Left Free Wall Research Articles

BS-400-37 TARGETED ATRIAL EXPRESSION OF NGF SHRNA ATTENUATES NEW PARASYMPATHETIC AND SYMPATHETIC NERVE SPROUTING AND RESULTING DEVELOPMENT OF PERSISTENT ATRIAL FIBRILLATION IN A CANINE MODEL - A NOVEL GENE THERAPY APPROACH TO ATRIAL FIBRILLATION

The autonomic nervous system plays an important role in development of atrial fibrillation (AF). We previously showed marked autonomic remodeling in a canine rapid atrial pacing (RAP) model of persistent AF. Nerve growth factor (NGF), a neurotrophin essential for the growth and survival of peripheral neurons, was upregulated in fibrillating atria. However, the role of NGF in the development of autonomic remodeling in AF remains to be demonstrated. To prevent autonomic remodeling and development of persistent AF in a canine RAP model of AF. NGF shRNA was injected in the atria of 8 dogs followed by electroporation to facilitate atrial gene delivery. The animals were then subjected to RAP for up to 12 weeks. Time to AF onset was determined. At the terminal EP study, episodes of AF were recorded with high-density mapping in the posterior left atrium (PLA), left atrial free wall (LAFW) and left atrial appendage (LAA) for offline analysis of AF characteristics. Tissue of each atrial region was harvested and used for immunohistochemistry with markers for parasympathetic (acetylcholinesterase, brown) or sympathetic nerves (dopamine beta-hydroxylase, blue). After initiation of RAP, control animals developed persistent atrial fibrillation (>8 hours) after a median of 14 days. In contrast, NGF shRNA animals never developed this burden of AF over the duration of the study. Residual AF recorded at time of terminal EP study was slower (lower dominant frequency; PLA: 10.5±0.8Hz Vs 11.0±0.7Hz; LAFW: 9.7±0.8Hz Vs 10.4±0.7Hz; LAA: 8.8±0.5Hz Vs 9.9±0.5Hz; two-way ANOVA p<0.001), less fractionated (longer fractionation interval; PLA: 80.4±8.1ms Vs 68.1±5.2ms; LAFW: 79.3±9.3ms Vs 70.9±3.1ms; LAA: 87.9±7.8ms Vs 80.3±2.0ms; two-way ANOVA p<0.001) and more organized (higher organization index and lower Shannon's entropy). Tissue analysis showed that RAP induced hypertrophy of nerve bundles was significantly attenuated in dogs receiving NGF shRNA. This decrease in bundle size was accompanied by a significant decrease in parasympathetic and sympathetic fibers in the atrial myocardium. Targeted inhibition of atrial autonomic remodeling by NGF shRNA prevents development of persistent AF. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.

CE-542-01 PRECORDIAL ‘REVERSE PATTERN BREAK’: A NOVEL PREDICTOR FOR EPICARDIAL POSTEROSEPTAL ACCESSORY PATHWAYS

Posteroseptal (PS,also known as inferior paraseptal) accessory pathways(AP) may occasionally lie within the coronary sinus (CS), its tributaries, in a CS diverticulum (CSD) or along the epicardial surface. We encountered precordial reverse pattern break (RPB) of QRS morphology in some patients with epicardial APs and analysed all ECGs of posteroseptal accessory pathway(PSAP) cases. Inclusion criteria:Consecutive patients aged> 18 years, who underwent successful RF ablation in the PS region. Exclusion criteria- Failed ablation,Ablation at the left sided endocardium,Ablation deep inside the main CS, beyond 3 cm of the CS ostium (left free wall epicardial pathways). The cases were divided into two groups: Group En: Endocardial ablation; Group Ep: Ablation within the CS/CSD/epicardial surface. Definition:RPB is defined as monophasic tall R in V2 larger than V1 and V3 along with either (i) R/S < 1 in V3, or (ii) S wave in V3 > 4 mV. Among 66 cases [Age: 32±12 year, 40 males], 53 were ablated endocardially and 13 cases epicardially (12 inside a CS diverticulum, one in epicardium after gaining pericardial access).The baseline characteristics were comparable.RPB was present in 10/13 of Group Ep, but only in 6/53 cases of Group En.The sensitivity and specificity of RPB for epicardial location were 63% and 94% respectively, while the positive predictive value(PPV) was 77 %. The negative predictive value (NPV) was 89% and the accuracy was 87%. Among the patients who underwent ablation for PS accessory pathways,RPB was more often observed on the preexcited ECGs in patients having epicardial APs. This pattern may indicate the need for mapping within the CS/CSD or or epicardium.

Acute Cellular Rejection in Heart Transplant Patients: Insights of Global Longitudinal Strain, Myocardial Work, and an Exclusive Group of Chagas Disease.

BackgroundEchocardiographic markers associated with asymptomatic acute cellular rejection (ACR) in patients with orthotopic heart transplant (HT) are still under investigation. The aim of our study was to determine clinical and myocardial strain imaging (MSI) variables evaluated by echocardiography associated with ACR in the first year of HT. A separate analysis was performed to compare variables during the first 6 months of HT, when ACR has a prevalence in 60% of patients. Another analysis evaluated an exclusive population with Chagas disease as the cause of HT.MethodsWe prospectively studied 67 patients with less than 1 year of HT, 36 patients without ACR (41% men, age 49 ± 12 years, 52% Chagas disease as the cause of heart failure), and 31 patients with ACR (59% men, age 55 ± 8 years, 74% Chagas disease as the cause of heart failure). Conventional echocardiographic measurements and MSI by global longitudinal strain (GLS) from the left ventricle (LV) and right ventricle free wall (RV-FWLS) and myocardial work (MW) from the left ventricle were obtained by experienced echocardiologists. Clinical variables, such as the presence of diabetes, hypertension, and immunosuppressant drugs, were compared between groups.ResultsHT patients with ACR were older and used more cyclosporine for immunosuppression. The positive ACR group had an increased relative wall thickness and LV mass index and similar LVGLS and RV-FWLS compared to the negative ACR group. Nevertheless, MW analysis observed increased global work efficiency (GWE) in positive ACR. Multivariate analysis identified older age, cyclosporine use, LV mass index, and GWE as independent predictors for detecting rejection. A separate analysis was performed for patients with less than 6 months of HT. Similar MSI was observed in both groups, with a trend for increased GWE in patients with ACR and significantly increased LV mass index in the ACR group. An exclusive group of Chagas patients as the primary cause of HT was analyzed, and similar MSI results for LVGLS, RV-FWLS, and MW were observed for both ACR and the no rejection groups. Additionally, the survival rates at 2 years were similar between the Chagas disease groups.ConclusionLVGLS and RV-FWLS were similar between patients with or without ACR in the first year after HT. Conversely, GWE, a derivative of LVGLS, and LV mass index were increased in positive ACR and could be markers for rejection. Increased LV mass index was also found in a subgroup analysis of patients less than 6 months after HT; however, MSI was similar regardless of ACR. For chagasic patients, rejection in the first year did not increase mortality at the 2-year follow-up, and MSI parameters were similar between patients with or without ACR. In a multivariate analysis to predict ACR, the independent parameters in this study were older age, cyclosporine use, LV mass index, and GWE.

An Exploratory Study on Vectorcardiographic Identification of the Site of Origin of Focally Induced Premature Depolarizations in Horses, Part I: The Atria.

Simple SummaryArrhythmias are common in horses, but in order to offer adequate treatment, the anatomical location from where the arrhythmia originates must first be known. The objective of this study was to differentiate between the various anatomical origins of atrial premature depolarizations and to further differentiate these from normal sinus rhythm based upon the vectorcardiography characteristics of seven horses without cardiovascular disease. With vectorcardiography, the magnitude and direction of the cardiac electrical forces were derived from an electrocardiographic recording and were plotted in three dimensions. The three directions were represented by the right–left axis, head–tail axis, and dorsoventral axis. Under general anaesthesia, atrial premature depolarizations were induced by pacing inside the heart, guided by a 3D mapping system that allowed us to see the 3D position of the pacing catheter inside the heart in real-time. An adapted statistical test optimized for spherical data was used to demonstrate that the maximal directions of the first and second half of the P wave showed significant differences between the paced locations and between the paced complexes and sinus rhythm. The current study provides a practical approach to identifying the approximate site of origin of an atrial arrhythmia using a custom 12-lead ECG.In human cardiology, the anatomical origin of atrial premature depolarizations (APDs) is derived from P wave characteristics on a 12-lead electrocardiogram (ECG) and from vectorcardiography (VCG). The objective of this study is to differentiate between anatomical locations of APDs and to differentiate APDs from sinus rhythm (SR) based upon VCG characteristics in seven horses without cardiovascular disease. A 12-lead ECG was recorded under general anaesthesia while endomyocardial atrial pacing was performed (800–1000 ms cycle length) at the left atrial free wall and septum, right atrial free wall, intervenous tubercle, as well as at the junction with the cranial and caudal vena cava. Catheter positioning was guided by 3D electro-anatomical mapping and transthoracic ultrasound. The VCG was calculated from the 12-lead ECG using custom-made algorithms and was used to determine the mean electrical axis of the first and second half of the P wave. An ANOVA for spherical data was used to test if the maximal directions between each paced location and the maximal directions between every paced location and SR were significantly (p < 0.05) different. Atrial pacing data were not available from the LA septum in three horses, the intervenous tubercle in two horses, and from the LA free wall in one horse. The directions of the maximal electrical axes showed significant differences between all paced locations and between the paced locations and SR. The current results suggest that VCG is useful for identifying the anatomical origin of an atrial ectopy.

Comprehensive echocardiographic and speckle tracking strain analysis in rheumatic mitral stenosis patients before and after transvenous mitral commissurotomy.

Percutaneous Transvenous Mitral Commissurotomy (PTMC) is the first line treatment for rheumatic mitral stenosis (MS). We sought to evaluate (1) changes in 2-dimensional (2D) echocardiographic and strain values and (2) differences in these values for patients in atrial fibrillation (AF) and sinus rhythm (SR) pre, immediately and 6months post PTMC. Retrospective study of 136 patients who underwent PTMC between 2011 and 2021. We analyzed their 2D echocardiogram, Global Longitudinal Strain (GLS), Left Atrial Reservoir Strain (LAr-S) and Right Ventricle Free Wall Strain (RVFW-S) pre, immediately and 6months post PTMC. At 6months, mitral valve area increases from 0.94 ± 0.23cm2 to 1.50 ± 0.42cm2. Ejection fraction (EF) did not change post PTMC (pre; 55.56 ± 6.62%, immediate; 56.68 ± 7.83%, 6months; 56.28 ± 7.00%, p = 0.218). Even though EF is preserved, GLS is lower pre-procedure; -11.52 ± 3.74% with significant improvement at 6months; -15.16 ± 4.28% (p < 0.001). Tricuspid annular plane systolic excursion (TAPSE) improved at 6months from 1.95 ± 0.43 to 2.11 ± 0.49 (p = 0.004). RVFW-S increases at 6months from -17.37 ± 6.03% to -19.75 ± 7.19% (p = 0.011). LAr-S improved from 11.23 ± 6.83% pre PTMC to 16.80 ± 8.82% at 6months (p < 0.001) post PTMC. Pre-procedure patients with AF have lower strain values (More LV, RV and LA dysfunction) with statistically significant difference for LAr-S (p < 0.001), GLS (p < 0.001) and RVFW-S (p < 0.001) than patients in SR. Patients with severe rheumatic MS have subclinical left and right ventricle dysfunction despite preserved EF and relatively normal TAPSE with significant improvement seen at 6months post PTMC. AF patients have lower baseline strain values than SR patients.

Measurement of local orientation of cardiomyocyte aggregates in human left ventricle free wall samples using X-ray phase-contrast microtomography.

Most cardiomyocytes in the left ventricle wall are grouped in aggregates of four to five units that are quasi-parallel to each other. When one or more "cardiomyocyte aggregates" are delimited by two cleavage planes, this defines a "sheetlet" that can be considered as a "work unit" that contributes to the thickening of the wall during the cardiac cycle. In this paper, we introduce the skeleton method to measure the local three-dimensional (3D) orientation of cardiomyocyte aggregates in the sheetlets in three steps: data segmentation; extraction of the skeleton of the sheetlets; and calculation of the local orientation of the cardiomyocyte aggregates inside the sheetlets. These data include a series of virtual tissue volumes and five transmural human left ventricle free wall samples, imaged with 3D synchrotron radiation phase-contrast microtomography, and reconstructed with a 3.5×3.5×3.5μm3voxel size. We computed the local orientation of the cardiomyocyte aggregates inside the sheetlets with a working window of 112×112×112μm3 in size. These data demonstrate that the skeleton method can provide accurate 3D measurements and reliable screening of the 3D evolution of the orientation of cardiomyocyte aggregates within the sheetlets. We showed that in regions that contain one population of quasi-parallel sheetlets, the orientation of the cardiomyocyte aggregates undergo "oscillations" along the perpendicular direction of the sheetlets. In regions that contain two populations of sheetlets with a different angular range, we demonstrate some discontinuity of the helix angle of the cardiomyocyte aggregates at the interface between the two populations.

107 Left ventricular intramural haematoma secondary to transcatheter aortic valve replacement

Abstract An 80-year-old woman was electively hospitalized at our institution to undergo transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis symptomatic for exertional dyspnoea (NYHA III). At the admission she presented a normal electrocardiogram (EKG), a creatinine clearance (CrCl) of 36 ml/min, a normal size and hypertrophic left ventricle with a preserved ejection fraction (EF 70%). A pre-procedure coronary angiography was performed and showed absence of significant epicardic stenoses. A balloon-expandable valve (Edwards Sapien 26 mm) was successfully implanted via the trans-femoral access without intra-procedural complication and the patient was transferred to cardiology ward for monitoring; in the post-procedure, the patient complained of nausea and a feeling of vomiting, without other cardiologic symptoms; she had low blood pressure (BP 95/70 mmHg) with normal heart rate and oxygen saturation (Killip 1). An EKG was performed and showed a ST-elevation in antero-lateral leads, so a bed-side echocardiogram was performed showing a good function of TAVR but an ipo-akinesia of the left ventricle’s lateral wall. The patient was transferred to the Cath lab and at the emergent coronary angiography no clear epicardic stenoses were seen, with a diffuse narrowing of an early obtuse marginal (OM) branch and of the distal branches of circumflex artery, suggestive for a spasm, that was refractory to repeated nitroglycerine infusions. A clear mismatch between coronary angiogram findings and EKG was detected. Considering the hemodynamic compromise and symptoms persistence a percutaneous transluminal coronary angioplasty of OM was performed with a partial ST resolution. The patient was transferred to the Coronary Unit Care where an echocardiogram was repeated confirming the good function of TAVR but outlining the presence of a voluminous intramural haematoma (&amp;gt;30 mm of maximum diameter) with anterior, lateral and posterior wall akinesia and depressed left ventricle ejection fraction (EF 35%). A conservative management of the haematoma was chosen. The hospital stay was complicated by an acute pulmonary oedema, requiring non-invasive ventilation, a cardiogenic shock, requiring inotropic (dobutamine) support, and an acute renal failure (creatinine peak 2.9 mg/dl with CrCl of 15 ml/min) with anuria, requiring continuous renal replacement therapy for two days; she developed a left branch block with no complete atrioventricular block. The pre-discharged echocardiogram showed a partially organized moderate pericardial effusion (1.3 cm) and moderate mitral regurgitation. After six months, she was asymptomatic, with a significant improvement of functional status (NYHA II) and a stable renal function (CrCl &amp;gt; 30 ml/min); no more echocardiographic signs of pericardial effusion were shown but the persistence of akinesia of the postero-lateral- and anterior-wall with depressed left ventricle ejection fraction (EF 37%) and moderate-severe mitral regurgitation. The persistence of good result of TAVR (aortic mean gradient 9 mmHg, absence of peri-valvular leak) was confirmed. Intramural dissecting haematoma (IDH) is a rare complication of myocardial infarction, chest trauma and percutaneous interventions; it consists of a cavity filled with blood, with the integrity of both the outer wall (myocardium and pericardium) and the inner wall (myocardium and endocardium) and it can develop in the left ventricle free wall, the right ventricle and the interventricular septum. IDH’s formation may result from intra-myocardial vessels’ rupture in the interstitial space. Never understimate nausea as symptom: think about heart is challenging but mandatory!

Coumel's sign reversed: What is the mechanism?

A patient presented with documented narrow QRS tachycardia. During electrophysiological study, he has orthodromic reciprocating tachycardia with atrial activation consistent with left free wall accessory pathway. With induction of tachycardia, beats with LBBB morphology have shorter cycle length than those with narrow QRS. What is the mechanism?

Abstract 17074: Primary Cardiac Sarcoma In Elderly Patient And Need For High Index Of Suspicion

Case Presentation: Primary cardiac tumors are rare with an incidence between 0.0017 and 0.2%. Most cardiac tumors are benign such as myxomas, lipomas, and papillary fibroelastomas. Primary malignant cardiac tumors are even more uncommon, with cardiac sarcomas being the most common. We present a case of an 87-year old female who presented initially for progressive shortness of breath and concern for potential endocarditis vs intra-cardiac thrombus noted on outside hospital transthoracic echocardiogram. Blood cultures were negative, no leukocytosis or sequelae of infection were noted. Transesophageal echocardiogram (TEE) noted a large lesion attached to the anterior mitral leaflet, with additional lesions noted on the left atrial free wall just medial to the right sided pulmonary veins. Obstruction of mitral inflow was noted with a mean gradient through the mitral valve of 5mmHg. Cardiac MRI was performed for further delineation of lesions and based on tissue characteristics were felt to be thrombus (Figure 1). Hypercoagulability workup was negative, and there was no improvement in lesion size with systemic anticoagulation. Cardiothoracic surgery was consulted for surgical removal of the mass. Pre-operative cardiac catheterization showed multi-vessel obstructive coronary artery disease. It was also noted that the left circumflex artery appeared to supply blood into a discrete area in the left atrium. The patient was ultimately taken for surgical removal. Surgical pathology demonstrated primary high grade cardiac sarcoma. Discussion: The rarity and heterogeneity of primary cardiac tumors, along with many potential mimickers pose a diagnostic and therapeutic challenge. This, combined with the location and aggressive nature of the tumors, make them difficult to treat and incur a high mortality rate. This highlights the importance of maintaining a high index of suspicion and keeping a broad differential when evaluating intra-cardiac masses.

Abstract 12592: Acute Administration of N-Acytylcysteine Leads to Highly Specific Sub-Regional Changes in AF Electrogram Characteristics - A New Way to ‘Uncover’ Regions of High Oxidative Injury in the Fibrillating Atrium?

Introduction: It is currently not possible to measure and therapeutically target oxidative injury (OI) in the intact fibrillating atrium. Hypothesis: We postulated that measurement of AF electrogram characteristics after acute administration of a reactive oxygen species (ROS) scavenger can help ‘uncover’ regions of high OI in the fibrillating human atrium. Methods: We mapped in both atria pre/post NAC (intravenous, 100mg/kg) in 15 persistent AF dogs (3-14 weeks rapid atrial pacing) using a high-density epicardial mapping-plaque (6 atrial regions in both atria, 130 electrodes, electrode-distance 2.5mm) and in 4 patients using the HD-grid catheter. We quantified the OS-levels as ratio of oxidatively damaged nuclei ( Figure A ) against the total number in 8-OHdG staining (N=36) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24) using Qupath. We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-region sizes with &gt;10% change pre vs. post NAC. Results: Oxidative stress (OS) levels, highest in the left atrial free wall, lowest in the appendages increased with increasing degree of fibro-fatty tissue (R=0.6,P&lt;0.05) and with decreasing cycle length (R=0.5, P&lt;0.05) in all regions ( Figure C ). NAC selectively reduced AF characteristics in ‘hot spot’-sub-regions ( Figure D ). OS level correlated with delta CL, delta DF, and delta Organization Index in delta maps (NAC - baseline) (R=0.5, P&lt;0.05, all comparisons) ( Figure E) . In patients, NAC ( Figure G) reduced AF characteristics in subregions ( Figure H) and increased cycle length from 210±50ms to 252±18ms (P&lt;0.05) in the left atrium ( Figure I ). Conclusions: OS-level correlated with the degree of dense fibro-fatty tissue and with electrogram measures in both atria. Acute scavenging of ROS reduced AF characteristics in the left atrium in dogs and patients. We might have found a new way to target regions of high OS in the atrium in the individual patient.

Comparison of Outcomes of Catheter Ablation in Asymptomatic Versus Symptomatic Preexcitation to Guidelines and Beyond

Management of asymptomatic subjects with preexcitation remains controversial. Our objective was to analyze the reasons an electrophysiological study (EPS) was performed in an asymptomatic population referred for the procedure, and compare the results of catheter ablation between asymptomatic and symptomatic patients. Patients ≥18years of age with preexcitation referred for an EPS and ablation were grouped as either symptomatic or asymptomatic. We analyzed in both subsets for (1) reasons for the procedure, (2) EPS results (anterograde effective refractory period of the accessory pathway, tachycardia/atrial fibrillation inducibility, anatomical localization), (3) success of the procedure, and (4) incidence of complications. We included 175 patients, 121 of which were symptomatic (39 ± 16 years) and 54 were asymptomatic (35 ± 14 years, p = NS not significant). The most frequent symptoms were palpitations (87%) and syncope (7%). EPS was performed in 44 of 54 asymptomatic patients mainly because of involvement in sports (60%) or high-risk employment (14%). Anterograde effective refractory period was significantly longer in asymptomatic patients (314 ± 55milliseconds) than in symptomatic patients (278 ± 46milliseconds; p <0.001). Orthodromic tachycardia inducibility was significantly higher in symptomatic than in asymptomatic patients (69% and 27%, respectively; p <0.001). A total of 170 accessory pathways (49% left free wall, 12% right free wall, 39% septal) were observed without significant differences in the anatomical location between groups. Catheter ablation was attempted in all patients, succeeding in 98% of symptomatic and 95% of asymptomatic patients, without major complications in either group. In conclusion, the reasons for invasive evaluation of asymptomatic patients with preexcitation may be outside the scope of current guidelines. Catheter ablation produces excellent results without major complications.

A histological study of the atria in patients with isolated rheumatic mitral regurgitation with and without atrial fibrillation.

There is a high incidence of atrial fibrillation (AF) in patients with isolated rheumatic mitral regurgitation (MR). The histopathologic changes in the atria of patients with isolated rheumatic MR with and without AF are unknown. We aimed to determine the histological findings in patients with isolated severe rheumatic MR with and without AF. Patients with severe isolated rheumatic MR undergoing valve replacement surgeries underwent endocardial biopsies from right atrial appendage, left atrial appendage, right free wall, left free wall, left posterior wall, and mitral valve. Group I consisted of patients in sinus rhythm (SR), and Group II included patients with AF. We analyzed and compared these 10 histological features in the biopsies of patients in Groups I and II. Of the 25 patients, 12 were in Group I and 13 in Group II. In Group I, patients had severe myocyte hypertrophy (60% vs. 18%,p = .04) that was significantly more in the right atrium (22.7% vs. 11.4%, p = .059). Interstitial adipose tissue deposition was more common in Group I (30% vs. 25%, p = .06). Interstitial fibrosis was evenly distributed at all sites without significant difference between the two groups. Group II patients had a higher prevalence and severity of vacuolar degeneration (91% vs. 60%,p = .09). Patients with isolated severe rheumatic MR and AF have more vacuolar degeneration in the atrial tissue. Patients with SR have myocyte hypertrophy and interstitial adipose tissue deposition. Interstitial fibrosis is uniformly distributed in patients in SR and AF.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients’ myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Characteristics of a large-scale cohort with accessory pathway(s): A cross-sectional retrospective study highlighting over a twenty-year experience.

Catheter ablation following electrophysiologic study (EPS) is the mainstay of diagnosis and treatment for patients with atrioventricular reentrant tachycardia (AVRT), demonstrating excellent long-term outcome and a low rate of complications. In this study, our aim was to assess our experience in patients with accessory pathway (AP) and to compare our data with the literature. We included 1,437 patients who were diagnosed and treated for AP in our hospital between 1998 and 2020. The demographic data of all the patients, AP location, and periprocedural results were recorded. Of the 1,437 patients, 1,299 (90.4%) were men; and the mean age of the population was 26.67 years. The location of 1,418 APs were along the left free wall (647 [45.6%] patients), in the posteroseptal region (366 [25.3%] patients), in the anteroseptal region (290 [20.4%] patients), and along the right free wall (115 [8.1%] patients). The ratio of the second AP existence was 3.0% and AVNRT co-existence was 2.0%. A total of 55 (3.8%) patients had recurrent sessions for relapse. Our center's total success rate was 95.5%, and total complication rate was 0.26%. According to our retrospective analysis, EPS is a highly functional tool in the diagnosis and management of arrhythmias such as AVRT for high-risk patient groups like military personnel with the aim of risk stratification and medical management.

Traumatic Left Ventricular Aneurysm and Ventricular Septal Defect in a Child.

Cardiac injuries following blunt trauma are rare but potentially lethal in children. We present a 23-month-old child who sustained an aneurysm of the left ventricle free wall and ventricular septum with associated ventricular septal defect following blunt trauma. She underwent successful surgical repair 6 weeks following her date of injury. Surgical decision-making surrounding this case is discussed.

B-PO01-084 DIAGNOSTIC UTILITY OF EARLY PREMATURE VENTRICULAR COMPLEXES IN DIFFERENTIATING ATRIOVENTRICULAR REENTRY AND AV NODE REENTRY TACHYCARDIAS

His refractory PVC (HrPVC) perturbing a supraventricular tachycardia (SVT) establishes the presence of an accessory pathway (AP). Earlier PVCs may perturb AVNRT or AVRT and are currently considered non-diagnostic. We hypothesize that an early PVC will always show a minimum differential of >30 ms in its advancement of AVNRT because of minimum retrograde conduction time (stimulus to His plus His to AV node) of 30 ms from any ventricular pacing site to the AV node. The site of pacing, on the other hand, can be in close proximity to some AVRT circuits resulting in greater advancements. Thus, if an early PVC (H1S2) advances the subsequent atrial activation (A1-A2) more than this minimum differential (A1A2 ≤ H1S2+30 ms), AVRT diagnosis is established. Thirty-seven consecutive patients with either AVNRT or AVRT undergoing ablation were retrospectively evaluated. PVCs were delivered during SVT at RV apex or septum based on operator preference. Early PVCs were defined when the pacing stimulus was >30 ms ahead of the His. When early PVCs resulted in A1A2 ≤ H1S2+30 ms, it was considered an AP response. Final diagnosis of AVRT and AVNRT, based on tachycardia features and standard established maneuvers, were matched to the above responses by an observer blinded to the diagnosis. Among the 38 cases, 21 were AVNRT (20 typical, 1 atypical) and 17 were AVRT (2 right free wall, 2 right septal, 1 left septal, 12 left free wall). SVTs were divided into those with the AP response and those without AP response to early PVCs. Eight cases had an AP response with a mean H1S2+30 ms of 333 ± 60 ms and A1A2 of 307 ± 56 ms, and all cases were confirmed AVRT. The specificity of AP response to early PVC in predicting AVRT was 100%. The sensitivity of the test to predict AVRT was low, 45%. No AVNRT cases had AP response. All 9 AVRTs without an AP response were left free wall. An AP response to early PVCs (A1A2 ≤ H1S2+30 ms) is 100% specific for AVRT diagnosis. The degree of atrial advancement after early PVCs may contain information to differentiate AVRT and AVNRT in select cases.

B-PO02-029 REDUCED ATRIAL FIBRILLATION DRIVERS IN RESPONSE TO REACTIVE OXYGEN SCAVENGING - A NOVEL THERAPEUTIC TARGET IN ATRIAL FIBRILLATION?

Oxidative Stress (OS) is thought to be a mediator of atrial fibrillation (AF), but the precise role of OS in AF is unknown. We assessed reactive oxygen species (ROS) scavenging on slow conduction and maintenance of rotational drivers. We hypothesized that ROS are dynamically involved in a vulnerable substrate and that ROS scavenging reduces AF drivers and arrhythmogenic slow conduction zones. AF was induced in 48 dogs by rapid atrial pacing (RAP) for 3-14 weeks. Epicardial high-density mapping was performed (130 electrodes, dist. 2.5mm) in the atrial regions: posterior left atrium (PLA), left atrial free wall (LAFW), left atrial appendage (LAA), posterior right atrium (PRA), right atrial free wall (RAFW), right atrial appendage (RAA). N-acetylcysteine (NAC) was given intravenously (100mg/kg) in 15 AF dogs. We mapped all atrial regions pre and post NAC. We detected rotational activity in activation time maps and quantified slow conduction as activation delay in neighboring electrodes. We detected rotational activity in all regions (Figure A) with the stability of 376±255ms in the LAA, 422±174ms in the PLA, and 317±174ms in the LAFW (Figure B). The cycle length of rotational activity was shorter in the PLA (CL 94±7 ms) compared to other regions (P<0.05) (Figure C) and increased in remote regions with increasing distance to the PLA (Figure D). After providing NAC, rotational activities reduced in the left atrium by 40% in the LAFW, by 39% in the PLA, and by 12% in the LAFW (Figure E). Acute scavenging of ROS reduces arrhythmogenic slow conduction and AF triggers. These results show that ROS is dynamically involved in the maintenance of AF.

The relation of 12 lead ECG to the cardiac anatomy: The normal CineECG

BackgroundThe interpretation of the 12‑lead ECG is notoriously difficult and requires experts to distinguish normal from abnormal ECG waveforms. ECG waveforms depend on body build and electrode positions, both often different in males and females. To relate the ECG waveforms to cardiac anatomical structures is even more difficult. The novel CineECG algorithm enables a direct projection of the 12‑lead ECG to the cardiac anatomy by computing the mean location of cardiac activity over time. The aim of this study is to investigate the cardiac locations of the CineECG derived from standard 12‑lead ECGs of normal subjects. MethodsIn this study we used 6525 12‑lead ECG tracings labelled as normal obtained from the certified Physionet PTB XL Diagnostic ECG Database to construct the CineECG. All 12 lead ECGs were analyzed, and then divided by age groups (18–29,30-39,40-49,50-59,60-69,70–100 years) and by gender (male/female). For each ECG, we computed the CineECG within a generic 3D heart/torso model. Based on these CineECG's, the average normal cardiac location and direction for QRS, STpeak, and TpeakTend segments were determined. ResultsThe CineECG direction for the QRS segment showed large variation towards the left free wall, whereas the STT segments were homogeneously directed towards the septal/apical region. The differences in the CineECG location for the QRS, STpeak, and TpeakTend between the age and gender groups were relatively small (maximally 10 mm at end T-wave), although between the gender groups minor differences were found in the 4 chamber direction angles (QRS 4°, STpeak 5°, and TpeakTend 8°) and LAO (QRS 1°, STpeak 13°, and TpeakTend 30°). ConclusionCineECG demonstrated to be a feasible and pragmatic solution for ECG waveform interpretation, relating the ECG directly to the cardiac anatomy. The variations in depolarization and repolarization CineECG were small within this group of normal healthy controls, both in cardiac location as well as in direction. CineECG may enable an easier discrimination between normal and abnormal QRS and T-wave morphologies, reducing the amount of expert training. Further studies are needed to prove whether novel CineECG can significantly contribute to the discrimination of normal versus abnormal ECG tracings.

Left atrial \u0131ntramural hematoma after radiofrequency catheter ablation of left lateral accessory pathway

We report a case of left atrial hematoma after ablation of left lateral concealed accessory pathway. A 46-year-old male patient experienced chest pain after radiofrequency ablation. Transthoracic echocardiography and computed tomography revealed the intramural mass consistent with hematoma in the left atrium. He was hemodynamically stable, and conservative approach was decided. Atrioventricular groove is a vulnerable part of left atrium, and ablation of left free wall accessory pathway may require targeting both atrial and ventricular surfaces of the mitral annulus. Avoidance of forceful catheter manipulation during the electrophysiological procedure is important for prevention of this complication. Optimal periprocedural anticoagulation might reduce the risk of procedure-related thromboembolic complications, but electrophysiologists should always pay attention to an intramural hematoma that may occur after radiofrequency catheter ablation.

Contemporary procedure characteristics and outcomes of accessory atrioventricular pathway ablations in an integrated community-based health care system using a tiered approach

BackgroundSince the early descriptions of large series of accessory atrioventricular pathway ablations in adults and adolescents over 20 years ago, there have been limited published reports based on more recent experiences of large referral centers. We aimed to characterize accessory pathway distribution and features in a large community-based population that influence ablation outcomes using a tiered approach to ablation.MethodsRetrospective analysis of 289 patients (age 14–81) who underwent accessory ablation from 2015–2019 was performed. Pathways were categorized into anteroseptal, left freewall, posteroseptal, and right freewall locations. We analyzed patient and pathway features to identify factors associated with prolonged procedure time parameters.ResultsInitial ablation success rate was 94.7% with long-term success rate of 93.4% and median follow-up of 931 days. Accessory pathways were in left freewall (61.6%), posteroseptal (24.6%), right freewall (9.6%), and anteroseptal (4.3%) locations. Procedure outcome was dependent on pathway location. Acute success was highest for left freewall pathways (97.1%) with lowest case times (144 ± 68 min) and fluoroscopy times (15 ± 19 min). Longest procedure time parameters were seen with anteroseptal, left anterolateral, epicardial-coronary sinus, and right anterolateral pathway ablations.ConclusionsIn this community-based adult and adolescent population, majority of the accessory pathways are in the left freewall and posteroseptal region and tend to be more easily ablated. A tiered approach with initial use of standard ablation equipment before the deployment of more advance tools, such as irrigated tips and 3D mapping, is cost effective without sacrificing overall efficacy.