Tachycardia and bradycardia-dependent bundle branch block alternans: clinical observations.

Eleven patients with tachycardia-dependent, bradycardia-dependent, or "pseudobradycardia-dependent" bundle branch block (BBB) alternans were studied. This classification is based on the following criteria: 1) When alternans is initiated by a sudden acceleration in ventricular rate, or it appears with aberration of the second beat after a pause, the alternans is tachycardia-dependent and results from a 2:1 bidirectional block in the affected bundle branch. 2) When alternans begins with the aberrant complex terminating a pause it is bradycardia-dependent; such an alternans results from alternating bundle branch cycle lengths and refractoriness, possibly produced by alternating transseptal retrograde penetration of the affected bundle branch. 3) In cases referred to as "pseudobradycardia-dependent BBB" alternans, a change from alternans to persiscardia-dependent BBB" alternans, a change from alternans to persistent BBB occurs as the cycle lengthens; however, the disappearance of BBB with further increase of the cycle length proves the tachycardia-dependence of the conduction defect.     

Bradycardia-dependent bundle branch block Relation to supernormal conduction and phase 4 depolarization

An electrocardiogram is presented in which spontaneous conversion of 2:1 block with first degree block and incomplete left bundle branch block resulted in 3:2 block with normal conduction of the QRS complex after the short R-R interval. Alternation of rate and block with every second beat is a variation of previously described bradycardia-dependent bundle branch block.

Phase 4 depolarization and supernormal conduction are inseparable concepts, and both may play a causal role in bradycardia-dependent bundle branch block. Criteria for recognition of this type of block should not disqualify cases in which supernormal conduction may be present, particularly since proximity of the QRS interval to the preceding T wave may not be an adequate test for supernormal conduction in clinical situations.

A knowledge of phase 3 and phase 4 events allows one to relate different types of clinical aberrance, from premature aberrance through early beat “normalization,” as in bradycardia-dependent bundle branch block, to normal rate aberrance as in typical bundle branch block and, finally, to escape beat aberrance.     

Disappearance of bundle branch block with slowing of normal heart rate

Four patients are presented with varied mechanisms of converting bundle branch block to normal ventricular conduction with slowing of normal heart rate. One patient had a relatively constant range of critical heart rates for left bundle branch block, incomplete left bundle branch block, and normal conduction during a three-year period of observation.This report emphasized that bradycardia-dependent normalization of bundle branch block is not uncommon.     

Local activation variability during monomorphic ventricular tachycardia in the dog.

OBJECTIVE: The aim was to determine the beat to beat variability in local activation time during sustained monomorphic ventricular tachycardia in a canine model of experimental myocardial infarction. METHODS: A digital template matching algorithm was developed for detecting subtle beat to beat variability in local activation timing at each of multiple ventricular sites. Ten electrically induced sustained ventricular tachycardia episodes, mean cycle length 211 (SD 40) ms, were endocardially and epicardially mapped in mongrel dogs weighing 15-20 kg. Digitised data were analysed for beat to beat local activation time variability. Similar data recorded during ventricular pacing at comparable rates and during sinus rhythm served as controls. RESULTS: The overall mean variability of local activation time for all 10 ventricular tachycardias was 3.2(1.6) ms, range 1.8(1.1) ms to 4.7(2.8) ms, in contrast to the overall mean variability of 0.2(0.4) ms (p = 0.0001) for ventricular pacing and 0.7(0.6) ms (p = 0.0001) for sinus rhythm. Oscillations in local activation time manifested alternans type periodicity during seven of 10 ventricular tachycardias independent of any alternans in local electrogram morphology. CONCLUSIONS: During sustained, monomorphic ventricular tachycardia, beat to beat variability and alternans type oscillations in local activation time are common and may be an intrinsic property of re-entry since they are negligibly small during ventricular pacing.     

Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length

Clinical and experimental evidence relate action potential duration(APD) alternans to ischaemic heart disease and ventricular arrhythmias.The present investigation was performed to study the quantitativerelationship between APD alternans and the degree ofischaemia,loading conditions and cycle length (CL) in an intact heart. Monophasic action potentials (MAP) were simultaneously recordedby contact electrodes from two left (LV) undone right ventricular(RV) sites in 20 Langendorff-perfused rabbit hearts. The preparationswere subjected to global ischaemia at flow rates ranging from40% of normal flow to complete cessation of flow. Pacing wasperformed at either constant or regularly changing CL. The magnitudeof APD alternans was expressed as beat-to-beat differences inaction potential duration of two consecutive MAPs. During normalper fusion, neither very fast pacing at a CL of 200 ms nor periodicalrate switches resulted in persistent APD alternans. Pacing ata constant CL of 800 ms did not induce A PD alternans at completecessation of flow for 6 min. However, alternans developed progressivelyat a constant CL of 400 ms after 2.8±0.3 min of completeischaemia at the pre-loaded LV, andafter 4.6±0.4 minat the unloaded RV (P<0.01). The reduction of preload atthe LV from 15 to 5 mmftg end-diastolic pressure delayed developmentof APD alternans from 2.8±0.3 min to 4.3±0.4 min(P < 0.05) at 400 ms CL. Following graded under per fusionof 40%, 20% and 10% of initial flow, persistent APD alternansdeveloped in relation to the degree of flow reduction and increasedprogressively with duration ofischaemia. APD alternans at theLV always preceded the onset of APD alternans at the RV. Inexperiments with identical flow rates the shortest CL of 200ms resulted in the greatest and earliest initiation of APD alternanscompared to the longer CL (P<0.01, P<0.001). An increasein CL from 400 to 800 ms immediately abolished APD alternans,generated by the shorter CL, at any time during the 6 min periodof complete ischaemia. Similarly, increasing the cycle lengthfrom 200 or 400 to 600 ms eliminated APD alternans up to 6 minof ischaemia and significantly reduced its magnitude between7 and 10 min within a few beats. We conclude that persistent APD alternans is a characteristicfinding in the rabbit heart during global ischaemia. It is asensitive parameter of the severity of ischaemia and dependson the degree and duration of ischaemia as well as on the preload.The CL appears to have an independent effect on the generationof APD alternans, which is functionally separate from the effectof CL on the ischaemic burden. An eventual impact of these observationscould be the application of APD alternans as a diagnostic toolin electrophysiological examinations of myocardial ischaemiain experimental and clinical settings.     

Hemodynamics and myocardial oxygen metabolism of pulsus alternans in patients with dilative cardiomyopathy

The hemodynamic and myocardial energetic changes due to pulsus alternans were investigated by left and right heart catheterization and by oxygen consumption measurements in three patients with dilative cardiomyopathy. In all three patients, pulsus alternans developed after intravenous administration of the phosphodiesterase inhibitor enoximone. Following enoximone (Patients 1/2/3), left ventricular peak systolic pressure was reduced, in the respective patients, from 100/103/115 mmHg (normal beat) to 91/96/94 mmHg (strong beat) and further to 59/80/85 mmHg (weak beat); left ventricular end-diastolic pressure was reduced from 24/23/22 mmHg (normal beat) to 5/10/6 mmHg (strong beat) and further to 3/7/4 mmHg (weak beat). Cardiac output increased by an average of 16%. Heart rate increased by an average of 12%. Stroke work (during pulsus alternans mean between strong and weak beats) did not change (less than 5%) in any of the three patients. Arterial-coronary-sinus oxygen content difference decreased by 5%/13%/22, respectively. Myocardial oxygen consumption per beat decreased in Patient 1 by 8%, in Patient 2 by 8% and remained unchanged in Patient 3. It is concluded that pulsus alternans occurred in consequence of alternating systolic performance. The alternation in systolic performance most probably resulted from a disturbance in excitation-contraction coupling induced by enoximone. The pronounced reduction of left ventricular preload following administration of enoximone may have augmented further the differences between the strong and the weak beat. A disturbance in myocardial oxygen metabolism was ruled out as the cause of pulsus alternans in these patients.     

Alternating bundle branch block

Mechanisms postulated for alternating bundle branch block are incomplete-and cycle-length-dependent-block in both the right and left bundle branches. A patient with severe longstanding cardiac conduction disease who developed alternating bundle branch block during treatment for advanced ischemic heart disease and malignant ventricular arrhythmia is presented. In this patient alternation was induced by atrial premature beats as well as spontaneous and pacemaker induced premature ventricular beats. Right bundle branch block which followed a premature atrial beat resulted from the longer refractory period of the right bundle. The maintenance of right bundle branch block at long cycle lengths was presumed to be due to continuous retrograde reentry. This was terminated when a pause following a premature beat allowed functional recovery of the right bundle branch. This patient died suddenly at home with a functioning pacemaker, demonstrating the high risk of death from ventricular dysrhythmia in the post myocardial infarction patient with a new conduction defect.     

Bundle branch block on alternate beats during atrial fibrillation

This article reports a case of tachycardia-dependent right bundle branch block (RBBB) occurring during atrial fibrillation. In some sections of the recording, an alternans occurs between complexes with a complete RBBB pattern and complexes showing normal intraventricular conduction or incomplete RBBB. Alternans is frequently observed during phases of fast and nearly regular rhythm, but it occurs even in the presence of a markedly irregular ventricular response. The RBBB alternans associated with short and regular RR intervals is likely to represent a manifestation of 2:1 bundle branch supernormal conduction, whereas alternans occurring with irregular cycles expresses a complex interaction between the RR cycle length and some mechanisms affecting intraventricular conduction, such as tachycardia-dependent bundle branch block, supernormal conduction and concealed retrograde activation of the anterogradely blocked bundle branch (the so-called "linking" phenomenon).     

Significance of pacing cycle lengths in manifest entrainment of orthodromic circus movement tachycardia by ventricular pacing

The physiology of entrainment of orthodromic circus movement tachycardia (CMT) was studied using ventricular pacing during 18 episodes of induced CMT in 7 patients with atrioventricular (AV) accessory pathways. The first paced impulse was delivered as late as possible in the tachycardia cycle (mean 88 +/- 5% of the spontaneous cycle length [CL]). Entrainment was demonstrated by the following criteria: 1:1 retrograde conduction via the accessory pathway; capture of atrial, ventricular and His bundle electrograms at the pacing rate; and resumption of tachycardia at its previous rate after cessation of pacing. The number of ventricular paced impulses ranged from 5 to 14 (mean 8 +/- 3), and entrainment occurred in 2 to 7 paced cycles (mean 4 +/- 2). Orthodromic activation of a major part of the reentry circuit (manifest entrainment) was demonstrated during 9 episodes by the occurrence of His bundle electrogram preceding the first CMT QRS at the time anticipated from the last paced beat. In the 9 other episodes, persistent retrograde His bundle activation and AV nodal penetration by each paced impulse caused a delay (mean 79 +/- 25 ms) in activation of the His bundle preceding the first CMT QRS after the last paced beat. The mean pacing CL achieving manifest entrainment was 92 +/- 3% of the tachycardia CL, compared with 84 +/- 3% for retrograde AV nodal penetration (p less than 0.01). In conclusion, manifest entrainment of orthodromic CMT can be demonstrated by ventricular pacing at very long CLs; shorter CLs may cause CMT termination due to retrograde AV nodal penetration.     

Effect of pacing rate and intensity on mechanical alternans amplitude

The aim of this paper is to report the effect of variations in stimulus frequency (SF) and intensity (SI) of right ventricular pacing on the left ventricular mechanical alternans (MA) amplitude, (MAA) which is defined as 100 (S-W)/S, where S is the ventricular pressure of the strong beat and W that of the weak beat. In 30 dogs the right ventricle was paced at SF ranging from the sinus frequency up to 400/min and at SI ranging from threshold up to 270 mA, while the left ventricular pressure was recorded. Increasing SF at near threshold values of SI resulted in an increase of MAA up to a maximal value. Further increase in SF might cause a diminution of MAA. A slight raise in SI then could increase abruptly MAA. Further increase in SI while keeping a constant SF caused a reduction in MAA which was an approximate logarithmic function of SI. Digoxin, adrenaline or calcium reduced or abolished MA, even in experiments which left atrial and mean aortic pressure were kept constant by suitably placed open-air reservoirs. Pindolol increased MAA. Raising the height of the atrial constant pressure reservoir reduced the MAA while lowering its height increased the MAA. Changing the height of the aortic constant pressure reservoir did not produce consistent changes in MAA.The effects of SF and SI on the MAA could possibly be explained on the basis of the hypothesis that the MA is a complex oscillatory phenomenon. A different, number of myocardial fibers contracting at each, systole depending on SF and SI may play a role in the genesis of MA and may explain the present findings. It is concluded that, in addition to hemodynamic and inotropic factors, stimulating the ventricles at a high SI may ameliorate the MA at a given heart rate.     

Functional Bundle Branch Block as a Delayed Manifestation of Retrograde Concealment in the His-Purkinje System

Delayed Manifestation of Retrograde HPS Concealment. Introduction: The mechanism of functional bundle branch block induced at the onset of supraventricular tachycardia (SVT) is well established. However, no data exist to address the underlying mechanism of functional bundle branch block occurring in the second beat of SVT, when the first beat is conducted with a narrow QRS morphology and preceded by ventricular stimulation. Methods and Results: Two patients showing such a phenomenon form the basis of this report. Patient 1 with AV nodal reentrant tachycardia of the common variety persistently demonstrated functional right bundle branch block in the second SVT complex when a short train of ventricular pacing was introduced during SVT. This occurred without any discernible change in the SVT cycle length. Patient 2 bad a manifest posteroseptal accessory pathway and inducible orthodromic reentrant tachycardia. Functional bundle branch block during propagation of the second SVT complex invariably occurred either in the left bundle when SVT was induced by a bundle branch reentrant complex during premature ventricular stimulation, or in the right bundle when SVT was induced with a short train of ventricular pacing. The development of functional bundle branch block was preceded by minimal or no cycle length variations in the His-bundle inputs. Conclusion: These observations suggest that the type of functional bundle branch block occurring in the second SVT complex as a de novo phenomenon may be related to the relative timing of the retrograde penetration of the right versus left bundle during ventricular pacing or bundle branch reentrant complex. Therefore, due to its longest cycle length of activation and refractoriness, the earliest site of retrograde penetration is the most likely site of functional block during propagation of the second SVT complex. This delayed manifestation of retrograde concealment may provide new information regarding the electrophysiologic behavior of the His-Purkinje system.     

Role of cycle length, cycle length alternans, and electrocardiographic lead in electrical alternans with rapid atrial pacing

The role of cycle length and cycle length alternans in the induction of tachycardia-related QRS electrical alternans was investigated using an atrial pacing protocol in 16 patients. Pacing was performed at a cycle length less than 400 ms in 5 patients, greater than 400 ms in 5 and at both in 6 with 0, 6, 10, 20, 40 and 60 ms of atrial cycle length alternans. A 12-lead electrocardiogram and high right atrial, His bundle and right ventricular apical electrograms were simultaneously recorded after 30 to 60 seconds of pacing. Alternans was produced in 88% of patients. Alternans was 3 times more frequent at short (less than 400 ms) than long paced cycle lengths (greater than 400 ms) (66% vs 22%, p less than 0.0001). Alternans increased with increasing cycle length alternans and occurred with very little (less than or equal to 10 ms) atrioventricular nodal, His-Purkinje and ventricular cycle length alternans when paced cycle length was short. Alternans was more frequent in the precordial than the limb leads (45% vs 17%, p less than 0.001) and was most frequent in V3 and V2 (sensitivity 69% and 65%) and least frequent in leads I and aVL (sensitivity 4% and 10%). More leads per electrocardiogram showed alternans at short compared with long paced cycle lengths and the number of leads per electrocardiogram increased with increasing cycle length alternans. Occurrence of alternans was highly related to QRS amplitude by Spearman rank correlation (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Postextrasystolic transient contractile alternans in canine hearts

Summary We found that postextrasystolic potentiated contractility after a spontaneous extrasystole most frequently decayed as a transient alternans over several beats in excised, cross-circulated, atrially paced canine hearts. This type of heart preparation, which we have been using consistently in mechanoenergetic studies, had normal coronary blood perfusion pressure as well as flow and mechanoenergetic performance. Spontaneous atrial and ventricular extrasystoles occurred occasionally in every heart. Arrhythmic changes in left ventricular (LV) pressure at a fixed volume reflected corresponding changes in contractility. We analyzed nearly 3,600 cases of postextrasystolic potentiation in 68 hearts; 84% decayed as transient alternans, 6% decayed exponentially, and 10% belonged to neither type. We found that a postextrasystolic compensatory pause always preceded the transient alternans after either an atrial or ventricular extrasystole at any constant atrial pacing rate (85–188 beats/min). The decay was either exponential or nonalternating when the pause did not exist after an atrial extrasystole during occasional pacing failure. Therefore, the compensatory pause after either an atrial or ventricular extrasystole seems essential for the postextrasystolic transient alternans of LV contractility in the type of canine heart preparation we have been using.Part of this study was presented in 1993 at a meeting of the Japanese Pathophysiology Society. The abstract of the presentation appeared in Jpn J Pathophysiol 1: 45, 1993.     

Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine.

The ventricular tachyarrhythmias associated with the LQT3 syndrome are typically bradycardia-dependent. However, some episodes can be associated with exercise or emotional stress, suggesting a different arrhythmogenic mechanism when sympathetic activity predominates. This study examined the potential arrhythmogenic mechanisms during periods of autonomically mediated transient heart rate acceleration in a canine anthopleurin-A model of LQT3 syndrome. Using plunge needle electrodes, transmural unipolar electrograms of the left ventricle were recorded from endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) sites. The activation-recovery interval (ARI) was measured to estimate local refractoriness. The cardiac cycle length was gradually shortened by cessation of vagal stimulation (vagal stimulation protocol (VSP)), and intramural electrograms and onset mode of ventricular tachyarrhythmias were analyzed in 7 experiments. The VSP was performed 8 times before and 5 times after administration of mexiletine in each experiment. Before mexiletine, vagal stimulation slowed the heart rate and created large transmural ARI dispersion because of a greater ARI prolongation at Mid rather than Epi/Endo sites. After cessation of vagal stimulation, unipolar electrograms started to show ARI alternans and ventricular premature beats developed sporadically. Sustained ventricular tachyarrhythmias were induced in 12 of the 56 trials of the VSP. Initiation of ventricular tachyarrhythmias was associated with delayed conduction at Mid/Endo sites. Mexiletine attenuated transmural ARI dispersion, and neither ARI alternans nor ventricular tachyarrhythmias was observed during all 35 trials of the VSP after mexiletine administration. Heart rate acceleration induced by an abrupt shift to a state of predominant sympathetic activity enhances arrhythmias in this LQT3 model. Mexiletine homogenizes ventricular repolarization, suppresses premature complexes and was antiarrhythmic during ventricular tachyarrhythmias induced by the VSP.     

Alternans of action potential duration after abrupt shortening of cycle length: differences between dog Purkinje and ventricular muscle fibers

The purpose of this study was to determine whether the alternans of action potential duration (APD) occurring in Purkinje and ventricular muscle fibers after an abrupt shortening of cycle length can be explained by the two factors controlling the cycle length-dependent APD changes (i.e., restitution and memory effect). Action potentials were recorded simultaneously from dog Purkinje fibers and ventricular muscle fibers using conventional microelectrode techniques. APD change during alternans was dependent on the preceding diastolic interval in the same manner as during restitution in Purkinje fibers but not in ventricular muscle fibers. The course of memory change was not affected by the presence of alternans in either fiber type. In Purkinje fibers, APD alternans was attenuated by a Ca2+ channel blocker, nisoldipine (2 X 10(-6) M), and augmented by a Ca2+ channel agonist, Bay K 8644 (3 X 10(-8) M). These effects were attributed to the changes in the kinetics and the amplitude of restitution. In ventricular muscle fibers, APD alternans was always preceded and accompanied by alternans of action potential shape. Alternans of both action potential shape and APD was suppressed by nisoldipine (2 X 10(-6) M) and attenuated by Bay K 8644 (3 X 10(-8) M). These results show that in Purkinje fibers, APD during alternans can be explained by restitution and memory effect. However, in ventricular muscle fibers, the mechanism of APD alternans is linked to factors controlling action potential shape. These findings are compatible with the hypothesis that APD alternans in Purkinje fibers depends on the differences in the recovery of membrane currents generated by the preceding action potential and in ventricular muscle fibers on the differences in the concentration and/or handling of intracellular calcium.     

Tachycardia- and bradycardia-dependent atrioventricular block: observations regarding the mechanism of block

A case of paroxysmal bradycardia- and tachycardia-dependent atrioventricular (AV) block is described in a patient with right bundle branch block. The His bundle recordings demonstrated the site of the AV block to be distal to the His bundle recording site (probably in the left bundle branch). Whereas AV block distal to the His bundle occurred at an atrial paced cycle length of 700 ms, intact ventriculoatrial (VA) conduction was present up to a ventricular paced cycle length of 400 ms. Resumption of AV conduction was dependent on a critical HH or RH (in case of escapes) interval. These findings suggest that the bradycardia-dependent block is related to a time-dependent decrease in the amplitude of the current intensity of the proximal segment during late diastole. Spontaneous diastolic depolarization during late diastole resulted in impaired anterograde (AV) conduction but facilitated retrograde (VA) conduction. These findings are consistent with experimental "in vitro" observation in the sucrose gap model of AV block.     

Effects of the ventricular premature beat on the alternation of the repolarization phase in ischemic myocardium during acute coronary occlusion in dogs

Effects of ventricular premature beats (VPB) on the alternans of the ST segment (ST alternans, STA) in the epicardial ECG and of the monophasic action potential (MAP) were examined during acute coronary occlusion in dogs. When STA was recorded simultaneously from four different points it was discordant in most cases. The discordant STA was accompanied by discordant alternation of the repolarization phase of MAP. A VPB transformed the discordant alternans into a concordant one and potentiated the degree of alternans. Transient prolongation or shortening of the cycle length showed effects similar to those of the VPB. The concordant alternans which was transformed from a discordant one by a VPB was not remarkably potentiated by a VPB, or by prolongation or shortening of the cycle length. It is possible that the transformation of the discordant alternans into a concordant one may contribute to the potentiation of STA by a VPB, and that the effects of VPB are due to the effects of the compensatory pause as well as the short cycle length associated with the VPB.     

Alternans of action potential duration and amplitude in rabbits with left ventricular dysfunction following myocardial infarction

T-wave alternans may predict the occurrence of ventricular arrhythmias in patients with left ventricular dysfunction and experimental work has linked discordant repolarization alternans to the induction of re-entry. The aim of this study was to examine the occurrence of transmural repolarization alternans and to investigate the link between alternans and ventricular arrhythmia in rabbits with left ventricular dysfunction following myocardial infarction. Optical mapping was used to record action potentials from the transmural surface of left ventricular wedge preparations from normal and post-infarction hearts during a progressive reduction in pacing cycle length at 30 and 37°C. Data were analyzed using custom software, including spectral analysis. There were no significant differences in baseline transmural electrophysiology between the groups. Post-infarction hearts had a lower threshold for both repolarization alternans (286 vs. 333 bpm, p<0.05) and ventricular arrhythmias (79 vs. 19%, p<0.01) during rapid pacing, which was not accounted for by increased transmural discordant alternans. In VF-prone hearts, alternans in optical action potential amplitude was observed and increased until 2:1 block occurred. The degree of optical action potential amplitude alternans (12.0 ± 7.0 vs. 1.8 ± 0.3, p<0.05), but not APD(90) alternans (1.4 ± 0.6 vs. 1.1 ± 0.1, p>0.05) was associated with VF inducibility during rapid pacing. Post-infarction hearts are more vulnerable to transmural alternans and ventricular arrhythmias at rapid rates. Alternans in optical action potential amplitude was associated with conduction block and VF. The data suggest that changes in optical action potential amplitude may underlie a mechanism for alternans-associated ventricular arrhythmia in left ventricular dysfunction.