Arrhythmogenic Substrate In Patients Research Articles

Spatial relationship between left peri-atrial fat with underlying arrhythmogenic substrate in patients with atrial fibrillation - innocent bystander or culprit?

Abstract Introduction Peri-atrial fat may have pro-inflammatory and pro-fibrotic effects on atrial myocardium and increase the risk of developing atrial fibrillation. Consistent with prior evidence, we have previously shown that peri-atrial fat volume, but not fat attenuation (an imaging biomarker of inflammation), was associated with prevalent atrial fibrillation. Whether this association is secondary to "outside-to-inside" tissue cross talk with local adverse electrical remodelling of adjacent atrial cardiomyocytes is not known. Purpose In this novel proof of concept study, we aimed to identify a spatial relationship between left peri-atrial fat and potentially arrhythmogenic substrate (low voltage areas and slow conduction pathways) in the left atrial myocardium. Methods Contrast-enhanced cardiac computed tomography (CT) imaging and electroanatomic mapping, during coronary sinus pacing, were performed pre-ablation in atrial fibrillation patients (n=27). The left atrium and surrounding peri-atrial fat were segmented and quantified using seg3D2 and CEMRGapp. We performed registration of the electroanatomic map onto the CT-derived left atrial mesh using OpenEP and EP Workbench. Mean fat volume and attenuation around each electroanatomic point (within a 3mm radial region of interest) were correlated with local voltage and conduction velocity. Results A total of 24,839 electroanatomic points were registered onto the 3D CT-derived left atrial mesh, with a median of 935 points (range 673 to 1150) per patient. The average bipolar voltage and conduction velocity in the left atrium was 1.92±1.91 mV and 0.66±0.47 ms-1 respectively. In comparison to areas with little/no surrounding periatrial fat (Quartile 1, ≤0.93 mm3 fat per electroanatomic point), areas with the highest burden of fat (Quartile 4, ≥17.6 mm3) had significantly lower bipolar voltage (1.69±1.7 vs 2.09±2.0 mV, p<0.001) and conduction velocity (0.627±0.43 vs 0.700±0.47 ms-1, p<0.001). However, the overall correlation between periatrial fat volume with bipolar voltage (r=-0.06, p<0.001) and conduction velocity (r=-0.07, p<0.001) was weak. High, not low, fat attenuation (Quartile 4; >-46.5HU vs Quartile 1; ≤-75.5HU) was associated with increased bipolar voltage (2.23±2.1 vs 1.63±1.6 mV) and conduction velocity (0.703±0.42 vs 0.623±0.39 ms-1 respectively). Conclusion There is a weak correlation between periatrial fat and localized adverse electrical remodelling. The relationship between fat attenuation and electrophysiological properties was inverted. These findings confirm an association between peri-atrial fat burden but call question as to whether peri-atrial fat inflammation is implicated in atrial fibrillation pathogenesis.

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy

BackgroundAtrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. ObjectiveThe purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. MethodsIntraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. ResultsConduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%–3.6%] vs 2.6% [2.1%–6.4%], P = .541; CB: 1.7% [0.9%–3.1%] vs 1.5% [0.5%–2.8%], P = .600; LVA: 4.7% [1.6%–7.7%] vs 2.9% [2.1%–7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. ConclusionIn patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population.

Cardiovascular Magnetic Resonance for the Evaluation of Arrhythmogenic Substrates in Patients with Systemic Autoimmunity: An Update

Cardiovascular Magnetic Resonance for the Evaluation of Arrhythmogenic Substrates in Patients with Systemic Autoimmunity: An Update

Long-term toxicity of radiosurgery for ablation of ventricular tachycardia

Abstract Introduction There is a rising interest in using radiosurgery to modify arrhythmogenic substrate in patients with recurrent VT. However, data on the safety are still inadequate. Purpose This is update of toxicity evaluation based on the compilation from our case series, NIRA-VT and STAR-VT. Methods Between 2014 and March 2021, 36 patients (33 male, 3 females; mean age 66±10 years) with structural heart disease (ischemic cardiopathy, dilated cardiopathy or fibroma associated scar) from two electrophysiology centers in the Czech Republic (Trinec, Prague) underwent radiosurgery for recurrent VT. Radiosurgery was performed after at least one failed catheter ablation for VT. The critical part of the VT substrate was identified by electroanatomic mapping using a combination of voltage mapping, pace mapping, and activation mapping; and it was marked on a contrast-enhanced computer tomography study as a CTV. In NIRA-VT trial, CTV included scar based on PET/CT evaluation. Radiosurgery system with real-time motion tracking using the tip of the electrode of an indwelling defibrillator as a fiducial marker was used. A total radiation dose of 25 Gy was delivered to the ablation target in a single session during free breathing. Radiation-induced toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only patients with follow up longer than 6 months were included in long term radiation related side effects evaluation. Results The mean CTV and PTV were 26±11 ml and 41±22 ml respectively. No patient exhibited acute (up to 3 months) elevation of troponin, pericardial effusion, or a decrease in left ventricular ejection fraction from baseline. Four patients developed acute mild nausea, which waned after antiemetic drugs. Long-term radiation related side effects were evaluated in 19 patients. Two patients (11%) presented radiological signs of lung fibrosis in small area in close distance from PTV. There was no significant decrease in left ventricular ejection fraction during follow up. Six patients (33%) gradually developed significant progression of known mitral regurgitation after SBRT, two (11%) of them had to undergo mitral valve replacement (grade 4 toxicity). Two cases of esophagitis (12%) were seen with one radiation toxicity related death (grade 5 toxicity) due to the unresectable esophagi-pericardial fistula (6%). Conclusions Our data indicate the feasibility of radiosurgery, majority of patients presented no/mild radiation related toxicity and decrease of VT burden. However, we have seen three cases of grade 4,5 toxicity. To further investigate long-term safety and efficacy of radiosuergery for VT, enrolling into a randomized prospective study is in progress. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020

Transmural voltage gradient dispersion and heterogeneity in brugada syndrome phenotype - a novel workflow for advanced mapping using endocardial unipolar electrograms J-point elevation

Abstract Funding Acknowledgements Type of funding sources: None. Background Differential action potential duration shortening across the right ventricular (RV) myocardial wall is primarily responsible for the Brugada Syndrome (BrS) phenotype [1]. To date, data on electrical substrate characterization in humans with BrS phenotype is limited and risk evaluation is still controversial. Purpose We hypothesized that Uni-JEl mapping could be used as a marker of transmural voltage gradient dispersion resulting. Our aim was to evaluate Uni-JEl mapping in defining arrhythmogenic substrates in patients with BrS phenotype. Methods 12 patients were included in our analysis. 2 normal patients provided control data and 10 asymptomatic subjects with spontaneous type-1 BrS underwent 3D RV mapping (CARTO3 System, Biosense Webster). Among BrS patients we had 3 patients with arrhythmic events (aborted sudden death or appropriate ICD therapies) during follow-up (median 56, interquartile range: 46-74 months) and 7 patients without arrhythmic events. In the former group we had 1 patient with inducibility of VT/VF during EPS (EPS+) and 2 patients non-inducibles during EPS (EPS-), in the latter group we had 3 patients with EPS+ and 4 patients with EPS-. Electrophysiological data and signals were exported and OpenEP [2] was used to convert Carto proprietary data formats into Matlab format (Fig.1). Uni-JEl was calculated for each point map as the unipolar value at J point on surface electrocardiogram. Uni-JEl values were then interpolated in Paraview to create Uni-JEl maps, interpolating data points on the mesh cell (Fig.1). Finally, a region of interest (ROI) was selected and the calculation of mean Uni-JEI (MUni-JEI, as a measure of voltage gradient dispersion), interquartile range and range (intrqUni-JEI and ∆Uni-JEI, as markers of heterogeneity of dispersion) was performed. Results are shown as mean ± standard deviation for the group of BrS patients and the actual values for the two controls. Results BrS patients showed Muni-JEl, intrqUni-JEl and ∆Uni-JEI higher than controls (2.03 mV ± 0.31 mV vs 0,82 mV and 1,1 mV, 1.90 mV ± 0.82 mV vs 1,04 mV and 1,18 mV 6.26 mV ± 1.98 mV vs 3,54 mV and 4,01 mV, respectively). BrS patients with arrhythmic events during the follow-up showed higher intrqUni-JEl and the ∆Uni-JEI respect to BrS with EPS+ and without arrhythmic events during follow-up (2.31 mV ± 0.44 mV vs 0.78 mV ± 0.11 mV and 6.69 mV ± 2.27 mV vs 3.98 mV ± 0.31 mV). Figure 2 shows some examples of calculated Uni-JEl maps for each group under study. Conclusions In this work we introduced a novel workflow for the electrical substrate characterization of subjects with BrS phenotype. The results from our preliminary analysis indicate that a higher transmural voltage gradient dispersion and heterogeneity can be found in type-1 BrS with respect to normal subjects. Voltage gradient dispersion heterogeneity could be used to better recognize high risk BrS patients regardless of VT/VF inducibility during EPS.

Relevant anatomy of epicardial space for the electrophysiologists

The arrhythmogenic substrate in patients with Chagas cardiomyopathy, arrhythmogenic dysplasia, postmyocarditis nonischemic dilative cardiomyopathy as well as after extensive posterior or anterior wall myocardial infarction is predominantly located epicardially. This can necessitate epicardial access for an effective, substrate-based catheter ablation of the ventricular tachycardia (VT). Anterior percutaneous epicardial puncture represents the standard approach for epicardial VT ablation. The most important anatomical particularities that must be taken into account when performing an epicardial puncture or epicardial VT ablation are epicardial coronary arteries, left phrenic nerve and epicardial fat. The typical anatomic characteristics of the epicardial structures and resulting considerations for epicardial access are discussed here in detail.

Dark-blood late gadolinium enhancement CMR improves detection of papillary muscle fibrosis in patients with mitral valve prolapse

PurposePapillary muscle fibrosis may act as an arrhythmogenic substrate in patients with mitral valve prolapse (MVP). Previous studies used conventional bright-blood late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) imaging to assess papillary muscle fibrosis, although this technique suffers from poor scar-to-blood contrast which may limit its sensitivity, in contrast to dark-blood LGE. This study sought to compare bright-blood and dark-blood LGE for the detection of papillary muscle fibrosis in patients with MVP. Method60 patients with known isolated MVP referred for CMR were prospectively recruited. A routine CMR protocol was used to obtain cine imaging, dark-blood LGE and bright-blood LGE in three long-axis views and a stack of short-axis views. Flow mapping of the proximal aorta was performed to calculate mitral regurgitant volume. Images were analysed for cardiac volumes, ejection fraction, mitral regurgitation severity, MVP characteristics (mitral annular disjunction, prolapse volume) and presence of LGE at the papillary muscles and myocardium. ResultsDark-blood LGE detected significantly more subjects with LGE at the papillary muscles than bright-blood LGE (35% vs 15%, p = 0.002). There was no difference between LGE techniques regarding myocardial (non-papillary muscle) fibrosis (present in 25% each). No statistical differences were observed between patients with or without LGE at the papillary muscles regarding demographics, clinical data (including ventricular arrhythmia) and MVP characteristics. Furthermore, no association was found between LGE at the papillary muscles and at the myocardium. ConclusionsCompared to bright-blood LGE, dark-blood LGE CMR improves the detection of LGE at the papillary muscles in patients with MVP.

Interleukin-6-Mediated-Ca2+ Handling Abnormalities Contributes to Atrial Fibrillation in Sterile Pericarditis Rats.

Pre-existing Ca2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 μg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo. IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.

Role of endocardial ablation in eliminating an epicardial arrhythmogenic substrate in patients with Brugada syndrome.

Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF). The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation. This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs. EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively). EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.

A novel algorithm for 3-D visualization of electrogram duration for substrate-mapping in patients with ischemic heart disease and ventricular tachycardia.

BackgroundMyocardial slow conduction is a cornerstone of ventricular tachycardia (VT). Prolonged electrogram (EGM) duration is a useful surrogate parameter and manual annotation of EGM characteristics are widely used during catheter-based ablation of the arrhythmogenic substrate. However, this remains time-consuming and prone to inter-operator variability. We aimed to develop an algorithm for 3-D visualization of EGM duration relative to the 17-segment American Heart Association model.MethodsTo calculate and visualize EGM duration, in sinus rhythm acquired high-density maps of patients with ischemic cardiomyopathy undergoing substrate-based VT ablation using a 64-mini polar basket-catheter with low noise of 0.01 mV were analyzed. Using a custom developed algorithm based on standard deviation and threshold, the relationship between EGM duration, endocardial voltage and ablation areas was studied by creating 17-segment 3-D models and 2-D polar plots.Results140,508 EGMs from 272 segments (n = 16 patients, 94% male, age: 66±2.4, ejection fraction: 31±2%) were studied and 3-D visualization of EGM duration was performed. Analysis of signal processing parameters revealed that a 40 ms sliding SD-window, 15% SD-threshold and >70 ms EGM duration cutoff was chosen based on diagnostic odds ratio of 12.77 to visualize rapidly prolonged EGM durations. EGMs > 70 ms matched to 99% of areas within dense scar (<0.2 mV), in 95% of zones within scar border zone (0.2–1.0 mV) and detected ablated areas having resulted in non-inducibility at the end of the procedure. Ablation targets were identified with a sensitivity of 65.6% and a specificity of 94.6% avoiding false positive labeling of prolonged EGMs in segments with healthy myocardium.ConclusionThe novel algorithm allows rapid visualization of prolonged EGM durations. This may facilitate more objective characterization of arrhythmogenic substrate in patients with ischemic cardiomyopathy.

Intracardiac Echocardiography to Guide Non-fluoroscopic Electrophysiology Procedures.

Intracardiac echocardiography (ICE) is the most practical method for online imaging during electrophysiological procedures. It allows guiding of complex catheter ablation procedures together with electroanatomical mapping systems, either with minimal or with zero fluoroscopy exposure. Besides safe and reproducible transseptal puncture, ICE helps to assess location and contact of the tip of the ablation catheter relative to specific anatomical structures. Another option is visualization of the arrhythmogenic substrate in patients with ventricular arrhythmias. This article describes the clinical utility of ICE in non-fluoroscopic electrophysiology procedures more in detail.

Comparison of Unipolar and Bipolar Voltage Mapping for Localization of Left Atrial Arrhythmogenic Substrate in Patients With Atrial Fibrillation.

Background: Presence of left atrial low voltage substrate in bipolar voltage mapping is associated with increased arrhythmia recurrences following pulmonary vein isolation for atrial fibrillation (AF). Besides local myocardial fibrosis, bipolar voltage amplitudes may be influenced by inter-electrode spacing and bipole-to-wavefront-angle. It is unclear to what extent these impact low voltage areas (LVA) in the clinical setting. Alternatively, unipolar electrogram voltage is not affected by these factors but requires advanced filtering.Objectives: To assess the relationship between bipolar and unipolar voltage mapping in sinus rhythm (SR) and AF and identify if the electrogram recording mode affects the quantification and localization of LVA.Methods: Patients (n = 28, 66±7 years, 46% male, 82% persistent AF, 32% redo-procedures) underwent high-density (>1,200 sites, 20 ± 10 sites/cm2, using a 20-pole 2-6-2 mm-spaced Lasso) voltage mapping in SR and AF. Bipolar LVA were defined using four different thresholds described in literature: <0.5 and <1 mV in SR, <0.35 and <0.5 mV in AF. The optimal unipolar voltage threshold resulting in the highest agreement in both unipolar and bipolar mapping modes was determined. The impact of the inter-electrode distance (2 vs. 6 mm) on the correlation was assessed. Regional analysis was performed using an 11-segment left atrial model.Results: Patients had relevant bipolar LVA (23 ± 23 cm2 at <0.5 mV in SR and 42 ± 26 cm2 at <0.5 mV in AF). 90 ± 5% (in SR) and 85 ± 5% (AF) of mapped sites were concordantly classified as high or low voltage in both mapping modes. Discordant mapping sites located to the border zone of LVA. Bipolar voltage mapping using 2 vs. 6 mm inter-electrode distances increased the portion of matched mapping points by 4%. The unipolar thresholds (y) which resulted in a high spatial concordance can be calculated from the bipolar threshold (x) using following linear equations: y = 1.06x + 0.26mV (r = 0.994) for SR and y = 1.22x + 0.12mV (r = 0.998) for AF.Conclusion: Bipolar and unipolar voltage maps are highly correlated, in SR and AF. While bipole orientation and inter-electrode spacing are theoretical confounders, their impact is unlikely to be of clinical importance for localization of LVA, when mapping is performed at high density with a 20-polar Lasso catheter.

Late gadolinium-enhanced cardiac magnetic resonance in repaired tetralogy of Fallot: characterization of the right ventricular arrhythmogenic substrate

Abstract Introduction Ventricular arrhythmias are one of the main causes of morbidity and mortality in patients with repaired tetralogy of fallot (rTF). These life-threatening arrhythmias are related to specific isthmuses of viable tissue between areas of scar and/or valve rings of the right ventricle (RV) that have been already described in the literature. Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) has proven useful in characterizing the arrhythmogenic substrate in several heart diseases. Nevertheless, LGE-CMR evidence in patients with rTF is scarce. Purpose To compare the characterization of the ventricular arrhythmogenic substrate by means of LGE-CMR and electroanatomic mapping (EAM) of the right ventricle (RV) in patients with rTF. Methods Unicentric and observational study of consecutive patients with rTF who underwent LGE-CMR performed with 1.5T equipment and RV high-density voltage map, performed with multipolar catheter and completed with contact force-sensing catheter. The LGE-CMR segmentation was performed with dedicated software. The extent (area and percentage) and location of the dense scar (defined as &amp;lt;0.5 mV in EAM and &amp;lt;40% of the maximum intensity pixel in LGE-CMR) were compared, as well as the location of the isthmuses of viable tissue. Results Eight patients were included (45.7±10.4 years; 50% male). The extent of the scar was 20.7±13.6 cm2 (15.1±9.3%) by EAM and 21.7±8.8 cm2 (11.8±7.6%) by LGE-CMR. There was an absolute correlation regarding the location of the dense scar and the distribution of the isthmuses of viable tissue. The quantification of the dense scar evidenced a positive linear correlation between both techniques (area correlation: ρ = 0.71, p=0.047; percentage correlation: ρ = 0.88; p=0.004). The average time spent for the segmentation of the LGE-CMR with the dedicated software was 19.9±3.0 minutes. Conclusions Characterization of the RV arrhythmogenic substrate in patients with rTF with LGE-CMR is feasible. An absolute association regarding the location of the dense scar and the distribution of the isthmuses of viable tissue was observed when compared to the RV high-density EAM. In the same way, a statistically significant linear correlation in the quantification of the dense scar between both techniques was documented. LGE-CMR and EAM of two patients with rTF Funding Acknowledgement Type of funding source: None

Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation.

Aims Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation–contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF.Methods and results Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25–8 Hz).Conclusions Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.

Detection of arrhythmogenic substrate within QRS complex in patients with cardiac sarcoidosis using wavelet-transformed ECG.

Signal-averaged electrocardiography (SAECG) has been known to be useful for prediction of lethal ventricular arrhythmias (VA). However, this technique has limitations in patients with intraventricular conduction disturbance (IVCD), which is common in cardiac sarcoidosis (CS). Meanwhile, wavelet-transformed ECG (WTECG) has been reported to be useful for detecting arrhythmogenic substrate hidden within QRS complex. The objective of this study was to assess the utility of WTECG for detecting arrhythmogenic substrate in patients with CS. Forty-four CS patients including 18 patients with VA were retrospectively investigated. The parameters on the signal-averaged electrocardiography (SAECG) and the power of frequency components on WTECG were compared between VA group and non-VA group. Eighteen patients have VA (VT: n = 17, VF: n = 1). LP were detected in 17 in VA group and 24 in non-VA group. WTECG showed that high-frequency components (HFC; 80-150Hz) were developed in VA group. Peak power value at 150Hz (P150) was significantly higher in VA group than that in non-VA group (442.9 ± 160.2 vs 316.7 ± 100.8, p = 0.006). The receiver operating characteristic (ROC) curve analysis showed an optimal cutoff point of 336 of P150 for detecting patients with VA, with 82.4% sensitivity, 61.5% specificity, and area under the curve of 0.74 (95% confidence interval [CI] 0.59-0.89). WTECG may be useful for detecting CS patients who are prone to VA.

Does Ventricular Tachycardia Ablation Targeting Local Abnormal Ventricular Activity Elimination Reduce Ventricular Fibrillation Incidence?

Various strategies for ablation of ventricular tachycardia (VT) have been described, but their impact on ventricular fibrillation (VF) is largely unknown. The aim of our study was to assess the effect of substrate-based VT ablation targeting local abnormal ventricular activity (LAVA) on recurrent VF events in patients with structural heart disease. A retrospective 2-center study was performed on patients with structural heart disease and both VT and VF, with incident VT ablation procedures targeting LAVAs. Generalized estimating equations with a Poisson loglinear model were used to assess the impact of catheter ablation on VF episodes. The change in VF events before and after catheter ablation was compared with matched controls without ablation. From a total of 686 patients with an incident VT ablation procedure targeting LAVAs, 21 patients (age, 57±14 years; left ventricular ejection fraction, 30±10%) had both VT and VF and met inclusion criteria. A total of 80 VF events were recorded in the implantable cardioverter-defibrillator logs the 6 months preceding ablation. Complete and partial LAVA elimination was achieved in 11 (52%) and 10 (48%) patients, respectively. Catheter ablation was associated with a highly significant reduction in VF recurrences (P<0.0001), which were limited to 3 (14%) patients at 6 months. The total number of VF events thereby decreased from 80 to 3, from a median of 1.0 (range, 1-29) to 0.0 (range, 0-1) in the 6 months before and after ablation, respectively. The reduction in VF events was significantly greater in patients with catheter ablation compared with 21 matched controls during 6-month periods following and preceding a baseline assessment (Poisson β-coefficient, 1.39; P=0.0003). Substrate-guided VT ablation targeting LAVAs may be associated with a significant reduction in recurrent VF, suggesting that VT and VF share overlapping arrhythmogenic substrates in patients with structural heart disease.

P605Correlation of left atrial phasic transport function and arrhythmogenic substrate in patients with atrial fibrillation: cardiac magnetic resonance feature tracking and bipolar voltage mapping

Abstract Background Bipolar voltage mapping is a widely accepted approach to identify areas of arrhythmogenic substrate in patients presenting for atrial fibrillation (AF) ablation. However, until now little is known about the correlation of left atrial (LA) bipolar voltage distribution and LA transport function. Purpose To study the impact of LA low voltage zones (LVZ) on LA transport function. Methods 107 consecutive patients presenting for ablation of symptomatic AF (34 paroxysmal AF, 73 persistent AF) were prospectively enrolled. Each patient underwent cardiac magnetic resonance imaging (CMR) within 24 hours prior to the ablation procedure. 59 patients were in sinus rhythm (SR) and 48 in AF. LA phasic indexed volumes (LAVi) and ejection fractions were calculated using biplane area length formula. In addition LA phasic strains and strain rates were analyzed using dedicated software (Figure 1A &amp; B). LA bipolar voltage mapping was performed prior to beginning of ablation in sinus rhythm using a 3-dimensional mapping system and LVZ were defined as areas of bipolar voltage &lt;0.5mV. Results LVZ were present in 47 patients (23 in SR). The area of LVZ was 14.6cm2 (5.3–34.0). For patients in AF at the time of CMR only elevated minimal and maximal LAVi (p=0.001 and p=0.002 respectively) but no LA functional parameter was predictive for the occurrence of LVZ. In contrast for patients in SR all LA phasic volumes (endsystolic, pre atrial contraction and enddiastolic LAVi) and LA function parameters (passive, active and total ejection fraction (EF), reservoir, conduit and booster pump strains and strain rates) were predictive for the occurrence of LVZ. After clustered and pooled multivariate logistic regression only impaired booster pump strain rate was still predictive for occurrence of LVZ (OR 0.974, 95% CI 0.950–0.998, p=0.036). In addition Pearson correlation analysis revealed a strong link between LA booster pump functional parameters and cm2 expansion of LVZ areas: LA active EF, LA booster pump strain and SR (r=−0.42, p=0.044; r=−0.47, p=0.024; r=−0.65, p=0.001 [Figure 1C] respectively). Conclusion For patients in SR LA transport function is closely linked to the occurrence of LA LVZ and outperforms LA volumetric measurements for the prediction of LA LVZ. Furthermore LA booster pump function parameters show robust correlation to the extension of LA LVZ.

P1030Elevated baseline brain natriuretic peptide level was associated with poor outcome after multiple catheter ablation for paroxysmal atrial fibrillation

Abstract Background Serum Brain Natriuretic Peptide (BNP) level is associated with various cardiovascular events. Because elevated BNP level reflects increased left ventricular end-diastolic pressure and LA pressure promoting left atrial (LA) remodeling, BNP level might be associated with the extent of arrhythmogenic substrate in patients with atrial fibrillation (AF). We hypothesized that elevated BNP level has impact on outcome after catheter ablation (CA) for AF. Purpose We investigated the impact of baseline BNP level on outcome after multiple CA for paroxysmal atrial fibrillation (PAF), and assessed the association between baseline BNP level and extent of LA remodeling. Methods This was a retrospective, single-center observational study. A total of 287 patients who underwent CA for PAF in our institute from March 2012 to March 2014. All patients had dataset of baseline BNP level and LA volume measured by multi-detector computed tomography (MDCT) in sinus rhythm. First we performed receiver operating characteristic (ROC) analysis for recurrence after multiple CA and obtained the best cut-off value of BNP. Patients were divided into Low BNP and High BNP group based on BNP cut-off value, and AF-free survival was analyzed with log-rank test. To assess the impact of BNP level on recurrence, multivariate Cox regression model were performed. Finally, we assessed the extent of baseline LA remodeling in low BNP and high BNP group. Results During follow-up period, AF recurred in 65/287 patients (26.2%) after multiple CA procedure (follow up 3.4 [2.2, 4.0] years, total number of sessions: 1.39±0.63). Patients with recurrence had greater baseline BNP than those without recurrence (99.8 pg/mL [30.0, 128] vs. 60.7 pg/mL [17.3, 80.8], recurrence vs. no-recurrence, P&lt;0.05). In ROC analysis, baseline BNP had mild accuracy for the prediction of recurrence (AUC: 0.63, P=0.002, best cut-off value: 57.3 pg/mL). We divided patients into High BNP group (BNP≥57.3, N=106) and Low BNP group (BNP&lt;57.3, N=181). AF-free survival was higher in Low BNP than in High BNP (Figure 1) (83.4% vs. 67.0%, Low vs. High, P&lt;0.001). After adjustment with age, gender, hypertension, heart failure, body mass index, LA diameter and LV ejection fraction, High BNP (BNP≥57.3) was associated with recurrence (Hazard ratio: 2.31, 95% CI 1.42–3.75, P&lt;0.001). In baseline parameters of LA remodeling measured with MDCT, Low BNP group had higher LA emptying fraction (41.7±9.5 vs. 32.0±8.5%, Low vs. High, P&lt;0.001) and lower indexed maximum LA volume (48.5±12.0 vs. 61.3±16.7 mL/m2, P&lt;0.001) (Figure 2). Conclusion Baseline serum BNP level was associated with recurrence after multiple procedures for PAF. The baseline extent of LA remodeling was greater in High BNP than in Low BNP. Elevated BNP level might reflect the severe LA remodeling causing ablation-refractory AF even after multiple CA. The preoperative assessment of BNP might be helpful for prediction of multiple CA outcome.

3256Long-term safety of stereotactic body radiotherapy for ablation of ventricular tachycardia: a multicentric study

Abstract Background Contemporary stereotactic body radiotherapy (SBRT) enables to accurately concentrate high radiation doses to small volumes of myocardial tissue. There is a rising interest in using SBRT to modify arrhythmogenic substrate in patients with previously failed radiofrequency catheter ablation. However, data on the safety of SBRT for the treatment of VT are lacking. Purpose This study evaluated the long-term safety of SBRT for the treatment of VT. Methods SBRT was performed in patients with structural heart disease and failed catheter ablation for VT. The critical part of the VT substrate was identified by electroanatomic mapping (EAM) using a combination of voltage mapping, pace mapping, and activation mapping; and it was marked on a contrast-enhanced computer tomography study as a target for radioablation. SBRT was performed using a radiosurgery system with real-time motion tracking using the tip of the electrode of an indwelling defibrillator as a fiducial marker. A total radiation dose of 25 Gy was delivered to the ablation target in a single session during free breathing. Radiation-induced toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Between 2014 and 2018, 18 patients from two electrophysiology centres underwent SBRT for recurrent, drug-resistant VT after previously failed catheter ablation (17 male, 1 female; mean age 63±9 years; 14 ischemic cardiopathy, 3 dilated cardiopathy, 1 fibroma). The mean volume of the ablation target was 34±17 ml, and the mean duration of the therapy was 78±14 minutes. No patient exhibited acute (up to 3 months) elevation of troponin, pericardial effusion, or a decrease in left ventricular ejection fraction from baseline. Four patients developed acute mild nausea, which waned after antiemetic drugs. Two patients gradually developed significant progression of mitral regurgitation after SBRT. One of the patients was treated medically (grade 3 toxicity), but the other had to undergo mitral valve replacement (grade 4 toxicity). No other cardiac or pulmonary radiation related toxicity was observed during a median follow-up of 23 months. Three patients died at 54, 43, and 18 month after SBRT. None of the deaths was related to VT recurrence or complication of SBRT. CARTO, Radiation dose and Survival Conclusions This is the largest series of patients who underwent EAM-guided SBRT for VT as a bailout therapy after previously failed radiofrequency catheter ablation. Our preliminary data indicate the feasibility and safety of the procedure. To further investigate long-term safety and efficacy of SBRT for VT, we initiated a prospective multicentric study (NCT03819504). Acknowledgement/Funding Supported by RVO-FNOs/2014

Image-based criteria to identify the presence of epicardial arrhythmogenic substrate in patients with transmural myocardial infarction

Patients with transmural myocardial infarction (MI) who undergo endocardial-only substrate ablation are at increased risk for ventricular tachycardia recurrence. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) can be used to assess infarct transmurality (IT). However, the degree of IT associated with an epicardial arrhythmogenic substrate (AS) has not been determined. The purpose of this study was to determine the degree of IT observed by LGE-CMR and multidetector computed tomography (MDCT) that predicts the presence of epicardial AS. The study included 38 post-MI patients. Ten patients with a subendocardial infarction underwent endocardial-only mapping, and 28 with a classic transmural MI (C-TMI), defined as hyperenhancement ≥75% of myocardial wall thickness (WT), underwent endo-epicardial mapping. LGE-CMR/MDCT data were registered to high-density endocardial or epicardial maps to be analyzed for the presence of AS. Of the 28 post-MI patients with C-TMI, 18 had epicardial AS (64%) and 10 (36%) did not. An epicardial scar area ≥14 cm2 on LGE-CMR identified patients with epicardial AS (sensitivity 1, specificity 1). Mean WT in the epicardial scar area in these patients was lower than in patients without epicardial AS (3.14 ± 1.16 mm vs 5.54 ± 1.78 mm; P = .008). A mean WT cutoff value ≤3.59 mm identified patients with epicardial AS (sensitivity 0.91, specificity 0.93). An epicardial scar area ≥14 cm2 on LGE-CMR and mean CT-WT ≤3.59 mm predict epicardial AS in post-MI patients.