Effect of electrode size and spacing on electrograms: Optimized electrode configuration for near-field electrogram characterization.

BACKGROUND: Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined. OBJECTIVES: We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction. METHODS: This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and interelectrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2. RESULTS: Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P < .001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P < .05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P < .0001) with longer and more reproducible AF cycle length (P < .0001) compared to PentaRay. CONCLUSION: Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

Atrial tachycardia circuits include low voltage area from index atrial fibrillation ablation relationship between RF ablation lesion and AT.

BACKGROUND: No study to date has used high-density mapping to investigate the relationship between prior radiofrequency (RF) lesions for persistent atrial fibrillation (PsAF) ablation and subsequent atrial tachycardias (ATs). METHODS: From 41 consecutive patients who underwent AT ablation at a second procedure using an ultrahigh-density mapping system, 22 patients (38 ATs) were included as they also had complete maps with a multipolar catheter and three-dimensional (3D) mapping system at the time of the first PsAF ablation procedure. We, therefore, compared voltage maps from the first AF ablation procedure to those from the subsequent AT ablation procedure, as well as the lesion sets used for AF ablation vs the activation patterns in AT during the second procedure. RESULTS: In the 38 ATs, 211 of 285 analyzed atrial areas displayed low voltage area (LVA) (74%). Eighteen percent (38/211) existed before the index ablation for AF while 82% (173/211) were newly identified as LVA during the second procedure. Ninety-nine percent (172/173) of the newly developed LVA colocalized with RF lesions delivered for PsAF. Of the 38 ATs, 89.5% (34/38) AT circuits were associated with newly developed LVA due to RF lesions whilst 10.5% (4/38) AT circuits were associated with pre-existing LVA observed at the index procedure. No AT circuit was completely independent from index RF lesions in this series. CONCLUSIONS: Analysis of detailed 3D electroanatomical mapping demonstrates that most ATs after PsAF ablation are involving LVAs due to index RF lesions.

Ultra-High-Density Activation Mapping to Aid Isthmus Identification of Atrial Tachycardias in Congenital Heart Disease.

OBJECTIVES: A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). BACKGROUND: The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system's ability to accurately define the tachycardia circuit. METHODS: Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. RESULTS: Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. CONCLUSIONS: We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra-high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

Post-Myocardial Infarction Scar With Fat Deposition Shows Specific Electrophysiological Properties and Worse Outcome After Ventricular Tachycardia Ablation.

Background Fat deposition (FD) is part of the healing process after myocardial infarction. The characteristics of FD and its impact on the outcome in patients undergoing ventricular tachycardia (VT) ablation have not been thoroughly studied. Methods and Results We studied consecutive patients undergoing post-myocardial infarction VT ablation with pre-procedural cardiac computed tomography. FD was defined as intra-myocardial attenuation ≤ -30 HU on computed tomography. Clinical, anatomical, and post-procedural outcome was assessed in the overall population. Electrophysiological characteristics were assessed is a subgroup of patients with high-density electro-anatomical maps. Sixty-nine patients were included (66±12 years). FD was detected in 44 (64%) patients. The presence of FD related to scar age (odds ratio [OR]: 1.14 per year; P=0.001) and scar extent (OR: 1.27 per segment; P=0.02). On electro-anatomical maps, FD was characterized by lower bipolar amplitude (P<0.001) and prolonged electrogram duration (P<0.001). Although the proportion of local abnormal ventricular activation was similar (P=0.22), local abnormal ventricular activation showed lower amplitude (P<0.001) and were more delayed (P<0.001) in scars with FD. After a mean follow-up of 26 months, patients with FD experienced a worse outcome including all-cause mortality and VT recurrence (70% versus 28%, P log rank=0.009). On multivariate analysis, FD (hazard ratio=2.69; 95% CI, 1.12-6.46; P=0.027) and left ventricular systolic dysfunction (hazard ratio=2.57; 95% CI, 1.13-5.85; P=0.024) were independent predictors of adverse outcomes. Conclusions FD in patients with post-myocardial infarction VT undergoing catheter ablation relates to scar age and size and may be a marker of adverse outcomes including all-cause mortality and VT recurrence.

Noninvasive Mapping and Electrocardiographic Imaging in Atrial and Ventricular Arrhythmias (CardioInsight).

Electrocardiographic imaging is a mapping technique aiming to noninvasively characterize cardiac electrical activity using signals collected from the torso to reconstruct epicardial potentials. Its efficacy has been demonstrated clinically, from mapping premature ventricular complexes and accessory pathways to of complex arrhythmias. Electrocardiographic imaging uses a standardized workflow. Signals should be checked manually to avoid automatic processing errors. Reentry is confirmed in the presence of local activation covering the arrhythmia cycle length. Focal breakthroughs demonstrate a QS pattern associated with centrifugal activation. Electrocardiographic imaging offers a unique opportunity to better understand the mechanism of cardiac arrhythmias and guide ablation.

Larger and deeper ventricular lesions using a novel expandable spherical monopolar irrigated radiofrequency ablation catheter.

BACKGROUND: Radiofrequency (RF) ablation is an established treatment for ventricular tachycardia (VT). However, the inability of current RF catheters to address deep or large substrate may explain most of the clinical failures. OBJECTIVES: The aim of this study is to assess the efficacy and safety of ablation in the left ventricle (LV) in sheep using a novel 8-Fr deflectable ablation catheter (Sphere-9; Affera, Inc) with a 9-mm expandable spherical monopolar irrigated RF tip vs a standard RF irrigated catheter (Biosense Webster, Diamond Bar, CA). The impact on tissue was assessed on local bipolar electrograms (from nine uniformly distributed mini surface electrodes and an internal central reference electrode), as well as on direct lesion measurement post mortem. METHODS AND RESULTS: Eleven sheep underwent LV endocardial ablation in healthy tissue using the Sphere-9 catheter (n = 6), or a conventional irrigated RF catheter (n = 5). Twenty lesions were created with the Sphere-9 (current limit: 2.7 A; temp. limit: 60°C; irrigation: 30 mL/min; and duration: 60-120 seconds). Local bipolar electrograms at the surface of the catheter disappeared during RF delivery in 17 of 20 (85%) lesions. The mean lesion volume was 1707 ± 771 mm 3 (length: 15.8 ± 3.3 mm; width: 11.6 ± 4.2 mm; and depth: 10.3 ± 2.9 mm). Twenty-five lesions were created with a standard RF irrigated catheter (power control 35 W; irrigation: 30 mL/min; duration: 60 seconds; volume 537 ± 398 mm 3 ; length: 8.2 ± 2.3 mm; width: 5.2 ± 1.8 mm; and depth: 5.5 ± 2.4 mm). The novel spherical RF catheter created significantly larger lesions ( P < .001 for measurements in all dimensions). There were no steam pops with the novel ablation catheter vs one with the conventional catheter. CONCLUSIONS: This novel spherical monopolar irrigated RF catheter creates lesions that are twice as large and deep as a standard irrigated RF catheter.

Are wall thickness channels defined by computed tomography predictive of isthmuses of postinfarction ventricular tachycardia?

BACKGROUND: Wall thickness (WT) in post-myocardial infarction scar is heterogenous, with channels of relatively preserved thickness bordered by thinner scar. OBJECTIVE: This study sought to determine whether 3-dimensionally-reconstructed computed tomography (CT) channels correlate with electrophysiological isthmuses during ventricular tachycardia (VT). METHODS: We retrospectively studied 9 postinfarction patients (aged 57 ± 15 years, 1 female) with 10 complete VT activation maps (cycle length 429 ± 77ms) created using high-resolution mapping. Three-dimensionally-reconstructed WT maps from CT were merged with the activation map during sinus rhythm (SR) and VT. The relationship between WT and electrophysiological characteristics was analyzed. RESULTS: A total of 41 CT channels were identified (median 4 per patient), of median (range) length 21.2 mm (17.3-36.8 mm), width 9.0 mm (6.7-16.5 mm), and area 1.49 cm2(1.00-1.75 cm2). WT in the channel was significantly thicker in the center than in the edge (median 2.4 mm vs 1.5 mm, P < .0001). Of 3163 (2493-5960) mapping points in SR, 382 (191-1115) local abnormal ventricular activities (LAVAs) were identified. One patient had a maximal proportion of LAVAs in 3-4 mm, 3 patients in 2-3 mm, 2 in 1-2 mm, and 2 in 0-1 mm. The VT isthmuses of all 10 VTs corresponded with 1-4 CT channels. Twenty-one of the 41 CT channels (51.2%) corresponded to a VT isthmus (entrance, mid, or exit). Electrophysiological VT isthmuses were more likely to be associated with CT channels that were longer (P = .04, odds ratio [OR] 1.05/mm), thinner (but not less than 1 mm) (P = .03, OR 0.36/mm), or parallel to the mitral annulus (P = .07, OR 3.93). CONCLUSION: VT isthmuses were always found in CT channels (100% sensitivity), and half of CT channels hosted VT isthmuses (positive predictive value 51%). Longer and thinner (but >1 mm) CT channels were significantly associated with VT isthmuses.

Effect of Activation Wavefront on Electrogram Characteristics During Ventricular Tachycardia Ablation.

Background Catheter ablation of ventricular tachycardia (VT) in structural heart disease is challenging because of noninducibility or hemodynamic compromise. Ablation often depends on elimination of local abnormal ventricular activities (LAVAs) but which may be hidden in far-field signal. We investigated whether altering activation wavefront affects activation timing and LAVA characterization and allows a better understanding of isthmus anatomy. Methods Patients with ischemic cardiomyopathy underwent mapping using the ultra-high density Rhythmia system (Boston Scientific). Maps were generated for all stable VTs and with pacing from the atrium, right ventricular apex, and an left ventricular branch of the coronary sinus. Results Fifty-six paced maps and 23 VT circuits were mapped in 22 patients. In 79% of activation maps, there was ≥1 line of block in the paced conduction wavefront, with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular (31.7±18.5 versus 27.6±16.3 cm2, P=0.003) or left ventricular pacing (31.7±18.5 versus 27.0±19.2 cm2, P=0.009); LAVA areas were smaller with atrial than right ventricular (12.3±10.5 versus 18.4±11.0 cm2, P<0.001) or left ventricular pacing (12.3±10.5 versus 17.1±10.7 cm2, P<0.001). LAVA areas were larger with wavefront propagation perpendicular versus parallel to the line of block along isthmus boundaries (19.3±7.1 versus 13.6±7.4 cm2, P=0.01). All patients had successful VT isthmus ablation. In 11±8 months follow-up, 2 patients had a recurrence. Conclusions Wavefronts of conduction slowing/block may aid identification of critical isthmuses in unmappable VTs. Altering the activation wavefront leads to significant differences in conduction properties of myocardial tissue, along with scar and LAVA characterization. In patients where few LAVAs are identified during substrate mapping, using an alternate activation wavefront running perpendicular to the VT isthmus may increase sensitivity to detect arrhythmogenic substrate and critical sites for reentry.

Insights from atrial surface activation throughout atrial tachycardia cycle length: A new mapping tool.

BACKGROUND: A novel "LUMIPOINT" software in the Rhythmia system (Boston Scientific) displays a histogram of activated area over the entire atrial tachycardia (AT) cycle length (CL) with a normalized score. OBJECTIVE: The purpose of this study was to examine whether the pattern of this global activation histogram (GAH) identified reentrant vs focal AT and whether a decrease in atrial activation area, shown as valleys in the GAH, identifies isthmuses. METHODS: One hundred eight activation maps of ATs (17 focal, 57 macroreentrant, 21 localized, 13 multiple loop) in 67 patients were reviewed retrospectively with the LUMIPOINT software. The ACTIVATION SEARCH feature highlighted the activated area in a given time period irrespective of the activation map. A 30-ms unit time interval was set, and the GAH patterns and electrophysiological properties of highlighted areas were examined. RESULTS: Focal ATs systematically displayed a plateau with GAH-Score <0.1 for at least 30% of the CL. Most reentrant ATs (90/91 [98.9%]) lacked this plateau and displayed activity covering the entire CL, with 2 [1-2] GAH-Valleys per tachycardia. Each GAH-Valley highlighted 1 [1-2] areas in the map. Among 264 highlighted areas, 198 (75.0%) represented slow conduction, 19 (7.2%) lines of block, 27 (10.2%) wavefront collision, 3 (1.1%) unknown, and 17 (6.4%) absence of activation in focal ATs. Practical ablation sites all matched one of the highlighted areas based on GAH-Valleys, and they corresponded better with areas highlighted by GAH-Score ≤0.2 (P <.0001). CONCLUSION: GAH shows focal vs reentrant mechanisms at first glance. Decrease in activated areas (displayed by GAH-Valleys) is mostly due to slow conduction and highlights areas of special interest, with 100% sensitivity for isthmus identification.

Use of Novel Electrogram "Lumipoint" Algorithm to Detect Critical Isthmus and Abnormal Potentials for Ablation in Ventricular Tachycardia.

OBJECTIVES: This study reports the use of a novel "Lumipoint" algorithm in ventricular tachycardia (VT) ablation. BACKGROUND: Automatic mapping systems aid rapid acquisition of activation maps. However, they may annotate farfield rather than nearfield signal in low voltage areas, making maps difficult to interpret. The Lumipoint algorithm analyzes the complete electrogram tracing and therefore includes nearfield signals in its analysis. METHODS: Twenty-two patients with ischemic cardiomyopathy and 5 with dilated cardiomyopathy underwent mapping using the ultra-high density Rhythmia system. Lumipoint algorithms were applied retrospectively. RESULTS: In all left ventricular substrate maps, changing the window of interest to the post-QRS phase automatically identified late potentials. In 25 of 27 left ventricular VT activation maps, a minimum spatial window of interest correctly identified the VT isthmus as seen by the manually annotated map, entrainment, and response to ablation. In 6 maps, the algorithm identified the isthmus where the standard automatically annotated map did not. CONCLUSIONS: The Lumipoint algorithm automatically highlights areas with electrograms having specific characteristics or timings. This can identify late and fractionated potentials and regions that exhibit discontinuous activation, as well as the isthmus of a VT circuit. These features may enhance human interpretation of the electrogram signals during a case, particularly where the circuit lies in partial scar with low amplitude nearfield signals and potentially allow a more targeted ablation strategy.

Is it feasible to offer 'targeted ablation' of ventricular tachycardia circuits with better understanding of isthmus anatomy and conduction characteristics?

Successful mapping and ablation of ventricular tachycardias remains a challenging clinical task. Whereas conventional entrainment and activation mapping was for many years the gold standard to identify reentrant circuits in ischaemic ventricular tachycardia ablation procedures, substrate mapping has become the cornerstone of ventricular tachycardia ablation. In the last decade, technology has dramatically improved. In parallel to high-density automated mapping, cardiac imaging and image integration tools are increasingly used to assess the structural ventricular tachycardia substrate. The aim of this review is to describe the technologies underlying these new mapping systems and to discuss their possible role in providing new insights into identification and visualization of reentrant tachycardia mechanisms.

Detailed comparison between the wall thickness and voltages in chronic myocardial infarction.

BACKGROUND: The relationship between the local electrograms (EGMs) and wall thickness (WT) heterogeneity within infarct scars has not been thoroughly described. The relationship between WT and voltages and substrates for ventricular tachycardia (VT) was examined. METHODS: In 12 consecutive patients with myocardial infarction and VT, WT, defined by a multidetector computed tomography, and voltage were compared. In multicomponent EGMs, amplitudes of both far- and near-field components were manually measured, and the performance of the three-dimensional-mapping system automatic voltage measurement was assessed. RESULTS: Of 15 748 points acquired, 2677 points within 5 mm of the endocardial surface were analyzed. In total, 909 (34.0%) multicomponent EGMs were identified; 785 (86.4%) and 883 (97.1%) were distributed in the WT less than 4 and 5 mm, respectively. Far-field EGM voltages increased linearly from 0.14 mV (0.08-0.28 mV) in the WT: 0 to 1 mm to 0.70 mV (0.43-2.62 mV) in the WT: 4 to 5 mm (ρ = 0.430; P < 0.001), and a significant difference was demonstrated between any two WT-groups (P ≤ 0.001). In contrast, near-field EGM voltages varied from 0.27 mV (0.11-0.44 mV) in the WT: 0 to 1 mm to 0.29 mV (0.17-0.53 mV) in the WT: 4 to 5 mm with a poorer correlation (ρ = 0.062, P = 0.04). The proportion of points where the system automatically measured the voltage on near-field EGMs increased from less than 10% in areas of WT: 4 to 5 mm to 50% in areas less than 2 mm. Of 21 VTs observed, seven hemodynamically stable VTs were mapped and terminated in WT: 1 to 4 mm area. CONCLUSIONS: Although far-field voltages gradually increase with the WT, near-field does not. The three-dimensional-mapping system preferentially annotates the near-field components in thinner areas (center of the scar) and the far-field component in thicker areas when building a voltage map. Critical sites of VT are distributed in WT: 1 to 4 mm areas.

A simple mechanism underlying the behavior of reentrant atrial tachycardia during ablation.

BACKGROUND: Ablation of complex atrial tachycardias (ATs) is difficult. OBJECTIVE: The purpose of this study was to elucidate a mechanism underlying the behavior of ATs during ablation and to create an algorithm to predict it. METHODS: An algorithm predicting termination/conversion of AT and the second AT circuit associated with the ablation site was developed from 52 index reentrant AT high-resolution activation maps in 45 patients (retrospective phase). First, the wavefront collision site was identified. Then, the N or N-1 beat was defined for each collision associated with the ablation site. When the AT involved wavefront collision solely between N-1/N-1 (N/N) beats, the AT would terminate during ablation. Conversely, when the AT included wavefront collision between N/N-1 beats, the index AT would convert to a second AT. The algorithm was then prospectively tested in 172 patients with 194 ATs (127 anatomic macroreentrant ATs [AMATs], 44 non-AMATs, 23 multiple-loop ATs). RESULTS: Accuracy in predicting AT termination/conversion and the second AT circuit was 95.9% overall, 96.1% in AMATs, 95.5% in non-AMATs, and 95.7% in multiple-loop ATs. Median (25th-75th percentile) absolute variation between predicted and actually observed cycle length of the second AT was 6 (4-9) ms. Prediction failure occurred in 8 ATs; either the second AT used an unmapped chamber or structure in the index map (n = 7) or a line of block was misinterpreted as very slow conduction in the index map (n = 1). CONCLUSION: A simple mechanism underlies the behavior of ATs during ablation, even in complex ATs. With a simple algorithm using high-resolution mapping, AT termination/conversion and the second AT circuit and cycle length may be predicted from the index activation map.

Proteasomal inhibition after injury prevents fibrosis by modulating TGF-ß(1) signalling.

BACKGROUND: The development of organ fibrosis after injury requires activation of transforming growth factor ß(1) which regulates the transcription of profibrotic genes. The systemic administration of a proteasomal inhibitor has been reported to prevent the development of fibrosis in the liver, kidney and bone marrow. It is hypothesised that proteasomal inhibition would prevent lung and skin fibrosis after injury by inhibiting TGF-ß(1)-mediated transcription. METHODS: Bortezomib, a small molecule proteasome inhibitor in widespread clinical use, was administered to mice beginning 7 days after the intratracheal or intradermal administration of bleomycin and lung and skin fibrosis was measured after 21 or 40 days, respectively. To examine the mechanism of this protection, bortezomib was administered to primary normal lung fibroblasts and primary lung and skin fibroblasts obtained from patients with idiopathic pulmonary fibrosis and scleroderma, respectively. RESULTS: Bortezomib promoted normal repair and prevented lung and skin fibrosis when administered beginning 7 days after the initiation of bleomycin. In primary human lung fibroblasts from normal individuals and patients with idiopathic pulmonary fibrosis and in skin fibroblasts from a patient with scleroderma, bortezomib inhibited TGF-ß(1)-mediated target gene expression by inhibiting transcription induced by activated Smads. An increase in the abundance and activity of the nuclear hormone receptor PPARγ, a repressor of Smad-mediated transcription, contributed to this response. CONCLUSIONS: Proteasomal inhibition prevents lung and skin fibrosis after injury in part by increasing the abundance and activity of PPARγ. Proteasomal inhibition may offer a novel therapeutic alternative in patients with dysregulated tissue repair and fibrosis.

Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells.

Long-term use of nonsteroidal anti-inflammatory drugs is associated with a reduction in the incidence of a range of cancers, the mechanism of which is thought to be cyclooxygenase (COX) inhibition. Because long-term ingestion of foods rich in isoflavones, such as legumes (beans, peas, lentils) has been associated with reduced cancer incidence, it was considered useful to examine the COX-inhibitory activities of individual isoflavones. Red clover dietary supplements also contain varying ratios of the 4 isoflavones commonly found in legume-based diets, namely, daidzein, genistein, formononetin, and biochanin. Using 2 separate cell assays, this study examined the ability of the isoflavones found in red clover to inhibit COX enzyme activity in both the murine macrophage cell line RAW 264.7 and human monocytes. Within the range of 1-40 microM in RAW 264.7 cells and 10-100 microM in human monocytes, isoflavones were able to reduce significantly the synthesis of prostaglandin E2 and/or thromboxane B2 (P < 0.001 to P < 0.05), indicating COX inhibition. Thus, it is possible that the lower rates of some cancers in populations with a high intake of dietary isoflavones is linked to their inhibition of COX activity.