Linking: A Mechanism of Intermittent Preexcitation in the Wolff-Parkinson-White Syndrome

MIDDLEKAUFF, H.R., ET AL.: Linking: A Mechanism of Intermittent Preexcitation in the Wolff-Parkinson-White Syndrome. Intermittent preexcitation in the Wolff-Parkinson-White syndrome has been equated with a long accessory pathway refractory period and long R-R interval between preexcited beats in atrial fibrillation and therefore a low risk for sudden death. A case of Wolff-Parkinson-White syndrome in which preexcitation became intermittent following procainamide infusion, with only moderate prolongation of the accessory pathway refractory period but marked prolongation of the shortest preexcited R-R interval in atrial fibrillation, is described. Programmed ventricular and atrial stimulation demonstrated that intermittent preexcitation was caused by concealed conduction producing a linking phenomenon, facilitated by the antiarrhythmic drug. Linking due to concealed retrograde penetration of a propagated impulse into the accessory pathway may contribute to the disparity between accessory pathway refractory period and shortest preexcited R-R interval in atrial fibrillation in some patients and may be a confounding factor in the interpretation of noninvasive tests of accessory pathway conduction.     

Nonclinical Ventricular Tachycardia in the WolflF-Parkinson-White Syndrome

Between September 1980 and June 1984 we assessed the specificity of induction of ventricular tachycardia (VT) with one or two ventricular extrastimuli in a consecutive series of 148 patients undergoing electrophysiological assessment for the Wolff-Parkinson-White (WPW) syndrome by standard electrophysiological techniques. Fifteen patients (10%) had six or more beats of VT induced by one ventricular extrastimulus after a ventricular drive (9 patients), two ventricular extrastimuli during reciprocating tachycardia (6 patients), and during a single atrial extrastimulus (1 patient). None of the six men and nine women, aged 16-61 years, had apparent heart disease. VT lasted for 20 +/- 14 (mean +/- standard deviation) cycles with a cycle length of 235 ms +/- 27 and was generally polymorphic. One patient had ventricular fibrillation. These patients were compared to 15 age- and sex-matched patients studied in the same time period. There was no difference in anterograde effective refractory period of the accessory pathway (316 +/- 92 vs 319 +/- 68 ms), ventricular effective refractory period (218 +/- 12 vs 227 +/- 23), shortest pacing cycle length maintaining 1:1 anterograde conduction over the accessory pathway (306 +/- 132 vs 320 +/- 67) or minimum R-R interval between preexcited beats during atrial fibrillation (280 +/- 68 vs 294 +/- 105). All patients are alive and well over a follow-up interval of 20 +/- 11 months on no antiarrhythmic therapy (13 patients) or on propranolol (2 patients).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Propafenone on Induction and Maintenance of Atrioventricular Nodal Reentrant Tachycardia

Electrophysiologic studies were performed in 10 patients with atrioventricular (A-V) nodal reentrant paroxysmal supraventricular tachycardias (PSVT), before and after intravenous administration of propafenone (1.5 mg/kg). All patients utilized an A-V nodal slow pathway for anterograde conduction and an A-V nodal fast pathway for retrograde conduction of the reentrant impulse. Propafenone depressed retrograde fast pathway conduction which was manifested by: 1) complete V-A block at all ventricular paced cycle lengths after propafenone in 3 cases; 2) increase in mean +/- SD of ventricular paced cycle length producing V-A block from less than 308 +/- 37 ms to 432 +/- 63 ms in the remaining 7 patients. Nine of the 10 patients had induction of sustained PSVT before propafenone. In 7 of the 9, PSVT could not be induced or sustained after propafenone, reflecting depression of the retrograde fast pathway conduction with either absence of atrial echoes (5 patients) or induction of nonsustained PSVT, with termination occurring after the QRS (2 patients). In 1 patient, single atrial echoes were induced before propafenone but none were noted after the drug. In only 2 patients was a sustained PSVT inducible after propafenone. In conclusion, propafenone inhibited induction of sustained A-V nodal reentrant PSVT in most patients, reflecting depression of retrograde A-V nodal fast pathway conduction.     

Fast-Slow Type of Atrioventricular Nodal Reentrant Tachycardia: Horizontal Dissociation of the AV Node During Tachycardia

Two patients with recurrent supraventricular tachycardia are presented. The tachycardia was initiated and terminated by atrial extrastimulation beyond the atrial relative refractory period and the atrial activation sequence during the tachycardia was low to high. The induction of tachycardia was dependent on a critical AH interval. In patient 1 who had ventriculoatrial conduction, the tachycardia was initiated by the premature ventricular stimulation followed by double atrial response. In patient 2 the ventriculoatrial conduction was not observed. In both patients, the unchanged atrial cycle length during the tachycardia with antegrade Wenckebach AH block was observed. When AH block occurred during tachycardia the first AH interval was shorter than the subsequent HA interval. In patient 2 verapamil (5 mg) prolonged the atrial cycle length during tachycardia and rapid intravenous injection of adenosine triphosphate (10 mg) terminated the tachycardia. Oral diltiazem (280 mg/day) suppressed the tachycardia in patient 1. These findings suggest that the mechanism of tachycardia may be fast-slow type of AV nodal reentry in the upper portion of the AV node and this type of arrhythmia has tendency to show incessant form.     

Atrial and Ventricular Vulnerability in a Patient with the Wolff-Parkinson-White Syndrome

An electrophysiologic study was carried out in a patient with the Wolff-Parkinson-White syndrome and a history of spontaneous atrial fibrillation but with no evidence of organic cardiac disease. A single induced premature ventricular depolarization resulted in ventricular tachycardia followed by ventricular fibrillation. Similarly, atrial pacing or premature atrial stimulation resulted in frequent episodes of atrial fibrillation or flutter, The atrial and ventricular effective refractory periods were 180 ms and < 160 ms, respectively, at a driven cycle length of 480 ms. Intravenous administration of procainamide resulted in lengthening of the refractory periods and failure to induce either atriaJ or ventricular arrhythmias with pacing. In most patients with enhanced atrioventricular nodal or accessory atrioventricular nodal bypass, the mechanism of ventricular tachycardia is related to an inordinately rapid ventricular response during supraventricular arrhythmias. In our patient, a unique mechanism was apparent: atrial and ventricular vulnerability to fibrillation was associated with extremely short myocardial effective refractory periods. The relationship of this finding to sudden cardiac death bears further study.     

Acute effects of simvastatin to terminate fast reentrant tachycardia through increasing wavelength of atrioventricular nodal reentrant tachycardia circuit

Simvastatin (SV) leads to reduction of ventricular rhythm during atrial fibrillation on rabbit atrioventricular (AV) nodes. The aim of our study was (i) to determine the frequency‐dependent effects of SV in a functional model, and (ii) to assess the effects of SV to suppress experimental AV nodal reentrant tachycardia (AVNRT). Selective stimulation protocols were used with two different pacing protocols, His to atrial, and atrial to atrial (AA). An experimental AVNRT model with various cycle lengths was created in three groups of perfused rabbit AV nodal preparations (n = 24) including: SV 3 μm , SV 7 μm , and verapamil 0.1 μm . SV increased nodal conduction time and refractoriness by AA pacing. Different simulated models of slow/fast and fast/slow reentry were induced. SV caused inhibitory effects on the slow anterograde conduction (origin of refractoriness) more than on the fast anterograde conduction time, leading to an increase of tachycardia cycle length, tachycardia wavelength and termination of slow/fast reentrant tachyarrhythmia. Verapamil significantly suppressed the basic and frequency‐dependent intrinsic nodal properties. In addition, SV decreased the incidence of gap and echo beats. The present study showed that SV in a concentration and rate‐dependent manner increased the AV effective refractory period and reentrant tachycardia wavelength that lead to slowing or termination of experimental fast AVNRT. The direction‐dependent inhibitory effect of SV on the anterograde and retrograde dual pathways explains its specific antireentrant actions.     

An integrated overview of AV node physiology

The atrioventricular (AV) node generates half of the AV delay needed for blood pumping and filters atrial impulses that could otherwise induce life‐threatening ventricular arrhythmias. It is also a pacemaker and a key target in the treatment of cardiac arrhythmias. The special roles of the AV node primarily arise from its slow conduction, long refractory period, and cellular automaticity. However, efforts to establish the dynamics of these properties and their interaction led to many controversies. In fact, the AV node's behavior is so complex that it seems to escape broadly applicable rules. This review summarizes progresses made in resolving these issues and in integrating the multiple roles of the AV node within a common functional model. Presented evidence shows that the rate‐dependent conduction and refractory properties of the AV node can be reliably characterized and reconciled from nodal responses to S₁S₂S₃ protocols. It also supports the concept that dual pathways constitute a feature of the normal AV node and account for its overall conduction and refractory properties. In this model, the posterior extension and compact node provide the core of the slow and fast pathway, respectively. The transitional tissues and lower nodal bundle provide a common proximal and distal pathway, respectively. These pathways would also support bidirectional conduction. The dual pathway involvement can also be extended to widely variable AV nodal responses, such as Wenckebach cycles, hysteresis, and ventricular response to atrial fibrillation. In brief, the intricate AV nodal behavior may obey a limited set of accessible and definable rules.     

An Analysis of Post-Pacing R-R Intervals During Atrial Fibrillation

Bursts of ventricular pacing at cycle lengths of 350-260 ms were introduced during atrial fibrillation in nine patients, and the post-pacing R-R intervals were compared to the R-R intervals of spontaneous QRS complexes. In eight of nine patients, the mean post-pacing R-R interval was 126-199 ms longer than the mean spontaneous R-R interval (p less than 0.005). Spontaneous runs of aberrantly conducted supraventricular complexes were recorded during atrial fibrillation in one patient. The mean R-R interval following the runs of aberrantly conducted supraventricular complexes was significantly longer than the mean R-R interval of spontaneous narrow QRS complexes (p less than 0.001), but not significantly different than the mean post-pacing R-R interval. The findings of this study suggest that the R-R interval that follows a wide-complex tachycardia during atrial fibrillation is unlikely to be of value in differentiating ventricular tachycardia from aberrantly conducted supraventricular complexes. Analysis of R-R intervals that follow bursts of ventricular pacing suggests that there is likely to be considerable overlap between the R-R intervals that follow runs of ventricular tachycardia and the spontaneous R-R intervals during atrial fibrillation. Furthermore, even when the post-tachycardia R-R interval clearly exceeds the longest spontaneous R-R interval during atrial fibrillation, this is still of little diagnostic value, because a long pause may occur after either a run of ventricular tachycardia or a run of aberrantly conducted QRS complexes of supraventricular origin.     

Unmasking of Retrograde Conduction by Isoproterenol in a Concealed Accessory Pathway

A 52-year-old female with no structural heart disease presented with a right bundle branch block (RBBB)/right axis deviation tachycardia with a cycle length of 300 msec. P waves were not discernible on the surface ECG. Baseline electrophysiology study in the drug-free state revealed no evidence for anterograde or retrograde conducting accessory pathways (APs) or for dual AV node physiology. Retrograde VA block with AV dissociation was present at a ventricular paced cycle length of 600 msec (sinus cycle length of 635–700 msec). AV nodal Wenckebach occurred during decremental atrial pacing at a cycle length of 300 msec. During isoproterenol administration, a left lateral AP with retrograde only conduction became manifest with 1:1 VA conduction to 380 msec. No anterograde AP conduction was present. Orthodromic reciprocating tachycardia with a cycle length of 285–315 msec was easily induced. We conclude that total functional conduction block can exist in APs, and unmasking of total conduction block can be accomplished with isoproterenol. All patients with undiagnosed tachycardias should have full repeat stimulation studies during adrenergic stimulation if the initial baseline evaluation is nondiagnostic.     

Low Energies and Helifix Electrodes in the Successful Ablation of Atrioventricular Conduction

High energies delivered via standard pacing catheter electrodes produce permanent atrioventricular conduction block and generate high pressures. We investigate the use of lower energies and an active fixation electrode. Ten patients with refractory supraventricular tachycardias (six with paroxysmal atrial fibrillation, three with dual AV nodal pathways, and one with a concealed accessory atrioventricular pathway) were treated. A 6F Vitatron Helifix electrode was positioned to give the maximum His bundle deflection. Four shocks of only 50 joules each were delivered at 1-minute intervals. Long-term follow-up showed that seven patients (70%) had persistent complete heart block and two had atrial fibrillation with slower ventricular rates. Nine patients (90%) were symptom-free without antiarrhythmic therapy. Permanent pacemakers were implanted in eight patients. There were no complications resulting from the procedure. Transvenous ablation of atrioventricular conduction can be safely achieved using a Vitatron Helifix electrode and much lower energy values than have been previously employed.     

Syncope in the Wolff-Parkinson-White Syndrome: Incidence and Electrophysiologic Correlates

Syncope in the patient with Wolff-Parkinson-White (WPW) syndrome raises the specter of rapid tachyarrhythmias and the possibility of sudden cardiac death. We reviewed the records of 55 consecutive WPW patients referred for electrophysiologic evaluation of known or suspected arrhythmias to determine the incidence and significance of syncope. Twelve patients (22.6%) reported the occurrence of at least one episode of syncope. In eleven (20%) of these, syncope was preceded by rapid palpitations. Forty-three patients (77.4%) had no syncopal episodes. These two groups did not differ significantly with regard to age, sex, presence of associated cardiac or neurologic disease, drug history or accessory pathway location. There was no significant difference in cycle length of reciprocating tachycardia (syncope = 295.6 ± 59.8 vs non-syncope = 334.5 ± 59.6 ms, p < .5), shortest R-R intervals between preexcited beats (260 ± 78.6 vs 246.7 ± 55.4 ms, p < .5) and average R-R interval (364.4 ± 37.9 vs 367.4 ± 77.5 ms, p < .5) measured during atrial fibrillation. The anterograde effective refractory period of the accessory pathway (292.1 ± 31.9 vs 299 ± 58.1 ms, p < .5) and the shortest cycle length with 1:1 conduction over the accessory pathway (306.7 ± 75 vs 289.1 ± 77.5 ms, p < .5) similarly did not differ. We conclude that syncope occurs in approximately 20% of patients with the Wolff-Parkinson-White syndrome referred for assessment of tachycardia. Patients with syncope do not have distinct clinical features or a more malignant electrophysiologic profile, suggesting that other extracardiac factors may play an important roe in the genesis of syncope in this group.     

Double Atrial Responses to a Single Ventricular Impulse in Long RP' Tachycardia

Double atrial responses (DARs) to a single ventricular impulse have been described in patients with long RP' tachycardia. To define the determinants for the occurrence of DARs. 8 cases with long RP' tachycardia were examined. The mechanism of long RP' tachycardia was the orthodromic atrioventricular reciprocating tachycardia (AVRT) involving a slow conducting concealed accessory pathway in 4 cases and uncommon (fast-slow) type of atrioventricular nodal reentrant tachycardia (AVNRT) in the other 4 cases. Programmed and rapid ventricular pacing was performed during sinus rhythm and also rapid ventricular pacing during tachycardia (i.e., entrainment). The retrograde effective refractory period (ERP) and the retrograde maximal 1:1 conduction rate of the fast and slow conducting pathways were examined. In 1 of the 4 cases with AVRT, DARs were observed during programmed and rapid ventricular pacing, performed during sinus rhythm and also during entrainment. In 1 of the 4 cases with AVNRT, DARs were observed only during entrainment. The determinants of DARs in cases with long RP' tachycardia were: (1) presence of two different retrogradely conducting pathways; (2) short ERP of the retrograde fast and slow conducting pathways and a short minimal pacing cycle length at which 1:1 ventriculoatrial conduction occurs via these pathways; (3) crucial conduction delay in the slow conducting pathway: and (4) preexisting antegrade unidirectional block in the slow conducting pathway or the antegrade block in the slow conducting pathway produced by collision with a previous retrograde impulse during entrainment.     

Computer Model of the Atrioventricular Node Predicts Reentrant Arrhythmias

Introduction: Following atrial premature beats, the AV node may exhibit sustained reentrant tachyarrhyth-mias, isolated echo beats, or discontinuities in the recovery curve (the plot of conduction time versus atrial cycle length). A computer model was used to examine the hypothesis that spatial variation of AV nodal passive electrical resistance may account for these phenomena. Methods and Results: A computer model of a rectangular lattice of elecirotonically linked elements whose ionic kinetics simulated nodal ionic flux was developed. the model showed that there exists a resistance value that minimizes the effective refractory period, because high resistance prevents depolarization of distal elements, while low resistance allows leakage of depolarizing current by electrotonic transmission, preventing activation of proximal elements. High resistances stabilized reentry by slowing conduction. Simulations incorporating equal resistance values between elements predicted increased AV nodal conduction times with increasing prematurity of atrial impulses. A model with a gradual change in resistance between fibers produced discontinuities and tachycardia, but not both simultaneously. Uniform anisotropy produced preferential transverse block, leading to echo beats and “fast-slow” tachycardia, but not recovery curve discontinuities. Nonuniform anisotropy could produce reentry, but tachycardia often occurred without discontinuities. Dividing the lattice into two electrotonically linked parallel pathways with different resistance values (“dual pathway model”) predicted recovery curve discontinuities, echo beats, and tachycardia. At critical atrial cycle lengths, only the (high resistance) slow pathway conducted antegradely, while the fast pathway conducted retrogradely, to generate the typical “slow-fast” tachycardia. Responses of the dual pathway model to ablation were consistent with clinical data, including the previous observation of a decrease in fast pathway effective refractory period after slow pathway ablation. Conclusion: Differences in passive electrical resistance of electrotonically linked dual pathways within the AV node may account for functional longitudinal dissociation, reentrant arrhythmias, and responses to catheter ablation therapy.     

Programmed Chest-Wall Stimulation to Evaluate the Progress of A-V Block After Pacemaker Insertion in Patients with Trifascicular Disease

Twenty six patients (aged 46-80, mean age 64) with bifascicular block in the presence of prolonged H-V interval (trifascicular block), were followed for an average of 31 months after inserting an R-wave inhibited pacemaker (PM) because of syncope and/or dizzy attacks. The underlying rhythm was evaluated at 4-6-month intervals by three different techniques: 1) 12-lead ECG when intrinsic patient rate was faster than PM rate; 2) abrupt PM inhibition (APMI) by the rapid chest-wall stimulation technique, and 3) progressive PM inhibition (PPMI) using a programmed chest-wall stimulation technique capable of decreasing the PM rate gradually to 30 beats/min before complete PM inhibition. In addition, the PPMI allowed the underlying rhythm to be induced and sustained and properly evaluated without any discomfort to the patient. Following PM insertion, 4 patients (15%) developed complete heart block after a mean follow-up of 43 months, and one patient (4%) developed 2nd degree 2:1 A-V block (VX) after 83 months. The P-R interval increased in 5 patients (19%) and decreased in 2 (8%). No change of A-V conduction was found in 9 patients (34%). Three patients developed low atrial rhythm, atrial flutter and atrial fibrillation, respectively (12%). After PM insertion 2 patients still complained of dizziness. None reported syncope. Two patients died during follow-up, both of congestive heart failure (8%). By detection of intrinsic rhythm it was recognized that a long symptomatic paroxysmal phase may precede the development of chronic complete A-V block. Therefore, the insertion of a permanent PM is recommended in patients with unexplained neurologic symptoms and trifascicular disease, without waiting for documented episodes of complete A-V block.     

Incessant Reciprocating Atrioventricular Tachycardia

The case of a patient suffering from incessant supraventricular tachycardia is presented. The electrophysiological study showed the presence of an accessory atrioventricular (A-V) bundle with nodal-like properties and long conduction times. This structure was used as the retrograde arm of the tachycardia circuit. Tachycardia was intermittent at rest, but had a sustained character during slight exercise. Administration of atropine and isoproterenol failed to sustain the arrhythmia and spontaneous initiation during sinus rhythm was no longer observed. During handgrip exercise a sustained tachycardia developed immediately. During ventricular stimulation a dual atrial response to a single paced ventricular premature beat was repeatedly observed, proving the availability of two separate A-V pathways for retrograde conduction. The case illustrates the labile nature of this type of accessory pathway, and suggests that autonomic changes can play an important role in the initiation, maintenance, termination, or even spontaneous cure of tachycardia in patients with this anomaly.     

Inhibition of ventricular stimulation in patients with dual chamber pacemakers and prolonged AV conduction

Episodes of repetitive P wave undersensing have been described in dual chamber pacemakers due to automatic extension of the postventricular atrial refractory period (PVARP). Pacemaker stimulation was completely inhibited despite the presence of adequate P waves. This study sought to determine whether cycles of repetitive P wave undersensing occur even in the absence of PVARP extension. Two-hundred fifty-five patients were investigated after DDD or VDD pacemaker implantation for intermittent atrioventricular (AV) block. Forty-six episodes of repetitive atrial undersensing were found during 24-hour Holter ECG in nine patients. Pacemaker syndrome-like symptoms occurred. Episodes were elicited by atrial or ventricular premature contractions when (1) native AV conduction was present but considerably prolonged, (2) intrinsic sinus rate exceeded pacemaker intervention rate, and (3) native AV interval plus PVARP exceeded sinus cycle length. Programming of a particularly short AV interval and PVARP helped to reduce the incidence of repetitive P wave undersensing. Patients with dual chamber devices and prolonged native AV conduction are prone to develop episodes of output inhibition. Standard timing cycles may be inappropriate in these patients.     

The efficacy, electrophysiologic and electrocardiographic effects of intravenous pirmenol, a new class I antiarrhythmic agent, in patients with ventricular tachycardia: comparison with procainamide

The electrophysiologic and electrocardiographic effects of intravenous pirmenol were compared with intravenous procainamide in 17 patients with symptomatic ventricular tachycardia. Pirmenol was found to prolong the PR interval, the QRS duration, the QTc interval, the HV interval, the atrial effective refractory period, and the ventricular effective refractory period. The sinus cycle length decreased following pirmenol administration. The sinus node recovery time, the PA interval, the AH interval, the Wenckebach cycle length, and the AV nodal ERP were unchanged. In patients whose ventricular tachycardias remained inducible on pirmenol, the cycle length was significantly prolonged compared to baseline. These changes were similar to those seen following the administration of procainamide. All 17 patients had sustained ventricular tachycardia inducible during programmed ventricular stimulation in the baseline state. In four patients the ventricular tachycardia was suppressed with both primenol and procainamide. In the remaining 13 patients ventricular tachycardia remained inducible on procainamide. Of these 13 patients, an additional two patients had their ventricular tachycardias rendered noninducible on pirmenol. In conclusion: (1) the electrophysiologic and electrocardiographic effects of pirmenol are similar to those of procainamide; (2) although ventricular tachycardia inducibility following procainamide was similar to that of pirmenol, an occasional patient with ventricular tachycardia inducible on procainamide had ventricular tachycardias suppressed on pirmenol.     

Beat-to-beat variability of echocardiographic measurements of left ventricular end diastolic diameter and performance.

Echocardiographic measurements of left ventricular dimensions and performance correlate well with similar data from other sources. However, little attention has been paid to the beat-to-beat variations in these parameters in individual subjects. Considerable variability in measurements of left ventricular end diastolic diameter (EDD), R-R interval, mean circumferential fiber shortening velocity (V_cf), and ejection fraction (EF) has been demonstrated in subjects in both sinus rhythm and atrial fibrillation. The coefficients of variation have varied from 2.5 to 9 percent, 2.1 to 11.2 percent, 4.4 to 11.0 percent, and 3.4 to 7.8 percent, respectively, in different individuals in sinus rhythm and from 2.0 to 7.9 percent, 2.1 to 20.7 percent, 4.9 to 30.0 percent, and 1.9 to 90.0 percent, respectively, in different patients in atrial fibrillation. Recent ultrasound studies of the interrelationships among preload, afterload, cycle length, and indices of left ventricular performance have yielded variable results. In this study the relationships between both EDD and R-R interval and echocardiographic measurements of left ventricular function were analyzed in individual subjects in both sinus rhythm and atrial fibrillation. Changes in EDD and, to a lesser extent, cycle length were shown to be accompanied by predictable changes in indices of left ventricular function. EDD correlated better than did R-R interval with V_cf and EF in 8 of 10 and 10 of 10 normal subjects, respectively, and in 9 of 11 and 7 of 11 patients in atrial fibrillation, respectively. The data suggest that preload has a more important effect than cycle length on left ventricular performance.     

Dose-ranging studies of clofilium, an antiarrhythmic quaternary ammonium

Clofilium, a new quaternary ammonium antiarrhythmic without apparent ganglion-blocking effect, was evaluated in 25 patients, 22 with a history of ventricular arrhythmias and three with paroxysmal supraventricular arrhythmias. The study, including programmed atrial and ventricular stimulation, was carried out before and after infusion of 20 to 240 micrograms/kg IV as a single dose. Continuous Holter monitoring was carried out the day before the study through the fourth day after study, and laboratory parameters were monitored for up to 2 wk. There were no changes in intra-atrial and intraventricular conduction times or in AH or HV intervals. There were increases in QT interval, atrial effective refractory period, and ventricular refractory period. The atrioventricular nodal effective refractory period was unchanged. No side effects were noted, nor were changes in blood pressure or laboratory parameters. Monitoring revealed no change in frequency of premature ventricular complexes between the 24 hr before drug infusion and the 96 hr thereafter. In one patient refractoriness of the His-Purkinje system was increased and in two patients atrial fibrillation converted to sinus rhythm after clofilium. Three patients had sustained ventricular tachycardia with programmed stimulation before clofilium infusion; none had more than three repetitive ventricular responses after it. Clofilium increases atrial and ventricular effective refractory period without changing conduction time and, despite no apparent change in premature ventricular complex frequency, it can abolish the ability to induce ventricular tachycardia by programmed stimulation and is also well tolerated.     

Relationship between beat to beat interval and left ventricular function in patients with atrial fibrillation

In atrial fibrillation, the relation between the rhythm and volume of the pulse has long been of interest. However, changes in preload in this condition have not been fully addressed since beat to beat measurement of filling volume have been difficult until recently. In the present study, we evaluated left ventricular outflow and inflow velocity using pulsed Doppler echocardiography and correlated these results with the R-R interval in the individual patient. The study population consisted of 12 patients with atrial fibrillation, aged 36 to 69 years (mean 54 years). The etiology of atrial fibrillation was idiopathic in 10 and 2 patients had dilated cardiomyopathy. Stroke and filling volume were calculated as a pruduct of the flow velocity integral of left ventricular outflow and inflow velocity, and the cross-sectional area of aortic and mitral annulus, respectively. In 10 patients with idiopathic atrial fibrillation, significant positive correlations were observed between the preceding R-R interval and both the stroke volume and the filling volume of the preceding beat when the R-R interval was shorter than 600 msec. Stroke volume and filling volume of the preceding beat were almost constant, independent of the preceding R-R interval when the preceding R-R interval was longer than 600 msec, the interval necessary for the completion of the preceding rapid filling. In the same preceding R-R interval, a larger stroke volume was observed in a shorter pre-preceding R-R interval. In 2 patients with dilated cardiomyopathy no relationship could be observed between the preceding R-R interval and the filling volume of the preceding beat or the stroke volume. In patients with a normally functioning left ventricle (idiopathic atrial fibrillation), reduced cycle length and filling volume in the preceding cardiac cycle appear to be the underlying cause of the regulation of stroke volume, dependent on Starling's law. However, in patients with dilated cardiomyopathy no significant correlation was observed between the preceding R-R interval and both the filling volume of the preceding beat and the stroke volume. In these patients the left ventricle may have limited contractile reserve and altered diastolic re-coil forces possibly due to degenerative changes of myocardium. Pulsed Doppler echocardiography provides a non-invasive method of evaluating the instantaneous changes in left ventricular flow dynamics caused by atrial fibrillation and understanding its fundamental mechanism.