Effects of incremental doses of procainamide on ventricular refractoriness, intraventricular conduction, and induction of ventricular tachycardia

The short-term effects of incremental doses of procainamide (7.5, 15, 22.5, and 30 mg/kg) on right ventricular effective refractory period, intraventricular conduction, and induction of ventricular tachycardia were determined in 31 patients who had a history of sustained, unimorphic ventricular tachycardia. QRS duration during incremental ventricular pacing was used as an index of rate-dependent changes in intraventricular conduction. The mean plasma procainamide concentrations corresponding to the incremental doses were 5.5 +/- 1.2 (+/- SD), 9.0 +/- 1.6, 12.6 +/- 2.2, and 16.3 +/- 3.2 mg/liter. Each incremental dose of procainamide up to a dose of 30 mg/kg resulted in a significant increment in right ventricular effective refractory period and each dose up to 22.5 mg/kg potentiated a rate-dependent prolongation of QRS duration. After the 7.5 mg/kg dose of procainamide, induction of ventricular tachycardia was suppressed in eight of 31 patients. After higher doses of procainamide, induction of ventricular tachycardia was suppressed in two additional patients. In three of 10 patients in whom the induction of ventricular tachycardia was suppressed by 7.5, 15, or 22.5 mg/kg of procainamide, sustained unimorphic ventricular tachycardia was again inducible after a higher dose of procainamide. In three of 31 patients, only nonsustained ventricular tachycardia was inducible after a 7.5 to 22.5 mg/kg dose of procainamide; however, in two of these three patients, sustained ventricular tachycardia was again inducible after administration of a higher dose of procainamide. In conclusion, during electropharmacologic testing with procainamide, it is worthwhile to test a dose of 7.5 mg/kg, because this dose is often effective in patients who respond to this drug. However, the results of this study indicate that procainamide may be effective in suppressing the induction of sustained ventricular tachycardia at a relatively low plasma concentration, but not at a higher plasma concentration. Therefore, during long-term therapy with procainamide it may be important to avoid plasma procainamide concentrations not only lower, but also higher than the concentration that results in the suppression of induction of tachycardia.     

Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle: Implications for possible antiarrhythmic and proarrhythmic mechanisms

We studied the effects of intravenous fiecainide (2 mg.kg^–1)on atrial and ventricular refractoriness and conduction duringsinus rhythm, induced atrial fibrillation and atrial pacingat rates of 100, 120 and 150 ppm, in 14 patients with normalleft ventricle. Flecainide caused a significant increase inQRS duration during sinus rhythm (mean ± SD: 87·2± 8·4 ms vs 102·8 ± 9·1 ms,P<0·001) atrial fibrillation (87·8 ±10·0 ms vs 108·8 ± 13·7 ms, P<0·001)and at all paced rates. The duration of the atrial electrogramwas significantly increased during sinus rhythm (54·9± 13·2 ms vs 64·8 ± 16·6ms, P=0·003) and at all pacing rates. The PA intervalwas also signficantly prolonged, as was the pacing stimulus-to-atrial-electrograminterval at all pacing rates. There was increased QRS durationand atrial electrogram prolongation at higher pacing rates.Atrial refractoriness was prolonged during sinus rhythm (216·4± 28·2 vs 228·6 ± 36·1, P=0·02),but not during atrial pacing at any rate. The QT interval, butnot the JT interval or ventricular refractoriness, was significantlyprolonged during sinus rhythm and at all pacing rates. Flecainideslows atrial conduction in a use-dependent manner and increasesatrial refractoriness during sinus rhythm but not during fasteratrial pacing, thus not displaying a use-dependent effect. QRSduration is prolonged in a use-dependent manner without a commensurateincrease in ventricular refractoriness. In the presence of rapidlyconducted atrial fibrillation, which was not found to be slowedby flecainide, this effect may constitute a proarrhythmic mechanismeven in patients with no apparent myocardial abnormality.     

Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle: Implications for possible antiarrhythmic and proarrhythmic mechanisms

We studied the effects of intravenous fiecainide (2 mg.kg^–1)on atrial and ventricular refractoriness and conduction duringsinus rhythm, induced atrial fibrillation and atrial pacingat rates of 100, 120 and 150 ppm, in 14 patients with normalleft ventricle. Flecainide caused a significant increase inQRS duration during sinus rhythm (mean ± SD: 87.2 ±8.4 ms vs 102.8 ± 9.1 ms, P<0.001) atrial fibrillation(87.8 ± 10.0 ms vs 108.8 ± 13.7 ms, P<0.001)and at all paced rates. The duration of the atrial electrogramwas significantly increased during sinus rhythm (54.9 ±13.2 ms vs 64.8 ± 16.6 ms, P=0.003) and at all pacingrates. The PA interval was also signficantly prolonged, as wasthe pacing stimulus-to-atrial-electrogram interval at all pacingrates. There was increased QRS duration and atrial electrogramprolongation at higher pacing rates. Atrial refractoriness wasprolonged during sinus rhythm (216.4 ± 28.2 vs 228.6± 36.1, P=0.02), but not during atrial pacing at anyrate. The QT interval, but not the JT interval or ventricularrefractoriness, was significantly prolonged during sinus rhythmand at all pacing rates. Flecainide slows atrial conductionin a use-dependent manner and increases atrial refractorinessduring sinus rhythm but not during faster atrial pacing, thusnot displaying a use-dependent effect. QRS duration is prolongedin a use-dependent manner without a commensurate increase inventricular refractoriness. In the presence of rapidly conductedatrial fibrillation, which was not found to be slowed by flecainide,this effect may constitute a proarrhythmic mechanism even inpatients with no apparent myocardial abnormality.     

Clinical usefulness of head-up tilt test in patients with syncope and intraventricular conduction defect.

Head-up tilt test was performed in 99 patients with syncope of unknown origin and intraventricular conduction defect. Twenty-five per cent had a positive response to tilt with reproduction of spontaneous clinical symptoms. Holter recording revealed paroxysmal atrioventricular (AV) block in three patients. Carotid sinus massage was positive in four patients. An electrophysiological study was performed in 76 patients with abnormal findings in 17 (22%). Thus, vasovagal syncope was the discharge diagnosis in 25 patients (25%). Therefore, tilt test should be considered in patients with intraventricular conduction defect presenting with syncope of unknown origin, especially if clinical findings suggest the possibility of a vasovagal mechanism, or if the results of the electrophysiological study are inconclusive.     

Electropharmacologic effect of a standard dose of intravenous procainamide in patients with sustained ventricular tachycardia

BACKGROUND: Patients with inducible sustained ventricular tachycardia (VT) sometimes receive intravenous procainamide during electrophysiologic testing. Unfortunately, the responses to intravenous and subsequent oral drug therapy are variable and may be discordant. HYPOTHESIS: It was the aim of this study to determine whether this variability might be explained by heterogeneity in the electropharmacologic response, even in a homogeneous population. METHODS: We studied 42 patients who had spontaneous malignant ventricular arrhythmia and were inducible to sustained monomorphous VT during electrophysiologic testing. Each received 15 mg/kg of intravenous procainamide followed by a 2 mg/min infusion. Serum levels were drawn immediately following programmed stimulation. The mean procainamide level was 6.7 +/- 1.4 mcg/ml with an N-acetyl procainamide level of 1.0 +/- 0.5 mcg/ml. The 14 procainamide responders (5 of whom were noninducible and 9 whose VT cycle length increased > 100 ms) and the 28 nonresponders had similar procainamide and NAPA levels (6.5 +/- 1.4 vs. 6.7 +/- 1.4 mcg/ml). RESULTS: There was no significant difference in baseline clinical parameters, His to ventricular electrogram (HV) interval, effective refractory period, or VT cycle length. Prolongation of the effective refractory period and infra His conduction time occurred to a similar extent in responders and nonresponders. CONCLUSION: We conclude that procainamide has a consistent dose-response relationship with respect to refractoriness and conduction in patients with malignant arrhythmias. However, acute antiarrhythmic efficacy of procainamide cannot be predicted by clinical factors, drug levels, or drug-induced changes in common electrophysiologic parameters.     

A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80

In 20 patients undergoing coronary arteriography, the hemodynamiceffects of an experimental preparation of i.v. amiodarone 5mg kg^–1 without Tween 80 (N) (10 patients) were comparedwith those of the commercial form with Tween 80 (A) (10 patients).Analysis of variance demonstrated differences during the 3 minof injection and for 3 min afterwards: left ventricular systolicpressure decreased from 110+ 11 to 86±11 mmHg (p=0.001)after A and from 114±22 to 106±19 (p=0.05) afterN (comparison p=0.01) while related tachycardia was also morepronounced after A (comparison P=0.001). Left ventricular enddiastolic pressure transiently decreased after A while continuouslyincreasing after N (P=0.05). During the following 30 min bothA and N caused similar bradycardia, increase in ventricularfilling pressure, vascular resistance and decrease in cardiacand contractility indexes. Amiodarone blood levels were similarafter A or N. These data document a significant initial shortduration vasoplegia, mainly related to Tween 80, after A, whenamiodarone itself after producing a similar very slight effectcauses bradycardia, and a moderate and progressive negativeinotropic effect. It was concluded that while the experimental form would be ofinterest, the risk of severe hypotension after i.v. Cordaronecan be largely avoided by using a slower rate of infusion, especiallyin patients with hypovolemic status.     

Effect of amiodarone on dispersion of atrial refractoriness and cycle length in patients with atrial fibrillation

INTRODUCTION: Amiodarone is effective in preventing the recurrence of atrial fibrillation (AF) after cardioversion (CV). Dispersion of atrial refractoriness may be relevant to the generation of AF. We designed a study to determine the electrophysiologic effects of amiodarone in patients with previous early recurrence of AF after CV. METHODS AND RESULTS: Fifteen patients with previous AF recurrence (without antiarrhythmic drugs) after CV (CV1) were selected for amiodarone therapy and repeat CV (CVamio). Prior to CV1, mean AF cycle length (AFCL) had been recorded at four atrial sites (right atrial appendage [RAA], distal coronary sinus [DCS], right atrial lateral wall [LAT], and interatrial septum [IAS]) and dispersion of AFCL had been calculated. These patients were treated with amiodarone and, prior to CVamio, AFCL was recorded at the four atrial sites as for CV1. Between CV1 and CVamio, AFCL increased at all atrial sites: 153 +/- 13 msec to 179 +/- 14 msec at RAA, 144 +/- 12 msec to 174 +/- 18 msec at DCS, 158 +/- 13 msec to 182 +/- 16 msec at LAT, and 161 +/- 18 msec to 181 +/- 17 msec at IAS. Dispersion of AFCL decreased from 24 +/- 10 msec at CV1 to 15 +/- 11 msec at CVamio (P = 0.01). The median time in sinus rhythm increased from 3.12 hours post CV1 to 28 days post CVamio, (P < 0.02). CONCLUSION: Amiodarone causes a reduction in the dispersion of AFCL. This action may be relevant to the beneficial effects of amiodarone in patients with AF.     

Rate-dependent effects of intravenous lidocaine, procainamide and amiodarone on intraventricular conduction

In this study, the duration of the QRS complex during ventricular pacing was used as an index of intraventricular conduction to quantitate the rate-dependent effects of intravenous lidocaine, procainamide and amiodarone. Right ventricular apical pacing (15 to 20 beats) was performed at cycle lengths of 600, 500, 400, 350, 300, 275 and 250 ms, before and 5 minutes after the intravenous administration of lidocaine in 11 patients (serum level 3.2 +/- 0.8 micrograms/ml [mean +/- SD] ), procainamide in 14 patients (serum level 8.2 +/- 1.9 micrograms/ml) and amiodarone in 12 patients (serum level 3.9 +/- 1.2 micrograms/ml). Electrocardiographic recordings were made at a paper speed of 150 mm/s. QRS duration was measured in a blinded fashion, with reproducibility within 5%. In the control state, QRS duration was the same at all paced cycle lengths. After lidocaine, procainamide and amiodarone administration, the shortest paced cycle length with complete ventricular capture was 250 +/- 0, 275 +/- 38 and 264 +/- 20 ms, respectively. At a paced cycle length of 600 ms, the increase in QRS duration compared with the control state was 1 +/- 2% with lidocaine (p greater than 0.05), 21 +/- 7% with procainamide (p less than 0.001) and 6 +/- 6% with amiodarone (p less than 0.05). At the shortest paced cycle length with complete capture, the increase in QRS duration compared with the control state was 20 +/- 6% with lidocaine (p less than 0.001), 42 +/- 11% with procainamide (p less than 0.001) and 26 +/- 4% with amiodarone (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The tetrafascicular nature of the intraventricular conduction system

The existence of a tetrafascicular intraventricular conduction system remains debatable. A consensus statement ended up with some discrepancies and, despite agreeing on the possible existence of an anatomical left septal fascicle, the electrocardiographic and vectorcardiographic characteristics of left septal fascicular block (LSFB) were not universally accepted. The most important criteria requested to confirm the existence of LSFB is its intermittent nature. So far, our group has published cases of transient ischemia‐induced LSFB and phase 4 or bradycardia‐dependent LSFB. Finally, anatomical, anatomopathological, histological, histopathological, electrocardiographic, vectorcardiographic, body surface potential mapping, and electrophysiology studies support the fact that the left bundle branch divides into three fascicles or a “fan‐like interconnected network.”     

Effects of AWD 23-111, a new antiarrhythmic substance, on cardiac conduction and refractoriness

Summary In isolated spontaneously beating guinea pig hearts, the effects of AWD 23-111 (N-(dicyclohexylcarbamoylmethyl)-N-(3-diethylamino-propyl)-4-nitrobenzamid-hydrochloride), a new synthetic class III antiarrhythmic agent with sodium antagonistic properties, were investigated on cardiac electrophysiological parameters, that is, conduction and refractoriness. Concentration-dependent prolongation of the atrioventricular, intraventricular, and His bundle conduction times and of sinus node cycle length were present. At 0.3 M the repolarization period was prolonged significantly. No reverse use-dependent effect on the repolarization period was observed. During rapid pacing (pacing cycle length = 120 ms for the ventricle and 180 ms for the atrium) the rate-dependent intraventricular (QRS) or atrioventricular conduction time (AVCT) prolongation follows an exponential function of the beat number and is characterized by a drug-specific time constant. The time constant for the intraventricular conduction time prolongation in the presence of 0.1 M AWD 23-111 was very long at 150±29 beats (mean±SEM; n=6), indicating a slow binding kinetic to the sodium channel. At 0.1 M AWD 23-111, a significant increase in the ventricular effective refractory period was reached when the interstimulus interval (S1-S1) was 120 ms and the number of conditioning stimuli (S1) was higher than the time constant. The time constant for the rate-dependent AVCT prolongation in the presence of 0.3 M AWD 23-111 was 34±6 beats (n=6). The effective refractory period of the atrioventricular conduction significantly increased with the number of conditioning stimuli (S1), until the number was comparable with the time constant. In conclusion, AWD 23-111 exerts a wide variety of actions on the cardiac conduction system. Its combined effects on the potassium and sodium channels seem to be responsible for the marked rate-dependent effect on ventricular refractoriness and for the lack of a reverse use-dependency on JT prolongation.     

Association of congenital, diffuse electrical disease in children with normal heart: sick sinus syndrome, intraventricular conduction block, and monomorphic ventricular tachycardia

Introduction: Rhythm disturbances in children with structurally normal hearts are usually associated with abnormalities in cardiac ion channels. The phenotypic expression of these abnormalities ("channelopathies") includes: long and short QT syndromes, Brugada syndrome, congenital sick sinus syndrome, catecholaminergic polymorphic ventricular tachycardia, Lènegre-Lev disease, and/or different degrees of cardiac conduction disease.
Methods: The study group consisted of three male patients with sick sinus syndrome, intraventricular conduction disease, and monomorphic sustained ventricular tachycardia. Clinical data and results of electrocardiography, Holter monitoring, electrophysiology, and echocardiography are described.
Results: In all patients, the ECG during sinus rhythm showed right bundle branch block and long QT intervals. First-degree AV block was documented in two subjects, and J point elevation in one. A pacemaker was implanted in all cases due to symptomatic bradycardia (sick sinus syndrome). Atrial tachyarryhthmias were observed in two patients. The common characteristic ventricular arrhythmia was a monomorphic sustained ventricular tachycardia, inducible with ventricular stimulation and sensitive to lidocaine. In one patient, radiofrequency catheter ablation was successfully performed. No structural abnormalities were found in echocardiography in the study group.
Conclusion: Common clinical and ECG features suggest a common pathophysiology in this group of patients with congenital severe electrical disease.     

双心室起搏治疗慢性心力衰竭伴心室内传导阻滞患者的近期疗效

目的观察双心室起搏治疗慢性心力衰竭（心衰）的临床效果。方法慢性心衰患者13例均伴心室内传导阻滞,体表心电图QRS波时限为146±9 m s,心功能（NYHA）ⅢⅣ级,超声心动图显示左心室射血分数（LVEF）为0.28±0.06,左心室舒张末径（LVEDD）为68±5 mm。患者植入三腔起搏器行心房感知,双心室起搏。结果术后体表心电图QRS波时限缩短至122±7 m s（P<0.01）,心功能平均提高1级。术后1月超声心动图显示LVEF增至0.36±0.06（P<0.05）,舒张期充盈改善,二尖瓣返流减少。结论双心室起搏可有效改善慢性心衰伴心室内传导阻滞患者近期的心功能。     

Comparison of the effects of pirmenol and lidocaine on intraventricular conduction in canine myocardial infarction

Effects of pirmenol hydrochloride and lidocaine hydrochloride on intraventricular conduction were examined in the infarcted heart of anesthetized dogs. The effects of the drugs on the excitation induced by ventricular stimulations were determined with coupling intervals between 150 and 1,000 ms. Effects of the drugs on the His bundle electrocardiograms were also examined. Pirmenol in doses of 1-5 mg/kg prolonged the conduction time in the infarcted zones over a wide range of coupling intervals. Pirmenol at 5 mg/kg blocked the delayed conduction at a short coupling interval in the infarcted zones. The effect of pirmenol on the conduction time in the normal zone was slight. Lidocaine in doses of 3 and 10 mg/kg prolonged the conduction time in the infarcted zone at a short coupling interval. Pirmenol did not significantly prolong PQ or AH interval. In conclusion, pirmenol selectively depressed the delayed conduction in the infarcted zone, which could result in a reentrant pathway. The effect of pirmenol on delayed conduction was dependent on the coupling interval and was quite different from that of lidocaine.     

Effect of intravenous amiodarone in patients with intraventricular conduction disorders

Using His bundle recordings and stimulation techniques, theelectrical effects of amiodarone (5 mg/kg intravenously) wereassessed in 12 patients aged 34–80 years (mean 65) exhibitingin sinus rhythm, intraventricular conduction disturbances. Bundlebranch block was present in 10 patients: left bundle branchblock in three patients, right bundle branch block in three,bilateral bundle branch block in four. All the patients hada long H-V interval (65–80 ms; mean 71). As has been previouslyreported, amiodarone slowed the sinus rate, prolonged the QTinterval, increased the atrial effective refractory period anddepressed A-V nodal conduction. Despite the presence of advancedconduction disturbances within the His-Purkinje system, amiodaronedid not alter the H-V interval in 11 patients and increasedit in one by only 5 ms. Thus, clinically, the use of amiodaronein patients with bundle branch block should be safe.     

Effects of intravenous amiodarone in patients with inducible repetitive ventricular responses and ventricular tachycardia

We studied the effects of intravenous amiodarone administration (5 mg/kg) on reproducible repetitive ventricular responses and ventricular tachycardia (VT) induced by programmed electrical stimulation of the heart in 32 patients. Intravenous amiodarone prevented induction of bundle branch reentry in only 2 of 11 patients (18.2%) and did not change His-Purkinje conduction and refractoriness in the remaining 9 of 11 (81.8%) patients. In contrast to the small effect of intravenous amiodarone on bundle branch reentry, the drug completely abolished intraventricular reentry in three of nine (33.3%) patients and in the remaining six of nine (66.7%) patients decreased the number of intraventricular reentrant beats from up to five beats in control to one to two beats after the drug. The drug also prevented induction of VT (greater than or equal to 5 ventricular ectopic beats in a row) in three of five (60%) patients with nonsustained VT and in three of seven (42.9%) patients with sustained VT. In two of seven (28.6%) patients with sustained VT, only nonsustained tachycardia could be induced after drug administration. In another two of seven (28.6%) patients, sustained VT with slower rates was induced after the drug. In 11 of 12 (91.7%) patients with VT the coupling interval between the last stimulus and the first ventricular beat increased after drug administration. These effects of intravenous amiodarone occurred in the absence of effect on ventricular effective refractory period. These findings suggest that intravenous amiodarone might have greater effect on diseased ventricular tissue, the site of reentry in VT, than on healthy ventricular tissue.     

Electrophysiological evaluation of the sinus node in patients with atrioventricular and/or intraventricular conduction defects

The authors evaluated retrospectively sinoatrial conduction time (SACT), sinus node recovery time (SNRT), and corrected sinus node recovery time (CSNRT) in 272 patients with atrioventricular and/or intraventricular conduction defects without evidence of overt sinus node dysfunction. The study was designed to determine the prevalence of electrophysiologic sinus node abnormalities in patients with overt atrioventricular and/or intraventricular conduction defects. One or more sinus node electrophysiological abnormalities were observed in 133 cases (48.9%). There was a significant prevalence of electrophysiologic sinus node abnormalities only in patients older than 71 years of age. The data suggest that the involvement of the specialized conduction system is much more diffuse than one might expect simply observing the single recorded ECG defect and that the prevalence of associated defects of the conduction system increases with increasing age of patients.     

胺碘酮对室性心律失常患者QT离散度的影响

要：目的观察胺碘酮对室性心律失常患叩离散度的影响。方at400例室性心律失常患应用口服或静脉注射胺碘酮治疗,其中18例持续性室性心动过速患静脉应用胺碘酮治疗,负荷量为24h总量900～1500mg,同时口服胺碘酮600mg/d。382例频发室早伴或不伴短阵室速的患口服胺碘酮治疗,负荷量为第1周600mg/d,并根据病情逐渐减量。结果400例室性心律失常患应用胺碘酮治疗均有效,并发现该药能减少叽离散度,未见严重毒副作用．结论胺碘酮治疗室性心律失常安全有效．能影响患的QT离散度．且能减少室颤的发生。     

Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients

Twenty-six consecutive patients (14 males, 12 females—meanage 66.6) were admitted to an intensive care unit (ICU) becauseof a rapid ventricular response to atrial fibrillation (RAF).Fourteen of them had been unsuccessfully treated by drugs (otherthan amiodarone) and/or DC shock before admission. A loading dose of i.v. amiodarone was administered (repeatedboluses of 3 mg/kg in 3 min, or 30 min-infusions of 5 to 7.5mg/kg), followed by continuous infusion, in order to reach amaximal total dosage of 1500 mg in 24 h. This treatment was considered efficacious if a reversion tostable sinus rhythm (SSR) occurred within 24 h and was maintainedfor more than 48 h. This was achieved in 21 out of 26 patients(80.8%). The mean time between the administration of therapyand the occurrence of SSR was 171 min. The total dose of amiodaronedelivered to effect SSR was 6.9 ± 2.3 mg/kg. No adversereactions were encountered during the bolus injection but werecommend that continuous infusion be carried out through acentral venous catheter to avoid phlebitis. The administration of 7 mg/kg of intravenous amiodarone deliveredin 30 min proved a safe and successful first choice of managementin atrial fibrillation with a rapid ventricular response.