Normal Ventricular Activation Research Articles

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Dyssynchrony assessment by ultra-high-frequency electrocardiography: a single numerical parameter to identify the relationship between right and left ventricular depolarization

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): grant number NU21-02-00584, the CAS project RVO:68081731, the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) - Funded by the European Union – Next Generation EU. Background The common criterion for assessing synchronous activation during single and biventricular pacing is QRS duration (QRSd). The novel conduction system pacing (CSP) techniques provide more physiological ventricular activation but less clear effects on QRSd. In these circumstances, a more detailed and visual assessment of ventricular synchrony than QRSd alone can be insightful. Purpose To investigate whether differences between various modes of CSP can be better differentiated by ultra-high-frequency ECG (UHF-ECG) than by QRSd. Methods UHF-ECG recordings were acquired in 199 bradycardia patients with narrow QRS complex during intrinsic rhythm, selective (sHBP) and non-selective His bundle (nHBP), selective (sLBBP) and non-selective left bundle branch (nsLBBP) pacing, and left (LVSP) and right ventricular septal pacing (RVSP). Lead positions were certified using X-ray and QRS morphology. Electrical dyssynchrony (e-DYS) was calculated from UHF-ECG activation times as the maximal time difference between the peaks of ECG leads V1-V6. Positive e-DYS indicates delayed left ventricular (LV) activation, whereas negative e-DYS means delayed right ventricular (RV) activation. Results The Figure shows the relationship between QRSd and e-DYS for individual types of stimulation on an intrinsic background (black). All pacing, except sHBP, modes significantly increased QRSd. QRSd was significantly larger during RVSP than all other pacing modes, but QRSd was not able to differentiate between nsHBP, sLBBP, nsLBBP and LVsp. In contrast to QRSd, e-DYS was positive during nsHBP and RVSP and negative during sLBBP, nsLBBP and LVSP (p<0.001). Conclusion e-DYS assessed with UHF-ECG provides more detailed information on the ventricular activation and is more superior in differentiating between CSP pacing modes, compared to standard QRSd. sHBP, nsHBP, nsLBBp, and LVSP create activation patterns closest to normal ventricular activation.

Subepicardial ischemia vs cardiac memory after tachycardia by intranodal reentry. case report and literature review

Cardiac memory is an electrophysiological property that is expressed as persistent electrophysiological changes in response to variations in the rate and sequence of cardiac electric activation and is defined as the persistent changes of the T wave on the electrocardiogram after a period of rhythms of wide QRS widened, and that becomes evident once the normal ventricular activation pattern is restored.1 The first evidence of its existence arises from case reports where changes in the polarity of the T wave were observed after transient episodes of tachyarrhythmias. Subsequently, it was demonstrated how ventricular activation by external sources in a prolonged way induces persistent changes in the electrocardiogram, and those changes persist after eliminating this source.6,8 Electrical memory can occur in a short and long term, when it is short-term, the changes are due to the modulation of the electrical activity of individual cardiac cells or cell to cell interaction, while long-term memory involves the synthesis of proteins and / or structural changes.8

Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation

Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.

Adaptation of ventricular repolarization dispersion during heart rate increase in humans: A roller coaster process

BackgroundRegional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis). MethodsWe measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers. ResultsFollowing pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state. ConclusionsOur results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias.

Comparison of QRSarea and left ventricular activation time during left bundle branch pacing and left ventricular septal pacing

Abstract Funding Acknowledgements Type of funding sources: None. Background Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). Objective To compare acute electrocardiographic (ECG) and vectorcardiographic (VCG) effects of LBBP and LVSP as compared to intrinsic conduction. Methods In 50 patients with normal cardiac function and pacemaker indication for bradycardia, ECG characteristics of LBBP and LVSP were evaluated during RVSP and pacing at various depths in the septum: starting at the RV side of the septum: the last position with QS morphology, the first position with r’ morphology, LVSP and – in patients where LBB capture was achieved – LBBP. From the ECG’s QRS duration and QRS morphology in V1, and the stimulus-LVAT interval were measured. After conversion of the ECG into VCG (Kors conversion matrix), QRS area was calculated. Results In LVSP, QRS area significantly decreased from 82 ± 29 µVs during RVSP to 46 ± 12 µVs during LVSP. In patients where LBB capture was achieved QRS area significantly decreased from 78 ± 23 µVs to 38 ± 15 µVs in LBBP. In patients with LBB capture, QRS area was significantly smaller during LBBP compared to LVSP (figure A), but LVAT was not significantly different (figure B, p = 0.138). In patients with normal ventricular activation where LBBP was achieved (n = 20), QRS area was significantly larger during LVSP (48 ± 17) compared to LBBP (37 ± 16), the latter being not significantly different from normal intrinsic ventricular activation (35 ± 19 µVs). Conclusions ECG and VCG indices demonstrate that ventricular dyssynchrony is comparable but slightly more synchronous during LBBP compared to LVSP. Abstract Figure. QRS area and S-LVAT in LVSP and LBBP

Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients

Background: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). Objective: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction. Methods: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r’ morphology, LVSP and—in patients where left bundle branch (LBB) capture was achieved—LBBP. From the ECG’s QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined. Results: QRS area significantly decreased from 82 ± 29 µVs during RV septal pacing (RVSP) to 46 ± 12 µVs during LVSP. In the subgroup where LBB capture was achieved (n = 31), QRS area significantly decreased from 46 ± 17 µVs during LVSP to 38 ± 15 µVs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 ± 16 vs. 35 ± 19 µVs, respectively). The Azimuth significantly changed from RVSP (−46 ± 33°) to LVSP (19 ± 16°) and LBBP (−22 ± 14°). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman’s R = 0.58). Conclusions: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP.

Effect of His bundle pacing on right bundle branch block located distal to site of pacing

BackgroundIt is generally accepted that bundle branch block (BBB) may be corrected simply by selective His bundle pacing (S-HBP) distal to site of block. However, clinical HBP is often non-selective (NS), the site of block unknown and moving the HB lead is not always an option. Thus, while correction of right (R) BBB in NS-HBP has been reported, its mechanism is unknown. MethodsThreshold testing was done during His bundle pacing in 39 patients with RBBB. We compared NS-HBP and S-HBP and analyzed the role of pacing voltage and capture threshold of the parallel pathway, in partially or completely correcting RBBB. ResultsDuring NS-HBP, higher pacing voltage completely corrected RBBB in 22/35 patients as compared to 5/18 patients at lower voltage. Remaining patients showed incomplete correction of RBBB. NS-HBP group with lower capture threshold of 1.3 ± 0.5 V completely resolved RBBB in 9/14 vs 3/11 patients in NS-S HBP group with higher capture threshold of 2.4 ± 0.8 V. QRS activation time in NSHBP was 91 ± 8 ms (baseline 97 ± 7 ms p = ns). S-HBP resolved RBBB in only 1/21 patients. Conclusions1.) Lack of correction with S-HBP suggests that RBBB was distal to site of HBP and yet was corrected with NS-HBP. 2.) Voltage dependent correction of RBBB in NS-HBP suggests that conduction via a specialized parallel pathway maintains normal ventricular activation time. 3.) Correction of RBBB in all patients with NS-HBP, suggests that conduction block was either bypassed or right ventricular free wall pre-excited by conduction via parallel pathway.

Clinical outcomes of His-Purkinje conduction system pacing.

His-Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP hasbeen extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms.

P508Biventricular pacing versus His bundle pacing after atrioventricular node ablation in heart failure patients with permanent atrial fibrillation and narrow QRS

Abstract Background Atrioventricular (AV) node ablation with biventricular (BiV) pacemaker implantation is a feasible rate control strategy for symptomatic permanent atrial fibrillation (AF) with rapid ventricular response and tachycardia-induced heart failure (HF). However, certain controversy exists since BiV pacing delivers non-physiological ventricular resynchronization and does not return left ventricular (LV) activation times to those seen in individuals with intrinsically narrow QRS. Permanent His bundle pacing (HBP) is a physiological alternative to conventional and BiV pacing. By capturing the native conduction system, depolarization of the ventricles through the His-Purkinje system induces normal synchronous ventricular activation. Purpose The aim of the study was to compare short-term outcomes between BiV pacing and HBP after AV node ablation in HF patients with symptomatic permanent AF and narrow QRS. Methods A total of 25 consecutive HF patients with permanent AF and narrow QRS (≤110 ms) who underwent AV node ablation in conjunction with BiV pacing or HBP in our centre were enrolled. Post-implant QRS duration, echocardiographic data, and New York Heart Association (NYHA) functional class were assessed in short-term follow-up. Results Among 25 HF patients (aged 68 ± 7 years, 52% female, QRS 96 ± 9 ms, LVEF 37 ± 7%, NYHA II-IV), 13 received BiV pacing and 12 HBP. Implant and ablation procedures were acutely successful in both groups. In BiV group 1 patient had a LV lead dislodgement and 1 patient in the HBP group had an acute HB lead threshold increase after AV node ablation. In HBP group post-implant QRS duration was shorter compared to BiV (103 ± 15 ms vs. 177 ± 13 ms, p < 0.001). At a median follow-up of 6 months, patients treated with HBP had greater increase in LV ejection fraction compared to BiV (44 ± 10 vs. 37 ± 6, p = 0.045). A trend toward greater reduction of LV volumes (EDV 119 ± 54 ml vs. 153 ± 33 ml, p = 0.07; ESV 75 ± 34 ml vs. 97 ± 26 ml, p = 0.09) and improvement of NYHA class (2.1 ± 0.7 vs. 2.7 ± 0.8, p = 0.08) was also observed in HBP group compared to BiV group. Conclusion In rate control refractory HF patients with permanent AF and narrow QRS atrioventricular node ablation in conjunction with HBP demonstrated superior electrical resynchronization and greater increase in LV ejection fraction compared to BiV pacing. Larger prospective studies are warranted to address clinical outcomes between both pace and ablate strategies.

His-Purkinje conduction system pacing and atrioventricular node ablation.

His-Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing and left bundle branch pacing allows normal ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. One potential area where HPCSP could be used is in the field of atrioventricular (AV) node ablation in patients with atrial fibrillation refractory to medical therapy and/or catheter ablation. His bundle pacing has been established for several years, with centres from North America, Europe and China publishing their experience. The differing patterns of His bundle capture are clearly described with established guidance as to how to implant such systems. Left bundle branch pacing has only recently been reported, but there are several advantages with better pacing parameters and lower risk of threshold change after AV node ablation. Six studies have been identified in the literature which describe the experience of His bundle pacing in patients requiring AV node ablation. Overall the results are positive and favour this new technique; however, they are limited by low numbers of patients and non-randomised study design. An observational study was recently published demonstrating better outcomes with left bundle branch pacing in asmall number of patients with left ventricular dysfunction and atrial fibrillationthat underwent AV node ablation. HPCSP has thepotential to be the primary pacing modalityin patients with atrial fibrillationrequiring AV node ablation. However, it is essential that this is confirmed in large randomised clinical trials.

GENDER DIFFERENCES IN ARRHYTHMIA BURDEN FOLLOWING CRT-D UTILIZING HIS BUNDLE PACING: A CARELINK ANALYSIS

Cardiac resynchronization therapy (CRT) with biventricular pacing involves pacing of the left ventricle through a pacing lead in the coronary sinus (or epicardial or endocardial left ventricle) which mimics normal ventricular activation, but is not physiologic. His bundle pacing allows pacing

Acute management of ventricular tachycardia.

Acute management of patients with ventricular arrhythmia (VA) is aimed at immediate VA termination if the patient is hemodynamically instable and early termination after initial diagnostic work-up if tolerated. Prolonged episodes of VA may lead to hemodynamic and metabolic decompensation and early resumption of normal ventricular activation is warranted. Termination is best performed by electrical cardioversion, anti-tachycardia pacing (if available, in cases with an implanted defibrillator [ICD]) or defibrillation. Antiarrhythmic drug treatment may lead to rhythm stabilization in cases of VA recurrence. Scrutinizing the electrocardiogram (ECG) of VA is extremely helpful to differentiate potential mechanisms, underlying cardiac pathologies and identify treatment options, as well as a differential diagnosis if a ventricular origin is unclear. In general, structural VA should be differentiated from idiopathic and non-structural (idiopathic) VA. On the other hand, based on ECG morphology VA should be classified into monomorphic versus polymorphic ventricular tacyhcardia (VT)/ventricular fibrillation (VF). Polymorphic VT/VF may be related to reversible causes as well as genetically determined arrhythmia syndromes and aspecialized treatment pathway may be chosen: (1)VA termination, (2)evaluation and treatment of potential VA causes, (3)acute (medical treatment) and chronic (interventional treatment using catheter ablation) prevention of recurrence and (4)treatment of underlying heart disease, if identified, are crucial pillars of VA management. These patients can be managed in dedicated VT units and by multispecialty teams integrating all potential aspects of rhythm stabilization and treating underlying cardiac abnormalities. Heart failure management in patients with reduced left ventricular function may be crucial for the long-term prognosis.

Reversion of cardiac memory during left bundle branch pacing

Cardiac memory (CM) is identified as an altered T wave when normal ventricular activation resumes after an abnormal myocardial activation period. We present a case who initially underwent temporary right ventricular apex (RVA) pacing for one week which induced typical pseudo-primary T wave changes. The T wave inversion was observed after the end of RVA pacing when left bundle branch pacing (LBBP) was initiated, and the abnormal T waves gradually return to almost normal repolarization during LBBP 40 days later.

Cardiac memory: diagnostic tool in the making.

Classic definition of the term cardiac memory (CM) refers to the persistent T-wave changes on the ECG after a period of wide QRS rhythms that become evident once normal ventricular activation pattern is restored. It is related to the term ventricular electric remodeling sometimes used in basic science literature. Although CM itself is considered as an adaptive reaction to the change in the ventricular activation sequence, its manifestations (usually T-wave inversions, TWIs) are often confused with pathological conditions manifesting with TWI, such as myocardial ischemia or infarction. Although originally CM was described after restoration of the normal ventricular activation (narrow QRS), recently it was described and studied in wide QRS rhythms significantly expanding the clinical relevance of this phenomenon. Although complex molecular mechanisms of CM have been previously reviewed extensively, practical clinical application of this phenomenon received much less attention. In this article, we will focus on the clinically relevant aspects of CM including its diagnostic use in narrow and wide QRS rhythms. We will also examine how the fundamental CM property of being initiated by the changes in the geometry of the ventricular contraction might open new perspectives in wide QRST morphology analysis by establishing parallels between electric and mechanical functions of the heart. In 1915, White1 was the first to observe the phenomenon of transient TWI after single ventricular premature beats. Later in the 1940s, TWIs after conversion to sinus rhythm were described after paroxysmal tachycardias.2 Since then abnormal T waves of various duration have been documented after intermittent ventricular pre-excitation,3–5 ventricular pacing,6,7 intermittent left bundle branch block (LBBB),8,9 ventricular tachycardia,10 and even QRS widening associated with sodium channel blocker toxicity.11 In 1982, Rosenbaum et al10 introduced the term heart memory and presented the …

The multiple electrocardiographic manifestations of ventricular repolarization memory.

T wave “memory” is a peculiar variety of cardiac remodeling caused by a transient change in the course of ventricular depolarization (due to ventricular pacing, rate-dependent intraventricular block, ventricular preexcitation or tachyarrhythmias with wide QRS complexes). It is usually manifested by inverted T waves that appears when normal ventricular activation is restored. This phenomenon is cumulative and occurs earlier if the ventricular myocardium has previously been exposed to the same conditioning stimuli. In this article the different conditions giving rise to “classical” T wave memory development are reviewed and also “another” type of T wave memory is described. It is also shown that cardiac memory may induce not only negative (pseudo-primary) T waves but also a reversal of primary and pseudo-primary T waves leading to “normalization” of ventricular repolarization. The knowledge of these dissimilar consequences of T wave memory is essential to assess the characteristics of ventricular repolarization.

QRS and QT Interval Changes and Ventricular Arrhythmias Following Continuous Flow Mechanical Unloading of the Failing Human Heart

Purpose The effect of continuous flow left ventricular assist devices (CF-LVAD) on the arrhythmogenicity of the failing heart is a controversial issue. We sought to investigate the association of CF-LVAD unloading on the electrical properties of the failing heart including the incidence of sustained ventricular tachycardia (VT)/ ventricular fibrillation (VF). Methods and Materials The records of 80 CF-LVAD patients from the UTAH Cardiac Transplant Program implanted between 2008 and 2011 were retrospectively reviewed. 12-lead ECGs and ICD interrogations were reviewed. We examined 12 lead ECGs for QRS and QT intervals before, 4 and 12 weeks after CF-LVAD implant. ICD recording episodes of VT and VF were checked before and after LVAD implantation. Results The average age was 55±15 years (75% males) and 53% had non-ischemic cardiomyopathy. The QRS duration was found to be decreased at 4 weeks following CF-LVAD implant and this decrease was sustained at 12 weeks (Table). The QT interval also decreased at 4 and 12 weeks (Table). QRS and QT changes were observed in patients with both paced (n=43; 68.3%) and normal ventricular activation. Twenty eight patients had a history of sustained VT/VF pre CF-LVAD. Twenty one patients had VT/VF episodes following CF-LVAD implant; 8 patients presented with de novo arrhythmias. The majority of ventricular arrhythmias were monomorphic VTs (66.7%); 4 (50%) occurred in the first 4 weeks, while 4 (50%) occurred 4-12 weeks following CF-LVAD. Conclusions Chronic CF-LVAD unloading is associated with shortening of QRS and QT intervals. Ventricular arrhythmias occurred de novo following surgery despite those changes. Further studies are needed to understand the effect of unloading on the ventricular arrhythmogenic milieu and substrate. 4 Weeks post 12 weeks post Pre-LVAD LVAD LVAD P value QT 155±37 ms 128±34 ms 120±41 ms * QRS 446±62 ms 409±77 ms 404±78 ms * * Pre-LVAD to 4 weeks post LVAD

Sudden arrhythmic death: from basic science to clinical practice

EDITORIAL article Front. Physiol., 25 November 2013Sec. Cardiac Electrophysiology Volume 4 - 2013 | https://doi.org/10.3389/fphys.2013.00339

Connexin43 and NaV1.5: Partners in crime?

c c i m t h s t Propagation of the electrical impulse through the myocardium depends on the critical interplay of various factors, including excitability, cell-to-cell coupling, and tissue architecture. Although intercellular transfer of current through gap junctions is essential for proper impulse propagation, mild-tomoderate reduction of the ventricular gap junctional protein connexin43 (Cx43) is generally well tolerated by the normal, uncompromised heart. Indeed, transgenic mice with 50% reduction of Cx43 display normal ventricular activation patterns and conduction velocities, while conduction slowing and increased arrhythmia susceptibility is observed only in those mice in which Cx43 levels are reduced by more than 90%. In the ischemic and failing myocardium, however, heterogeneous reduction in Cx43 expression contributes to conduction abnormalities and arrhythmogenesis. Thus, Cx43 reduction appears to be detrimental only when severely or heterogeneously suppressed or in the presence of additional contributing factors, such as structural abnormalities and/or reduced tissue excitability. This concept is further highlighted in the current issue of HeartRhythm by the study of Jansen et al on entricular arrhythmias in mice with a postnatally induced evere reduction in Cx43. More importantly, this study also mplicates a modulatory effect of Cx43 on the expression and unction of cardiac sodium channels, further underlining the ncreasing complex role of connexins. In recent years, it has become increasingly clear that conexins are not isolated entities simply involved in the conducion of ions and signals between adjacent myocytes, but that hey also physically and functionally interact with other proeins within the cell. A large number of connexin interacting roteins have now been identified, including structural proeins, cytoskeletal components, and adhesion molecules. These interacting proteins are incorporated into a macromolecular complex through which connexins can exert regulatory effects on intracellular signaling, cytoskeletal organization, and cell adhesion. Desmosomal proteins such as plakoglobin and

Vectorcardiography shows cardiac memory and repolarization heterogeneity after ablation of accessory pathways not apparent on ECG

BackgroundPacing induced cardiac memory is an established phenomenon, but following successful WPW ablation, cardiac memory was present on ECG in variable proportions of patients depending on accessory pathway (AP) location. We hypothesized that vectorcardiography (VCG), which is more sensitive than ECG, would show cardiac memory after WPW ablation independent of AP location. MethodsThirty-six patients were followed after successful AP ablation, 11 with overt posteroseptal (PS), 13 with overt left-sided (LS) and 12 with concealed APs (controls). VCGs were recorded the day before and after the procedure, ≥once/week for 6–8weeks and after ≥3months. T vector and T-vector loop parameters were analyzed and compared. ResultsAfter ablation of overt APs, there was a correlation between the directions of the preexcited maximum QRS-vector and the post-ablation maximum T-vector, confirming the presence of cardiac memory. Ablation of overt APs was followed by cardiac memory apparent in different directions. Thus, ablation of PS APs was followed by most pronounced changes in T-vector elevation and LS APs with significant changes only in T-vector azimuth. Cardiac memory disappeared within a month in >80% of cases. Furthermore, T-vector loop morphology changes suggested a period of repolarization heterogeneity immediately after ablation of overt APs. ConclusionsAccording to VCG analysis cardiac memory was present after ablation of overt APs independent of location as consistently as after ventricular pacing, and disappeared within a similar time frame during normal ventricular activation. In addition, signs of transient repolarization heterogeneity were observed after ablation of overt APs.