Multielectrode Mapping Research Articles

Temporal-component analysis of diastolic electrograms in ventricular tachycardia differentiates nonvulnerable regions of the circuit.

Successful activation mapping of ventricular tachycardia (VT) is dependent on the identification of a region of diastolic conduction by use of point-by-point sequential mapping. It is important to identify the site of transition from diastolic conduction to systolic activation of healthy myocardium (exit site) and differentiate this from nonvulnerable regions of the circuit. We sought to determine the temporal and component characteristics of exit-site electrograms using simultaneous multielectrode endocardial mapping and to differentiate them from bystander sites during activation mapping. Sixteen VTs induced in 12 patients with ischemic cardiomyopathy who underwent multielectrode mapping during VT performed with a custom-made 112-bipolar-electrode endocardial array were analyzed retrospectively. The activation sequence in systole and diastole was annotated, and the timing at exit and bystander sites of the near-field component was characterized in relation to surface electrocardiogram activation and to the far-field component. Spectral content of bipolar electrograms recorded at these sites was additionally analyzed to identify the near-field to far-field interval. The mean activation time at exit sites was 60.0 ± 31.5 ms (range 21-113 ms) ahead of surface QRS but was not significantly different from bystander sites (72.0 ± 55.0 ms, P = .63). However, the time delay from local to far-field activity was significantly lower at exit sites than at bystander sites (24.9 ± 15.6 vs. 86.6 ± 92.0 ms, P = .003), which was confirmed by spectral analysis (10.0 ± 13.1 vs. 89.0 ± 64.5 ms, P = .003). Our analysis suggests that temporal-component analysis of diastolic electrograms during activation mapping of VT provides a practical method to differentiate nonvulnerable sites from the exit site without the need for pacing maneuvers.

Imaging of Ventricular Fibrillation and Defibrillation: The Virtual Electrode Hypothesis.

Ventricular fibrillation is the major underlying cause of sudden cardiac death. Understanding the complex activation patterns that give rise to ventricular fibrillation requires high resolution mapping of localized activation. The use of multi-electrode mapping unraveled re-entrant activation patterns that underlie ventricular fibrillation. However, optical mapping contributed critically to understanding the mechanism of defibrillation, where multi-electrode recordings could not measure activation patterns during and immediately after a shock. In addition, optical mapping visualizes the virtual electrodes that are generated during stimulation and defibrillation pulses, which contributed to the formulation of the virtual electrode hypothesis. The generation of virtual electrode induced phase singularities during defibrillation is arrhythmogenic and may lead to the induction of fibrillation subsequent to defibrillation. Defibrillating with low energy may circumvent this problem. Therefore, the current challenge is to use the knowledge provided by optical mapping to develop a low energy approach of defibrillation, which may lead to more successful defibrillation.

Clinical utility of multielectrode contact mapping for scar-related ventricular tachycardia ablation: A prospective single-center experience

BackgroundAs with the use of circular catheters for pulmonary vein antral ablation, it may be favorable to use multipolar catheters for substrate mapping of the left ventricle (LV). The purpose of this study was to investigate the clinical feasibility of using multielectrode mapping combined with an impedance-based electroanatomic mapping system for scar-mediated ventricular tachycardia (VT). MethodsBy using the multielectrode catheter in conjunction with the Velocity system, we obtained both geometric and electrogram data simultaneously, through transseptal and transsubxiphoid approaches. Higher-density mapping was performed in areas of dense scar (<0.5mV) and border zones (0.5–1.5mV). All late potentials (LPs) observed on the multipoles were tagged, and pace mapping was performed at those sites for comparison with the targeted VT morphology. Ablation was performed at target sites on the multipolar catheter that were identified by pace mapping, as well as at sites identified to have LPs and to be the origin of the premature ventricular complexes (PVCs) that triggered the VT. ResultsSixteen patients (8/8: ischemic/nonischemic cardiomyopathy) underwent endocardial (n=16) and epicardial (n=8) mapping. The mean number of endocardial and epicardial mapping points was 504±136 and 670±211, respectively, with an average mapping time of 21±6min. LPs were seen in 13 patients (81%), and good (56%) and perfect (31%) pace maps were seen in 14 patients (88%). In two patients, sites with the earliest activation of PVCs that triggered VT were successfully identified with multipolar catheter mapping. A distinct geometric distortion of the endocardial LV was confirmed in two patients, and those were modified by dividing the LV into two chambers. After 10.0±3.7 months, 71% of the patients have remained free of VT episodes. ConclusionMultipolar catheter mapping combined with the Velocity system results in a high-density delineation of the LV substrates in a relatively short time, suggesting that this is a feasible alternative mapping strategy for scar-related VT.

Initial results of using a novel irrigated multielectrode mapping and ablation catheter for pulmonary vein isolation

Pulmonary vein isolation (PVI) as a cornerstone for catheter ablation of atrial fibrillation (AF) remains a complex and time-consuming procedure. To assess feasibility, safety, and acute efficacy of a novel irrigated multielectrode ablation catheter guided by an electroanatomic mapping system for PVI in patients with paroxysmal AF. Twenty-five consecutive patients (60 ± 10 years) with paroxysmal AF underwent PVI by using a novel decapolar mapping and ablation catheter (nMARQ catheter, Biosense Webster Inc, Diamond Bar, CA). Ablation was guided by electroanatomic mapping allowing radiofrequency (RF) energy delivery in the antral region of pulmonary veins (PVs) from 10 irrigated electrodes simultaneously. The day after ablation, cardiac magnetic resonance imaging was performed routinely in order to assess for potential acute PV stenosis. Overall, 97 of 97 (100%) targeted PVs could be isolated with a mean of 27 ± 11 RF applications and a mean total burning time of 15 ± 6 minutes per patient. The total procedure time from femoral vein access to catheter withdrawal was 110 ± 31 minutes, including a mean total fluoroscopy time of 23 ± 9 minutes. On average, 6 ± 3 RF impulses with a maximum of 25 W were applied per vein. After a short learning curve, procedure, fluoroscopy, and total burning times decreased to 94 ± 16, 16 ± 3, and 9 ± 2 minutes, respectively (P < .05). Entrance and exit blocks could be verified by placing the ablation catheter into 90 of 97 (93%) PVs in 18 of 25 (72%) patients. No procedure-related complications were observed, especially no acute PV stenosis could be detected. The use of a novel irrigated multielectrode ablation system for PVI is feasible and safe, resulting in acute isolation of all targeted PVs with no complications and short procedure times. Sustainability of these initial results has to be confirmed in long-term efficacy and follow-up trials.

Mapping and modeling gastrointestinal bioelectricity: from engineering bench to bedside.

A key discovery in gastrointestinal motility has been the central role played by interstitial cells of Cajal (ICC) in generating electrical slow waves that coordinate contractions. Multielectrode mapping and multiscale modeling are two emerging interdisciplinary strategies now showing translational promise to investigate ICC function, electrophysiology, and contractions in the human gut.

Ventricular interaction rather than electrical resynchronisation determines haemodynamic response to cardiac resynchronisation therapy in dyssynchronous heart failure

Purpose: It is still unclear why left ventricular and biventricular pacing (LVP and BiVP, respectively) have comparative positive effects on haemodynamic function of patients with dyssynchronous heart failure (HF). To enhance understanding of the working mechanism of cardiac resynchronisation therapy (CRT), we assessed haemodynamic and local electromechanical consequences of LVP in comparison to BiVP. Methods: Haemodynamic response to LVP and BiVP (%-change LVdP/dtmax) was measured in 6 dogs with HF and left-bundle branch block (LBBB) and in 40 HF patients with QRS-width ≥120ms, followed by computer simulations of local myofibre mechanics during LVP and BiVP in the failing heart with LBBB. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode epicardial electrocardiographic mapping technique. Results: LVP and BiVP similarly increased LVdP/dtmax in dogs (p=0.33) and in patients (p=0.93), but only BiVP significantly decreased electrical dyssynchrony (Figure). In the simulations, LVP and BiVP increased total ventricular myofibre work to the same extent (Figure). While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofibre work, the BiVP-induced increase was due to enhanced myofibre work of both the LV and RV. Overall, LVdP/dtmax correlated better with total ventricular myofibre work than with LV or RV myofibre work alone. ![Figure][1] Conclusions: Experimental, human, and computational data support the similarity of haemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by CRT. [1]: pending:yes

Introduction to the Series on Computational Approaches to Cardiac Arrhythmias

Of all the cardiac arrhythmias seen in clinical practice, atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are among the leading causes of morbidity and mortality in the developed world. AF is the most common sustained arrhythmia and is associated with an increased risk of stroke, heart failure, dementia, and death.1–3 In developed nations overall prevalence of AF is 0.9% and the number of people affected is projected to more than double over the next 2 decades.3,4 VT/VF is the most important immediate cause of sudden cardiac death (SCD). Incidence of SCD is estimated to be 4 to 5 million cases per year worldwide.5,6 Thus arrhythmias and SCD are among the most significant manifestations of cardiovascular diseases worldwide, but their underlying mechanisms remain elusive. Arrhythmogenic substrates may be established by ischemia, infarction, heart failure and genetic mutations, all of which may cause inflammation, extracellular matrix remodeling, interstitial fibrosis, fatty infiltration, and changes in the 3-dimensional cellular architecture of the working myocardium.7,8 Over the last 17 years, the study of the molecular genetic basis of monogenic cardiac rhythm disorders, together with characterization of functional expression and biophysical properties of mutant channels from patients with inheritable ion channel diseases, has significantly advanced our understanding of the molecular basis of cardiac arrhythmias.9 Yet, this clearly has not been sufficient. Despite such advances, predictable prevention of AF or VF is currently not possible and the development of effective antiarrhythmic pharmacological agents has been extremely difficult. Not all questions related to arrhythmia mechanisms are directly answerable by reductionist experiments such as DNA sequencing or patch clamping. There is a hierarchy of questions whose levels are determined by the generality of the answers sought. Thus the question of what a mutation in an ion …

Transplantation of engineered heart tissue as a biological cardiac assist device for treatment of dilated cardiomyopathy

The aim of this study was to characterize an alternative treatment for dilated cardiomyopathy (DCM) using a novel cardiac biological assist device created from engineered heart tissue (EHT). The EHTs were constructed in vitro from matrigel, collagen, and neonatal rat cardiomyocytes as small ring-like spontaneously contracting devices. DCM was induced in 50 rats by 6 weeks doxorubicin treatment (2.5 mg/kg/week). After 38 drug-free days, rats underwent either implantation of EHT (DCM-EHT, n = 13), which was sutured around the ventricles, or sham operation (DCM-Sham, n = 12). Eleven untreated healthy rats served as the control group. Rats were investigated using a Millar catheter for pressure-volume loop recording, and by echocardiography 30 days after operation. Thereafter, the hearts were excised and investigated functionally, histologically, and biochemically. Doxorubicin led to the development of DCM with reduced fractional shortening (FS), reduced dP/dt(max), increased systolic and diastolic LV diameters, and reduced response to dobutamine. In DCM-Sham, these changes were further enhanced, while in DCM-EHT we found improved FS, dP/dt(max), and dobutamine responsiveness. In isolated hearts, electrical multielectrode mapping revealed that EHT was electrically activated synchronously to the recipient heart. Histologically, we found increased vascularization in the EHT and the recipient heart, and EHT vessels connected to the coronary system. Implantation of EHT improves LV performance in rats with doxorubicin-induced DCM.

Rapid acquisition of high-resolution electroanatomical maps using a novel multielectrode mapping system

Conventional electroanatomical mapping systems employ roving catheters with one or a small number of electrodes. Maps acquired using these systems usually contain a small number of points and take a long time to acquire. Use of a multielectrode catheter could facilitate rapid acquisition of higher-resolution maps through simultaneous collection of data from multiple points in space; however, a large multielectrode array could potentially limit catheter maneuverability. The purpose of this study was to test the feasibility of using a novel, multielectrode catheter to map the right atrium and the left ventricle. Electroanatomical mapping of the right atrium and the left ventricle during both sinus and paced rhythm were performed in five swine using a conventional mapping catheter and a novel, multielectrode catheter. Average map acquisition times for the multielectrode catheter (with continuous data collection) ranged from 5.2 to 9.5 min. These maps contained an average of 2,753 to 3,566 points. Manual data collection with the multielectrode catheter was less rapid (average map completion in 11.4 to 18.1 min with an average of 870 to 1,038 points per map), but the conventional catheter was slower still (average map completion in 28.6 to 32.2 min with an average 120 to 148 points per map). Use of this multielectrode catheter is feasible for mapping the left ventricle as well as the right atrium. The multielectrode catheter facilitates acquisition of electroanatomical data more rapidly than a conventional mapping catheter. This results in shorter map acquisition times and higher-density electroanatomical maps in these chambers.

Abstract 19432: Exit Site of Ischemic Ventricular Tachycardia: Lessons from Simultaneous Multi-Electrode Mapping Era Applied to Sequential Mapping Era

Background: Ventricular tachycardia mapping in the sequential era is dependent on determining the exit site using entrainment mapping and or activation mapping. During entrainment mapping, VT has the potential of degenerating into ventricular fibrillation, requiring cardioversion that may distort the electroanatomic map. In addition entrainment may change the activation sequences and initiate another VT. Thus it is of importance to identify the exit site based on temporal characteristics of the activation map and characterize the exit site. In the era of point by point sequential mapping it is unclear how much time ahead of surface activation is the activation at the exit site. We sought to determine the temporal characteristics of the exit site where successful ablation was performed in relation to the surface activation. Methods and Results: Twelve patients with ischemic VT who had multi-electrode simultaneous endocardial mapping during ventricular tachycardia were retrospectively reviewed. 16 VTs induced in these twelve patients were analyzed and the activation sequence in systole, diastole, and the presystolic period was annotated. Activation time in relation to surface activation was characterized at the exit site where ablation was performed. Mapping was performed with a custom-made system consisting of a 112 electrode endocardial array with simultaneous uni and bipolar recording. Filter settings for uni was 0.1 - 200 Hz, bipolar 28 - 700Hz, sampling rate was 1 kHz for uni and 2 kHz for bipolar electrograms.The mean activation time at the exit site was 60 +/- 24 msec ahead of surface VT activation. The range of the timing of the activation at the exit site preceding surface activation was was 18 - 114 ms. The unipolar characteristic at the site was not useful in identifying timing on a consistent basis. Conclusion: The exit site of an ischemic ventricular tachycardia is on average 60 ms ahead of surface activation. This presytolic timing is earlier than what is generally believed in the current sequential mapping era of VT ablation. Our analysis suggests that catheter position at shorter activation times would indicate a location in the post exit site and unlikely to produce a useful outcome.

734 Exit Site of Ischemic Ventricular Tachycardia: Lessons From Simultaneous Multi-Electrode Mapping Era Applied to Sequential Mapping Era

Ventricular tachycardia mapping in the sequential era is dependent on determining the exit site using entrainment mapping and or activation mapping. During entrainment mapping, VT has the potential of degenerating into ventricular fibrillation, requiring cardioversion that may distort the electroanatomic map. In addition entrainment may change the activation sequences and initiate another VT. Thus it is of importance to identify the exit site based on temporal characteristics of the activation map and characterize the exit site. In the era of point by point sequential mapping it is unclear how much time ahead of surface activation is the activation at the exit site. We sought to determine the temporal characteristics of the exit site where successful ablation was performed in relation to the surface activation. Twelve patients with ischemic VT who had multi-electrode simultaneous endocardial mapping during ventricular tachycardia were retrospectively reviewed. 16 VTs induced in these twelve patients were analyzed and the activation sequence in systole, diastole, and the presystolic period was annotated. Activation time in relation to surface activation was characterized at the exit site where ablation was performed. Mapping was performed with a custom-made system consisting of a 112 electrode endocardial array with simultaneous uni and bipolar recording. Filter settings for uni was 0.1 - 200 Hz, bipolar 28 - 700Hz, sampling rate was 1 kHz for uni and 2 kHz for bipolar electrograms.The mean activation time at the exit site was 60 +/− 24 msec ahead of surface VT activation. The range of the timing of the activation at the exit site preceding surface activation was was 18 - 114 ms. The unipolar characteristic at the site was not useful in identifying timing on a consistent basis. The exit site of an ischemic ventricular tachycardia is on average 60 ms ahead of surface activation. This presytolic timing is earlier than what is generally believed in the current sequential mapping era of VT ablation. Our analysis suggests that catheter position at shorter activation times would indicate a location in the post exit site and unlikely to produce a useful outcome.

Multielectrode contact mapping to assess scar modification in post-myocardial infarction ventricular tachycardia patients

Substrate-based approaches for ablation of unmappable ventricular tachycardia (VT) are strictly dependent on high-density mapping of the scar. Ultra-high-density mapping with multielectrode catheters facilitates an accurate and faster definition of sites critical for re-entry, due to the possibility of simultaneous recordings of local potential from different pairs of electrodes. Multipolar catheters can be advanced to map the endocardial or the epicardial surface. A strong correlation between the scar area determined by electroanatomical mapping and the histopathological scar size has been demonstrated. A double-transeptal technique allows for an accurate definition of target sites. The complex scar architecture has been investigated by ultra-high-density mapping, let the identification of islets of heterogeneity where electrograms adjacent to the preserved myocardium have an higher incidence of late potentials. Pacing manoeuvres can easily be performed from any pair of electrode, to demonstrate the involvement of late potentials into the VT circuit. This strategy allows for a clear-cut validation of late potential abolishment, and may offer advantages to shorten procedural and fluoroscopy times. Large series are necessary to definitively assess the potential role of multielectrode mapping as a guide for the substrate ablation approach in post-myocardial infarction VT patients.

ORAL PRESENTATION

ORAL PRESENTATION

Treatment of persistent atrial fibrillation using phased radiofrequency ablation technology

A novel ablation system consisting of a duty-cycled phased radiofrequency generator and multielectrode mapping and ablation catheters has been introduced to provide ablation therapy in patients with symptomatic atrial fibrillation (AF). Contiguous lesions may be created using anatomically designed ablation catheters maneuvered under fluoroscopic guidance without the use of a 3D electroanatomic mapping system. In addition to pulmonary vein isolation using a circular, decapolar ablation catheter, an ablation strategy targeting complex fractionated atrial electrograms can be performed using two supplemental multiarray catheters specifically designed for ablation at the left atrial septum and within the left atrial body. Procedural times for treating persistent AF using phased radiofrequency are reported as being between 2 and 2.5 h. Freedom from AF ranges between 33 and 75% after a single procedure, which is comparable to other conventional ablation approaches (utilizing electroanatomic mapping). Additional studies in larger patient numbers are needed to understand the long-term maintenance of results and potential adverse effects of the technology.

High‐resolution spatial analysis of slow wave initiation and conduction in porcine gastric dysrhythmia

The significance of gastric dysrhythmias remains uncertain. Progress requires a better understanding of dysrhythmic behaviors, including the slow wave patterns that accompany or promote them. The aim of this study was to use high-resolution spatiotemporal mapping to characterize and quantify the initiation and conduction of porcine gastric dysrhythmias. High-resolution mapping was performed on healthy fasted weaner pigs under general anesthesia. Recordings were made from the gastric serosa using flexible arrays (160-192 electrodes; 7.6mm spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings (from 8 of 16 pigs), and these events were characterized, quantified and classified using isochronal mapping and animation. All observed dysrhythmias originated in the corpus and fundus. The range of dysrhythmias included incomplete conduction block (n=3 pigs; 3.9±0.5cpm; normal range: 3.2±0.2cpm) complete conduction block (n=3; 3.7±0.4cpm), escape rhythm (n=5; 2.0±0.3cpm), competing ectopic pacemakers (n=5, 3.7±0.1cpm) and functional re-entry (n=3, 4.1±0.4cpm). Incomplete conduction block was observed to self-perpetuate due to retrograde propagation of wave fragments. Functional re-entry occurred in the corpus around a line of unidirectional block. 'Double potentials' were observed in electrograms at sites of re-entry and at wave collisions. Intraoperative multi-electrode mapping of fasted weaner healthy pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including patterns not previously reported. The techniques and findings described here offer new opportunities to understand the nature of human gastric dysrhythmias.

A Novel Phenotype of Glycogen Storage Disease Presenting as Gastrointestinal Neuromuscular Disease

Introduction Gastric smooth muscle layers are electrically excited by slow waves. In the normal stomach, slow waves propagate longitudinally in ring wavefronts from the upper corpus to the distal antrum. Circumferential propagation does not appear to occur, likely because there is no excitable tissue available circumferentially in these rings. However, rapid circumferential propagation has been observed in isolated gastric tissues and during gastric pacing. In this study, the propagation profiles of slow wave behaviors in diabetic gastroparesis were defined at high resolution (HR). The hypothesis was that circumferential propagation occurs during dysrhythmia, presenting a novel marker of gastric electrical dysfunction. Methods HR (multi-electrode) mapping was performed in 7 patients with diabetic gastroparesis undergoing laparotomy for stimulator implantation. Anterior serosal recordings were taken using flexible PCB arrays (256 electrodes; 4 mm spacing; 36cm2), and activation mapping was performed. Velocity fields were calculated using a finite difference approach incorporating a Gaussian filter smoothing function. Amplitudes were calculated using a peak-trough detection algorithm. Longitudinal and circumferential propagation data from corpus recordings were compared with Student's t-test. Means±SEM are reported. Results Atypical or dysrhythmic propagation was observed in 6/7 patients, including incomplete conduction block, complete block with escape, ectopic pacemaking in the corpus and antral tachygastria (freq range: 2.7-4.2 cpm). Circumferential propagation was associated with all of these events (circumferential velocity 6.6 ± 0.9 mm/s vs longitudinal velocity 2.9 ± 0.2 mm/s; p<0.01). Extracellular slow wave amplitudes were also ~2.5x higher during circumferential propagation (411±66 uV vs 170±27 uV; p<0.01). Isochronalmapping demonstrated that circumferential propagation led to the rapid restoration of a normal longitudinal wavefront distal to the source of the dysrhythmia. However, circumferential propagation also promoted organized retrograde propagation in the case of antral tachygastria. Conclusions Propagation abnormalities in diabetic gastroparesis include conduction blocks, escape, and ectopic events, potentially as a consequence of known ICC network degradation. Circumferential propagation emerges in many of these abnormal patterns because excitable tissue becomes available in the circumferential direction. Circumferential conduction is found to be associated with high velocities and high amplitudes, which could therefore serve as useful clinical indicators for abnormal slow wave propagation. Functionally, rapid circumferential propagation serves to restore normal slow wave propagation distal to conduction defects, however it can also promote organized retrograde tachygastria.

Increased Dopamine and DA2 Receptor Expression in the Gastric Myenteric Plexus (MP) is Responsible for Gastroparesis in Parkinson's Disease Rat Model Treated With 6-Ohda

Introduction Gastric smooth muscle layers are electrically excited by slow waves. In the normal stomach, slow waves propagate longitudinally in ring wavefronts from the upper corpus to the distal antrum. Circumferential propagation does not appear to occur, likely because there is no excitable tissue available circumferentially in these rings. However, rapid circumferential propagation has been observed in isolated gastric tissues and during gastric pacing. In this study, the propagation profiles of slow wave behaviors in diabetic gastroparesis were defined at high resolution (HR). The hypothesis was that circumferential propagation occurs during dysrhythmia, presenting a novel marker of gastric electrical dysfunction. Methods HR (multi-electrode) mapping was performed in 7 patients with diabetic gastroparesis undergoing laparotomy for stimulator implantation. Anterior serosal recordings were taken using flexible PCB arrays (256 electrodes; 4 mm spacing; 36cm2), and activation mapping was performed. Velocity fields were calculated using a finite difference approach incorporating a Gaussian filter smoothing function. Amplitudes were calculated using a peak-trough detection algorithm. Longitudinal and circumferential propagation data from corpus recordings were compared with Student's t-test. Means±SEM are reported. Results Atypical or dysrhythmic propagation was observed in 6/7 patients, including incomplete conduction block, complete block with escape, ectopic pacemaking in the corpus and antral tachygastria (freq range: 2.7-4.2 cpm). Circumferential propagation was associated with all of these events (circumferential velocity 6.6 ± 0.9 mm/s vs longitudinal velocity 2.9 ± 0.2 mm/s; p<0.01). Extracellular slow wave amplitudes were also ~2.5x higher during circumferential propagation (411±66 uV vs 170±27 uV; p<0.01). Isochronalmapping demonstrated that circumferential propagation led to the rapid restoration of a normal longitudinal wavefront distal to the source of the dysrhythmia. However, circumferential propagation also promoted organized retrograde propagation in the case of antral tachygastria. Conclusions Propagation abnormalities in diabetic gastroparesis include conduction blocks, escape, and ectopic events, potentially as a consequence of known ICC network degradation. Circumferential propagation emerges in many of these abnormal patterns because excitable tissue becomes available in the circumferential direction. Circumferential conduction is found to be associated with high velocities and high amplitudes, which could therefore serve as useful clinical indicators for abnormal slow wave propagation. Functionally, rapid circumferential propagation serves to restore normal slow wave propagation distal to conduction defects, however it can also promote organized retrograde tachygastria.

Aberrant Initiation and Conduction of Slow Wave Activity in Diabetic and Idiopathic Gastroparesis

Introduction Gastric smooth muscle layers are electrically excited by slow waves. In the normal stomach, slow waves propagate longitudinally in ring wavefronts from the upper corpus to the distal antrum. Circumferential propagation does not appear to occur, likely because there is no excitable tissue available circumferentially in these rings. However, rapid circumferential propagation has been observed in isolated gastric tissues and during gastric pacing. In this study, the propagation profiles of slow wave behaviors in diabetic gastroparesis were defined at high resolution (HR). The hypothesis was that circumferential propagation occurs during dysrhythmia, presenting a novel marker of gastric electrical dysfunction. Methods HR (multi-electrode) mapping was performed in 7 patients with diabetic gastroparesis undergoing laparotomy for stimulator implantation. Anterior serosal recordings were taken using flexible PCB arrays (256 electrodes; 4 mm spacing; 36cm2), and activation mapping was performed. Velocity fields were calculated using a finite difference approach incorporating a Gaussian filter smoothing function. Amplitudes were calculated using a peak-trough detection algorithm. Longitudinal and circumferential propagation data from corpus recordings were compared with Student's t-test. Means±SEM are reported. Results Atypical or dysrhythmic propagation was observed in 6/7 patients, including incomplete conduction block, complete block with escape, ectopic pacemaking in the corpus and antral tachygastria (freq range: 2.7-4.2 cpm). Circumferential propagation was associated with all of these events (circumferential velocity 6.6 ± 0.9 mm/s vs longitudinal velocity 2.9 ± 0.2 mm/s; p<0.01). Extracellular slow wave amplitudes were also ~2.5x higher during circumferential propagation (411±66 uV vs 170±27 uV; p<0.01). Isochronalmapping demonstrated that circumferential propagation led to the rapid restoration of a normal longitudinal wavefront distal to the source of the dysrhythmia. However, circumferential propagation also promoted organized retrograde propagation in the case of antral tachygastria. Conclusions Propagation abnormalities in diabetic gastroparesis include conduction blocks, escape, and ectopic events, potentially as a consequence of known ICC network degradation. Circumferential propagation emerges in many of these abnormal patterns because excitable tissue becomes available in the circumferential direction. Circumferential conduction is found to be associated with high velocities and high amplitudes, which could therefore serve as useful clinical indicators for abnormal slow wave propagation. Functionally, rapid circumferential propagation serves to restore normal slow wave propagation distal to conduction defects, however it can also promote organized retrograde tachygastria.

Antiproliferative treatment of myofibroblasts prevents arrhythmias in vitro by limiting myofibroblast-induced depolarization

Cardiac fibrosis is associated with increased incidence of cardiac arrhythmias, but the underlying proarrhythmic mechanisms remain incompletely understood and antiarrhythmic therapies are still suboptimal. This study tests the hypothesis that myofibroblast (MFB) proliferation leads to tachyarrhythmias by altering the excitability of cardiomyocytes (CMCs) and that inhibition of MFB proliferation would thus lower the incidence of such arrhythmias. Endogenous MFBs in neonatal rat CMC cultures proliferated freely or under control of different dosages of antiproliferative agents (mitomycin-C and paclitaxel). At Days 4 and 9, arrhythmogeneity of these cultures was studied by optical and multi-electrode mapping. Cultures were also studied for protein expression and electrophysiological properties. MFB proliferation slowed conduction from 15.3 ± 3.5 cm/s (Day 4) to 8.8 ± 0.3 cm/s (Day 9) (n = 75, P < 0.01), whereas MFB numbers increased to 37.4 ± 1.7 and 62.0 ± 2%. At Day 9, 81.3% of these cultures showed sustained spontaneous reentrant arrhythmias. However, only 2.6% of mitomycin-C-treated cultures (n = 76, P < 0.0001) showed tachyarrhythmias, and ectopic activity was decreased. Arrhythmia incidence was drug-dose dependent and strongly related to MFB proliferation. Paclitaxel treatment yielded similar results. CMCs were functionally coupled to MFBs and more depolarized in cultures with ongoing MFB proliferation in which only L-type Ca(2+)-channel blockade terminated 100% of reentrant arrhythmias, in contrast to Na(+) blockade (36%, n = 12). Proliferation of MFBs in myocardial cultures gives rise to spontaneous, sustained reentrant tachyarrhythmias. Antiproliferative treatment of such cultures prevents the occurrence of arrhythmias by limiting MFB-induced depolarization, conduction slowing, and ectopic activity. This study could provide a rationale for a new treatment option for cardiac arrhythmias.

Duty-Cycled Bipolar/Unipolar RF-Energy Ablation with Multipolar-Circular and Linear Catheters

Radiofrequency (RF) has been the most widespread energy source for catheter ablation. Pulmonary vein (PV) isolation is a cornerstone in catheter ablation for any type of atrial fibrillation (AF). In complex cases of persistent AF, additional linear ablation can be added, or complex fractionated electrograms (CFAE) can be targeted for ablation. Although the evolution in ablation strategies led to increasingly complex and lengthy procedures, little progress has been made in the development of new ablation catheters. Traditional catheter ablation is performed in a single-tip, point-by-point ablation process. This technique requires an operator skill and procedures are lengthy, due to the number of potential targets. In addition, creating reliable contiguous transmural lesions with a single-point catheter is difficult. Recently, multi-electrode mapping and ablation catheters that allow simultaneous delivery of duty-cycled bipolar and unipolar RF energy from multiple points have been developed (Ablation Frontiers, Medtronic, Minneapolis, MN, USA). Available designs include a circular ring catheter (PVAC) for PV isolation, a linear array (TVAC) for creating linear lesions, and multi-array catheters (MASC and MAAC) for CFAE ablation. The generator (GENius, Medtronic) has five preset bipolar-to-unipolar energy settings, which, according to experimental data allow creation of different lesion depths. In this presentation, we will summarize our experience and current status of this new technology including some complications recently reported.