Accurate Conduction Velocity Maps and Their Association With Scar Distribution on Magnetic Resonance Imaging in Patients With Postinfarction Ventricular Tachycardias.

BACKGROUND: Characterizing myocardial conduction velocity (CV) in patients with ischemic cardiomyopathy (ICM) and ventricular tachycardia (VT) is important for understanding the patient-specific proarrhythmic substrate of VTs and therapeutic planning. The objective of this study is to accurately assess the relation between CV and myocardial fibrosis density on late gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR) in patients with ICM. METHODS: We enrolled 6 patients with ICM undergoing VT ablation and 5 with structurally normal left ventricles (controls) undergoing premature ventricular contraction or VT ablation. All patients underwent LGE-CMR and electroanatomic mapping (EAM) in sinus rhythm (2960 electroanatomic mapping points analyzed). We estimated CV from electroanatomic mapping local activation time using the triangulation method that provides an accurate estimate of CV as it accounts for the direction of wavefront propagation. We evaluated the association between LGE-CMR intensity and CV with multilevel linear mixed models. RESULTS: Median CV in patients with ICM and controls was 0.41 m/s and 0.65 m/s, respectively. In patients with ICM, CV in areas with no visible fibrosis was 0.81 m/s (95% CI, 0.59-1.12 m/s). For each 25% increase in normalized LGE intensity, CV decreased by 1.34-fold (95% CI, 1.25-1.43). Dense scar areas have, on average, 1.97- to 2.66-fold slower CV compared with areas without dense scar. Ablation lesions that terminated VTs were localized in areas of slow conduction on CV maps. CONCLUSIONS: CV is inversely associated with LGE-CMR fibrosis density in patients with ICM. Noninvasive derivation of CV maps from LGE-CMR is feasible. Integration of noninvasive CV maps with electroanatomic mapping during substrate mapping has the potential to improve procedural planning and outcomes. Visual Overview: A visual overview is available for this article.

Ablation Lesion Characterization in Scarred Substrate Assessed Using Cardiac Magnetic Resonance.

OBJECTIVES: This study examined radiofrequency catheter ablation (RFCA) lesions within and around scar by cardiac magnetic resonance (CMR) imaging and histology. BACKGROUND: Substrate modification by RFCA is the cornerstone therapy for ventricular arrhythmias. RFCA in scarred myocardium, however, is not well understood. METHODS: We performed electroanatomic mapping and RFCA in the left ventricles of 8 swine with myocardial infarction. Non-contrast-enhanced T1-weighted (T1w) and contrast-enhanced CMR after RFCA were compared with gross pathology and histology. RESULTS: Of 59 lesions, 17 were in normal myocardium (voltage >1.5 mV), 21 in border zone (0.5 to 1.5 mV), and 21 in scar (<0.5 mV). All RFCA lesions were enhanced in T1w CMR, whereas scar was hypointense, allowing discrimination among normal myocardium, scar, and RFCA lesions. With contrast-enhancement, lesions and scar were similarly enhanced and not distinguishable. Lesion width and depth in T1w CMR correlated with necrosis in pathology (both; r2 = 0.94, p < 0.001). CMR lesion volume was significantly different in normal myocardium, border zone, and scar (median: 397 [interquartile range (IQR): 301 to 474] mm3, 121 [IQR: 87 to 201] mm3, 66 [IQR: 33 to 123] mm3, respectively). RFCA force-time integral, impedance, and voltage changes did not correlate with lesion volume in border zone or scar. Histology showed that ablation necrosis extended into fibrotic tissue in 26 lesions and beyond in 14 lesions. In 7 lesions, necrosis expansion was blocked and redirected by fat. CONCLUSIONS: T1w CMR can selectively enhance necrotic tissue in and around scar and may allow determination of the completeness of ablation intra- and post-procedure. Lesion formation in scar is affected by tissue characteristics, with fibrosis and fat acting as thermal insulators.

Multimodal Examination of Atrial Fibrillation Substrate: Correlation of Left Atrial Bipolar Voltage Using Multi-Electrode Fast Automated Mapping, Point-by-Point Mapping, and Magnetic Resonance Image Intensity Ratio.

Background: Bipolar voltage mapping, as part of atrial fibrillation (AF) ablation, is traditionally performed in a point-by-point (PBP) approach using single-tip ablation catheters. Alternative techniques for fibrosis-delineation include fast-anatomical mapping (FAM) with multi-electrode circular catheters, and late gadolinium-enhanced magnetic-resonance imaging (LGE-MRI). The correlation between PBP, FAM, and LGE-MRI fibrosis assessment is unknown. Objective: In this study, we examined AF substrate using different modalities (PBP, FAM, and LGE-MRI mapping) in patients presenting for an AF ablation. Methods: LGE-MRI was performed pre-ablation in 26 patients (73% males, age 63±8years). Local image-intensity ratio (IIR) was used to normalize myocardial intensities. PBP- and FAM-voltage maps were acquired, in sinus rhythm, prior to ablation and co-registered to LGE-MRI. Results: Mean bipolar voltage for all 19,087 FAM voltage points was 0.88±1.27mV and average IIR was 1.08±0.18. In an adjusted mixed-effects model, each unit increase in local IIR was associated with 57% decrease in bipolar voltage (p<0.0001). IIR of >0.74 corresponded to bipolar voltage <0.5 mV. A total of 1554 PBP-mapping points were matched to the nearest FAM-point. In an adjusted mixed-effects model, log-FAM bipolar voltage was significantly associated with log-PBP bipolar voltage (ß=0.36, p<0.0001). At low-voltages, FAM-mapping distribution was shifted to the left compared to PBP-mapping; at intermediate voltages, FAM and PBP voltages were overlapping; and at high voltages, FAM exceeded PBP-voltages. Conclusion: LGE-MRI, FAM and PBP-mapping show good correlation in delineating electro-anatomical AF substrate. Each approach has fundamental technical characteristics, the awareness of which allows proper assessment of atrial fibrosis.

Impact of number of co-existing rotors and inter-electrode distance on accuracy of rotor localization.

BACKGROUND: Conflicting evidence exists on the efficacy of focal impulse and rotor modulation on atrial fibrillation ablation. A potential explanation is inaccurate rotor localization from multiple rotors coexistence and a relatively large (9-11mm) inter-electrode distance (IED) of the multi-electrode basket catheter. METHODS AND RESULTS: We studied a numerical model of cardiac action potential to reproduce one through seven rotors in a two-dimensional lattice. We estimated rotor location using phase singularity, Shannon entropy and dominant frequency. We then spatially downsampled the time series to create IEDs of 2-30mm. The error of rotor localization was measured with reference to the dynamics of phase singularity at the original spatial resolution (IED=1mm). IED has a significant impact on the error using all the methods. When only one rotor is present, the error increases exponentially as a function of IED. At the clinical IED of 10mm, the error is 3.8mm (phase singularity), 3.7mm (dominant frequency), and 11.8mm (Shannon entropy). When there are more than one rotors, the error of rotor localization increases 10-fold. The error based on the phase singularity method at the clinical IED of 10mm ranges from 30.0mm (two rotors) to 96.1mm (five rotors). CONCLUSIONS: The magnitude of error of rotor localization using a clinically available basket catheter, in the presence of multiple rotors might be high enough to impact the accuracy of targeting during AF ablation. Improvement of catheter design and development of high-density mapping catheters may improve clinical outcomes of FIRM-guided AF ablation.

Current management and clinical outcomes for catheter ablation of atrioventricular nodal re-entrant tachycardia.

Aims: Historical studies of ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) have shown high long-term success rates and low complication rates. The potential impact of several recent practice trends has not been described. This study aims to characterize recent clinical practice trends in AVNRT ablation and their associated success rates and complications. Methods and results: Patients undergoing initial ablation of AVNRT between 1 July 2005 and 30 June 2015 were included in this study. Patient demographics and procedural data were abstracted from procedure reports. Follow-up data, including AVNRT recurrence and complications, was evaluated through electronic medical record review. In total, 877 patients underwent catheter ablation for AVNRT. By the last recorded year, three-dimension (3D) electroanatomical mapping (EAM) was used in 36.2%, 43.2% included anaesthesia, and 23.1% utilized irrigated catheters. Long-term procedural success was 95.5%. The use of anaesthesia, 3D EAM, and irrigated ablation catheters were not associated with differences in success. The presence of an atrial 'echo' or 'AH' jump at the end of an acutely successful procedure was not associated with long-term recurrence (P = 0.18, P = 0.15, respectively). Complications, including AV block requiring a pacemaker (0.4%), were uncommon. Conclusion: In a large, contemporary cohort, catheter ablation for AVNRT remains highly successful with low complications rates. The increased use of anaesthesia as well as modern mapping and ablation tools were not associated with changes in clinical outcomes. Further prospective evaluation of such contemporary practices is warranted given the lack of evidence to support their escalating use.

The Extent of Left Atrial Low-Voltage Areas Included in Pulmonary Vein Isolation Is Associated With Freedom from Recurrent Atrial Arrhythmia.

BACKGROUND: The extent of left atrial (LA) baseline low-voltage areas (LVA-B), which may be a surrogate for fibrosis, is associated with recurrent atrial fibrillation (AF) after ablation. This study aimed to assess the relationship between the extent of LVA-B isolated by ablation (LVA-I) and AF recurrence. METHODS: The study cohort included 159 consecutive patients with drug-refractory AF who underwent an initial AF ablation with LA voltage mapping during sinus rhythm. The extent of LVA-B was quantified while excluding the pulmonary veins, LA appendage, and mitral valve area. LVA-I was quantified as the percentage of LVA-B encircled by pulmonary vein isolation. Surveillance and symptom-prompted electrocardiograms, Holter monitors, and event monitors were used to document atrial arrhythmia recurrence for a median follow-up of 712 days (1.95 years). RESULTS: Of 159 patients, 72% were men and 27% had persistent AF. The mean number of sampled bipolar voltage points was 119 ± 56. The mean LA surface area was 102.3 ± 37.3 cm2, and the mean LVA-B was 1.9 ± 3.8 cm2. The mean LVA-I was 51.05% ± 36.8% of LVA-B. In the multivariable Cox proportional hazards model adjusted for LA volume, CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age [≥ 75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female] score), LVA-B, and AF type, LVA-I was inversely associated with recurrent atrial arrhythmia after the blanking period (hazard ratio, 0.42/percent LVA isolated; P = 0.037). CONCLUSIONS: The extent of LVA-I is independently associated with freedom from atrial arrhythmias after AF ablation, supporting ongoing efforts to target low LA voltage areas and other fibrosis indicators to improve ablation outcomes.

Association of left atrial epicardial adipose tissue with electrogram bipolar voltage and fractionation: Electrophysiologic substrates for atrial fibrillation.

BACKGROUND: Epicardial adipose tissue (EAdT) is metabolically active and likely contributes to atrial fibrillation (AF) through the release of inflammatory cytokines into the myocardium or through its rich innervation with ganglionated plexi at the pulmonary vein ostia. The electrophysiologic mechanisms underlying the association between EAdT and AF remain unclear. OBJECTIVE: The purpose of this study was to investigate the association of EAdT with adjacent myocardial substrate. METHODS: Thirty consecutive patients who underwent cardiac computed tomography as well as electroanatomic mapping in sinus rhythm before an initial AF ablation procedure were studied. Semiautomatic segmentation of atrial EAdT was performed and registered anatomically to the voltage map. RESULTS: In multivariable regression analysis clustered by patient, age (-0.01 per year) and EAdT (-0.29) were associated with log bipolar voltage as well as low-voltage zones (<0.5 mV). Age (odds ratio [OR]: 1.02 per year), male gender (OR: 3.50), diabetes (OR: 2.91), hypertension (OR: 2.55), and EAdT (OR: 8.56) were associated with fractionated electrograms, and age (OR: 2.80), male gender (OR: 3.00), and EAdT (OR: 7.03) were associated with widened signals. Age (OR: 1.03 per year) and body mass index (OR: 1.06 per kg/m2) were associated with atrial fat. CONCLUSION: The presence of overlaying EAdT was associated with lower bipolar voltage and electrogram fractionation as electrophysiologic substrates for AF. EAdT was not a statistical mediator of the association between clinical variables and AF substrate. Body mass index was directly associated with the presence of EAdT in patients with AF.

Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

BACKGROUND: Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation. METHODS AND RESULTS: LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and image intensity ratio in the left atrium (mean ± SD) were 0.98 ± 0.46 and 0.95 ± 0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, P<0.001). CONCLUSIONS: In this clinical in vivo study, we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias.

The association of left atrial low-voltage regions on electroanatomic mapping with low attenuation regions on cardiac computed tomography perfusion imaging in patients with atrial fibrillation.

BACKGROUND: Previous studies have shown that contrast-enhanced multidetector computed tomography (CE-MDCT) could identify ventricular fibrosis after myocardial infarction. However, whether CE-MDCT can characterize atrial low-voltage regions remains unknown. OBJECTIVE: The purpose of this study was to examine the association of CE-MDCT image attenuation with left atrial (LA) low bipolar voltage regions in patients undergoing repeat ablation for atrial fibrillation recurrence. METHODS: We enrolled 20 patients undergoing repeat ablation for atrial fibrillation recurrence. All patients underwent preprocedural 3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the LA during the ablation procedure. Epicardial and endocardial contours were manually drawn around LA myocardium on multiplanar CE-MDCT axial images. Segmented 3-dimensional images of the LA myocardium were reconstructed. Electroanatomic map points were retrospectively registered to the corresponding CE-MDCT images. RESULTS: A total of 2028 electroanatomic map points obtained in sinus rhythm from the LA endocardium were registered to the segmented LA wall CE-MDCT images. In a linear mixed model, each unit increase in the local image attenuation ratio was associated with 25.2% increase in log bipolar voltage (P = .046) after adjusting for age, sex, body mass index, and LA volume, as well as clustering of data by patient and LA regions. CONCLUSION: We demonstrate that the image attenuation ratio derived from CE-MDCT is associated with LA bipolar voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful alternative in patients with contraindications to magnetic resonance imaging.

Model of bipolar electrogram fractionation and conduction block associated with activation wavefront direction at infarct border zone lateral isthmus boundaries.

BACKGROUND: Improved understanding of the mechanisms underlying infarct border zone electrogram fractionation may be helpful to identify arrhythmogenic regions in the postinfarction heart. We describe the generation of electrogram fractionation from changes in activation wavefront curvature in experimental canine infarction. METHODS AND RESULTS: A model was developed to estimate the extracellular signal shape that would be generated by wavefront propagation parallel to versus perpendicular to the lateral boundary (LB) of the reentrant ventricular tachycardia (VT) isthmus or diastolic pathway. LBs are defined as locations where functional block forms during VT, and elsewhere they have been shown to coincide with sharp thin-to-thick transitions in infarct border zone thickness. To test the model, bipolar electrograms were acquired from infarct border zone sites in 10 canine heart experiments 3 to 5 days after experimental infarction. Activation maps were constructed during sinus rhythm and during VT. The characteristics of model-generated versus actual electrograms were compared. Quantitatively expressed VT fractionation (7.6±1.2 deflections; 16.3±8.9-ms intervals) was similar to model-generated values with wavefront propagation perpendicular to the LB (9.4±2.4 deflections; 14.4±5.2-ms intervals). Fractionation during sinus rhythm (5.9±1.8 deflections; 9.2±4.4-ms intervals) was similar to model-generated fractionation with wavefront propagation parallel to the LB (6.7±3.1 deflections; 7.1±3.8-ms intervals). VT and sinus rhythm fractionation sites were adjacent to LBs ≈80% of the time. CONCLUSIONS: The results suggest that in a subacute canine infarct model, the LBs are a source of activation wavefront discontinuity and electrogram fractionation, with the degree of fractionation being dependent on activation rate and wavefront orientation with respect to the LB.

Phrenic nerve injury: An underrecognized and potentially preventable complication of pulmonary vein isolation using a wide-area circumferential ablation approach.

INTRODUCTION: Phrenic nerve injury (PNI) is a well-known, although uncommon, complication of pulmonary vein isolation (PVI) using radiofrequency energy. Currently, there is no consensus about how to avoid or minimize this injury. The purpose of this study was to determine how often the phrenic nerve, as identified using a high-output pacing, lies along the ablation trajectory of a wide-area circumferential lesion set. We also sought to determine if PVI can be achieved without phrenic nerve injury by modifying the ablation lesion set so as to avoid those areas where phrenic nerve capture (PNC) is observed. METHODS AND RESULTS: We prospectively enrolled 100 consecutive patients (age 61.7 ± 9.2 years old, 75 men) who underwent RF PVI using a wide-area circumferential ablation approach. A high-output (20 mA at 2 milliseconds) endocardial pacing protocol was performed around the right pulmonary veins and the carina where a usual ablation lesion set would be made. A total of 30% of patients had PNC and required modification of ablation lines. In the group of patients with PNC, the carina was the most common site of capture (85%) followed by anterior right superior pulmonary vein (RSPV) (70%) and anterior right inferior pulmonary vein (RIPV) (30%). A total of 25% of PNC group had capture in all 3 (RSPV, RIPV, and carina) regions. There was no difference in the clinical characteristics between the groups with and without PNC. RF PVI caused no PNI in either group. CONCLUSION: High output pacing around the right pulmonary veins and the carina reveals that the phrenic nerve lies along a wide-area circumferential ablation trajectory in 30% of patients. Modification of ablation lines to avoid these sites may prevent phrenic nerve injury during RF PVI.

The critical isthmus sites of ischemic ventricular tachycardia are in zones of tissue heterogeneity, visualized by magnetic resonance imaging.

BACKGROUND: A need exists to develop alternative approaches to VT ablation that provide an improved delineation of the arrhythmogenic substrate. OBJECTIVE: The aim of this study was to evaluate the hypotheses that: (1) the heterogeneous zone (HZ, a mixture of normal-appearing tissue and scar) in magnetic resonance imaging (MRI) contains the critical isthmus(es) for ventricular tachycardia (VT), (2) successful ablation of VT would include ablation in the HZ, and (3) inadequate ablation of HZ allows for VT recurrence. METHODS: MRI and an electrophysiology study (EP) were performed in a model of chronic myocardial infarction in 17 pigs. In animals that were inducible for VT, ablations were done guided by standard EP criteria and blinded to the MRI. After ablation, electroanatomic mapping results were co-registered with MRI. RESULTS: In 8 animals, 22 sustained monomorphic VTs were generated. The HZ was substantially larger in inducible (n = 8) compared with noninducible animals (n = 9) [25% ± 10% vs 13% ± 5% of total scar, respectively, P = .007]. Acutely, all targeted VTs were successfully ablated, and postprocedure analysis showed that at least 1 ablation was in the HZ in each animal. In 5 animals, a second EP and MRI were performed 1 week after ablation. Three animals had inducible VTs, and MRI showed that the HZ had not been completely ablated. In contrast, the 2 animals without inducible VT revealed no remaining HZ. CONCLUSION: These findings show that MRI can define an HZ and determine the location of ablated lesions. The HZ may be a promising ablation target to cure ischemic VTs. Remnants of HZ after ablation may be the substrate for clinical relapses.

Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping.

BACKGROUND: Infarct border zone (IBZ) geometry likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established. OBJECTIVE: The purpose of this study was to determine characteristics of postinfarction ventricular tachycardia in the IBZ. METHODS: A geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block were expected to coincide with areas where IBZ thickness (T) is minimal and the local spatial gradient in thickness (DeltaT) is maximal, so that the degree of wavefront curvature rho proportional, variant DeltaT/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum DeltaT. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps after tachycardia induction. RESULTS: Mean IBZ thickness was 231 +/- 140 microm at the reentry isthmus and 1440 +/- 770 microm in the outer pathway (P <0.001). Mean curvature rho was 1.63 +/- 0.45 mm(-1) at functional block line locations, 0.71 +/- 0.18 mm(-1) at isthmus entrance-exit points, and 0.33 +/- 0.13 mm(-1) in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32 +/- 0.04 mm/ms at entrance-exit points, 0.42 +/- 0.13 mm/ms for the entire outer pathway, and 0.64 +/- 0.16 mm/ms at outer pathway regions with minimum DeltaT. Model sensitivity and specificity to detect isthmus location was 75.0% and 97.2%. CONCLUSIONS: Reentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships.