Local Electrogram Research Articles

Ibutilide Increases the Variability and Complexity of Atrial Fibrillation Electrograms: Antiarrhythmic Insights Using Signal Analyses

Intravenous ibutilide is used to convert atrial fibrillation (AF) to sinus rhythm (SR) due to its Class III antiarrhythmic mechanisms. However, the effects of ibutilide on local electrograms (EGMs) during AF have not been elucidated. We used EGM analysis techniques to characterize how ibutilide administration changes the frequency, morphology, and repeatability of AF EGM signals, thereby providing insight into ibutilide's antiarrhythmic mechanism of action. AF recordings were collected from 21 patients with AF, both before and after ibutilide administration. The effects of ibutilide on the following AF EGM parameters were assessed: (1) dominant frequency (DF), (2) variations in EGM amplitude and overall morphology, (3) repetition of EGM patterns, and (4) complexity of the AF frequency spectra. When comparing pre- versus post-ibutilide administration EGMs, DF decreased from 5.45 Hz to 4.02 Hz (P < 0.0001). There was an increase in the variability of both AF EGM amplitudes (P = 0.003) and overall AF EGM morphologies (P = 0.003). AF EGM pattern repetitiveness decreased (P = 0.01), and the AF frequency spectral profile manifested greater complexity (P = 0.02). Novel EGM signal analysis techniques reveal that ibutilide administration causes increased complexity in the atrial electrical activation pattern with decreasing rate. These findings may be explained by the progressive destabilization of higher frequency, more homogeneous primary drivers of AF over the course of ibutilide administration, and/or less uniform propagation of atrial activation, until AF maintenance becomes more difficult and either transforms to atrial tachycardia or terminates to SR.

Defibrillation Success Is Not Associated With Near Field Electrogram Complexity or Shock Timing

BackgroundIt has been suggested that more-complex fibrillation requires higher energy shocks to terminate. Furthermore, animal studies have demonstrated that shock timing also plays a role. The objective of this study was to test these assertions in a clinical context. MethodsNear- and far-field electrograms were collected during defibrillation threshold testing. Fibrillation complexity was measured by quantifying the organization in the signals with wavelet-based methods, scaling exponent, and cross-correlation analysis. Receiver operator characteristic curves were used to determine predictive value. The effect of the phase at which defibrillation shocks were applied was also determined. ResultsNo measure was able to classify whether a particular shock would be successful. All performed very poorly. Shock timing played no role in defibrillation outcome. ConclusionsSignal organization of a local electrogram and phase of shock delivery do not relate to minimum defibrillation shock energy immediately after ventricular fibrillation onset.

Understanding atrial arrhythmia mechanisms by mapping and ablation

strate for the arrhythmia. It is perhaps pertinent to note the limitations of the electrocardiogram diagnosis. The term ‘flutter’ is used to describe rapid atrial tachycardias (AT) with an undulating waveform without isoelectric baseline; however, this has been overlooked by many groups reporting left AT that, as in Coffey’s paper, show rather long cycle lengths, around 300 ms, and longer isoelectric baselines between P-waves. Since the term ‘flutter’ is so closely related to typical flutter, depending on the cavotricuspid isthmus, it tends to suggest a macroreentrant mechanism, and the term ‘atrial tachycardia’ would appear more appropriate, as it does not pre-judge the mechanism. 2 In fact, around one-third of the mechanisms described in this study were focal discharges. The mapping technique, leading to ablation of the critical isthmus or the focus responsible for the arrhythmia, is remarkable because it creates excellent activation maps on the virtual atrial anatomy and allows, with some limitations, better understanding of the arrhythmia mechanism. Reduction of pacing manoeuvres to the minimum necessary to confirm the role of critical areas of the circuit minimizes the chances of altering activation sequences, a significant concern in left atrial macroreentrant AT, in which complex combinations of anatomic and functional obstacles can support multiple reentrant circuits and/or focal mechanisms. The average number of AT mechanisms encountered was 1.9 per patient, and 21 patients had three or more AT mechanisms, underlining the importance of this method. Another point of interest is the extremely low voltage recorded at some of the critical isthmuses that would suggest that activation could course over thin epicardial layers of atrial myocardium over endocardial scars. The interpretation of these local electrograms would be very difficult in the absence of the full activation maps supported with critical entrainment runs to confirm participation of adjacent areas in the circuit. The complexity and low amplitude of the electrograms would make quite impossible to reliably measure local post-pacing intervals at these critical isthmuses. Atrial tachycardia mechanisms were based in both atria and one-third were called septal. Two-thirds of the AT had a macroreentrant mechanism, and about one-third were focal. It is not clear from the paper if combinations of focal and macroreentrant mechanisms were found in the same patient and if more than one AT could be localized at distant sites in the same patient, but the report does give the general impression of dealing with severely diseased (remodelled? injured?) atria. The worse performance with ‘septal’ AT raises questions about the ability to precisely locate foci or critical isthmuses in this anatomically complex area. This seems particularly relevant because fragmented electrograms are often recorded from the septal atrial walls 3 and this

Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation: stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms.

The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE). Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0-3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm(2); P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67). Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm(2), with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF.

Relationship between MRI-based mechanical activation delays and direct intraoperative measurements of electrical delay in patients undergoing cardiac resynchronization

Background Magnetic Resonance Imaging (MRI) can be used to create maps of left ventricular (LV) mechanical activation delay by analyzing time-dependent radial motion of the myocardium. Local electrograms (EGM) can be obtained during the CRT procedure to measure local electrical activation delay in the LV myocardium. Preoperative MRI assessment of regional dyssynchrony would be useful to guide CRT lead placement. However, the relationship between electrical and mechanical dyssynchrony has not been studied in humans. We hypothesized that intraoperative electrical delay times will correlate with MR-based mechanical delay times.

Differences of BiAtrial Substrate Properties in Patients with Different Types of AF.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and induces cardiac dysfunction and strokes. The development of AF requires a"trigger" and also an electroanatomic "substrate" capable of both initiating and perpetuating AF. Over the past decade, the understanding of the AF substrate properties in both atria has increased with fractionation and frequency analyses of the local atrial electrograms using three-dimensional electroanatomic mapping systems. The purpose of this review was to discuss the differences in the atrial substrate properties in patients with different types of AF.

Myocardial Structural Associations With Local Electrograms

Background— The association of scar on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) with local electrograms on electroanatomic mapping has been investigated. We aimed to quantify these associations to gain insights regarding LGE-CMR image characteristics of tissues and critical sites that support postinfarct ventricular tachycardia (VT). Methods and Results— LGE-CMR was performed in 23 patients with ischemic cardiomyopathy before VT ablation. Left ventricular wall thickness and postinfarct scar thickness were measured in each of 20 sectors per LGE-CMR short-axis plane. Electroanatomic mapping points were retrospectively registered to the corresponding LGE-CMR images. Multivariable regression analysis, clustered by patient, revealed significant associations among left ventricular wall thickness, postinfarct scar thickness, and intramural scar location on LGE-CMR, and local endocardial electrogram bipolar/unipolar voltage, duration, and deflections on electroanatomic mapping. Anteroposterior and septal/lateral scar localization was also associated with bipolar and unipolar voltage. Antiarrhythmic drug use was associated with electrogram duration. Critical sites of postinfarct VT were associated with &gt;25% scar transmurality, and slow conduction sites with &gt;40 ms stimulus-QRS time were associated with &gt;75% scar transmurality. Conclusions— Critical sites for maintenance of postinfarct VT are confined to areas with &gt;25% scar transmurality. Our data provide insights into the structural substrates for delayed conduction and VT and may reduce procedural time devoted to substrate mapping, overcome limitations of invasive mapping because of sampling density, and enhance magnetic resonance–based ablation by feature extraction from complex images.

Interventional Endocardial Motion Estimation from Electroanatomical Mapping Data: Application to Scar Characterization

Scar presence and its characteristics play a fundamental role in several cardiac pathologies. To accurately define the extent and location of the scar is essential for a successful ventricular tachycardia ablation procedure. Nowadays, a set of widely accepted electrical voltage thresholds applied to local electrograms recorded are used intraoperatively to locate the scar. Information about cardiac mechanics could be considered to characterize tissues with different viability properties. We propose a novel method to estimate endocardial motion from data obtained with an electroanatomical mapping system together with the endocardial geometry segmented from preoperative 3-D magnetic resonance images, using a statistical atlas constructed with bilinear models. The method was validated using synthetic data generated from ultrasound images of nine volunteers and was then applied to seven ventricular tachycardia patients. Maximum bipolar voltages, commonly used to intraoperatively locate scar tissue, were compared to endocardial wall displacement and strain for all the patients. The results show that the proposed method allows endocardial motion and strain estimation and that areas with low-voltage electrograms also present low strain values.

Abstract 9628: Association of Electrogram Features and Critical Reentrant Ventricular Tachycardia Sites with Nonischemic Scar on Late Gadolinium Enhanced Cardiac Magnetic Resonance

Introductions: The association of local electrogram features with nonischemic scar morphology and distribution on electroanatomic maps (EAM) has not been investigated. We aimed to quantitatively assess the association of nonischemic scar on late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) with local electrograms and critical sites in patients with nonischemic cardiomyopathy (NICM). Methods: LGE-CMR was performed in 19 patients with NICM. Scar characteristics were classified by scar transmurality and intramural scar types (endocardial, mid-wall, epicardial, patchy, transmural) on LGE-CMR short-axis planes (Figure, upper panel). EAM points were registered to the corresponding LGE-CMR images. Multivariable regression analysis clustered by patient was performed to assess the association of myocardium thickness, scar transmurality and intramural scar types, with electrogram bipolar/unipolar amplitude, duration and deflections. LGE-CMR characteristics of critical ventricular tachycardia (VT) sites were also investigated. Results: In pooled analyses, higher scar transmurality was significantly associated with lower bipolar (Figure, lower panel)and unipolar electrogram amplitude, longer duration and more deflections (P&lt;0.0001). Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P&lt;0.0001) and patchy scar (vs. endocardial, mid-wall, epicardial scar, P&lt;0.05). Most of the critical sites (16 sites; 89%) were located in scar with &gt;25% scar transmurality. Myocardial wall thickness, scar transmurality and intramural scar types were independently associated with electrogram features on multivariable regression analyses. Conclusions: Electrogram features on endocardial EAM are associated with scar morphology and distribution on LGE-CMR in NICM. This result may optimize procedural strategies including the decision to obtain epicardial access.

Nonlinear Analysis of Fibrillatory Electrogram Similarity to Optimize the Detection of Complex Fractionated Electrograms During Persistent Atrial Fibrillation

Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length-derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity. One hundred persistent atrial fibrillation patients that underwent catheter ablation were included. In patients who required CFE ablation (79%), the time-domain fibrillation signals (6 seconds) were acquired for a linear analysis (mean fractionation interval and dominant frequency [DF]) and nonlinear-based waveform similarity analysis of the local electrograms, termed the similarity index (SI). Continuous CFEs were targeted with an endpoint of termination. Predictors of the various signal characteristics on the termination and clinical outcome were investigated. Procedural termination was observed in 39% and long-term sinus rhythm maintenance in 67% of the patients. The targeted CFEs didn't differ based on the linear analysis modalities between the patients who responded and did not respond to CFE ablation. In contrast, the average SI of the targeted CFEs was higher in termination patients, and they had a better outcome. Multivariate regression analysis showed that a higher SI independently predicted sites of termination (≥ 0.57; OR = 4.9; 95% CI = 1.33-18.0; P = 0.017). In persistent AF patients, a cycle length-based linear analysis could not differentiate culprit CFEs from bystanders. This study suggested that sites with a high level of fibrillation electrogram similarity at the CFE sites were important for AF maintenance.

Prevalence and Types of Pitfall in the Assessment of Mitral Isthmus Linear Conduction Block

To identify and understand clinically encountered pitfalls in the assessment of transmitral conduction block using differential coronary sinus and left atrial appendage pacing techniques in patients with left mitral isthmus linear ablation. All the available assessments of mitral isthmus block were thoroughly reviewed in 271 mitral isthmus ablation procedures undertaken among 236 patients from October 2008 to April 2011. Bidirectional block was established in 186 of 271 (69%) procedures. Careful evaluation of electrograms recorded on the multipolar coronary sinus and ablation catheters was undertaken to identify and understand the characteristics of pitfall, if any. Pitfall was encountered in 55 of 271 (20%) procedures among 51 patients and categorized into 6 types (types 1, 3, 4, and 5 led to spurious diagnosis of block; types 2 and 6 led to erroneous diagnosis of absence of block). There were 14, 10, 17, 2, 15, and 3 (total=61) cases of pitfall types 1 through 6, respectively. Operator recognized 42 of 61 (69%) pitfalls intraprocedurally. Recognition of types 1 and 5 was difficult because of indiscernible electrograms at usual amplifier settings or presence of slow conduction mimicking block. Every fifth assessment of bidirectional block across mitral isthmus linear lesion using differential coronary sinus and left atrial appendage pacing techniques encounters a pitfall, which can lead to erroneous clinical diagnosis of block or absence of block. Recognition of pitfall during the procedure is feasible and necessitates careful distinction of far-field left atrium from the local coronary sinus electrograms besides appropriate adjustments in catheter position and pacing outputs.

Further Evidence for the “Muscle Bundle” Hypothesis of Cavotricuspid Isthmus Conduction: Physiological Proof, with Clinical Implications for Ablation

It has been suggested that the cavotricuspid isthmus (CTI) is composed of discrete muscle bundles with preferred paths of conduction. An ablation technique targeting high-voltage local electrograms (maximum voltage guided or MVG technique) has been described with the aim of preferentially targeting the muscle bundles. We hypothesized that the MVG technique could provide isthmus block even if the high voltage targets were clearly separated on different ablation lines. In contrast, conduction over a continuous sheet of muscle would require a single continuous ablation line. Twenty-two consecutive patients (mean age 65 ± 11.7, 5 females) underwent ablation using the MVG technique on 2 noncontiguous lines in the CTI. Ablation lesions were first applied at the septal aspect of the CTI, targeting only the ventricular (anterior) aspect of the annulus. A line distinctly lateral and noncontiguous to the first was then chosen to target high voltage potentials on the atrial (posterior) aspect of the CTI. Complete CTI block was achieved in all study patients without complication. A mean of 7.8 ± 3.7 ablation lesions were required. Mean ablation time was 401.0 ± 414.5 seconds. Two nonoverlapping incomplete lines of ablation in the CTI consistently lead to bidirectional conduction block. This further supports the hypothesis that conduction over the CTI occurs over discrete muscle bundles. These bundles can be targeted individually for ablation without the need to ablate a continuous line over the CTI.

Novel tips for engaging the coronary sinus guided by right ventricular lead

This study investigated the relationship between the ostia of the coronary sinus (CS) and the tricuspid annulus (TA) for CS cannulation using a right ventricular (RV) lead, which could map out the TA by forming a curve when placed at the apex or low septum. Seventy patients (45 males, 67 ± 12 years) who were admitted for CRT device implant were included in the evaluation of the relationship between the CS ostia and TA. An electrophysiological (EP) mapping catheter was used to probe the CS. The ostium was shown by the CS venography at the left anterior oblique (LAO) 20° and caudal 20°. Local electrograms were collected with CS catheters in the CS or RV. Transthoracic echocardiography was evaluated before each procedure. All CS ostia were located within 3.75 cm around the tip of TA. Sixty-two subjects (Group I, 89%) had CS ostia located under the TA. Eight patients (Group II) with CS ostia over the TA revealed larger left ventricular (LV) size and a smaller ratio of left atrium (LA)/LV size. LV enlargement predicted the presence of CS ostia over the TA. Typical CS electrograms were used to further confirm if the EP catheter was in the CS in all the subjects. Use of the RV lead revealed that the CS ostia had a close relationship with the TA.

Two distinct electrocardiographic forms of idiopathic ventricular arrhythmia originating in the vicinity of the His bundle

The objective is to assess electrocardiographic characteristics predicting the precise location of ventricular arrhythmia (VA) origin within the right ventricle (RV) close to the His bundle (HB) region. Twenty-five patients (14 men, age 65 ± 14 years) underwent successful catheter ablation of para-Hisian VA. Ventricular arrhythmias were considered to arise in the vicinity of the HB region based on the criteria that mapping exhibited the earliest RV activation before QRS onset in the HB region. Surface 12-lead electrocardiogram during the para-Hisian VAs was analysed. Of the 25 patients, 8 originated from the RV antero-septum just above the HB region, and 17 arose from the RV mid-septum just below the HB region. There was no significant difference in precedence of the local ventricular electrogram of the HB region from the onset of surface QRS during VAs. Surface electrocardiographic findings were characterized according to R-wave amplitude in lead I (0.43 ± 0.18 vs. 0.67 ± 0.19 mV, P = 0.005), mean R-wave amplitude in inferior leads (1.12 ± 0.32 vs. 0.71 ± 0.24 mV, P = 0.002), R-wave amplitude ratio of leads III/II (0.77 ± 0.10 vs. 0.50 ± 0.23, P = 0.005), incidence of S-wave in lead III [1/8 (13%) vs. 16/17 (94%), P < 0.001], and QS morphology in lead V1 [3/8 (38%) vs. 17/17 (100%), P = 0.001]. Despite their adjacent locations, para-Hisian VAs could be classified into two subgroups with distinctive electrocardiographic characteristics according to origin either above or below the HB region. The present findings can be helpful for planning catheter ablation of para-Hisian VAs, and can reduce the risk of inadvertent atrioventricular block.

Local electrogram delay recorded from left ventricular lead at implant predicts response to cardiac resynchronization therapy: Retrospective study with 1 year follow up

BackgroundConsiderable proportion of patients does not respond to the cardiac resynchronization therapy (CRT). This study investigated clinical relevance of left ventricular electrode local electrogram delay from the beginning of QRS (QLV). We hypothesized that longer QLV indicating more optimal lead placement in the late activated regions is associated with the higher probability of positive CRT response.MethodsWe conducted a retrospective, single–centre analysis of 161 consecutive patients with heart failure and LBBB or nonspecific intraventricular conduction delay (IVCD) treated with CRT. We routinely intend to implant the LV lead in a region with long QLV. Clinical response to CRT, left ventricular (LV) reverse remodelling (i.e. decrease in LV end-systolic diameter - LVESD ≥10%) and reduction in plasma level of NT-proBNP >30% at 12-month post-implant were the study endpoints. We analyzed association between pre-implant variables and the study endpoints.ResultsClinical CRT response rate reached 58%, 84% and 92% in the lowest (≤105 ms), middle (106-130 ms) and the highest (>130 ms) QLV tertile (p < 0.0001), respectively. Longer QRS duration (p = 0.002), smaller LVESD and a non-ischemic cardiomyopathy (both p = 0.02) were also univariately associated with positive clinical CRT response. In a multivariate analysis, QLV remained the strongest predictor of clinical CRT response (p < 0.00001), followed by LVESD (p = 0.01) and etiology of LV dysfunction (p = 0.04). Comparable predictive power of QLV for LV reverse remodelling and NT-proBNP response rates was observed.ConclusionLV lead position assessed by duration of the QLV interval was found the strongest independent predictor of beneficial clinical response to CRT.

Role of the coronary sinus ostium musculature in reentrant formation

Radiofrequency ablation of focal atrial tachycardias (AT) is a validated technique with high success rates. However, electrophysiological (EP) characteristics and ablation strategy of localized reentrant AT originating from the coronary sinus ostium (CSo) have not been reported in detail so far. From January 2009 to July 2010, 1,453 patients underwent clinically motivated EP studies. Four patients were diagnosed with localized reentrant AT originating from the CSo. P wave morphology and consistency of tachycardia cycle length were studied. Subsequently, if reentry was suggested as an underlying mechanism for AT, color-coded 3-dimensional (3D) entrainment mapping was performed to localize the reentrant circuit or differentiate a localized reentrant AT from macroreentant AT, and also confirm reentry as an underlying mechanism of AT by evaluating consistency of return cycles after entrainment at multiple sites in both atria. Finally, activation mapping was performed to localize the earliest activation site. The P wave morphologies and isoelectric line between the P waves suggested most likely an AT originating from the CSo with a centrifugal activation pattern, which was confirmed by activation mapping. Consistency of return cycles and continuously fragmented local electrograms at successful ablation sites suggested reentry as an underlying AT mechanism. Color-coded 3D entrainment mapping in all 4patients located the reentrant circuit in the CSo. There were also two specific features observed. One was fragmented and/or double potentials recorded in the CSo with prominent prolonged electrogram duration compared to those during sinus rhythm. The other is a significant conduction delay within the CS. The myocardium of the CSo was suggested as a part of the critical isthmus within the reentrant circuit, while the rest of atria distal to the CSo and myocardial coat of the distal CS were not involved in the tachycardia circuit, which was confirmed by entrainment mapping. Although CSo myocardium has been implicated to be a part of atrioventricular nodal reentrant tachycardia, to the best of our knowledge, this is the first report showing the localized reentrant AT confined to the CSo. Three of our patients (75%) had concomitant atrial fibrillation (AF). Further studies should be warranted to clarify the role of AT from the CS in triggering AF.

Intraoperative Electroanatomic Mapping

An electroanatomic mapping system using an electromagnetic navigation technology constructs a 3-dimensional structure of the heart with high geometric accuracy of the data that provides a precise localization of the substrates of arrhythmias. The system was tested for the feasibility and efficacy in intraoperative mapping. The strength of the magnetic field is measured by a location sensor with three different frequencies generated by a location pad placed beneath the operating table, and the spatial location of the sensor is determined. By roving the catheter on the heart while the local electrogram is recorded simultaneously, the 3-dimensional figure of the heart is reconstructed and an activation or voltage map is generated. The system was used in 19 patients with ventricular tachycardia or other arrhythmias. The focus or reentrant circuit of the tachycardia was precisely located and a map-guided procedure was successfully performed in all patients. Cardiopulmonary bypass allowed for the tachycardias to be mapped without any hemodynamic compromise. Intraoperative mapping using the electroanatomic mapping system enables a precise localization of the tachycardia substrate.

Hitting a moving target: Catheter ablation and respiration

Catheter ablation requires manipulating an electrode-tipped catheter to remotely target and modify arrhythmogenic myocardium. Ablation success is challenged by the inability to directly visualize complex 3-dimensional cardiac structures, necessitating the use of indirect observational methods. Fluoroscopy delineates the entire course of an electrode catheter but displays myocardial tissues poorly, leading to a reliance on other means of determining catheter position and contact. Local electrogram content such as the presence of a His bundle or vein potential aid in electrode localization, but reveal little information as to electrode tissue contact force.

SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic

Reentry accounts for most life-threatening arrhythmias, complicating myocardial infarction, and therapies that consistently prevent reentry from occurring are lacking. In this study, we compare antiarrhythmic effects of gene transfer of green fluorescent protein (GFP; sham), the skeletal muscle sodium channel (SkM1), the liver-specific connexin (Cx32), and SkM1/Cx32 in the subacute canine infarct. Immediately after ligation of the left anterior descending artery, viral constructs were implanted in the epicardial border zone (EBZ). Five to 7 days later, efficient restoration of impulse propagation (narrow QRS and local electrogram duration) occurred in SkM1, Cx32, and SkM1/Cx32 groups (P< 0.05 vs. GFP). Programmed electrical stimulation from the EBZ induced sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) in 15/22 GFP dogs vs. 2/12 SkM1, 6/14 Cx32, and 8/10 SkM1/Cx32 (P< 0.05 SkM1 vs. GFP). GFP, SkM1, and SkM1/Cx32 had predominantly polymorphic VT/VF, whereas in Cx32 dogs, monomorphic VT predominated (P< 0.05 for Cx32 vs. GFP). Tetrazolium red staining showed significantly larger infarcts in Cx32- vs. GFP-treated animals (P< 0.05). Whereas SkM1 gene transfer reduces the incidence of inducible VT/VF, Cx32 therapy to improve gap junctional conductance results in larger infarct size, a different VT morphology, and no antiarrhythmic efficacy.

Decomposition of fractionated local electrograms using an analytic signal model based on sigmoid functions

Microstructural heterogeneities in cardiac tissue, such as embedded connective tissue secondary to fibrosis, may lead to complex patterns of electrical activation that are reflected in the fractionation of extracellularly recorded electrograms. The decomposition of such electrograms into non-fractionated components is expected to provide additional information to allow a more precise classification of the microstructural properties adjacent to a given recording site. For the sake of this, an analytic signal model is introduced in this study that is capable of reliably identifying extracellular waveforms associated with sites of initiating, free-running, and terminating or colliding activation wavefronts. Using this signal model as a template, a procedure is developed for the automatic decomposition of complex fractionated electrograms into non-fractionated components. The decomposition method has been validated using electrograms obtained from one- and two-dimensional computer simulations in which all relevant intracellular and extracellular quantities are accessible at a very high spatiotemporal resolution and can be manipulated in a controlled manner. Fractionated electrograms were generated in these models by incorporating microstructural obstacles that mimicked inlays of connective tissue. Using this signal model, fractionated electrograms emerging from microstructural heterogeneities in the submillimeter range with latencies between components down to 0.6 ms can be decomposed.