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: 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.

Evaluation of a novel high-resolution mapping technology for ablation of recurrent scar-related atrial tachycardias.

BACKGROUND: Rhythmia is a new technology capable of rapid and high-resolution mapping. However, its potential advantage over existing technologies in mapping complex scar-related atrial tachycardias (ATs) has not yet been evaluated. OBJECTIVE: The purpose of this study was to examine the utility of Rhythmia for mapping scar-related ATs in patients who had failed previous ablation procedure(s). METHODS: This multicenter study included 20 patients with recurrent ATs within 2 years after a previous ablation procedure (1.8 ± 0.7 per patient). In all cases, the ATs could not be adequately mapped during the index procedure because of scar with fractionated electrograms, precluding accurate time annotation, frequent change in the tachycardia in response to pacing, and/or degeneration into atrial fibrillation. These patients underwent repeat mapping and ablation procedure with Rhythmia. RESULTS: From a total of 28 inducible ATs, 24 were successfully mapped. Eighteen ATs (75%) terminated during radiofrequency ablation and 4 (16.6%) with catheter pressure or entrainment from the site of origin or isthmus. Two ATs that were mapped to the interatrial septum slowed but did not terminate with ablation. In 21 of 24 ATs the mechanism was macroreentry, while in 3 of 24 the mechanism was focal. Interestingly, in 5 patients with previously failed ablation of an allegedly "focal" tachycardia, high-resolution mapping demonstrated macroreentrant arrhythmia. The mean mapping time was 28.6 ± 17 minutes, and the mean radiofrequency ablation time to arrhythmia termination was 3.2 ± 2.6 minutes. During a mean follow-up of 7.5 ± 3.1 months, 15 of 20 patients (75%) were free of AT recurrences. CONCLUSION: The Rhythmia mapping system may be advantageous for mapping complex scar-related ATs.

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.

Coexistent Types of Atrioventricular Nodal Re-Entrant Tachycardia: Implications for the Tachycardia Circuit.

BACKGROUND: There is evidence that atypical fast-slow and typical atrioventricular nodal re-entrant tachycardia (AVNRT) do not use the same limb for fast conduction, but no data exist on patients who have presented with both typical and atypical forms of this tachycardia. We compared conduction intervals during typical and atypical AVNRT that occurred in the same patient. METHODS AND RESULTS: In 20 of 1299 patients with AVNRT, both typical and atypical AVNRT were induced at electrophysiology study by pacing maneuvers and autonomic stimulation or occurred spontaneously. The mean age of the patients was 47.6±10.9 years (range, 32-75 years), and 11 patients (55%) were women. Tachycardia cycle lengths were 368.0±43.1 and 365.8±41.1 ms, and earliest retrograde activation was recorded at the coronary sinus ostium in 60% and 65% of patients with typical and atypical AVNRT, respectively. Thirteen patients (65%) displayed atypical AVNRT with fast-slow characteristics. By comparing conduction intervals during slow-fast and fast-slow AVNRT in the same patient, fast pathway conduction times during the 2 types of AVNRT were calculated. The mean difference between retrograde fast pathway conduction during slow-fast AVNRT and anterograde fast pathway conduction during fast-slow AVNRT was 41.8±39.7 ms and was significantly different when compared with the estimated between-measurement error (P=0.0055). CONCLUSIONS: Our data provide further evidence that typical slow-fast and atypical fast-slow AVNRT use different anatomic pathways for fast conduction.

Analysis of speed, curvature, planarity and frequency characteristics of heart vector movement to evaluate the electrophysiological substrate associated with ventricular tachycardia.

BACKGROUND: We developed a novel method of assessing ventricular conduction using the surface ECG. METHODS: Orthogonal ECGs of 81 healthy controls (age 39.0±14.2 y; 51.8% males; 94% white), were compared with iDower-transformed 12-lead ECGs (both 1000Hz), recorded in 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (age 68.0±7.8y, 37.5% male, mean LVEF 29±12%). Normalized speed at 10 QRS segments was calculated as the distance traveled by the heart vector along the QRS loop in three-dimensional space, divided by 1/10th of the QRS duration. Curvature was calculated as the magnitude of the derivative of the QRS loop tangent vector divided by speed. Planarity was calculated as the mean of the dihedral angles between 2 consecutive planes for all planes generated for the median beat. Orbital frequency (a scalar measure of rotation rate of the QRS vector) was calculated as a product of speed and curvature. RESULTS: Mixed regression analysis showed that speed was slower [6.6 (95%CI 4.4-8.9) vs. 24.6 (95%CI 11.5-37.7)µV/ms; P<0.0001]; orbital frequency was smaller [1.4 (95%CI 1.2-1.6) vs. 6.8 (95%CI 5.4-8.1)ms(-1); P<0.0001], and planarity was larger by 3.6° (95%CI 1.4°-5.8; P=0.002) in VT cases than in healthy controls. ROC AUC for orbital frequency was 0.940 (95%CI 0.935-0.944) across all frequencies and QRS segments. ROC AUC for planarity at 70-249Hz was 0.995 (95%CI 0.985-1.00). ROC AUC for speed at 70-79Hz was 0.979 (95%CI 0.969-0.989). CONCLUSION: This novel method reveals characteristic features of an abnormal electrophysiological substrate associated with VT.

Differential diagnosis of regular, narrow-QRS tachycardias.

We present an update on clinical and electrophysiological criteria used for the differential diagnosis of regular supraventricular tachycardias. Although several electrocardiographic clues may assist in the differential diagnosis, this is usually accomplished at electrophysiology study, and most often, the differential diagnosis is between atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia due to a concealed accessory pathway, and atrial tachycardia. Atrial and ventricular pacing maneuvers during sinus rhythm or tachycardia have been used with various success rates. In clinical practice, these techniques cannot be applied to all cases, and multiple criteria must be used for the differential diagnosis of narrow-complex tachycardias with atypical characteristics.

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.

Nonreentrant ventricular arrhythmias in patients with structural heart disease unrelated to abnormal myocardial substrate.

BACKGROUND: Ventricular arrhythmias in the absence of structural heart disease are commonly referred to as "idiopathic." Patients with structural heart disease have ventricular arrhythmias with the same mechanisms and sites of origin as idiopathic ventricular arrhythmias, but the prevalence of such arrhythmias is not well defined. OBJECTIVES: To identify the prevalence of nonreentrant ventricular arrhythmias unrelated to abnormal myocardial substrate in patients with structural heart disease and to compare these arrhythmias to ventricular arrhythmias in patients with structurally normal hearts. METHODS: Of 249 consecutive patients referred for ablation of ventricular arrhythmias, 97 (39%) patients had nonreentrant arrhythmias unrelated to underlying structural heart disease. Fifty-five (57%) patients had structurally normal hearts, and 42 (43%) had underlying structural heart disease. RESULTS: Compared with patients with structurally normal hearts, patients with structural heart disease were more likely to have nonreentrant ventricular arrhythmias unrelated to underlying abnormal myocardial substrate originating from the aortic cusps and left ventricular outflow tract whereas patients without structural heart disease more often had arrhythmias originating from the right ventricular outflow tract. There was a significant increase in the average left ventricular ejection fraction after ablation in patients with structural heart disease. CONCLUSION: Nonreentrant ventricular arrhythmias unrelated to abnormal myocardial substrate are common in patients with structural heart disease, and sites of origin differ from those seen in patients with structurally normal hearts. When managing structural heart disease in patients with ventricular arrhythmias, a focus on arrhythmia mechanism, origin, and relationship to underlying myocardial substrate may have important implications for future treatment options and patient outcomes.

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.

Characterization of respiratory and cardiac motion from electro-anatomical mapping data for improved fusion of MRI to left ventricular electrograms.

Accurate fusion of late gadolinium enhancement magnetic resonance imaging (MRI) and electro-anatomical voltage mapping (EAM) is required to evaluate the potential of MRI to identify the substrate of ventricular tachycardia. However, both datasets are not acquired at the same cardiac phase and EAM data is corrupted with respiratory motion limiting the accuracy of current rigid fusion techniques. Knowledge of cardiac and respiratory motion during EAM is thus required to enhance the fusion process. In this study, we propose a novel approach to characterize both cardiac and respiratory motion from EAM data using the temporal evolution of the 3D catheter location recorded from clinical EAM systems. Cardiac and respiratory motion components are extracted from the recorded catheter location using multi-band filters. Filters are calibrated for each EAM point using estimates of heart rate and respiratory rate. The method was first evaluated in numerical simulations using 3D models of cardiac and respiratory motions of the heart generated from real time MRI data acquired in 5 healthy subjects. An accuracy of 0.6-0.7 mm was found for both cardiac and respiratory motion estimates in numerical simulations. Cardiac and respiratory motions were then characterized in 27 patients who underwent LV mapping for treatment of ventricular tachycardia. Mean maximum amplitude of cardiac and respiratory motion was 10.2±2.7 mm (min = 5.5, max = 16.9) and 8.8±2.3 mm (min = 4.3, max = 14.8), respectively. 3D Cardiac and respiratory motions could be estimated from the recorded catheter location and the method does not rely on additional imaging modality such as X-ray fluoroscopy and can be used in conventional electrophysiology laboratory setting.

Inducibility of atrial fibrillation with a synchronized external low energy shock post-pulmonary vein isolation predicts recurrent atrial fibrillation.

BACKGROUND: Inducibility of atrial fibrillation (AF) with burst pacing after pulmonary vein (PV) isolation is associated with recurrent AF. OBJECTIVE: This study evaluated whether an external 30 Joule (J) shock synchronized to the R wave, during the vulnerable period of atrial repolarization, is able to risk-stratify patients further for AF recurrence after PV isolation. METHODS: One hundred and sixteen consecutive patients underwent PV isolation for AF. Atrial burst pacing was performed after PV isolation. In patients without AF induced by burst pacing, a biphasic external 30 J shock synchronized to the R wave was delivered as a further test for inducible AF. Patients were followed for a mean of 16 months, and recurrent AF was defined as more than 10 sec of AF on ambulatory monitoring. RESULTS: AF was induced in 19 (16%) of patients with burst pacing. Eighty-one patients who were noninducible with burst pacing had a 30 J shock administered, which induced AF in 16 (20%). In follow-up, 21% of patients who were noninducible with burst pacing or low-energy shock vs 54% who were inducible with either test developed recurrent AF at one year (HR 3.18, P = 0.0004 on multivariate analysis). Among patients who were noninducible with burst pacing, 18% who were noninducible with a low-energy shock vs 60% who were inducible with shock developed recurrent AF at one year (HR = 4.63, P = 0.0006 on multivariate analysis). CONCLUSION: Inducibility of AF by a 30 J shock delivered during atrial repolarization after PV isolation may predict AF recurrence. Evaluation of inducibility of AF with burst pacing and a biphasic external synchronized shock after PV isolation may help guide postprocedure management.

The role of electrophysiology study in risk stratification of sudden cardiac death.

Patients with ischemic heart disease and left ventricular systolic dysfunction are at high risk of sudden cardiac death. However, most of these high-risk patients will never develop potential fatal ventricular arrhythmias. Thus, modalities that stratify patients according to their risk of sudden cardiac death are needed. The electrophysiology study has, for decades, been used to prognosticate on patients' risk of sudden cardiac death. Recent data from the Multicenter Unsustained Tachycardia Trial (MUSTT) and Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) demonstrate that in patients with ischemic heart disease and left ventricular systolic dysfunction, an electrophysiology study can help identify patients who are at high risk of sudden cardiac death. However, in these patient populations, the prognostic ability of an electrophysiology study is only modest and the negative predictive value is poor. In the future, combining the results of noninvasive modalities with invasive electrophysiology testing may improve our prognostic ability. Furthermore, expanding the role of the electrophysiology study to include therapeutic ablations may alter a patient's future risk of sudden cardiac death.

Characterization of the infarct substrate and ventricular tachycardia circuits with noncontact unipolar mapping in a porcine model of myocardial infarction.

BACKGROUND: Conventional mapping of ventricular tachycardia (VT) after myocardial infarction is limited in patients with hemodynamically untolerated or noninducible VT. OBJECTIVES: The purpose of this study was to develop a unique strategy using noncontact unipolar mapping to define infarct substrate and VT circuits. METHODS: Dynamic substrate mapping (DSM) was performed in seven pigs with healed anterior myocardial infarction. This technique defined substrate as the intersection of low-voltage areas identified in sinus rhythm and during pacing around the infarct. Pacing was also performed within the substrate to determine exit sites. RESULTS: Anteroapical transmural scar was identified in all animals. A mean of three pacing sites was used for substrate definition. The mean area (+/- SD) was 18.4 +/- 8.8 cm2 by DSM and 15.4 +/- 6.9 cm2 by pathology (P >.5). A mean of 4.5 sites was paced within substrate. Ten of 18 paced wavefronts exited substrate adjacent to the pacing area, seven exited at distant areas, and one had two exits. VT was induced in five animals (1.6 morphologies per animal). Except for one VT, circuit exit sites were identified at substrate borders on the endocardium. VT exit sites were at (n = 6) or near (n = 3) a pacing exit site. Electrogram voltages differed significantly between substrate, border, and nonsubstrate areas in infarcted animals and in comparison with control animals. No substrate was identified in two control animals. CONCLUSION: DSM is a reliable method for infarct substrate localization in this model. Pacing within substrate can predict VT exit sites and may prove useful for ablation of unmappable VT after myocardial infarction.