Transient entrainment and interruption of atrioventricular node tachycardia

The possibility of transiently entraining and interrupting the common type of atrioventricular (AV) node tachycardia (anterograde slow, retrograde fast AV node pathway) was studied using atrial and ventricular pacing in 18 patients with paroxysmal AV node tachycardia. Transient entrainment occurred in all patients. During atrial pacing, localized block in the AV node for one beat followed by anterograde conduction over the fast pathway was observed in three patients. During ventricular pacing, localized block for one beat followed by retrograde conduction over the slow pathway was not observed in any patient. Neither atrial nor ventricular fusion beats were observed during entrainment.These observations indicate in a way not previously shown that reentry involving two functionally dissociated pathways in the AV node is the underlying mechanism of paroxysmal AV node tachycardia. The inability to demonstrate atrial or ventricular fusion beats during entrainment suggests a true intranodal location of the reentrant circuit. Finally, the ability to transiently entrain intranodal tachycardia demonstrates that this electrophysiologic phenomenon is not exclusively limited to macroreentrant circuits

Single site radiofrequency catheter ablation of atrial fibrillation: studies guided by simultaneous multisite mapping in the canine sterile pericarditis model

AbstractOBJECTIVESTo test the hypothesis that when activation of Bachmann’s bundle (BB) is critical to the unstable reentrant circuits that maintain atrial fibrillation (AF) in the sterile pericarditis canine model, a lesion in BB would prevent induction of stable AF.BACKGROUNDOne mechanism of induced AF in this model is multiple unstable reentrant circuits, which frequently include BB as part of the reentrant pathway.METHODSSimultaneous multisite mapping studies during AF and after ablation of BB were performed by recording (384 to 396 electrodes) from both atria and the atrial septum during six induced AF episodes in six dogs with sterile pericarditis. Activation maps of AF (mean duration, 24 ± 28 min) during 12 consecutive 100-ms windows were analyzed.RESULTSDuring AF, multiple unstable reentrant circuits (mean, 1.2 ± 0.2 per window; range, 1 to 4) were observed, 68% involving BB. Nonactivation zones (mean duration, 57 ± 16 ms in the right atrium and 53 ± 23 ms in the left atrium) observed during AF were reactivated by a wave front most often coming from the atrial septum via BB (right atrium, 62%; left atrium, 67%). After successful radiofrequency catheter ablation of the midportion of BB, AF >5 s was not induced in all dogs. Mapping studies of transient AF (≤5 s) induced after ablation showed neither reentrant circuits nor wave fronts activating the right atrium via BB.CONCLUSIONSIn this AF model, catheter ablation of BB terminates and prevents the induction of AF by preventing 1) formation of unstable reentrant circuits that involve BB, and 2) activation of the atrial-free walls after a nonactivation period

Insights into the electrophysiology study versus electrocardiographic monitoring trial: Its programmed stimulation protocol may introduce bias when assessing long-term antiarrhythmic drug therapy

AbstractObjectives. We hypothesized that if the Electrophysiology Study Versus Electrocardiographic Monitoring (ESVEM) trial programmed stimulation protocol misclassified some drug trials as effective, then the misclassification rate would be proportionally greater for drugs other than sotalol.Background. In the ESVEM trial, patients treated with sotalol had fewer arrhythmic recurrences than those treated with other antiarrhythmic drugs despite similar efficacy predictions during electrophysiologic testing.Methods. We retrospectively compared the standard programmed stimulation protocol used at Case Western Reserve University, which used three extrastimuli during all follow-up studies, with the ESVEM protocol in 176 antiarrhythmic drug trials: sotalol (n = 54), procainamide (n = 73) and quinidine/mexiletine (n = 49).Results. Predictions of efficacy were higher in the sotalol trials (14 of 54 standard, 20 of 54 ESVEM) than in procainamide trials (7 of 73 standard, 14 of 73 ESVEM) or quinidine/mexiletine trials (1 of 49 standard, 7 of 49 ESVEM). Thus, the two protocols classified 19 of 176 trials differently: not effective by the standard protocol but effective by the ESVEM trial. Discordant predictions of drug efficacy constituted a smaller proportion of ESVEM protocol efficacy predictions for sotalol (6 [30%] of 20) than for the other drugs (13 [62%] of 21, p ⩽ 0.05).Conclusions. In the present study, the ESVEM programmed stimulation protocol predicted efficacy more often than the standard protocol. Discordant predictions represented a smaller portion of efficacy predictions for sotalol than for the other drugs. Thus, in the ESVEM trial, the superior long-term follow-up observed in patients assigned to sotalol may have been an artifact of the stimulation protocol utilized by the ESVEM investigators

A new animal model of atrial flutter

A new, simple and reliable model of atrial flutter utilizing postpericardiotomy pericarditis was developed in the dog. Using a sterile technique, the pericardium was opened by way of a right thoracotomy, Teflon-coated, stainless steel wire electrodes were fixed to three selected sites on the atria and exteriorized, the atrial surfaces were generously dusted with talcum powder and a single layer of gauze was placed on the free left and right atrial walls. The dogs were allowed to recover. Subsequently, the inducibility of atrial flutter and selected electrophysiologic properties of the atria were determined by daily programmed atrial stimulation studies with the dogs in the conscious, nonsedated state.Atrial flutter could be induced in 23 of 25 dogs initially studied. It was sustained (that is, lasting ≥5 min) in 17 of the 23. Neither atrial excitability, Intraatrial conduction time nor atrial refractoriness determined by pacing and recording from the three fixed sites predicted the inducibility of atrial flutter. One hundred thirty-nine episodes of atrial flutter induced in these 23 dogs were analyzed. The mean sustained atrial flutter cycle length was 131 ± 20 ms (mean ± SD) (range 100 to 170); the atrial flutter cycle length was 150 ms or more in 23 episodes, between 120 and 150 ms in 64 episodes and 120 ms or less in 52 episodes.In five dogs, the stability of the atrial flutter cycle length during sustained atrial flutter was studied and shown to be remarkably stable in all five until interrupted by rapid atria) pacing 35 to 95 minutes after its induction. Seventeen dogs were submitted to reoperation for epicardial mapping purposes and atrial flutter could be induced in the open chest state in 12. In conclusion, this sterile pericarditis model of atrial flutter in the canine heart proved to be highly reliable, reproducible and easy to create

Characterization of double potentials in human atrial flutter: Studies during transient entrainment

AbstractDouble potentials, defined as atrial electrograms with two discrete deflections per beat separated by an isoelectric interval or a low amplitude baseline, have been observed during right atrial endocardial mapping of human atrial flutter. In this study, bipolar atrial electrograms were recorded during atrial flutter (mean cycle length 235 ± 27 ms [± SEM]) from the high Right atrium, the His bundle region, the coronary sinus and at least 30 right atrial endocardial napping sites in 10 patients. Double potentials were recorded from the right atrium in all patients during atrial flutter.Double potentials were evaluated during transient entrainment of atrial flutter by rapid high right atrial pacing in 5 of the 10 patients. In four of these five patients during such transient entrainment 1) one deflection of the double potential was captured with a relatively short activation time (mean interval 89 ± 45 ms) and the other deflection was captured with a relatively long activation time (mean interval 233 ± 24 ms), producing a paradoxical decrease in the short interdeflection interval from a mean of 75 ± 20 ms to a mean of 59 ± 24 ms; and 2) the configuration of the double potential remained similar to that observed during spontaneous atrial flutter. On pacing termination 1) the two double potential deflections were found to be associated with two different atrial flutter complexes in the electrocardiogram (ECG); 2) the previous double potential deflection relation resumed; and 3) when sinus rhythm was present, the double potentials were replaced by a broad, low amplitude electrogram recording at the same site. These functional double potentials probably represent collision of activation wave fronts in a functional center of the artial flutter reentrant circuit and therefore may serve as a marker for an area of functional block. In one of the five patients, double potentials were recorded from the site during transient entrainment of atrial flutter, during spontaneous atrial flutter and during sinus rhythm. These were called persistent double potentials and were associated with the same atrial flutter complex in the ECG, indicating that not all double potentials recorded during atrial flutter represent the same phenomenon

Characterization of double potentials in a functionally determined reentrant circuit Multiplexing studies during interruption of atrial flutter in the canine pericarditis model

AbstractObjectives. We tested the hypothesis that double potentials recorded during atrial flutter in a functionally determined reentrant circuit reflect activation of the reentrant wave front around an area of functional conduction block.Background. The center of the atrial flutter reentrant circuit in the sterile pericarditis canine model is characterized by double potentials.Methods. We studied 11 episodes of atrial flutter in eight dogs during interruption of atrial flutter while pacing the atria. A multielectrode mapping system was used to record simultaneously from 190 electrodes on the right atrium (location of reentry).Results. Interruption of atrial flutter occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction in the reentrant circuit. The response of the double potential with interruption of atrial flutter depended on the location of the recording site relative to this area of block. Two types of response were seen. When the double potential was recorded orthodromically distal to this area of block, interruption of atrial flutter was associated with disappearance of the second deflection, and continued pacing after interruption of atrial flutter was not associated with reappearance of the second potential. When the double potential was recorded at a site orthodromically proximal to the area of block, interruption of atrial flutter was not associated with disappearance of the second potential, and when rapid atrial pacing was continued, the double potential remained despite disappearance of the atrial flutter reentrant circuit.Conclusions. Double potentials represent functional conduction block in the center of the reentrant circuit, with each deflection of the double potential reflecting activation on either side of the area of functional block. The data also demonstrate that double potentials are not limited to a reentrant circuit, as they were recorded on either side of an area of block in the absence of such a circuit

Value of early postoperative epicardial programmed ventricular stimulation studies after surgery for ventricular tachyarrhythmias

The value of early postoperative epicardial programmed ventricular stimulation studies after electrophysiologically-directed surgery for ventricular tachyarrhythmia was assessed in 34 patients who underwent epicardial stimulation within 7 to 30 days (mean 9.8) of surgery and were followed up for at least 6 months. The antiarrhythmic operation performed was an endocardial ventriculotomy (full encircling or limited), an endocardial resection, a wall resection or a combination of these procedures. All these interventions were directed by intraoperative mapping during sinus rhythm. Temporary epicardial wire electrodes left at the time of surgery rather than endocardial catheter electrodes were used to perform the pacing. The stimulation protocol included the introduction of up to three ventricular extrastimuli and incremental burst ventricular pacing performed at twice diastolic threshold (9.2 ± 5.8 mA for the right ventricle and 6.0 ± 3.5 mA for the left ventricle). A study was considered positive when ventricular tachycardia, defined as 10 or more consecutive ventricular beats, was induced by any pacing modality.Nineteen patients (Group I) had a negative study: after stimulation of both ventricles in 15 patients and of the left ventricle only in 4. Fifteen patients (Group II) had a positive study: after stimulation of the right ventricle in nine patients and of the left ventricle in six. The two groups were comparable with respect to preoperative clinical status, surgical procedures performed and postoperative ejection fraction. No arrhythmic events were observed in Group I during a mean follow-up period of 19.5 months (range 4 to 37), whereas seven arrhythmic events (47% incidence) occurred (p = 0.0008) in Group II during a mean follow-up period of 17.7 months (range 5 to 39). These arrhythmic events were sudden death (five patients) and sustained ventricular tachycardia (two patients).It is concluded that temporary epicardially-placed electrodes can be used satisfactorily to perform programmed ventricular stimulation studies in the postoperative period, thereby avoiding the cardiac catheterizations otherwise necessary to perform these studies. In addition, the protocol used in this report of epicardial programmed ventricular stimulation early after surgery for ventricular tachyarrhythmia predicts a good outcome if the study is negative and identifies patients at a high risk for future arrhythmic events when positive

Novel Echocardiographic Biomarkers in the Management of Atrial Fibrillation

Purpose of Review: Atrial fibrillation (AF) is the most common arrhythmia in adults. The number of patients with AF is anticipated to increase annually, mainly due to the aging population alongside improved arrhythmia detection. AF is associated with a significantly elevated risk of hospitalization, stroke, thromboembolism, heart failure, and all-cause mortality. Echocardiography is one of the key components of routine assessment and management of AF. Therefore, the aim of this review is to briefly summarize current knowledge on “novel” echocardiographic parameters that may be of value in the management of AF patients. Recent Findings: Novel echocardiographic biomarkers and their clinical application related to the management of AF have been taken into consideration. Both standard parameters such as atrial size and volume but also novels like atrial strain and tissue Doppler techniques have been analyzed. Summary: A number of novel echocardiographic parameters have been proven to enable early detection of left atrial dysfunction along with increased diagnosis accuracy. This concerns particularly experienced echocardiographers. Hence, these techniques might improve the prediction of stroke and thromboembolic events among AF patients and need to be further developed and disseminated. Nonetheless, even the standard imaging parameters could be of significant value and should not be discontinued in everyday clinical practice. © 2019, The Author(s)

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered