Epicardial Origin Research Articles

Risk Factors for PVC Induced Cardiomyopathy and Post-Ablation Left Ventricular Systolic Dysfunction Reversibility: A Systematic Review and Meta-Analysis of Observational Studies.

Premature ventricular complex (PVC) induced cardiomyopathy (PVC-CMP) and exacerbated left ventricular systolic dysfunction (LVSD) are common in clinical scenarios. However, their precise risk factors are currently unclear. We performed a systematic review of PubMed, EMBASE, Web of Science, and Chinese-based literature database (CBM) to identify observational studies describing the factors associated with PVC-CMP and post-ablation LVSD reversibility. A total of 25 and 12 studies, involving 4863 and 884 subjects, respectively, were eligible. We calculated pooled multifactorial odds ratios (OR) and 95% confidence intervals (CI) for each parameter using random-effects and fixed-effects models. The results showed that 3 independent risk factors were associated with PVC-CMP: being asymptomatic (OR and 95% CI: 3.04 [2.13, 4.34]), interpolation (OR and 95% CI: 2.47 [1.25, 4.92]), and epicardial origin (epi-origin) (OR and 95% CI: 3.04 [2.13, 4.34]). Additionally, 2 factors were significantly correlated with post-ablation LVSD reversibility: sinus QRS wave duration (QRSd) (OR and 95% CI: 0.95 [0.93, 0.97]) and PVC burden (OR and 95% CI: 1.09 [0.97, 1.23]). the relatively consistent independent risk factors for PVC-CMP and post-ablation LVSD reversibility are asymptomatic status, interpolation, epicardial origin, PVC burden, and sinus QRS duration, respectively.

Epicardial catheter ablation of ventricular tachycardia in patients of acm - from a university hospital report in switzerland

Abstract Background Arrhythmogenic left ventricular cardiomyopathy (ALVC) as a subtype of arrhythmogenic cardiomyopathy (ACM) is increasingly being recognized. Cardiac magnetic resonance (CMR) has emerged as the primary imaging modality for the diagnosis of ACM. In patients with right-dominant ACM (ARVC) and recurrent sustained ventricular tachycardia (VT), endocardial +/-epicardial ablation yields good clinical outcomes in the long-term. However, studies on VT ablation in ACM with LV involvement are scarce. Purpose We sought to investigate clinical outcomes of VT ablation in ACM patients with LV involvement. Methods The study included patients from the Zurich ACM Registry who met 2020 "Padua Criteria" for ACM and underwent VT ablation between January 2018 and July 2023. Epicardial ablation was performed in patients with recurrent sustained VT despite endocardial ablation, those lacking and endocardial substrate or if the ECG of the VT / substrate on CMR was suggestive of an epicardial origin. Catheter ablation was guided by activation/entrainment mapping for mappable VT, and pace mapping/voltage mapping during sinus rhythm for unmappable VT. Consecutive follow-up of all patients was performed according to our protocol. Results Twenty-one ACM patients underwent n=24 VT ablation procedures. Of those 20 patients, 6 patients (30%) had LV involvement on CMR. Eight (33%) patients underwent epicardial +/- endocardial ablation. Among patients receiving epicardial ablation, 3 patients (38%) had LV involvement. These three underwent a single ablation procedure, which was epicardial only. Total follow-up was 30 months (range 4-43). Three-month sustained VT/VF recurrence rates were 12% in the ACM group with LV involvement vs 25% in ACM without LV involvement. All patients with sustained VT/VF recurrence underwent repeat ablation via an epicardial approach within 3 months and were free of sustained VT/VF thereafter during a median follow-up of 12 months. One-year recurrence rate did not differ between ACM patients with LV involvement vs. without LV involvement (7.7% vs 8.3%, P＝0.117). Seven out of eight epicardial ablations achieved freedom from VT/VF after one-year follow-up. One ARVC patient with previous endocardial ablation had recurrent VT one month after epicardial ablation, which was free of VT after Flecainide combined with beta-blocker. No significant differences were found in the use of beta-blockers and antiarrhythmic drugs between both groups (ACM with LV involvement vs. without LV involvement) at baseline and during one-year follow-up. Conclusions Single or adjuvant epicardial substrate ablation of VT in arrhythmogenic cardiomyopathy is promising in terms of postprocedural VT free survival, especially in patients with left ventricular involvement demonstrated by CMR.Figure 1Figure 2

Investigation into the importance of using natural PVCs and pathological models for potential-based ECGI validation.

Introduction: Premature ventricular contractions (PVCs) are one of the most commonly targeted pathologies for ECGI validation, often through ventricular stimulation to mimic the ectopic beat. However, it remains unclear if such stimulated beats faithfully reproduce spontaneously occurring PVCs, particularly in the case of the R-on-T phenomenon. The objective of this study was to determine the differences in ECGI accuracy when reconstructing spontaneous PVCs as compared to ventricular-stimulated beats and to explore the impact of pathophysiological perturbation on this reconstruction accuracy. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, and local hyperkalemia was induced through perfusion of a high-K+ solution (8mM) into the LAD. Recordings were taken simultaneously from the heart and tank surfaces during ventricular pacing and during spontaneous PVCs (including R-on-T), both at baseline and high K+. Epicardial potentials were reconstructed from torso potentials using ECGI. Results: Spontaneously occurring PVCs were better reconstructed than stimulated beats at baseline in terms of electrogram morphology [correlation coefficient (CC) = 0.74 ± 0.05 vs. CC = 0.60 ± 0.10], potential maps (CC = 0.61 ± 0.06 vs. CC = 0.51 ± 0.12), and activation time maps (CC = 0.86 ± 0.07 vs. 0.76 ± 0.10), though there was no difference in the localization error (LE) of epicardial origin (LE = 14 ± 6 vs. 15 ± 11mm). High K+ perfusion reduced the accuracy of ECGI reconstructions in terms of electrogram morphology (CC = 0.68 ± 0.10) and AT maps (CC = 0.70 ± 0.12 and 0.59 ± 0.23) for isolated PVCs and paced beats, respectively. LE trended worse, but the change was not significant (LE = 17 ± 9 and 20 ± 12mm). Spontaneous PVCs were less well when the R-on-T phenomenon occurred and the activation wavefronts encountered a line of block. Conclusion: This study demonstrates the differences in ECGI accuracy between spontaneous PVCs and ventricular-paced beats. We also observed a reduction in this accuracy near regions of electrically inactive tissue. These results highlight the need for more physiologically realistic experimental models when evaluating the accuracy of ECGI methods. In particular, reconstruction accuracy needs to be further evaluated in the presence of R-on-T or isolated PVCs, particularly when encountering obstacles (functional or anatomical) which cause line of block and re-entry.

PO-03-219 ANGIOGRAPHIC ASSESSMENT OF CORONARY VENOUS SYSTEM FOR CANNULATION: LESSONS FROM HIGH-SPEED ROTATIONAL RETROGRADE ANGIOGRAPHY

Venous ethanol ablation (VEA) is a novel effective therapy method for radiofrequency ablation refractory ventricular arrhythmias, especially the epicardial or intramural origin sites. Multielectrode catheters and balloons are usually used for mapping and VEA. However, there is limited data on the size and the collateral condition of the main tributaries of coronary venous system (CVS) in non-heart failure patients. To evaluate the size of the main tributaries of CVS for making better cannulation strategies via rotational retrograde angiography. We measured and analyzed the size of the great cardiac vein (GCV), the anterior ventricular vein (AIV) (including the first septal branch of AIV), and the main tributaries draining the posterior and lateral wall of the left ventricle in patients undergoing electrophysiology study. The diameters of the main tributaries of CVS were measured in the view that offered the least foreshortening and covering. High-speed rotational CVS angiography was performed on 60 patients. The diameter of GCV at the level of Vieussens valve (the “ostium” of GCV) and the distal end of GCV (junction of GCV-AIV) was larger in males than females (6.6±1.2 vs. 5.6±1.3mm, p=0.005; 5.1±0.9 vs. 4.6±0.8, p=0.045, respectively) while other tributaries showed no difference on genders. The diameter of middle cardiac vein (MCV), posterior vein (PV), lateral vein (LV), anterior ventricular vein and the first septal vein was 4.9±1.3, 3.0±1.0, 2.9±1.0, 4.4±1.0 and 1.4±0.7, respectively). 96% patients had collateral between main tributaries. Over half of them (62.5%) had collateral between MCV and AIV. We provide a systematic description and size measurement of CVS. Rotational angiography could be useful for the comprehensive assessment of CVS before ethanol ablation.

PO-04-201 A CASE OF PVC OCCURRING RIGHT BUNDLE BRANCH BLOCK AND PR INTERVAL PROLONGED DURING ETHANOL ABLATION VIA THE CORONARY VENOUS SYSTEM

Ethanol ablation via the coronary venous system (CVS) has been reported to be effective and safe as a novel therapy for ventricular arrhythmias, especially for the epicardial and intramural origin sites. Previous studies reported no heart block complications during retrograde coronary venous ethanol ablation, neither atrioventricular block (AVB) nor other types of conductive system block. N/A A 67-year-old female with symptomatic and drug-refractory premature ventricular contractions (PVCs) was admitted for ablation therapy. The PVC burden was 31.7%. The 12-lead ECG showed a PVC with LBBB, inferior axis with a precordial transition in lead V3, and QS pattern in lead I. The QRS duration of PVC was 143ms. The Q-wave ratio of lead aVL/aVR was 1.47. Endocardial mapping was performed using a 3.5mm open-irrigated-tip catheter (ThermoCool, Biosense Webster, CA, USA). The earliest activation time was -8ms and -10ms pre-QRS at the septal aspect of right ventricular outflow tract (RVOT) and the left coronary sinus (LCC), respectively (Fig 1A). Ablation with 35-40W, 45-50°C was attempted but no response. We considered it might be an intramural origin site. The CVS angiography was performed and the ablation catheter was positioned in LCC for reference (Fig 1B). The earliest activation time (-27ms) was mapped in a septal branch of the anterior interventricular vein (AIV) with a 3.3F quadripolar catheter and local pace mapping matched well. Selective angiography confirmed the quadripolar catheter was in the septal branch rather than AIV (Fig 1C-D). A balloon was used to deliver ethanal and prevent its backflow to AIV. 1ml 96% ethanol was infused slowly (Fig 1E-F). PVC was eliminated immediately as soon as the ethanol infusion. But we noticed the PR interval prolonged from 178 to 190ms. More ethanol was injected carefully to consolidate the effect but we stopped infusion after a total of 2.5ml ethanol because the ECG showed complete RBBB and PR interval prolonged further to 202ms. RBBB and I° AVB were persistent during the whole hospitalization for 3 days. However, at 1-month follow-up, the QRS morphology returned to normal and the PR interval shortened to 172ms (Fig 1G). 24-hour Holter showed no recurrence. Ethanol ablation via the CVS also might induce heart block complications due to the adjacent anatomical position with the conductive system, even though it might be reversible. Operators should be cognizant of the potential risk.

987 VENTRICULAR TACHYCARDIA CATHETER ABLATION: THE ROLE OF ARRHYTHMIA INTERRUPTION DURING RADIOFREQUENCY EROGATION.

Abstract Background Due to the complexity of the underlying substrate and to the difficulty in characterizing the arrhythmia mechanism and circuitry, every ventricular tachycardia (VT) catheter ablation (CA) represents a challenge. Nowadays VT CA is an increasingly recommended and used procedure. Objective Investigate whether VT interruption during radiofrequency (RF) delivery can be regarded as a marker indicating a lower risk VT recurrence at follow-up. Methods We conducted a retrospective cohort study and we enrolled 69 patients with VTs treated with CA using RF energy, from November 2018 to July 2022. First, in all patient substrate and late potential map was performed; than VT induction was attempted. In patients in whom activation mapping could be performed, we first targeted VT interruption, followed by substrate modification (fragmented/late potential elimination and/or dechanneling of the entire pathologic zone) [group1]. In 15 patients, it was not possible to perform activation mapping due to the poor hemodynamic VT tolerance and/or to the absence of VT inducibility with programmed ventricular stimulation. In these cases, substrate CA was performed, aiming to eliminate fragmented and/or late potentials [group2]. Recurrences were assessed with ICD in office interrogations and remote monitoring for a median of 12 (IQR 5-20) months of follow-up. Results Sixty-nine patients were included in the study. Respectively for the group1 and for the group2, the mean age at baseline was 60 ± 18,3 and 63 ± 12,3 p > 0,05) and the mean left ventricular ejection fraction was 41,3 ± 12,6% and 38,2 ± 11,8% (p > 0,05). In 41 (59%) patients, the indication for the procedure was electrical storm refractory to pharmacological therapies or multiple ICD shocks due to VT/VF. 12 (17%) patients underwent endo-epicardial CA due to the presumed epicardial VT origin and only 9 (13%) underwent right ventricular CA. Among the 31 patients in which it was possible to interrupt the arrhythmia through RF delivery, we observed 9 (23%) sustained VT recurrence at follow-up. Among the 38 patients in which VT was not interrupted with RF delivery or the VT had poor hemodynamic tolerance, there were 16 (42%) sustained VT recurrences at follow-up. Risk of recurrence at follow-up was numerically lower in patients in which VT was interrupted with RF delivery during the procedure, but not statistically significant (p value > 0,05). Conclusions In patients undergoing CA for VTs, activation mapping is useful to enhance the understanding of the arrhythmia circuitry. Our preliminary results seem to suggest that VT interruption during RF delivery may represent a positive prognostic marker, pointing to better outcomes and lower recurrence rates, even if the results were not statistically significant. Further investigations with a larger cohort of patients is required to confirm these findings.

161 ABLATION OF EPICARDIAL VENTRICULAR TACHYCARDIA ORIGINATING IN THE AREA OF PERICARDIAL ADHESIONS INDUCED BY STEREOTACTIC RADIOABLATION IN A PATIENT WITH ISCHEMIC CARDIOMYOPATHY

Abstract This is the case of a 64-year-old male patient with prior inferior wall myocardial infarction, wearing a cardiac resynchronization therapy defibrillator and suffering from recurrent ventricular tachycardia (VT). The patient had undergone a transitory successful endocardial radiofrequency catheter ablation (RFCA) in 2013 and a stereotactic ablative body radiotherapy (SABR) in 2021, targeting the VT originating in the inferior wall myocardial scar. The patient was referred to our institution due to recurrent highly symptomatic slow-VT. A coronary angiography ruled out coronary artery disease (CAD) progression and a RFCA was rescheduled. Given the suspected epicardial origin of VT based on a 12-lead ECG, the decision was made to perform a combined epi-endocardial ablation. SABR-induced pericardial adhesions prevented posterior pericardial access, thus requiring an anterior access approach (Figure 1, Panel A, yellow star). Following epicardial and endocardial electroanatomic mapping (EAM), VT ablation relied on a substrate-based approach. Local abnormal ventricular activities (LAVAs), detected both in the accessible epicardial inferior wall of the left ventricle and at the opposite endocardial site, were eliminated by radiofrequency (RF) current. Upon completion of endocardial ablation, ventricular pacing induced hemodynamically unstable VT, exiting from the epicardial region corresponding to the SABR-induced pericardial adhesions. Mechanical adhesiolysis, using the elbow of the open-irrigated ablation catheter, was performed to disrupt SABR-induced pericardial adhesions in the inferior wall. The epicardial EAM performed with the open-irrigated catheter recorded LAVAs in the infero-posterior wall of the left ventricle, corresponding to the SABR-disrupted pericardial adhesions. A RF current was delivered, targeting LAVAs at this site (Figure 1, Panel B: the central green dot corresponds to the area of disrupted pericardial adhesions). At the end of the procedure, no sustained VT was induced by programmed ventricular stimulation. Conclusion SABR constitutes a novel and promising non-invasive radioablative treatment of VT, potentially associated with cardiac toxicity. To our knowledge, this is the first reported case of combined epicardial and endocardial RFCA of recurrent VT after SABR. Based on the first RFCA report and exclusion of CAD progression, we hypothesized that SABR might have favoured progression of the inferior low voltage area. With this case report, we would like to demonstrate that even if pericardial adhesions could be a consequence of SABR, gentle catheter-driven manoeuvres can be enough to disrupt the adhesions and to achieve full EAM. Further research is mandatory to shed light on SABR's long-term arrhythmogenic role.

Risk factors for the development of premature ventricular complex-induced cardiomyopathy: a systematic review and meta-analysis

BackgroundPremature ventricular complexes (PVCs) are a potentially reversible cause of heart failure. However, the characteristics of patients most likely to develop impaired left ventricular function are unclear. Hence, the objective of this study is to systematically assess risk factors for the development of PVC-induced cardiomyopathy.MethodsWe performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). We investigated the reporting of PVC-CM risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis.ResultsA total of 26 studies (9 prospective and 17 retrospective studies) involving 16,764,641 patients were analyzed (mean age 55 years, 58% women, mean PVC burden 17%). Eleven RF were suitable for quantitative analysis (≥ 3 occurrences in multivariable model assessing a binary change in left ventricular (LV) function). Among these, age (OR 1.02 per increase in the year of age, 95% CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95% CI [0.05, 0.64]), non-sustained ventricular tachycardias (VT) (OR 3.01, 95% CI [1.39, 6.50]), LV origin (OR 2.20, 95% CI [1.14, 4.23]), epicardial origin (OR 4.72, 95% CI [1.81, 12.34]), the presence of interpolation (OR 4.93, 95% CI [1.66, 14.69]), PVC duration (OR 1.05 per ms increase in QRS-PVC duration [1.004; 1.096]), and PVC burden (OR 1.06, 95% CI [1.04, 1.08]) were all significantly associated with PVC-CM.ConclusionsIn this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VT, LV, epicardial origin, interpolation, and PVC burden, whereas the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up of patients presenting with frequent PVCs and normal LV function.

Risk factors for the development of premature ventricular complex-induced cardiomyopathy: a systematic review and meta-analysis

Abstract Background Premature ventricular complexes (PVCs) can be a reversible cause of heart failure. To date, it is unclear which risk factors contribute to the development of impaired left ventricular function. Objective Systematically assessing risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). Methods We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced Cardiomyopathy. We investigated the reporting of PVC-induced Cardiomyopathy risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis. Results A total of 26 studies (9 prospective and 17 retrospective studies) involving 16.764.641 patients were analyzed (mean age 55 y, 58% women, mean PVC burden 17%). Suitable for quantitative analysis were 25 studies examining 6738 (0.04%) patients and 11 RF (≥3 occurrences in multivariable model assessing a binary change in left ventricular - LV- function). Among these risk factors, age (OR 1.02 per increase in the year of age, 95%-CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95%-CI [0.05, 0.64]), non-sustained VTs (OR 3.01, 95%-CI [1.39, 6.50]), LV origin (OR 2.20, 95%-CI [1.14, 4.23]), epicardial origin (OR 4.72, 95%-CI [1.81, 12.34]), the presence of interpolation - PVCs that do not reset the RR interval (OR 4.93, 95%-CI [1.66, 14.69]) and overall PVC burden (OR 1.06, 95%-CI [1.04, 1.08]) were all significantly associated with PVC-induced Cardiomyopathy. (Figures 1,2) Conclusion In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VTs, LV and epicardial origin, interpolation, and PVC burden, while the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up to patients presenting with frequent PVCs and normal LV function. Funding Acknowledgement Type of funding sources: None.

Crosstalk between PKR1 and miR-124 is crucial for EMT regulation of tc21+epicardial mesothelial cells during cardiac development and repair process

Abstract Background The epicardial-mesothelial cells (EMCs) are essential regulators of cardiac growth and repairment process. The epicardial-to-mesenchymal transition (EMT) of epicardial fate determination are controlled by both cell autonomous and cardiomyocyte-originated mechanisms. Here, by using an in vitro and in vivo model of epicardial EMT, we investigated the role of miRNAs as regulators of these process and their potential targets. Methods EMT was induced in mice embryonic tcf21+EMCs through an angiogenic cytokine, prokineticin treatments. Cre-dependent tracing of TCF21-tm-iCRE-EMCs was utilized to abrogate prokineticin receptor-1 (PKR1) in mice epicardium. Human tcf21+ cardiac fibroblast (mainly originated from epicardial origin also utilized to study for their repairment signaling. Results Upon EMC-specific abrogation of PKR1 in early stages of cardiac development the TCF21-tm-iCREPKR1−/− mice exhibited 13±4% embryonic lethality due to a disconnection of epicardial cells from compact layer, failed expansion of the sub-epicardial space, and disruption of heterotypic cell interaction between epicardium and myocardium. EMT-RT profiler and enrichment analysis revealed an impaired EMT in TCF21-tm-iCREPKR1−/− hearts. Ingenuity Pathway Analysis on the EMT molecular network (e.g., Snai1, Snai2, B-catenin, N-cadherin, vimentin), specific to cardiac development and defects revealed MiR-124 as a part of this network that was inversely associated and down-stream of PKR1 in cultured Tcf21+ cells. Furthermore, protein expression of SNAIL2 was significantly downregulated in TCF21-tm-iCREPKR1−/− hearts and cultured Tcf21+ cells upon treatment with mir124 mimic. The luciferase reporter assay showed that miR124 directly targeted the 3'-untranslated region of SNAIL2 in EMCs. In a counter experiment, PKR1 gene replacement or mir124 inhibitor was able to rescue the impaired EMT-genes, and an increase in apoptosis and impaired proliferation in epicardium of embryonic TCF21-tm-iCREPKR1−/− hearts. Importantly, miRNA mimic in cultured tcf21 cells maintained epithelial features in EMCs, and increased EMT-associated transcripts and traits, such as apoptosis. In contrast, MiR124 is involved in wound healing process in tcf21+human CFs and EMCs. Conclusion This study shows the importance of a crosstalk between PKR1 and miR-124 with respect to EMT regulation during cardiac development and repair. Controlling fibroblast-committed EMT and pathological fibrotic remodeling is of increasing interest within the field of regenerative tissue engineering and development of interventional strategies after cardiac injury. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fondation de France

Epicardial adipose tissue of atrioventricular grooves is a reliable and early MRI biomarker of the effect of metabolic diseases on atrial myocardium

Abstract Introduction Epicardial adipose tissue (EAT), the visceral adipose tissue surrounding the heart, is implicated in a host of cardiovascular diseases playing a transducer role between systemic metabolic conditions and the myocardium, as illustrated by higher risk of atrial fibrillation in patients with diabetes or obesity. MRI affords comprehensive and non-invasive insights into myocardial structure, function and tissue properties. However, the clinical usefulness of whole atrial EAT is limited by its challenging measurability in clinical routine in several imaging modalities, including MRI. Purpose We hypothesized that atrioventricular groove epicardial adipose tissue (GEAT) which can be measured routinely based on established anatomic landmarks may be: 1) a relevant surrogate of atrial EAT and 2) a relevant imaging biomarker to characterize atrial alterations in patients with varied degrees of metabolic disorders. Methods Ninety-nine patients from the METACARDIS cohort (EU FP7) who had MRI, all in sinus rhythm and without overt clinical heart disease, were divided into 4 groups based on distinct metabolic profiles: metabolic syndrome (MS, n=24), severe obesity (SO, BMI ≥35 kg/m2, n=17), type-2 diabetes (T2D, n=41) and healthy controls (n=17). Atrioventricular groove EAT volume was measured from cine SSFP MRI images in four-, three-, two-chamber and short-axis views; atrial EAT volume was measured from four- and two-chamber views. Native T1-mapping values of EAT at the anterior atrioventricular groove excluding the coronary vessels were measured from the MOLLI sequence (basal short-axis slice). Results We found a high correlation between GEAT and atrial EAT volumes (r=0.96; p<0.0001) indicating that GEAT may reflect global atrial EAT volume. Next, we compared GEAT volume across study groups and found an increased GEAT volume in the 3 groups of patients with metabolic diseases compared to controls, with a significantly higher volume in MS (4.7±1.5 ml), SO (4.1±1.2 ml), and T2D (3.7±1.1 ml) than in Controls (2.6±0.6 ml; p≤0.001, p≤0.01, p≤0.05, respectively). In addition, T2D patients had lower native T1 values within GEAT compared to healthy controls (250±26 ms versus 280±31 ms; p≤0.01). Conclusion Atrioventricular groove EAT can be easily measured from conventional cine SSFP MRI images and could be used as a surrogate of global atrial EAT. Both volume and properties of GEAT are related to the metabolic status of patients. Furthermore, given its pure epicardial origin and pericoronary distribution, GEAT appears as a relevant biomarker of metabolic impacts on atrial myocardium. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Annee-recherche, Agence Regionale de Sante Ile-de-France

Early Development of Cardiac Fibrosis in Young Old-Father Offspring.

Cardiac aging is characterized by progressive fibrosis. Epidemiological studies have found that advanced paternal age is associated with an increased risk of heart failure in the next generation. This study is aimed at evaluating the effect of paternal age, in the young male rat progeny, on cardiac phenotype under circulatory stress conditions. Offspring rats were obtained by mating old males (24 months old) with young females (two months old) and by mating young males (two months old) with the same young females. Hypertension was induced in old father offspring (OFO) rats and young old father (YFO) offspring rats using L-NAME (N(ω)-nitro-L-arginine methyl ester). The OFO L-NAME rats showed a high blood pressure phenotype associated with substantial cardiac hypertrophy and an exacerbation of cardiac fibrosis compared to the YFO L-NAME rats. Histological analysis of heart tissue showed an expansion of the extracellular matrix, with fibroblasts displaying markers of epicardial origin (Tcf21, Tbx18, and Wt1) in the OFO group. Moreover, western blot and protein phosphorylation antibody array identified the TGF-β2 receptor pathway as preferentially activated in aged hearts as well as in OFO cardiac tissue treated with L-NAME. In addition, old father offspring rats (OFO+OFO L-NAME) had increased cardiac DNA methylation. In young hypertensive progeny, advanced paternal age at conception may be a risk factor for early progression towards cardiac fibrosis. An intergenerational transmission may be behind the paternal age-related cardiac remodeling in the young offspring.

Catheter ablation of atrial tachycardia originated from the left atrial epicardium.

A patient was referred with frequent atrial tachycardia (AT) attacks. Activation mapping showed that the left atrium (LA) roof was earlier activated with a broad region, and right atrial activation was delayed. The far-field A wave corresponding to the pulmonary artery area was advanced with failed ablation. Therefore, the AT could be left atrial epicardial origin, which was further confirmed by the successful ablation at earliest activated site at the epicardium.

Epicardial catheter ablation of idiopathic ventricular arrhythmias originating from uncommon epicardial sites.

Idiopathic epicardial ventricular arrhythmias (VAs) are clustered in the areas of the summit and crux. This study was to report a group of idiopathic epicardial VAs remote from the summit and crux areas. In total, 9 patients (6 males, mean age 32 ± 13 years) were enrolled. The locations were identified by epicardial mapping and ablation. The electrocardiographic and electrophysiological characteristics were compared to those of 9 patients who had VAs ablated at the opposite endocardial site. VAs were identified at the epicardium, with 4 patients had VAs located at the inferior wall, one at the anterior wall, one at the apex and 3 patients had VAs at the lateral wall. A "QS" type at the location-related leads was the only identified surface electrocardiogram indication suggesting epicardial origin (compared to that of the controls, 100% vs 0%, p<0.001). Endocardial and epicardial mapping revealed pre-maturities of -11 ± 4 ms and -25 ± 8 ms, respectively (VS. -28 ± 8 ms revealed by endocardial mapping in control patients, p<0.001 and p=0.389, respectively). All of the study cases demonstrated an "rS" pattern in the endocardial unipolar electrogram. Acute and long-term successful ablation (a median of 11 months of follow-up) was achieved in all patients without complications. A distinct group of idiopathic VAs remote from the summit and crux areas warranting ablation by a subxiphoid approach were identified. Morphological ECG features of a "QS" type among the location-related grouped leads combined with the mapping findings helped in the identification of the epicardial site of origin.

Electroanatomic visualization of coronary arteries: a case series to elicit safety, feasibility and diagnostic value in complex ablation procedures

Abstract Funding Acknowledgements Type of funding sources: None. Background Although three dimensional (3D) electroanatomic mapping systems allow detailed assessment of anatomy and substrates, ablation still carries substantial risk when close proximity to coronary arteries is suspected. 3D integration of coronary anatomy in mapping systems is still cumbersome, highlighting the need for an option of ad hoc acquirement of coronary artery anatomy. The goal of this case series was to evaluate the feasibility of a wire-based approach to the live visualization of coronary arteries and to assess its diagnostic information regarding procedure guiding. Methods For this single center case series, we included procedures in which close proximity of an ablation site to an epicardial vessel had to be suspected. An uninsulated-tip wire was then introduced into the relevant coronaries via diagnostic catheters after exclusion of critical stenosis by coronary angiography. The wire was connected to an impedance based 3D mapping system using a clamp and standard pin connection. Integrating this setup in the mapping system allows for live visualization of the wire tip, as well as the assessment of local electrograms within the respective vessel. Results We included a total of 9 procedures (4 ventricular tachycardia (VT) ablation procedures and 5 procedures for the ablation of premature ventricular contractions (PVCs)). The left coronary arteries were mapped in 8 cases, the right coronary artery was mapped in one case. In the majority of cases, the arrhythmogenic substrate was found in the left ventricle (5/9) or left ventricular summit area and the distal coronary sinus respectively (3/9). In two cases, epicardial mapping was performed combined with visualization of the right or left coronary arteries, respectively. There were no complications attributed to coronary wiring and mapping in this case series. In two cases, the diagnostic information from mapping of the coronary arteries could be used to rule out an epicardial origin of arrhythmia. In the majority of cases, coronary visualization was used to ascertain a proper distance between the ablation site and the vessel. Discussion In this case series, we could demonstrate the feasibility and safety of coronary artery visualization and its integration in a 3D mapping system. The data obtained was used for diagnostic, as well as safety aspects. The electrograms from the wire were used to quickly assess relative timing of arrhythmias, thus allowing for an estimation of possible epicardial origin. Conclusion Applying the same caveats as for any other wiring of coronary arteries, their electroanatomic visualization is achieved in a safe and straightforward manner, with minimal technical requirements. Mapping of the coronary arteries adds critical diagnostic information and their real-time visualization is feasible without exceeding costs or risks

PO-650-01 VENTRICULAR TACHYCARDIA ARISING POST-INFARCTION WITH APICAL ANEURYSM: CHARACTERISTICS &amp; OUTCOMES

Reentrant ventricular tachycardia (VT) in non-ischemic substrate with ventricular aneurysm is often established to be of epicardial (epi) origin. There is limited and conflicting data regarding the role of epi therapies in post-infarction cardiomyopathy with left ventricular apical aneurysm (AA).

PO-671-04 RATE OF CHANGE OF INITIAL INTRINSICOID DEFLECTION PREDICTS SITE OF ORIGIN OF ENDOCARDIAL VERSUS EPICARDIAL VENTRICULAR TACHYCARDIA

Electrophysiological mapping and ablation of ventricular tachycardia (VT) of epicardial origin requires precise definition of VT morphology to maximize successful outcomes. Several studies have published morphological characteristics derived from the 12-lead Electrocardiogram (ECG) that can be used to predict whether a VT is epicardial in origin. Unfortunately, for many of these criteria, when scaled to clinical practice the generalizability is limited.

390 Late pleuro-pericardial effusion after atrial fibrillation radiofrequency ablation

Abstract Aims Post-cardiac injury syndrome (PCIS) is an inflammatory state involving pericardium, epicardium, and myocardium causing a clinical picture in which epicardial and pericardial symptoms are prevalent. It appears mediated by autoimmune mechanisms and may appear as late post myocardial infarction pericarditis (Dressler’s Syndrome) or as a post traumatic pericarditis in the case of spontaneous thoracic trauma or iatrogenic pericarditis. Apart from the acute setting, pericardial effusion can be a manifestation of PCIS after interventional procedures. Methods and results A 57 years old hypertensive woman suffering from recurrent atrial fibrillation episodes underwent a technically difficult radio-frequency catheter ablation because of complex pulmonary veins anatomy and wide scar in the left atrial wall. During the procedure she developed cardiac tamponade and 410 ml of blood were drained by pericardiocentesis and re-infused without recurrent pericardial effusion during further in-hospital stay. She was discharged on apixaban 5 mg b.i.d. with Hb value of 10.2 g/dl. Two weeks later the patient was hospitalized for worsening cough, atypical chest pain, dyspnoea and modest orthopnea. C-reactive protein levels were 8.7 mg/dl, Hb was 9.9 g/dl and platelet count 484 000/ml; blood cultures were negative. An urgent thoracic CT scan showed bilateral pleural effusion and ubiquitous pericardial effusion (2.5–3 cm), without signs of active bleeding from the cardiac chambers into the pericardium. After stopping apixaban, the patient was given colchicine (1 mg/die). A total of 1200 ml of hematic pericardial fluid was drained from the pericardium over a 5-day period. Autoimmune blood tests were negative, as well as antibodies to pericardiotropic viruses. Pericardial fluid was negative for quantiferon and direct BK. On day 9, the drain was removed and steroidal treatment was started (prednisone 25 mg/die with scheduled tapering). Further echocardiographic exams were stable without pericardial effusion; a chest X-ray scan (at day 16) showed reversal of the water bottle shaped heart and of the pleural effusion. Conclusions Early myocardial infarct-associated pericarditis and Dressler’s syndrome account for about 20% of cases of PCIS accompanied by symptoms of epicardial and pericardial origin. PCIS is quite common after cardiac surgery, but it may be also observed even after iatrogenic trauma occurring during cardiac interventions: PCI, pacemaker lead insertion, radiofrequency ablation and Swan–Ganz catheterization. Blood entering the pericardium is thought to play a pivotal etiological role in iatrogenic PCIS, with consequent huge inflammatory reaction in the mesothelial tissue resulting in clinical manifestations of pericarditis. In animal models of PCIS, systemic release of cardiac antigens and self-antigen specific responses has been hypothesized. In our case cardiac tamponade complicating the ablation procedure probably initiated the epicardial and pericardial inflammatory response. Even if based on few data, the patient was treated with colchicine first, avoiding aspirin because of the hemorrhagic pericardial fluid; glucocorticoids were then started when symptoms and signs of PCIS slowly resolved despite colchicine treatment. The pericardial fluid was hemorrhagic (Hb 5.9 g/dl) and treatment with apixaban, in the context of an inflammatory mesothelial response, could have caused this peculiar, hemorrhagic, pericardial reaction.

Non-invasive mapping reduces procedure duration for catheter ablation of premature ventricular contractions using 12 lead ECG information: results from a prospective case-control study

Abstract Background Premature ventricular complexes (PVCs) result from early depolarisation of myocardial tissue in the ventricles and can ultimately lead to PVC-induced cardiomyopathy. Catheter ablation aims to completely eliminate the PVCs and is usually carried out using sequential activation mapping techniques. We report the results of a prospective case-control trial using the non-invasive, simultaneous 3D mapping system View into Ventricular Onset (VIVO) in combination with a 12 lead Holter ECG recording for catheter ablation of PVC. Methods and results A total of 16 patients (mean age 52.1±20.8 years, all structurally normal hearts, were enrolled and underwent VIVO mapping as a preparation of their invasive PVC ablation. Pre-ablation PVC burden had a median of 18.7% (IQR; 9.94 – 24.35). All but one patient (with very low PVC burden and epicardial origin) underwent a catheter ablation attempt guided by the 3D non-invasive maps integrated as VTK files in to the EAM. In 13/15 patients, acute elimination of the PVC was achieved which resulted in a PVC burden of &amp;lt;0.1% at 3 months' time. Procedure time amounted to in median 106 minutes (IQR 92.5 – 135.5), whereas in an age- and gender-matched control cohort (2:1) procedure time was significantly longer (145 (123.0 – 190.5). Conclusion Ward-based non-invasive 3D mapping (VIVO) of the origin of PVCs in patients with structurally normal hearts successfully guided the invasive ablation procedure and significantly reduced the invasive procedure time, as compared to a contemporary age- and gender-matched control cohort. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Catheter Precision 3D non-invasive mapping concept

Epicardial origin of cardiac arrhythmias: clinical evidences and pathophysiology.

Recent developments in imaging, mapping, and ablation techniques have shown that the epicardial region of the heart is a key player in the occurrence of ventricular arrhythmic events in several cardiac diseases, such as Brugada syndrome, arrhythmogenic cardiomyopathy, or dilated cardiomyopathy. At the atrial level as well, the epicardial region has emerged as an important determinant of the substrate of atrial fibrillation, pointing to common underlying pathophysiological mechanisms. Alteration in the gradient of repolarization between myocardial layers favouring the occurrence of re-entry circuits has largely been described. The fibro-fatty infiltration of the subepicardium is another shared substrate between ventricular and atrial arrhythmias. Recent data have emphasized the role of the epicardial reactivation in the formation of this arrhythmogenic substrate. There are new evidences supporting this structural remodelling process to be regulated by the recruitment of epicardial progenitor cells that can differentiate into adipocytes or fibroblasts under various stimuli. In addition, immune-inflammatory processes can also contribute to fibrosis of the subepicardial layer. A better understanding of such ‘electrical fragility’ of the epicardial area will open perspectives for novel biomarkers and therapeutic strategies. In this review article, a pathophysiological scheme of epicardial-driven arrhythmias will be proposed.