Patrizio Pascale

Elimination of Local Abnormal Ventricular Activities A New End Point for Substrate Modification in Patients With Scar-Related Ventricular Tachycardia

Background— Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping. Methods and Results— Seventy patients (age, 67±11 years; 7 female) with VT and structurally abnormal ventricle(s) were prospectively enrolled. Conventional mapping was performed in sinus rhythm in all, and a high-density Pentaray mapping catheter was used in the endocardium (n=35) and epicardially. LAVAs were recorded in 67 patients (95.7%; 95% confidence interval, 89.2–98.9). Catheter ablation was performed targeting LAVA with an irrigated-tip catheter placed endocardially via a transseptal or retrograde aortic approach or epicardially via the subxiphoid approach. LAVAs were successfully abolished or dissociated in 47 of 67 patients (70.1%; 95% confidence interval, 58.7–80.1). In multivariate analysis, LAVA elimination was independently associated with a reduction in recurrent VT or death (hazard ratio, 0.49; 95% confidence interval, 0.26–0.95; P =0.035) during long-term follow-up (median, 22 months). Conclusions— LAVAs can be identified in most patients with scar-related VT. Elimination of LAVAs is feasible and safe and is associated with superior survival free from recurrent VT. # Clinical Perspective {#article-title-32}Background— Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping. Methods and Results— Seventy patients (age, 67±11 years; 7 female) with VT and structurally abnormal ventricle(s) were prospectively enrolled. Conventional mapping was performed in sinus rhythm in all, and a high-density Pentaray mapping catheter was used in the endocardium (n=35) and epicardially. LAVAs were recorded in 67 patients (95.7%; 95% confidence interval, 89.2–98.9). Catheter ablation was performed targeting LAVA with an irrigated-tip catheter placed endocardially via a transseptal or retrograde aortic approach or epicardially via the subxiphoid approach. LAVAs were successfully abolished or dissociated in 47 of 67 patients (70.1%; 95% confidence interval, 58.7–80.1). In multivariate analysis, LAVA elimination was independently associated with a reduction in recurrent VT or death (hazard ratio, 0.49; 95% confidence interval, 0.26–0.95; P=0.035) during long-term follow-up (median, 22 months). Conclusions— LAVAs can be identified in most patients with scar-related VT. Elimination of LAVAs is feasible and safe and is associated with superior survival free from recurrent VT.

Inverse Relationship Between Fractionated Electrograms and Atrial Fibrosis in Persistent Atrial Fibrillation: Combined Magnetic Resonance Imaging and High-Density Mapping

OBJECTIVES This study sought to evaluate the relationship between fibrosis imaged by delayed-enhancement (DE) magnetic resonance imaging (MRI) and atrial electrograms (Egms) in persistent atrial fibrillation (AF). BACKGROUND Atrial fractionated Egms are strongly related to slow anisotropic conduction. Their relationship to atrial fibrosis has not yet been investigated. METHODS Atrial high-resolution MRI of 18 patients with persistent AF (11 long-lasting persistent AF) was registered with mapping geometry (NavX electro-anatomical system (version 8.0, St. Jude Medical, St. Paul, Minnesota)). DE areas were categorized as dense or patchy, depending on their DE content. Left atrial Egms during AF were acquired using a high-density, 20-pole catheter (514 ± 77 sites/map). Fractionation, organization/regularity, local mean cycle length (CL), and voltage were analyzed with regard to DE. RESULTS Patients with long-lasting persistent versus persistent AF had larger left atrial (LA) surface area (134 ± 38 cm(2) vs. 98 ± 9 cm(2), p = 0.02), a higher amount of atrial DE (70 ± 16 cm(2) vs. 49 ± 10 cm(2), p = 0.01), more complex fractionated atrial Egm (CFAE) extent (54 ± 16 cm(2) vs. 28 ± 15 cm(2), p = 0.02), and a shorter baseline AF CL (147 ± 10 ms vs. 182 ± 14 ms, p = 0.01). Continuous CFAE (CFEmean [NavX algorithm that quantifies Egm fractionation] <80 ms) occupied 38 ± 19% of total LA surface area. Dense DE was detected at the left posterior left atrium. In contrast, the right posterior left atrium contained predominantly patchy DE. Most CFAE (48 ± 14%) occurred at non-DE LA sites, followed by 41 ± 12% CFAE at patchy DE and 11 ± 6% at dense DE regions (p = 0.005 and p = 0.008, respectively); 19 ± 6% CFAE sites occurred at border zones of dense DE. Egms were less fractionated, with longer CL and lower voltage at dense DE versus non-DE regions: CFEmean: 97 ms versus 76 ms, p < 0.0001; local CL: 153 ms versus 143 ms, p < 0.0001; mean voltage: 0.63 mV versus 0.86 mV, p < 0.0001. CONCLUSIONS Atrial fibrosis as defined by DE MRI is associated with slower and more organized electrical activity but with lower voltage than healthy atrial areas. Ninety percent of continuous CFAE sites occur at non-DE and patchy DE LA sites. These findings are important when choosing the ablation strategy in persistent AF.

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

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.

Validation of novel 3-dimensional electrocardiographic mapping of atrial tachycardias by invasive mapping and ablation: A multicenter study

OBJECTIVES This study prospectively evaluated the role of a novel 3-dimensional, noninvasive, beat-by-beat mapping system, Electrocardiographic Mapping (ECM), in facilitating the diagnosis of atrial tachycardias (AT). BACKGROUND Conventional 12-lead electrocardiogram, a widely used noninvasive tool in clinical arrhythmia practice, has diagnostic limitations. METHODS Various AT (de novo and post-atrial fibrillation ablation) were mapped using ECM followed by standard-of-care electrophysiological mapping and ablation in 52 patients. The ECM consisted of recording body surface electrograms from a 252-electrode-vest placed on the torso combined with computed tomography-scan-based biatrial anatomy (CardioInsight Inc., Cleveland, Ohio). We evaluated the feasibility of this system in defining the mechanism of AT-macro-re-entrant (perimitral, cavotricuspid isthmus-dependent, and roof-dependent circuits) versus centrifugal (focal-source) activation-and the location of arrhythmia in centrifugal AT. The accuracy of the noninvasive diagnosis and detection of ablation targets was evaluated vis-à-vis subsequent invasive mapping and successful ablation. RESULTS Comparison between ECM and electrophysiological diagnosis could be accomplished in 48 patients (48 AT) but was not possible in 4 patients where the AT mechanism changed to another AT (n = 1), atrial fibrillation (n = 1), or sinus rhythm (n = 2) during the electrophysiological procedure. ECM correctly diagnosed AT mechanisms in 44 of 48 (92%) AT: macro-re-entry in 23 of 27; and focal-onset with centrifugal activation in 21 of 21. The region of interest for focal AT perfectly matched in 21 of 21 (100%) AT. The 2:1 ventricular conduction and low-amplitude P waves challenged the diagnosis of 4 of 27 macro-re-entrant (perimitral) AT that can be overcome by injecting atrioventricular node blockers and signal averaging, respectively. CONCLUSIONS This prospective multicenter series shows a high success rate of ECM in accurately diagnosing the mechanism of AT and the location of focal arrhythmia. Intraprocedural use of the system and its application to atrial fibrillation mapping is under way.

Endocardial ablation to eliminate epicardial arrhythmia substrate in scar-related ventricular tachycardia.

OBJECTIVES We evaluated the feasibility and safety of epicardial substrate elimination with endocardial radiofrequency (RF) delivery in patients with scar-related ventricular tachycardia (VT). BACKGROUND Epicardial RF delivery is limited by fat or associated with bleeding, extra-cardiac damages, coronary vessels and phrenic nerve injury. Alternative ablation approaches might be desirable. METHODS Forty-six patients (18 ischemic cardiomyopathy [ICM], 13 nonischemic dilated cardiomyopathy [NICM], 15 arrhythmogenic right ventricular cardiomyopathy [ARVC]) with sustained VT underwent combined endo- and epicardial mapping. All patients received endocardial ablation targeting local abnormal ventricular activities in the endocardium (Endo-LAVA) and epicardium (Epi-LAVA), followed by epicardial ablation if needed. RESULTS From a total of 173 endocardial ablations targeting Epi-LAVA at the facing site, 48 (28%) applications (ICM: 20 of 71 [28%], NICM: 3 of 39 [8%], ARVC: 25 of 63 [40%]) successfully eliminated the Epi-LAVA. Presence of Endo-LAVA, the most delayed and low bipolar amplitude of Epi-LAVA, low unipolar amplitude in the facing endocardium, and Epi-LAVA within a wall thinning area at computed tomography scan were associated with successful ablation. Endocardial ablation could abolish all Epi-LAVA in 4 ICM and 2 ARVC patients, whereas all patients with NICM required epicardial ablation. Endocardial ablation was able to eliminate Epi-LAVA at least partially in 15 (83%) ICM, 2 (13%) NICM, and 11 (73%) ARVC patients, contributing to a potential reduction in epicardial RF applications. Pericardial bleeding occurred in 4 patients with epicardial ablation. CONCLUSIONS Elimination of Epi-LAVA with endocardial RF delivery is feasible and might be used first to reduce the risk of epicardial ablation.

Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization.

BACKGROUND J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While ajmaline, a class 1a antiarrhythmic drug, accentuates the J wave in Brugada syndrome, its effect on ER is unreported. OBJECTIVE To describe the effect of ajmaline on the electrocardiogram in ER. METHODS We analyzed electrocardiograms before and after the administration of intravenous ajmaline (1 mg/kg) in 31 patients with ER, 21 patients with Brugada type 1 electrocardiogram (Br), and 22 controls. ER was defined as J-point elevation of ≥1 mm with QRS slurring or notching in ≥2 inferolateral leads (I, aVL, II, III, aVF, V4-V6). RESULTS Ajmaline decreased mean J-wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups, but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R-wave amplitude was similar in all the groups (ER group -0.14 mV; Br group -0.11 mV; controls -0.13 mV; P = ns), but mean inferolateral S-wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001). CONCLUSIONS Ajmaline significantly decreases the J-wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J-wave amplitude in ER, although a specific effect of ajmaline on J waves cannot be excluded.

Integration of Merged Delayed-Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation. Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation.

Regional Myocardial Wall Thinning at Multidetector Computed Tomography Correlates to Arrhythmogenic Substrate in Postinfarction Ventricular Tachycardia Assessment of Structural and Electrical Substrate

Background—A majority of patients undergoing ablation of ventricular tachycardia have implanted devices precluding substrate imaging with delayed-enhancement MRI. Contrast-enhanced multidetector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in postinfarction ventricular tachycardia. Methods and Results—We studied 13 consecutive postinfarction patients undergoing MDCT before ablation. MDCT data were integrated with high-density 3-dimensional electroanatomic maps acquired during sinus rhythm (endocardium, 509±291 points/map; epicardium, 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT <5 mm and endocardial low voltage (correlation-R=0.82; P=0.001), but no such correlation was found in the epicardium. The WT <5 mm area was smaller than the endocardial low-voltage area (54 cm2 [Q1–Q3, 46–92] versus 71 cm2 [Q1–Q3, 59–124]; P=0.001). Among a total of 13 060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT <5 mm (469/538 [87%]) or at its border (100% within 23 mm). Very late LAVA (>100 ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3 mm). Conclusions—Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of postinfarction ventricular tachycardia. The integration of MDCT WT with 3-dimensional electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

Heterogeneous response of J-wave syndromes to beta-adrenergic stimulation

BACKGROUND Inferolateral early repolarization (ER) and Brugada syndrome manifest with J waves. Isoproterenol suppresses recurrent ventricular arrhythmias while reducing J waves in both disorders. OBJECTIVE To characterize the effect of isoproterenol on J waves. METHODS We analyzed the impact of isoproterenol on J waves in 20 patients with Brugada-type electrocardiogram (Br group) and 38 patients with ER (ER group). RESULTS In the ER group, J waves were present in inferior leads in 32 patients (84%) and in lateral leads in 23 patients (61%). Isoproterenol increased the heart rate by 75 beats/min in the ER group and by 71 beats/min in the Br group (P = .20). The incidences of persistent (≤ 0.05-mV decrease), decreased, and normalized J waves (residual J wave ≤ 0.05 mV) were 20%, 80%, and 0% for Br group patients and 29%, 8%, and 63% for ER group patients, respectively (P <.001). Within the ER group, inferior J waves persisted in 34% of the cases, decreased in 9%, and normalized in 56% whereas lateral J waves always normalized (P <.001). Baseline QRS width was broader in ER group patients with persistent J waves (90 ms vs 80 ms; P = .003) and was unchanged with isoproterenol (90 ms; P = .19), whereas it decreased in the remaining patients (75 ms; P <.001). CONCLUSIONS J-wave syndromes have distinct regional sensitivity to beta-adrenergic stimulation. J waves may persist in a subset of patients with right precordial and inferior J waves but never in lateral location. This heterogeneous response to isoproterenol may indicate distinctive mechanisms for Brugada and ER patterns, including depolarization abnormalities or ion channel sensitivity.

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization

AIMS Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patients eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.