Electrophysiologic effects of isoproterenol in patients with atrioventricular reentrant tachycardia treated with flecainide

The electrophysiologic effects of isoproterenol in patients treated with flecainide for atrioventricular (AV) reentrant tachycardia were studied to evaluate the mechanism of tachycardia inducibility after isoproterenol and the value of isoproterenol challenge as a predictor of spontaneous arrhythmia recurrence. Seventeen patients underwent electrophysiologic study before and after oral flecainide administration and after the addition of isoproterenol to flecainide. No patient had inducible sustained supraventricular tachycardia after flecainide alone. Two patients had inducible sustained and six had inducible nonsustained tachycardia after isoproterenol was added to flecainide. The patients were then followed up on the same flecainide dose they received at the time of the electrophysiologic study. Findings: 1) Flecainide treatment prolonged HV and VA intervals, and the addition of isoproterenol did not affect these variables. 2) Isoproterenol shortened anterograde and retrograde block cycle length and the refractory period of the accessory pathway and the AV node. It also decreased the tachycardia cycle length, an effect that was due solely to shortening of AV node conduction time. 3) Flecainide treatment prevented tachycardia induction by affecting retrograde conduction over the accessory pathway. Isoproterenol allowed for tachycardia induction and for more sustained episodes of tachycardia by reversing the effect of flecainide on retrograde accessory pathway conduction. 4) Tachycardia recurred during follow-up in all three patients in whom tachycardia of greater than or equal to 10 s duration was induced after isoproterenol but in no patient who had no or shorter episodes of induced tachycardia (and who did not have a change in medical regimen). Conclusions: 1) Isoproterenol reverses flecainide-induced prolongation of block cycle length and refractory periods of the accessory pathway and AV node. 2) Isoproterenol reverses flecainide-induced prevention of tachycardia induction through reversal of the effects of flecainide on the retrograde accessory pathway. 3) The addition of isoproterenol during flecainide restudy is valuable in predicting long-term drug efficacy.     

Parasympathetic and sympathetic alterations of Mobitz type II heart block

This study examined the effects of changes in parasympathetic and sympathetic tone on the cycle length at which Mobitz type II second degree atrioventricular (AV) block occurred. Four patients who had electrocardiographic evidence of type II AV block and confirmation of block in the His-Purkinje system during electrophysiologic study were evaluated. These patients received intravenous atropine (1.0 to 2.4 mg), propranolol (0.15 mg/kg body weight) or isoproterenol (1 and 2 micrograms/min) alone or in combination. In two of three patients receiving propranolol, the atrial pacing cycle length at which 1:1 His-Purkinje conduction occurred was prolonged relative to control (from 360 to 470 ms and 440 to 590 ms, respectively). In contrast, atropine in the presence of beta-adrenergic blockade shortened the cycle length at which 1:1 His-Purkinje conduction occurred in three of four patients receiving the drug (470 to 390, 630 to 570 and 590 to 560 ms, respectively). Isoproterenol also improved His-Purkinje conduction in the one patient receiving this drug. No agent affected the duration of the HV interval during spontaneous sinus rhythm or right atrial pacing. Thus, drugs that alter autonomic tone influence abnormal His-Purkinje conduction minimally during sinus rhythm but, importantly, may modulate the atrial pacing cycle length at which type II AV block occurs.     

Autonomic dependence of ventriculoatrial conduction

To evaluate the effects of isoproterenol and atropine on patients with poor ventriculoatrial (VA) conduction, 17 patients were studied who did not have 1-to-1 VA conduction during ventricular pacing at a rate slightly faster than sinus rate (group I) and 11 patients were studied who had 1-to-1 VA conduction, but only at constant ventricular pacing cycle lengths longer than 600 ms (group II). Isoproterenol infusion at a rate causing a 20 to 30% increase in sinus rate or up to 4 micrograms/min shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. Atropine administration at a dose causing a 20 to 30% increase in sinus rate or up to a total dose of 2 mg also shortened the ventricular pacing cycle lengths that induced VA block in all group II patients. At similar pacing cycle lengths, isoproterenol and atropine induced shorter VA intervals than control. Nine of 17 group I patients had demonstrable 1-to-1 VA conduction either during isoproterenol infusion or after atropine administration. Of these 9 patients, 1-to-1 VA conduction could be found only during isoproterenol infusion in 3 patients and only after atropine administration in 4 patients. The improvement of VA conduction by these drugs was related to their effects on the atrioventricular node. The change in VA conduction mediated by autonomic changes induced by these drugs may explain why some patients without demonstrable VA conduction during rest may have, under certain circumstances, "endless-loop" tachycardia or paroxysmal supraventricular tachycardia using atrioventricular nodal conduction as the retrograde limb.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic studies in the denervated transplanted human heart: II. Response to norepinephrine, isoproterenol and propranolol

Five patients who had received a transplanted human heart 1 to 3 years previously were studied to determine the effects of norepinephrine, isoproterenol and propranolol on the atrioventricular (A-V) conduction system. Using the His bundle technique, atrial, His bundle and ventricular electrograms were recorded, and central aortic pressure was monitored during the administration of these drugs. Norepinephrine was given by continuous infusion to four patients in doses ranging from 4 to 8 μg/min, with the systolic arterial pressure increasing by an average of 72 mm Hg. Concomitantly, there was an average increase in the rate of the donor atrium of 32 beats/min, and a reflex slowing of the recipient atrium of 23 beats/min. The A-H interval shortened by an average of 27 msec. Isoproterenol dose-response curves were performed in three patients, with the maximal dose being 5.2 μg by intravenous bolus infusion. The rate of the donor atrium increased by an average of 40 beats/min, and that of the recipient atrium by 18 beats/ min. The A-H time shortened by an average of 25 msec, with a drop in systolic blood pressure averaging 23 mm Hg. Propranolol (7 mg intravenously) was given to three patients and the peak doses of norepinephrine and isoproterenol were again infused. Beta adrenergic blockade was achieved at this dose of propranolol since there was only a minimal increase in the donor atrial rate after infusion of the drug. The A-H interval was not altered by catecholamine infusion after achievement of beta blockade. However, the levels of systolic hypertension noted after infusion of norepinephrine were not altered by propranolol. The denervated transplanted human heart appears to respond normally to norepinephrine and isoproterenol, and the electrophysiologic effects of these agents are blocked by propranolol.

Extensive investigative work in the denervated canine model has demonstrated the presence of the alpha and beta cardiovascular receptors. Although the autonomic nervous system is important in cardiac performance, this work is the first validation in man that (1) the functional integrity of the beta receptor is maintained even when the autonomic nerves are absent, and (2) the intrinsic properties of the sinus and atrioventricular nodes are the keystone in stabilizing cardiac electrophysiology after denervation.     

Divergent Effect of Acute Ventricular Dilatation on the Electrophysiologic Characteristics of d,I-Sotalol and Flecainide in the Isolated Rebbit heart

Ventricular Dilatation and d,l-Sotalol/Flecainide in Isolated Rabbit Heart. Introduction: The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide. Methods and Results: The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 μM) resulted in a significant (P < 0.05) lengthening of refractoriness (+13.5%± 3.1%), MAP duration (+14.9%± 3.2%), and QT interval (+15.5%± 4.1%) (mean ± SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of WD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2μM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6%± 8.2%), prolongation of QRS (+48.8%± 5.6%), and conduction time (+78.6%± 8.6%) (mean ± SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7%± 5.5%) and conduction time (+17.1%± 4.3%). Conclusion: Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.     

Suppression of exercise-induced ventricular arrhythmias by propranolol and diltiazem in a woman without organic heart disease--a case report.

A thirty-five-year-old woman without organic heart disease who has exercise-induced ventricular arrhythmias suppressed by propranolol and diltiazem is reported. Treadmill exercise provoked reproducibly nonsustained ventricular tachycardia (NSVT) and salvos of ventricular premature contraction (VPC). QRS morphology of these ventricular arrhythmias showed left bundle branch block pattern and right axis deviation. Oral propranolol (20 mg) and diltiazem (90 mg) prevented exercise provocation of NSVT and VPC. However, oral mexiletine (200 mg) and procainamide (500 mg) could not prevent exercise provocation of these ventricular arrhythmias. No ventricular arrhythmias could be induced by any form of ventricular extrastimulations. Right ventricular pacing at a rate of 210 beats/minute provoked NSVT of which the QRS morphology was similar to that of exercise-induced NSVT. Triggered activity may be a possible electrophysiologic mechanism for exercise-induced ventricular arrhythmias in this patient, although other mechanisms such as reentry and enhanced automaticity could not be completely excluded.     

Refractoriness and Conduction Interaction During Modulation of Non-Ischemic Ventricular Fibrillation by Flecainide

Purpose: To study refractoriness and conduction interaction during modulation of non-ischemic ventricular fibrillation (VF) by flecainide. Methods: Isolated feline and rabbit hearts were used. (a) In the feline hearts (n = 8), electrophysiological parameters were measured before and after flecainide administration (0.6, 1.2 × 10^–6 M). During pacing the parameters were: epicardial conduction time, refractoriness and 1:1 pacing/response capture. During 8 min of electrically-induced tachyarrhythmias they included heart rate and normalized entropy reflecting the degree of organization. (b) In rabbit hearts (n = 4), three-dimensional mapping was performed before and after flecainide administration (2 × 10^–6 M). To follow changes in organization, local RR-intervals and differences in activation time between adjacent epicardial electrodes were measured immediately and 80 sec after VF induction. Results: In feline hearts with flecainide, fibrillation was more difficult to induce, more frequently terminated spontaneously and was slower and more organized; conduction time was markedly lengthened, and refractoriness less than 1:1 capture, was moderately prolonged. An inverse correlation was observed between arrhythmia properties, rate and organization, and changes in refractoriness and conduction time. In rabbit, the number of wave fronts was reduced, RR-intervals were prolonged but at the same time activation time differences between adjacent electrodes were smaller following flecainide administration. Conclusions: It is suggested that flecainide modulation of VF properties is associated with conduction suppression and refractoriness prolongation, which act in a synergistic, additive way.     

Efficacy of flecainide in pacing-induced sustained ventricular tachyarrhythmias: correlation to clinical parameters and tachycardia-characteristics

Seventy-two patients with sustained ventricular tachycardiaor syncope of unknown origin underwent electrophysiologic evaluationbefore and after therapy with flecainide (200–300 mg day^–1).In all patients, sustained ventricular tachycardia or ventricularfibrillation was inducible during control electrophysiologicstudy. During flecainide therapy, sustained ventricular tachycardia(VT) was no longer inducible in 18 patients (25%) whereas in54 patients, VT was still inducible. In five of the latter patients,VT became more difficult to induce (overall efficacy 32%). Therate of VT decreased from 214±49 beats min^–1 duringthe control electrophysiologic study to 178±48 beatsmin^–1 during flecainide (P<0.01). The ERP of the rightventricle increased from 251±27 ms during the controlstudy to 267±34 ms on flecainide (P<0.01). Mean ejectionfraction and mean LVEDP did not differ between responders andnon-responders, yet the presence of a left ventricular aneurysmcorrelated with a lack of antiarrhythmic response to flecainide.VT rate as well as VT morphology during the control study discriminatedbetween responders and non-responders; 11% of patients withVT-rate 230 beats min^–1 responded to oral flecainidecompared with 31% with a VT rate > 230 beats min^–1at control. 26% with induced monomorphic VT responded, comparedwith 100% with induced VF during the control study. 18 of 23responders were discharged on flecainide. During a mean follow-upof 26±18 months, two patients experienced a recurrenceof VT and in one patient, flecainide had to be discontinueddue to side-effects. Thus, the acute efficacy of flecainide, evaluated by serialdrug testing, correlates with haemodynamic parameters and thecharacteristics of tachycardia.     

Loss of efficacy of flecainide in the Wolff--Parkinson--White syndrome after isoproterenol administration

Although anterograde conduction through a Kent bundle with ashort refractory period was suppressed by 300 mg of flecainideacetate, the infusion of small amounts of isoproterenol causedthe reappearance of WPW and permitted the induction of an atrialtachycardia with I/I conduction through the accessory pathwayat a rate of 260 beats min^–1. This case shows that the effect of isoproterenol may be maintainedafter apparently successful flecainide therapy.     

The Use-Dependent Effects of Acute and Chronic Amiodarone Administration on His-Purkinje Conduction and the Interaction of β-Adrenergic Stimulation

Use-Dependent Effects of Amiodarone. Amiodarone is a highly effective antiarrhythmic agent. However, its exact mechanism of action remains uncertain. Prior studies suggest that intravenous amiodarone produces different electrophysiologic effects than chronic amiodarone administration. In addition, the effects of other antiarrhythmic agents and β-adrenergic stimulation on the electrophysiologic effects of amiodarone have not been well defined. In this study, we sought to evaluate the use-dependent effects of intravenous (acute) versus oral (chronic) amiodarone administration on His-Purkinje conduction in a closed-chest canine model. We also sought to evaluate the effects of intravenous lidocaine and isoproterenol on the use-dependent effects of chronically administered oral amiodarone. We found: (1) Acutely administered intravenous amiodarone (5 mg/kg bolus, followed by a 0.05 mg/kg/min infusion) does not produce a significant use-dependent effect on His-Purkinje conduction (serum amiodarone level 2.7 ± 1.1 mg/L), and acute beta blockade did not enhance use-dependent effects of amiodarone; (2) Chronically administered oral amiodarone (1,000 mg/day ± 2 weeks) produced significant use-dependent effects on His-Purkinje conduction at similar serum drug concentrations (mean level 2.6 ± 1.5 mg/L; (3) Intravenous lidocaine (10 mg/kg bolus, 0.2 mg/kg/min infusion) produced significant additional use-dependent effects to that of chronic oral amiodarone but only at rapid paced rates (cycle length 300-210 msec); and (4) Isoproterenol (5 μg/min infusion) significantly attenuated the use-dependent effects of chronically administered amiodarone. The mechanism of action of acutely administered intravenous amiodarone appears to be different from that of chronic oral amiodarone. In addition, the marked use-dependent effects observed after chronic amiodarone administration were reversed after catecholamine administration suggesting that attenuation of use dependence by sympathetic stimulation may negate some of salutary effects of amiodarone.     

The Electrophysiologic Characteristics in Patients with Only Ventricular-Pacing Inducible Slow–Fast Form Atrioventricular Nodal Reentrant Tachycardia

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) can be usually induced by atrial pacing or extrastimulation. However, it is less commonly induced only by ventricular pacing or extrastimulation. Objective: The purpose of this retrospective study was to investigate the electrophysiologic characteristics in patients with slow–fast form AVNRT that could be induced only by ventricular pacing or extrastimulation. Methods: The total population was 1497 patients associated with AVNRT. There were 1373 (91.7%) patients who had slow–fast form AVNRT included in our study. Group 1 (n = 45) could be induced only by ventricular pacing or extrastimulation, and Group 2 (n = 1328) could be induced by only atrial stimulation or both atrial and ventricular stimulation. The electrophysiologic characteristics of the group 1 and group 2 patients were compared. Results: Group 1 patients had a significantly lower incidence of both antegrade and retrograde dual AV nodal pathways. The pacing cycle length (CL) of the antegrade 1:1 fast pathway (FP) and antegrade ERP of the FP were both significantly shorter in Group 1 patients. Mean antegrade FRP of the fast and slow pathways were significantly shorter in Group 1 patients. The differences of pacing CL of 1:1 antegrade conduction, antegrade ERP and FRP were much longer in Group 2 patients. Conclusion: This study demonstrated the patients with slow–fast form AVNRT that could be induced only by ventricular stimulation had a lower incidence of dual AV nodal pathways and the different electrophysiologic characteristics (shorter pacing CL of the antegrade 1:1 FP, antegrade ERP of the FP and the differences of pacing CL of 1:1 antegrade conduction, antegrade ERP and FRP) from the other patients. The specific electrophysiologic characteristics in such patients could be the reason that could be induced only by ventricular stimulation.     

Efficacy of isoproterenol, magnesium sulfate and verapamil for torsade de pointes

The efficacy of isoproterenol, MgSO4 and verapamil for torsade de pointes was evaluated in 60 dogs. Torsade de pointes was induced in 28 out of 60 dogs (46.7%) by ventricular stimulation after administration of quinidine sulfate (30 mg/kg). The electrophysiologic effect of isoproterenol (0.5 micrograms/min drip infusion) was studied in 9 dogs with torsade de pointes, in 9 dogs with MgSO4 (30 mg/kg), and in 10 dogs with verapamil (0.1 mg/kg bolus injection followed by 0.01 mg/kg/min drip infusion). If the first dose of these drugs was ineffective, ventricular stimulation was performed after the additional administration of the same dose. Isoproterenol significantly decreased QTc, ERP and dispersion of ERP but increased ERP/QT. MgSO4 significantly increased ERP and ERP/QT, however dispersion of ERP did not change. Verapamil induced no electrophysiologic changes in ventricular refractions . Isoproterenol prevented the occurrence of torsade de pointes in all dogs (100%), MgSO4 in 7 of 9 dogs (77.8%, 30 mg/kg in three and 60 mg/kg in four) and verapamil in 4 of 10 dogs (40%, 0.1 mg/kg in two and 0.2 mg/kg in two). These findings suggest that isoproterenol and MgSO4 increased ERP/QT, showing one of their antiarrhythmic effects. It also shows that isoproterenol and MgSO4 may be useful in the treatment of torsade de pointes.     

Termination of recurrent supraventricular tachycardia by right ventricular endocardial pacing but not by left ventricular epicardial pacing

Externally controlled ventricular pacing was employed in a patient with recurrent disabling supraventricular tachycardia and frequent sinus pauses between attacks of tachyarrhythmia. A permanent transthoracic demand pacemaker was inserted after electrophysiologic study demonstrated the effectiveness of ventricular stimulation in terminating induced supraventricular tachycardia. Subsequently, spontaneous recurrences of tachyarrhythmia failed to respond to fixed rate left ventricular stimulation accomplished by placing a magnet externally over the pacemaker pack. During an induced supraventricular tachycardia, repeat electrophysiologic study demonstrated that paced left ventricular beats failed to invade the A-V junctional area before it was depolarized previously by the corresponding tachycardia beat. Right ventricular stimulation from a transvenous pacemaker could depolarize the site of the reentrant circuit and terminate an induced supraventricular tachycardia. The addition of propranolol increased the ease by which spontaneous attacks of tachyarrhythmia could be terminated by right ventricular endocardial pacing.     

Effect of Isoproterenol on Accessory Pathways Without Overt Retrograde Conduction

Effect of Isoproterenol on Accessory Pathways. Introduction : Absence of overt retrograde accessory pathway conduction may be related to low resting sympathetic tone in patients with apparent unidirectional anterogradely conducting accessory pathways (UACAP).
Methods and Results : To test this hypothesis, we studied the effect of isoproterenol on accessory pathway function and tachycardia induction in 18 patients (12 men and 6 women, ages 34 ± 16 years [mean ± SD]) with UACAP. After baseline study in the drug-free state, electrophysiologic testing was repeated during infusion of isoproterenol (0.5 to 1.5 μg/min, titrated to increase heart rate by 20%). Isoproterenol shortened the anterograde effective refractory period (398 ± 117 vs 305 ± 63 msec; P < 0.01; basic drive cycle length 600 msec) of the accessory pathway. However, retrograde accessory pathway conduction and atrioventricular reentrant tachycardia were exposed in only 3 (17%) patients by isoproterenol infusion. All 3 patients with retrograde accessory pathway revealed after isoproterenol had clinically documented tachycardia (supraventricular tachycardia in 2, atrial fibrillation in 1) during exercise, while none of the patients with persistent absence of retrograde accessory pathway conduction had this symptom.
Conclusions : We conclude that absence of overt retrograde conduction over accessory pathways may be related to low resting sympathetic tone in some individuals. Restoration of retrograde conduction with isoproterenol is unusual and most likely to be observed in patients with clinically documented paroxysmal supraventricular tachycardia related to exercise.     

Verapamil‐sensitive Ventricular Tachycardia in an Infant

Patients. We report on a 6‐month‐old patient with a right bundle, superior axis tachycardia at 197 beats per minute. The tachycardia was unresponsive to adenosine, propranolol, flecainide, or amiodarone, or synchronized cardioversion. Overdrive atrial pacing terminated the tachycardia and since initiating verapamil, no recurrences of his tachycardia have occurred. Conclusions. If an infant presents with a right bundle, superior axis ventricular tachycardia unresponsive to multiple antiarrhythmic medications and synchronized cardioversion, but responsive to overdrive atrial pacing, one must consider verapamil‐sensitive ventricular tachycardia and initiate appropriate therapy.     

Autonomic control of ventricular tachycardia: direct effects of beta-adrenergic blockade in 24 hour old canine myocardial infarction

The purpose of this study was to determine whether alpha- or beta-adrenergic influences directly modulate the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 41) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Neither intracoronary saline solution nor phenylephrine (0.3 to 12 micrograms) changed the rate of ventricular tachycardia; however, isoproterenol (0.01 to 10 micrograms) produced dose-dependent increases in the rate. In six dogs, metoprolol, 5 mg given intravenously, slowed ventricular tachycardia from 174 +/- 10 (mean +/- SE) to 140 +/- 17 beats/min (p less than 0.05). This was accompanied by decreases in mean arterial pressure from 106 +/- 7 to 95 +/- 8 mm Hg, cardiac output from 2.6 +/- 0.3 to 1.6 +/- 0.3 liters/min and prolongation of atrioventricular conduction from 134 +/- 10 to 189 +/- 29 ms (all p less than 0.05) during atrial pacing at a cycle length of 300 ms. In 10 dogs, metoprolol (0.5 mg) given intracoronary, a dose that shifted the isoproterenol dose-response curve to the right, slowed ventricular tachycardia from 174 +/- 7.2 to 140 +/- 9.7 beats/min (p less than 0.05) without hemodynamic changes. Additional metoprolol (4.5 mg) given intravenously produced hemodynamic alterations, but ventricular tachycardia did not slow further. Therefore, beta- but not alpha-adrenergic influences control the rate of ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Furthermore, beta-adrenergic blockade slows ventricular tachycardia solely by a direct electrophysiologic effect on the tachycardia foci and not indirectly as a result of hemodynamic effects.     

Sinus node function after cardiac transplantation

Objectives. This study aimed to examine changes over time in sinus node function after cardiac transplantation; to determine the incidence, natural history and etiology of sinus node dysfunction in transplant recipients; and to identify any early predictors of long-term sinus node function.Background. Bradyarrhythmias caused by sinus node dysfunction are common immediately after cardiac transplantation. Existing electrophysiologic studies have been limited by small numbers and have reported an unexpectedly high incidence of sinus node dysfunction (~50%) compared with the incidence of bradyarrhythmias in other studies, There have been no previous studies reporting serial electrophysiologic data. Thus, the natural history of sinus node dysfunction after transplantation has not been adequately described.Methods. Serial electrophysiologic studies of sinus node function and 24-h ambulatory electrocardiographic recordings were performed at 1, 2, 3 and 6 weeks and 3 and 6 months after transplantation in 40 adult recipients.Results. The overall incidence of sinus node dysfunction was 17.5% (7 of 40). Six patients (15%) had sinus node dysfunction from week 1; one developed sinus node dysfunction at 3 months. Sinus node recovery time returned to normal by 6 week in all six patients with early sinus node dysfunction, but abnormalities of sinoatrial conduction persisted in two. Two patients who required pacing during ambulatory monitoring at 2 weeks after transplantation (temporary pacemaker 50 beats/min, demand) received a permanent pacemaker. One patient required pacing at 3 weeks and continued to require pacing 6 months after transplantation.Conclusions. The incidence of sinus node dysfunction after cardiac transplantation is lower than has been previously reported in electrophysiologic studies. Sinus node automaticity improves with time, although abnormalities of sinoatrial conduction may persist. The best predictor of permanent pacing requirements is the temporary pacing requirements during 24-h Holter monitoring 2 and 3 weeks after transplantation, with temporary pacing set at 50 beats/min on demand.     

Mechanism of isoproterenol-induced angina pectoris in patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries

In 14 patients with obstructive hypertrophic cardiomyopathy and angiographically normal coronary arteries, 8 with angina (group B) and 6 without (group A), the effects of intravenous isoproterenol, 2 to 4 micrograms/min, followed by intravenous propranolol, 0.2 mg/kg, were studied. An intraventricular systolic gradient less than 50 mm Hg, high-quality echocardiograms and cineangiograms and high-fidelity pressure tracings were selection criteria. Hemodynamic and metabolic variables were assessed during basal conditions, after 5 minutes of isoproterenol infusion or at angina and ST-segment depression, and 5 and 10 minutes after intravenous propranolol infusion. Isoproterenol increased the intraventricular systolic gradient more significantly in group B than in group A (102.4 +/- 8.3 vs 52.2 +/- 8.2, p less than 0.0001). Group B also had higher left ventricular end-diastolic pressure (32.5 +/- 3.9 vs 20.2 +/- 5.7), lower mean arterial pressure (69.7 +/- 3.5 vs 84.7 +/- 4.8) and a smaller increase in coronary sinus flow (176.1 +/- 9.2 vs 261.5 +/- 33.9, all p less than 0.0001), concomitant with lactate release and ST-segment depression. Propranolol promptly reversed hemodynamic and metabolic changes caused by isoproterenol, except for a further coronary sinus flow increase (from 176.1 +/- 9.2 to 219 +/- 14.2 ml/min, p less than 0.001), and heart rate decrease below basal values (57.8 +/- 7.5 vs 79.9 +/- 9.8 beats/min, p less than 0.001) in group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans

BACKGROUND. Rate-dependent conduction slowing by class I antiarrhythmic agents has clinically important consequences. Class I drugs are known to produce use-dependent sodium channel blockade. If rate-dependent conduction slowing by class I agents is due to sodium channel blocking actions, the kinetics of conduction slowing should be similar to those of depression of sodium current indexes in vitro. The purpose of the present investigation was to study the onset time course of ventricular conduction slowing caused by a variety of class I agents in humans. METHODS AND RESULTS. Twenty-seven patients undergoing electrophysiological evaluation for antiarrhythmic therapy were studied. Changes in QRS duration at initiation of ventricular pacing at cycle lengths of 400 and 500 msec were used to evaluate the kinetics of drug action. Mean time constants for each drug were similar to values for Vmax depression reported in vitro studies: flecainide, 24.9 +/- 11.6 beats in eight patients (versus 34.5 beats reported for Vmax block); propafenone, 17.8 +/- 6.9 beats in five patients (versus 8.4-20.8 beats); quinidine, 7.0 +/- 2.4 beats in six patients (versus 5.6-6.2 beats); and amiodarone, 3.6 +/- 2.0 beats for eight patients (versus 3.0 beats). Time constants were significantly different among the various drugs tested (p = 0.0002 at a cycle length of 400 msec; p = 0.002 at 500 msec), and there was a strong correlation (r = 0.89, p less than 0.0001) between values obtained at a cycle length of 400 msec and those at a cycle length of 500 msec. No rate-dependent changes in QRS duration were seen at onset of ventricular pacing among eight age- and disease-matched control patients not taking class I antiarrhythmic drugs, including three patients subsequently showing such changes during type I antiarrhythmic drug therapy. CONCLUSIONS. We conclude that class I agents produce use-dependent QRS prolongation in humans with characteristic kinetics for each agent that are similar to the kinetics of Vmax depression in vitro. These results suggest that rate-dependent ventricular conduction slowing by antiarrhythmic drugs in humans is due to use-dependent sodium channel blockade.     

Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome

To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)