Cycle length dependence of human action potential duration in vivo. Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies.

Using a new method for long-term recording of monophasic action potentials from the human heart, we studied in 17 patients the effects on ventricular action potential duration (APD) of three clinically pertinent cycle length perturbations: (1) single extrastimuli, (2) abrupt sustained rate acceleration and deceleration, and (3) different steady-state cycle lengths. Results were: (a) APD after single extrastimuli at progressively longer cycle lengths were related to the extrastimulus cycle length with a biphasic electrical restitution curve which after an initial steep rise and a subsequent transient descent rose again more gradually to a plateau at cycle lengths above 800-1,000 ms. (b) After a sustained step decrease in cycle length, the first APD shortened abruptly while final steady-state adaptation required up to several minutes. The transition between the rapid and slow phase of APD change was characterized by a variable alternans of APD which correlated inversely with the preceding diastolic interval. (c) In the steady state, APD correlated linearly with cycle length, increasing an average of 23 ms per 100 ms cycle length increase (r = 0.995). The divergence between steady-state and non-steady-state APD, and the slowness of steady-state adaptation, are important factors to be considered in clinical electrophysiologic studies and in rate correction algorithms of APD or QT intervals, respectively.

Implantation of cardioverter defibrillators without induction of ventricular fibrillation.

BACKGROUND: The upper limit of vulnerability (ULV) is the weakest shock at which ventricular fibrillation (VF) is not induced by a T-wave shock. This study tested the hypothesis that a vulnerability safety margin based on the ULV can be used as an implantable cardioverter-defibrillator implantation criterion. METHODS AND RESULTS: Implantable cardioverter-defibrillators were implanted in 80 patients if T-wave shocks did not induce VF and the baseline-rhythm R wave was >/=7 mV. The T-wave shock was 10 J in the first 45 patients (group A) and 15 J in the last 35 patients (group B). After inductionless implantations, the first VF shock was programmed to the T-wave shock plus 5 J. If T-wave shocks induced VF, the ULV was measured and the first shock was programmed to the ULV+5 J. Inductionless implantations were performed in 58 patients (72%), 28 in group A (62%) and 30 in group B (86%; P=0.04). If T-wave scanning had been done at 15 J in group A patients, inductionless implantations could have been performed in 84% of them. At 3 months, VF was induced twice during electrophysiological study in 75 patients (94%). All VFs were detected in 80% of implantable cardioverter-defibrillator recipients using a vulnerability safety margin based on a T-wave scan at 15.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

BACKGROUND: To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. METHODS AND RESULTS: We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. CONCLUSIONS: A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Mechanisms of ventricular fibrillation induction by 60-Hz alternating current in isolated swine right ventricle.

BACKGROUND: The mechanisms by which 60-Hz alternating current (AC) can induce ventricular fibrillation (VF) are unknown. METHODS AND RESULTS: We studied 7 isolated perfused swine right ventricles in vitro. The action potential duration restitution curve was determined. Optical mapping techniques were used to determine the patterns of activation on the epicardium during 5-second 60-Hz AC stimulation (10 to 999 microA). AC captured the right ventricles at 100+/-65 microA, which is significantly lower than the direct current pacing threshold (0.77+/-0.45 mA, P:<0.05). AC induced ventricular tachycardia or VF at 477+/-266 microA, when the stimulated responses to AC had (1) short activation CLs (128+/-14 ms), (2) short diastolic intervals (16+/-9 ms), and (3) short diastolic intervals associated with a steep action potential duration restitution curve. Optical mapping studies showed that during rapid ventricular stimulation by AC, a wave front might encounter the refractory tail of an earlier wave front, resulting in the formation of a wave break and VF. Computer simulations reproduced these results. CONCLUSIONS: AC at strengths less than the regular pacing threshold can capture the ventricle at fast rates. Accidental AC leak to the ventricles could precipitate VF and sudden death if AC results in a fast ventricular rate coupled with a steep restitution curve and a nonuniform recovery of excitability of the myocardium.

Clinical predictors of arrhythmia inducibility in survivors of cardiac arrest: importance of gender and prior myocardial infarction.

Clinical characteristics that correlate with arrhythmia inducibility were determined in 150 consecutive survivors of cardiac arrest. All underwent electrophysiologic study with a uniform protocol when they were not receiving antiarrhythmic drugs. A ventricular tachyarrhythmia (sustained monomorphic ventricular tachycardia, ventricular fibrillation or nonsustained ventricular tachycardia) was induced in 113 patients (75%). The strongest correlates of inducing a tachyarrhythmia were male gender (p less than 0.0001) and a history of prior myocardial infarction (p less than 0.0001). Induction of sustained monomorphic tachycardia alone was also strongly related to gender and prior infarction; in particular, none of 26 women without prior infarction had induction of sustained monomorphic ventricular tachycardia. Among patients with induced sustained tachyarrhythmias, those with induced monomorphic ventricular tachycardia were distinguished from those with induced ventricular fibrillation in they were more likely to have coronary artery disease (p = 0.0001), healed myocardial infarction (p = 0.0002), left ventricular aneurysm (p = 0.0007) and ventricular tachycardia documented at the time of cardiac arrest (p = 0.02). Other variables showing significant correlations with arrhythmia inducibility were ejection fraction, documentation of ventricular tachycardia at the time of cardiac arrest and presence of an intraventricular conduction delay. However, stepwise logistic regression identified male gender and healed myocardial infarction as the only independent predictors of arrhythmia inducibility. On the basis of these two variables alone, arrhythmia inducibility or noninducibility could be correctly predicted in 89% of the patients in this series.

Long-term follow-up after surgical correction of Wolff-Parkinson-White syndrome.

The long-term efficacy of surgical correction of Wolff-Parkinson-White syndrome was evaluated in 45 consecutive patients. Before surgery, 42 patients had reciprocating tachycardia and 12 had atrial fibrillation. The principal operative procedure was endocardial incision in 42 patients, endocardial cryoablation in 2 patients and epicardial cryoablation without dissection of the atrioventricular (AV) fat pad in 1 patient. Two patients had perioperative complications. One patient had bleeding that necessitated reoperation, and one had a right cerebral stroke with subsequent clearing of neurologic deficit. At postoperative electrophysiologic study, only the patient who underwent epicardial cryoablation had conduction over an accessory connection. Two others had intermittent delta waves in the early postoperative period but no accessory connection conduction at electrophysiologic study. During a mean follow-up of 3.1 years, the patient with ineffective cryoablation had recurrent orthodromic tachycardia, and one other patient had late recurrence of delta waves without arrhythmias. Four other patients had frequent palpitation, which was caused by premature ventricular complexes in three and sinus tachycardia in one. Seventeen patients had occasional "skipped beats" without recurrence of tachyarrhythmias. Twelve of 13 patients whose arrhythmias limited employment before surgery returned to work after surgery. By actuarial analysis at 1, 2 and 3 years, all patients were alive and 98% were free from tachyarrhythmias. Surgical correction of Wolff-Parkinson-White syndrome provides excellent long-term results with low morbidity. Patients who are disabled by arrhythmias return to work after successful surgery. Delta waves may persist or recur without return of arrhythmias. Minor postoperative episodes of palpitation are common and do not correlate with tachyarrhythmias.

Tocainide for drug-resistant sustained ventricular tachyarrhythmias.

Eighty-two patients with drug-resistant ventricular tachycardia or fibrillation were treated with oral tocainide. Treatment in 54 patients, all with inducible ventricular tachycardia or fibrillation at baseline electrophysiologic testing, was based on the results of invasive electrophysiologic testing. Twenty-eight additional patients with frequent spontaneous ventricular tachycardia or no inducible arrhythmia during electrophysiologic testing were treated on the basis of the findings of electrocardiographic (ECG) Holter monitoring. Tocainide was effective in 7 (13%) and partially effective in 5 (8%) of the 54 patients in the electrophysiologic study group and was effective in 17 (61%) of the 28 patients in the ECG monitoring group. History of previous myocardial infarction and failure of response to lidocaine correlated with failure to respond to tocainide. Side effects were common both during initial therapy and during long-term treatment and necessitated discontinuation of tocainide therapy in 17% of the patients. At a mean follow-up period of 14 months, 13 patients are still receiving tocainide and are arrhythmia-free. In conclusion, the usefulness of oral tocainide in the management of drug-refractory sustained ventricular tachycardia or fibrillation is limited because of its low effectiveness and frequent side effects.

Discrimination of ventricular tachycardia from sinus tachycardia and atrial fibrillation in a tiered-therapy cardioverter-defibrillator.

OBJECTIVES: This study was conducted to evaluate criteria for discrimination of ventricular tachycardia from atrial fibrillation and sinus tachycardia in a tiered-therapy cardioverter-defibrillator (Medtronic PCD). BACKGROUND: Interval stability algorithms discriminate ventricular tachycardia from atrial fibrillation. Onset algorithms discriminate ventricular tachycardia from sinus tachycardia. Neither has been validated clinically. METHODS: The stability criterion requires that a ventricular tachycardia interval not vary from any of the three previous intervals by more than the programmable stability value. The onset criterion detects initiation of ventricular tachycardia only if the ratio of an interval to the mean of four previous intervals is less than a programmed onset ratio and either the second or third preceding interval exceeds the ventricular tachycardia detection interval. We evaluated these criteria in 100 patients at electrophysiologic study and exercise testing (65 patients) and during a mean (+/- SD) follow-up of 16.2 +/- 7.9 months. The PCDs were programmed to tiered therapy in 54 patients. In the remaining 46 patients, the PCD's memory for detected ventricular tachycardia was used to study the specificity of the chosen onset criterion for rejecting sinus tachycardia. We used stored intervals preceding appropriate (n = 99) and inappropriate (n = 54) detections to test a new onset criterion that was less sensitive to a single index interval. RESULTS: Programmed stability of 40 ms decreased detection of induced atrial fibrillation by 95% (20 patients), paroxysmal atrial fibrillation by 95% (6 patients) and chronic atrial fibrillation by 99% (9 patients); all episodes of spontaneous (n = 877) and induced (n = 339) ventricular tachycardia were detected. A programmed onset ratio of 87% rejected sinus acceleration (98%) but caused underdetection of 0.5% of ventricular tachycardias. The onset criterion permitted inappropriate detection of premature ventricular complexes during sinus tachycardia, but the new criterion reduced these inappropriate detections by 98%. CONCLUSIONS: The PCD's onset and stability criteria reduced inappropriate detection of atrial fibrillation and sinus acceleration while detecting 99.5% of ventricular tachycardias.

Upper limit of vulnerability is a good estimator of shock strength associated with 90% probability of successful defibrillation in humans with transvenous implantable cardioverter-defibrillators.

OBJECTIVES: The goals of this study were to determine the probability of successful defibrillation at the upper limit of vulnerability and to evaluate a minimal safety margin for implantable cardioverter-defibrillator first shocks based solely on the upper limit of vulnerability. BACKGROUND: The upper limit of vulnerability is the strength at or above which ventricular fibrillation is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It has been proposed as an estimate of defibrillation efficacy because it correlates with the defibrillation threshold and can be determined with a single episode of fibrillation. METHODS: We studied 40 patients prospectively at implantation of transvenous cardioverter-defibrillators. Defibrillation threshold was defined as the weakest biphasic shock that defibrillated after 10 s of ventricular fibrillation. The upper limit of vulnerability was defined as the weakest biphasic shock that did not induce ventricular fibrillation when given at 0, 20 and 40 ms before the peak of the T wave in ventricular paced rhythm at cycle length 500 ms. After determination of the upper limit of vulnerability and defibrillation threshold, patients underwent six additional fibrillation-defibrillation episodes. The strength of five of the defibrillation shocks was equal to the upper limit of vulnerability; the strength of one of the six shocks was randomly selected to be equal to the upper limit of vulnerability plus 3 J. The implantable cardioverter-defibrillator was tested at the upper limit of vulnerability plus 3 J in 28 patients. RESULTS: The defibrillation threshold was 8.8 +/- 5.0 J (mean +/- SD), and upper limit of vulnerability was 11.3 +/- 4.6 J; the defibrillation threshold and upper limit of vulnerability were highly correlated (r = 0.89, p < 0.001). The success rate for the 200 defibrillation shocks with strength equal to the upper limit of vulnerability was 90% (95% confidence intervals based on proportion of successes in 40 patients: 86% to 94%). All five defibrillation test shocks at the upper limit of vulnerability were successful in 24 patients (60%); four of five were successful in 12 patients (30%); and three of five were successful in 4 patients (10%). All 40 test shocks and 28 implantable cardioverter-defibrillator shocks with a strength equal to the upper limit of vulnerability plus 3 J were successful. CONCLUSIONS: The upper limit of vulnerability is a good estimator of the shock strength associated with 90% probability of successful defibrillation (DFT90). A strength of 3 J above the upper limit of vulnerability is a good estimate of the minimal acute safety margin for implantable cardioverter-defibrillator first shocks.

Atypical atrioventricular node reciprocating tachycardia masquerading as tachycardia using a left-sided accessory pathway.

OBJECTIVES: The study was performed to document that atrioventricular node reciprocating tachycardia (AVNRT) can be associated with eccentric retrograde left-sided activation, masquerading as tachycardia using a left accessory pathway. BACKGROUND: The eccentric retrograde left-sided activation during tachycardia is thought to be diagnostic of the presence of a left free wall accessory pathway. However, it is not known whether AVNRT can occur with eccentric retrograde left-sided activation. METHODS: We studied 356 patients with AVNRT who underwent catheter ablation. Retrograde atrial activation during tachycardia and ventricular pacing were determined by intracardiac recordings, including the use of a decapolar coronary sinus catheter. RESULTS: The retrograde atrial activation was eccentric in 20 patients (6%). Eight of these patients had the earliest retrograde atrial activation recorded in the lateral coronary sinus leads, and 12 had the earliest retrograde atrial activation recorded in the posterior coronary sinus leads, with the most proximal coronary sinus electrode pair straddling the coronary sinus orifice. These tachycardias were either the fast-slow or the slow-slow form of AVNRT. The slow-fast form of AVNRT was also inducible in 17 of the 20 patients. Successful ablation of the slow pathway in the right atrial septum near the coronary sinus ostium prevented the induction and clinical recurrence of reciprocating tachycardia in all patients. CONCLUSIONS: Atypical AVNRT with eccentric retrograde left-sided activation was demonstrated in 6% of all patients with AVNRT masquerading as tachycardia using a left-sided accessory pathway. Ablation of the slow pathway at the posterior aspects of the right atrial septum resulted in a cure in these patients.

Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator.

OBJECTIVES: The goal of this study was to determine the incidence and clinical significance of underdetection in 125 patients treated with a tiered-therapy cardioverter-defibrillator, the Medtronic PCD. BACKGROUND: Underdetection, distinct from undersensing, is a unique, potential complication of new algorithms that enhance specificity in tiered-therapy cardioverter-defibrillators. These algorithms may delay or prevent recognition of ventricular tachycardia even though electrograms are sensed accurately and RR intervals meet the programmed interval criterion. METHODS: Underdetection was defined as delay in detection > 5 s at electrophysiologic study or symptomatic delay or detection failure at follow-up of 15 +/- 8 months. RESULTS: We identified six specific mechanisms of underdetection caused by algorithms to discriminate sustained ventricular tachycardia from sinus tachycardia, atrial fibrillation, ventricular fibrillation and nonsustained ventricular tachycardia. Underdetection caused detection delays in 13 (1.9%) of 677 induced ventricular tachyarrhythmia episodes in 12 patients (9.6%). During follow-up, underdetection occurred in 7 (9.9%) of 71 patients in whom ventricular tachycardia therapies were programmed. Failure to detect ventricular tachycardia occurred in 6 (0.6%) of 988 spontaneous ventricular tachycardia episodes in four patients (5.6%); 2 episodes required external cardioversion. After defibrillator reprogramming, underdetection did not occur. CONCLUSIONS: Algorithms to enhance specificity cause underdetection of ventricular tachycardia in a significant minority of patients with tiered-therapy cardioverter-defibrillators. Optimal programming can minimize underdetection.

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)

Clinical factors predicting successful electrophysiologic-pharmacologic study in patients with ventricular tachycardia.

Data from 142 patients who had sustained ventricular tachycardia or ventricular fibrillation were analyzed to determine if clinical variables predict response to antiarrhythmic drugs at electrophysiologic study. Effective antiarrhythmic drugs were identified for 43 patients (30%). Ten of 25 variables analyzed were univariate predictors of drug response at the probability (p) level of less than 0.05. Stepwise logistic regression identified three variables independently predictive of drug response: fewer coronary arteries with 70% or greater stenosis (p less than 0.001), female sex (p less than 0.002) and fewer episodes of arrhythmia (p less than 0.03). A function incorporating these three variables was constructed to predict the probability of drug response, and ranges of the predictor function corresponding to high, intermediate and low probabilities of drug response were identified. Response rates in the high (greater than 50%), intermediate and low (less than 10%) probability ranges were 28 (58%) of 48, 10 (27%) of 37 and 5 (9%) of 57, respectively. Thus 40% of the patients who had a less than 10% likelihood of benefit from electrophysiologic-pharmacologic study were classified into the low probability range. When the predictor function was applied prospectively to 25 additional patients, response rates in the three probability ranges were 3 (50%) of 6, 1 (12%) of 8 and 0 (0%) of 11. These data show that analysis of clinical variables can be used to estimate the probability of benefit from electrophysiologic-pharmacologic study.

Safety and efficacy of intravenous quinidine.

The safety and efficacy of intravenous quinidine were evaluated in a patient population with a high prevalence of left ventricular dysfunction and intraventricular conduction delays. Quinidine gluconate (mean dose 9.1 +/- 1.6 mg/kg) was administered during electrophysiologic study to 100 patients with ventricular or supraventricular tachyarrhythmias. Clinical heart failure was present in 68 percent of the patients. Left ventricular end-diastolic pressure, cardiac index, and left ventricular ejection fraction were abnormal in 62, 48, and 70 percent, respectively. Major intraventricular conduction delays (QRS of 120 msec or more) were present in 27 percent, and the H-V interval was prolonged (over 55 msec) in 28 percent. Despite the prevalence of these abnormalities, quinidine was discontinued because of hypotension in only 10 patients. Saline solution was infused to maintain preload in 37 percent, and hypotension responded promptly to saline solution infusion or discontinuation of quinidine infusion in all subjects. Hypotension was not more common in patients with more severe left ventricular dysfunction. QRS duration, H-V interval, QTc, and right ventricular effective refractory period increased significantly (p less than 0.001) after quinidine administration. Heart block or QRS widening of 50 percent or more did not occur. Quinidine prevented arrhythmia induction in 26 percent of patients who received full doses. Ventricular tachycardia cycle length increased in all 41 patients in whom identical forms were induced before and after quinidine (287 +/- 71 msec versus 361 +/- 93 msec, p less than 0.001). Intravenous quinidine may be administered safely to patients with intraventricular conduction delays and moderate heart failure. When antiarrhythmic efficacy is assessed by electrophysiologic study, quinidine compares favorably with other antiarrhythmic agents.

Value of electropharmacologic testing in idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias.

Electrophysiologic studies in 64 patients with idiopathic dilated cardiomyopathy who had sustained ventricular tachycardia or ventricular fibrillation were performed. A sustained ventricular tachyarrhythmia was induced in 43 patients (67%). Electropharmacologic testing predicted an antiarrhythmic drug effective in 15 of 35 patients in whom sustained monomorphic ventricular tachycardia could be induced reproducibly (43% of tested patients, 23% of all patients). During median follow-up of 1.6 years, there were 32 arrhythmia recurrences and 24 cardiac arrests. Multivariate regression analysis identified treatment with a drug predicted to be effective at electropharmacologic testing as the only predictor of freedom from arrhythmia recurrence (p = 0.01); and treatment with a drug predicted to be effective at electropharmacologic testing and lower New York Heart Association functional class as independent predictors of freedom from cardiac arrest (p = 0.03 and p = 0.02, respectively). At median follow-up, the incidences of freedom from arrhythmia recurrence and from cardiac arrest were both 100% during treatment with a drug predicted to be effective at electropharmacologic testing versus 54 +/- 8% and 62 +/- 7%, respectively, during other treatments. These findings indicate that results of electropharmacologic testing accurately predict freedom from arrhythmia recurrence and cardiac arrest in patients with idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias.

Prospective comparison of Holter monitoring and electrophysiologic study in patients with coronary artery disease and sustained ventricular tachyarrhythmias.

Baseline 24-hour Holter monitoring (HM) and electrophysiologic study (EPS) were compared in 43 consecutive patients with coronary artery disease who had sustained ventricular tachyarrhythmias to determine the fraction of patients in whom each could be performed and the fraction in whom each could be used to guide therapy. Patients were excluded from HM if sustained ventricular tachycardia (VT) requiring termination occurred and from EPS if heart failure was sufficiently severe to cause excessive risk. More patients completed EPS than HM (90% vs 71%), but this difference was not statistically significant (p = 0.12). Overall, HM detected arrhythmias suitable for antiarrhythmic drug assessment in 50% of patients: 30 or more ventricular premature complexes (VPCs) per hour in 50%, 10 or more VPC pairs in 44%, 5 or more runs in 19%, and 10 or more pairs and runs in 44%. Sustained monomorphic VT suitable for electropharmacologic testing was induced at EPS in 82% (p = 0.003 vs HM). Drug efficacy could be assessed in 70% of patients evaluated by HM, compared with 96% evaluated by EPS (p = 0.02). Thus, in consecutive coronary patients with sustained ventricular tachyarrhythmias, EPS could be used to guide therapy more frequently than HM.

Effect of flestolol on ventricular rate during atrial fibrillation in Wolff-Parkinson-White syndrome.

The ultrashort-acting beta blocker flestolol was studied during atrial pacing and atrial fibrillation (AF) in 10 patients with Wolff-Parkinson-White syndrome. Flestolol was given as a 100-micrograms/kg bolus followed by a 10-micrograms/kg/min infusion for 15 minutes. The drug did not alter the antegrade effective refractory period of the accessory pathway or the atrial paced cycle length at which block occurred in the accessory pathway. After flestolol, the percent of preexcited QRS complexes during AF increased (60 +/- 10 vs 87 +/- 5%, p = 0.01). Despite this, the ventricular rate slowed, with increases in mean RR interval (382 +/- 20 vs 416 +/- 22 ms, p = 0.02) and in the shortest interval between preexcited QRS complexes (251 +/- 18 vs 270 +/- 17 ms, p less than 0.01). The effect of isoproterenol 3 to 5 micrograms/min was studied in 5 patients. During atrial pacing, isoproterenol decreased the antegrade refractory period and the atrial paced cycle length of block in the accessory pathway (p less than or equal to 0.05). During AF, it decreased the percent of preexcited QRS complexes, mean RR interval and shortest interval between preexcited QRS complexes (p less than 0.05). Flestolol reversed the effects of isoproterenol both during atrial pacing and AF. Thus, flestolol does not alter conduction over the accessory pathway during atrial pacing, but during AF it slows conduction over the accessory pathway and prevents isoproterenol-mediated increases in ventricular rate. This suggests that in patients with Wolff-Parkinson-White syndrome sympathetic stimulation after the onset of AF enhances conduction over the accessory pathway and is an important determinant of ventricular rate.

Strength-interval relation for ventricular functional refractoriness.

Successful initiation and termination of presumed reentrant ventricular tachycardia frequently depends on the ability to deliver closely coupled impulses to the region of the tachycardia origin. To evaluate systematically the relative influence of local latency and large-scale conduction delay in limiting the delivery of closely coupled impulses, the strength-interval relation of the effective refractory period (RP), and the local and remote functional RP in 35 patients at paced cycle length of 500 ms were measured. The pacing threshold was less than or equal to 0.25 mA in all patients. The drive-train (S1) and the extrastimulus (S2) were applied from the same site, the right ventricular (RV) apex, in 25 patients, and from separate sites (RV apex and RV outflow tract) in 10 patients. The effect of procainamide (plasma concentration 10.1 +/- 2.3 micrograms/ml) on the strength-interval relations in 10 patients was also assessed. Although effective RP decreased significantly with each successive increase in current strength (p less than 0.001), local functional RP decreased only up to current strength of 4 mA, and remote functional RP decreased only up to 2 mA. Procainamide shifted the effective RP and local and remote functional RP strength-interval curves uniformly to the right without altering their relation. These data indicate that large-scale conduction delay provides the principal limitation for using increasing current strengths of a single extrastimulus to initiate or terminate ventricular tachycardia.

Efficacy of verapamil in chronic, recurrent ventricular tachycardia.

Verapamil, 0.25 mg/kg, was given to 24 patients with chronic, recurrent ventricular tachycardia (VT) whose clinical tachyarrhythmias were reproduced at electrophysiologic study. Seven patients (29%) responded acutely to verapamil: VT was not inducible in 5 and spontaneously terminated within 5 seconds of induction in 2 patients in whom it was previously sustained. Four of the 7 responders had no identifiable structural heart disease, and 3 had coronary artery disease. Responders were younger and had better left ventricular function than did nonresponders. Long-term therapy with verapamil, attempted in 5 of the 7 responders, was effective in 3, ineffective in 1, and of uncertain efficacy in 1. Verapamil therapy was discontinued because of worsened congestive heart failure in 2 patients. The short-term efficacy of verapamil in these patients compares favorably with the efficacy of other antiarrhythmic agents against VT induction in patients with long-term, recurrent, drug-refractory VT. The short-term efficacy of verapamil correlated with its long-term efficacy. These observations provide preliminary evidence that verapamil may be useful in the treatment of some patients with recurrent VT. When standard drugs are not effective, verapamil should be given a trial, especially in young patients with good left ventricular function.

Clinical efficacy and electrophysiology of imipramine for ventricular tachycardia.

Invasive electrophysiologic studies were performed before and during treatment with imipramine in 18 patients with inducible ventricular tachycardia (VT). All received imipramine, 50 mg twice daily for 3 days, and then 100 mg twice daily for 3 days. Imipramine increased the infranodal conduction times (HV) (from 58 +/- 7.8 to 65 +/- 10 ms) and QRS duration (from 133 +/- 21 to 153 +/- 39 ms) and significantly decreased sinus cycle length (from 875 +/- 145 to 711 +/- 116 ms) and maximal corrected sinus nodal recovery time (from 457 +/- 656 to 380 +/- 603 ms). The Wenckebach cycle length tended to decrease and the QT interval to increase, but these changes were not statistically significant. Atrial and ventricular refractory periods, atrioventricular nodal conduction times and induced VT cycle length did not change significantly. Imipramine prevented induction of VT in 2 patients, and VT was more difficult to induce in 1 patient. These 3 patients received chronic imipramine therapy. The 2 patients in whom no VT could be induced while taking imipramine have had no recurrence of arrhythmia at 6 and 12 months of follow-up. The third patient died suddenly 4 months after discharge from the hospital. One patient had worsening of arrhythmias while taking imipramine and 61% had minor adverse effects. The mean combined plasma imipramine and desmethylimipramine concentration at the time of the repeat electrophysiologic study was 227 +/- 114 ng/ml. Imipramine is effective against VT in some patients; however, like other type I antiarrhythmic drugs, the rate of efficacy is low.