8] and Stevenson et al. [9], suggesting that elimination of any inducible ventricular tachycardias rather than only the clinical ventricular tachycardia should be the end point of catheter ablation of post miocardial infarction ventricular tachycardias. In addition to a favourable effect on ventricular tachycardia prevention, acute procedure success was shown in this study to be associated with increased survival due to a decreased incidence of late death due to heart failure. In fact, at multivariate analysis, both acute procedure success and left ventricular ejection fraction of 30% appeared to indipendently reduce the risk of death from heart failure during the follow up. These data may support the view that a prevention of arrhythmia recurrence, with the attending reduction of antiarrhythmic therapy, may avoid the progressive haemodynamic impairment that is the most common cause of cardiac death in our patient population. Ablation and antiarrhythmic drugs Almost all patients treated by ablation received amiodarone (85%) or beta-blockers or a combination of both. The main reason for this was that the majority of patients were on chronic treatment with amiodarone at the time of the procedure and therefore the electrophysiological study results reflect the modification of the substrate obtained under drug effect. One fourth of the study population had suffered from syncope at the onset of the first episode; this symptom, however, was no longer evident during the later recurrences, during antiarrhythmic treatment, probably due to the lower tachycardia rate. Further, the need of such treatment is related to the possibility of a variety of atrial and ventricular arrhythmias other than the one treated. The lowest use of antiarrhythmic drugs has been reported in the series of Rothman et al. [8]. In particular, treatment was interrupted among those (31% of the study population) with an acutely successful procedure; one late sudden death occurred in this group of 11 patients. A more widespread use of antiarrhythmic drugs is reported in the other series, as in the present. The reason for this choice is the overall favourable effect of amiodarone and beta-blocker treatment, alone or in combination, on the long-term survival in patients with coronary artery disease [18 24], and the overall low percentage of side effects encountered at the low dosage used. Ablation and ICD In the last decade, the advent of ICD therapy and the simplification of the implant procedures have substantially reduced the number of surgical interventions for ventricular tachycardia [15]. Treatment with an ICD was recently shown to enhance survival in patients with a variety of forms of ventricular arrhythmia [25]. These studies, however, have included mixed populations of patients with haemodynamically stable and unstable ventricular tachycardia or ventricular fibrillation, or survivors of cardiac arrest; at the moment no data are available allowing a direct comparison of the data presented in this study with those with a similar population of patients treated primarily by ICD. In spite of this, it is relevant to underline that the 3-year rate of sudden death and cardiac mortality recorded in this study is comparable to that reported in the most recent series of patients treated with ICD [26 29]. Overall, patients with ICD in our series show a threefold increase in risk of ventricular tachycardia recurrence during follow up; this is not surprising as they represent a selected high risk subset within our study population. No association between ICD and risk of death (from heart failure) is evident here. Control of excessive therapy for frequently recurring arrhythmias in patients with ICD is an estabilished indication for catheter ablation [30 31]. Eleven patients in this series were referred for this specific reason, and the procedure proved greatly effective in 10 of them, causing a decrease of the number of ICD shocks, from 113 to 0 9, over a 6 month period; the ICD was implanted in four of them for fast ventricular tachycardia or ventricular fibrillation and in the remaining seven for tolerated ventricular tachycardia. Complete disappearance of any ventricular tachycardia could be documented during the follow-up in five of them and a marked decrease (1 2 shocks per year) in the remaining five. These results were followed by an overall improvement of these patients status. From one standpoint, the cardioverter-defibrillator offers a high degree of protection against the most ominous consequences of ventricular tachycardia; on the other hand, however, this form of therapy, when frequent shocks are delivered, has a profound negative consequence on the overall quality of life. The data of this study show that in patients with haemodynamically stable ventricular tachycardia the long-term prognosis of catheter ablation is good and therefore the latter form of therapy can be considered as a reasonable alternative to ICD implant as the first choice, provided that no other ventricular tachycardias

10 Post infarction treatment for VT 423 are inducible after the procedure. A new ICD was implanted in 11% of the patients following ablation, mostly due to either acute complete failure or to persistent inducibility of ventricular tachycardia different from the initial arrhythmia. It is worth stressing that in these patients the interventions of the device were always related to the non-ablated tachycardias, similar to what has been described in other series. Thus, hybrid therapy (ablation +ICD) is foreseen in a small but consistent percentage of patients following a seemingly successful ablation, due to the complexity of the arrhythmogenic substrate. The fact that an appropriate intervention has been documented in all the patients with a newly implanted ICD underlines the good specificity of the programmed stimulation after radiofrequency catheter ablation to guide such a decision. Limitations A slightly higher prevalence of inferior or posterior infarction is represented in this series, as in previously published series [5,9]. This uneven distribution may be the consequence of a selection process, where patients with a well-defined aneurysm are more likely to be surgical candidates [15] ; multiple ventricular tachycardia morphologies and aneurysm formation are more common after an anterior wall infarction following occlusion of the left anterior descending coronary artery [32]. The favourable results observed in this series relate to a well defined subgroup of patients presenting with haemodinamically stable ventricular tachycardia, and may therefore not be expected to represent the outcome of catheter ablation of any type of sustained ventricular tachycardia following myocardial infarction. The study was designed to evaluate the outcome (in terms of recurrences and cardiac mortality) of patients undergoing radiofrequency ablation of ventricular tachycardia; therefore no definite statement can be made on whether radiofrequency catheter ablation or ICD is superior in preventing cardiac death. These data, however, support the establishment of a randomized trail assessing this issue. Conclusions This article presents the longest follow-up data of the largest consecutive series of patients with recurrent tolerated postinfarction ventricular tachycardia treated by radiofrequency catheter ablation. In spite of the abovementioned limitations, these clinical data support the effectiveness of the technique in a wide population of patients with drug-refractory haemodynamically tolerated arrhythmia; the long-term sudden death and cardiac mortality rates observed compare favourably to those achieved by other non-pharmacological modalities of treatment. radiofrequency catheter ablation can therefore be considered, often in conjunction with low-dose amiodarone treatment, as the alternative to ICD implant and as a therapeutic option in these patients. Persistent inducibility of untolerated sustained ventricular tachycardia, even if different from the clinical arrhythmia, is equivalent to failure of ablation in terms of recurrence and frequently requires ICD therapy. References [1] Stevenson WG, Khan H, Sager P et al. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 1993; 88: [2] Wilber D.J, Kopp D.E, Glascock DN, Kinder CA, Kall JG Catheter ablation of the mitral isthmus for ventricular tachycardia associated with inferior infarction. Circulation 1995; 92: [3] Bogun F, Bahu M, Knight BE et al. Comparison of effective and ineffective target sites that demonstrate concealed entrainment in patients with coronary artery disease undergoing radiofrequency ablation of ventricular tachycardia. Circulation 1997; 95: [4] Morady F, Harvey M, Kalbfleisch SJ, El-Atassi R, Calkins H, Langberg JJ Radiofrequency catheter ablation of ventricular tachycardia in patients with coronary artery disease. Circulation 1993; 87: [5] Kim YH, Sosa-Suarez G, Trouton TG et al. Treatment of ventricular tachycardia by transcatheter radiofrequency ablation in patients with ischemic heart disease. Circulation 1994; 89: [6] Gonska BD, Cao K, Schaumann A, Dorszewski A, Von Zur Muhlen F, Kreuzer H Catheter ablation of ventricular tachycardia in 136 patients with coronary artery disease: results and long-term follow-up. J Am Coll Cardiol 1994; 24: [7] Farré J, Rubio JM, Navarro F, Sanziani L, Rivas D, Romero J Current role and future perspectives for radiofrequency catheter ablation of postmyocardial infarction ventricular tachycardia. Am J Cardiol 1996; 78 (Suppl 5A): [8] Rothman SA, Hsia HH, Cossù SF, Chmielewski IL, Buxton AE, Miller JM Radiofrequency catheter ablation of postinfarction ventricular tachycardia. Long-term success and the significance of inducible nonclinical arrhythmias. Circulation 1997; 96: [9] Stevenson WG, Friedman PL, Kocovic D, Sager PT, Saxon LA, Pavri B Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction. Circulation 1998; 98: [10] Sarter BH, Finkle JK, Gerszten RE, Buxton AE What is the risk of sudden cardiac death in patients presenting with hemodynamically stable sustained ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996; 28: [11] Brugada P, Talajic M, Smeets J, Mulleneers R, Wellens HJJ The value of the clinical history to assess prognosis of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction. Eur Heart J 1989; 10: [12] DiMarco JP, Lerman BB, Kron IL, Sellers DT Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode. J Am Coll Cardiol 1985; 6: [13] Miller JM, Kienzle MG, Harken AH et al. Subendocardial resection for ventricular tachycardia: Predictors of surgical success. Circulation 1984; 70: [14] Nath S, Haines D, Hobson CE et al. Ventricular tachycardia surgery. J Cardiovasc Electrophysiol 1992; 3: [15] Hargrove III WC, Addonizio VP, Miller JM Surgical therapy of ventricular tachyarrhythmias in patients with coronary artery disease. J Cardiovasc Electrophysiol 1996; 7:

11 424 P. Della Bella et al. [16] Raitt MH, Renfroe EG, Epstein AE et al. Stable ventricular tachycardia is not a benign rhythm. Insights from the AVID registry. Circulation 2001; 103: [17] Bocker D, Block M, Isbruch F et al. Benefits of treatment with implantable cardioverter-defibrillators in patients with stable ventricular tachycardia without cardiac arrest. Br Heart J 1995; 73: [18] Yusuf S, Wittles J, Friedman L Overview of results of randomized clinical trials in heart disease. JAMA 1988; 260: [19] Kendall MJ, Lynch KP, Hjalmarson A et al. Beta-blockers and sudden cardiac death. Ann Inter med 1995; 123: [20] Burkart F, Pfisterer M, Kiowski W et al.effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: basel antiarrythmic study of infarct survival (BASIS). J Am Coll Cardiol 1990; 16: [21] Pfisterer ME, Kiowski W, Brunner H et al. Long term benefit of 1 year Amiodarone treatment for persistent complex ventricular arrhythmias after myocardial infarction. Circulation 1993; 87: [22] Julian DG, Camm AJ, Franglin G, Janse MJ, Munoz A, Schwartz PJ for the European myocardial infarct Amiodarone trial investigators. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997; 349: [23] Cairns JA, Connolly SJ, Roberts R, Gent M, for the Canadian Amiodarone myocardial infarction arrhythmia trial investigators. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Lancet 1997; 349: [24] Sims I, McDonald KM, Lavori PW et al. Quantitative overview of randomized trials of Amiodarone to prevent sudden death. Circulation 1997; 96: [25] The antiarrhythmics versus implantable defibrillators (AVID) investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337: [26] Sweeney MO, Ruskin JN Mortality benefits and the implantable cardioverter-defibrillator. Circulation 1994; 89: [27] Brooks R, Garan H, Torchiana D et al. Three-year outcome of a nonthoracotomy approach to cardioverter-defibrillator implantation in 189 consecutive patients. Am J Cardiol 1994; 74: [28] Schlepper M, Neuzner J, Pitschner HF Implantable cardioverter defibrillator: Effect on survival. PACE 1995; 18: [29] Trappe HJ, Pfitzner P, Achtelik M, Fieguth HG Age dependent efficacy of implantable cardioverter defibrillator treatment: observations in 450 patients over an 11 year period. Heart 1997; 78: [30] Stevenson WG, Friedman PL, Sweeney MO Catheter ablation as an adjunct to ICD therapy (Editorial). Circulation 1997; 96: [31] Strickberger A, Man KC, Daoud EG et al. A prospective evaluation of catheter ablation of ventricular tachycardia as adjuvant therapy in patients with coronary disease and an implantable cardioverter-defibrillator. Circulation 1997; 96: [32] Svenson RH, Litman L, Gallagher JJ et al. Termination of ventricular tachycardia with epicardial laser photocoagulation: a clinical comparison with patients undergoing successful endocardial photocoagulation alone. J Am Coll Cardiol 1990; 15: