- Email: [email protected]
Determinants of inducibility of ventricular tachycardia
Determinants of Inducibility of Ventricular Tachycardia Mercedes Ortiz, PhD, Jesu´s Almendral, MD, Ramo´n Lo´pez-Palop, Julian Villacastı´n, MD, and Angel Arenal, MD
MD,
We analyzed the incidence and predictive factors for induction of clinical ventricular tachycardia (VT) during an electrophysiologic study in 127 patients with structural heart disease and spontaneous VT documented by 12-lead electrocardiography. Eighty-five patients had coronary artery disease (CAD), 24 had idiopathic dilated cardiomyopathy (IDC), and 18 had right ventricular dysplasia (RVD). Clinical variables were age, gender, electrocardiographic patterns of spontaneous arrhythmia, cardiac diagnosis, left ventricular (LV) ejection fraction (EF), infarct location, and presence of LV aneurysm. Clinical VT was induced in 76 patients (60%, group 1) and was not induced in 51 patients (group 2). Clinical VT was induced in 83% of patients with RVD, 58% of patients with CAD, and 50% of patients with IDC (p ⴝ 0.07). LVEF tended to be significantly higher in group 1
than in group 2 (p ⴝ 0.06). The presence of left QRS axis in the frontal plane during spontaneous VT was significantly associated with a higher inducibility both in the general group (69% vs 46%, p <0.02) and in patients with CAD (70% vs 44%, p <0.02). In patients with CAD, only the presence of a left QRS axis was significantly associated with a higher inducibility. A multivariate analysis identified only the left QRS axis as a significant and independent predictor of induction of clinical VT. The association of a leftward axis with inducibility suggests that vectorial factors in the depolarization wavefronts may be related to inducibility since conventional stimulation is performed from the right ventricle, producing a leftward axis in most cases. 䊚2001 by Excerpta Medica, Inc. (Am J Cardiol 2001;87:1255–1259)
atheter ablation has been recently developed as a therapeutic option for certain subsets of patients C with monomorphic ventricular tachycardia (VT). In
they met the following inclusion criteria: (1) ⱖ1 spontaneous episode of monomorphic tachycardia that after clinical and electrophysiologic evaluation was considered VT; (2) complete 12-lead ECG documentation of all spontaneous episodes that prompted the patient to seek medical attention; and (3) a complete programmed electrical stimulation protocol from the right ventricle had been performed. Patients without structural heart disease, those who required isoproterenol for induction, those with bundle branch reentry, and patients in whom antiarrhythmic therapy was not discontinued before the study were excluded from the study. All electrically induced sustained monomorphic VTs had 12-lead ECG documentation of morphology regardless of hemodynamic sequelae. Variables included in the analysis were age, gender, ECG patterns of spontaneous arrhythmia (right vs left bundle block pattern, superior vs inferior QRS axis, left vs right QRS axis, and cycle length), cardiac diagnosis, left ventricular (LV) ejection fraction (EF), number of infarctions, infarct location, and presence of LV aneurysm. Electrophysiologic study: All patients underwent electrophysiologic study after they gave written informed consent. All antiarrhythmic therapies were discontinued for ⱖ5 half-lives before the baseline study. Multipolar electrode catheters (interelectrode distance 2 to 5 mm) were placed under fluoroscopic guidance in the high right atrium, across the tricuspid valve to record a His bundle electrogram and in the right ventricular apex or outflow tract, or both, for recording and stimulation. Cardiac stimulation was performed with a constant current programmable stimulator (Biotronik UHS 20, Berlin, Germany).
1– 6
most of the reported series, for a patient to be considered as a candidate for this therapy, a tachycardia morphologically similar to the spontaneous tachycardia (so-called “clinical” VT) had to be induced during the electrophysiologic study.3–5 It is well known that in some patients a “clinical” tachycardia cannot be induced in the electrophysiology laboratory, either because no monomorphic VT can be induced or, more commonly, because a morphologically different VT is the only VT induced.7–15 In this context, the likelihood for induction of a “clinical” VT gains practical importance, because it is one of the factors that influences the potential for a patient with VT to become candidate for catheter ablation, especially in patients with coronary artery disease (CAD). This study retrospectively analyzes the incidence and determines the clinical, electrocardiographic (ECG), and angiographic factors that predict the induction of a “clinical” VT during a baseline electrophysiologic study.
METHODS
Patients and clinical characteristics: The study population consisted of 127 consecutive patients who underwent electrophysiologic evaluation from July 1989 to November 1998. Patients were included if From the Department of Cardiology, Hospital General Universitario Gregorio Maran˜on, Madrid, Spain. Manuscript received August 4, 2000; revised manuscript received and accepted January 2, 2001. Address for reprints: Jesu´s Almendral, MD, Cardiologı´a (planta 5), Hospital General Gregrorio Maran˜o´n, Doctor Esquerdo, 46, 28007Madrid, Spain. E-mail: almendral@softmed-s. ©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 87 June 1, 2001
0002-9149/01/$–see front matter PII S0002-9149(01)01545-4
1255
Stimuli were rectangular pulses with a duration of 1 ms and a current strength twice the diastolic capture threshold. Recordings were obtained with a photographic recorder (VR 12, Electronics for Medicine, New York) or with a temperature recorder (Marquette Hellige, Midas 2500⫹OHR, Freiburg in Breisgau, Germany) at a paper speed of 25 to 100 mm/s. All intracardiac electrograms were filtered at 30 to 500 Hz. A conventional programmed stimulation protocol was performed. In all patients, this included atrial pacing up to the rate at which atrioventricular node Wenckebach block occurred. Up to 3 ventricular extrastimuli were introduced during sinus rhythm and ventricular pacing at a paced cycle length of 600 (or 550) and 400 ms at the right ventricular apex and the outflow tract. Our stimulation protocol included LV stimulation whenever the clinical VT was not induced with atrial or right ventricular stimulation in patients with CAD and idiopathic dilated cardiomyopathy. However, these results were not analyzed because they were not routinely performed. The end point of stimulation was either induction of the clinically documented VT or the achievement of ventricular refractoriness. If an induced ventricular tachyarrhythmia required electrical cardioversion, it was the decision of the electrophysiologist responsible for the study to continue the stimulation protocol or not. Induced polimorphic VTs (sustained or not) and induced nonsustained monomorphic VTs were excluded from the analysis. VTs that occurred spontaneously or during catheter manipulation during the electrophysiologic study were considered to be induced VTs. Definitions: Sustained monomorphic VT was defined as a VT that lasted ⬎30 seconds or that caused hemodynamic compromise requiring immediate termination by pacing or cardioversion. Clinical VT was defined as a sustained monomorphic VT induced during programmed electrical stimulation with similar surface ECG configuration (same QRS duration, same bundle branch, ⬍45° difference in frontal and horizontal axes) as a documented spontaneous episode, and nonclinical VT was defined as a sustained monomorphic VT induced during programmed electrical stimulation that differed in surface ECG morphology (different bundle branch or a change in either frontal or horizontal axis by ⬎45°) from that observed during spontaneous episodes. Morphologic ECG criteria were defined during VT16; a QRS complex was considered to have a right bundle branch block morphology if it had a dominant R wave in lead V1; if the dominant wave in V1 was an S wave, the QRS complex was considered to have a left bundle branch block morphology. Left QRS axis deviation was considered when the QRS axis in the frontal plane was between ⫺30° and ⫺90°. Right QRS axis deviation was considered when the QRS axis in the frontal plane was between ⫺90° and ⫾180°. LVEF was obtained from the echocardiographic measurement and was classified as normal (ⱖ55%) or depressed (⬍55%). Analysis of ventricular tachycardia morphologies: In each patient, the 12-lead electrocardiogram of all in1256 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE 1 Clinical Characteristics of Patients With Documented Sustained Monomorphic Ventricular Tachycardia (n ⫽ 127) Age (mean ⫾ SD) (yrs) Men/women LVEF ⬍0.31 0.31–0.4 0.41–0.55 ⬎0.55 Cardiac diagnosis Right ventricular dysplasia Idiopathic dilated cardiomyopathy CAD with previous myocardial infarction: ⬎1 myocardial infarction Myocardial infarction location Anterior Inferior Lateral Indeterminate Left ventricular aneurysm
59 ⫾ 15 113/14 41 42 27 17
(32%) (33%) (21%) (13%)
18 24 85 12
(14%) (19%) (67%) (14%)
42 51 2 3 28
(49%) (60%) (2%) (4%) (33%)
TABLE 2 Characteristics of Spontaneous Documented Ventricular Tachycardia (n ⫽ 127) Cycle length (ms) Configuration of QRS complex Right bundle branch block Left bundle branch block Superior axis Inferior axis Left axis Right axis
341 ⫾ 86 73 54 79 48 75 52
duced sustained monomorphic VT was compared with the 12-lead electrocardiogram of the spontaneous episode of sustained monomorphic VT. All electrocardiograms were recorded at a standard paper speed (25 mm/s) and amplitude (1 mV/mm). VTs were considered similar in morphology if the vectors of the QRS complex were the same in all the 12 recorded leads. Statistical analysis: Statistical analysis was performed with the JMP 3.0.1 statistical software (SAS Institute Inc., Cary, North Carolina, 1994). Data are reported as distributions and mean ⫾ SD values. Statistical comparisons for the 2 groups were performed using the paired t test. A separate subanalysis was performed for patients with CAD, because this was the larger group of patients. The variables with suspected influence on inducibility were included in a multiple logistic regression analysis to determine the independence of its contribution in such inducibility.
RESULTS
Patients and clinical characteristics: Patients’ clinical characteristics are summarized in Table 1. Eighty-five patients had CAD with previous myocardial infarction, 24 patients had idiopathic dilated cardiomyopathy, and the remaining 18 patients had right ventricular dysplasia. Eleven patients (9%) developed documented clinical arrhythmias on drug therapy and the stimulation protocol was performed off drug therapy. Spontaneous ventricular tachycardia: All patients included in this study had only 1 morphology of JUNE 1, 2001
the clinical VT (69% vs 46%, p ⬍0.02). In patients with CAD, a higher inducibility was also signifiGroup 1 Group 2 cantly related to the presence of a left QRS axis (70% vs 44%, p ⬍0.02). No. of CSMVT ⫹ No SMVT Diagnosis Patients CSMVT NCSMVT NCSMVT Induced Furthermore, a multivariate analysis, including cardiac diagnosis, cycle CAD 85 31 18 23 13 length of clinical VT, LVEF, and VT Idiopathic dilated cardiomyopathy 24 11 1 6 6 Right ventricular dysplasia 18 12 3 2 1 left or right axis, identified only the Total 127 76 (60%) 51 (40%) left QRS axis as a significant and independent predictor of clinical VT CSMVT ⫽ clinical sustained monomorphic VT; NCSMVT ⫽ nonclinical sustained monomorphic VT; SMVT ⫽ sustained monomorphic VT. induction (odds ratio 2.67; p ⬍0.02). However, left or right bundle branch block pattern and superior or inferior spontaneous VT. The characteristics of these VTs are QRS axis morphologies did not predict induction clinlisted in Table 2. ical VT. For patients with CAD, the multivariate analIncidence of induced clinical and nonclinical ventric- ysis, including cycle length of the clinical VT, LVEF, ular tachycardia: Table 3 shows the inducibility rate left or right QRS axis in the ECG frontal plane, depending on the cardiac diagnosis. A total of 144 number of previous myocardial infarctions, infarction distinct VTs were induced, 76 of them were clinical location, and presence of aneurysm, also identified the VTs and the remaining were nonclinical. Patients presence of left QRS axis as a significant and indewere divided in 2 groups: group 1 included 76 patients pendent predictor of inducibility of the clinical VT in whom the clinical VT was induced and group 2 (odds ratio 3.16, p ⬍0.02). The inducibility rate of the included 51 patients in whom a sustained VT was not induced or only nonclinical VTs were induced. In 22 clinical VT among patients who developed clinical of the 76 group 1 patients, clinical and nonclinical arrhythmias on drugs and stimulation off drug therapy VTs were induced. In 20 of the 51 group 2 patients no was similar to that of the remaining patients (64% vs VTs were induced and in the remaining 31 patients 58%). only nonclinical VTs were induced. Twelve patients (24%) of those in whom the clinical VT was not induced did not have a complete stimulation protocol, DISCUSSION Main information: This study analyzes for the first 10 of these patients had inducibility of nonclinical time the clinical and ECG predictors of inducibility of VTs only. Tachycardia cycle length: The mean cycle length of the clinically documented VT using a conventional spontaneous episodes of VT was 341 ⫾ 88 ms. There stimulation protocol during a baseline electrophysiwas no significant difference between the cycle length ologic study. The main information is that an ECG of the spontaneous and induced episodes with a clin- variable, the presence of a left QRS axis in the frontal ical morphology (330 ⫾ 92 ms). However, the mean plane, is a strong predictor of inducibility of the clincycle length of induced nonclinical VT (296 ⫾ 60 ms) ical tachycardia, and in fact, was the only independent was significantly shorter than that of spontaneous ep- predictor in a multivariate analysis. Furthermore, this isodes (p ⬍0.001) and induced clinical VTs (p was also the only independent predictor in the subset ⬍0.02). of patients with CAD. Mode of induction of clinical and nonclinical ventricIncidence: The inducibility rate of clinical VT has ular tachycardia: Tables 4 and 5 show the mode of been reported in previous studies.7,9,14 Morady et al7 induction of clinical and nonclinical morphologies induced clinical VT in 85% of all patients included in depending on the cardiac diagnosis. No differences their series and in 91% of patients with CAD. Brugada were found comparing the mode of induction of clin- and Wellens9 reported that clinical VT was induced in ical and nonclinical VTs. 93% of patients with prior myocardial infarction. In Determinants of inducibility of clinical ventricular the present series, we observed smaller percentages, tachycardia: Univariated comparisons showed that pa60% for the whole series and 58% for patients with tients in whom the clinical VT was induced tended to have a normal LVEF (82% vs 56%, p ⫽ 0.06). The CAD. An important methodologic detail could actype of cardiac diagnosis also tended to be different: count for this difference: we considered an induced 58% of patients with CAD, 50% of patients with VT to be clinical VT only if it matched the spontanedilated cardiomyopathy, and 83% of patients with ous episode in all 12 ECG leads. In contrast, in the 7 right ventricular dysplasia belonged to group 1 (p ⫽ study of Morady et al, the analysis of the QRS 0.07). However, in patients with CAD neither the morphology was limited to 3 leads (V1, I, and III) and LVEF nor the presence and/or absence of LV aneu- in the study of Brugada and Wellens9 the number of rysm or the myocardial infarction location differed ECG leads used for comparing QRS morphologies between the 2 groups. The presence of left QRS axis was not clearly specified. Wilber et al14 using the 12 in the frontal plane during spontaneous VT was sig- ECG leads reported an incidence of inducibility of the nificantly associated with a higher inducibility rate of clinical VT closer to ours (66%). TABLE 3 Incidence of Induced Clinical and Nonclinical Ventricular Tachycardia (VT)
ARRHYTHMIAS AND CONDUCTION DISTURBANCES/INDUCIBILITY OF VT
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TABLE 4 Mode of Induction of Ventricular Tachycardia Clinical VT
CAD Idiopathic dilated cardiomyopathy Right ventricular dysplasia
Nonclinical VT
1 or 2 EE
3 EE
RP
Sp
St VT
1 or 2 EE
3 EE
RP
Sp
St VT
32 (65) 7 (58) 6 (40)
6 (12) 1 (8) 7 (47)
7 (14) — 1 (7)
3 (6) 4 (33) 1 (7)
1 (2) — —
35 (65) 5 (71) 2 (29)
12 (22) 1 (14) 4 (57)
2 (4) — —
1 (2) 1 (14) 1 (14)
4 (7) — —
Numbers in parentheses are percentages. EE ⫽ extrastimuli; RP ⫽ rapid pacing; Sp ⫽ spontaneously; St VT ⫽ stimulation during VT.
TABLE 5 Inducibility of Ventricular Tachycardia Depending on Stimulation Site Clinical VT
CAD Idiopathic dilated cardiomyopathy Right ventricular dysplasia
Nonclinical VT
Sp
HRA
RVA
RVOT
Sp
HRA
RVA
RVOT
3 (6) 4 (33) 1 (7)
1 (2) — —
32 (65) 8 (67) 10 (67)
13 (27) 0 4 (27)
1 (2) 1 (14) 1 (14)
— 2 (29) —
42 (78) 4 (57) 6 (86)
11 (20) 4 6
Numbers in parentheses are percentages. HRA ⫽ high right atrium; RVA ⫽ right ventricular apex; RVOT ⫽ right ventricular outflow tract; Sp ⫽ spontaneously.
Determinants of inducibility of clinical ventricular tachycardia: CARDIAC DIAGNOSIS AND LEFT VENTRICULAR EJECTION FRACTION: In the univariate analysis, both the cardiac diagnosis and the LVEF tended to be different in patients in whom clinical VT was inducible compared with those in whom it was not. Patients with arrhythmogenic right ventricular dysplasia manifested a higher inducibility of clinical VT. However, when included in a multivariate analysis, both variables lost their significance. These could also be related to a preserved left ventricle. In fact, in patients with a lower LVEF (idiopathic dilated cardiomyopathy and CAD) showed a lower inducibility rate of clinical VT. In contrast, the condition in which the substrate for VT is probably less well understood, dilated cardiomyopathy, was the one in which the inducibility rate was lowest. Reasons for that may include the presence of different mechanism for VT, some of which may not be reproduced by programmed stimulation and, the potential for induction of multiple morphologies in cases with such a diffuse substrate.
Electrocardiographic patterns of spontaneous ventricular tachycardia: To our surprise, a leftward axis of
the spontaneous VT was an independent predictor (and the only identified independent predictor) of inducibility of clinical VT, both in the whole series and in patients with CAD. There are at least 2 potential explanations for this finding. (1) The initiation of tachycardia may depend on the location of the stimulation site, relative to the particular components of the reentrant circuit in ventricular reentry in an analogous way, as is known to be the case in atrioventricular nodal reentry.17 Most clinical VTs were induced from the right ventricle apex, and pacing from the right ventricle apex usually produces a left axis QRS complex (pacing from the right ventricular outflow tract can also produce a left axis QRS complex in some cases). It is conceivable that the similarity in the direction of the exiting wave front of a left QRS axis 1258 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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VT with right ventricular pacing could produce a more favorable situation for initiation of reentry. It could be argued that in such a case bundle branch block morphology would also be related to inducibility because right ventricular stimulation usually produces a left bundle branch block ECG pattern, but, in contrast, the bundle branch block pattern may be less discriminative than the frontal plane axis. It is well known that LV stimulation can induce VTs in patients with spontaneous VT that are not inducible from the right ventricle.7,18 To our knowledge, the morphology of these VTs has not been described and it may well be that most of these VTs have a rightward axis. However, in our series this was not studied, given the conventional nature of the stimulation protocol. (2) Tachycardias with right QRS axis morphology could be less amenable to initiation by programmed electrical stimulation. We are aware of no information in this respect. A complete stimulation protocol from the right ventricle was not performed in 24% of the patients in whom clinical VT was not induced. We therefore cannot exclude the possibility that a higher inducibility rate would have been observed if a complete stimulation protocol had been performed. Acknowledgment: We thank Estrella Munilla, Maria Fe Miguel, and Antonio Moratalla for their technical assistance.
1. Klein LS, Shih HT, Hackett FK, Zipes DP, Miles WM. Radiofrequency
catheter ablation of ventricular tachycardia in patients without structural heart disease. Circulation 1992;85:1666 –1674. 2. Coggins DL, Lee RJ, Sweeney J, Chein WW, Van Hare G, Epstein L, Gonzalez R, Griffin JC, Lesh MD, Scheinman MM. Radiofrequency catheter ablation as a cure for idiopathic tachycardia of both left and right ventricular origen. J Am Coll Cardiol 1994;23:1333–1341. 3. 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;87:363–372. 4. Kim HY, Sosa-Suarez G, Trouton TG, O’Nunain SS, Osswald S, McGovern BA, Ruskin JN, Garan H. Treatment of ventricular tachycardia by transcatheter
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radiofrequency ablation in patients with isquemic heart disease. Circulation 1994;89:1094 –1102. 5. Rothman SA, Hsia HH, Cossu´ SF, Chmielewski IL, Buxton AE, Miller JM. Radiofrequency catheter ablation of postinfarction ventricular tachycardia. Longterm success and the significance of inducible nonclinical arrhythmias. Circulation 1997;96:3499 –3508. 6. Stevenson WG, Friedman PL, Kocovic D, Sagger PT, Saxon LA, Pavri B. Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction. Circulation 1998;98:308 –314. 7. Morady F, DiCarlo L, Winston S, Davis JC, Scheinman MM. A prospective comparison of triple extrastimuli and left ventricular stimulation in studies of ventricular tachycardia induction. Circulation 1984;70:52–57. 8. Estes NAM III, Garan H, McGovern B, Ruskin JN. Influence of drive cycle length during programmed stimulation on induction of ventricular arrhythmias: analysis of 403 patients. Am J Cardiol 1986;57:108 –112. 9. Brugada P, Wellens HJJ. Comparison in the same patient of two programmed ventricular stimulation protocols to induce ventricular tachycardia. Am J Cardiol 1985;55:380 –383. 10. McPherson CA, Rosenfeld LE, Batsford WP. Day-to-day reproducibility of responses to right ventricular programmed electrical stimulation: implications for serial drug testing. Am J Cardiol 1985;55:689 – 695. 11. Josephson ME, Horowitz LN, Farshidi A, SpielmanSR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia, 4. Pleomorphism. Circulation 1979;59:459 – 468. 12. Buxton AE, Waxman HL, Marchlinski FE, Untereker WJ, Waspe LE, Josephson ME. Role of triple extrastimuli during electrophysiologic study of
patients with documented sustained ventricular tachyarrhythmias. Circulation 1984;69:532–540. 13. Hummel JD, Strickberger SA, Daoud E, Niebauer M, Bakr O, Ching Man K, Williamson BD, Morady F. Results and efficiency of programmed ventricular stimulation with four extrastimuli compared with one, two, and three extrastimuli. Circulation 1994;90:2827–2832. 14. Wilber DJ, Davis MJ, Rosenbaum M, Ruskin JN, Garan H. Incidence and determinants of multiple morphologically distinct sustained ventricular tachycardia. J Am Coll Cardiol 1987;10:583–591. 15. Mitrani RD, Biblo LA, Carlson MD, Gatzoylis CA, Henthorn RW, Waldo AL. Multiple monomorphic ventricular tachycardia configurations predict failure of antiarrhythmic drug therapy guided by electrophysiological study. J Am Coll Cardiol 1993:1117–1122. 16. Alberca T, Almendral J, Sanz P, Almazan A, Cantalapiedra JL, Delcan JL. Evaluation of the specificity of morphological electrocardiographic criteria for the differential diagnosis of wide QRS complex tachycardia in patients with intraventricular conduction defects. Circulation 1997;96:3527–3533. 17. Ross DL, Brugada P, Bar FW, Vanagt EJ, Weiner I, Farre J, Wellens HJ. Comparisions of right and left atrial stimulation in demonstration of dual atrioventricular nodal pathways and induction of intranodal reentry. Circulation 1981;64:1051–1058. 18. Robertson JF, Cain ME, Horowitz LN, Spielman SR, Greenspan AM, Waxman HL, Josephson ME. Anatomic and electrophysiologic correlates of ventricular tachycardia requiring left ventricular stimulation. Am J Cardiol 1981; 48:263–268.
ARRHYTHMIAS AND CONDUCTION DISTURBANCES/INDUCIBILITY OF VT
1259
MD,
We analyzed the incidence and predictive factors for induction of clinical ventricular tachycardia (VT) during an electrophysiologic study in 127 patients with structural heart disease and spontaneous VT documented by 12-lead electrocardiography. Eighty-five patients had coronary artery disease (CAD), 24 had idiopathic dilated cardiomyopathy (IDC), and 18 had right ventricular dysplasia (RVD). Clinical variables were age, gender, electrocardiographic patterns of spontaneous arrhythmia, cardiac diagnosis, left ventricular (LV) ejection fraction (EF), infarct location, and presence of LV aneurysm. Clinical VT was induced in 76 patients (60%, group 1) and was not induced in 51 patients (group 2). Clinical VT was induced in 83% of patients with RVD, 58% of patients with CAD, and 50% of patients with IDC (p ⴝ 0.07). LVEF tended to be significantly higher in group 1
than in group 2 (p ⴝ 0.06). The presence of left QRS axis in the frontal plane during spontaneous VT was significantly associated with a higher inducibility both in the general group (69% vs 46%, p <0.02) and in patients with CAD (70% vs 44%, p <0.02). In patients with CAD, only the presence of a left QRS axis was significantly associated with a higher inducibility. A multivariate analysis identified only the left QRS axis as a significant and independent predictor of induction of clinical VT. The association of a leftward axis with inducibility suggests that vectorial factors in the depolarization wavefronts may be related to inducibility since conventional stimulation is performed from the right ventricle, producing a leftward axis in most cases. 䊚2001 by Excerpta Medica, Inc. (Am J Cardiol 2001;87:1255–1259)
atheter ablation has been recently developed as a therapeutic option for certain subsets of patients C with monomorphic ventricular tachycardia (VT). In
they met the following inclusion criteria: (1) ⱖ1 spontaneous episode of monomorphic tachycardia that after clinical and electrophysiologic evaluation was considered VT; (2) complete 12-lead ECG documentation of all spontaneous episodes that prompted the patient to seek medical attention; and (3) a complete programmed electrical stimulation protocol from the right ventricle had been performed. Patients without structural heart disease, those who required isoproterenol for induction, those with bundle branch reentry, and patients in whom antiarrhythmic therapy was not discontinued before the study were excluded from the study. All electrically induced sustained monomorphic VTs had 12-lead ECG documentation of morphology regardless of hemodynamic sequelae. Variables included in the analysis were age, gender, ECG patterns of spontaneous arrhythmia (right vs left bundle block pattern, superior vs inferior QRS axis, left vs right QRS axis, and cycle length), cardiac diagnosis, left ventricular (LV) ejection fraction (EF), number of infarctions, infarct location, and presence of LV aneurysm. Electrophysiologic study: All patients underwent electrophysiologic study after they gave written informed consent. All antiarrhythmic therapies were discontinued for ⱖ5 half-lives before the baseline study. Multipolar electrode catheters (interelectrode distance 2 to 5 mm) were placed under fluoroscopic guidance in the high right atrium, across the tricuspid valve to record a His bundle electrogram and in the right ventricular apex or outflow tract, or both, for recording and stimulation. Cardiac stimulation was performed with a constant current programmable stimulator (Biotronik UHS 20, Berlin, Germany).
1– 6
most of the reported series, for a patient to be considered as a candidate for this therapy, a tachycardia morphologically similar to the spontaneous tachycardia (so-called “clinical” VT) had to be induced during the electrophysiologic study.3–5 It is well known that in some patients a “clinical” tachycardia cannot be induced in the electrophysiology laboratory, either because no monomorphic VT can be induced or, more commonly, because a morphologically different VT is the only VT induced.7–15 In this context, the likelihood for induction of a “clinical” VT gains practical importance, because it is one of the factors that influences the potential for a patient with VT to become candidate for catheter ablation, especially in patients with coronary artery disease (CAD). This study retrospectively analyzes the incidence and determines the clinical, electrocardiographic (ECG), and angiographic factors that predict the induction of a “clinical” VT during a baseline electrophysiologic study.
METHODS
Patients and clinical characteristics: The study population consisted of 127 consecutive patients who underwent electrophysiologic evaluation from July 1989 to November 1998. Patients were included if From the Department of Cardiology, Hospital General Universitario Gregorio Maran˜on, Madrid, Spain. Manuscript received August 4, 2000; revised manuscript received and accepted January 2, 2001. Address for reprints: Jesu´s Almendral, MD, Cardiologı´a (planta 5), Hospital General Gregrorio Maran˜o´n, Doctor Esquerdo, 46, 28007Madrid, Spain. E-mail: almendral@softmed-s. ©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 87 June 1, 2001
0002-9149/01/$–see front matter PII S0002-9149(01)01545-4
1255
Stimuli were rectangular pulses with a duration of 1 ms and a current strength twice the diastolic capture threshold. Recordings were obtained with a photographic recorder (VR 12, Electronics for Medicine, New York) or with a temperature recorder (Marquette Hellige, Midas 2500⫹OHR, Freiburg in Breisgau, Germany) at a paper speed of 25 to 100 mm/s. All intracardiac electrograms were filtered at 30 to 500 Hz. A conventional programmed stimulation protocol was performed. In all patients, this included atrial pacing up to the rate at which atrioventricular node Wenckebach block occurred. Up to 3 ventricular extrastimuli were introduced during sinus rhythm and ventricular pacing at a paced cycle length of 600 (or 550) and 400 ms at the right ventricular apex and the outflow tract. Our stimulation protocol included LV stimulation whenever the clinical VT was not induced with atrial or right ventricular stimulation in patients with CAD and idiopathic dilated cardiomyopathy. However, these results were not analyzed because they were not routinely performed. The end point of stimulation was either induction of the clinically documented VT or the achievement of ventricular refractoriness. If an induced ventricular tachyarrhythmia required electrical cardioversion, it was the decision of the electrophysiologist responsible for the study to continue the stimulation protocol or not. Induced polimorphic VTs (sustained or not) and induced nonsustained monomorphic VTs were excluded from the analysis. VTs that occurred spontaneously or during catheter manipulation during the electrophysiologic study were considered to be induced VTs. Definitions: Sustained monomorphic VT was defined as a VT that lasted ⬎30 seconds or that caused hemodynamic compromise requiring immediate termination by pacing or cardioversion. Clinical VT was defined as a sustained monomorphic VT induced during programmed electrical stimulation with similar surface ECG configuration (same QRS duration, same bundle branch, ⬍45° difference in frontal and horizontal axes) as a documented spontaneous episode, and nonclinical VT was defined as a sustained monomorphic VT induced during programmed electrical stimulation that differed in surface ECG morphology (different bundle branch or a change in either frontal or horizontal axis by ⬎45°) from that observed during spontaneous episodes. Morphologic ECG criteria were defined during VT16; a QRS complex was considered to have a right bundle branch block morphology if it had a dominant R wave in lead V1; if the dominant wave in V1 was an S wave, the QRS complex was considered to have a left bundle branch block morphology. Left QRS axis deviation was considered when the QRS axis in the frontal plane was between ⫺30° and ⫺90°. Right QRS axis deviation was considered when the QRS axis in the frontal plane was between ⫺90° and ⫾180°. LVEF was obtained from the echocardiographic measurement and was classified as normal (ⱖ55%) or depressed (⬍55%). Analysis of ventricular tachycardia morphologies: In each patient, the 12-lead electrocardiogram of all in1256 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE 1 Clinical Characteristics of Patients With Documented Sustained Monomorphic Ventricular Tachycardia (n ⫽ 127) Age (mean ⫾ SD) (yrs) Men/women LVEF ⬍0.31 0.31–0.4 0.41–0.55 ⬎0.55 Cardiac diagnosis Right ventricular dysplasia Idiopathic dilated cardiomyopathy CAD with previous myocardial infarction: ⬎1 myocardial infarction Myocardial infarction location Anterior Inferior Lateral Indeterminate Left ventricular aneurysm
59 ⫾ 15 113/14 41 42 27 17
(32%) (33%) (21%) (13%)
18 24 85 12
(14%) (19%) (67%) (14%)
42 51 2 3 28
(49%) (60%) (2%) (4%) (33%)
TABLE 2 Characteristics of Spontaneous Documented Ventricular Tachycardia (n ⫽ 127) Cycle length (ms) Configuration of QRS complex Right bundle branch block Left bundle branch block Superior axis Inferior axis Left axis Right axis
341 ⫾ 86 73 54 79 48 75 52
duced sustained monomorphic VT was compared with the 12-lead electrocardiogram of the spontaneous episode of sustained monomorphic VT. All electrocardiograms were recorded at a standard paper speed (25 mm/s) and amplitude (1 mV/mm). VTs were considered similar in morphology if the vectors of the QRS complex were the same in all the 12 recorded leads. Statistical analysis: Statistical analysis was performed with the JMP 3.0.1 statistical software (SAS Institute Inc., Cary, North Carolina, 1994). Data are reported as distributions and mean ⫾ SD values. Statistical comparisons for the 2 groups were performed using the paired t test. A separate subanalysis was performed for patients with CAD, because this was the larger group of patients. The variables with suspected influence on inducibility were included in a multiple logistic regression analysis to determine the independence of its contribution in such inducibility.
RESULTS
Patients and clinical characteristics: Patients’ clinical characteristics are summarized in Table 1. Eighty-five patients had CAD with previous myocardial infarction, 24 patients had idiopathic dilated cardiomyopathy, and the remaining 18 patients had right ventricular dysplasia. Eleven patients (9%) developed documented clinical arrhythmias on drug therapy and the stimulation protocol was performed off drug therapy. Spontaneous ventricular tachycardia: All patients included in this study had only 1 morphology of JUNE 1, 2001
the clinical VT (69% vs 46%, p ⬍0.02). In patients with CAD, a higher inducibility was also signifiGroup 1 Group 2 cantly related to the presence of a left QRS axis (70% vs 44%, p ⬍0.02). No. of CSMVT ⫹ No SMVT Diagnosis Patients CSMVT NCSMVT NCSMVT Induced Furthermore, a multivariate analysis, including cardiac diagnosis, cycle CAD 85 31 18 23 13 length of clinical VT, LVEF, and VT Idiopathic dilated cardiomyopathy 24 11 1 6 6 Right ventricular dysplasia 18 12 3 2 1 left or right axis, identified only the Total 127 76 (60%) 51 (40%) left QRS axis as a significant and independent predictor of clinical VT CSMVT ⫽ clinical sustained monomorphic VT; NCSMVT ⫽ nonclinical sustained monomorphic VT; SMVT ⫽ sustained monomorphic VT. induction (odds ratio 2.67; p ⬍0.02). However, left or right bundle branch block pattern and superior or inferior spontaneous VT. The characteristics of these VTs are QRS axis morphologies did not predict induction clinlisted in Table 2. ical VT. For patients with CAD, the multivariate analIncidence of induced clinical and nonclinical ventric- ysis, including cycle length of the clinical VT, LVEF, ular tachycardia: Table 3 shows the inducibility rate left or right QRS axis in the ECG frontal plane, depending on the cardiac diagnosis. A total of 144 number of previous myocardial infarctions, infarction distinct VTs were induced, 76 of them were clinical location, and presence of aneurysm, also identified the VTs and the remaining were nonclinical. Patients presence of left QRS axis as a significant and indewere divided in 2 groups: group 1 included 76 patients pendent predictor of inducibility of the clinical VT in whom the clinical VT was induced and group 2 (odds ratio 3.16, p ⬍0.02). The inducibility rate of the included 51 patients in whom a sustained VT was not induced or only nonclinical VTs were induced. In 22 clinical VT among patients who developed clinical of the 76 group 1 patients, clinical and nonclinical arrhythmias on drugs and stimulation off drug therapy VTs were induced. In 20 of the 51 group 2 patients no was similar to that of the remaining patients (64% vs VTs were induced and in the remaining 31 patients 58%). only nonclinical VTs were induced. Twelve patients (24%) of those in whom the clinical VT was not induced did not have a complete stimulation protocol, DISCUSSION Main information: This study analyzes for the first 10 of these patients had inducibility of nonclinical time the clinical and ECG predictors of inducibility of VTs only. Tachycardia cycle length: The mean cycle length of the clinically documented VT using a conventional spontaneous episodes of VT was 341 ⫾ 88 ms. There stimulation protocol during a baseline electrophysiwas no significant difference between the cycle length ologic study. The main information is that an ECG of the spontaneous and induced episodes with a clin- variable, the presence of a left QRS axis in the frontal ical morphology (330 ⫾ 92 ms). However, the mean plane, is a strong predictor of inducibility of the clincycle length of induced nonclinical VT (296 ⫾ 60 ms) ical tachycardia, and in fact, was the only independent was significantly shorter than that of spontaneous ep- predictor in a multivariate analysis. Furthermore, this isodes (p ⬍0.001) and induced clinical VTs (p was also the only independent predictor in the subset ⬍0.02). of patients with CAD. Mode of induction of clinical and nonclinical ventricIncidence: The inducibility rate of clinical VT has ular tachycardia: Tables 4 and 5 show the mode of been reported in previous studies.7,9,14 Morady et al7 induction of clinical and nonclinical morphologies induced clinical VT in 85% of all patients included in depending on the cardiac diagnosis. No differences their series and in 91% of patients with CAD. Brugada were found comparing the mode of induction of clin- and Wellens9 reported that clinical VT was induced in ical and nonclinical VTs. 93% of patients with prior myocardial infarction. In Determinants of inducibility of clinical ventricular the present series, we observed smaller percentages, tachycardia: Univariated comparisons showed that pa60% for the whole series and 58% for patients with tients in whom the clinical VT was induced tended to have a normal LVEF (82% vs 56%, p ⫽ 0.06). The CAD. An important methodologic detail could actype of cardiac diagnosis also tended to be different: count for this difference: we considered an induced 58% of patients with CAD, 50% of patients with VT to be clinical VT only if it matched the spontanedilated cardiomyopathy, and 83% of patients with ous episode in all 12 ECG leads. In contrast, in the 7 right ventricular dysplasia belonged to group 1 (p ⫽ study of Morady et al, the analysis of the QRS 0.07). However, in patients with CAD neither the morphology was limited to 3 leads (V1, I, and III) and LVEF nor the presence and/or absence of LV aneu- in the study of Brugada and Wellens9 the number of rysm or the myocardial infarction location differed ECG leads used for comparing QRS morphologies between the 2 groups. The presence of left QRS axis was not clearly specified. Wilber et al14 using the 12 in the frontal plane during spontaneous VT was sig- ECG leads reported an incidence of inducibility of the nificantly associated with a higher inducibility rate of clinical VT closer to ours (66%). TABLE 3 Incidence of Induced Clinical and Nonclinical Ventricular Tachycardia (VT)
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TABLE 4 Mode of Induction of Ventricular Tachycardia Clinical VT
CAD Idiopathic dilated cardiomyopathy Right ventricular dysplasia
Nonclinical VT
1 or 2 EE
3 EE
RP
Sp
St VT
1 or 2 EE
3 EE
RP
Sp
St VT
32 (65) 7 (58) 6 (40)
6 (12) 1 (8) 7 (47)
7 (14) — 1 (7)
3 (6) 4 (33) 1 (7)
1 (2) — —
35 (65) 5 (71) 2 (29)
12 (22) 1 (14) 4 (57)
2 (4) — —
1 (2) 1 (14) 1 (14)
4 (7) — —
Numbers in parentheses are percentages. EE ⫽ extrastimuli; RP ⫽ rapid pacing; Sp ⫽ spontaneously; St VT ⫽ stimulation during VT.
TABLE 5 Inducibility of Ventricular Tachycardia Depending on Stimulation Site Clinical VT
CAD Idiopathic dilated cardiomyopathy Right ventricular dysplasia
Nonclinical VT
Sp
HRA
RVA
RVOT
Sp
HRA
RVA
RVOT
3 (6) 4 (33) 1 (7)
1 (2) — —
32 (65) 8 (67) 10 (67)
13 (27) 0 4 (27)
1 (2) 1 (14) 1 (14)
— 2 (29) —
42 (78) 4 (57) 6 (86)
11 (20) 4 6
Numbers in parentheses are percentages. HRA ⫽ high right atrium; RVA ⫽ right ventricular apex; RVOT ⫽ right ventricular outflow tract; Sp ⫽ spontaneously.
Determinants of inducibility of clinical ventricular tachycardia: CARDIAC DIAGNOSIS AND LEFT VENTRICULAR EJECTION FRACTION: In the univariate analysis, both the cardiac diagnosis and the LVEF tended to be different in patients in whom clinical VT was inducible compared with those in whom it was not. Patients with arrhythmogenic right ventricular dysplasia manifested a higher inducibility of clinical VT. However, when included in a multivariate analysis, both variables lost their significance. These could also be related to a preserved left ventricle. In fact, in patients with a lower LVEF (idiopathic dilated cardiomyopathy and CAD) showed a lower inducibility rate of clinical VT. In contrast, the condition in which the substrate for VT is probably less well understood, dilated cardiomyopathy, was the one in which the inducibility rate was lowest. Reasons for that may include the presence of different mechanism for VT, some of which may not be reproduced by programmed stimulation and, the potential for induction of multiple morphologies in cases with such a diffuse substrate.
Electrocardiographic patterns of spontaneous ventricular tachycardia: To our surprise, a leftward axis of
the spontaneous VT was an independent predictor (and the only identified independent predictor) of inducibility of clinical VT, both in the whole series and in patients with CAD. There are at least 2 potential explanations for this finding. (1) The initiation of tachycardia may depend on the location of the stimulation site, relative to the particular components of the reentrant circuit in ventricular reentry in an analogous way, as is known to be the case in atrioventricular nodal reentry.17 Most clinical VTs were induced from the right ventricle apex, and pacing from the right ventricle apex usually produces a left axis QRS complex (pacing from the right ventricular outflow tract can also produce a left axis QRS complex in some cases). It is conceivable that the similarity in the direction of the exiting wave front of a left QRS axis 1258 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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VT with right ventricular pacing could produce a more favorable situation for initiation of reentry. It could be argued that in such a case bundle branch block morphology would also be related to inducibility because right ventricular stimulation usually produces a left bundle branch block ECG pattern, but, in contrast, the bundle branch block pattern may be less discriminative than the frontal plane axis. It is well known that LV stimulation can induce VTs in patients with spontaneous VT that are not inducible from the right ventricle.7,18 To our knowledge, the morphology of these VTs has not been described and it may well be that most of these VTs have a rightward axis. However, in our series this was not studied, given the conventional nature of the stimulation protocol. (2) Tachycardias with right QRS axis morphology could be less amenable to initiation by programmed electrical stimulation. We are aware of no information in this respect. A complete stimulation protocol from the right ventricle was not performed in 24% of the patients in whom clinical VT was not induced. We therefore cannot exclude the possibility that a higher inducibility rate would have been observed if a complete stimulation protocol had been performed. Acknowledgment: We thank Estrella Munilla, Maria Fe Miguel, and Antonio Moratalla for their technical assistance.
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