ORALABST

RACTS

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and a majorcause of heart failure and thromboembolic stroke. Genetic factors contribute to the path-ogenesis of AF, but the causative variants and the underlying molecular mechanisms areincompletely understood. The first familial AF locus was mapped to a region on chro-mosome 10 (10q22-q24), but to date, no disease-causing genes have been identified. TheKCNMA1 gene that encodes the a-subunit of the large conductance Ca2+-activated K+

channel BKCa is positioned within this locus, but its potential role as a candidate gene islimited by the paucity of data regarding its role in normal cardiac function.Objectives: The objective of this study was to characterise BKCa channel distribution inhuman tissue and to determine the functional effects of BKCa deficiency in BKCa knockoutzebrafish.Methods: Immunofluorescence and immunogold labelling with electron microscopystudies were performed to assess BKCa distribution in human tissue biopsies. QuantitativeRT-PCR analysis of the KCNMA1 mRNA and Western blots were used to identify BKCa

isoforms present in the human atrium. Translation-blocking morpholinos were used forgeneration of BKCa knockout zebrafish that were subjected to cardiophysiological evaluation.Results: BKCa is abundantly expressed in the sinoatrial node and in atrial and ventricularmyocytes. In the atrial tissue specifically, BKCa was localised to the sarcoplasmic reticulum,mitochondria, nucleus and cell membrane. A number of different BKCa isoforms wereidentified in atrial tissue ranging in size from 50-110 kDa. Altered levels of expression ofthese isoforms were observed in the atrial tissue from patients with AF. Expression patternsof the zebrafish orthologs of KCNMA1, kcnma1a and kcnma1b, were evaluated in 72 hpf fish.Both genes were expressed in the heart. Knockdown of the kcnma1b gene resulted in cardiacabnormalities in 84% of embryos. Zebrafish morphants showed decreased heart rate (123 vs140 beats/min compared with controls), increase in atrial end-diastolic diameter (108 vs 79mm) and mild ventricular dysfunction (reduced fractional shortening: 18% vs 30%).Conclusion: BKCa has diverse subcellular localisation and isoforms in the human atriumand morpholino zebrafish knockout of the KCNMA1 gene results in a predominant atrialphenotype with bradycardia and atrial dilatation. Our data highlights an unrecognised rolefor BKCa in cardiac function and supports KCNMA1 as a promising candidate gene for AF.Disclosure of Interest: None Declared

O021

Ventricular tachycardia reentrant circuits arise early after myocardial infarction andare amenable to cure with radiofrequency ablation: Validation in a chronic ovinemodel

Calvin H. C. Hsieh*, Ee-May Chia, Kaimin Huang, Jim Pouliopoulos, Juntang Lu, Michael Barry,David L. Ross, Stuart Thomas, Pramesh KovoorCardiology, Westmead Hospital, Sydney, Australia

Introduction: Ventricular tachycardia (VT) accounts for the majority of sudden deathsfollowing myocardial infarction (MI).It is accepted that VT develops late after MI. Implantation of a defibrillator (ICD) within

40 days post-MI has not been of value unless based on programmed ventricular stimulation(PVS). Early post-MI PVS studies have suggested early development of the VT arrhyth-mogenic substrate. Also, post-MI VT is considered not amenable to cure with radio-frequency ablation (RFA), thus requiring life-long palliative ICD therapy.Objectives: To determine that the:

1. Macro-reentrant circuit and substrate of VT develop within 8 days post-MI2. Post-MI day-8 RFA can abolish or diminish post-MI VT

Methods:1. Experiment 1. MI was induced in 36 sheep. In 21 survivors, serial electro-

anatomical mapping was performed pre-infarct and days 3, 8 and 100 post-MI andPVS at days 8 and 100.

2. Experiment 2.MIwas induced in 35 sheep. In 25 survivors, RFAwas performed if VTwas induced day-8. All animals were followed by repeat PVS day-100 and day-200.

Results:1. Experiment 1. 9/21 and 12/21 were VT inducible and non-inducible respectively

on both day-8 and day-100. Earliest endocardial activation, and other character-istics of VT were similar between days. There was no statistical difference insubstrate (low voltage, or slowed conduction velocity) between days 3 to 100, butthere was continued increase in electrogram fractionation with time.

2. Experiment 2. Of the 25 survivors, 12 had inducible VT at day-8. There was 100%success with day-8 RFA in VT inducible animals. One animal was euthanized fornon-arrhythmic reasons. Remaining 11 ablated and 13/25 non-inducible animalsremained arrhythmia-free on PVS day-100 and day-200 (p<0.001). There was asustained decrease in split (p¼0.013), late (p<0.001) and fractionated (p¼0.006)electrograms within the left ventricular endocardium at day-100 and day-200compared to day-8 following RFA.

Conclusion:1. Experiment 1. The stability of VT characteristics and substrate between days 8 to

100 suggest development of VT prior to day-8 post-MI, supporting the role of earlyPVS for risk stratification post-MI, and raising the potential for early interventionwith RFA.

2. Experiment 2. Day 8 RFA resulted in high acute and chronic success suggestingcure of post-MI VT. If confirmed in human studies, this could revolutionise themanagement of post-MI VT with early curative RFA rather than life-long palliativeICD implantation.

Disclosure of Interest: None Declared

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O022

Striking Differences In The Role of Distinct Endothelial Progenitor Cell PopulationsIn Ischaemia-Mediated Neovascularisation And Coronary Collateral Formation -Implications On Therapeutic Angiogenesis

Sui Ching G. Yuen*1,2, Kim H. Chan1,2,3, Philippa Simpson1, Zoe Clayton1,2,Ashanti Dantanarayana1, Laura Lecce1,2, Louise Dunn4, Andy Yong2,5, Chi-Jen Hsu1,2,3,Matt Guillou1, Shisan Bao6, Chirapan Chawantanpipat3, David Celermajer2,3,7, Joseph Wu8,Martin Ng1,2,31Translational Research Group, Heart Research Institute, Newtown, 2Sydney Medical School,University of Sydney, 3Department of Cardiology, Royal Prince Alfred Hospital, Sydney,4Vascular Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, 5Departmentof Cardiology, Concord Repatriation General Hospital, 6School of Medical Sciences, University ofSydney, Sydney, 7Clinical Research Group, Heart Research Institute, Newtown, Australia,8Department of Medicine & Radiology, Stanford Cardiovascular Institute, Stanford, United States

Introduction: Endothelial progenitor cells (EPCs) are implicated in angiogenesis. However,the use of EPCs in clinical trials has had underwhelming and contradictory results, possiblydue to the use of unselected cell populations. Two distinct EPC populations (early EPCsand late-outgrowth endothelial cells, OECs) have been found to exhibit different angiogenicproperties in vitro but have rarely been compared in vivo.Objectives: To compare properties of two distinct EPC populations in murine models andpatients with coronary artery disease (CAD).Methods: EPCs were assessed in preclinical studies using two murine hindlimb ischaemiamodels: 1)in vivo tracking of EPCs from transgenic L2G mice (expressing FLuc) trans-planted into syngeneic mice by bioluminescent imaging (BLI); 2)xenotransplantation ofhuman EPCs into nude mice. In patients with isolated left anterior descending arterydisease we evaluated the relationship between EPCs and the extent of coronary collater-alisation (invasively assessed by collateral flow index, CFI).Results: Assessment of the in vivo biokinetics of intravenously transplanted L2G OECs andearly EPCs using BLI showed comparable homing to ischaemic sites on days 2-4. BLI showedthat OECs and early EPCs exhibit similar cell survival in ischaemic tissue (EarlyEPC vs OECBLI, p�0.42) with some cell survival �6 weeks. Nevertheless, in intravenous and intramus-cular EPC transplantation studies, OECs were superior to early EPCs for enhancement ofperfusion recovery (0.50�0.04vs0.39�0.06,p<0.01 and 0.65�0.05vs0.35�0.04,p<0.0001respectively) and ischaemia-induced angiogenesis, showing �36% increase in capillary den-sity (138�16vs91�9 and 129�17vs95�11,p>0.05 respectively). Similar findings wereobserved in the xenotransplantation model (0.30�0.02vs0.21�0.02,p<0.05). In patientswithCAD (n¼26,age¼63�10,male¼81%) therewas a positive correlation between the extentof coronary collateralisation and OEC numbers (r¼0.405,p¼0.045), migration(r¼0.578,p¼0.006) and tubulogenesis (r¼0.65,p¼0.005). Patients with adequatevsinade-quate collateralisation (CFI�0.25vs<0.25) had better OEC characteristics (p<0.02). Nocorrelation was found with early EPCs.Conclusion: Despite similarities in cell homing and survival, OECs are markedly superiorto early EPCs for improvement of ischaemia-mediated neovascularisation. Furthermore,adequate coronary collateralisation in CAD is associated with enhanced OEC but not earlyEPC characteristics. Selection for OECs may enhance cell therapies for augmentation ofangiogenesis.Disclosure of Interest: None Declared

O023

Does transtelephonic electrocardiography improve in-hospital mortality rate ofpatients with acute coronary syndrome?

Gyorgy Papai1, Daniel Czuriga2, Ildiko Racz2, Gabor T. Szabo*2, Istvan Edes21Hungarian National Ambulance Service, 2Institute of Cardiology, University of Debrecen,Medical and Health Science Center, Debrecen, Hungary

Introduction: The transtelephonic electrocardiography (TTECG) system is a fast andconvenient tool for transmission of locally recorded ECG, as well as for patient referral torelatively remote cardiac centers.Objectives: We examined the efficacy of the TTECG system in the management of STsegment elevation myocardial infarction (STEMI) with regard to the ambulance servicecontact and transport times, percutaneous coronary intervention (PCI)-related delay times,prehospital medical therapy and in-hospital mortality rate.Methods: The study was conducted between January 1, 2009 and December 31, 2010 inthe north-eastern region of Hungary (approximately 1.5 million residents) as a collaborativeeffort between the University of Debrecen, Hungary and the Hungarian National Ambu-lance Service. Altogether 776 patients were recruited in our study. The TTECG groupcomprised 397 patients, while 379 patients transported to the PCI center without TTECGserved as controls.Results: Significantly more patients received sodium heparin (84.3% vs. 59.1% in TTECGand Control groups, respectively; p<0.0001) and narcotics (56.99% vs. 13.76% in TTECGand Control groups, respectively; p¼<0.0001) in the TTECG group than among controls.The PCI-related delay times revealed that the door to sheath insertion and door to balloontimes were both significantly shorter for the TTECG group than for controls. In addition,the in-hospital mortality rate was significantly lower in the TTECG group compared tocontrols (4.28% vs. 8.44% in TTECG and Control groups, respectively; p¼0.0350).Conclusion: The findings clearly illustrate the value of TTECG in the regional managementof STEMI patients, with significant shortening of the PCI-related delay times and im-provements of the prehospital medical therapy and in-hospital mortality rate.Disclosure of Interest: None Declared

GHEART Vol 9/1S/2014 j March, 2014 j ORAL/2014 WCC Orals