The role of atrial sensing for new-onset atrial arrhythmias diagnosis and management in single-chamber implantable cardioverter-defibrillator recipients: Results from the THINGS registry.

INTRODUCTION: Atrial tachycardia/fibrillation (AT/AF) episodes are common in implantable cardioverter-defibrillator (ICD) recipients and can be undetected by standard single-chamber devices. This study aims to explore whether a single-lead ICD with an atrial dipole (ICD DX; BIOTRONIK SE & Co, Berlin, Germany) could improve the AT/AF diagnosis and management as compared to standard ICD (ICD VR). METHODS AND RESULTS: We selected patients without AT/AF history from the THINGS registry which included consecutive patients implanted with ICD for standard indications. The ICD VR and the ICD DX groups included 236 (62.8%) and 140 (37.2%) patients, respectively, and had no significant differences in baseline characteristics. During a median follow-up of 27 months, there were 7 AT/AF diagnoses in the ICD VR and 18 in the ICD DX group. The 2-year incidence of AT/AF diagnosis was 3.6% (95% confidence interval [CI]: 1.6%-9.6%) for the ICD VR and 11.4% (95% CI: 6.8%-18.9%) for the ICD DX group (adjusted hazard ratio [HR]: 3.85 [95% CI: 1.58-9.41]; P = .003). Initiation of oral anticoagulation (OAC) due to AT/AF diagnosis was reported in 15 patients. The 2-year incidence of OAC onset was 3.6% (95% CI: 1.6%-7.8%) for the ICD VR and 6.3% (95% CI: 3.0%-12.7%) for ICD DX group (adjusted HR: 1.99 [95% CI: 0.72-5.56]; P = .184). CONCLUSION: We observed that atrial sensing capability in single-chamber ICD patients without evidence of atrial arrhythmias at implant is associated with a greater likelihood of detecting AT/AF episodes. The management of these diagnosed arrhythmias often led to clinical interventions, mainly represented by initiation of OAC therapy.

Impact of atrial programmed electrical stimulation techniques on unipolar electrogram morphology.

INTRODUCTION: Intra-atrial conduction abnormalities are associated with the development of atrial fibrillation (AF) and cause morphological changes of the unipolar atrial electrogram (U-AEGM). This study examined the impact of different atrial programmed electrical stimulation (APES) protocols on U-AEGM morphology to identify the most optimal APES protocol provoking conduction abnormalities. METHODS: APES techniques (14 protocols) were applied in 30 patients referred for an electrophysiology study, consisting of fixed rate, extra, and decremental stimuli at different frequencies. U-AEGM morphologies including width, amplitude, and fractionation for patients without (control group) and with a history of AF (AF group) were examined during APES. In addition, sinus rhythm (SR) U-AEGMs preceding different APES protocols were compared to evaluate the morphology stability over time. RESULTS: U-AEGM morphologies during SR before the APES protocols were comparable (all P > .396). Atrial refractoriness was longer in the AF group compared to the control group (298 ± 48 vs 255 ± 33 ms; P ≤ .020), but did not differ between AF patients with and without amiodarone therapy (278 ± 48 vs 311 ± 40 ms; P ≥ .126). Compared to the initial SR morphology, U-AEGM width, amplitude, and fractionation changed significantly during the 14 different APES protocols, particularly in the AF group. In both groups, U-AEGM changes in morphology were most pronounced during fixed-rate stimulation with extra stimuli (8S1-S2 = 400-250 ms). CONCLUSION: APES results in significant changes in U-AEGM morphology, including width, amplitude, and fractionation. The impact of APES differed between APES sequence and between patients with and without AF. These findings suggest that APES could be useful to identify AF-related conduction abnormalities in the individual patient.

Probabilistic Interpolation of Uncertain Local Activation Times on Human Atrial Manifolds.

OBJECTIVE: Local activation time (LAT) mapping of the atria is important for targeted treatment of atrial arrhythmias, but current methods do not interpolate on the atrial manifold and neglect uncertainties associated with LAT observations. In this paper, we describe novel methods to, first, quantify uncertainties in LAT arising from bipolar electrogram analysis and assignment of electrode recordings to the anatomical mesh, second, interpolate uncertain LAT measurements directly on left atrial manifolds to obtain complete probabilistic activation maps, and finally, interpolate LAT jointly across both the manifold and different S1-S2 pacing protocols. METHODS: A modified center of mass approach was used to process bipolar electrograms, yielding a LAT estimate and error distribution from the electrogram morphology. An error distribution for assigning measurements to the anatomical mesh was estimated. Probabilistic LAT maps were produced by interpolating on a left atrial manifold using Gaussian Markov random fields, taking into account observation errors and characterizing LAT predictions by their mean and standard deviation. This approach was extended to interpolate across S1-S2 pacing protocols. RESULTS: We evaluated our approach using recordings from three patients undergoing atrial ablation. Cross-validation showed consistent and accurate prediction of LAT observations both at different locations on the left atrium and for different S1-S2 intervals. SIGNIFICANCE: Interpolation of scalar and vector fields across anatomical structures from point measurements is a challenging problem in biomedical engineering, compounded by uncertainties in measurements and meshes. New methods and approaches are required, and in this paper, we have demonstrated an effective method for probabilistic interpolation of uncertain LAT.

Pharmacological investigation of activities pertaining to modulation of gastrointestinal, respiratory and cardiovascular parameters by Indigofera argentea in experimental models.

Indigofera argentea is widely used for the management of gastrointestinal, respiratory and cardiac disorders. This study was done to explore scientific basis of its uses. Aqueous methanolic extract of Indigofera argentea and its fractions were studied on isolated tissues of rabbit's jejunum, trachea, aorta and atrium. Castor oil induced diarrheal model was used for the study of the antidiarrheal effect and pre-anesthetized rats were used for hypotensive study. Concentration dependent spasmolytic effect of the extract upon isolated jejunum, trachea and aorta was observed. Concentration response curves constructed upon isolated rabbit jejunum, revealed the presence of calcium channel blocker in the plant extract. Moreover, significant reduction (P<0.05) in atrial force of contraction but non-significant reduction in rate of contraction was seen by the application of plant extract. Protection (P<0.05) against diarrhea was observed by the administration of crude extract to rats which were pretreated with castor oil. When given to rats intravenously, the extract showed hypotensive effect. Experimental findings justified the traditional uses of Indigofera argentea on pharmacological basis for the management of disorders pertaining to gut, airway and hypertensive situation.

A constant postpacing interval in response to overdrive pacing with variable number of beats: An aid in the identification of entrainment for a particular pacing train during macroreentrant atrial tachycardias.

BACKGROUND: When pacing trains with a constant cycle length (CL) but increasing number of beats are introduced during a macroreentrant atrial tachycardia (MAT), the postpacing interval (PPI) is expected to increase if entrainment does not occur but could be stable if entrainment occurs. We tested the ability of PPI analysis to detect entrainment. METHODS: Synchronized pacing trains with increasing number of beats (1-20) were delivered from the coronary sinus (CS) and lateral right atrium (RA) at a CL 20 ms shorter than the MAT CL. Pacing trains were grouped in pairs differing by one-paced beat, and the ∆PPI measured. RESULTS: In an initial prospective cohort of 21 patients (48% had left atrial flutter) the mean ∆PPI was 21.3 ± 5.6 ms for pairs of pacing trains in which neither entrained the MAT and 2.8 ± 1.4 ms for those in which both entrained the MAT (P < .0001). Results were similar for common vs atypical flutter, PPI-TCL ≤30 ms vs PPI-TCL >30 ms, presence vs absence of antiarrhythmic drugs and faster vs slower MAT. When an index pacing train was compared to one with two-paced beats less, a PPI difference of <19 ms identified entrainment with 95% sensitivity and 98% specificity. In a validation cohort of 16 patients, this cut-off value resulted in sensitivity and specificity of 90% and 94%. CONCLUSIONS: A relatively constant ∆PPI in response to overdrive pacing with identical CL but different number of beats allows accurate discrimination between trains that entrained vs those which did not entrain a MAT.

The stationary wavelet transform as an efficient reductor of powerline interference for atrial bipolar electrograms in cardiac electrophysiology.

OBJECTIVE: The most relevant source of signal contamination in the cardiac electrophysiology (EP) laboratory is the ubiquitous powerline interference (PLI). To reduce this perturbation, algorithms including common fixed-bandwidth and adaptive-notch filters have been proposed. Although such methods have proven to add artificial fractionation to intra-atrial electrograms (EGMs), they are still frequently used. However, such morphological alteration can conceal the accurate interpretation of EGMs, specially to evaluate the mechanisms supporting atrial fibrillation (AF), which is the most common cardiac arrhythmia. Given the clinical relevance of AF, a novel algorithm aimed at reducing PLI on highly contaminated bipolar EGMs and, simultaneously, preserving their morphology is proposed. APPROACH: The method is based on the wavelet shrinkage and has been validated through customized indices on a set of synthesized EGMs to accurately quantify the achieved level of PLI reduction and signal morphology alteration. Visual validation of the algorithm's performance has also been included for some real EGM excerpts. MAIN RESULTS: The method has outperformed common filtering-based and wavelet-based strategies in the analyzed scenario. Moreover, it possesses advantages such as insensitivity to amplitude and frequency variations in the PLI, and the capability of joint removal of several interferences. SIGNIFICANCE: The use of this algorithm in routine cardiac EP studies may enable improved and truthful evaluation of AF mechanisms.

A compact matrix model for atrial electrograms for tissue conductivity estimation.

Finding the hidden parameters of the cardiac electrophysiological model would help to gain more insight on the mechanisms underlying atrial fibrillation, and subsequently, facilitate the diagnosis and treatment of the disease in later stages. In this work, we aim to estimate tissue conductivity from recorded electrograms as an indication of tissue (mal)functioning. To do so, we first develop a simple but effective forward model to replace the computationally intensive reaction-diffusion equations governing the electrical propagation in tissue. Using the simplified model, we present a compact matrix model for electrograms based on conductivity. Subsequently, we exploit the simplicity of the compact model to solve the ill-posed inverse problem of estimating tissue conductivity. The algorithm is demonstrated on simulated data as well as on clinically recorded data. The results show that the model allows to efficiently estimate the conductivity map. In addition, based on the estimated conductivity, realistic electrograms can be regenerated demonstrating the validity of the model.

Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: Muscarinic receptor-linked vasorelaxant and cardiotonic effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Eruca sativa Mill., (Brassicaceae) is a popular remedy for the treatment of hypertension in Pakistan. However, direct effect of the extract and its fractions on blood pressure and vascular tone are unknown. AIM OF THE STUDY: This investigation was aimed to explore the pharmacological base for the traditional use of E. sativa in hypertension. MATERIALS AND METHODS: In-vivo blood pressure study was carried out using normotensive and high salt-induced hypertensive rats under anaesthesia. The cardiovascular mechanisms were explored using rat aorta and atria in-vitro. Preliminary phytochemical analysis, spectrophotometric detection of total phenols, flavonoids and HPLC analysis of crude extract were performed using quercetin and erucin as marker compounds. RESULTS: Intravenous injection of crude extract induced a fall in mean arterial pressure (MAP) in both normotensive (max fall: 41.79 ±â€¯1.55% mmHg) and hypertensive (max fall: 58.25 ±â€¯0.91% mmHg) rats. Atropine (1 mg/kg) pretreatment attenuated this effect significantly (p < 0.001), suggesting the involvement of muscarinic receptor in its antihypertensive effect. Fractions also induced atropine-sensitive antihypertensive effect. Similarly, oral administration of crude and aqueous extracts resulted a fall in MAP in the hypertensive rats. In isolated rat aortic rings from normotensive rats, crude extract and fractions induced an endothelium-dependent relaxation. This relaxation was partially inhibited with L-NAME and atropine pretreatment and with denudation of aortic rings, indicating involvement of muscarinic receptor-linked nitric oxide (NO). In aorta from the hypertensive rats, crude extract and fractions induced endothelium-independent relaxation. This relaxation was not affected by pretreatment with L-NAME or atropine. Crude extract and fractions also suppressed phenylephrine contractions in Ca+2 free/EGTA medium. In isolated rat atrial preparations, crude extract and fractions induced negative inotropic and chronotropic effects with a positive inotropic effect by the n-hexane fraction, which were not affected with atropine pretreatment. Phytochemical screening and spectrophotometric analysis indicated the presence of phenols and flavonoids, whereas HPLC analysis of crude extract revealed the presence of quercetin (flavonoid) and erucin (isothiocyanate). CONCLUSION: The results suggest that E. sativa is an antihypertensive remedy which is mainly due to its vasodilatory and partly cardiac effects. Muscarinic receptors-linked NO release and dual inhibitory effect on Ca+2 influx and release underlie the vasodilation. This finding provides pharmacological base to the traditional use of E. sativa in hypertension. The presence of quercetin and erucin further support this finding.

A Novel Mapping System for Panoramic Mapping of the Left Atrium: Application to Detect and Characterize Localized Sources Maintaining Atrial Fibrillation.

Objectives: This study sought to use a novel panoramic mapping system (CARTOFINDER) to detect and characterize drivers in persistent atrial fibrillation (AF). Background: Mechanisms sustaining persistent AF remain uncertain. Methods: Patients undergoing catheter ablation for persistent AF were included. A 64-pole basket catheter was used to acquire unipolar signals, which were processed by the mapping system to generate wavefront propagation maps. The system was used to identify and characterize potential drivers in AF pre- and post-pulmonary vein (PV) isolation. The effect of ablation on drivers identified post-PV isolation was assessed. Results: Twenty patients were included in the study with 112 CARTOFINDER maps created. Potential drivers were mapped in 19 of 20 patients with AF (damage to the basket and noise on electrograms was present in 1 patient). Thirty potential drivers were identified all of which were transient but repetitive; 19 were rotational and 11 focal. Twenty-six drivers were ablated with a predefined response in 22 of 26 drivers: AF terminated with 12 and cycle length slowed (≥30 ms) with 10. Drivers with rotational activation were predominantly mapped to sites of low-voltage zones (81.8%). PV isolation had no remarkable impact on the cycle length at the driver sites (138.4 ± 14.3 ms pre-PV isolation vs. 137.2 ± 15.2 ms post-PV isolation) and drivers that had also been identified on pre-PV isolation maps were more commonly associated with AF termination. Conclusions: Drivers were identified in almost all patients in the form of intermittent but repetitive focal or rotational activation patterns. The mechanistic importance of these phenomena was confirmed by the response to ablation.

Regional conduction velocity calculation from clinical multichannel electrograms in human atria.

BACKGROUND: During atrial fibrillation, heterogeneities and anisotropies result in a chaotic propagation of the depolarization wavefront. The electrophysiological parameter called conduction velocity (CV) influences the propagation pattern over the atrium. We present a method that determines the regional CV for deformed catheter shapes, which result due to the catheter movement and changing wall contact. METHODS: The algorithm selects stable catheter positions, finds the local activation times (LAT), considers the wall contact and calculates all CV estimates within the area covered by the catheter. The method is evaluated with simulated data and then applied to four clinical data sets. Both sinus rhythm activity as well as depolarization wavefronts initiated by stimulation are analyzed. The regional CV is compared with the fractionation duration (FD) and peak-to-peak (P2P) voltages. A speed of 0.5 m/s was defined to create the simulated LAT. RESULTS: After analyzing the simulated LAT with clinical catheter spatial coordinates, the median CV of 0.5 m/s with an interquartile range of 0.22 and exact CV direction vectors were obtained. For clinical cases, the CV magnitude range of 0.08 m/s to 1.0 m/s was obtained. The P2P amplitude of 0.7 mV to 3.7 mV and the mean FD from 40.79ms to 48.66ms was obtained. The correlation of 0.86 was observed between CV and P2P amplitude, and 0.62 between CV and FD. CONCLUSION: In this paper, a method is presented and validated which calculates the CV for the deformed catheter and changing wall contact. In an exemplary clinical data set correlation between regional CV with FD and the P2P voltage was observed.

Local activation time sampling density for atrial tachycardia contact mapping: how much is enough?

Aims: Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach. Methods and results: In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry. In silico activation was simulated on a 4×4cm atrial monolayer, sampled randomly at 0.25-10 points/cm2 and used to re-interpolate LAT maps. Activation patterns were studied in the geometrically simple porcine right atrium (RA) and complex human left atrium (LA). Activation complexity was introduced into the porcine RA by incomplete inter-caval linear ablation. In all cases, optimal sampling density was defined as the highest density resulting in minimal further error reduction in the re-interpolated maps. Optimal sampling densities for LA tachycardias were 0.67 ± 0.17 points/cm2 (focal activation), 1.05 ± 0.32 points/cm2 (macro-re-entry) and 1.23 ± 0.26 points/cm2 (localized re-entry), P = 0.0031. Increasing activation complexity was associated with increased optimal sampling density both in silico (focal activation 1.09 ± 0.14 points/cm2; re-entry 1.44 ± 0.49 points/cm2; spiral-wave 1.50 ± 0.34 points/cm2, P < 0.0001) and in vivo (porcine RA pre-ablation 0.45 ± 0.13 vs. post-ablation 0.78 ± 0.17 points/cm2, P = 0.0008). Increasing chamber geometry was also associated with increased optimal sampling density (0.61 ± 0.22 points/cm2 vs. 1.0 ± 0.34 points/cm2, P = 0.0015). Conclusion: Optimal sampling densities can be identified to maximize diagnostic yield of LAT maps. Greater sampling density is required to correctly reveal complex activation and represent activation across complex geometries. Overall, the optimal sampling density for LAT map interpolation defined in this study was ∼1.0-1.5 points/cm2.

MRI use for atrial tissue characterization in arrhythmias and for EP procedure guidance.

We review the utilization of magnetic resonance imaging methods for classifying atrial tissue properties that act as a substrate for common cardiac arrhythmias, such as atrial fibrillation. We then review state-of-the-art methods for mapping this substrate as a predicate for treatment, as well as methods used to ablate the electrical pathways that cause arrhythmia and restore patients to sinus rhythm.

Intra-atrial re-entrant tachycardia in congenital heart disease: types and relation of isthmus to atrial voltage.

Background: Intra-atrial re-entrant tachycardia (IART) is a frequent and severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is also frequent. Objective: The main objective of this study was to describe the types of IART and circuit locations and to define a cut-off value for unhealthy tissue in the atria. Methods and results: This observational study included all consecutive patients with CHD who underwent a first ablation procedure for IART from January 2009 to December 2015 (94 patients, 39.4% female, age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). Cavotricuspid isthmus-related IART was the only arrhythmia in 51% (n = 48) of patients, non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented both types of IART. In cases of non-CTI-related IART, the most frequent location of IART isthmus was the lateral or posterolateral wall of the venous atria, and a voltage cut-off value for unhealthy tissue in the atria of 0.5 mV identified 95.4% of IART isthmus locations. Conclusion: In our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% of patients (alone or with concomitant CTI-related IART). A cut-off voltage of 0.5 mV could identify 95.4% of the substrates in non-CTI-related IART.

Tissue-Level Cardiac Electrophysiology Studied in Murine Myocardium Using a Microelectrode Array: Autonomic and Thermal Modulation.

Cardiac electrophysiology is regulated by the autonomic nervous system, and this has both pathophysiological, and possibly therapeutic importance. Furthermore, chamber differences in electrophysiology exist between atria and ventricles, yet there have been few direct comparisons. There is substantial literature on ion channel modulation at the single-cell level but less work on how this affects tissue-level parameters. We used a microelectrode array system to explore these issues using murine atrial and ventricular tissue slices. Activation time, conduction velocity and repolarisation were measured, and their modulation by temperature and pharmacological autonomic agonists were assessed. The system recorded reliable measurements under control conditions in the absence of drug/thermal challenge, and significant baseline differences were found in chamber electrophysiology. The sodium channel blocker mexiletine, produced large magnitude changes in all three measured parameters. Carbachol and isoprenaline induced differing effects in atria and ventricles, whereas temperature produced similar effects on activation and repolarisation.

Personalized Models of Human Atrial Electrophysiology Derived From Endocardial Electrograms.

OBJECTIVE: Computational models represent a novel framework for understanding the mechanisms behind atrial fibrillation (AF) and offer a pathway for personalizing and optimizing treatment. The characterization of local electrophysiological properties across the atria during procedures remains a challenge. The aim of this work is to characterize the regional properties of the human atrium from multielectrode catheter measurements. METHODS: We propose a novel method that characterizes regional electrophysiology properties by fitting parameters of an ionic model to conduction velocity and effective refractory period restitution curves obtained by a s1-s2 pacing protocol applied through a multielectrode catheter. Using an in-silico dataset we demonstrate that the fitting method can constrain parameters with a mean error of 21.9 ± 16.1% and can replicate conduction velocity and effective refractory curves not used in the original fitting with a relative error of 4.4 ± 6.9%. RESULTS: We demonstrate this parameter estimation approach on five clinical datasets recorded from AF patients. Recordings and parametrization took approx. 5 and 6 min, respectively. Models fitted restitution curves with an error of ~ 5% and identify a unique parameter set. Tissue properties were predicted using a two-dimensional atrial tissue sheet model. Spiral wave stability in each case was predicted using tissue simulations, identifying distinct stable (2/5), meandering and breaking up (2/5), and unstable self-terminating (1/5) spiral tip patterns for different cases. CONCLUSION AND SIGNIFICANCE: We have developed and demonstrated a robust and rapid approach for personalizing local ionic models from a clinically tractable.

Towards personalized computational modelling of the fibrotic substrate for atrial arrhythmia.

: Atrial arrhythmias involving a fibrotic substrate are an important cause of morbidity and mortality. In many cases, effective treatment of such rhythm disorders is severely hindered by a lack of mechanistic understanding relating features of fibrotic remodelling to dynamics of re-entrant arrhythmia. With the advent of clinical imaging modalities capable of resolving the unique fibrosis spatial pattern present in the atria of each individual patient, a promising new research trajectory has emerged in which personalized computational models are used to analyse mechanistic underpinnings of arrhythmia dynamics based on the distribution of fibrotic tissue. In this review, we first present findings that have yielded a robust and detailed biophysical representation of fibrotic substrate electrophysiological properties. Then, we summarize the results of several recent investigations seeking to use organ-scale models of the fibrotic human atria to derive new insights on mechanisms of arrhythmia perpetuation and to develop novel strategies for model-assisted individualized planning of catheter ablation procedures for atrial arrhythmias.

Modelling methodology of atrial fibrosis affects rotor dynamics and electrograms.

AIMS: Catheter ablation is an effective technique for terminating atrial arrhythmia. However, given a high atrial fibrillation (AF) recurrence rate, optimal ablation strategies have yet to be defined. Computer modelling can be a powerful aid but modelling of fibrosis, a major factor associated with AF, is an open question. Several groups have proposed methodologies based on imaging data, but no comparison to determine which methodology best corroborates clinically observed reentrant behaviour has been performed. We examined several methodologies to determine the best method for capturing fibrillation dynamics. METHODS AND RESULTS: Patient late gadolinium-enhanced magnetic resonance imaging data were transferred onto a bilayer atrial computer model and used to assign fibrosis distributions. Fibrosis was modelled as conduction disturbances (lower conductivity, edge splitting, or percolation), transforming growth factor-ß1 ionic channel effects, myocyte-fibroblast coupling, and combinations of the preceding. Reentry was induced through pulmonary vein ectopy and the ensuing rotor dynamics characterized. Non-invasive electrocardiographic imaging data of the patients in AF was used for comparison. Electrograms were computed and the fractionation durations measured over the surface. Edge splitting produced more phase singularities from wavebreaks than the other representations. The number of phase singularities seen with percolation was closer to the clinical values. Addition of fibroblast coupling had an organizing effect on rotor dynamics. Simple tissue conductivity changes with ionic changes localized rotors over fibrosis which was not observed with clinical data. CONCLUSION: The specific representation of fibrosis has a large effect on rotor dynamics and needs to be carefully considered for patient specific modelling.

Low-Level But Not High-Level Baroreceptor Stimulation Inhibits Atrial Fibrillation in a Pig Model of Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) increases susceptibility to atrial fibrillation (AF) by a combined sympatho-vagal hyperactivation. The purpose of this study was to investigate the effect of autonomic nervous system modulation by low-level baroreceptor stimulation (LL-BRS) compared to high-level BRS (HL-BRS) on atrial arrhythmogenic changes in a pig model of OSA. METHODS AND RESULTS: Sixteen pigs received tracheotomy under general urethane/chloralose anesthesia. Group 1 pigs (n = 8) received LL-BRS (at 80% of that slowing sinus rate) for 3 hours and group 2 pigs (n = 8) received HL-BRS (slowing sinus rate). Changes in atrial effective refractory period (AERP) and AF-inducibility were determined during applied negative thoracic pressure (NTP) for 2 minutes before and at the end of the 3-hour stimulation protocol. Group 1: LL-BRS prolonged AERP from 150 ± 5 to 172 ± 19 milliseconds (P < 0.001). After 3 hours of LL-BRS, NTP-induced AERP-shortening was diminished from -51 ± 10 milliseconds (-34%) to -22 ± 4 milliseconds (-13%) (P < 0.01). AF-inducibility during NTP maneuvers decreased from 90% at baseline to 15% (P < 0.01). Group 2: HL-BRS shortened AERP from 150 ± 17 to 132 ± 8 milliseconds (P = 0.024). After 3 hours of HL-BRS, NTP-induced AERP-shortening was increased from -55 ± 7 milliseconds (-36%) to -72 ± 11 milliseconds (-54%) (P < 0.05) and AF-inducibility was not affected. NTP-induced changes in blood gases and blood pressure were not different between the groups. CONCLUSION: LL-BRS suppressed NTP-induced AERP-shortening and AF-inducibility. By contrast HL-BRS further perpetuated NTP-induced AERP-shortening and increased AF-inducibility. These findings support only the use of LL-BRS as a novel therapeutic modality to treat AF in OSA.

QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.

Local Heterogeneous Electrical Restitution Properties of Rabbit Atria.

INTRODUCTION: This study aims to characterize the regional variability in rate-adaptation in the atria. METHODS AND RESULTS: Action potential (AP) responses to pulses with uniform as well as pseudo-random non-uniform pacing intervals were recorded from rabbit sino-atrial node, right and left atrial pectinate as well as pulmonary vein antrum tissue preparations using conventional intracellular glass microelectrodes. Steady-state restitution curves were reconstructed for various AP waveform metrics. We observed significant variability between the four regions under basal pacing representing the rabbit resting heart rate as well as regional variability in rate-adaptation to increased pacing frequencies. Right-left atrial restitution differences were further confirmed using the non-uniform pacing protocol, with significant differences in AP amplitude, duration (APD) as well as maximum phase 0 depolarization rate restitution curves in response to an identical sequence of non-uniform pacing intervals. In addition, we report regional differences in alternans of AP waveform metrics, over a wide range of pacing frequencies and not simply prior to 1:1 entrainment being lost. We also observed an increase in APD90 along the conduction pathway from the left atrium to pulmonary vein junction. CONCLUSIONS: Our results identified significant regional differences in electrical restitution in the rabbit atria and suggest their dependency on both baseline AP morphology and local intrinsic differences in rate-adaptation. We propose that the atrial heterogeneity in rate-adaptation could contribute to arrhythmogenesis and the greater susceptibility of pulmonary vein myocardial sleeves to ectopic foci and reentrant activity.