Electroanatomic Substrate Research Articles

P1145Different electroanatomic substrates plays different role as the substrate of atrial fibrillation in human

P1145Different electroanatomic substrates plays different role as the substrate of atrial fibrillation in human

P864Association between an extent of electroanatomical substrate, circulating pro-fibrotic biomarkers and myocardial tissue morphology in patients with atrial fibrillation and heart failure

P864Association between an extent of electroanatomical substrate, circulating pro-fibrotic biomarkers and myocardial tissue morphology in patients with atrial fibrillation and heart failure

Characterization of the Electroanatomic Substrate in Cardiac Sarcoidosis: Correlation With Imaging Findings of Scar and Inflammation.

This study sought to characterize the electroanatomic (EAM) substrate in patients with cardiac sarcoidosis (CS) and ventricular tachycardia and its relationship to imaging findings of inflammation and fibrosis. CS is characterized by coexistence of active inflammation and replacement fibrosis. A total of 42 patients with CS based on established criteria and ventricular tachycardia underwent high-density EAM mapping. Abnormal electrograms (EGM) were collected and independently classified as multicomponentfractionated, isolated, late, and split according to standard criteria and regardless of the peak-to-peak bipolar/unipolar voltage. A total of 29 patients (69%) underwent pre-procedural cardiac magnetic resonance (CMR) and positron emission tomography (PET)/computed tomography (CT). The distribution of EAMsubstrate was correlated with regions of late gadolinium enhancement (LGE) on CMR and increased 18F-fluorodeoxyglucose uptake on PET/CT. Of 21,451 bipolar and unipolar EGM, 4,073 (19%) were classified as abnormal with a predominant distribution in the basal perivalvular segments and interventricular septum. Using the standard bipolar (<1.5 mV) and unipolar (<8.3mV for left ventricle<5.5 mV for the right) voltage cutoff values, 40% and 22% of the abnormal EGM were located outside the EAM low-voltage areas, respectively. LGE was present in 26 of 29 patients (90%), whereas abnormal 18F-fluorodeoxyglucose uptake in 14 of 29 patients (48%) with imaging. Segments with abnormal EGM had more LGE-evident scar transmurality [median: 24% (interquartile range [IQR]: 4% to 40%) vs. median: 5%(IQR: 0% to 15%); p< 0.001] and lower metabolic activity (median: 20 g glucose [IQR: 14 g to 30 g] vs. median: 29 g glucose [IQR: 18 g to 39 g]; p< 0.001). Overall, the agreement between the presence of abnormal EGM was higher with the presence of LGE (κ= 0.51; p< 0.001) than with the presence of active inflammation (κ=-0.12; p= 0.003). In patients with CS and ventricular tachycardia, pre-procedural imaging with CMR and PET/CT can be useful in detecting EAM abnormalities that are potential targets for substrate ablation. Abnormal EGM were more likelylocated in segments with more scar transmurality (LGE) at CMR and a lower degree of inflammation on PET.

Role of Ventricular Tachycardia Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT). These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes.

073_17038P-C4 Characterization of the Electroanatomic Substrate in Cardiac Sarcoidosis and its Correlation with Imaging Findings of Scar and Inflammation

Cardiac sarcoidosis (CS) is characterized by varying degree of active inflammation and replacement fibrosis. The electroanatomic (EAM) substrate features in patients with CS and ventricular tachycardia (VT) and the relationship with imaging findings of inflammation and fibrosis have not been

P3627Relationship between an extent of electroanatomical substrate, serum pro-fibrotic biomarkers and histopathological data in patients with atrial fibrillation and heart failure

P3627Relationship between an extent of electroanatomical substrate, serum pro-fibrotic biomarkers and histopathological data in patients with atrial fibrillation and heart failure

P850LA size and ANP predict electro-anatomical substrate in AF patients undergoing radiofrequency catheter ablation

P850LA size and ANP predict electro-anatomical substrate in AF patients undergoing radiofrequency catheter ablation

12-Lead Electrocardiogram to Localize Region of Abnormal Electroanatomic Substrate in Arrhythmogenic RightVentricular Cardiomyopathy.

The purpose of this study was to evaluate the relationship between electrocardiogram (ECG) QRS fragmentation (fQRS) and right ventricular (RV) endocardial (ENDO) and epicardial (EPI) electroanatomic substrate abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). fQRS is frequently observed in patients with ARVC and reflects delayed conduction due to RV fibrosis. A total of 30 consecutive patients met the task force criteria for ARVC (19 men, mean age 41.1 ± 14.3 years) presenting for ventricular tachycardia ablation with detailed RV ENDO and EPI electroanatomic maps were included. Of these, 25 patients had depolarization abnormalities (fragmentation during and/or immediately after the QRS complex [fQRS]) in≥2 contiguous ECG leads. Inferior (II, III, aVF) fQRS was identified in 23 patients, anterior (V1 to V3) in 15patients,and basal superior (I/aVR) in 11 patients. The surface area and anatomic distribution of ENDO and EPI bipolar low-voltage regions (ENDO≤1.5 mV,<0.5 mV "dense scar"/EPI≤1.0 mV) and degree of isolated late potential activity consistent with a marked substrate abnormality were compared to the location of region-specific fQRS. In fQRS patients, ENDO very low bipolar voltage area (27.4 ± 24.9 cm2 [median 19 cm2] vs. 5.8 ± 5.4 cm2 [median 5 cm2]; p= 0.02) and EPI late potential percentage (22.6 ± 9.6% [median 24%] vs. 6.8 ± 3.9% [median 8%]; p= 0.002) were significantly larger than in patients without fQRS. Overall, ENDO and EPI bipolar low voltage area andlate potential density increased as the number of fQRS ECG regions (0 to 3) increased. Inferior fQRS most frequently identified EPI inferior substrate (82% sensitivity, 100% specificity), anterior fQRS identified RV EPI mid-free wall substrate (55% sensitivity, 100% specificity), and basal superior fQRS identified ENDO (45.8% sensitivity, 100% specificity) and EPI (52% sensitivity, 100% specificity) RV outflow tract substrate abnormalities. The extent and distribution of RV voltage substrate abnormalities can be predicted by region-specific ECG depolarization changes in patients with ARVC and ventricular tachycardia.

Optogenetics Design of Mechanistically-Based Stimulation Patterns for Cardiac Defibrillation

Current rescue therapies for life-threatening arrhythmias disregard the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope operating at 2 KHz (100 x 100 pixel) was developed to optically map action potential propagation with a red-shifted voltage sensitive dye (di-4-ANBDQPQ) in whole mouse hearts. Control of the electrical activity was achieved by employing transgenic mouse hearts expressing Channel Rhodopsin-2 (ChR2). In order to draw arbitrarily-chosen ChR2 stimulation patterns with sub-millisecond temporal resolution, the macroscope was implemented with a random-access scanning head based on acousto-optic deflectors (AODs). AODs rapidly scan the laser beam across the whole field of view exciting different volume with a commutation time of few μs. At the end of one cycle the AODs return to the initial position and repeat the stimulation cycle. Alternatively, a simpler optical solution based on digital micromirror device (DMD) in combination with a high power LED was used to manipulate light positioning in a real simultaneous manner. We employed the macroscope to study the mechanistic features of ventricular tachycardia and we designed mechanistically-based cardioversion/defibrillation patterns exploiting the transient refractoriness of myocardium produced by the ChR2 stimulation. Multiple regions of conduction block revealed to efficiently defibrillate arrhythmic hearts but with lower energy requirements as compared to whole ventricle interventions. To confirm that the cardioversion efficiency is rigorously dependent on the mechanistic-based design, we positioned multiple regions of conduction block regardless of the re-entry arrhythmic wavefront obtaining a dramatically reduced cardioversion rate. In conclusion, this work demonstrates that defibrillation energies can be substantially reduced by applying discrete stimulation patterns and promotes the investigation of new anti-arrhythmic strategies.

LEFT ATRIAL ELECTROANATOMIC SUBSTRATE AS A PREDICTOR OF ATRIAL FIBRILLATION RECURRENCE AFTER CIRCULAR RADIOFREQUENCY PULMONARY VEINS ISOLATION. OBSERVATIONAL PROSPECTIVE STUDY RESULTS

Aim . To evaluate an extent of left arrial (LA) electroanatomical substrate (EAS) by the method of high density contact mapping in patients with atrial fibrillation (AF) and estimate its impact on recurrence rate following circular radiofrequency pulmonary veins (PV) isolation in prospective observational study. Material and methods. Totally 181 high symptomatic subjects with paroxysmal (142 pts) and persistent (39 pts) AF, who underwent circular RF PVI were enrolled. We created and prospectively analyzed LA electroanatomical high density bipolar maps. Bipolar signals ≤0.75mV, associated with local conduction velocity delay &lt;1 m/s were tagged on LA maps and considered as EAS. Relative EAS areas outside PV ostia were consistently measured. All of the patients were followed up at least for 3 years and AF recurrence rate and redo procedures were recorded. Results . A mean relative EAS area was 13.8±10.3% and 32.6±18.5% in patients with paroxysmal and persistent AF, respectively (P=0,02). During a mean follow-up of 32±7 months, AF recurrence was diagnosed in 69 (38%) of patients. Following a redo ablation in 51 (28%) of patients, subsequent AF recurrence developed in 31 pts (19%). Multivariate analysis showed that only relative EAS areas was independently associated with AF recurrence (HR 1.05, CI 95% 1.02-1.09, P=0.002) and ach 10% increase in the extent of relative EAS area was associated with a 1.6-fold elevation of AF recurrence rate after the index ablation. But the impact of the EAS on clinical outcome after redo ablation was even higher (HR =1,09, p=0,0018) and each 10% increase in the extent of relative EAS area was associated with a 2.4-fold elevation of AF recurrence rate after a redo ablation. Conclusion. The present study suggests that an extent of LA EAS in patients undergoing PVI — is a significant and independent predictor of AF recurrence. This data can have important role for further development and personalization of strategy of interventional treatment in patients with AF.

Ventricular arrhythmias associated with left ventricular noncompaction: Electrophysiologic characteristics, mapping, and ablation

Left ventricular noncompaction (LVNC) is a primary cardiomyopathy that can present with recurrent ventricular arrhythmias (VAs). Data on the benefit of catheter ablation of VAs in LVNC are lacking. The purpose of this study was to describe the electrophysiologic features and outcomes of catheter ablation of VAs in LVNC. The cohort consisted of 9 patients (age 42 ± 15 years) with diagnosis of LVNC based on established criteria and VA (ventricular tachycardia [VT] in 3 and frequent premature ventricular contractions (PVCs) in 6) despite treatment with a mean of 2 ± 1 antiarrhythmic drugs. Ablation sites were identified using a combination of entrainment, activation, late/fractionated potential ablation, and pace-mapping. A total of 8 patients (89%) had left ventricular (LV) systolic dysfunction (mean ejection fraction 40% ± 13%). Patients who presented with VT had evidence of abnormal electroanatomic substrate involving the mid- to apical segments of the LV, which matched the noncompacted myocardial segments identified by preprocedural magnetic resonance imaging or echocardiography. In patients presenting with frequent PVCs, the site of origin was identified at the papillary muscles (50%) and/or basal septal regions (67%). After median follow-up of 4 years (range 1-11) and a mean of 1.8 ± 1.1 procedures, VAs recurred in 1 patient (11%). Significant improvement in LV function occurred in 4 of 8 cases (50%). No patients died or underwent heart transplantation. The VA substrate in patients with LVNC and VT typically involves the mid-apical LV segments, whereas focal PVCs often arise from LV basal-septal regions and/or papillary muscles. Catheter ablation is safe and effective in achieving good VA control over long-term follow-up in most patients.

Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation.

Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2). We employed this optical system in the setting of ventricular tachycardia to optimize mechanistic, multi-barrier cardioversion/defibrillation patterns. Multiple regions of conduction block were created with a very high cardioversion efficiency but with lower energy requirements as compared to whole ventricle interventions to interrupt arrhythmias. This work demonstrates that defibrillation energies can be substantially reduced by applying discrete stimulation patterns and promotes the progress of current anti-arrhythmic strategies.

16-04: Association between biomarkers of fibrotic turnover, PR interval and electro-anatomical substrate in AF patients undergoing radiofrequency catheter ablation

16-04: Association between biomarkers of fibrotic turnover, PR interval and electro-anatomical substrate in AF patients undergoing radiofrequency catheter ablation

97-06: Fragmented QRS is Not Associated with Conduction Delay and Ventricular Arrhythmias in Patients with Repaired Tetralogy of Fallot

Introduction: Fragmented QRS complexes (fQRS) on 12-lead ECG may reflect conduction delay due to myocardial scarring and have been associated with ventricular tachyarrhythmia (VT) in patients with ischemic and nonischemic cardiomyopathy. Non-invasive risk stratification for VT in patients with repaired TOF (rTOF) has limited predictive value. This study evaluates the potential electroanatomical substrate underlying fQRS and the value of fQRS for VT risk stratification in rTOF. Methods: Fifty-three rTOF patients (46 ± 16 yrs, 64% male) at risk for VT (n = 42) or with documented VT (n = 11) underwent VT induction and detailed RV electroanatomical voltage and activation mapping (EAM) during SR to evaluate total RV activation time (RVAT) and areas of local conduction delay. Routine 12-lead ECGs prior to EAM were assessed for QRS duration, bundle branch block and fQRS defined as RSR' patterns (>1 R' or notching of R or S wave) in patients with a narrow QRS complex or >2 notches in R or S wave in patients with a wide QRS complex, present in ≥2 contiguous leads. Presence of fQRS, local conduction delay (<0.5m/s) and RVAT were compared between patients with and without spontaneous and/or induced VT. Results: Mean QRSd was 156 ± 33ms; 7 patients had narrow QRS, 46 broad QRS (24 RBBB, 7 RBBB + LAFB, 9 LBBB, 6 other). RVAT was 126 ± 37ms. Localized conduction delay confined to anatomical isthmuses was observed in 23 pts. Twenty-four patients were inducible for 37 VTs, including all with prior documented VT. Thirty-three of 37 VTs could be mapped to a slow conducting anatomical isthmus (SCAI).FQRS was present in 19 (36%) patients (3 narrow, 16 wide QRS complex) and did not differ significantly between patients with and without VT (8/24 versus 11/29 patients respectively, p = 0.728). FQRS was not associated with longer RVAT (131 ± 46ms in patients with fQRS versus 122 ± 32ms without fQRS; p = 0.402) and was not related to the presence of SCAI (SCAI present in 7 patients with fQRS versus 15 patients without fQRS p = 0.857). Conclusion: Fragmented QRS is a frequent finding and not associated with conduction delay and VA in patients with rTOF. It may be due to changes in wavefront propagation as a consequence of the surgical intervention.

96-24: Association of Left Atrial Electroanatomical Substrate and Risk of Thromboembolic Events in Patients with Atrial Fibrillation

96-24: Association of Left Atrial Electroanatomical Substrate and Risk of Thromboembolic Events in Patients with Atrial Fibrillation

Recent advances in ablation of ventricular tachycardia associated with structural heart disease: overcoming the challenges of functional and fixed barriers.

Ablation of ventricular tachycardia in structural heart disease has evolved to include techniques to ablate the myocardial substrate in sinus rhythm for ventricular tachycardias that are noninducible or hemodynamically unstable. The intricacies of the complex functional and fixed components of the myocardial scar involved in the arrhythmic mechanisms require careful consideration in identifying targets for substrate ablation identified in sinus rhythm. The substrate ablation approach referred to as 'scar homogenization' aims to thoroughly abolish any abnormal electrical activity inside the scar. However, this extensive approach may target bystander abnormal activity that is not necessarily related to arrhythmias. Recently, different substrate ablation strategies have been developed to more selectively target areas of the scar responsible for ventricular tachycardia. New technologies have also been introduced to provide offline analysis of the electroanatomical substrate, and to improve high-density mapping of the myocardial scar. Recent advances have improved the ability to ablate ventricular tachycardia using techniques that allow targeting the responsible myocardial substrate while in sinus rhythm. Further research using higher-density mapping with more sophisticated online and offline analysis will aid in the assessment of the complex arrhythmogenicity of the scar and improve efficacy of ventricular tachycardia ablation.

Procedural Outcomes and Survival After Catheter Ablation of Ventricular Tachycardia in Relation to Electroanatomical Substrate in Patients With Nonischemic-Dilated Cardiomyopathy: The Role of Unipolar Voltage Mapping.

In patients with ischemic cardiomyopathy the size of bipolar low-voltage areas (LVA) in electroanatomical maps (EAM) was associated with poorer outcomes after catheter ablation (CA) of ventricular tachycardia (VT). However, the effect of LVA size on the survival after VT ablation in patients with nonischemic dilated cardiomyopathy (NIDCM) has not been studied. In 55 patients with NIDCM (48 male, age 61 ± 16 years, ejection fraction 32 ± 13%) an EAM to delineate the bipolar and unipolar LVAs was performed in 52 (94.5%) patients endocardially, in 24 (43.6%) patients epicardially, and in 21 (38.2%) patients on both surfaces. Additionally, activation mapping of the VT was possible in 22 (40%) patients. CA with lines transecting the scar and targeting late potentials was performed in all patients. Complete VT noninducibility at the end was achieved in 40 (72.7%) patients. During the median follow-up of 22 (interquartile range IQR 6, 34) months, VT recurrences were observed in 30 (54.5%) and cardiac death in 14 (25.5%) patients. The ROC analysis revealed that the size of endocardial unipolar LVA (<8.3 mV) was associated with cardiac death (AUC 0.89, 95% CI 0.79-0.98, P <0.0001). UVA = 145 cm2 discriminates for cardiac death with 83% sensitivity and 78% specificity. Endocardial UVA > 145 cm2 was a predictor for cardiac death (adjusted HR = 6.9; P = 0.014) and UVA ≥ 54% (of total endocardial LV surface) for VT recurrence (adjusted HR = 3.5; P = 0.016). The size of endocardial unipolar LVA (<8.3 mV) was a strong and independent predictor for cardiac mortality and VT recurrence in patients with NIDCM.

Outcomes and ventricular tachycardia recurrence characteristics after epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Variable success rates have been reported after epicardial radiofrequency catheter ablation (RFA) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The details of the electroanatomic substrate are limited to a few studies, and the characteristics of the recurrent ventricular tachycardia (VT) in ARVD/C remain largely unknown. The purpose of this study was to report procedural strategy, safety, and efficacy of epicardial RFA at a tertiary single center with a focus on the characteristics of the substrate and recurrent VT. We included 30 ARVD/C patients (mean age 33.1 ± 11.1 years, 53% male) who underwent endocardial/epicardial mapping and epicardial catheter ablation of VT at the Johns Hopkins Hospital. Implantable cardioverter-defibrillator interrogations were evaluated for VT recurrence. The majority of critical VT circuits (69%) were on the epicardial surface, mostly in the subtricuspid region. Eight patients (27%) experienced VT recurrence after epicardial RFA, and the VT-free survival was 83%, 76%, and 70% at 6,12, and 24, months respectively. A significant reduction of VT burden was observed (P <.001), even among those with VT recurrence. No complications occurred except for acute pericarditis in 1 patient. The majority of VT recurrences occurred during the first year after RFA, during exercise, had fast cycle lengths, and required implantable cardioverter-defibrillator shock for termination. The vast majority of critical VT circuits were epicardial, mostly in the subtricuspid region. Epicardial RFA of VT appears to be both safe and effective in achieving arrhythmia control in ARVD/C. The features of the recurrent VT suggest a possible catecholamine-mediated mechanism with an origin in a region not targeted for ablation.

Variations of electroanatomic substrates and markers of successful ablation in idiopathic left ventricular tachycardia: role of electroanatomic substrates and potential mechanism of tachycardia.

The variation of the substrates of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) was not understood. The purpose of this study was to investigate the variation of electroanatomic substrate [slow conduction zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control individuals and markers of successful ablation. Electroanatomical mapping was performed during sinus rhythm in 20 ILVT patients and 26 control individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were tagged in geometry and the anatomic aspects were investigated. According to the distribution of Purkinje potential, LVCS was distinguished into three types: left bundle branch (LBB) was divided into two discrete fascicles without interconnections; divided into three separate fascicles; and fanlike structure distribution over septum broadly. The length of LBB and its fascicles in patients with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT group, the SCZ was located at the inferoposterior septum in 17, inferior apical septum in one and two SCZs were located at the posterior and mid-septal in the other two patients, which were greater in size and longer in length than those of six controls (P < 0.05). At the crossover junction area with diastolic potential and Purkinje potential, with the size of 1.5 ± 0.4 cm(2), concealed entertainment and ablation were obtained successfully in all patients with ILVT. The anatomy of the LVCS and SCZ is highly variable in patients with ILVT, and the crossover junction area with diastolic potential and Purkinje potential might be a marker of ablation.

Ventricular tachycardia mapping and ablation in arrhythmogenic right ventricular cardiomyopathy/dysplasia: Lessons Learned.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is primarily believed to be an inherited cardiomyopathy that subsequently results in significant myocardial fibrosis. The arrhythmogenic consequences that result from the development of fibrosis are similar to other nonischemic cardiomyopathies, but the unique endocardial-epicardial disease process of ARVC/D requires a specialized approach for arrhythmia treatment in the electrophysiology laboratory. Although the association between ARVC/D and development of ventricular arrhythmias has become increasingly clear over the last 2 decades, our understanding of the arrhythmia mechanisms, underlying electrophysiologic substrate, and treatment strategies were significantly limited. Prospective studies performed in the electrophysiology laboratory allowed detailed characterization of the electrophysiologic and electroanatomic substrate underlying ventricular tachycardia in patients with ARVC/D. This has allowed clinician scientists to better characterize the arrhythmia mechanism and develop the necessary strategies to perform successful catheter ablation. Early in this experience, catheter ablation was considered a limited and largely unsuccessful treatment for patients experiencing painful and recurrent defibrillator therapy. Through our increased understanding of the disease process, catheter ablation has evolved to become an effective and preferred therapy for a majority of these patients. Our understanding of the disease and necessary approaches to provide successful treatment continues to evolve as the clinical experience grows. This article will review these important insights from the electrophysiology laboratory and how application of this knowledge has facilitated the development of a methodical approach to successfully perform ventricular tachycardia ablation in patients with ARVC/D.