Difference between endocardial and epicardial application of pulsed fields for targeting Epicardial Ganglia: An in-silico modelling study.

BACKGROUND: Pulsed Field Ablation (PFA) has recently been proposed as a non-thermal energy to treat atrial fibrillation by selective ablation of ganglionated plexi (GP) embedded in epicardial fat. While some of PFA-technologies use an endocardial approach, others use epicardial access with promising pre-clinical results. However, as each technology uses a different and sometimes proprietary pulse application protocol, the comparation between endocardial vs. epicardial approach is almost impossible in experimental terms. For this reason, our study, based on a computational model, allows a direct comparison of electric field distribution and thermal-side effects of both approaches under equal conditions in terms of electrode design, pulse protocol and anatomical characteristics of the tissues involved. METHODS: 2D computational models with axial symmetry were built for endocardial and epicardial approaches. Atrial (1.5-2.5 mm) and fat (1-5 mm) thicknesses were varied to simulate a representative sample of what happens during PFA ablation for different applied voltage values (1000, 1500 and 2000 V) and number of pulses (30 and 50). RESULTS: The epicardial approach was superior for capturing greater volumes of fat when the applied voltage was increased: 231 mm3/kV with the epicardial approach vs. 182 mm3/kV with the endocardial approach. In relation to collateral damage to the myocardium, the epicardial approach considerably spares the myocardium, unlike what happens with the endocardial approach. Although the epicardial approach caused much more thermal damage in the fat, there is not a significant difference between the approaches in terms of size of thermal damage in the myocardium. CONCLUSIONS: Our results suggest that epicardial PFA ablation of GPs is more effective than an endocardial approach. The proximity and directionality of the electric field deposited using an epicardial approach are key to ensuring that higher electric field strengths and increased temperatures are obtained within the epicardial fat, thus contributing to selective ablation of the GPs with minimal myocardial damage.

Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

Effects of Aging and Hypertension on the Antithrombotic Function of Atrial Endocardium in Rats.

We have previously reported that atrial endocardial remodeling is induced by atrial fibrillation (AF), and the endocardial dysfunction may be partly responsible for the thrombus formation in the left atrium associated with AF. However, the relationship between the endocardial dysfunction and the epidemiologically determined risk factors of AF-related strokes, including aging, hypertension, and diabetes mellitus, is yet to be elucidated.To test the hypothesis that aging, hypertension, and diabetes mellitus individually impair the atrial endocardial function in conjunction with AF, we have analyzed the expression of the tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) in the atrial endocardium in 30-week-old Wister-Kyoto (WKY), 60-week-old WKY, 30-week-old spontaneously hypertensive rats (SHR), and 30-week Goto-Kakizaki (GK) rats during normal sinus rhythm and after rapid atrial pacing at 1200 bpm for 8 hours, using Western blotting and immunohistochemical analysis. Even during sinus rhythm, the TFPI and TM expressions were noted to be remarkably downregulated in the atrial endocardium among 60-week-old WKY rats. In contrast, in SHR rats, only the TFPI expression has significantly decreased, while TM was preserved to the same level of control 30-week-old WKY rats. Rapid atrial pacing significantly reduced the TM and TFPI expression similarly in each model, thereby augmenting the endocardial dysfunction during normal sinus rhythm individually induced by the risk factors themselves prior to AF.Aging and hypertension, both of which are epidemiologically well-known risk factors for strokes in AF, have been associated with a specific atrial endocardial impairment prior to AF that could additionally disturb the antithrombotic function of the atrial endocardium.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Ccn2a is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish.

The ability of zebrafish to heal their heart after injury makes them an attractive model for investigating the mechanisms governing the regenerative process. In this study, we show that the gene cellular communication network factor 2a (ccn2a), previously known as ctgfa, is induced in endocardial cells in the injured tissue and regulates CM proliferation and repopulation of the damaged tissue. We find that, whereas in wild-type animals, CMs track along the newly formed blood vessels that revascularize the injured tissue, in ccn2a mutants CM proliferation and repopulation are disrupted, despite apparently unaffected revascularization. In addition, we find that ccn2a overexpression enhances CM proliferation and improves the resolution of transient collagen deposition. Through loss- and gain-of-function as well as pharmacological approaches, we provide evidence that Ccn2a is necessary for and promotes heart regeneration by enhancing the expression of pro-regenerative extracellular matrix genes, and by inhibiting the chemokine receptor gene cxcr3.1 through a mechanism involving Tgfß/pSmad3 signaling. Thus, Ccn2a positively modulates the innate regenerative response of the adult zebrafish heart.

Simultaneous Endo-Epicardial Mapping of the Human Right Atrium: Unraveling Atrial Excitation.

Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA. Areas of CB were defined as conduction delays of ≥12 ms, EEA as activation time differences of opposite electrodes of ≥15 ms and transmural CB as CB at similar endo-epicardial sites. CB was more pronounced at the endocardium (all locations P<0.025). Amount, extensiveness and severity of CB was higher at the superior RA. Transmural CB at the inferior RA was associated with a higher incidence of post-operative AF (P=0.03). EEA occurred up to 84 ms and was more pronounced at the superior RA (superior: 27 ms [interquartile range, 18.3-39.3], versus mid-RA: 20.3 ms [interquartile range, 0-29.9], and inferior RA: 0 ms [interquartile range, 0-21], P<0.001). Hypertension (P=0.009), diabetes mellitus (P=0.018), and hypercholesterolemia (P=0.015) were associated with a higher degree of EEA. CB (P=0.007) and EEA (P=0.037) were more pronounced in patients with a history of persistent AF compared with patients without AF history. Conclusions This study provides important insights into complex atrial endo-epicardial excitation. Significant differences in conduction disorders between the endo- and epicardium and a significant degree of EEA are already present during sinus rhythm and are more pronounced in patients with cardiovascular risk factors or a history of persistent AF.

Endocardial-Epicardial Phase Mapping of Prolonged Persistent Atrial Fibrillation Recordings: High Prevalence of Dissociated Activation Patterns.

BACKGROUND: Endocardial-epicardial dissociation and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study, we used simultaneous endo-epi phase mapping to characterize endo-epi activation patterns on long segments of human persistent AF. METHODS: Simultaneous intraoperative mapping of endo- and epicardial lateral right atrium wall was performed in patients with persistent AF using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms of continuous 2-minute AF recordings and electrodes locations were exported for phase analyses. We defined endocardial-epicardial dissociation as phase difference of ≥20 ms between paired endo-epi electrodes. Wavefronts were classified as rotations, single wavefronts, focal waves, or disorganized activity as per standard criteria. Endo-Epi wavefront patterns were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with ≥5 directional changes occupying at least 70% of sample duration. RESULTS: Fourteen patients with persistent AF undergoing cardiac surgery were included. Endocardial-epicardial dissociation was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (Endo: 41.3% versus Epi: 46.8%, P=0.0194) and single wavefronts (Endo: 31.3% versus Epi: 28.1%, P=0.129) were the dominant patterns. Transient rotations (Endo: 22% versus Epi: 19.2%, P=0.169; mean duration: 590±140 ms) and nonsustained focal waves (Endo: 1.2% versus Epi: 1.6%, P=0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. Electrogram fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P<0.0001). CONCLUSIONS: Simultaneous endo-epi phase mapping of prolonged human persistent AF recordings shows significant Endocardial-epicardial dissociation marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insight into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Graphic Abstract: A graphic abstract is available for this article.

Leadless left ventricular endocardial pacing in nonresponders to conventional cardiac resynchronization therapy.

BACKGROUND: Endocardial pacing may be beneficial in patients who fail to improve following conventional epicardial cardiac resynchronization therapy (CRT). The potential to pace anywhere inside the left ventricle thus avoiding myocardial scar and targeting the latest activating segments may be particularly important. The WiSE-CRT system (EBR systems, Sunnyvale, CA) reliably produces wireless, endocardial left ventricular (LV) pacing. The purpose of this analysis was to determine whether this system improved symptoms or led to LV remodeling in patients who were nonresponders to conventional CRT. METHOD: An international, multicenter registry of patients who were nonresponders to conventional CRT and underwent implantation with the WiSE-CRT system was collected. RESULTS: Twenty-two patients were included; 20 patients underwent successful implantation with confirmation of endocardial biventricular pacing and in 2 patients, there was a failure of electrode capture. Eighteen patients proceeded to 6-month follow-up; endocardial pacing resulted in a significant reduction in QRS duration compared with intrinsic QRS duration (26.6 ± 24.4 ms; P = .002) and improvement in left ventricular ejection fraction (LVEF) (4.7 ± 7.9%; P = .021). The mean reduction in left ventricular end-diastolic volume was 8.3 ± 42.3 cm3 (P = .458) and left ventricular end-systolic volume (LVESV) was 13.1 ± 44.3 cm3 (P = .271), which were statistically nonsignificant. Overall, 55.6% of patients had improvement in their clinical composite score and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%. CONCLUSION: Nonresponders to conventional CRT have few remaining treatment options. We have shown in this high-risk patient group that the WiSE-CRT system results in improvement in their clinical composite scores and leads to LV remodeling.

Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue.

Cardiac pathologies associated with arrhythmic activity are often accompanied by inflammation. The contribution of inflammatory cells to the electrophysiological properties of injured myocardium is unknown. Myocardial scar cell types and intercellular contacts were analyzed using a three-dimensional reconstruction from serial blockface scanning electron microscopy data. Three distinct cell populations were identified: inflammatory, fibroblastic and endocardial cells. While individual fibroblastic cells interface with a greater number of cells, inflammatory cells have the largest contact area suggesting a role in establishing intercellular electrical connections in scar tissue. Optical mapping was used to study the electrophysiological properties of scars in fetal liver chimeric mice generated using connexin43 knockout donors (bmpKO). Voltage changes were elicited in response to applied current pulses. Isopotential maps showed a steeper pattern of decay with distance from the electrode in scars compared with uninjured regions, suggesting reduced electrical coupling. The tissue decay constant, defined as the distance voltage reaches 37% of the amplitude at the edge of the scar, was 0.48 ± 0.04 mm (n = 11) in the scar of the bmpCTL group and decreased 37.5% in the bmpKO group (n = 10). Together these data demonstrate inflammatory cells significantly contribute to scar electrophysiology through coupling mediated at least partially by connexin43 expression.

Left Atrial Appendage Closure: Technical Considerations of Endocardial Closure.

Left atrial appendage closure (LAAC) is a safe and effective therapy for the prevention of stroke in patients with nonvalvular atrial fibrillation and high bleeding risk with oral anticoagulants. Multimodality imaging with transesophageal echocardiography and computed tomography angiography to define the anatomy and its implications on endocardial exclusion is becoming increasingly important. The only LAAC device currently approved for clinical use in the United States is the WATCHMAN device. Systematic assessment of the transseptal crossing site, left atrial appendage anatomy, adequate device size selection, and device postdeployment evaluation is essential for the safety and efficacy of the procedure.

Fragmented endocardial signals and early afterdepolarizations during torsades de pointes tachycardia.

BACKGROUND: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon. METHODS: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. A standard (USCI) temporary bipolar endocardial catheter positioned at the apex of the right ventricle (RV) and bipolar chest leads from two precordial leads V1 and V4 were used to record the tracings during TdP. RESULTS: The presence of a wide spectrum of fragmentations was noted on endocardial electrograms (EGMs), which were invisible on the surface electrocardiogram (ECG) tracing. Endocardial signals indicated that TdP started in the proximity of the RV apex, since the local EGM began prior to the QRS complex on the surface ECG. Early afterdepolarizations (EADs) were observed in 2 out of 5 cases confirming a common opinion about the mechanism of TdP. However, this phenomenon was not observed in 3 other patients suggesting that the arrhythmia was the result of a different mechanism originating in proximity to the RV apex. CONCLUSIONS: This work demonstrated early endocardial signals in the RV apex during TdP associated with high-degree AVB in humans, and exhibits a spectrum of fragmented signals in this area occurring on a single or multiple beats. These fragmentations indicate areas of poor conduction and various degrees of intramyocardial block, and therefore a new mechanism of TdP tachycardia in some patients with spontaneous high-degree AVB.

Short and Intermediate Term Outcomes of the Convergent Procedure: Initial Experience in a Tertiary Referral Center.

PURPOSE: The Convergent procedure is a hybrid, multidisciplinary treatment for symptomatic atrial fibrillation (AF) consisting of minimally invasive surgical epicardial ablation and percutaneous/catheter endocardial ablation. We investigated outcomes following introduction of the Convergent procedure at our institution. METHODS: Retrospective study examining single-center outcomes. Demographic, procedural, and post-procedural variables were collected with follow-up data obtained at 3, 6, and 12 months. RESULTS: In all, 36 patients with paroxysmal (11%) or persistent/long-standing persistent (89%) AF underwent the Convergent procedure. 36% also underwent concomitant left atrial appendage (LAA) exclusion by thoracoscopic placement of an epicardial clip. Mean age 60.6 ± 8.0 years with mean arrhythmia burden of 3.9 ± 2.7 years. All patients had failed prior attempts at medical management, 81% had failed prior cardioversion, and 17% had failed prior catheter ablation. Convergent was performed successfully in all patients with no peri-procedural deaths or major complications. At 3 and 12 months, 77.8% and 77.3% of patients, respectively, were free from symptomatic arrhythmia. 65.8% were off anti-arrhythmic medication at 12 months. CONCLUSIONS: The Convergent procedure is safe and has good short- and intermediate-term clinical success rates. This unique hybrid approach combines strengths of surgical and catheter ablation and should be part of any comprehensive AF treatment program.

Endocardial contact mapping of the left atrial appendage in persistent atrial fibrillation.

INTRODUCTION: Isolation of the left atrial appendage (LAA) is often performed in persistent atrial fibrillation (AF). Propagation patterns in the LAA during AF remain to be elucidated. We sought to characterize propagation patterns in the LAA during AF in persistent AF. METHODS: Persistent AF patients undergoing catheter ablation were studied. Pulmonary vein isolation (PVI) was performed during continuous AF. If AF was not terminated by PVI, bi-atrial mapping was performed using a multi-electrode catheter during AF. Maps were collected at each site for 30 seconds and analyzed offline with a novel software, CARTOFINDER. This software made automatic determinations of whether activation was focal or rotational. The left atrium (LA) was divided into five regions, of which the LAA was one, and the right atrium (RA) into three. RESULTS: Eighty patients were studied (62 ± 10 years, 65 males). On average, 9.6 ± 2.2 and 4.1 ± 1.2 maps were created in the LA and RA, respectively. The LAA was mapped in 70 patients, resulting in 85 maps. In the LAA, activation was identified as focal more often than rotational (64 [91%] vs 10 [14%] patients, P < .001), seven patients displayed both. The number of focal activation events was greatest in the LAA (28.5 events/30 seconds [interquartile range, 15-54]) of the eight atrial regions. During focal activation, sites designated as earliest activation frequently covered a wide area, rather than being localized to a discrete site (5.4 ± 3.1 electrodes). CONCLUSIONS: The results of this study suggest that focal activation is a major mechanism underlying the arrhythmogenicity of the LAA in persistent AF.

Hybrid Ventricular Tachycardia Ablation after Failed Percutaneous Endocardial and Epicardial Ablation.

INTRODUCTION: Recurrent ventricular tachycardia (VT) after percutaneous ablation is associated with a high morbidity and mortality. We assessed the feasibility of open chest extracorporeal circulation (ECC)-supported 3D multielectrode mapping and targeted VT substrate ablation in patients with previously failed percutaneous endocardial and epicardial VT ablations. METHODS: In patients with previously failed percutaneous endocardial and epicardial VT ablations and a high risk of hemodynamic collapse during the procedure, open chest ECC-supported mapping and ablation were performed in a hybrid EP lab setting. Electro-anatomic maps (3D) were acquired during sinus rhythm and VT using a multielectrode mapping catheter (HD grid; Abbott or Pentaray, Biosense Webster). Irrigated radiofrequency ablations of all inducible VT were performed with a contact force ablation catheter. RESULTS: Hybrid VT ablation was performed in 5 patients with structural heart disease (i.e., 3 with previous old myocardial infarction and 2 with nonischemic cardiomy-opathy) and recurrent VT. Acute procedural success was achieved in all patients. Four patients were successfully weaned off the ECC. In 1 patient with a severely reduced LVEF (16%), damage to the venous graft occurred after sternotomy and that patient died after 1 month. Four patients (80%) remained VT free after a median follow-up of 6 (IQR 4-10) months. CONCLUSION: In high-risk patients with previously failed percutaneous endocardial and epicardial VT ablations, open chest ECC-supported multielectrode epicardial mapping revealed a VT substrate in all of the patients, and targeted epicardial ablation abolished VT substrate in these patients.

High Frame Rate Ultrasound for Electromechanical Wave Imaging to Differentiate Endocardial From Epicardial Myocardial Activation.

Differentiation between epicardial and endocardial ventricular activation remains a challenge despite the latest technologies available. The aim of the present study was to develop a new tool method, based on electromechanical wave imaging (EWI), to improve arrhythmogenic substrate activation analysis. Experiments were conducted on left ventricles (LVs) of four isolated working mode swine hearts. The protocol aimed at demonstrating that different patterns of mechanical activation could be observed whether the ventricle was in sinus rhythm, paced from the epicardium or from the endocardium. A total of 72 EWI acquisitions were recorded on the anterior, lateral and posterior segments of the LV. A total of 54 loop records were blindly assigned to two readers. EWI sequences interpretations were correct in 89% of cases. The overall agreement rate between the two readers was 83%. When in a paced ventricle, the origin of the wave front was focal and originated from the endocardium or the epicardium. In sinus rhythm, wave front was global and activated within the entire endocardium toward the epicardium at a speed of 1.7 ± 0.28 m·s-1. Wave front speeds were respectively measured when the endocardium or the epicardium were paced at a speed of 1.1 ± 0.35 m·s-1 versus 1.3 ± 0.34 m·s-1 (p = NS). EWI activation mapping allows activation localization within the LV wall and calculation of the wave front propagation speed through the muscle. In the future, this technology could help localize activation within the LV thickness during complex ablation procedures.

Transmural and rate-dependent profiling of drug-induced arrhythmogenic risks through in silico simulations of multichannel pharmacology.

In vitro human ether-à-go-go related gene (hERG) inhibition assay alone might provide insufficient information to discriminate "safe" from "dangerous" drugs. Here, effects of multichannel inhibition on cardiac electrophysiology were investigated using a family of cardiac cell models (Purkinje (P), endocardial (Endo), mid-myocardial (M) and epicardial (Epi)). We found that: (1) QT prolongation alone might not necessarily lead to early afterdepolarization (EAD) events, and it might be insufficient to predict arrhythmogenic liability; (2) the occurrence and onset of EAD events could be a candidate biomarker of drug-induced arrhythmogenicity; (3) M cells are more vulnerable to drug-induced arrhythmias, and can develop early afterdepolarization (EAD) at slower pacing rates; (4) the application of quinidine can cause EADs in all cell types, while INaL is the major depolarizing current during the generation of drug-induced EAD in P cells, ICaL is mostly responsible in other cell types; (5) drug-induced action potential (AP) alternans with beat-to-beat variations occur at high pacing rates in P cells. These results suggested that quantitative profiling of transmural and rate-dependent properties can be essential to evaluate drug-induced arrhythmogenic risks, and may provide mechanistic insights into drug-induced arrhythmias.

Spatial Accuracy of a Clinically Established Noninvasive Electrocardiographic Imaging System for the Detection of Focal Activation in an Intact Porcine Model.

BACKGROUND: Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited. METHODS: Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated. RESULTS: A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, P=0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8-25.6) mm (median and [first-third] quartile). Distances were not significantly different across cardiac chambers. CONCLUSIONS: The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.

Anti-Ischemic Activity of Fabomotizole Hydrochloride under Conditions of Endothelial Dysfunction.

Anti-ischemic activity of fabomotizole hydrochloride was studied on the model of subendocardial ischemia in rats with endothelial dysfunction. Endothelial dysfunction was modeled by intragastric administration of methionine (3 g/kg, once a day for 7 days). Acute subendocardial ischemia was induced in narcotized rats by intraperitoneal injection of isoproterenol (20 µg/kg/min over 5 min). Fabomotizole hydrochloride (intraperitoneally, 15 mg/kg) significantly reduced isoproterenol-induced ST segment depression in animals with endothelial dysfunction and with intact vasculature.