Showing papers in "Circulation-arrhythmia and Electrophysiology in 2015"

Five-Year Outcome of Catheter Ablation of Persistent Atrial Fibrillation Using Termination of Atrial Fibrillation as a Procedural Endpoint

Abstract: Background— This study aimed to determine 5-year efficacy of catheter ablation for persistent atrial fibrillation (AF) using AF termination as a procedural end point. Methods and Results— One hundred fifty patients (57±10 years) underwent persistent AF ablation using a stepwise ablation approach (pulmonary vein isolation, electrogram-guided, and linear ablation) with the desired procedural end point being AF termination. Repeat ablation was performed for recurrent AF or atrial tachycardia. AF was terminated by ablation in 120 patients (80%). Arrhythmia-free survival rates after a single procedure were 35.3%±3.9%, 28.0%±3.7%, and 16.8%±3.2% at 1, 2, and 5 years, respectively. Arrhythmia-free survival rates after the last procedure (mean 2.1±1.0 procedures) were 89.7%±2.5%, 79.8%±3.4%, and 62.9%±4.5%, at 1, 2, and 5 years, respectively. During a median follow-up of 58 (interquartile range, 43–73) months after the last ablation procedure, 97 of 150 (64.7%) patients remained in sinus rhythm without antiarrhythmic drugs. Another 14 (9.3%) patients maintained sinus rhythm after reinitiation of antiarrhythmic drugs, and an additional 15 (10.0%) patients regressed to paroxysmal recurrences only. Failure to terminate AF during the index procedure (hazard ratio 3.831; 95% confidence interval, 2.070–7.143; P <0.001), left atrial diameter ≥50 mm (hazard ratio 2.083; 95% confidence interval, 1.078–4.016; P =0.03), continuous AF duration ≥18 months (hazard ratio 1.984; 95% confidence interval, 1.024–3.846; P <0.04), and structural heart disease (hazard ratio 1.874; 95% confidence interval, 1.037–3.388; P =0.04) predicted arrhythmia recurrence. Conclusions— In patients with persistent AF, an ablation strategy aiming at AF termination is associated with freedom from arrhythmia recurrence in the majority of patients over a 5-year follow-up period. Procedural AF nontermination and specific baseline factors predict long-term outcome after ablation.

Brugada Syndrome Phenotype Elimination by Epicardial Substrate Ablation

Abstract: Background —Whether Brugada Syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation (RFA), remains unknown. Methods and Results —BrS patients underwent epicardial mapping to identify areas of abnormal electrograms as target for RFA. Substrate identification consisted in mapping RV epicardial surface before and after flecainide (2 mg/Kg/10 min). After RFA, flecainide (F) and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and VT/VF inducibility. F testing was performed at each follow-up visits up to 6 months. Fourteen BrS patients, median age 39 years (30.3 to 42.3) with ICD implantation were enrolled. Low voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after F from 17.6 cm2 (12.1 to 24.2) to 28.5 cm2 (21.6 to 30.2) (P=0.001). Similarly, areas with abnormal electrograms increased after F from 19.0 cm2 (17.5 to 23.6) to 27.3 cm2 (24.0 to 31.2) (P=0.001). After 23.8 min (18.1 to 28.5) of RFA, abnormal electrograms disappeared, while low-voltage areas were replaced by scar areas (<0.5mV) of 25.9 cm2 (19.6 to 31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no VT/VF inducibility without complications. After a median follow-up of 5 months (3.8 to 5.3) ECG remained normal despite F. Conclusions —In BrS patients there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate and VT/VF inducibility. Ablation of the substrate identified in the presence of F can eliminate the BrS phenotype and warrants further study.

High-Resolution Mapping of Scar-Related Atrial Arrhythmias Using Smaller Electrodes With Closer Interelectrode Spacing

Abstract: Background— The resolution of mapping is influenced by electrode size and interelectrode spacing. Smaller electrodes with closer interelectrode spacing may improve mapping resolution, particularly in scar. The aims of this study were to establish normal electrogram criteria in the atria for both 3.5-mm electrode tip linear catheters (Thermocool) and 1-mm multielectrode-mapping catheters (Pentaray) and to compare their mapping resolution in scar-related atrial arrhythmias. Methods and Results— Normal voltage amplitude cutoffs for both catheters were validated in 10 patients with structurally normal atria. In 20 additional patients with scar-related atrial arrhythmias, similar sequential mapping with both catheters was performed. Normal bipolar voltage amplitude was similar between 3.5- and 1-mm electrode catheters with a fifth percentile of 0.48 and 0.52 mV, respectively ( P =0.65). In patients with scar-related atrial arrhythmias, the total area of bipolar voltage <0.5 mV measured using 1-mm electrode catheters was smaller than that measured using 3.5-mm catheter (14.7 versus 20.4 cm2; P =0.02). The mean bipolar voltage amplitude in this area of low voltage was significantly higher with 1-mm electrode catheters (0.28 and 0.17 mV; P =0.01). Importantly, 54.4% of all low voltage data points recorded with 1-mm electrode catheter had distinct electrograms that allowed annotation of local activation time compared with only 21.4% with 3.5-mm electrode tip catheters ( P =0.01). Overdrive pacing with capture of the tachycardia from within the area of low voltage was more frequent with 1-mm electrode catheters (66.7 versus 33.4; P =0.01). Conclusions— Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.

Ventricular Tachycardia in Cardiac Sarcoidosis: Characterization of Ventricular Substrate and Outcomes of Catheter Ablation

Abstract: Background— Cardiac sarcoid–related ventricular tachycardia (VT) is a rare disorder; the underlying substrate and response to ablation are poorly understood. We sought to examine the ventricular substrate and outcomes of catheter ablation in this population. Methods and Results— Of 435 patients with nonischemic cardiomyopathy referred for VT ablation, 21 patients (5%) had cardiac sarcoidosis. Multiple inducible VTs were observed with mechanism consistent with scar-mediated re-entry in all VTs. Voltage maps showed widespread and confluent right ventricular scarring. Left ventricular scarring was patchy with a predilection for the basal septum, anterior wall, and perivalvular regions. Epicardial right ventricular scar overlay and exceeded the region of corresponding endocardial scar. After ≥1 procedures, ablation abolished ≥1 inducible VT in 90% and eliminated VT storm in 78% of patients; however, multiple residual VTs remained inducible. Failure to abolish all inducible VTs was because of septal intramural circuits or extensive right ventricular scarring. Multiple procedure VT-free survival was 37% at 1 year, but VT control was achievable in the majority of patients with fewer antiarrhythmic drugs compared with preablation (2.1±0.8 versus 1.1±0.8; P <0.001). Conclusions— Patients with cardiac sarcoidosis and VT exhibit ventricular substrate characterized by confluent right ventricular scarring and patchy left ventricular scarring capable of sustaining a large number of re-entrant circuits. Catheter ablation is effective in terminating VT storm and eliminating ≥1 inducible VT in the majority of patients, but recurrences are common. Ablation in conjunction with antiarrhythmic drugs can help palliate VT in this high-risk population.

Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry.

Abstract: Background— Catecholaminergic polymorphic ventricular tachycardia is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flecainide and left cardiac sympathetic denervation are not well validated. We sought to define treatment outcomes in children with catecholaminergic polymorphic ventricular tachycardia. Methods and Results— This is a Pediatric and Congenital Electrophysiology Society multicenter, retrospective cohort study of catecholaminergic polymorphic ventricular tachycardia patients diagnosed before 19 years of age. The cohort included 226 patients, including 170 probands and 56 relatives. Symptomatic presentation was reported in 176 (78%). Symptom onset occurred at 10.8 (interquartile range, 6.8–13.2) years with a delay to diagnosis of 0.5 (0–2.6) years. Syncope ( P <0.001), cardiac arrest ( P <0.001), and treatment failure ( P =0.008) occurred more often in probands. β-Blockers were prescribed in 205 of 211 patients (97%) on medication, and 25% experienced at least 1 treatment failure event. Implantable cardioverter defibrillators were placed in 121 (54%) and was associated with electrical storm in 22 (18%). Flecainide was used in 24% and left cardiac sympathetic denervation in 8%. Six deaths (3%) occurred during a cumulative follow-up of 788 patient-years. Conclusions— This study demonstrates a malignant phenotype and lengthy delay to diagnosis in catecholaminergic polymorphic ventricular tachycardia. Probands were typically severely affected. β-Blockers were almost universally initiated; however, treatment failure, noncompliance and subtherapeutic dosing were often reported. Implantable cardioverter defibrillators were common despite numerous device-related complications. Treatment failure was rare in the quarter of patients on flecainide. Left cardiac sympathetic denervation was not uncommon although the indication was variable.

Scar dechanneling: new method for scar-related left ventricular tachycardia substrate ablation.

Abstract: Background Ventricular tachycardia (VT) substrate ablation usually requires extensive ablation. Scar dechanneling technique may limit the extent of ablation needed. Methods and results The study included 101 consecutive patients with left ventricular scar-related VT (75 ischemic patients; left ventricular ejection fraction, 36 ± 13%). Procedural end point was the elimination of all identified conducting channels (CCs) by ablation at the CC entrance followed by abolition of residual inducible VTs. By itself, scar dechanneling rendered noninducibility in 54.5% of patients; ablation of residual inducible VT increased noninducibility to 78.2%. Patients needing only scar dechanneling had a shorter procedure (213 ± 64 versus 244 ± 71 minutes; P = 0.027), fewer radiofrequency applications (19 ± 11% versus 27 ± 18%; P = 0.01), and external cardioversion/defibrillation shocks (20% versus 65.2%; P Conclusions Scar dechanneling alone results in low recurrence and mortality rates in more than half of patients despite the limited ablation extent required. Residual inducible VT ablation improves acute results, but patients who require it have worse outcomes. Recurrences are mainly related to incomplete CC-electrogram elimination.

Quantitative analysis of localized sources identified by focal impulse and rotor modulation mapping in atrial fibrillation.

Abstract: Background— New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms used to identify rotors and describe acute procedural outcomes of FIRM-guided ablation. Methods and Results— All FIRM-guided ablation procedures (n=24; 50% paroxysmal) at University of California, Los Angeles Medical Center were included for analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation in most patients (n=19; 79%). All patients had rotors identified (mean, 2.3±0.9 per patient; 72% in left atrium). Prespecified acute procedural end point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1 cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient showed interpretable atrial electrograms. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23 of 24 patients (96%). Conclusions— FIRM-identified rotor sites did not exhibit quantitative atrial electrogram characteristics expected from rotors and did not differ quantitatively from surrounding tissue. Catheter ablation at these sites, in conjunction with pulmonary vein isolation, resulted in AF termination or organization in a minority of patients (4/24; 17%). Further validation of this approach is necessary.

Atrial Fibrillation Burden and Short-Term Risk of Stroke: Case-Crossover Analysis of Continuously Recorded Heart Rhythm From Cardiac Electronic Implanted Devices

Abstract: Background— The temporal relationship of atrial fibrillation (AF) and stroke risk is controversial. We evaluated this relationship via a case-crossover analysis of ischemic strokes in a large cohort of patients with cardiac implantable electronic devices. Methods and Results— We identified 9850 patients with cardiac implantable electronic devices remotely monitored in the Veterans Administration Health Care System between 2002 and 2012. There were 187 patients with acute ischemic stroke and continuous heart rhythm monitoring for 120 days before the stroke (age, 69±8.4 years; 98% with an implantable defibrillator). We compared each patient’s daily AF burden in the 30 days before stroke (case period) with their AF burden during days 91 to 120 pre stroke (control period). Defining positive AF burden as ≥5.5 hours of AF on any given day, 156 patients (83%) had no positive AF burden in both periods and, in fact, had little to no AF; 15 (8%) patients had positive AF burden in both periods. Among the discordant (informative) patients, 13 exceeded 5.5 hours of AF in the case period but not in the control period, whereas 3 had positive AF burden in the control but not in the case period (warfarin-adjusted odds ratio for stroke, 4.2; 95% confidence interval, 1.5–13.4). Odds ratio for stroke was highest (17.4; 95% confidence interval, 5.39–73.1) in the 5 days immediately after a qualifying occurrence of AF and decreased toward 1.0 as the period after the AF occurrence increased beyond 30 days. Conclusions— In this population with continuous heart rhythm recording, multiple hours of AF had a strong but transient effect raising stroke risk.

Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia

Abstract: A 71-year-old man with coronary artery disease, coronary artery bypass grafting in 2000, baseline ejection fraction of 0.24, and implantation of a single chamber implanted cardioverter defibrillator (ICD) in 2009 for ventricular tachycardia (VT) presented with continuous episodes of nonsustained and sustained VT refractory to sotalol and mexiletine. Despite angioplasty and stent for coronary artery disease, VT continued for 2 years. Medical history included atrial fibrillation and oxygen-dependent chronic obstructive pulmonary disease. Baseline electrocardiogram (ECG) showed atrial fibrillation with a ventricular rate of 82 beats per minute with inferior Q waves and QRS duration of 90 ms. Twelve-lead ECG during VT showed a regular, wide-complex tachycardia at 160 beats per minute (CL 380–400 ms), with a right bundle branch block pattern, superior axis, precordial transition at V3–V4. His ICD log showed numerous VT episodes, with a single morphology seen on intracardiac ventricular electrogram, cycle length 380–411ms. Episodes were nonsustained, pace-terminated, and shock-terminated. As catheter ablation was relatively medically contraindicated, he consented to a Food and Drug Administration and Institutional Review Board–approved compassionate-use protocol of stereotactic arrhythmia radioablation (STAR), noninvasive ablation of VT substrate by stereotactic ablative radiotherapy (SABR) techniques for tumors. STAR therapy was delivered in October, 2012. Baseline echocardiogram showed a dilated left ventricle (LV), ejection fraction of 0.24, with basal inferior aneurysm, and apical and infero-posterior akinesis. Positron emission tomography–computed tomography showed extensive hypometabolic scar in the LV extending between the LV base and the apex, involving the inferior, inferoseptal, and inferolateral walls. A target for STAR was delineated using proprietary visualization and contouring software (CardioPlan™, CyberHeart™, Portola Valley, CA), outlining the target volume corresponding to what would have been the …

Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Abstract: Background— Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. Methods and Results— We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO–EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56±44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on β-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. Conclusions— The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs.

Core isolation of critical arrhythmia elements for treatment of multiple scar-based ventricular tachycardias.

Abstract: Background— Radiofrequency ablation of multiple or unmappable ventricular tachycardias (VTs) remains a challenge with unclear end points. We present our experience with a new strategy isolating core elements of VT circuits. Methods and Results— Patients with structural heart disease presenting for VT radiofrequency ablation at 2 centers were included. Strategy involved entrainment/activation mapping if VT was hemodynamically stable, and voltage mapping with electrogram analysis and pacemapping. Core isolation (CI) was performed incorporating putative isthmus and early exit site(s) based on standard criteria. If VT was noninducible, the dense scar (<0.5 mV) region was isolated. Successful CI was defined by exit block (20 mA at 2 ms) within the isolated region. VT inducibility was also assessed. Forty-four patients were included (mean age, 63; 95% male; 73% ischemic cardiomyopathy; mean left ventricular ejection fraction, 31%; 68% with multiple unstable VTs [mean, 3+2]). CI area was 11+12 versus 55+40 cm2 total scar area. Additional substrate modification was performed in 27 (61%), and epicardial radiofrequency ablation was performed in 4 (9%) patients. CI was achieved in 37 (84%) and led to better VT-free survival (log rank P =0.013). Conclusions— CI is a novel strategy with a discrete and measurable end point beyond VT inducibility to treat patients with multiple or unmappable VTs. The CI region can be selected based on standard characterization of suspected VT isthmus surrogates thus limiting ablation target size. Exit block within the isolated area is achievable in most and may further improve long-term success.

Five-year follow-up after catheter ablation of persistent atrial fibrillation using the stepwise approach and prognostic factors for success

Abstract: Background—In the meantime, catheter ablation is widely used for the treatment of persistent atrial fibrillation (AF). There is a paucity of data about long-term outcomes. This study evaluates (1) ...

The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism.

Abstract: Background— Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety Methods and Results— HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone’s negative inotropic effect—see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations Neither placebo nor either drugs alone significantly reduced AFB Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo ( P =0008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% ( P =0072) Both combinations were well tolerated Conclusions— HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled Clinical Trial Registration— [ClinicalTrialsgov][1]; Unique identifier: [NCT01522651][2] [1]: http://ClinicalTrialsgov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01522651&atom=%2Fcircae%2F8%2F5%2F1048atom

Acute hemodynamic decompensation during catheter ablation of scar-related ventricular tachycardia: incidence, predictors, and impact on mortality.

Abstract: Background— The occurrence of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing radiofrequency catheter ablation of scar-related ventricular tachycardia (VT) has not been previously investigated. Methods and Results— We identified univariate predictors of periprocedural AHD in 193 consecutive patients undergoing radiofrequency catheter ablation of scar-related VT. AHD was defined as persistent hypotension despite vasopressors and requiring mechanical support or procedure discontinuation. AHD occurred in 22 (11%) patients. Compared with the rest of the population, patients with AHD were older (68.5±10.7 versus 61.6±15.0 years; P =0.037); had a higher prevalence of diabetes mellitus (36% versus 18%; P =0.045), ischemic cardiomyopathy (86% versus 52%; P =0.002), chronic obstructive pulmonary disease (41% versus 13%; P =0.001), and VT storm (77% versus 43%; P =0.002); had more severe heart failure (New York Heart Association class III/IV: 55% versus 15%, P <0.001; left ventricular ejection fraction: 26±10% versus 36±16%, P =0.003); and more often received periprocedural general anesthesia (59% versus 29%; P =0.004). At 21±7 months follow-up, the mortality rate was higher in the AHD group compared with the rest of the population (50% versus 11%, log-rank P <0.001). Conclusions— AHD occurs in 11% of patients undergoing radiofrequency catheter ablation of scar-related VT and is associated with increased risk of mortality over follow-up. AHD may be predicted by clinical factors, including advanced age, ischemic cardiomyopathy, more severe heart failure status (New York Heart Association class III/IV, lower ejection fraction), associated comorbidities (diabetes mellitus and chronic obstructive pulmonary disease), presentation with VT storm, and use of general anesthesia.

Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit: outcomes and electrocardiogram correlates of success.

Abstract: Background— Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit is limited by the presence of major coronary vessels and epicardial fat. We report the outcomes of percutaneous epicardial mapping and ablation of ventricular arrhythmias arising from the left ventricular summit and the ECG features associated with successful ablation. Methods and Results— Between January 2003 and December 2012, a total of 23 consecutive patients (49±14 years; 39% men) with ventricular arrhythmias arising from the left ventricular summit underwent percutaneous epicardial instrumentation for mapping and ablation because of unsuccessful ablation from the coronary venous system and multiple endocardial LV/right ventricular sites. Successful epicardial ablation was achieved in 5 (22%) patients. In the remaining 18 (78%) cases, ablation was aborted for either close proximity to major coronary arteries or poor energy delivery over epicardial fat. The Q-wave amplitude ratio in aVL/aVR was higher in the successful group, with a ratio of >1.85 present in 4 (80%) patients in the successful group versus 2 (11%) in the unsuccessful group ( P =0.008). The ratio of R/S wave in V1 was greater in the successful group, with 4 (80%) patients in the successful group having a R/S ratio of >2 in V1 versus 5 (28%) in the unsuccessful group ( P =0.056). None of the patients in the successful group had an initial q wave in lead V1, as opposed to 6 (33%) in the unsuccessful group. The presence of at least 2 of the 3 ECG criteria above predicted successful ablation with 100% sensitivity and 72% specificity. Conclusions— Epicardial instrumentation for mapping and ablation of ventricular arrhythmias arising from the left ventricular summit is successful only in a minority of patients because of close proximity to major coronary arteries and epicardial fat. A Q-wave ratio of >1.85 in aVL/aVR, a R/S ratio of >2 in V1, and absence of q waves in lead V1 help identify appropriate candidates for epicardial ablation.

Relationship between sinus rhythm late activation zones and critical sites for scar-related ventricular tachycardia: systematic analysis of isochronal late activation mapping.

Abstract: Background— It is not known whether the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits. Methods and Results— Isochronal late activation maps were constructed to display ventricular activation during sinus rhythm over 8 isochrones. Analysis was performed at successful VT termination sites and prospectively tested. Thirty-three patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those who underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5%–100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1-cm radius. Ten consecutive patients underwent ablation prospectively guided by isochronal late activation maps, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone. Conclusions— Late potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification.

Validation of the 2014 European Society of Cardiology Guidelines Risk Prediction Model for the Primary Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Abstract: Background— The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. Methods and Results— The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57–0.82; P =0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47–0.63; P =0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50–0.70; P =0.07). Conclusions— The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD.

Prognostic value of programmed electrical stimulation in Brugada syndrome: 20 years experience.

Abstract: Background— The prognostic value of electrophysiological investigations in individuals with Brugada syndrome remains controversial. Different groups have published contradictory data. Long-term follow-up is needed to clarify this issue. Methods and Results— Patients presenting with spontaneous or drug-induced Brugada type I ECG and in whom programmed electric stimulation was performed at our institution were considered eligible for this study. A total of 403 consecutive patients (235 males, 58.2%; mean age, 43.2±16.2 years) were included. Ventricular arrhythmias during programmed electric stimulation were induced in 73 (18.1%) patients. After a mean follow-up time of 74.3±57.3 months (median 57.3), 25 arrhythmic events occurred (16 in the inducible group and 9 in the noninducible). Ventricular arrhythmias inducibility presented a hazard ratio for events of 8.3 (95% confidence interval, 3.6–19.4), P <0.01. Conclusions— Programmed ventricular stimulation of the heart is a good predictor of outcome in individuals with Brugada syndrome. It might be of special value to guide further management when performed in asymptomatic individuals. The overall accuracy of the test makes it a suitable screening tool to reassure noninducible asymptomatic individuals

Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract Efficacy of Sequential Versus Simultaneous Unipolar Catheter Ablation

Abstract: Backgrounds— Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Methods and Results— Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <–30 ms was recorded at those ablation sites. Conclusions— LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides.

On the Quest for the Best Freeze: Predictors of Late Pulmonary Vein Reconnections After Second-Generation Cryoballoon Ablation.

Abstract: Background— The second-generation cryoballoon is effective in achieving acute pulmonary vein isolation (PVI) and favorable clinical outcome. To date, no data are available on factors affecting late PV reconnection after second-generation cryoballoon ablation. Methods and Results— A total of 29 consecutive patients (25 male, 86.2%; mean age 57.8±13.8 years) underwent a repeat procedure, after a mean 11.6±4.5 months (range, 3.5–19.7 months), after index ablation using the 28-mm second-generation cryoballoon. All repeat ablations were performed using a 3-dimensional electroanatomical mapping system. Among all 115 PVs, including 1 left common ostiums (LCOs), 25 (21.7%) showed a PV reconnection in 20 patients (1.25 per patient). Persistent PVI could be documented in 90 of 115 PVs (78.2%). In 9 of 29 patients (31%), all PVs were electrically isolated. In the multivariable analysis, time to PVI ( P =0.03) and failure to achieve −40°C within 60 s ( P =0.05) independently predicted late PV reconnection. At receiver-operator curve analysis, time to PVI <60 s identified the absence of PV reconduction (sensitivity, 86.7%; specificity, 86.2%; positive predictive value, 59.1%; and negative predictive value, 96.4%; area under the curve, 0.85; confidence interval, 0.73–0.97; P <0.001). Conclusions— The rate of late PV reconnection after second-generation cryoballoon ablation is low (1.25 PVs/patient). Faster time to isolation and achievement of −40°C within 60 s independently predict durable PVI. In addition, 60-s cut-off for time to PVI indicates persistent isolation with 96.4% negative predictive value. These parameters might guide the operator whether to perform further applications to ensure a long-lasting PVI.

Atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation.

Abstract: Background— Atrial fibrosis is an important component of the arrhythmogenic substrate in patients with atrial fibrillation (AF). We studied the effect of interstitial fibrosis on conduction velocity (CV) in the left atrial appendage of patients with AF. Methods and Results— Thirty-five left atrial appendages were obtained during AF surgery. Preparations were superfused and stimulated at 100 beats per minute. Activation was recorded with optical mapping. Longitudinal CV (CVL), transverse CV (CVT), and activation times (>2 mm distance) were measured. Interstitial collagen was quantified and graded qualitatively. The presence of fibroblasts and myofibroblasts was assessed immunohistochemically. Mean CVL was 0.55±0.22 m/s, mean CVT was 0.25±0.15 m/s, and the mean activation time was 9.31±5.45 ms. The amount of fibrosis was unrelated to CV or patient characteristics. CVL was higher in left atrial appendages with thick compared with thin interstitial collagen strands (0.77±0.22 versus 0.48±0.19 m/s; P =0.012), which were more frequently present in persistent patients with AF. CVT was not significantly different ( P =0.47), but activation time was 14.93±4.12 versus 7.95±4.12 ms in patients with thick versus thin interstitial collagen strands, respectively ( P =0.004). Fibroblasts were abundantly present and were associated with the presence of thick interstitial collagen strands ( P =0.008). Myofibroblasts were not detected in the left atrial appendage. Conclusions— In patients with AF, thick interstitial collagen strands are associated with higher CVL and increased activation time. Our observations demonstrate that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry.

Management of Brugada Syndrome: Thirty-Three-Year Experience Using Electrophysiologically Guided Therapy With Class 1A Antiarrhythmic Drugs.

Abstract: Background— Information on long-term clinical outcome of patients with Brugada syndrome treated with electrophysiologically guided class 1A antiarrhythmic drugs (AAD) is limited. Methods and Results— An aggressive protocol of programmed ventricular stimulation was performed in 96 patients with Brugada syndrome (88% males; mean age, 39.8±15.9 years). Ten patients were cardiac arrest survivors, 27 had presented with syncope, and 59 were asymptomatic. Ventricular fibrillation was induced in 66 patients, including 100%, 74%, and 61% of patients with cardiac arrest, syncope, and no symptoms, respectively. All but 6 of the 66 patients with inducible ventricular fibrillation underwent electrophysiological testing on quinidine (n=54), disopyramide (n=2), or both (n=4). Fifty-four (90%) patients were electrophysiological responders to >1 AAD with similar efficacy rates (≈90%) in all patients groups. Patients with no inducible ventricular fibrillation at baseline were left on no therapy. After a mean follow-up of 113.3±71.5 months, 92 patients were alive, whereas 4 died from noncardiac causes. No arrhythmic event occurred during class 1A AAD therapy in any of electrophysiological drug responders and in patients with no baseline inducible ventricular fibrillation. Arrhythmic events occurred in only 2 cardiac arrest survivors treated with implantable cardioverter–defibrillator alone but did not recur on quinidine. All cases of recurrent syncope (n=12) were attributed to a vasovagal (n=10) or nonarrhythmic mechanism (n=2). Class 1A AAD therapy resulted in 38% incidence of side effects that resolved after drug discontinuation. Conclusions— Our data suggest that electrophysiologically guided class 1A AAD treatment has a place in our therapeutic armamentarium for all types of patients with Brugada syndrome.

Common Genetic Variants and Response to Atrial Fibrillation Ablation

Abstract: Background— Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2 ), 1q21 (rs13376333 in KCNN3 ), and 16q22 (rs7193343 in ZFHX3 ) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results— Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; P =0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions— Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery: One Year Follow Up of a Randomized Pilot Study

Abstract: Background— Animal models suggest that the neurotransmitter inhibitor, botulinum toxin, when injected into the epicardial fat pads can suppress atrial fibrillation inducibility. The aim of this prospective randomized double-blind study was to compare the efficacy and safety of botulinum toxin injection into epicardial fat pads for preventing atrial tachyarrhythmias. Methods and Results— Patients with history of paroxysmal atrial fibrillation and indication for coronary artery bypass graft surgery were randomized to botulinum toxin (Xeomin, Merz, Germany; 50 U/1 mL at each fat pad; n=30) or placebo (0.9% normal saline, 1 mL at each fat pad; n=30) injection into epicardial fat pads during surgery. Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder. All patients in both groups had successful epicardial fat pad injections without complications. The incidence of early postoperative atrial fibrillation within 30 days after coronary artery bypass graft was 2 of 30 patients (7%) in the botulinum toxin group and 9 of 30 patients (30%) in the placebo group ( P =0.024). Between 30 days and up to the 12-month follow-up examination, 7 of the 30 patients in the placebo group (27%) and none of the 30 patients in the botulinum toxin group (0%) had recurrent atrial fibrillation ( P =0.002). There were no complications observed during the 1-year follow-up. Conclusions— Botulinum toxin injection into epicardial fat pads during coronary artery bypass graft provided substantial atrial tachyarrhythmia suppression both early as well as during 1-year follow-up, without any serious adverse events. Clinical Trial Registration— URL: . Unique identifier: [NCT01842529][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01842529&atom=%2Fcircae%2F8%2F6%2F1334.atom

Once Isolated, Always Isolated? Incidence and Characteristics of Pulmonary Vein Reconduction After Second-Generation Cryoballoon-Based Pulmonary Vein Isolation.

Abstract: Background— The second-generation cryoballoon delivers effective pulmonary vein isolation (PVI) associated with superior 1-year clinical outcome. However, data on reconduction of previously isolated PV are sparse. Methods and Results— A total of 421 patients underwent second-generation 28-mm cryoballoon-based PVI in 2 centers (St. George’s hospital and Harburg hospital, Hamburg, Germany) between June 2012 and May 2015. Sixty-six of 421 (16%) patients (39/66, 59% women; mean age, 63±10 years, mean left atrium diameter, 45±6 mm) with a history of paroxysmal (40/66, 61%) or persistent atrial fibrillation and atrial tachyarrhythmia recurrences despite previous successful second-generation 28-mm cryoballoon-based PVI were included in this analysis. During the index PVI, the standard freeze cycle duration was 240 s. After successful PVI, a bonus freeze cycle of 240 s was applied in the first 15 of 66 (23%) patients, whereas no bonus freeze cycle was applied in the remaining patients. Repeat procedures were performed after a median of 205 (131–357) days following the index ablation. Electric reconduction was assessed for all PVs, and reablation was performed using radiofrequency energy. Persistent electric isolation was noted in 178 of 258 (69%) PVs. In 17 of 66 (26%) patients, all previously targeted PVs remained isolated. A significant difference toward highest reconduction rate for the posteroinferior segment of the right inferior PV was found ( P =0.0002). Conclusions— The second-generation cryoballoon ablation is associated with a high rate of persistent PVI. The posteroinferior segment of the right inferior PV showed the highest reconduction rate and seems to be a predilection site for PV reconduction.

Re-Entry Using Anatomically Determined Isthmuses: A Curable Ventricular Tachycardia in Repaired Congenital Heart Disease

Abstract: Background— Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. Methods and Results— Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1–2) VT, median cycle length: 295 ms (interquartile range, 242–346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. Conclusions— In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative.

Sympathetic Nerve Stimulation, Not Circulating Norepinephrine, Modulates T-Peak to T-End Interval by Increasing Global Dispersion of Repolarization

Abstract: Background— T-peak to T-end interval (Tp-e) is an independent marker of sudden cardiac death. Modulation of Tp-e by sympathetic nerve activation and circulating norepinephrine is not well understood. The purpose of this study was to characterize endocardial and epicardial dispersion of repolarization (DOR) and its effects on Tp-e with sympathetic activation. Methods and Results— In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia were exposed. A 56-electrode sock and 64-electrode basket catheter were placed around the epicardium and in the left ventricle (LV), respectively. Activation recovery interval, DOR, defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral stellate ganglia stimulation and norepinephrine infusion. LV endocardial and epicardial activation recovery intervals significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial versus endocardial differences in activation recovery interval during sympathetic stimulation, and regional endocardial activation recovery interval patterns were similar to the epicardium. Tp-e prolonged during left (from 40.4±2.2 ms to 92.4±12.4 ms; P <0.01), right (from 47.7±2.6 ms to 80.7±11.5 ms; P <0.01), and bilateral (from 47.5±2.8 ms to 78.1±9.8 ms; P <0.01) stellate stimulation and strongly correlated with whole heart DOR during stimulation ( P <0.001, R =0.86). Of note, norepinephrine infusion did not increase DOR or Tp-e. Conclusions— Regional patterns of LV endocardial sympathetic innervation are similar to that of LV epicardium. Tp-e correlated with whole heart DOR during sympathetic nerve activation. Circulating norepinephrine did not affect DOR or Tp-e.

Role of Alternative Interventional Procedures When Endo- and Epicardial Catheter Ablation Attempts for Ventricular Arrhythmias Fail

Abstract: Background— Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. Methods and Results— Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P <0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. Conclusions— A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.

Left Atrial Transcriptional Changes Associated With Atrial Fibrillation Susceptibility and Persistence

Abstract: Background— Prior transcriptional studies of atrial fibrillation (AF) have been limited to specific transcripts, animal models, chronic AF, right atria, or small samples. We sought to characterize the left atrial transcriptome in human AF to distinguish changes related to AF susceptibility and persistence. Methods and Results— Left atrial appendages from 239 patients stratified by coronary artery disease, valve disease, and AF history (no history of AF, AF history in sinus rhythm at surgery, and AF history in AF at surgery) were selected for genome-wide mRNA microarray profiling. Transcripts were examined for differential expression with AF phenotype group. Enrichment in differentially expressed genes was examined in 3 gene set collections: a transcription factor collection, defined by shared conserved cis -regulatory motifs, a miRNA collection, defined by shared 3′ untranslated region motifs, and a molecular function collection, defined by shared Gene Ontology molecular function. AF susceptibility was associated with decreased expression of the targets of CREB/ATF family, heat-shock factor 1, ATF6, SRF, and E2F1 transcription factors. Persistent AF activity was associated with decreased expression in genes and gene sets related to ion channel function consistent with reported functional changes. Conclusions— AF susceptibility was associated with decreased expression of targets of several transcription factors related to inflammation, oxidation, and cellular stress responses. In contrast, changes in ion channel expression were associated with AF activity but were limited in AF susceptibility. Our results suggest that significant transcriptional remodeling marks susceptibility to AF, whereas remodeling of ion channel expression occurs later in the progression or as a consequence of AF.

Differentiation of Papillary Muscle From Fascicular and Mitral Annular Ventricular Arrhythmias in Patients With and Without Structural Heart Disease

Abstract: Background— Idiopathic left ventricular arrhythmias (VAs) and those caused by structural heart disease can originate from the papillary muscles, fascicles, and mitral annulus. Differentiation of these arrhythmias can be challenging because they present with a right bundle branch block morphology by electrocardiography. We sought to identify clinical, electrocardiographic, and electrophysiological features that distinguish these left VAs in patients with and without structural heart disease. Method and Results— Patients undergoing catheter ablation for papillary muscle, fascicular, or mitral annular VAs were studied. Demographic data and electrocardiographic and electrophysiological findings were analyzed. Fifty-two VAs in 51 patients (32 [63%] male; mean age 61±15 years) with papillary muscle (n=18), fascicular (n=15), and mitral annular (n=19) origins were studied. Patients with papillary muscle VAs were older and had higher prevalence of left ventricular dysfunction (67% versus 13% of fascicular VA patients [ P =0.009]) and coronary artery disease (78% versus 37% of mitral annular VA patients [ P =0.036]). Papillary muscle VAs were distinguished electrocardiographically from fascicular VAs by longer QRS durations and lower prevalence of r