a Arrhythmia Department, Centro Cardiologico Monzino, Institute of Cardiology, University of Milan, Via Parea 4, Milan 20138, Italy
b Biometry and Clinical Epidemiology, Research Department, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
* Corresponding author. Tel.: +39-2-580021/58002340/58002275; fax: +39-2-504-667
E-mail address: pdellabella{at}cardiologicomonzino.it
Received 14 February 2003; revised 15 January 2004; accepted 22 January 2004
Abstract
Aims The prognostic significance of multiple ventricular tachycardia (VT) morphologies, whether spontaneous or induced, was investigated in patients who underwent radiofrequency catheter ablation (RFCA) for postinfarction ventricular tachycardia.
Methods and results We studied 137 patients with postinfarction ventricular tachycardia. Catheter ablation of all induced ventricular tachycardias was attempted.
A single ventricular tachycardia morphology was documented in 102/137 patients (MONO group); 35 patients had spontaneous pleomorphism (PLEO group). Multiple VT morphologies were induced in 58/102 (57%) MONO patients and in all PLEO patients. A higher rate of arrhythmia suppression was obtained in MONO as compared to PLEO patients (162/212 [76%] vs. 43/110 [39%]). Clinical presentation (VT pleomorphism) (OR: 0.22, CI: 0.080.62) and the induced VT cycle (mean PLEO/MONO: 338/385 ms, OR: 1.06) were independent predictors of acute RFCA success. Among MONO patients, the procedure was successful in 75% of the patients with a single induced ventricular tachycardia compared to 64% of those with multiple tachycardias. The acute success rate was lower in PLEO patients (23%). PLEO patients had a significantly higher 3- and 5-year arrhythmia recurrence rate than MONO patients. RFCA acute success was the only independent predictor of long-term outcome in multivariate analysis.
Conclusions Spontaneous, but not induced, VT pleomorphism in patients with prior myocardial infarction adversely affects the acute and long-term success rate of RFCA.
Key Words: Ventricular tachycardia Catheter ablation
Introduction
Multiple morphologies of sustained monomorphic ventricular tachycardia (VT) may occur spontaneously or by induction during electrophysiological testing at different times in the same patient. This phenomenon, defined as pleomorphism,1,2 is frequently observed following a myocardial infarction. The presence of multiple exit sites from a single or multiple re-entry circuits is one possible explanation and this feature is potentially present in all patients with a prior myocardial infarction.39
Previous studies have demonstrated the relation between VT pleomorphism and multiple infarctions, compromised ventricular function, and the extent of coronary artery disease.1,2 The number of documented VT morphologies is influenced by clinical variables, such as the number of VT occurrences and the number of antiarrhythmic drug treatments.2
A reduced efficacy of antiarrhythmic drugs has been described in patients with multiple VT morphologies10,11; likewise, multiple VT configurations are less likely to be cured by surgery, particularly when various sites of origin can be demonstrated in intraoperative mapping.3,12,13
The creation of a line of blockade between the mitral annulus and posterior rim of infarcted myocardial areas resulted in the ablation of dual VT morphologies in a selected series of patients with previous inferior myocardial infarction.14 Aside from this series of patients with a very distinct arrhythmia pattern, the relation between the occurrence of multiple clinical VTs and the results of catheter ablation has not been investigated.
This issue was addressed in the present study, where the occurrence of multiple VT morphologies, both spontaneous and induced, was related to the acute and long-term outcome of catheter ablation in a consecutive series of patients suffering from recurrent ventricular tachycardia following myocardial infarction.
Methods
Population
The clinical and electrophysiological data of 177 consecutive patients who underwent catheter ablation for recurrent sustained monomorphic VT following a myocardial infarction from April 1993 to November 2000 were retrospectively analysed.
The inclusion criteria were:
The final population included 137 patients (91 males) with a mean age of 67±6 years.
An ethics committee approved the study and all patients gave written consent to the procedure.
Electrophysiological mapping and ablation data
Under local anaesthesia, multiple electrode catheters were introduced percutaneously and advanced to the right atrium, His bundle region, and right ventricular apex. A 4-mm tip 7 F steerable catheter was introduced into the left ventricle by a retrograde transaortic or a transseptal approach. Patients were kept mildly sedated by intravenous boluses of morphine and/or midazolam while blood pressure and oxygen saturation were continuously monitored invasively. Anticoagulation with heparin infusion, titrated to achieve an ACT value near 200250 s, was instituted before the procedure. Programmed stimulation with up to three extrastimuli at multiple drives (600500430 ms) from the right and the left ventricle was performed to induce clinical arrhythmia or other sustained VTs. Computerised multichannel recordings of all 12 standard ECG leads and bipolar intracardiac tracings were obtained.
Sustained VTs causing a persistent systolic blood pressure reduction to 50 mm Hg 30 s after induction and requiring termination by overdrive pacing or external DC shock were considered hemodynamically intolerable and were not targeted unless non-conventional mapping techniques had been instituted (see below).
Catheter ablation was guided by conventional activation mapping and entrainment techniques, as previously described,1521 and was performed under temperature (up to 60 °C) and impedance control. All the VTs considered in this study were ablated in the left ventricle. VT ablation was considered effective if VT interruption occurred within 10 seconds of the onset of delivery of radiofrequency energy, without any ventricular premature beat.
Thereafter, a repeated stimulation protocol was undertaken to assess the inducibility of the target or any other sustained monomorphic VT.
In 12 patients (9 with multiple clinical VT morphologies), non-contact mapping (10 patients)2225 or electroanatomical mapping (2 patients)26 were used to guide catheter ablation.
Definitions
Spontaneous pleomorphism
Multiple clinical VT configurations were defined by ECGs recorded at different times showing different bundle-branch-block patterns in V1 or a QRS axis on the frontal plane differing by 45° or more.2 The same criteria were also used to define multiple VT morphologies induced by electrophysiological study. Minor changes in VT cycle length (50 ms) were not considered to define different VT morphologies.
Acute result
The procedure was defined as successful (Class A) any sustained monomorphic VT was interrupted and inducibility was prevented.27
Effective ablation of clinical VT and/or other VT morphologies with persistent inducibility of one or more non-clinical sustained VTs was defined as a partial success (Class B).
Failure to interrupt even clinical VT was defined as a Class C result.
In patients without an ICD implanted before the procedure, the device was implanted following a Class B or C ablation result.
In patients presenting with intolerable VT, an ICD was implanted even after a completely successful procedure.
Ablation site
When two distinct VT morphologies were ablated at the same site, a single slow conduction isthmus was judged to be shared by the VTs.
Electrophysiological confirmation of this definition was provided:
Multiple isthmuses and/or exit sites were considered to be present when ablation had to be performed at clearly different sites (spaced at least 2 cm apart as judged by fluoroscopy). In 12 patients either non-contact mapping (ESI) for intolerable VT or electroanatomical mapping (CARTO) for tolerated VT was undertaken to define the endocardial activation pattern during VT or the scar contour during SR. In patients undergoing a non-contact mapping procedure, the following definitions were used22,23,25:
For any induced VT, both the exit point and the part of the diastolic pathway that could be reliably tracked were marked on the same ventricle as defined by virtual geometry.
Activation mapping during multiple morphologies of hemodynamically tolerated VTs was obtained by electroanatomical mapping by the CARTO system; the landmarks of the ablation sites for different VTs were superimposed typically on the sinus rhythm voltage map to visually relate the ablation site to defined areas of the infarction.
In these cases, a precise estimate of the distance between ablation sites was made and used to confirm findings derived from fluoroscopic observations.
Follow-up
All patients, in the absence of major side effects, were discharged with amiodarone therapy (200 mg/day), which was continued during follow-up unless contraindicated.
Follow-up after hospital discharge was carried out by visits to the outpatient clinic at 2-month intervals and by ICD interrogation every 4 months or whenever an arrhythmic event occurred.
The endpoints were recurrence of any VT, documented either by 12-lead ECG and/or by ICD interrogation, sudden death (defined as death after sudden cardiocirculatory collapse occurring within an hour of the onset of symptoms)29, and cardiac death.
Statistical analysis
Descriptive statistics were computed as the mean and standard deviation (SD) for continuous variables, median and quartiles (IQR) for skewed distributions, and absolute frequencies and percentage for categorical variables. Clinical and electrophysiological characteristics were compared between patients with monomorphic or pleomorphic clinical VT by means of the unpaired t test, MannWhitney U test for continuous variables, or the Fisher exact test for categorical variables, or by logistic modelling with robust standard errors to account for intrapatient correlation when evaluating the characteristics of single VTs.
Multiple logistic regression analysis with a robust standard error was used to assess the association between VT pleomorphism and the acute catheter ablation result, controlled for clinically meaningful potential confounders (site of previous myocardial infarction, left ventricular ejection fraction, induction of multiple VTs, and induced VT cycle). All covariates considered were included in the multivariate model after checking for co-linearity. The goodness of fit, calibration, and discrimination of the model were assessed.
Both VT-free survival and survival after the procedure were evaluated by means of KaplanMeier estimation. To evaluate the prognostic value of VT pleomorphism while controlling for clinically meaningful confounding factors (site of previous myocardial infarction, left ventricular ejection fraction, induction of multiple VTs, and acute ablation results), a multivariate Cox model was used. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated. The event rates per 100 person-years were computed. All covariates considered were included in the multivariate model after checking for co-linearity. The proportional hazard assumption was tested by means of Shoenfeld residuals. Model validation was performed by calculating explained variation and by evaluating calibration and discrimination.
No selection technique was used in any of the multivariate models.
Stata 8 (StataCorp, College Station, TC) was used for computation. A P value0.05 was retained for statistical significance.
Results
A single VT morphology was documented in 102/137 (74%) patients (MONO Group); the remaining 35 (26%) patients with spontaneous pleomorphism constituted PLEO Group.
As shown in Table 1, there were no differences in the clinical variables between groups, except for a lower left ventricular ejection fraction in patients with clinical pleomorphism, where the proportion of patients with impaired LVEF (30%) was higher, although not significantly so.
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At electrophysiological evaluation, 322 episodes of sustained monomorphic VT were induced and targeted for ablation. Among patients presenting with a single VT morphology, multiple configurations (27) were induced by programmed electrical stimulation in 58 patients (57%). Two or more VTs were induced in all the PLEO group patients.
A significantly higher median number of sustained VTs were induced in patients with clinical pleomorphism (2 vs. 3 VTs/patient), with a significantly shorter average cycle length (338 vs. 385 ms) (Table 1). The proportion of intolerable VTs induced was higher in patients with pleomorphism (49/110 vs. 23/212). Finally, a higher percentage of VT suppression was obtained in patients presenting with a single VT as compared to those with VT pleomorphism (162/212 vs. 43/110).
Determinants of the acute result of the ablation procedure
The ablation procedure was successful in 78 patients (57%), partially successful in 28 patients (20%), and a failure in 31 (23%); RFCA was successful in 70/102 patients (69%) in the MONO group and in only 8/35 patients (23%) in the PLEO group. Partial success was achieved in 14/102 (13%) patients in the MONO group and 14/35 (40%) patients in the PLEO group, while the procedure was a complete failure in 18/102 (18%) MONO group and 13/35 (37%) PLEO group patients.
The distribution of acute results differed significantly between PLEO and MONO patients (): of 78 patients in whom all induced VTs (Class A) were prevented, 70 patients (90%) had a single clinical VT as compared to 8 with clinical pleomorphism. Conversely, partial success (Class B result) or failure (Class C result) occurred more frequently in the patients with clinical pleomorphism, in whom hemodynamically intolerable and, therefore, unmappable VTs were induced more frequently (14/28 [50%] and 13/31 [42%],
for both Class B and C vs. Class A post hoc comparisons). The odds of success (Class A result) for patients with pleomorphic VTs was 5 times lower than for patients with monomorphic VTs, after accounting for possible confounders (Table 2). The only other independent predictor was the induced VT cycle length, which was about 15% longer when the ablation procedure was fully successful. Particularly, inducing a single VT morphology or 2 or more VT morphologies was irrelevant in determining RFCA success in MONO patients (33/44 [75%] and 37/58 [64%], respectively,
).
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At variance with this, successful abolition of all induced VTs was achieved in only 39% of patients with multiple isthmuses or areas of slow conduction. In an additional 34%, only clinical VTs could be ablated and persistent inducible non-clinical morphologies remained (Fig. 1).
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Non-contact mapping
In 10 patients (8 presenting with clinical pleomorphism), non-contact mapping of the left ventricle was undertaken to guide catheter ablation of at least one form of hemodynamically intolerable VT. Twenty-six episodes of VT were induced and mapped (23 per patient). Details are shown in Table 3.
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Sudden death and cardiac death
Of 12 deaths, two were sudden. They were observed in patients with a single VT presentation, reduced LVEF, and fully successful RFCA procedure. The remaining 10 patients died from heart failure, with a 3 and 5-year cumulative survival of 93% (95%CI: 8797%) and 90% (95%CI: 8195%), respectively. Table 5 presents the univariate survival analysis for the potential risk factor considered. Due to the low number of deaths, no multivariate model could be fitted. A low ejection fraction was the only predictor of death and the risk increased with decreasing LVEF.
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The spontaneous occurrence of multiple distinct morphologies has been reported in 2364.2%1,10,17 of patients suffering from recurrent sustained VT following myocardial infarction. The incidence of clinical pleomorphism recorded in the present series was low (25%), which may be related to one or more of the following factors:
In spite of this, the average rate of induction of multiple VTs increased to 65% of patients, including more than 50% of those who presented with a single VT morphology.
This finding indicates that the arrhythmia substrate can support multiple re-entry circuits or different exit sites from a given circuit in the majority of patients with prior infarction.59 Yet the clinical arrhythmia history is different in patients presenting with VT pleomorphism since the likelihood of effective antiarrhythmic drug therapy is lower in these patients10; likewise, the presence of multiple VT configurations and various sites of origin of VT has been described as a predictor of failure of surgical arrhythmia treatment.12,13
The complexity of the arrhythmia substrate is probably the most important limitation to more extensive use of catheter ablation in treating postmyocardial infarction VT. It is a widespread concern that selective interruption of the diastolic pathway resulting in effective ablation of the target arrhythmia may not be sufficient to prevent further recurrences due to the possible onset, in the subsequent period, of functional re-entry circuits related to the scar tissue.
The induction of multiple VT morphologies has been seen as a relative contraindication to catheter ablation by some authors1719 since the persistent inducibility of non-clinical VT after catheter ablation is associated with an increased likelihood of arrhythmia recurrence.20,21,27
On the other hand, in patients presenting with hemodynamically tolerated VTs, the long-term outcome is primarily related to the acute result of catheter ablation and is unaffected by the number of presenting or induced VT morphologies.27
The question of whether the occurrence of spontaneous pleomorphism carries the same adverse prognostic significance as the induction of multiple VTs has never been addressed. Furthermore, it remains unclear whether the induction of multiple VTs in a patient with only a single clinically documented morphology carries the same adverse prognostic significance as the spontaneous occurrence of multiple VTs.
Clinical vs. induced VTs
In our study, the induction of multiple VT morphologies was the rule among patients with clinical pleomorphism but it also occurred in more than 55% of those who had had only one VT morphology, as has also been described in other series.20,21
Prevention of the target arrhythmia (fully successful and partially successful RFCA) was achieved in 75% of patients in whom a single VT was induced compared to 86% of those with 2 or more induced morphologies; overall prevention of any inducible VT was obtained in 64% of patients who had suffered only one VT but in whom multiple VTs could be induced at electrophysiological study. It appears, therefore, that in patients with a single clinical VT morphology the induction of multiple VT morphologies did not affect the acute success of catheter ablation.
At variance with this, acute results were much poorer among patients with clinically documented VT pleomorphism, in whom a fully successful procedure could be achieved in only 23%; a partial result (i.e., prevention of single clinical VT, with persistent inducibility of other VTs) was achieved in an additional 40% of these patients. The most frequent cause for the impossibility to achieve a complete success in this group of patients was hemodynamic intolerance of the induced VTs, that could be demonstrated in a significantly higher percentage of patients with VT pleomorphism. This may result from the more advanced degree of left ventricular dysfunction in this group of patients and the shorter cycle length of the induced VTs, both features that have already been recognised in other series20 describing the electrophysiological properties of patients with multiple VTs.
The possibility of demonstrating multiple separate sites of origin of arrhythmias adversely affects the outcome of the acute procedure. On the one hand, detailed experimental mapping studies in a canine post-MI VT model5 have shown that in a substantial number of cases different surface VT morphologies are related to different patterns of endocardial activation that, however, spread from the same single site of breakthrough (probably a shared isthmus).
The non-contact mapping data in the small subgroup of this patient population support this view. A shared part of the diastolic pathway followed by different patterns of endocardial activation in a later phase of diastole and clearly separate exit points was a frequent finding in pleomorphic VTs. Usually, in spite of these findings, distinct ablation lines crossing the diastolic pathways were required to prevent further induction of the different VTs. It follows that information on the activation pattern of any induced VT should probably be part of the mapping procedure for patients undergoing catheter ablation of pleomorphic VT. The use of non-contact mapping techniques offers a significant advantage in this setting, since it can be also applied to hemodynamically intolerable arrhythmia.
Determinants of long-term outcome
While clinical presentation with multiple VT morphologies adversely affected long-term arrhythmia-free survival, the induction of different VTs in the pre-ablation electrophysiological study did not confer a worse prognosis, provided that complete arrhythmia suppression could be achieved by the catheter ablation procedure. The data of our study, however, stress the importance of so-called non-clinical VT induced after ablation in predicting arrhythmia recurrence. The target of a VT-ablation procedure should be the complete prevention of any induced VT.
The relevance of the extent of arrhythmia suppression is further supported by the finding at multivariate analysis that the only factor associated to enhanced arrhythmia-free survival was a fully successful procedure; partially successful results, i.e., prevention of clinical VT with persistent inducibility of other forms of sustained ventricular arrhythmias, are in fact equivalent to complete failure.
Conclusions
Caution is advised before considering documented morphology as the only relevant target in patients with recurrent VTs following myocardial infarction.20,21,27
Treatment with different antiarrhythmic drugs may affect the functional properties of the arrhythmia substrate, originating a different QRS configuration.5 The extent of abnormal myocardial tissue and number of arrhythmia recurrences are factors facilitating the onset of multiple VT morphologies,2 and it may well be that the ultimate fate of patients with VT following myocardial infarction is the occurrence of multiple arrhythmia morphologies.
However, patients who present a single VT morphology seem to be more favourably suited to a catheter ablation procedure, even if multiple VT morphologies are demonstrated in the electrophysiological study.
As shown in a recent study,27 catheter ablation and antiarrhythmic drug treatment are a reasonable strategy in patients presenting with hemodynamically tolerated postmyocardial infarction ventricular tachycardias refractory to pharmacological treatment. The number of previously induced VTs did not affect arrhythmia recurrence, while prevention of any induced arrhythmia following the procedure was a significantly favourable prognostic factor.
A second relevant point is the poorer result of catheter ablation in patients presenting with multiple VT morphologies, where the higher occurrence of intolerable arrhythmias poses major limitations.
More advanced mapping techniques allowing the analysis of endocardial activation during fast VTs, such as non-contact mapping2325 or electroanatomical location and isolation of the scar tissue,26 should probably be used to guide catheter ablation when the treatment of a patient with spontaneous multiple VTs is considered, since the result of the procedure rather than the clinical presentation is what affects long-term outcome.
References