Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia.

The refinement of the techniques of programmed stimulation and intracardiac recording has led to understanding of the mechanism of ventricular tachycardia and these techniques can be applied clinically to the development of therapeutic regimens. The efficacy of drug therapy can be assessed in sequential studies evaluating the ability of drugs to prevent initiation of the arrhythmia by electrical stimulation. The efficacy of pacemaker therapy can be evaluated by assessing the effects of stimulation during the tachycardia. The recent development of endocardial mapping provides the surgeon with a tool to guide therapeutic surgical ablation of the site of origin of the tachycardia. Such an electrophysiologic approach to recurrent ventricular tachycardia can lead to the rapid development of successful therapy under controlled conditions.     

Electrophysiologic effects and clinical efficacy of oral propafenone therapy in patients with ventricular tachycardia

The effects of the antiarrhythmic agent propafenone were evaluated in 25 patients with recurrent symptomatic ventricular tachycardia. Oral propafenone was given to a maximal dose of 300 mg every 8 hours. Ten of the 25 patients developed side effects or had inadequate suppression of spontaneous ventricular arrhythmias during propafenone therapy. Electrophysiologic studies were performed before and during drug therapy on the 15 patients who had a satisfactory clinical response. Propafenone increased the PR interval from 168 +/- 46 to 188 +/- 25 ms (p less than 0.007), the HV interval from 47 +/- 10 to 65 +/- 13 ms (p less than 0.005), the shortest atrial pacing cycle length to maintain 1:1 atrioventricular (AV) nodal conduction from 385 +/- 44 to 436 +/- 42 ms (p less than 0.005), the ventricular effective refractory period from 231 +/- 17 to 255 +/- 19 ms (p less than 0.001) and the ventricular functional refractory period from 260 +/- 15 to 278 +/- 17 ms (p less than 0.002). Before propafenone therapy, all 15 patients had ventricular tachycardia induced by programmed ventricular stimulation. During propafenone treatment, 12 patients still had ventricular tachycardia induced, and the tachycardia cycle length significantly increased from 236 +/- 44 to 374 +/- 103 ms (p less than 0.001). Ten patients were considered to have satisfactory electrophysiologic response to propafenone on the basis of either the inability to initiate ventricular tachycardia or a marked increase in ventricular tachycardia cycle length associated with lack of symptoms during the induced tachycardia. These patients were discharged receiving propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacologic therapy of ventricular tachycardia using electrophysiologic techniques

Serial pharmacologic trials guided by electrophysiologic techniques provide an objective method for instituting effective medical therapy in patients with sustained ventricular arrhythmias. Suppression of induced ventricular tachycardia by administered antiarrhythmic agents predicts the results of chronic treatment with a high degree of accuracy. Although some controversy exists with regard to precise stimulation protocols, the ability to evaluate the advantages and potentially detrimental actions of individual drugs in a controlled environment contributes substantially to the utility of electrophysiologic testing in the selection of an optimal antiarrhythmic regimen.     

Verapamil responsive ventricular tachycardia: clinical and electrophysiologic characteristics.

Ventricular tachycardia is a rare arrhythmia in young patients without associated heart disease. Electrophysiologic studies were performed in thirteen young patients (mean age 26.4 +/- 7 years) with recurrent sustained ventricular tachycardia (VT) responsive to intravenous verapamil. The QRS duration during VT was less than 0.14 sec in all patients. The VT showed a right bundle branch block (RBBB) morphology in all cases, with left axis deviation in 12 and right axis deviation in one. Eleven patients were free of organic heart disease. VT could be induced in the laboratory in 10 patients, out of whom the electrophysiologic mechanism of VT could be assessed in 9 cases. The data were consistent with reentry in 8 patients and suggested triggered activity in one patient. Atrial pacing induced the VT in two cases. Nine patients were restudied 48 to 72 hours after oral verapamil (240 to 320 mg/day). VT was not inducible in 8 patients and was markedly slowed in one. VT of RBBB morphology occurring in young patients has distinct electrocardiographic and electropharmacologic properties. Reentry is the usual underlying mechanism. Verapamil is highly effective in terminating and preventing the VT.     

Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.

BACKGROUND. Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined. METHODS AND RESULTS. Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03). CONCLUSIONS. QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.     

Electrophysiologic effects of ethmozin in patients with ventricular tachycardia

Ten patients with recurrent episodes of ventricular tachycardia (VT) had electrophysiologic studies in the basal state and on chronic oral ethmozin (12.1 ± 0.6 SE mg/kg/day). Ethmozin significantly prolonged the AH interval (basal: 75 ± 8 SE msec; ethmozin: 91 ± 10 msec, p < 0.05), the HV interval (51 ± 3; 66 ± 5 msec, p < 0.01), and the QRS duration (101 ± 4; 118 ± 4 msec, p < 0.001). Atrial and ventricular refractory periods and the corrected QT interval were not significantly affected by ethmozin. VT was induced in 7 of 10 patients in the basal state by means of programmed right ventricular extrastimulation or rapid burst ventricular pacing. On oral ethmozin nine patients had inducible VT. VT cycle length was consistently prolonged on ethmozin (250 ± 13; 326 ± 14 msec, p < 0.001). Four of the seven patients with VT on basal ambulatory monitoring had total abolition of spontaneous VT on ethmozin. Ethmozin failed to prevent induction of VT in most patients despite significant reductions in ventricular arrhythmia on ambulatory monitoring. Further studies comparing VT induction with ambulatory monitoring in patients on ethmozin are needed to confirm these findings and to define the clinical significance of this dissociation.     

Predictors of ventricular tachycardia recurrence in 100 patients receiving tiered therapy defibrillators

BACKGROUND AND HYPOTHESIS: Programmed electrical stimulation (PES) is a time-honored diagnostic tool in patients with ventricular tachyarrhythmias. The response to PES can be used to assess efficacy of pharmacologic or electrical therapy, as well as to obtain prognostic information. Reproducible induction of ventricular tachycardia with invasive electrophysiologic testing, or stimulation through defibrillator lead systems, can help optimize antiarrhythmic drug therapy and device programming during clinical follow-up. METHODS: We present our experience with 100 patients who had inducible sustained monomorphic ventricular tachycardia (SMVT) during invasive PES at baseline, and received a third-generation implantable cardioverter-defibrillator (ICD) alone, or in combination with antiarrhythmic drug therapy. Noninvasive programmed stimulation (NIPS) was performed prior to hospital discharge in 61 patients. RESULTS: The inducibility of SMVT was concordant between the invasive study and NIPS in a subgroup of 40 (82%) patients who had invasive PES on the same drug regimen. During a mean follow-up of 16 months, there were 12 nonarrhythmic deaths and recurrence of spontaneous SMVT in 36 (40%) of the surviving patients. Using a Cox proportional hazards model, the following variables were associated with early arrhythmia recurrence: persistent inducibility of SMVT during the NIPS session (relative risk 11, range 2.6-47); induction of SMVT with a cycle length > 280 ms during invasive baseline PES (2.5, 1.2-5) and presence of prior inferior myocardial infarction (2.1, 1-4.2). Timing to initial recurrence of spontaneous tachycardia was unaffected by other clinical variables or concomitant antiarrhythmic drug use. CONCLUSION: Programmed electrical stimulation techniques offer insight into the patterns of spontaneous ventricular tachycardia recurrence and have significant practical utility in the management of patients receiving third-generation ICDs.     

Value of electrophysiologic testing in patients with nonsustained ventricular tachycardia

This study was undertaken to determine the value of electrophysiologic testing in 61 patients with nonsustained ventricular tachycardia (VT) (3 or more beats) on ambulatory monitoring and no history of sustained ventricular arrhythmia. The study group consisted of 38 patients with coronary artery disease (CAD), 9 with idiopathic dilated cardiomyopathy and 14 with a normal heart. Nonsustained VT (at least 3 but not more than 15 beats) was induced in 46%, sustained VT (more than 15 beats) in 15% and no VT in 39%. Sustained VT was induced more frequently in the presence of left ventricular dysfunction (p = 0.005) but was not related to the presence of CAD. Over a mean follow-up of 26 months, 10 patients died from cardiac causes (4 suddenly), including 1 patient with inducible sustained VT, 2 with nonsustained VT and 7 with no inducible VT. Inducibility was not related to survival, either as a single variable or when combined with CAD, left ventricular dysfunction or recent myocardial infarction. Left ventricular function alone was a good predictor of outcome. Of 46 patients with an ejection fraction of 35% more or in New York Heart Association functional class I or II, 3 (7%) died from cardiac causes, compared with 7 of 13 patients (54%) with an ejection fraction of less than 35% or in functional class III or IV (p = 0.0001). Thus, in patients with nonsustained VT, the incidence of sustained VT during electrophysiologic testing is low and is related to the degree of left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic testing in assessment of therapy with sotalol for sustained ventricular tachycardia

Eighteen patients with sustained ventricular tachycardia underwent electrophysiologic studies to establish the therapeutic efficacy of sotalol. In each patient ventricular tachycardia could be reproducibly initiated by programmed stimulation during control studies. Sotalol prevented induction of sustained ventricular tachycardia in 12 of the 18 patients (67%). Prolongation of the QTC interval and of ventricular refractoriness was regularly observed after sotalol but did not reliably predict prophylactic efficacy. Severe adverse effects, including congestive heart failure and sinus node dysfunction, were noted early during sotalol therapy in three patients. Nine patients were placed on long-term oral treatment with sotalol and four patients on another effective agent. In these 13 patients, complete (12 patients) or partial (one patient) long-term prophylaxis against ventricular tachycardia was documented over a mean follow-up period of 16 months (range 8 to 24). The study suggests that sotalol can provide effective prophylaxis against sustained ventricular tachycardia; this prophylactic efficacy is not typical for pure beta-adrenergic antagonism but may at least partly result from experimentally observed prolongation of the ventricular action potential duration.     

Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia

This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Idiopathic sustained ventricular tachycardia responsive to verapamil: clinical electrocardiographic and electrophysiologic considerations

Fifteen cases of idiopathic VT responsive to verapamil were studied to examine its clinical, electrocardiographic and electrophysiologic features. All patients were male, aged 15-49, average age 28. Initial onset of VT occurred at ages 9-48 (average 21). Time from onset of VT to first admission was 1-20 years (average 8.2 years), and patients had been followed for 17-40 months (average 27 months). 13 cases had palpitations, 5 had faintness, 1 had syncope, but no deaths were reported. ECG's at time of VT exhibited CRBBB + LAD pattern in 12 cases, CRBBB + RAD pattern in 1, and LBBB in 2. VT rate was 130-200 bpm (average 163 bpm), with QRS width of 0.11 - 0.16 sec (average 0.14 sec). ECG's during sinus rhythm revealed no ST/T abnormalities, although in 6 cases they were found post-VT. 5 cases had recognizable H waves during VT, and HV intervals were shorter than that during sinus rhythm. VT could be induced by programmed electrical stimulation in 14 cases. VT or RVR could be induced by atrial pacing in 6 of 14, single RV extra-stimuli in 12 of 14, paired pulses in 5 of 12, RV overdrive pacing in 7 of 14, and burst pacing in 6 of 14 cases. VT could be terminated by RV burst pacing in 14 of the 15 cases, while single RV stimuli were effective in 5 out of 12 cases. Among the 12 cases in which VT could be induced by single RV extra-stimuli, the relationship between changes in premature interval for the induction of VT and the echo interval of VT (extrastimulus to first VT complex) was examined. 8 showed an inverse relationship, 3 showed a concordant relationship and 1 case could not be assessed. An inverse relationship was found between changes in paced cycle length and echo interval for the 2 cases in which VT could be induced by rapid pacing. Verapamil terminated sustained VT in 12 out of 13 cases, and in another case had a pronounced decelerating effect. Prior to termination, VT rate was drastically reduced (from 163 +/- 29 bpm to 128 +/- 29 bpm). Verapamil was able to prevent the induction of VT in 6 out of 14 cases, while in 6 cases the VT zone was expanded and in 2 cases the VT zone was narrowed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Amiodarone: risk factors for recurrence of symptomatic ventricular tachycardia identified at electrophysiologic study

Ventricular tachycardia induced by programmed electrical stimulation during amiodarone therapy often does not preclude a good clinical response. The purpose of this study was to determine whether use of discriminant analysis could distinguish patients who remained asymptomatic from those who subsequently developed symptomatic ventricular tachycardia or cardiac arrest. Studies were performed in 37 patients with sustained ventricular tachycardia who still had ventricular tachycardia induced during programmed electrical stimulation during amiodarone therapy. The mean follow-up time was 14.1 +/- 1.3 months (+/- SEM). Twenty-three patients remained asymptomatic, whereas 14 patients had symptomatic recurrence of their ventricular tachycardia. In patients with recurrence of arrhythmia compared with asymptomatic patients, administration of amiodarone caused a longer ventricular effective refractory period (296 +/- 8 versus 271 +/- 7 ms, p less than 0.05) and a greater change in corrected QT [QTc] interval (90 +/- 18 versus 44 +/- 9 ms, p less than 0.02), but no difference in the decrease in premature ventricular complexes after treatment with amiodarone. During amiodarone therapy, nonbundle branch reentrant repetitive ventricular responses were induced by a single ventricular extrastimulus during sinus rhythm in 9 of 14 patients with recurrent arrhythmias compared with 2 of 21 asymptomatic patients (p = 0.001). Also, less aggressive pacing techniques were required to induce ventricular tachycardia in 9 of 14 symptomatic patients compared with 4 of 23 asymptomatic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of early electrophysiologic studies for ventricular tachycardia recurrence in patients with coronary artery disease treated with amiodarone

Amiodarone was used in 86 patients with ventricular tachycardia (VT) (67 patients) or ventricular fibrillation (19 patients) secondary to coronary artery disease. The mean +/- standard deviation left ventricular ejection fraction was 30 +/- 12% (range 8 to 65%). Prior trials with 4 +/- 1.2 alternate antiarrhythmic agents had been unsuccessful. Amiodarone was loaded at dosages of 1,200 to 1,800 mg/day, with maintenance dosages of 400 to 600 mg/day. Drug efficacy was evaluated by programmed stimulation at 10 to 14 days in 68 patients. In 38 patients sustained VT or ventricular fibrillation was inducible (group I), whereas 30 patients (group II) had either no inducible VT (8) or had nonsustained VT induced (22). Holter monitoring was used to assess drug efficacy in 18 patients (group III). All patients were evaluated at 3- to 6-month intervals with Holter monitors for efficacy and a standard protocol for toxicity. During a long-term follow-up of 18 +/- 16 months, sudden death occurred in 5 patients and nonfatal arrhythmia recurrences were detected in 16. The actuarial probability of freedom from fatal and nonfatal arrhythmia recurrences at 24 months was 0.52 for group I, 0.97 for group II and 0.68 for group III. The mode of induction, rate change or hemodynamic tolerance of the induced ventricular tachycardia did not predict arrhythmia recurrence. Among the clinical variables analyzed, only an ejection fraction of less than or equal to 30% was identified as a significant predictor of arrhythmia recurrence. Nonsudden cardiac death occurred in 21 patients, including 19 from heart failure and 2 from myocardial infarction. Noncardiac death occurred in 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic and clinical factors influencing response to class IA antiarrhythmic agents in patients with inducible sustained monomorphic ventricular tachycardia

Clinical and electrophysiologic data from 51 consecutive patients with sustained monomorphic ventricular tachycardia inducible during programmed ventricular stimulation were evaluated to determine what variables predict the response to intravenous class IA antiarrhythmic agents. All patients received acute drug testing in the electrophysiologic laboratory with either intravenous procainamide or intravenous quinidine. Ventricular tachycardia suppression was achieved in 9 out of 51 patients (18%). The age, gender, left ventricular ejection fraction, baseline right ventricular effective refractory period, baseline HV interval, and baseline ventricular tachycardia cycle length were not predictive of ventricular tachycardia suppression with intravenous procainamide or quinidine during programmed ventricular stimulation. The degree of prolongation of the right ventricular effective refractory period after drug administration did not predict success or failure to suppress inducible ventricular tachycardia. The degree of prolongation of the HV interval was also not predictive. In addition, the degree of prolongation of the right ventricular effective refractory period or the HV interval did not predict the change in the ventricular tachycardia cycle length after drug administration in patients who remained inducible. These data indicate that the response to class IA antiarrhythmic agents in patients with inducible sustained monomorphic ventricular tachycardia cannot be predicted on the basis of various clinical and electrophysiologic parameters.     

Antagonism of quinidine's electrophysiologic effects by epinephrine in patients with ventricular tachycardia

The purpose of this study was to determine whether pharmacologically induced elevations in the plasma epinephrine concentration within reported physiologic limits alter the response to quinidine during electropharmacologic testing. Twenty-one patients with coronary artery disease and a history of unimorphic ventricular tachycardia were found to have inducible sustained unimorphic ventricular tachycardia that was suppressed by treatment with oral quinidine gluconate. Epinephrine was then infused at a rate of either 25 or 50 ng/kg per min and testing was repeated. These infusion rates of epinephrine were previously demonstrated to result in elevations of the plasma epinephrine concentration in the range of concentrations that occur during a variety of stresses. Quinidine significantly lengthened the ventricular refractory periods and the QRS duration at a ventricular pacing cycle length of 350 ms, which was used as an index of intraventricular conduction. Epinephrine partially or completely reversed the effects of quinidine on ventricular refractory periods, but had no effect on QRS duration. During electropharmacologic testing of quinidine, no ventricular tachycardia was inducible in 12 patients, and only nonsustained ventricular tachycardia, 8 to 48 beats in duration, was inducible in 9 patients. Retesting during infusion of epinephrine demonstrated inducible sustained unimorphic ventricular tachycardia in 2 of the 12 patients in whom quinidine had completely suppressed the induction of ventricular tachycardia and in 8 of the 9 patients in whom only nonsustained ventricular tachycardia had been inducible during testing of quinidine. In conclusion, physiologic elevations in the plasma epinephrine concentration may reverse quinidine-induced prolongation of ventricular refractoriness but not intraventricular conduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy

Eleven consecutive patients with idiopathic dilated cardiomyopathy and spontaneous, sustained ventricular tachycardia (VT) of uniform morphology underwent programmed ventricular stimulation and serial antiarrhythmic drug testing. The mean ejection fraction was 30 +/- 6.4%. Sustained VT was induced by programmed electrical stimulation in all 11 patients. A mean of 3.7 +/- 2.4 antiarrhythmic drugs were evaluated by programmed stimulation, including at least one experimental agent in eight patients. In nine of 11 patients VT remained inducible on all drug therapy. During a mean follow-up period of 21 +/- 14 months there were four sudden deaths and two patients with recurrences of VT. In all six patients with sudden death or recurrence of VT, the arrhythmia remained inducible on drug therapy. Three patients who died suddenly had a hemodynamically stable, induced tachycardia on antiarrhythmic therapy. Of eight patients treated with amiodarone, only two were successfully treated. We conclude that in patients with sustained VT and idiopathic dilated cardiomyopathy, VT can be induced by programmed electrical stimulation. VT will usually remain inducible on antiarrhythmic therapy, and sudden death can occur despite slowing and improved tolerance of the induced arrhythmia. Amiodarone may have limited efficacy, and more aggressive therapy, such as surgery or implantation of an automatic internal defibrillator, should be considered in this patient population.