Low-voltage Areas Research Articles

Plasma 8-Hydroxy-2'-Deoxyguanosine, a Potential Valuable Biomarker for Atrial Fibrosis Is Influenced by Polymorphism of DNA Methylation Gene.

Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Case report: Mutation in NPPA gene as a cause of fibrotic atrial myopathy

Early-onset atrial fibrillation (AF) can be the manifestation of a genetic atrial myopathy. However, specific genetic identification of a mutation causing atrial fibrosis is rare. We report a case of a young patient with an asymptomatic AF, diagnosed during a routine examination. The cardiac MRI revealed extensive atrial fibrosis and the electrophysiology study showed extensive areas of low voltage. The genetic investigation identified a homozygous pathogenic variant in the NPPA gene in the index case and the presence of the variant in heterozygosity in both parents.

Functional substrate mapping characteristics during sinus rhythm predicts critical isthmus of reentrant atrial tachycardia.

Atrial tachycardia (AT)is a commonly encountered rhythm disorder in patients with underlying atrial scar. The role of atrial late activation mapping during sinus rhythm to predict the critical isthmus (CI) of AT has yet to be systematically evaluated. We aimed to investigate the relationship between the functional substrate mapping (FSM)characteristics and the CI of reentrant ATs in patients with underlying atrial low-voltage areas. Patients with history of left AT who underwent catheter ablation with 3D mapping using high-density mapping were enrolled. Voltage map and isochronal late activation mapping were created during sinus/paced rhythm to detect deceleration zones (DZ).Electrograms with continuous-fragmented morphology were also tagged. After induction of AT, activation mapping was performed to detect CI of the tachycardia. Atrial tachyarrhythmia (ATa) recurrence was defined as detection of atrial fibrillation or AT (≥30 s) during the follow-up. Among 35 patients [mean age: 62 ± 9, gender: 25 (71.5%) female] with left AT, a total of 42 reentrant ATs induced. Voltage mapping during sinus rhythm revealed low-voltage area of 37.1 ± 23.8% of the left atrium. The mean value of bipolar voltage, EGM duration, and conduction velocity during sinus rhythm corresponding to CI of ATs were 0.18 ± 0.12 mV, 133 ± 47 ms, and 0.12 ± 0.09 m/s, respectively. Total number of DZs per chamber was 1.5 ± 0.6, which were located in the low-voltage zone (<0.5 mV) detected by high-density mapping. All CIs of reentry were colocalized with DZs detected during FSM. The positive predictive value of DZs to detect CI of inducible ATs is 80.4%. Freedom from ATa after the index procedure was 74.3% during a mean follow-up of 12.2 ± 7.5 months. Our findings demonstrated the utility of FSM during sinus rhythm to predict the CI of AT. DZs displayed continuous-fragmented signal morphology with slow conduction which may guide to tailor ablation strategy in case of underlying atrial scar.

3D Atrial Strain for Predicting Recurrence of Atrial Fibrillation after Pulmonary Vein Isolation.

Association of two-(2D) and three-dimensional (3D) left atrial strain (LAS) and low-voltage area (LVA) with recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) was assessed. 3D LAS, 2D LAS, and LVA were obtained in 93 consecutive patients undergoing PVI and recurrence of AF was analyzed prospectively. AF recurred in 12 patients (13%). The 3D left atrial reservoir strain (LARS) and pump strain (LAPS) were lower in patients with recurrent AF than without (p = 0.008 and p = 0.009, respectively). In univariable Cox regression, 3D LARS or LAPS were associated with recurrent AF (LARS: HR = 0.89 (0.81-0.99), p = 0.025; LAPS: HR = 1.40 (1.02-1.92), p = 0.040), while other values were not. Association of 3D LARS or LAPS with recurrent AF was independent of age, body mass index, arterial hypertension, left ventricular ejection fraction, and end-diastolic volume index and left atrial volume index in multivariable models. Kaplan-Meier curves revealed that patients with 3D LAPS < -5.9% did not exhibit recurrent AF, while those >-5.9% had a significant risk of recurrent AF. 3D LARS and LAPS were associated with recurrent AF after PVI. Association of 3D LAS was independent of relevant clinical and echocardiographic parameters and improved their predictive value. Hence, they may be applied for outcome prediction in patients undergoing PVI.

Beat to beat P wavelet analysis in addition to standard P wave indices as correlates of left atrial extent of low voltage areas in patients with PAF undergoing catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. BACKROUND Left atrium (LA) fibrosis has been shown to be an important factor associated with atrial fibrillation recurrence after catheter ablation (CA). Morphological features of the P wave have been related to the extent of atrial fibrosis as identified with electroanatomic mapping (EAM) in patients with paroxysmal atrial fibrillation (PAF) undergoing catheter ablation (CA). The ability to assess, by means of non-invasive markers, the electroanatomical substrate of the LA and the likelihood of PAF recurrence after CA, could be very useful in PAF management, patient selection for CA and improving outcomes. Purpose In the current prospective cohort study we aimed at establishing a pathophysiological basis of beat-to-beat (B2B) P-wave morphological and wavelet analysis, showing that it is associated with areas of considerable fibrosis, as identified with EAM in patients with PAF. Methods 44 patients with symptomatic paroxysmal AF, diagnosed at least 6 months before, were enrolled. 12-lead electrocardiogram (ECG) recordings, as well as 12 min vectorcardiogram (VCG) recordings were obtained from all patients, while EAM of left atrium (LA) was performed in all patients before radiofrequency CA. B2B P-wave morphological and wavelet analysis was performed according to a methodology described in previous publications. Results The 35 patients who were valid for statistical analysis were divided into 2 groups: in Group A the total low-voltage (&amp;lt;0.5 mV in EAM) area was greater than the median value of 5.55% (large low-voltage area), while in Group B the total low-voltage area was &amp;lt;5.55% (small low-voltage area). From the correlation between standard P-wave indices derived from 12-lead ECG and low-voltage areas only P-wave duration was significantly different between the two groups. From orthogonal ECG parameters analysis X axis was the most representative of low-voltage areas. B2B P-wave analysis revealed 3 features which showed a statistically significant difference between the 2 groups and no collinearity (Table 1). Logistic regression analysis of the non correlated variables for the prediction of low-voltage areas is shown in Table 2. It seems that a longer distance between the P-wave peak and the P-wave end, as well as a more «flattened» P-wave (small area with long duration) is associated with larger low-voltage areas and consequently more extensive LA fibrosis. Conclusions In patients with PAF and no overt atrial myopathy, B2B wavelet analysis may be a useful non-invasive tool for the prediction of low-voltage areas, representing fibrosis in the LA. Further studies in larger cohorts of patients are needed in order to confirm these findings and enable the use of B2B wavelet analysis in clinical practice.

Left atrium substrate and wave speed mapping using Omnipolar technology in patients undergoing paroxysmal atrial fibrillation catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background The new Ensite X Cardiac Mapping (Abbott) system, with the introduction of Omnipolar technology (OT), provides three-dimensional information on voltage, direction of activation and conduction velocity of endocardial potentials, regardless of catheter orientation. OT thus enables the creation of more defined voltage maps and a wave speed map, a color map encoded by the numerical value of conduction velocity. Purpose We aimed to evaluate the feasibility and reliability of left atrium (LA) substrate and wave speed mapsperformed with OT in patients undergoing pulmonary vein isolation of paroxysmal atrial fibrillation (AF). Methods We included 39 patients undergoing catheter ablation for paroxysmal AF with the new Ensite X Cardiac Mapping System at five Italian Institution. In all patients the left atrium (LA) was mapped with the Advisor HD Grid catheter (Abbott). A sinus rhythm high-density voltage map and wave speed map were obtained and analyzed to compare low-voltage areas and to identify high conduction velocity areas. Results Thirty-nine pts were included in this analysis (61±10 years, 64% male, 68% with paroxysmal AF, CHA2DS2-VASc = 1.6±1.1, left atrial diameter = 46±9 mm, left ventricle ejection fraction 63±4%). The voltage maps were obtained by acquiring and, after point validation, analyzing significantly more points in the OT analysis than in the bipolar analysis (11455±8833 vs 8186±5826 and 2611±1728 vs 1753±1324, respectively; p &amp;lt; 0.001). Low-voltage area (&amp;lt; 0.05 mV) was significantly less extensive using OT (low-voltage OT area 8.9 cm2 [5.8; 24.2] vs low-voltage bipolar area 10.8 [6.4; 31.4]; p &amp;lt; 0.05), Fig 1. Considering wave speed maps, the pulmonary veins showed significantly higher values than the atrial values (LSPV: 2.89 ms/s ± 1.99; LIPV 2.86 ms/s ± 1.78; RSPV 3.31 ms/s ± 2.07; RIPV 2.86 ms/s ± 1.96; LA 1.67 ms/s ± 0.80; p&amp;lt; 0.001) while, in the atrium, the area of greatest speed was located on the roof (2.35 ms/s ± 1.53; p 0.02) almost drawing a bundle from the RSPV to the LA appendage that could coincide with the anatomical Bachmann’s bundle location, Fig 2. Conclusion OT makes it possible to obtain voltage maps by analyzing a larger number of points and providing a better substrate definition. Wave speed mapping is a promising new map type, allowing characterization and identification of high velocity areas. Further studies are needed to assess the impact of this new technology on procedural workflow and clinical outcome.

Predictive value of clinical risk scores for determination of left atrial low voltage area and arrhythmia recurrences in patients undergoing atrial fibrillation ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Presence of left atrial low voltage area (LVA) is an independent predictor of atrial tachyarhythmia (ATa) recurrences after atrial fibrillation (AF) ablation. Thus identifying patients with LVA by using non-invasive methods is an important endeavour. Purpose In this study; we investigated the predictors of LVA and postablation recurrences especially focusing on clinical risk scores. Methods We enrolled 328 consecutive patients who underwent initial AF ablation procedure using high density mapping. LVAs were assessed and segmental distribution was noted in each patient. CHA2DS2-VASc, HATCH, APPLE and SPEED scores were calculated. Predictive value and arrhythmia recurrences were evaluated. Results Two hundred and twenty one patients (67.37%) were paroxysmal AF and 107 (32.62%) patients were non-paroxysmal AF at the time of ablation. Mean CHA2DS2-VASc score was 1.88±1.66, mean APPLE score was 1.20±1.20, HATCH score was 0.93±1.00 and SPEED score was 1.54±1.27 in the whole study group. LVA was detected in 131 patients (39.93%). Female gender [OR:2.94, CI: 1.34-6.43, p=0.007), non-paroxsymal AF (OR: 2.49 CI:1.13-5.46, p=0.023), APPLE score ≥1 (OR:1.69 CI:1.12-2.55, p=0.012) and SPEED score ≥ 1 (OR: 1.47 CI:1.00-2.14, p=0.045] were independent predictors for the presence of LVA in multivariate analysis. Presence of LVA (OR:1.98; CI:1.13-4.15; p=0.017) and HT (OR:2.00; CI:1.19-3.38; p=0.009) were the independent predictors of recurrences. Conclusion Higher clinical scores are associated with more LVA which is associated with ATa recurrence. However the predictive value of these risk scores is limited. Better risk scoring systems are needed to precisely identify the underlying atrial substrate in this patient group.

Identification of the fossa ovalis by voltage mapping using a high-density mapping catheter

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transseptal puncture (TP) is routinely performed under fluoroscopy and/or echocardiography guidance. Additional methods to localize the fossa ovalis (FO) may decrease radiation exposure, as well as periprocedural risk. In the recent years, high-density mapping (HDM) catheters have been used for mapping and ablation of left atrial (LA) arrhythmias. Purpose The aim of this study is to determine whether a HDM catheter can reliably identify the specific FO electrogram (EGM) patterns. Methods During atrial fibrillation (AF) ablation, a voltage map of the right-sided atrial septum was created using a HDM catheter (Pentaray, Biosense Webster, USA, spacing 2-6-2 mm). The location of the FO was identified by transesophageal echocardiogram and fluoroscopy guidance prior to TP. At the end of the procedure, a 3D phantom was created during catheter retrieval from the left to the right atrium through the TP. Post ablation analysis was done to evaluate whether the HDM catheter was able to record EGM characteristics of the FO. Results Fifteen patients were included (male 63%, mean age 61.2±11.7 y. o.); 80% of the cases were in sinus rhythm, 53% had a normal LA size, and the mean CHADS2-VA2SC score was 1.5 ± 1.6. One patent fossa ovalis and one septal pouch of the left atrium were seen. In all patients, an area of low voltage could be identified in the vicinity of the transseptal puncture. In 74%, the location of transseptal puncture was inside of the area of low voltage. The mean voltage value of this area was 0.6 ± 0.3 mV, whereas the mean voltage value of the myocardium surrounding the "low voltage area" was 4.3 ± 2.1 mV (P&amp;lt;0.01). The surface of the low voltage could be best demarcated using a scale from 0.05 -1.5 mV with an area measured at 3.8 ± 2.6 cm2 [Figure 1]. At other voltage scales, the FO surface demonstrated smaller areas of low voltage (scale/surface [mV/cm2] : 0.05-0.5/ 0.8 ± 1.3; 0.05-1.0/2.2 ± 1.8; 0.5-1.0/2.3±1.6). In 63%, fractionated potentials were recorded in the area of the FO [Figure 1]. Conclusions Based on its EGM characteristics, the fossa ovalis can be accurately localized with a high-density mapping catheter. This finding will certainly help to implement radiation free procedure particularly when echocardiographic modalities are not available. Figure 1: Mapping of the region of the fossa ovalis with a high density mapping catheter revealed an area of low voltage with fractionnated electrogram. Fossa ovalis was identified by transseptal puncture. TP: phantom of the catheters, CS: coronary sinus, H: His, IVC: inferior vena cava, SVC: superior vena cava, * fractionnated electrogram

Atrial myocardial substrate has a significant influence on local impedance data - clinical experience from high power short duration and standard radio frequency ablations

Abstract Funding Acknowledgements Type of funding sources: None. Background Local impedance is a new clinically used RF ablation parameter used to predict RF lesion creation. By now, data about the influence of atrial substrate on local impedance is still scarce. The aim of this study was to investigate local impedance data of different atrial tissues (healthy myocardium vs. Low Voltage areas) and the importance of local impedance drops during HPSD and standard RF ablation in atrial tissue. Methods A total of n=1319 clinical RF applications in n=51 clinical left atrial ablation procedures were analyzed regarding underlying RF ablation parameters (RF power, duration, contact force, global and local impedance data). 3D mapping data were used to differentiate RF ablations in low voltage areas (&amp;lt;=1.0mv) from those in healthy atrial myocardium (&amp;gt;1.0mV). Local and global impedance baseline values and drops, RF electrogram amplitude attenuation, as well as RF data were calculated and registered for statistical analysis. Results Local impedance drops were significantly higher during RF application in healthy myocardium when compared to low voltage areas (18,6 vs. 16,6 Ohm, p&amp;lt;0.01). Baseline local impedance was significantly higher in healthy atrial myocardium when compared to low voltage areas (105,4 vs. 99,1 Ohm, p&amp;lt;0.01). There was no significant difference in global impedance values between low voltage areas and healthy atrial myocardium (p=0.34). These findings were confirmed in HPSD (60W, 10s) as well as in standard (30-40W, 30-60s) RF applications. Impedance drops were significantly larger in HPSD when comapred to standard RF ablation (p&amp;lt;0.01). Detailed boxplot results are presented in the Figure. Conclusions Local impedance drop is a good predictor of RF lesion creation in HPSD as well standard RF ablations. Interestingly, different local impedance but not global impedance values were observed in healthy and low voltage areas. In clinical practice, local impedance may be a useful parameter to identify atrial substrate.

Pulmonary vein isolation and additional selective ablation of low voltage areas and atrial late potentials for persistent atrial fibrillation (SOLVE-AF-Study)

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Introduction Novel catheter ablation technologies (e.g. RF with contiguous lesions) for pulmonary vein isolation (PVI) achieve high (80-85%) arrhythmia freedom rates at 12 months in both paroxysmal and persistent AF. However, success rates are importantly reduced (45-50%) in persistent AF patients presenting atrial cardiomyopathy with additional low voltage areas in the left atrial body. Aim SOLVE-AF study is a prospective randomized multicenter study, in which the standard approach "circumferential PVI" is compared to "additional ablation of low voltage areas and ablation of slow conducting "atrial late potentials (ALPs)" during sinus rhythm (SR)". Methods 320 patients with persistent AF will be included. Patients undergo left atrial high definition voltage mapping in SR. 160 patients with low voltage areas (&amp;lt;0.5mV at &amp;gt;5cm2) within the LA body will be randomized to "circumferential-PVI" vs. "additional low-voltage-guided ablation". The remaining 160 without low voltage substrate (registry group) will undergo "circumferential-PVI". Arrhythmia recurrences (defined as AF/AT &amp;gt;30 sec) will be assessed at 6 and 12 months (7-day-Holter and event-recorder) following ablation therapy (top panel). Results Currently, 120 patients have been included into the registry group and 120 patients with low voltage substrate have been randomized. Results of the SOLVE-AF-pilot study including a total of 210 patients (110 registry patients without LA-LVS and 100 patients with LA-LVS who were assigned to PVI-only versus additional substrate-based ablation) at the University-Heart-Center-FR-BK favor "PVI plus substrate-based ablation" in those patients who do present significant low voltage areas (see KM-curve bottom panel). Conclusions Results from the pilot trial suggests improved arrhythmia freedom rate with PVI plus additional substrate-based ablation during sinus rhythm. Final results of the prospective randomized multi-center trial SOLVE-AF are expected in June 2024.

Voltage characterization of abnormal conduction zones in patients affected by atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background In case of persistent atrial fibrillation (AF), atrial substrate assumes a dominant role in sustaining the arrhythmia. Recent studies prove that low voltage areas (LVA, Voltage Amplitude &amp;lt; 0,5 mV) represent an additional target for ablation of AF patients. Purpose The purpose of this study is to analyse whether structural atrial conduction abnormalities (i.e., pivot sites and slow conduction corridors) may occur outside low voltage areas. Methods The study is based on the retrospective analysis of 31 consecutive maps of patients undergoing AF ablation (16 paroxysmal and 15 persistent cases). The clinical procedures have been performed with the support of a mapping system. Sinus rhythm activation maps and bipolar maps used for this analysis have been created with a multipolar mapping catheter. Map points were only acquired when the electrode was in contact with the endocardial tissue to avoid misleading voltage amplitude information. Slow conduction corridors and pivot sites have been analysed. At these sites, EGMs characterization included voltage amplitude (mV), signal duration (ms) and fractionation. Results The average value of EGMs amplitude reported at pivot sites and slow conduction zones, respectively, amounted to 2,08 ± 0,63 mV and 2,1 ± 0,66 mV in paroxysmal cases. In persistent cases, there were slight decreased values to 1,95 ± 0,93 mV and 1,89 ± 0,89 mV. Characterization at pivot sites documented a mean duration value of 45,4 ± 4,64 ms and 49,93 ± 5,51 ms in paroxysmal and persistent patients, respectively, while in slow conduction zones 41,53 ± 7,94 ms and 49,04 ± 6,41 ms have been reported. As for fractionation, more than five deflections per signal have been identified in all abnormal conduction areas. Conclusion Our study proves that functional electrophysiological phenomena can occur outside low voltage areas, even in persistent cases. According to this analysis, not all LVA represent the correct target for catheter ablation, encouraging the development of further methods for investigation of atrial substrate.

Incremental value of low-voltage area ablation in persistent atrial fibrillation: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction The optimal ablation approach for patients with persistent atrial fibrillation (AF) is a topic of high controversy. The efficacy of adjunctive ablation strategy beyond conventional pulmonary vein isolation remains uncertain. Purpose We sought to investigate the effectiveness of individualized low-voltage area (LVA) substrate modification in patients with persistent AF receiving conventional catheter ablation. Methods We systematically searched PubMed, Cochrane Library, and grey literature sources including clinicaltrials.gov, from inception to 1st November 2022, to identify relevant randomized controlled trials (RCTs). Patients with persistent AF undergoing conventional catheter ablation vs. ablation with additional LVA substrate modification were compared. Freedom from arrhythmia was set as the primary efficacy outcome and total procedure time as the secondary efficacy outcome. A prespecified subgroup analysis was performed for patients with presence of LVAs. We did not impose any filter regarding the study setting, sample size, study duration, or publication language. All analyses were performed using R version 4.1.0 and a two-sided p-value&amp;lt;0.05 was considered statistically significant. Results We pooled data from 5 RCTs with a total of 989 participants (31% female) with persistent AF. Ablation with additional LVA substrate modification resulted in a significantly increased likelihood for freedom from arrhythmia by 60%, compared to conventional AF ablation (odds ratio 1.60; 95% confidence interval 1.13-2.28; I2=39%; p=0.009). No difference in the total procedure time was identified between the two approaches (mean difference -28.94 min; 95% confidence interval -69.39 to 11.51 min; I2 = 98%, p=0.16). In patients with LVAs (n=240), additional LVA substrate modification yielded a higher probability for freedom from arrhythmia than conventional AF ablation (odds ratio 1.73; 95% confidence interval 1.03-2.90; I2=0%; p=0.04). Conclusion This meta-analysis demonstrates that an individualized ablation approach with low-voltage area substrate modification is associated with improved outcomes in patients with persistent AF.

Refinement of voltage-based atrial scar assessment using pacing thresholds and local impedance

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific Background Common cut-offs for dense scar and ‘low-voltage areas’ on atrial 3D electroanatomical mapping are 0.05mV and 0.50mV respectively. These are not physiologically validated and may not fully represent underlying scar compared with unipolar readings or the novel parameter local impedance (LI). Objectives Investigate the relationship of bipolar voltage, unipolar voltage and LI with pacing threshold (PT). Establish cut-offs for electrically inert (EI), partially active (PA) and electrically active (EA) atrial tissue based upon pacing capture. Methods Patients undergoing AF ablation were recruited. 3D electroanatomical maps were created. PTs were assessed using the MiFi and Stablepoint (SP) ablation catheters between the tip and first ring electrodes. PTs were assessed with a 2ms pulse duration commencing at 5mA and moved up or down accordingly. LI was referenced against a blood pool reading (LIr). EI sites were defined as no pacing capture, PA capture between 5-20mA and EA less than 5mA. Results 292 PTs and LI readings were recorded in 40 patients (Male: 21/40; Age: 66.7 ± 8.8; Paroxysmal AF: 10, Persistent AF: 30, De novo 21, Redo 19). A weak correlation exists between SR voltages and PT (Spearman's Rho - Bipolar: -0.35, Unipolar: -0.26, both p &amp;lt;0.0005). Weak correlations exist between LI and PT, (Spearman's Rho - MiFi = -0.35, SP = - 0.33, both p &amp;lt; 0.0005), but moderate-strong correlations exists between LIr and PT (Rho - MiFi = -0.52, SP = -0.57, both p &amp;lt;0.0005, [Figure 1]). For the EI-PA cut-off, the ability to distinguish capture / no capture for bipolar voltages was fair (AUROC = 0.74), but poor for unipolar, (AUROC = 0.68). The lowest tissue voltage values with capture were 0.03mV and 0.31mV respectively. In contrast, LIr had excellent discriminatory ability (AUROC – MiFi = 0.87, SP = 0.90, lowest value with tissue capture = 1Ω for both MiFi and SP). For the PA-EA cut-off, the ability to distinguish PT above/below 5mA for bipolar voltages was fair (AUROC = 0.69, optimal cut-off 1.29mV), and poor for unipolar voltages, (AUROC = 0.63). In contrast, LIr had good discrimination, (AUROC - MiFi = 0.82, optimal cut-off 12.5Ω, SP = 0.89, optimal cut-off 10.5Ω). Using these cut-offs, there was a significant difference between PTs between EI, PA and EA, for bipolar voltage, (EI: 20mV, PA 6.0 ± 6.3mV, EA: 2.6 ± 2.6mV, p &amp;lt; 0.0005) and LIr, (MiFi: EI: 20mV, PA 7.8 ± 7.5mV, EA: 2.8 ± 2.8mV. SP: EI 20mV, PA: 4.0 ± 2.5mV, EA: 2.2 ± 0.9mV, both p &amp;lt; 0.0005, [Figure 2]). Conclusions PTs suggest conventional voltage cut-offs could be improved. LIr shows potential as a novel parameter in assessing tissue health complimentary to bipolar voltages. Based on pacing capture data, what has previously been labelled dense scar is not electrically inert and should be ablated if clinically indicated. Values of 0.03mV and 1.31mV, and for potential future LIr mapping, 0.5Ω and 10.5Ω are suggested as dense scar and low voltage area thresholds.

Electrophysiological findings in HFpEF patients presenting for AF ablation

Abstract Funding Acknowledgements Type of funding sources: None. Aims The prevalence of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) patients is high. Impaired left atrial (LA) function is a major determinant in HFpEF. The extent of arrhythmogenic left atrial tissue degeneration in HFpEF patients is unknown. Methods and results We prospectively enrolled consecutive patients presenting for first time AF ablation. Each patient underwent baseline laboratory and transthoracic echocardiography assessment. The HFA-PEFF score was utilized to identify HFpEF patients. Bipolar high density voltage mapping [1213 (825 to 1606) mapping points] was created in sinus rhythm prior to PVI to evaluate the general LA bipolar voltage and quantify areas of low voltage, a well known surrogate for fibrosis and arrhythmogenesis. 160 patients were enrolled (55 % male). 42 patients (26 %) suffered from HFpEF. Low voltage areas (LVAs) were present in 84 patients (53 %). HFpEF was associated with generally decreased LA bipolar voltage (0.95 ± 0.45 mV vs. 1.59 ± 0.91 mV respectively; p &amp;lt; 0.001) (Fig. 1) and predictive for the existence of low voltage areas (81 % vs. 45 % low voltage area positive, respectively; p = 0.006). The HFA-PEFF score inversely correlated with LA bipolar voltage (r = - 0.380; p &amp;lt; 0.001) (Fig. 1). Furthermore, the HFA-PEFF score closely correlated to the extent of LVAs (r = 0.275; p = 0.001) and to the low voltage amplitude of atrial myocardium excluding areas of low voltage (r = - 0.403; p &amp;lt; 0.001). Conclusion HFpEF is highly predictive for generally decreased LA bipolar voltage and for the existence of fibrotic and arrhythmogenic left atrial tissue degeneration.

Unraveling direction- and rate-dependent unipolar electrogram morphology using spontaneous atrial extraystoles

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial extrasystoles (AES) are notorious for triggering episodes of atrial fibrillation (AF). AES provoke conduction disorders due to (dispersion in) refractoriness and enhanced non-uniform anisotropy of atrial tissue, which are related to initiation and perpetuation of AF. However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Purpose To examine the impact of spontaneous AES on potential amplitude, -type (single-, double-, fractionated), -duration and low-voltage areas (LVA), and to correlate these differences with various degrees of prematurity and aberrancy. Methods Intra-operative high-resolution epicardial mapping of the right and left atrium (RA, LA), Bachmann’s Bundle (BB) and pulmonary vein area (PVA) was performed during SR in 298 patients. EGM characteristics were quantified during SR and AES, and subsequently compared. AES were categorized according their prematurity index (&amp;gt; 25% shortening) and degree of aberrancy (none, mild, moderate and severe). LVA were defined as the amount of unipolar voltages &amp;lt;1 mV. Results During 917 unique AES (495 premature; 364 mild-, 186 moderate- and 167 severe aberrant), average voltage decreased (-1.1 [-1.2, -0.9] mV, P&amp;lt;0.001) at all atrial regions, whereas the amount of LVA and fractionation increased (respectively +3.6 [2.9, 4.3]% and +3.2 [2.7, 3.7]%, P&amp;lt;0.001). Although potential voltages were mainly decreased during AES, in 910 (99.2%) AES, at least 0.8% (median 33.3 [19.0–52.1] %) of the recorded voltages was locally larger during AES compared to SR. Only weak or moderate correlations were found between each of the parameters and prematurity indices (R2&amp;lt;0.592, P&amp;lt;0.001). On the other hand, voltages decreased and the amount of fractionation increased with increasing degree of aberrancy. The effect of AES with opposite propagation direction was frequently similar as compared to severely aberrant AES. All parameters were most severely affected by either opposite or severely aberrant AES, without clear relation with degree of prematurity. Conclusions Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. This indicates enhanced non-uniform anisotropy that is induced by spontaneous AES.

A novel method to define critical isthmus of left atrial tachycardia; late potential mapping during sinus rhythm

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial tachycardia (AT) is a commonly encountered rhythm disorder in patients with underlying atrial scar. The role of late potential (LP) based mapping in the detection of AT critical isthmus has yet to be systematically evaluated. Purpose We aimed to investigate the relationship between the atrial LPs (ALP) localization in sinus rhythm and the critical isthmus of re-entrant ATs in patients with underlying atrial low-voltage areas. Methods Thirty-five symptomatic patients [mean age: 62 ±9, gender: 25 (71.4%) female] with left AT, who had undergone catheter ablation, were enrolled. Voltage and LP mapping were performed in sinus rhythm in both atriums. Low voltage areas and signals with continuous-fragmented morphology were tagged. Isochronal late activation mapping (ILAM) was also performed in all procedures. After induction of AT, activation mapping was performed during tachycardia in all patients to detect critical sites of the tachycardia. Results Activation mapping indicated single re-entry in 30 patients and ≥1 re-entry in 5 patients. Localized re-entry was observed in 20 (51.2%) patients, macro re-entry in 18 (46.1%), and biatrial re-entry in 1(2.5%). The mean fractionated electrogram duration in the AT termination site was calculated at 134.3±46.7 ms and the mean bipolar voltage at 0.17±0.12 mV. The ALPs were tagged in 25 (64.1%) patients on the anterior wall, 12 (34.3%) on the roof, 5 (12.8%) on the septal wall and 2 (5.7%) in the Bachmann’s Bundle region. All ALPs were in the latest activated zones of ILAM in patients with localized re-entry and predicted successful ablation sites to terminate the AT. Freedom from atrial tachyarrhythmias (ATAs) was 78.7% at six months during a mean follow-up duration of 338 ±226 days. Conclusion Our findings demonstrated the utility of ALPs during sinus rhythm to predict the successful termination sites for left ATs. These areas displayed continuous-fragmented signal morphology during sinus/paced rhythm in correlation with the critical isthmus of AT detected during activation mapping.

The relationship between high dominant frequency and low voltage areas in patients with atrial fibrillation: digital twin study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a grant [2022R1I1A1A0106342211] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT &amp; Future Planning (MSIP) Background It has been suggested that the high dominant frequency (DF) site plays an atrial fibrillation (AF) driver, but its relationship with the atrial substrate voltage map (Vm) in the entire chamber AF map has yet to be studied. We explored the relationship between the DF site during AF and Vm in the entire chamber maps by applying the human left atrial (LA) electroanatomical map (EAM) to the digital twin AF map. Methods We acquired LA substrate Vm (at sinus rhythm, &amp;gt;800 points bipolar electrograms) of 110 patients with persistent AF (male 72.7%, 58.7±9.8 years old) who underwent AF catheter ablation. We applied EAM to digital twins (0.4 million nodes), reflecting anatomy, histology, and electrophysiology. We evaluated the highest 10% DF areas for 6 sec after inducing virtual AF. The correlation between the highest 10% DF and the low Vm areas (&amp;lt;0.2mV) was evaluated in the LA region of 10 segments. Results The mean voltage of the entire LA area was 1.96±0.85 mV (2.19±0.82 mV extra-PV area, 1.33±0.93 mV PV area) in 110 patients. The correlation between low Vm and high DF areas was not significant in the entire LA (r=0.106, p&amp;lt;0.001), extra-PV (r=0.157, p&amp;lt;0.001), and PV (r=0.079, p=0.097) areas. In the LA 10 segment regional analysis, 72 patients (65.5%) showed the co-localization of the highest DF in the region with the lowest Vm, and 14 patients (12.7%) had the lowest Vm segment in the region with the highest DF. The mean voltage where high DF appeared was 0.69±1.35 mV, and the mean voltage of the region where high DF did not appear was 0.59±1.15 mV (p=0.171). Conclusion High DF site, a parameter representing a localized focal source, had statistically significant but very poor correlations with LA extra-PV voltage substrate in patients with persistent AF.

Characterization of right ventricular low voltage areas in patients with arrhythmogenic right ventricular cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement in the myocardium progressing from the epicardium towards the endocardium and affecting primarily the right ventricle (RV). Little data is available on the distribution of RV electrical abnormalities at the era of epicardial and high-resolution mapping. Purpose To evaluate the extent and distribution of RV epicardial and endocardial low voltage areas and their relationship with ECG abnormalities in ARVC patients. Methods Patients with a definite ARVC diagnosis according to the 2020 Task Force Criteria, who underwent ventricular tachycardia ablation between 2016 and 2022 with a high-density RV 3-dimensional electroanatomic mapping, were included. A custom RV segmentation dividing the RV into 10 segments from endocardial maps was used: anterior and lateral right ventricular outflow tract (RVOT); basal and mid inferior wall; apex; septum; basal anterolateral, basal inferolateral, mid anterolateral and mid inferolateral RV free wall (Figure). A standard definition of electrical scar was used (bipolar voltage ≤0.5 mV), and scar areas were manually delineated. Percentage of scar was defined by the ratio between scar area and the total segment area. ECG abnormal findings, such as epsilon wave and T-wave inversion in precordial leads, were measured before ablation procedure. Results Twenty-nine consecutive definite ARVC patients were included, among whose 24 had epicardial mapping in addition to endocardial mapping. When considering all segments, the epicardial scar (median:70%, interquartile range [IQR] 37-97%) was larger (p&amp;lt;0.0001) than the endocardial scar (9% [IQR] 0-32%). The higher percentage of epicardial scar was found in the basal inferolateral (100% [IQR] 73-100%), basal anterolateral (94% [IQR] 67-100%), RV free wall and lateral RVOT (89% [IQR] 48-100%) segments (Table). Transmural scar was observed mostly in basal inferolateral RV free wall (10 patients, 41%) and basal inferior wall (8 patients, 33%). Patients with major depolarization criteria had a higher percentage of epicardial and endocardial scar as compared to those with no or minor depolarization criteria (respectively 93% [IQR] 59-100% versus 62% [IQR] 28-89%, p&amp;lt;0.0001 and 17% [IQR] 0-42% versus 4% [IQR] 0-23%, p=0.001). There was no significant difference of the percentage of epicardial or endocardial scar in patients with and without major repolarization criteria (respectively 90% [IQR] 49-98% versus 84% [IQR] 43-100%, p=0.91 and 14% [IQR] 11-35% versus 16% [IQR] 0-41%, p=0.73). Conclusion In ARVC, the electrical abnormalities predominate in the basal epicardium. Patients with major depolarization criteria had a higher extent of epicardial and endocardial scar, but there was an association between scar extent and repolarization abnormalities.

Pulsed-field ablation for redo procedures after failed radiofrequency or cryo ablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulsed-field ablation (PFA) has recently been introduced for pulmonary vein isolation (PVI). It might also be of potential value for redo procedures after failed radiofrequency or cryo ablation for atrial fibrillation (AF). Purpose To describe our initial experience using a multipolar PFA catheter for redo procedures after failed AF ablation. Methods Consecutive patients undergoing a redo procedure for recurrent atrial arrhythmias at our institution using a multipolar PFA catheter from Mai 2021 until October 2022 were included. A 3D electro-anatomical bipolar voltage map was generated to identify pulmonary vein (PV) reconnection, quantify the level of isolation (antral vs. ostial isolation), and characterize the extent of extra-PV low-voltage tissue. In case of PV reconnection, re-isolation was performed using PFA, with at least four applications in both basket and flower configuration. In case of only ostial PV isolation, additional PFA applications in flower configuration were delivered to widen the isolation to a more antral level. If all veins were already isolated on an antral level and/or if low-voltage areas were found on the posterior wall, a posterior wall ablation was added with the same PFA device at the discretion of the operator. Results We identified 170 patients (mean age: 64 ±11years, 45 (27%) women), undergoing a redo procedure using PFA. The median number of previous ablations was 1 (range 1-6), the most recent ablation was performed using radiofrequency in 122 (72%), cryo in 42 (25%), and surgery in 5 (3%) patients. In 104 (61%) patients, at least one reconnected PV was found. In total, 244 of 680 PV (36%) showed reconnection. In addition to PV reisolation, additional antral applications were delivered in 205 of 436 still isolated veins (47%). Posterior wall ablation was added in 112 (66%) patients (43% in paroxysmal AF, 78% in persistent AF, Figure). Median procedure duration was 101 minutes (IQR 80-137). There was no cardiac tamponade, no stroke, and no esophageal fistula observed in this cohort. Conclusion For patients with recurrence after catheter ablation of atrial fibrillation, re-ablation using PFA is feasible and safe. Most common ablation targets were the pulmonary veins and the posterior wall. Whether the complementary effect of a different technology improves outcome needs further investigation.

Wave speed guided point-by-point cavo-tricuspid isthmus ablation to reduce ablation and fluoroscopy in typical atrial flutter

Abstract Funding Acknowledgements Type of funding sources: None. Background Ablation procedures for cavo-tricuspid isthmus (CTI) dependent typical atrial flutter (AFL) have traditionally been performed with conventional electrophysiology mapping guided by fluoroscopy. Three-dimensional electroanatomical mapping (EAM) systems have routinely been used to guide ablation of more complex arrhythmias, but in recent years, have been used for simple ablations with the aim of reducing irradiation. High voltage regions in the CTI have been described as a target in order to minimize procedure times, but there is a lack of knowledge regarding the utility of slow conduction zones for this purpose. Methods In a prospective cohort of patients undergoing 3D EAM assisted AFL ablation, we evaluated a novel strategy (NS) based on omnipolar vectors, using both wave speed and voltage information to focus radiofrequency (RF) lesions (see figure), and compared with a recent retrospective cohort of patients undergoing voltage-guided ablation (VG). Results A group of 26 consecutive patients with mean age 68±12 years and 88% male, underwent NS ablation, and were compared to 23 patients undergoing VG ablation, with no differences among patient characteristics. Of the 26 patients in group NS, 16 (53.9%) were successfully ablated targeting only 2 sites, representing the 2 most confluent areas of low wave speed and high voltage. A total of 24 (92.5%) were ablated successfully with targeting all sites of low wave speed. Only a single patient in the NS group required the completion of a classic CTI line. Average fluoroscopy time and radiation dose were lower in the NS group compared to VG group (1.1±2.4 min 19.5±41.7 mGray vs 8.2±10.2 min and 64.4±76.5 mGray, p=0.0014 and p=0.013, respectively). Furthermore, RF time trended towards reduction in the NS group. Conclusions A strategy based on targeting only areas of low wave speed is effective, limiting the need to complete a traditional CTI line, and reducing fluoroscopy in patients undergoin CTI ablation.