P-wave morphology and multipolar intracardiac atrial activation to facilitate nonpulmonary vein trigger localization.

INTRODUCTION: Nonpulmonary vein (non-PV) triggers of atrial fibrillation (AF) are targets for ablation but their localization remains challenging. The aim of this study was to describe P-wave (PW) morphologic characteristics and intra-atrial activation patterns and timing from multipolar coronary sinus (CS) and crista terminalis (CT) catheters that localize non-PV triggers. METHODS AND RESULTS: Selective pacing from six right and nine left atrial common non-PV trigger sites was performed in 30 consecutive patients. We analyzed 12 lead ECG features based on PW duration, amplitude and morphology, and patterns and timing of multipolar activation for all 15 sites. Regionalization and then precise localization required criteria present in at least 70% of assessments at each pacing site. The algorithm was then prospectively evaluated by four blinded observers in a validation cohort of 18 consecutive patients undergoing the same pacing protocol and 60 consecutive patients who underwent successful non-PV trigger ablation. The algorithm for site regionalization included 1) negative PW in V1, ≥30 µV change in PW amplitude across the leads V1-V3, and PW duration ≤100 milliseconds in lead 2 and 2) unique intra-atrial activation patterns and timing noted in the multipolar catheters. Specific ECG and intra-atrial activation timing characteristics included in the algorithm allowed for more precise site localization after regionalization. In the prospective evaluation, the algorithm identified the site of origin for 72% of paced and 70% of spontaneous non-PV trigger sites. CONCLUSION: An algorithm based on PW morphology and intra-atrial multipolar activation pattern and timing can help identify non-PV trigger sites of origin.

Three-dimensional myocardial scar characterization from the endocardium: Usefulness of endocardial unipolar electroanatomic mapping.

Epicardial ablation may be required to eliminate ventricular tachycardia (VT) in patients with underlying structural heart disease. The decision to gain epicardial access is frequently based on the suspicion of an epicardial origin for the VT and/or presence of an arrhythmogenic substrate. Epicardial pathology and VT is frequently present in patients with nonischemic right and/or left cardiomyopathies even in the setting of modest or no endocardial bipolar voltage substrate. In this setting, unipolar voltage mapping from the endocardium serves to help identify midmyocardial and/or epicardial VT substrate. The additional value of endocardial unipolar mapping includes its usefulness to predict the clinical outcome after VT ablation, to determine the irreversibility of myocardial disease, and to guide endomyocardial biopsy procedures to specific areas of intramural scarring. In this review, we aim to provide a guide to the use of endocardial unipolar mapping and its appropriate interpretation in a variety of clinical situations.

Infarct-Related Ventricular Tachycardia: Redefining the Electrophysiological Substrate of the Isthmus During Sinus Rhythm.

OBJECTIVES: In this study, the scientific objective was to characterize the electrophysiological substrate of the ventricular tachycardia (VT) isthmus during sinus rhythm. BACKGROUND: The authors have recently described the electrophysiological characteristics of the VT isthmus using a novel in vivo high-resolution mapping technology. METHODS: Sixteen swine with healed infarction were studied using high-resolution mapping technology (Rhythmia, Boston Scientific, Cambridge, Massachusetts) in a closed-chest model. The left ventricle was mapped during sinus rhythm and analyzed for activation, conduction velocity, electrogram shape, and amplitude. Twenty-four VTs allowed detailed mapping of the common-channel "isthmus," including the "critical zone." This was defined as the zone of maximal conduction velocity slowing in the circuit, often occurring at entrance and exit from the isthmus caused by rapid angular change in activation vectors. RESULTS: The VT isthmus corresponded to sites displaying steep activation gradient (SAG) during sinus rhythm with conduction velocity slowing of 58.5 ± 22.4% (positive predictive value [PPV] 60%). The VT critical zone displayed SAG with greater conduction velocity slowing of 68.6 ± 18.2% (PPV 70%). Critical-zone sites were consistently localized in areas with bipolar voltage ≤0.55 mV, whereas isthmus sites were localized in areas with variable voltage amplitude (1.05 ± 0.80 mV [0.03 to 2.88 mV]). Importantly, critical zones served as common-site "anchors" for multiple VT configurations and cycle lengths. Isthmus and critical-zone sites occupied only 18.0 ± 7.0% of the low-voltage area (≤1.50 mV). Isolated late potentials were present in both isthmus and nonisthmus sites, including dead-end pathways (PPV 36%; 95% confidence interval: 34.2% to 39.6%). CONCLUSIONS: The VT critical zone corresponds to a location characterized by SAG and very low voltage amplitude during sinus rhythm. Thus, it allows identification of a re-entry anchor with high sensitivity and specificity. By contrast, voltage and electrogram characteristics during sinus rhythm have limited specificity for identifying the VT isthmus.

Atrial Substrate and Triggers of Paroxysmal Atrial Fibrillation in Patients With Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with atrial remodeling, atrial fibrillation (AF), and increased incidence of arrhythmia recurrence after pulmonary vein (PV) isolation. We aimed to characterize the atrial substrate, including AF triggers in patients with paroxysmal AF and OSA. METHODS AND RESULTS: In 86 patients with paroxysmal AF (43 with ≥moderate OSA [apnea-hypopnea index ≥15] and 43 without OSA [apnea-hypopnea index <5]), right atrial and left atrial voltage distribution, conduction velocities, and electrogram characteristics were analyzed during atrial pacing. AF triggers were examined before and after PV isolation and targeted for ablation. Patients with OSA had lower atrial voltage amplitude (right atrial, P=0.0005; left atrial, P=0.0001), slower conduction velocities (right atrial, P=0.02; left atrial, P=0.0002), and higher prevalence of electrogram fractionation (P=0.0001). The areas of atrial abnormality were consistent among patients, most commonly involving the left atrial septum (32/43; 74.4%). At baseline, the PVs were the most frequent triggers for AF in both groups; however, after PV isolation patients with OSA had increased incidence of additional extra-PV triggers (41.8% versus 11.6%; P=0.003). The 1-year arrhythmia-free survival was similar between patients with and without OSA (83.7% and 81.4%, respectively; P=0.59). In comparison, control patients with paroxysmal AF and OSA who underwent PV isolation alone without ablation on extra-PV triggers had increased risk of arrhythmia recurrence (83.7% versus 64.0%; P=0.003). CONCLUSIONS: OSA is associated with structural and functional atrial remodeling and increased incidence of extra-PV triggers. Elimination of these triggers resulted in improved arrhythmia-free survival.

High-Resolution Mapping of Ventricular Scar: Evaluation of a Novel Integrated Multielectrode Mapping and Ablation Catheter.

OBJECTIVES: This study sought to evaluate an investigational catheter that incorporates 3 microelectrodes embedded along the circumference of a standard 3.5-mm open-irrigated catheter. BACKGROUND: Mapping resolution is influenced by both electrode size and interelectrode spacing. Multielectrode mapping catheters enhance mapping resolution within scar compared with standard ablation catheters; however, this requires the use of 2 separate catheters for mapping and ablation. METHODS: Six swine with healed infarction and 2 healthy controls underwent mapping of the left ventricle using a THERMOCOOL SMARTTOUCH SF catheter with 3 additional microelectrodes (0.167 mm2) along its circumference (Qdot, Biosense Webster, Diamond Bar, California). Mapping resolution in healthy and scarred tissue was compared between the standard electrodes and microelectrodes using electrogram characteristics, cardiac magnetic resonance, and histology. RESULTS: In healthy myocardium, bipolar voltage amplitude was similar between the standard electrodes and microelectrodes, with a fifth percentile of 1.19 and 1.30 mV, respectively. In healed infarction, the area of low bipolar voltage (defined as <1.5 mV) was smaller with microelectrodes (16.8 cm2 vs. 25.3 cm2; p = 0.033). Specifically, the microelectrodes detected zones of increased bipolar voltage amplitude, with normal electrogram characteristics occurring at the end of or after the QRS, consistent with channels of preserved subendocardium. Identification of surviving subendocardium by the microelectrodes was consistent with cardiac magnetic resonance and histology. The microelectrodes also improved distinction between near-field and far-field electrograms, with more precise identification of scar border zones. CONCLUSIONS: This novel catheter combines high-resolution mapping and radiofrequency ablation with an open-irrigated, tissue contact-sensing technology. It improves scar mapping resolution while limiting the need for and cost associated with the use of a separate mapping catheter.

High-Resolution Mapping of Ventricular Scar: Comparison Between Single and Multielectrode Catheters.

BACKGROUND: Mapping resolution is influenced by electrode size and interelectrode spacing. The aims of this study were to establish normal electrogram criteria for 1-mm multielectrode-mapping catheters (Pentaray) in the ventricle and to compare its mapping resolution within scar to standard 3.5-mm catheters (Smart-Touch Thermocool). METHODS AND RESULTS: Three healthy swine and 11 swine with healed myocardial infarction underwent sequential mapping of the left ventricle with both catheters. Bipolar voltage amplitude in healthy tissue was similar between 3.5- and 1-mm multielectrode catheters with a 5th percentile of 1.61 and 1.48 mV, respectively. In swine with healed infarction, the total area of low bipolar voltage amplitude (defined as <1.5 mV) was 22.5% smaller using 1-mm multielectrode catheters (21.7 versus 28.0 cm2; P=0.003). This was more evident in the area of dense scar (bipolar amplitude <0.5 mV) with a 47% smaller very low-voltage area identified using 1-mm electrode catheters (7.1 versus 15.2 cm(2); P=0.003). In this region, 1-mm multielectrode catheters recorded higher voltage amplitude (0.72±0.81 mV versus 0.30±0.12 mV; P<0.001). Importantly, 27% of these dense scar electrograms showed distinct triphasic electrograms when mapped using a 1-mm multielectrode catheter compared with fractionated multicomponent electrogram recorded with the 3.5-mm electrode catheter. In 8 mapped reentrant ventricular tachycardias, the circuits included regions of preserved myocardial tissue channels identified with 1-mm multielectrode catheters but not 3.5-mm electrode catheters. Pacing threshold within the area of low voltage was lower with 1-mm electrode catheters (0.9±1.3 mV versus 3.8±3.7 mV; P=0.001). CONCLUSIONS: Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.

A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization.

BACKGROUND: Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. OBJECTIVE: We aimed to develop and characterize a swine model of scar-related reentrant VT. METHODS: Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6-8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. RESULTS: Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with "pseudo-block" due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1-4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. CONCLUSION: This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT.

High-resolution mapping of scar-related atrial arrhythmias using smaller electrodes with closer interelectrode spacing.

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.

Radiofrequency ablation annotation algorithm reduces the incidence of linear gaps and reconnection after pulmonary vein isolation.

BACKGROUND: A common mechanism of atrial fibrillation recurrence after catheter ablation is resumption of pulmonary vein (PV) conduction due to gaps in the ablation line. These gaps may go unrecognized owing to inadequate ablation lesion annotation. OBJECTIVE: To examine the utility of an automated radiofrequency (RF) ablation annotation algorithm for the detection and treatment of ablation gaps during pulmonary vein isolation (PVI). METHODS: Eighty-four patients with paroxysmal atrial fibrillation underwent PVI. In 42 patients (group A), RF ablation was guided by an automated algorithm with predefined criteria of catheter stability range of motion ≤2 mm and impedance decrease ≥5% for individual ablation applications. In 42 control patients (group B), ablation was guided by the operator. Successful PVI, conduction recovery, and dormant conduction with adenosine were compared between the groups. RESULTS: Ipsilateral PVI at the completion of the initial anatomical line was obtained in 90.5% of group A patients (76 of 84 ipsilateral pairs of PVs) but only in 66.7% of group B patients (56 of 84 ipsilateral pairs of PVs) (P = .0001). Ineffective energy delivery was detected in 23% (1005 of 4362) of group A applications but only in 9% (368 of 4071) of group B applications (P = .0001). The frequency of conduction recovery was lower in group A than in group B (5.9% vs 25%; P = .001). Arrhythmia-free survival at 6 months trended higher in group A (38 of 42 [90%]) than in group B (32 of 42 [76%]; P = .07). CONCLUSION: Automated ablation lesion annotation provides real-time feedback of RF ablation that may improve effective energy delivery.

Layered activation of epicardial scar in arrhythmogenic right ventricular dysplasia: possible substrate for confined epicardial circuits.

BACKGROUND: Ventricular tachycardia ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more successful when including epicardial ablation. Scarring may cause independent, layered epicardial activation and promote epicardially confined ventricular tachycardia circuits. We aimed to characterize transmural right ventricular activation in ARVD patients and to compare this with reference patients without structural heart disease. METHODS AND RESULTS: Eighteen ARVD patients underwent detailed endocardial and epicardial sinus rhythm electroanatomic mapping. Bipolar activation was annotated at the sharpest intrinsic deflection including late potentials and compared with 6 patients with normal hearts. Total scar area was larger on the epicardium (97±78 cm(2)) than the endocardium (57±44 cm(2); P=0.04), with significantly more isolated potentials. Total epicardial activation time was longer than endocardial (172±54 versus 99±27 ms; P<0.01), and both were longer than in reference patients. Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference patients, epicardial activation directly opposite endocardial sites occurred in 5.2±1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients had major activation delay to the epicardium with laminar central scar activation from the scar border, not by direct transmural spread from the endocardium. CONCLUSIONS: Transmural right ventricular activation is modified by ARVD scarring with a delayed epicardial activation sequence suggestive of independent rather than direct transmural activation. This may predispose ventricular tachycardia circuits contained entirely within the epicardium in ARVD and explains observations on the need for direct epicardial ablation to eliminate ventricular tachycardia.

Isolated septal substrate for ventricular tachycardia in nonischemic dilated cardiomyopathy: incidence, characterization, and implications.

BACKGROUND: The substrate for ventricular tachycardia (VT) in nonischemic cardiomyopathy (NICM) has a predilection for the basolateral left ventricle with right bundle branch block VT morphology. OBJECTIVE: The purpose of this study was to describe a unique group of NICM patients with septal VT substrate. METHODS: Between 1999 and 2010, 31 (11.6%) of 266 patients with NICM undergoing VT ablation had septal substrate and no lateral involvement. Mean age was 59 ± 12 years, and ejection fraction was 30% ± 14%. Eight patients had heart block. RESULTS: Cardiac magnetic resonance showed septal delayed enhancement in 8 of 9 patients. Electroanatomic mapping demonstrated bipolar low voltage (<1.5 mV) extending from the basal septum in 22 of 31 patients. The remaining 9 patients had normal endocardial bipolar voltage but abnormal unipolar septal voltage (<8.3 mV) consistent with intramural abnormalities. Epicardial mapping in 14 patients showed no scar in 9 and patchy basal left ventricular summit scar in 5. VTs were mapped to the septal substrate, with 62% having right bundle branch block morphology and V(2) precordial transition pattern break in 17% suggesting periseptal exit. After substrate and targeted VT ablation, no VT was inducible in 66% and no "clinical targeted" VT in 86%. Over a mean follow-up of 20 ± 28 months, VT recurred in 10 (32%) patients. CONCLUSION: Isolated septal VT substrate is uncommon in NICM. Biventricular low-voltage zones extending from the basal septum are characteristic, but septal scarring can be entirely intramural as evidenced by unipolar/bipolar electrograms and imaging. Multiple unmappable morphologies are the rule, often requiring several procedures aggressively targeting the septal substrate to achieve moderate long-term VT control.