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Monday, September 12, 2016 8:15 M1 Rosanna Degani Young Investigator Finals Chairs: Rob MacLeod and Leif Sornmo Room: Pinnacle II & III 1-107 Left Atrial Hypertrophy Increases P-Wave Terminal Force Through Amplitude but not Duration Axel Loewe*, Robin Andlauer, Olaf Dössel, Gunnar Seemann and Pyotr G. Platonov P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P- wave terminal force (PTF) in ECG lead V1. However, PTF- V1 has been shown to correlate poorly with LA size. We hypothesize that LA hypertrophy, i.e. a thickening of the myocardial wall, also contributes to increased PTF-V1 and is part of the reason for the rather low specificity of increased PTF-V1 regarding LA enlargement. To show this, atrial excitation propagation was simulated in a cohort of four anatomically individualized models including rule-based myocyte orientation and spatial electrophysiological heterogeneity using the monodomain approach. The LA wall was thickened symmetrically in steps of 0.66 mm by up to 3.96 mm. Body surface ECGs were computed using realistic, heterogeneous torso models. During the early P-wave stemming from sources in the RA, no changes were observed. Once the LA got activated, the voltage in V1 tended to lower values for higher degrees of hypertrophy. Thus, the amplitude of the late positive P-wave decreased while the amplitude of the subsequent terminal phase increased. PTF-V1 and LA wall thickening showed a correlation of 0.95. The P-wave duration was almost unaffected by LA wall thickening (≤2 ms). Our results show that PTF-V1 is a sensitive marker for LA wall thickening and elucidate why it is superior to P-wave area. The interplay of LA hypertrophy and dilation might cause the poor empirical correlation of LA size and PTF-V1. 2-366 Index of T-wave Variation as a Predictor of Sudden Cardiac Death in Chronic Heart Failure Patients with Atrial Fibrillation Alba Martin*, Iwona Cygankiewicz, Antoni Bayés-De-Luna, Pablo Laguna, Enrico G Caiani and Juan Pablo Martinez Aim: Chronic heart failure (CHF) together with atrial fibrillation (AF) are worldwide leading causes of morbidity and mortality in elders, where an important part of these deaths are due to sudden cardiac deaths (SCD). The high irregularity of ventricular response in AF patients makes the use of standard ECG-based SCD-risk markers inappropriate in this target population. The aim of this study was twofold: i) to propose a new index, suitable for AF patients, sensitive to ventricular repolarization changes; and ii) to evaluate its prognostic value in a population with CHF and AF. Materials and Methods: Holter ECG recordings from 176 consecutive CHF patients with AF, including 22 SCD events were analyzed (2 or 3 leads available, sampling frequency 200 Hz). The index of T-wave variation (ITV), quantifying the average T-wave changes in pairs of consecutive beats under stable rhythm conditions, was computed using a fully-automatic method based on the selective averaging technique. Survival analysis was performed considering SCD as an independent endpoint. Results: ITV was higher for SCD than for non-SCD victims (median (25th;75th percentile): 12.44 (7.21;42.71) µV vs 8.57 (5.63;14.08) µV, p=0.06). In a survival analysis where patients were classified as ITV(+) and ITV(-), setting the cut point at the third quartile of ITV values, ITV (+) outcome was successfully associated to SCD (Hazard Ratio (CI): 3.217 (1.365,7.581) per µV, p=0.008). Conclusion: In this study we have shown that ITV stratifies CHF patients with AF according to their risk of SCD, with larger T-wave variability associated to lower survival probability. 3-435 Modelling the Effects of Disopyramide on Short QT Syndrome Variant 1 in the Human Ventricles Dominic G Whittaker*, Haibo Ni, Alan P Benson, Jules C Hancox and Henggui Zhang Introduction: The short QT syndrome (SQTS) is a recently identified genetic disorder associated with ventricular and/or atrial arrhythmias and increased risk of sudden cardiac death. The SQTS variant 1 (SQT1) N588K mutation to the hERG gene causes a gain-of-function to IKr which shortens the ventricular effective refractory period (ERP), as well as reducing the potency of drugs which block the hERG channel. This study used computational modelling to assess the effects of disopyramide (DSP), a class 1a anti-arrhythmic agent, on human ventricular electrophysiology and re-entrant wave dynamics in SQT1. Methods: The O’Hara-Rudy dynamic (ORd) model of the human ventricular action potential (AP) was modified to incorporate a Markov chain model of IKr/hERG including formulations for wild type (WT) and SQT1 N588K mutant hERG channels. The blocking effects of DSP on IKr, INa, and ICaL were modelled using IC50 and nH (Hill coefficient) values from the literature, including different blocking potencies for IKr in WT and SQT1 mutant hERG channels. The ability of DSP to prolong the QT interval was evaluated using a 1D model of human ventricle with transmural heterogeneities and the corresponding pseudo-ECG. An idealised 3D left ventricular wedge model was also constructed in order to investigate the effects of DSP on re-entrant excitation wave dynamics. Results: Upon application of 10 µM DSP, which lies within the clinically-relevant range, the corrected QT interval in the SQT1 case was prolonged from 282 ms to 346 ms. Furthermore, this concentration of DSP increased the ventricular effective refractory period such that sustained re-entrant activity was no longer inducible in the left ventricular wedge model. Conclusion: We have used computational modelling to dissect ionic mechanisms of QT prolongation and anti-arrhythmic effects of DSP on SQT1 in the human ventricles. This study provides new insights into a potential pharmacological treatment in hERG-mediated SQTS. 4-418 Highest Dominant Frequency and Rotor Sites are Robust Markers for Atrial Driver Location in Non-invasive Mapping of Atrial Fibrillation Miguel Rodrigo*, Andreu M Climent, Alejandro Liberos, Francisco Fernández-Avilés, Omer Berenfeld, Felipe Atienza and Maria S Guillem Background: Inverse-computed Dominant Frequency (DF) and rotor maps have been proposed as non-invasive mapping techniques to locate atrial drivers maintaining atrial fibrillation (AF). This study evaluates the robustness of both techniques in localizing atrial drivers under the effect of electrical noise or uncertainties in the heart-torso structure. Methods: Anatomically realistic model of the atria within the torso was built. Inverse-computed DFs and phase maps were obtained on a population of 30 different mathematical AF simulations maintained by a single rotor and subjected to model variations. Simulated atrial highest DF (HDF) regions and rotor locations were compared with the same inverse-computed measurements following each variation: (i) ECG with white noise to the ECG (60-0 dB signal-to- noise ratio), (ii) linear (0-5 cm) or (iii) angular (0-45º) variation in the location and orientation of the atria inside the torso, or (iv) varying blood conductivity (0.5-9 S/m). Results: Individual inverse-computed EGMs showed a poor correlation coefficient of 0.45±0.12 with the actual EGMs in the absence of variations. The correlation coefficient worsened further to 0.22±0.11 with 10 dB noise, 0.01±0.02 with 3 cm displacement and 0.02±0.03 with 36º angular variation. However, inverse-computed HDF regions showed robustness in correlations against variations: from 82±18% match for the HDF region for the best conditions, down to 73±23% for 10 dB of noise, 77±21% for 5 cm displacement and 60±22% for 36º angular variation. The rotor location also presented a robust measurement: the distance from the inverse- computed rotor to the actual rotor was 0.8±1.61 cm for the best conditions, 2.4±3.6 cm for 10 dB of noise, 4.3±3.2 cm for 4 cm displacement and 4.0±2.1 cm for 36º. Conclusions: Localization of AF sources based on HDF and rotor location from non-invasive mapping is accurate even in the presence of noise and uncertainties in the atrial location or torso/blood conductance. Monday, September 12, 2016 10:00 S21 System Studies in Cardiovascular Autonomic Function Chairs: Andrew Blaber and Sonia Gouveia Room: Pinnacle II 5-248 Controlling the Inspiration/Expiration Ratio Benefits the Deceleration Capacity Index of Heart Rate in Assessing the Sympatho-vagal Balance Qing Pan, Chenglong Gao, Gongzhan Zhou, Ruofan Wang, Yihua Yu, Luping Fang* and Gangmin Ning Introduction: Deceleration capacity (DC) of heart rate is a novel index for evaluating the activity of the autonomic nervous system (ANS). We examined whether controlling the inspiration/expiration (I/E) ratio benefits the DC analysis based on a model-generated RR interval (RRI) database. A cardiovascular system model was adopted to simulate RRI time series. The model allows analyzing the role of sympathetic and vagal activities in the ANS. The respiratory pattern can be controlled in the model. Methods: Three hundred RRI time series with random sympathetic and vagal activities were simulated. According to the ratio between the sympathetic and vagal activities (S/V ratio), these subjects were categorized into a case group (S/V>1) and a control group (S/V<1). DC was computed for each subject. The performance of DC in distinguishing the two groups was examined by the receiver operating characteristic (ROC) analysis. The respiratory period is set to 6 s. The I/E ratio was controlled as 1:2, 1:1 and 2:1, respectively, and the performances of DC under different I/E ratios were compared. Results: The numbers of subjects in the case group and the control group are 161 and 139.
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