Wenckebach Point Research Articles

Prevalence and predictors of ventriculo-atrial conduction in structurally normal hearts

BackgroundThe prevalence of ventriculo-atrial (VA) conduction varies from 20% to 90%, depending on the population studied (Militianu et al., 1997; Inoue et al., 1985; Kazmierczak et al., 1993; Ciemniewski et al., 1990; Hayes and Furman, 1983; Westveer et al., 1984). This wide range is mostly based on studies done in patients with implanted devices or impaired atrioventricular conduction. However, the prevalence of VA conduction in structurally normal heart has not been well documented till date. ObjectiveTo study the prevalence and identify predictors of retrograde conduction via the His-Purkinje system and AV node in structurally normal hearts. MethodsWe included 54 consecutive adults without structural heart disease who underwent electrophysiological (EP) study for various tachycardias. The basic parameters including PR, AH and HV intervals, atrioventricular Wenckebach point (AVWP) and anterograde effective refractory period (ERP) of atrioventricular node (AVNERP), were measured after ablation. The VA conduction was assessed basally and if absent, after isoprenaline. The VA Wenckebach point (VAWP) and retrograde ERP(VAERP) were recorded in patients showing VA conduction. ResultsThe mean age was 37.1±12.6years. Twenty five (46%) of the patients were men. VA conduction was present in 30 (55%) patients at baseline. Of the remaining 24 patients, 18 (34%) showed VA conduction after isoprenaline. Only 6 (11%) patients failed to reveal VA conduction even after adequate response to isoprenaline. Amongst all clinical and EP variables analysed, only the HV interval was shorter (p<0.01) in patients with VA conduction. ConclusionIn structurally normal hearts, VA conduction was present at baseline in 55% of patients. Isoprenaline unmasked VA conduction in an additional 34% of the subjects. The HV interval was longer in patients without VA conduction.

Normal Values for Heart Electrophysiology Parameters of Healthy Swine Determined on Electrophysiology Study.

Swine are a well-recognized animal model for human cardiovascular diseases. Despite the widespread use of porcine model in experimental electrophysiology, still no reference values for intracardiac electrical activity and conduction parameters determined during an invasive electrophysiology study (EPS) have been developed in this species thus far. The aim of the study was to develop a set of normal values for intracardiac electrical activity and conduction parameters determined during an invasive EPS of swine. The study included 36 healthy domestic swine (24-40 kg body weight). EPS was performed under a general anesthesia with midazolam, propofol and isoflurane. The reference values for intracardiac electrical activity and conduction parameters were calculated as arithmetic means ± 2 standard deviations. The reference values were determined for AH, HV and PA intervals, interatrial conduction time at its own and imposed rhythm, sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), anterograde and retrograde Wenckebach points, atrial, atrioventricular node and ventricular refractory periods. No significant correlations were found between body weight and heart rate of the examined pigs and their electrophysiological parameters. The hereby presented reference values can be helpful in comparing the results of various studies, as well as in more accurately estimating the values of electrophysiological parameters that can be expected in a given experiment.

Cardiac nodal and cardiac autonomic functions in children with vasovagal syncope.

In the present study, cardiac nodal (sinoatrial node and atrioventricular node) and cardiac autonomic functions have been investigated in children with vasovagal syncope (VVS). Thus, the effect of existing autonomic status on the characteristics of cardiac conduction system has been demonstrated in children with VVS. The study included 51 pediatric patients (the mean age was 14.01±2.79 years, range 7 to 18 years; 30 females), who were evaluated for syncope using ECG, Holter monitoring, and echocardiography, all of which showed normal findings. All patients underwent head-up tilt testing (HUTT), and the parameters of heart rate variability (HRV) (SDNN, SDANN, SDANNi, rMSSD, pNN50, HF, LF, VLF) were evaluated with the analysis of 24-hour Holter testing. Corrected sinus node recovery time (CNRT) and Wenckebach point (WP) were measured in all patients using transesophageal atrial stimulation. The patients were divided into groups according to HUTT results and evaluated accordingly. Cardiac nodal functions were normal in all patients. HRV parameters (HF, rMSSD, pNN50) indicating parasympathetic effect were higher in patients with positive HUTT results. CNRT did not differ significantly between patients with positive HUTT results and patients with negative HUTT results. However, WP was found to be higher in patients with positive HUTT results. The studies evaluating the parameters of HRV has demonstrated increased parasympathetic tonus in children with VVS. Impairment in cardiac nodal functions may not be expected in children with VVS. However, these patients may exhibit prolonged WP due to increased autonomic tonus in favor of parasympathetic activity.

Analysis of atrioventricular function and its efficacy in patients with AVNRT undergoing atrioventricular junction ablation of slow conduction pathway

Objective The electrophysiological parameters of atrioventricular conduction function in patients with atrioventricular nodal reentry tachycardia (AVNRT) were analyzed, and to explore the effect of different ablation endpoints on atrioventricular conduction function in patients with AVNRT. Methods 96 cases with AVNRT underwent radiofrequency catheter ablation (RFCA) of slow conduction pathway.According to whether the slow pathway eliminated, the patients were divided into the slow pathway disappeared group and slow tracks remaining group.Preoperative and postoperative intracavitary electrophysiological examination and atrioventricular function data were recorded, including before and after radiofrequency ablation of bundle of HIS, PA, AH, HV interval, atrioventricular prequel venturi point(AVN-WKB), ventriculoatrial retrograde venturi point(VAN-WKB), atrioventricular node prequel effective refractory period(AVB-WKB). Patients were followed up by telephone for a year.Then, a comparative analysis of preoperative and postoperative was done. Results RFCA of AVNRT patients with atrioventricular node prequel time effect: RFCA and preoperative ratio, after his bundle electrogram PA, ah, HV interval had no significant changes(P>0.05). Effect of RFCA surgery on patients with AVNRT refractory atrioventricular node prequel: compared with RFCA before surgery, postoperative slow pathway disappear fast pathway shortening of effective refractory period[preoperative(287.5±46.2)ms, postoperative(260.2±55.6)ms, t=2.901, P=0.005], slow pathway effective refractory period[disappear preoperative(243.3±43.2), postoperative(0.0±0.0)ms, t=43.290, P=0.000], AV node Wenckebach point in advance before operation[(261.3±44.3)ms, postoperative(293.2±46.2)ms, t=3.828, P=0.000]; group after slow pathway to improve fast pathway effective refractory period without obvious change(P>0.05), the slow pathway effective refractory period in high concentration[preoperative(242.2±42.8)ms, postoperative(281.2±41.3)ms, t=3.879, P=0.000], atrioventricular node Wenckebach point in advance before operation[(261.5±43.5)ms, postoperative(291.3±46.5)ms, t=2.769, P=0.007]. Comparison between groups, after slow pathway disappeared group fast pathway effective refractory period was significantly shorter in the slow diameter improvement group, but between the two groups in the atrioventricular node Wenckebach point differences was not statistically significant(P>0.05). There was no recurrence in the follow-up after a year of slow path loss and slow pathway. Conclusion RFCA caused by slow pathway to disappear or modified two slow pathway ablation right AVNRT patients atrioventricular time had no effect, but all the atrioventricular junction the prequel's point advance.The atrioventricular node slow pathway disappear fast and effective pathway refractory period shortened, slow pathway improved the slow pathway effective refractory period.RFCA surgery done by the slow pathway disappeared or slow pathway ablation is effective in patients with AVNRT, and there was no significant recurrence rate in both groups within 1 year. Key words: Ablation; Tachycardia; Atrioventricular conduction function

AV WENCKEBACH POINT AS A LONG-TERM PREDICTOR OF RIGHT VENTRICULAR PACING DEPENDENCE

Patients presenting symptomatic sick sinus syndrome with preserved AV node function with indication for permanent pacemaker implantation theoretically benefit form single chamber device (AAI) as it represents a more physiologic pacing mode and it reduces complication rates. The incidence of high degree AV block in patients with sick sinus syndrome was reported to be between 0.6 and 3 % annually. We hypothesized that the baseline AV wenckebach point (WP) at the time of AAI pacemaker implantation represent a valid predictor of the futur need for a ventricular lead implantation. We retrospectively analyzed 211 patients who underwent double chamber pacemaker (DDD) implantation who had more than one AV WP measure over a follow-up of up to 7 years. The primary outcome was the percentage of right ventricular pacing at follow-up stratified for the baseline WP. Secondary outcomes included the evolution of the mean WP and right ventricular pacing percentage over time. There is a linear relationship between baseline WP and right ventricular pacing at follow-up (correlation coefficient -0.68) With a baseline value greater than 120 bpm, patients have 9% RV pacing burden at follow-up while an initial value ≤ 100 bpm will result in a 54% RV pacing burden at follow-up. Also, there was no significant difference in the mean WP and percentage of right ventricular pacing at 6 years of follow-up. Routine measurement of the WP should be part of the assessment of patients with sick sinus syndrome in order to better determine if they are candidate for single chamber AAI pacemaker implantation. If the WB is > than 120 bpm, implantation of an AAI pacemaker seems reasonable as suggested by a low burden of ventricular pacing at follow-up and a stable WP measure over time.

Hypervagotonic binodal dysfunction in children. Features of the natural course

Aim. To evaluate the clinical and electrophysiological picture of binodal disease in children, as well as studying the clinical course of this disease.&#x0D; Methods. To study the clinical and electrophysiological picture of autonomic binodal disease, 426 patients under 18 years old were examined; the average age was 15.35±2.43 years (3-17.9). Patient’s complaints, medical history were examined, ECG, 24-hour ECG, stress ECG (treadmill or bicycle test), echocardiography, transesophageal electrophysiologic study were performed. In the case of a combination with pathological signs of sinus node dysfunction and atrioventricular node conduction disorders with the normalization of all parameters after the atropine administration, hypervagotonic binodal dysfunction was diagnosed. To assess the clinical course of the disease, a group of 72 children was selected, who were monitored repeatedly. Mean follow-up duration was 33 months.&#x0D; Results. During the study period, sinus node dysfunction and atrioventricular blocks completely resolved in 14 (19.44%), seen as normal clinical picture with no complaints, normal heart rate, no signs of sinoatrial block or atrioventricular block, normalization of Wenckebach point position. Another 35 (48.62%) had only one node dysfunction resolved (either sinoatrial or atrioventricular - Wenckebach point position within the age normal values and/or atrioventricular block resolved). In 23 (31.94%) - deterioration of the sinus node and atrioventricular node dysfunction was observed.&#x0D; Conclusion. There are significant differences in the frequency characteristics of heart rhythm and electrophysiological parameters of sinus node function in children with a favorable clinical course of binodal disease and progressive course of the disease.

Renal Denervation Suppresses Atrial Fibrillation in a Model of Renal Impairment

BackgroundA close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity.ObjectiveThe main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI.MethodsUnilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured.ResultsEmbolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN.ConclusionsRDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue.

Establishment of a model of renal impairment with mild renal insufficiency associated with atrial fibrillation in canines.

BackgroundChronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF.MethodsUnilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed.ResultsEmbolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group.ConclusionsWe successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model.

Atrial septal pacing in small dogs: A pilot study

ObjectiveTo determine the feasibility of atrial septal pacing via a delivery catheter-guided small non-retracting helix pacing lead. AnimalsSix healthy beagles (8.3-12.9 kg). MethodsUsing single plane fluoroscopic guidance, Medtronic® 3830 SelectSecure leads were connected to the atrial septum via Medtronic® Attain Select® II standard 90 Left Heart delivery catheter. Pacing threshold and lead impedance were measured at implantation. The Wenckebach point was tested via atrial pacing up to 220 paced pulses per minute (ppm). Thoracic radiographs were performed following implantation to identify the lead position, and repeated at 24 h, 1 month, and 3 months post-operatively. ResultsMacro-lead dislodgement occurred in two dogs at 24 h and in three dogs at one-month post-implantation. Lead impedance, measured at the time of implantation, ranged from 583 to 1421 Ω. The Wenckebach point was >220 ppm in four of the six dogs. The remaining two dogs had Wenckebach points of 120 and 190 ppm. ConclusionsThis pilot study suggests the selected implantation technique and lead system were inadequate for secure placement in the atrial septum of these dogs. The possible reasons for inadequate stability include unsuitable lead design for this location, inadequate lead slack at the time of implantation and inadequate seating of the lead as evidenced by low impedance at the time of implantation. Other implantation techniques and/or pacing leads should be investigated to determine the optimal way of pacing the atria in small breed dogs that are prone to sinus node dysfunction.

Blackout during meals: A case report of swallow syncope due to sinus arrest

A 79-year-old male, with a history of percutaneous coronary intervention (PCI), was referred to our cardiovascular department for a detailed examination of blackout caused by sinus arrest only during meals. Ultrasound echocardiography showed normal cardiac contraction with no asynergy, irrespective of the remaining stenotic coronary lesion. An electrophysiological study revealed deteriorated atrioventricular nodal conduction at a Wenckebach point of 70 beats per minute. However, sinus node function was normal as demonstrated by a sinus node recovery time of 1369ms. Coronary angiography showed triple-vessel disease including the remaining stenotic coronary lesion, and a PCI was performed on the right coronary artery. Nevertheless, sinus arrest during meals was unchanged. Swallow syncope was partially improved by dietary modification; however, pacemaker implantation (PMI) was performed eventually, and the patient became asymptomatic after PMI.<Learning objective: Swallow syncope is a rare cause of syncope that belongs to the neurally mediated reflex syncopal syndromes, which can induce a variety of bradyarrhythmias: sinus bradycardia, sinus arrest, sinoatrial block, atrioventricular block, or atrial and ventricular asystole. In this case, we demonstrated that dietary modification or pacemaker implantation improved swallow syncope due to sinus arrest.>

PP-207 Transient Heart Block is a Result of Pepper Gas Inhalation as a Chemical Weapon

ducted atrioventricular blockwithventricular rate about 35bpm, please note that p wave on DII derivation was shown with arrows. In Figure 2 (below) electrophysiological study documented sinus node and atrioventricular node conductionwas normal (SinusNode Recovery Time-SNRT:800msn, Anterograde Wenckebach Point: 310msn, HisVentricle-HV interval:38msn, Atrium-His interval:110msn). MARCH 13e16, 2014

Atrioventricular conduction properties in patients with prolonged pauses undergoing ablation of longstanding persistent atrial fibrillation: do pauses during atrial fibrillation matter?

Atrioventricular (AV) conduction disturbances have often been considered as an etiology of prolonged pauses during atrial fibrillation (AF). We aimed to test whether there was a significant difference in the AV conduction properties between patients with and without clinically significant pauses who underwent ablation of longstanding persistent AF. Ninety-nine patients undergoing ablation of longstanding persistent AF were divided into three groups according to the extent of pauses documented on the ambulatory electrocardiogram during AF; patients without pauses (n = 25), with pauses of <3 s (n = 52), and with pauses of ≥3 s (n = 22). The AV conduction properties, heart rate variability, and bradycardia-related symptoms after conversion to sinus rhythm were compared across the three groups plus a control group (n = 35). Sinus conversion was achieved in all patients after ablation. No differences were found across the groups in the AV conduction properties including the AH and HV intervals, AV nodal effective refractory period, or Wenckebach point. A male gender (β = 0.32; p = 0.0016), structural heart disease (β = 0.24; p = 0.02), and the AA interval right after ablation (β = 0.35; p = 0.0014), rather than the AV conduction properties, were independent determinants of the longest normal RR interval during AF. No patients experienced any bradycardia-related symptoms after ablation. No AV conduction abnormalities were necessarily identified after the ablation even among the patients suspected of having an AV conduction disturbance during AF.

Immediate and long-term eff icacy and safety of catheter ablation of right anteroseptal atrio-ventricular accessory pathways

This study investigated long-term outcome of catheter ablation of right anteroseptal atrio-ventricular (AV) accessory pathways (AP) located close to the His bundle. MethodsBetween April 2003 and June 2011, 26 patients (6 females, age 35±13 years) underwent catheter ablation of right anteroseptal AP. These APs represented 10% of all 248 APs ablated within the given reference period. Elimination of AP conduction in both directions and preservation of normal AV conduction were the ablation procedure endpoints. ResultsFirst ablation was effective in 18 (69%) patients. After repeat ablation, AP was permanently eliminated in 22 (85%) patients (one, two, and three ablation procedures in 16, 5, and 1 patient, respectively). Ablation failed in 4 patients (1 procedure in 3 patients, 2 procedures in 1 patient). During 56±27 (4–102) month follow-up period since the last ablation, no late AP conduction recovery was found, and no late advanced AV block occurred. Post-ablation AV node Wenckebach point was present at the pacing rate of 176±26 (130–230) beats per minute. Of the two engaged operators, more experienced operator successfully accomplished first, second, and third ablation procedure in 14/16 (88%), 5/5 (100%), and 1/1 (100%) patients, respectively, the latter operator attained successful ablation in 4/10 (40%) and 1/2 (50%) patients at the first and second ablation procedures, respectively. ConclusionAblation of right anteroseptal AP close to the His bundle is feasible and safe. Late advanced AV block was not observed. Individual operator's experience influenced ablation efficacy.

Anatomical-guided ‘cardioneuroablation’ to treat neurocardiogenic syncope associated with functional AV block

BackgroundYoung patients with severe symptomatic functional atrioventricular block will receive permanent pacemaker implantation. Unfortunately, implantation may bring these patients inestimable barriers to their life. Our study discussed the methods, efficacy...

Avaliação eletrofisiológica cardíaca em pacientes com sarcoidose

FUNDAMENTO: Sarcoidose é uma doença granulomatosa multissistêmica de origem desconhecida que pode causar morte súbita. OBJETIVO: Avaliação eletrofisiológica de pacientes com sarcoidose com suspeita de comprometimento cardíaco. MÉTODOS: Foram estudados 22 pacientes com média de idade de 55,32 ±13,13 anos, com diagnóstico de sarcoidose e suspeita de comprometimento cardíaco. Foram submetidos à avaliação clínica, exames laboratoriais, eletrocardiograma, ecocardiograma, Holter de 24h, cintilografia com gálio ou tecnécio e estudo eletrofisiológico. Em casos selecionados foi realizada tomografia por emissão de pósitrons ou ressonância magnética. Os pacientes foram seguidos ambulatoriamente com consultas trimestrais. RESULTADOS: Comprometimento cardíaco foi comprovado em quatro (18,2%) pacientes. Extrassístoles ventriculares com densidade > 100/24h foram documentadas no Holter de 24h em 12 (54,5 %) pacientes. O estudo eletrofisiológico revelou aumento do intervalo HV em sete (31,8%) e ponto de Wenckebach aumentado em quatro (18,2%) pacientes. Houve indução de fibrilação atrial em sete (31,8%) e de taquicardia ventricular sustentada em um (4,5%). Nos quatro pacientes com sarcoidose cardíaca confirmada, extrassístoles ventriculares, com densidade > 100/24h foram documentadas em todos, dois apresentavam intervalo HV prolongado e fibrilação atrial foi induzida em dois. Taquicardia ventricular sustentada não foi induzida em nenhum desses pacientes. Após período médio de acompanhamento de 20,9 ± 15,7 meses, um paciente com sarcoidose cardíaca apresentou morte súbita. CONCLUSÃO: Pacientes com sarcoidose e suspeita de envolvimento cardíaco apresentam alta prevalência de EVs e distúrbios do sistema de condução.

244 High incidence of AV block and prophylactic pacing in familial amyloid polyneuropathy

Familial amyloid polyneuropathy (FAP) is an autosomic dominant inherited disease. FAP cardiopathy is characterized by conduction disorders, denervation, and cardiac infiltration. Because of the risk of high degree atrioventricular (AV) block and sudden death, prophylactic pacing can be suggested when there is evidence of amyloid infiltration of the AV conduction pathways. Our purpose was to estimate prevalence of AV block and pacing dependence for high risk FAP patients. In a cohort of 51 FAP patients, we performed standard ECG and electrophysiological study. Patients with conduction disorders underwent prophylactic pacing. During follow up, AV conduction was studied by using data from the Holter memories of pacemakers. Baseline characteristics of the patients are summarized on table 1. During the follow up, permanent high degree AV block occurred in 23.5% of the patients (12/51)(cf. fig. 1). Average percentage was 23 ± 35% for ventricular pacing and 18 ± 24% for atrial pacing. Paroxystic AV block was recorded for all patients but 3 (94%). Prevalence of AV conduction disorders was 283 ± 465 events per month (epm) and was distributed in 14 ± 46 epm for third degree AV block, 195 ± 386 epm for second degree AV block, 73 ± 225 epm for first degree AV block and 0.2 ± 0.7 epm for pauses. During the study, sustained atrial arrhythmias occurred in three patients. No sustained ventricular arrhythmia was recorded. Patients with FAP cardiomyopathy present high incidence of AV blocks. For FAP patients with involvement of the AV conduction pathway, prophylactic pacemaker insertion should be performed. Incidence of permanent AV block Table 1: Baseline characteristics Mean ± SD age (years) 54 ± 13 % of men 64.7% Lenght of fu (months) 34 ± 33 % Val30 Met 64% Surface ECG Conduction disorders 74% AVB type 1 38% PR interbal (ms) 191 ± 41 QRS interval (ms) 94 ± 21 Electrophysiological study corrected sinus recovery time (ms) 546 ± 438 AH interval (ms) 117 ± 43 HV interval (ms) 68 ± 11 Anterior Wenckebach point (bpm) 128 ± 33

Apparent short PR interval during atrial tachycardia: what is the mechanism?

A 69-year-old woman with an incessant narrow QRS tachycardia underwent catheter ablation 5 days after failed ablation attempt at another center. Figure 1a shows 12-lead ECG of the tachycardia with a PR interval = 80 ms and cycle length of 450 ms. Ventricular overdrive pacing showed ventriculoatrial dissociation. Figure 1b shows atrial overdrive pacing with the cycle length of 420 ms, with PR interval of 160 ms, which excludes very long PR interval manifesting as apparent short PR interval. In addition incremental atrial pacing showed a Wenckebach point of 350 ms and no preexcitation. Pacing during sinus rhythm with the same cycle length (420 ms) generated a PR interval of 160 ms. Figure 2 shows activation mapping of atrial tachycardia in right atrium with the earliest activation recorded in fast pathway region near His (Fig. 2b). Activation mapping also showed slow conduction from this point (Fig. 2a, b) to the rest of atria (Fig. 2c), which was responsible for the apparent short PR interval. Radiofrequency ablation (Navistar 4 mm, Biosense Webster Inc, Diamond Bar, California, USA) at the earliest activation point (30 W, 50 C) slowed down and then terminated the atrial tachycardia with transient first degree atrioventricular (AV) block. The P wave morphology was not compatible with a septal atrial tachycardia; however, we postulated that delayed and changed atrial activation pattern due to earlier linear ablation lesions as shown in activation mapping may have resulted the observed apparent short PR interval and unusual changed P wave morphology (Fig. 2) [1, 2]. In conclusion, the slow conduction from the earliest activation point to the rest of the right and left atria despite normal conduction to and through the AV node resulted in the delayed atrial depolarization which in turn caused the apparent short PR interval during atrial tachycardia in the absence of an accessory pathway. During catheter ablation the patient transiently developed first degree AV Block. We used a low power setting to avoid high-degree AV block; however, using cryoablation with EnSite NavX Navigation system (St. Jude Medical, Inc. St. Paul, MN) could have been a safe alternative for catheter ablation in this area. Junctional tachycardia should be considered in the differential diagnosis. However, in this case the earliest activation would be at the AV node region. As shown in Fig. 2, the earliest activation during tachycardia was superior and posterior to the fast pathway/AV node region. In addition, the polarity of the P wave and its relation to QRS complex (short PR) argues against junctional tachycardia. Finally, the total atrial activation time was 160 ms which excludes macro-reentry as the underlying mechanism of the tachycardia. True focal atrial tachycardia due to abnormal automaticity or microreentry remains the possible mechanism of this tachycardia.

Sertindole and impaired atrioventricular function, in the absence of Q–T prolongation: A case report

SERTINDOLE IS AN atypical antipsychotic agent with high-affinity and concomitant moderate-potency blocking effect to the rapid component of the human cardiac delayed rectifier potassium current (IKr),1 encoded by the human Ether-à-go-go-related (hERG) gene. This property underlies the prolongation of the Q–T interval observed during sertindole administration and may cause life-threatening ventricular arrhythmias. We report the case of a 52-year-old male patient who was diagnosed with schizophrenia and was treated with antipsychotic medication from the age of approximately 40 years old, and who was recently started on sertindole. Sertindole was initiated following serious tardive dyskinesia (TD) caused by his previous medication (quetiapine). After 6 weeks of sertindole treatment (16 mg/day), TD remitted and improvement in his psychotic symptoms was observed. The electrocardiograms (ECG) showed normal Q–T intervals (baseline ECG, QTc = 400 msec; heart rate [HR], 70/min; PR, 180 msec; second ECG [2 weeks later following 8 mg/day of sertindole], QTc = 424 msec; HR, 105/min; PR, 180 msec; third ECG [3 weeks later following 16 mg/day of sertindole], QTc = 413 msec; HR, 100/min; PR, 180 msec; and fourth ECG without further changes). Six months following the initiation of sertindole the patient reported five syncopal episodes without clear prodromal symptoms. The patient recalled two sporadic syncopal episodes in his mid 20s. Electroencephalography (EEG) and brain computed tomography were carried out and were within normal limits. Non-interventional cardiological investigation (echocardiography, stress-test, Holter ECG and head-up tilting test) were normal. During the tilting test, blood pressure changed from 135/75 mmHg (baseline) to 130/68 mmHg immediately after tilting, ruling out orthostatic hypotension. Throughout the test, blood pressure and HR range were 15 mmHg and 10 beats per minute, respectively, ruling out vasovagal syncope. Electrophysiological study was negative for sinus node dysfunction and ventricular arrhythmogenesis, but documented an abnormal atrioventricular conduction: (i) H–V interval of 72 (normal values: 35–55 msec); and (ii) Wenckebach point of atrioventricular conduction at an atrial pacing cycle length of 490 msec. Two weeks after the discontinuation of sertindole, H–V was not shortened (70 msec) and based on the current indications for pacemaker implantation and considering the co-morbid psychiatric disease, a pacemaker was implanted and the patient has remained free of symptoms. Since the recurrent syncopal episodes coincided with sertindole administration, sertindole was implicated as a possible triggering factor, unmasking a subclinical defect in the conduction system. This may be attributed to the effect of sertindole on (i) the IKr current and its predominance in the atrioventricular conduction;2 and (ii) the Purkinje fibers.3 Clinicians should be aware of this possible effect of the drug.

Effects of AZD0837, a Novel Direct Thrombin Inhibitor, on the Electrophysiological Properties of the Human Heart

AZD0837 is an investigational oral anticoagulant that is bioconverted to its active form, AR-H067637, a selective direct thrombin inhibitor. The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 micromol/L, approximate target of 10 micromol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 micromol/L, target 1-2 micromol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 micromol/L, target 0.5-1.0 micromol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or repolarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top) - QT(end)). AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment.

Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice

Desmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is strongly expressed in striated muscle cells and in Purkinje fibers of the ventricular conduction system. The aim of the present study was to characterize electrophysiological cardiac properties in a desmin-deficient mouse model. The impact of desmin deficiency on cardiac electrophysiological characteristics was examined in the present study. In vivo electrophysiological studies were carried out in 29 adult desmin deficient (Des-/-) and 19 wild-type (Des+/+) mice. Additionally, epicardial activation mapping was performed in Langendorff-perfused hearts. Intracardiac electrograms showed no significant differences in AV, AH, and HV intervals. Functional testing revealed equal AV-nodal refractory periods, sinus-node recovery times, and Wenckebach points. However, compared to the wild-type situation, Des-/- mice were found to have a significantly reduced atrial (23.6+/-10.3 ms vs. 31.8+/-12.5 ms; p=0.045), but prolonged ventricular refractory period (33.0+/-8.7 ms vs. 26.7+/-6.5 ms; p=0.009). The probability of induction of atrial fibrillation was significantly higher in Des-/- mice (Des-/-: 38% vs. Des+/+: 27%; p=0.0255), while ventricular tachycardias significantly were reduced (Des-/-: 7% vs. Des+/+: 21%; p<0.0001). Epicardial activation mapping showed slowing of conduction in the ventricles of Des-/- mice. Des-/- mice exhibit reduced atrial but prolonged ventricular refractory periods and ventricular conduction slowing, accompanied by enhanced inducibility of atrial fibrillation and diminished susceptibility to ventricular arrhythmias. Desmin deficiency does not result in electrophysiological changes present in human desminopathies, suggesting that functional alterations rather than loss of desmin cause the cardiac alterations in these patients.