Rapid self-terminating ventricular tachycardia induced during electrophysiologic study: a prospective evaluation

The clinical significance of rapid self-terminating ventricular tachycardia induced during electrophysiologic study was prospectively evaluated in three patient groups with clinical ventricular arrhythmias. Group A (11 patients) had inducible rapid self-terminating ventricular tachycardia only (mean cycle length less than or equal to 250 ms and greater than or equal to 10 beats in duration). In Group B (22 patients) induction of this arrhythmia was followed by the induction of sustained ventricular tachycardia. In Group C (82 patients) sustained ventricular tachycardia was induced without preceding rapid self-terminating ventricular tachycardia. All clinical characteristics of Group B patients were similar to those of Group C patients but differed markedly from those of Group A patients. Compared with Group A patients, Group B patients had a lower left ventricular ejection fraction (32 +/- 13% versus 52 +/- 17%, p = 0.004) and a greater prevalence of coronary artery disease (82% versus 0%, p less than 0.0001), structural heart disease and a history of clinical sustained ventrical arrhythmias. Similarly, the induced self-terminating ventricular tachycardia differed in Group A and Group B patients. The arrhythmias in Group B patients were more often monomorphic, were more often induced with one or two extrastimuli and had a longer cycle length than those in Group A patients. In Group B patients, the electrophysiologic characteristics of the self-terminating and the sustained induced ventricular tachycardias were similar. Cardioversion was required in 50% of Group B patients compared with 27% of Group C patients (p = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of propafenone in preventing ventricular tachycardia: inverse correlation with rate-related prolongation of conduction time

The efficacy of propafenone in preventing induction of ventricular tachycardia was evaluated in 25 consecutive patients (mean age 62 +/- 8 years) with remote myocardial infarction who underwent programmed electrical stimulation for ventricular arrhythmia using up to three extra-stimuli after basic drive at the right ventricular apex. In nine patients (Group A), propafenone prevented induction of sustained ventricular tachycardia (noninducible in four, nonsustained [less than 30 s] in five). In the other 16 patients (Group B), sustained ventricular tachycardia was still inducible; in 11 of the 16, the tachycardia configuration was unchanged but the cycle length was significantly longer (431 +/- 99 versus 284 +/- 44 ms, p less than 0.001). Propafenone did not significantly affect either sinus cycle length or AH and HV intervals. However, it prolonged QRS duration during sinus rhythm equally in both groups of patients. With ventricular pacing, propafenone also prolonged right ventricular effective and functional refractory periods and surface QRS duration. There was greater lengthening of the paced surface QRS duration when drug therapy was ineffective (for example, +35 +/- 12 ms in Group A versus +69 +/- 23 ms in Group B at a basic drive of 400 ms, p less than 0.01). Drug-induced prolongation of a paced QRS complex greater than 40 ms had a 94% positive predictive value for drug failure to prevent induction of ventricular tachycardia. Drug-induced percent prolongation of ventricular tachycardia cycle length in Group B did not correlate well with percent QRS prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The plasma catecholamine response to ventricular tachycardia induction and external countershock during electrophysiologic testing

Adrenergic activation during electrophysiologic study could potentially alter the electrophysiologic properties of the arrhythmia substrate. However, the catecholamine response to ventricular tachycardia induction and termination during electrophysiologic testing has to date not been quantitated. Therefore, in 13 patients undergoing electrophysiologic study, arterial plasma norepinephrine and epinephrine were measured before, during and 1, 3, 5, 10 and 15 minutes after ventricular tachycardia induced by programmed stimulation and terminated by a single 100 J external countershock. Sinus rate and the effective refractory period at the right ventricular apex at a basic drive cycle length of 400 ms were measured after the countershock at the same time intervals used for the catecholamine measurements. The mean ventricular tachycardia cycle length (+/- SD) was 187 +/- 30 ms, and the mean duration of ventricular tachycardia was 18 +/- 4 seconds. Plasma norepinephrine and epinephrine increased, respectively, from a baseline of 286 +/- 141 and 119 +/- 40 pg/ml to 770 +/- 330 (169%) and 597 +/- 467 pg/ml (402%), (p less than 0.01) at 1 minute after the countershock. The mean plasma norepinephrine and epinephrine levels during ventricular tachycardia and at times greater than 1 minute after the shock did not differ significantly from baseline levels. Sinus rate increased from a baseline of 74 +/- 13 to 103 +/- 26/min (39%) at 1 minute after the shock (p less than 0.05) and then returned to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Signal-averaged electrocardiographic late potentials in patients with ventricular fibrillation or ventricular tachycardia: correlation with clinical arrhythmia and electrophysiologic study

High-frequency potentials measured in the terminal 40 ms of the signal-averaged QRS complex during sinus rhythm are of abnormally low amplitude in most patients with ventricular tachycardia (VT). However, less is known about high-frequency late potentials in patients with ventricular fibrillation (VF), and the relation between late potentials and arrhythmia inducibility during electrophysiologic study has not been established. Signal-averaged electrocardiography was used to measure high-frequency (more than 25 Hz) late potentials in 24 patients with spontaneous VF, 27 patients with spontaneous sustained VT, and 19 normal subjects, none of whom were receiving antiarrhythmic drugs. Late-potential amplitude in patients with VT was significantly lower than that in patients with VF (p less than 0.02). Late-potential amplitude in patients with VF was not significantly different from that in normal subjects. Ventricular arrhythmia induction was attempted during electrophysiologic study in 46 of the patients with VF or VT. Late-potential amplitude was significantly lower in 26 patients with reproducibly inducible sustained ventricular arrhythmias than in 20 without (p less than 0.001). The correlation between late-potential amplitude and arrhythmia inducibility was independent of that between late-potential amplitude and clinical arrhythmia (VT vs VF).     

Drug response at electropharmacologic study in patients with ventricular tachyarrhythmias: the importance of ventricular refractoriness

The clinical and electrophysiologic predictors of successful antiarrhythmic drug therapy for patients with inducible ventricular tachycardia were evaluated in 59 consecutive patients undergoing serial electropharmacologic trials. Structural heart disease was less frequently present in patients for whom effective therapy was found (p less than 0.05). The presence of coronary artery disease and a history of prior myocardial infarction were significantly more frequently present in patients for whom antiarrhythmic drug therapy could not be found (p less than 0.05). The corrected QT interval and ventricular effective refractory period measured at a pacing cycle length of 400 ms were significantly shorter in responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59 ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p less than 0.05). In addition, the interelectrogram coupling interval of the ventricular extrastimulus initiating ventricular tachycardia was significantly shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33 ms; p = 0.003). Logistic regression analysis identified a short ventricular interelectrogram coupling interval (p less than 0.01) and absence of prior myocardial infarction (p less than 0.05) as the only independent predictors of antiarrhythmic drug suppression of the induction of ventricular tachycardia. Greater drug-induced increments in the ventricular effective and functional refractory periods were observed in responders than in nonresponders as was the shortest ventricular interelectrogram coupling interval. Thus, baseline electrophysiologic measurements identify patients with inducible ventricular tachycardia who are likely to respond to antiarrhythmic drug therapy. Furthermore, these patients demonstrate greater drug-induced electrophysiologic changes.     

Electrophysiologic assessment of antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with dilated cardiomyopathy

To determine the benefit of serial electrophysiologic drug testing in patients with ventricular tachyarrhythmias related to dilated cardiomyopathy, programmed ventricular stimulation was performed in 38 patients. In the baseline study, sustained ventricular tachycardia (VT) was induced in 18 patients, ventricular fibrillation in 7 and nonsustained VT in 13. The patients underwent a total of 84 trials of drug therapy (mean 2.3 +/- 1.4 trials/patient). Complete success (induction of fewer than 6 repetitive responses) was recorded in 19 trials and partial success (induction of at least 6 but no more than 15 repetitive responses) in 7. Potential proarrhythmic effects were observed in 9 trials. Overall, at least 1 successful regimen was identified for 20 patients (53%). During a mean follow-up of 21 +/- 13 months, there were no arrhythmia recurrences or episodes of sudden death among patients discharged with a drug regimen determined to be effective by serial drug testing. In comparison, among patients taking regimens that failed to prevent arrhythmia induction, there were 3 arrhythmia recurrences and 2 sudden deaths (p less than 0.05). Serial electrophysiologic drug testing provides an effective method of identifying successful medical therapy for patients with ventricular arrhythmia related to dilated cardiomyopathy.     

Anatomic and electrophysiologic correlates of ventricular tachycardia requiring left ventricular stimulation

In 108 patients with reproducible initiation of ventricular tachycardia by programmed ventricular stimulation, the ventricular tachycardia was initiated only by left ventricular stimulation in 12 (11 percent). Programmed ventricular stimulation included single and double extrastimuli at three cycle lengths and bursts of rapid pacing to cycle lengths of 250 ms. Clinical, electrocardiographic, angiographic, hemodynamic and electrophysiologic data were available in 74 of 96 patients with ventricular tachycardia initiated by right ventricular stimulation (Group A) and in all 12 patients with ventricular tachycardia initiated only by left ventricular stimulation (Group B). There were no significant differences between Groups A and B in clinical characteristics, hemodynamics or presence and site of infarction or aneurysm. Comparison of electrophysiologic variables revealed no significant differences between Groups A and B in mean A-H interval (92 ± 22 versus 89 ± 15 ms, respectively), H-V interval (59 ± 15 versus 59 ± 15 ms) or right ventricular (241 ± 38 versus 260 ± 40 ms) or left ventricular (232 ± 28 versus 251 ± 42 ms) effective refractory period. Ventricular tachycardia with right bundle branch block and superior axis was more prevalent in Group B (92 percent versus 31 percent, p <0.001) but was observed in 32 patients in Group A.It is concluded that 11 percent of patients with clinically documented sustained ventricular tachycardia will require left ventricular programmed stimulation to reproducibly initiate the tachycardia. No clinical, anatomic, electrocardiographic or electrophysiologic features can predict whether left ventricular programmed stimulation will be required. Because initiation of ventricular tachycardia by programmed ventricular stimulation has important prognostic and therapeutic implications in such patients, stimulation should be performed from the left ventricle when the tachycardia is not initiated by stimulation from the right ventricle.     

Late potentials on the signal-averaged electrocardiogram after canine myocardial infarction: correlation with induced ventricular arrhythmias during the healing phase

Signal-averaged electrocardiograms (ECGs) and programmed ventricular stimulation were serially performed in 12 dogs (3 weeks of age) after experimental anteroapical myocardial infarction. At electrophysiologic study, sustained ventricular tachyarrhythmia was induced in seven dogs on at least one occasion. Of a total of 39 electrophysiologic studies, sustained monomorphic ventricular tachycardia was induced in seven studies and ventricular fibrillation in eight studies. In the remaining studies, no ventricular arrhythmia could be induced with triple ventricular extrastimuli. There was considerable day to day variability in the response to programmed stimulation and the results of the signal-averaged ECG. The signal-averaged QRS complex was significantly longer in dogs with inducible ventricular tachycardia or fibrillation (61 +/- 5 versus 57 +/- 3 ms, p = 0.02), had a lower terminal QRS amplitude (24 +/- 20 versus 46 +/- 33 microV, p = 0.04) and a longer late potential duration (19 +/- 4 versus 15 +/- 3 ms, p = 0.003) compared with that in animals with no inducible ventricular arrhythmia. Late potentials were defined as a total QRS duration greater than 58 ms, a terminal QRS amplitude less than 20 microV and a late potential duration greater than 18 ms. Using this definition, late potentials were seen in two distinct phases--immediately after coronary ligation and then beyond the first 72 h after infarction. The appearance of late potentials coincided with a change in arrhythmia inducibility from no ventricular arrhythmia to initiation of sustained monomorphic ventricular tachycardia. There is a close relation between inducibility of ventricular tachycardia in experimental canine myocardial infarction and the appearance of late potentials on the surface ECG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term outcome in patients who survive out of hospital ventricular fibrillation and undergo electrophysiologic studies: evaluation by electrophysiologic subgroups

The long-term outcome of 241 survivors of out of hospital ventricular fibrillation who underwent programmed electrical stimulation was evaluated. Patients were categorized according to the rhythm induced at baseline drug-free electrophysiologic testing. Ventricular fibrillation was induced in 39 patients (16%) (Group 1), sustained ventricular tachycardia in 66 patients (27%) (Group 2) and nonsustained ventricular tachycardia in 34 patients (14%) (Group 3); 102 patients (42%) (Group 4) did not have an arrhythmia inducible at baseline electrophysiologic testing. Antiarrhythmic drugs were administered over the long term to 92% of patients in Group 2, 91% of patients in Group 1 and 47% of patients in Group 4. At a mean follow-up time of 30 +/- 15 months, recurrent sudden cardiac death or nonfatal ventricular fibrillation occurred in 11 (28%) of 39 patients with inducible ventricular fibrillation (Group 1), 14 (21%) of 66 patients with inducible sustained ventricular tachycardia (Group 2), 4 (12%) of 34 patients with inducible nonsustained ventricular tachycardia (Group 3) and 16 (16%) of 102 patients without inducible arrhythmias (Group 4). Actuarial analysis revealed a 2 year cumulative arrhythmia-free survival rate of 65% for patients in Group 2, 71% for patients in Group 1, 79% for patients in Group 3 and 81% for patients in Group 4 (p = 0.02). Actuarial survival of patients with inducible sustained ventricular tachycardia or ventricular fibrillation suppressed by electrophysiologically guided drug therapy was not significantly different from that in patients whose arrhythmia was not suppressed. Multivariate regression analysis revealed that only the presence of congestive heart failure was an independent predictor of outcome in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Programmed ventricular stimulation in patients with left ventricular dysfunction and ventricular tachycardia: effects of acute hemodynamic improvement due to nitroprusside

To assess the electrophysiologic effects of acute hemodynamic improvement in patients with left ventricular systolic dysfunction, 12 patients with a left ventricular ejection fraction less than 0.40 and a history of sustained monomorphic ventricular tachycardia were studied. All patients had underlying coronary artery disease. Patients underwent programmed cardiac stimulation in random order during a baseline period and with nitroprusside infusion. Mean pulmonary capillary wedge pressure decreased from 20 +/- 8 mm Hg at baseline study to 8 +/- 3 mm Hg during nitroprusside infusion (p less than 0.0001). Pulmonary artery, right atrial and systemic arterial pressures also decreased with nitroprusside (p less than 0.01). Cardiac output did not change. Left ventricular dimensions, determined by two-dimensional echocardiography, decreased significantly during nitroprusside infusion. The right ventricular effective refractory period, measured during ventricular drive trains at cycle lengths of 400 and 600 ms, were similar during baseline and nitroprusside periods (271 +/- 30 versus 274 +/- 31 ms at 600 ms, and 249 +/- 25 versus 246 +/- 18 ms at 400 ms). In 2 patients no ventricular arrhythmias were induced during either study period; in the other 10, ventricular tachyarrhythmias were induced during both periods. The mean number of extrastimuli required to induce a ventricular tachyarrhythmia was similar during the baseline period (1.8 +/- 0.6) and during nitroprusside infusion (1.9 +/- 0.7). As well, the mean cycle length of ventricular tachycardia induced was similar during the baseline period (347 +/- 61 ms) and during nitroprusside infusion (342 +/- 70 ms).(ABSTRACT TRUNCATED AT 250 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)     

Influence of infarct age on reproducibility of ventricular tachycardia induction in a canine model

The inducibility and reproducibility of ventricular tachycardia were evaluated in 97 dogs after myocardial infarction produced by single stage coronary artery ligation. Arrhythmia induction was performed with use of an endocardial electrode catheter positioned at the right ventricular apex before each study. An aggressive protocol of programmed stimulation was used, employing up to seven extrastimuli and three attempts at arrhythmia induction in each study. Electrophysiologic study was performed in individual dogs at the following times after infarction: 1) 7.7 +/- 0.3 and 15 +/- 0.2 days (34 consecutive dogs); 2) 14 +/- 0.6 and 26 +/- 1.7 days (24 selected dogs); 19 +/- 2 and 43 +/- 3 days (12 selected dogs); 4) 36 +/- 2 and 60 +/- 6 days (8 selected dogs); and 5) 59 +/- 12 and 130 +/- 10 days (3 selected dogs). Inducibility of ventricular tachycardia decreased significantly from 74% 1 week after infarction to 41% 2 weeks after infarction. Thus, early reproducibility was low (48%). Reproducibility increased thereafter, with 88% of the dogs having reproducible ventricular tachycardia between 2 and 4 weeks (p less than 0.025) and 100% having reproducibly inducible ventricular tachycardia between 4 weeks and 4 months after infarction. Dogs with no inducible arrhythmia early after infarction did not develop inducible ventricular tachycardia or fibrillation at later studies. Twelve dogs developed spontaneous ventricular tachycardia or sudden arrhythmic death late after infarction. Overall, 22% of dogs with inducible ventricular tachycardia with a cycle length greater than 140 ms developed spontaneous ventricular tachycardia or sudden death. Arrhythmia induction decreases significantly during the 1st 2 weeks after myocardial infarction, but long-term reproducibility of ventricular tachycardia induced greater than or equal to 2 weeks after infarction is very high. This canine model of long-term, reliably inducible ventricular tachycardia is suitable for investigation of antiarrhythmic drugs, surgery and other interventions.     

Prognostic significance of the number of induced ventricular complexes during assessment of therapy for ventricular tachyarrhythmias

We analyzed 255 long-term trials of antiarrhythmic therapy, each of which had been evaluated at electrophysiologic study, to identify the maximum number of induced ventricular complexes consistent with the long-term efficacy of antiarrhythmic therapy. All patients had spontaneous and inducible sustained ventricular tachycardia or ventricular fibrillation. The incidence of therapeutic efficacy at 1 month and throughout follow-up was similar for trials in which zero, one, two, three, four, five, six to 10, and 11 to 15 complexes were induced, but significantly lower (p less than .001) for trials in which 16 or more complexes were induced. The cumulative incidence of efficacy at 1 year was 75 +/- 5% for 0 to 5 induced complexes, 72 +/- 11% for six to 10 complexes, 83 +/- 15% for 11 to 15 complexes, 42 +/- 10% for 16 complexes to 15 sec, and 48 +/- 6% for sustained ventricular tachycardia. At 1 year, the incidence of "sudden death-free" survival was higher for patients in trials that prevented initiation of sustained ventricular tachycardia than for those in trials that permitted initiation of sustained ventricular tachycardia (91 +/- 3% vs 75 +/- 6%; p = .01). The duration of the arrhythmia induced at therapy assessment was in the range of 11 to 20 complexes for only 4% of trials. Antiarrhythmic therapy is likely to be effective if as many as 15 complexes are induced at therapy assessment. The best cutoff, between 11 and 20 complexes, is difficult to identify because of the small fraction of trials in this range. Patients in whom initiation of sustained ventricular tachycardia is not prevented are at high risk for arrhythmia recurrence and sudden death.     

Determinants of prognosis in ventricular tachyarrhythmia patients without induced sustained arrhythmias

We studied 59 patients with sustained ventricular tachycardia (VT) or ventricular fibrillation in whom programmed stimulation induced 15 or fewer repetitive ventricular complexes. During follow-up of 2.2 +/- 1.5 years, 13 patients had an arrhythmia recurrence and seven died suddenly. At 1, 2, and 3 years, the actuarial incidence of arrhythmia recurrence was 15 +/- 5%, 17 +/- 5%, and 23 +/- 6%, and that of sudden death was 6 +/- 4%, 15 +/- 6%, and 21 +/- 8%. Prior myocardial infarction (MI) was the only independent predictor of arrhythmia recurrence (p less than 0.02) and sudden death (p = 0.05): at 2 years, 36 +/- 12% of 18 patients with MI and 8 +/- 4% of 41 patients without MI had arrhythmia recurrence, and 24 +/- 12% with MI and 3 +/- 3% without MI died suddenly. None of the nine patients with greater than or equal to 70% coronary stenosis but no MI had arrhythmia recurrence after anti-ischemic therapy. Possible arrhythmia-precipitating conditions were present during all arrhythmias in 14 patients, but did not predict freedom from arrhythmia recurrence (p = 0.52) or sudden death (p = 0.81). The maximum number of induced ventricular complexes did not predict arrhythmia recurrence or sudden death: for patients with 0 to 2, 3 to 5, and 6 to 15 induced complexes, the 2-year incidence of arrhythmia recurrence was 16 +/- 7%, 15 +/- 10%, and 18 +/- 10%; for sudden death, it was 9 +/- 6%, 0 +/- 0%, and 14 +/- 9%. In this group of patients, prior MI predicted arrhythmia recurrence and sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Increased vagal cardiac nerve traffic prolongs ventricular refractoriness in patients undergoing electrophysiology testing

Stimulation of the vagus nerve in animals causes prolongation of sinus cycle length, atrioventricular nodal conduction and ventricular refractoriness. Vagal stimulation appears to have a protective effect in animal models of sudden death. The electrophysiologic effects of enhanced vagal activity on right ventricular (RV) refractoriness in man have not been studied previously. The comparative effects of enhanced vagal tone (neck suction to -60 mm Hg) on sinus cycle length and RV refractoriness were assessed in 26 patients. The electrophysiologic effects of vagal activation by stimulation of carotid baroreceptors with neck suction were compared to the effect of carotid and aortic baroreceptor stimulation with phenylephrine infusion in 12 patients. During neck suction, mean sinus cycle length (819 +/- 32 ms) was prolonged by 146 +/- 20 ms (p less than 0.0001). The mean RV effective refractory period (ERP) and functional refractory period (FRP) were prolonged by 4 +/- 1 ms and 5 +/- 1 ms (p = 0.0001 and 0.0002, respectively). The mean change in RV ERP and FRP correlated with the peak change in sinus cycle length during neck suction (r = 0.46 and r = 0.58, respectively). During intravenous phenylephrine infusion, the mean change in RV ERP and FRP was 5 +/- 2 ms (p less than 0.04) and 10 +/- 3 ms (p less than 0.01), respectively. These results show that reflex vagal stimulation with neck suction or phenylephrine infusion causes a small but significant prolongation in RV refractoriness. These findings imply that the potential benefits of enhanced vagal tone in preventing sudden death may be indirectly mediated by changes in ventricular refractoriness.     

Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia

The combination of mexiletine and a class IC antiarrhythmic agent (encainide, propafenone or flecainide) was evaluated by electrophysiologic testing in 14 patients with a history of sustained ventricular tachycardia whose tachycardia remained inducible during therapy with the class IC drug alone. During the control drug-free state, all patients had inducible ventricular tachycardia, with a mean cycle length of 260 ms (range 190 to 400). During monotherapy with the IC agent the tachycardia remained inducible in each patient, but there was a significant increase in the cycle length to 340 ms (240 to 500) (p less than 0.001). The effective refractory period of the ventricle was not altered. Treatment with mexiletine (oral in 13 and intravenous in 1) was begun and electrophysiologic testing was repeated. Ventricular tachycardia in one patient was rendered noninducible and one patient had arrhythmia aggravation. The tachycardia in the remaining 12 patients remained inducible but its average cycle length increased further to 392 ms (340 to 460) (p = NS). Nine patients had rate slowing and the average cycle length of the ventricular tachycardia in this group was significantly increased (302 to 388 ms, p less than 0.05). The average effective refractory period was significantly increased during combination therapy (267 ms) compared with no drug therapy (235 ms) and therapy with the class IC drug alone (247 ms) (p less than 0.05). After a mean follow-up interval of 22 months, seven patients continue on the combined treatment and have no ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution

The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo-treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy.     

Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state.

Abnormal dispersion of repolarization may contribute to the arrhythmogenic physiologic substrate of ventricular arrhythmia. Geographic dispersion of monophasic action potential duration was determined in steady state (drive cycle lengths 600 and 430 ms) between widely spaced right ventricular endocardial sites (geographic dispersion) in 10 control patients with right ventricular disease and complicating ventricular tachycardia (n = 9), 6 patients with right and left ventricular disease and complicating ventricular tachycardia and 7 patients with ischemic heart disease and complicating ventricular tachycardia. No significant difference in geographic dispersion could be demonstrated among the groups. Difference of monophasic action potential duration at adjacent right ventricular endocardial sites (adjacent dispersion) was determined after ventricular extrastimulation during construction of simultaneous electrical restitution curves in the same patient groups. Maximal adjacent dispersion over the electrical restitution curve was compared between disease and control groups. There was a significant difference in observations of maximal adjacent dispersion in patients with right ventricular disease and complicating ventricular tachycardia (range 5 to 85 ms, median 22.5; 14 pairs of sites; p less than 0.05) and patients with right and left ventricular disease and complicating ventricular tachycardia (range 5 to 50 ms, median 17.5; 14 pairs of sites; p less than 0.05) compared with control patients (range 5 to 20 ms, median 10; 15 pairs of sites). This difference was not evident when patients with ischemic heart disease and complicating ventricular tachycardia (range 5 to 25 ms, median 12.5; 12 pairs of sites) were compared with control patients. Maximal percent monophasic action potential shortening from steady state was significantly greater (p less than 0.001) in both groups with greater adjacent dispersions, and prolongation of activation time at monophasic action potential recording sites after premature extrastimulation tended to be greater in patients with right or right and left ventricular disease and complicating ventricular tachycardia. It is concluded that in disease, exaggeration of monophasic action potential shortening after premature ventricular extrastimulation may contribute to the electrophysiologic arrhythmogenic substrate.     

Induction of sustained ventricular tachycardia after surgical repair of tetralogy of Fallot

Between 1980 and 1996, 89 unselected consecutive patients with repaired tetralogy of Fallot (TOF) underwent examination, including a prospective right ventricular programmed stimulation with the same protocol (S1 S2, S3, S4). Age at surgery was 4.2 +/- 3.5 years and age at electrophysiologic study was 10.9 +/- 6.5 years. Follow-up since surgery was 14.4 +/- 4.8 years and patient follow-up after programmed stimulation was 7.8 +/- 4.2 years. The aim of this study was to evaluate the main predictors of the inducibility of a sustained monomorphic ventricular tachycardia (VT) and its significance to identify a group of patients at risk of sudden death: 21 (group A) had and 68 (group B) had no induced sustained VT. The induction of VT was related to older age at programmed stimulation, prolonged QRS duration, presence of complex ventricular arrhythmia, symptoms, right ventricular overload, and increased right ventricular systolic pressure. Predictors of induced VT selected by multivariate analysis were age at electrophysiologic study (p <0.0001), previous palliative shunts (p <0.001), right ventricular systolic pressure (p <0.007), and symptoms (p <0.005). Among group A patients, 4 had previous sustained VT before stimulation, and 1 had sustained VT only during follow-up after stimulation. No patients of group B had clinical sustained VT. Late mortality was low but similar between both groups. A negative electrophysiologic study may be helpful for the management of patients after surgical repair of TOF, but because the arrhythmic event rate is low, the findings of even a positive electrophysiologic study should be interpreted with caution.