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ABSTRACT There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent... more
ABSTRACT There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent conduction in chronically stretched atria. Twenty-four patients with chronic atrial stretch due to mitral stenosis and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, and coronary sinus (CS) characterized direction-dependent conduction along linear catheters and across the crista terminalis. Bi-atrial electroanatomic maps were created in both sinus rhythm and an alternative wavefront direction by pacing from the distal CS. This allowed an assessment of conduction velocities, electrogram, and voltage characteristics during wavefronts propagating in different directions. While differing wavefront directions caused changes in both chronic atrial stretch and reference patients (P< 0.001 for all), these direction-dependent changes were greater in chronic atrial stretch compared with reference patients, who exhibited greater slowing in conduction velocities (P= 0.09), prolongation of bi-atrial activation time (P= 0.04), increase in number (P< 0.001) and length (P< 0.001) of lines of conduction block, increase in fractionated electrograms (P< 0.001), and decrease in voltage (P= 0.08) during left-to-right compared with right-to-left atrial activation. These direction-dependent changes were associated with a greater propensity for chronically stretched atria to develop atrial fibrillation (P= 0.02). Atrial remodelling in chronic atrial stretch exacerbates physiological direction-dependent conduction characteristics. Our data suggest that the greater direction-dependent conduction seen in patients with chronic atrial stretch may promote arrhythmogenesis due to ectopic triggers from the left atrium.
Conventional mapping of complex atrial tachycardias (AT) can be challenging. Thus, we evaluated feasibility and utility of a novel, ultra high-density 3D mapping approach to characterize and map AT in these cases. Overall, 21 patients... more
Conventional mapping of complex atrial tachycardias (AT) can be challenging. Thus, we evaluated feasibility and utility of a novel, ultra high-density 3D mapping approach to characterize and map AT in these cases. Overall, 21 patients (67.4±7.6 years; male: 52.4%, 1.9±1.4 previous ablation procedures) with documented AT referred to our center underwent catheter ablation including ultra high-density mapping using a novel 64-electrode mini-basket catheter and an adjunctive 3D mapping system. A total of 24 AT (20 left atrial, 4 right atrial AT) were analyzed in 19 cases. In 2 patients map acquisition failed due to scarce local electrograms and unstable AT cycle length, respectively. Underlying mechanisms were focal (n = 3), as well as local (n = 8) and macro (n = 13) reentry tachycardias with a mean cycle length of 311.8±67.7 ms. The analysis of propagation waves, activation and voltage revealed complex activation patterns and allowed for the identification of critical sites of AT init...
BACKGROUND Regional cardiac sympathetic denervation causes electrophysiological heterogeneity and has been found to be a predictor of potentially lethal VT. CASE REPORT We present the case of 69-year-old patient admitted with recurrent... more
BACKGROUND Regional cardiac sympathetic denervation causes electrophysiological heterogeneity and has been found to be a predictor of potentially lethal VT. CASE REPORT We present the case of 69-year-old patient admitted with recurrent ventricular tachycardia and a history of anterior myocardial infarction. In line with Tc-99m-MIBI-SPECT perfusion imaging, electroanatomical mapping revealed extensive LV anterior scarring as detected by low-voltage areas. Surprisingly, I-123-MIBG-SPECT showed an extensive deficit of sympathetic innervation inferior (mismatch) and anterolateral (match). CONCLUSIONS Combination of electroanatomical mapping with tomographic imaging of innervation and perfusion might improve our understanding of the neural trigger of VT after myocardial infarction or substrate-based catheter ablation.
To explore technical challenges of phase singularity mapping during Atrial Fibrillation (AF) using direct contact electrograms. AF mapping was performed in high-density epicardial recordings of human paroxysmal (PAF) or persistent... more
To explore technical challenges of phase singularity mapping during Atrial Fibrillation (AF) using direct contact electrograms. AF mapping was performed in high-density epicardial recordings of human paroxysmal (PAF) or persistent (PersAF) (N=20 pts) AF with an array of 16x16 electrodes placed on atrial epicardium. Phase singularity (PS) points were detected using subsets of electrodes forming rings of varying size. PS detection using a 2x2 electrode ring identified 0.88±1.00 PS/s in PAF group and 3.91±2.51 per s in PersAF group (p<0.001) in 2.4x2.4 cm mapping area. All detected PS had a short lifespan with the longest being 1100 ms (6.8 rotations). Exploration of the PS detection in a numerical model demonstrated that at least 8 electrodes are required to avoid frequent false positive PS detection due to chance. Application of a detection grid consisting a double ring of electrodes (2x2 and 4x4 rings) decreased the number of false positive detections. The double ring was more resilient to electrode swapping (with just 3 instances of false positives vs. 4380 false positives using 2x2 ring). The number of detected rotors critically depends the parameters of the detection algorithm, especially the number of electrodes used to detect PS. Based on our results, we recommend double ring comprised of 2x2 and 4x4 grid of electrodes for robust rotor detection. Great methodological care has to be taken before equating detected PS with rotating waves and using PS detection algorithms to guide catheter ablation of atrial fibrillation.
The success rate of catheter ablation for persistent atrial fibrillation (AF) is still far from satisfactory. Identification of patients who will benefit from ablation is highly desirable. We investigated the predictive value of... more
The success rate of catheter ablation for persistent atrial fibrillation (AF) is still far from satisfactory. Identification of patients who will benefit from ablation is highly desirable. We investigated the predictive value of noninvasive AF complexity parameters derived from standard 12-lead ECGs for AF termination and long-term success of catheter ablation and compared them with clinical predictors. The study included a training (93 patients) and a validation set (81 patients) of patients with persistent AF undergoing stepwise radiofrequency ablation. In the training set AF terminated in 81% during catheter ablation, 77% were in sinus rhythm after 6 years and multiple ablations. ECG-derived complexity parameters were determined from a baseline 10-s 12-lead ECG. Prediction of AF termination was similar using only ECG (cross-validated mean area under the curve [AUC], 0.76±0.15) or only clinical parameters (mean AUC, 0.75±0.16). The combination improved prediction to a mean AUC of 0.79±0.13. Using a combined model of ECG and clinical parameters, sinus rhythm at long-term follow-up could be predicted with a mean AUC of 0.71±0.12. In the validation set AF terminated in 57%, 61% were in sinus rhythm after 4.6 years. The combined models predicted termination with an AUC of 0.70 and sinus rhythm at long-term follow-up with an AUC of 0.61. Overall, fibrillation-wave amplitude provided the best rhythm prediction. The predictive performance of ECG-derived AF complexity parameters for AF termination and long-term success of catheter ablation in patients with persistent AF is at least as good as known clinical predictive parameters, with fibrillation-wave amplitude as the best predictor.
We describe a novel approach for simultaneously determining regional differences in action potential (AP) morphology and tissue electrophysiological properties in isolated atria. The epicardial surface of rat atrial preparations was... more
We describe a novel approach for simultaneously determining regional differences in action potential (AP) morphology and tissue electrophysiological properties in isolated atria. The epicardial surface of rat atrial preparations was placed in contact with a multi-electrode array (9 × 10 silver chloride electrodes, 0.1 mm diameter and 0.1 mm pitch). A glass microelectrode (100 MΩ) was simultaneously inserted into the endocardial surface to record intracellular AP from either of 2 regions (A, B) during pacing from 2 opposite corners of the tissue. AP duration at 80% of repolarisation and its restitution curve was significantly different only in region A (p < 0.01) when AP was initiated at different stimulation sites. Alternans in AP duration and AP amplitude, and in conduction velocity were observed during 2 separate arrhythmic episodes. This approach of combining microelectrode array and intracellular membrane potential recording may provide new insights into arrhythmogenic mechan...
Loss of side-to-side electrical connections between atrial muscle bundles is thought to underlie conduction disturbances predisposing to atrial fibrillation (AF). Putatively, disruption of electrical connections occurs not only within the... more
Loss of side-to-side electrical connections between atrial muscle bundles is thought to underlie conduction disturbances predisposing to atrial fibrillation (AF). Putatively, disruption of electrical connections occurs not only within the epicardial layer but also between the epicardial layer and the endocardial bundle network, thus impeding transmural conductions ('breakthroughs'). However, both clinical and experimental studies have shown an enhancement of breakthroughs during later stages of AF. We tested the hypothesis that endo-epicardial uncoupling enhances endo-epicardial electrical dyssynchrony, breakthrough rate (BTR), and AF stability. In a novel dual-layer computer model of the human atria, 100% connectivity between the two layers served as healthy control. Atrial structural remodelling was simulated by reducing the number of connections between the layers from 96 to 6 randomly chosen locations. With progressive elimination of connections, AF stability increased. Reduction in the number of connections from 96 to 24 resulted in an increase in endo-epicardial dyssynchrony from 6.6 ± 1.9 to 24.6 ± 1.3%, with a concomitant increase in BTR. A further reduction to 12 and 6 resulted in more pronounced endo-epicardial dyssynchrony of 34.4 ± 1.15 and 40.2 ± 0.52% but with BTR reduction. This biphasic relationship between endo-epicardial coupling and BTR was found independently from whether AF was maintained by re-entry or by ectopic focal discharges. Loss of endo-epicardial coupling increases AF stability. There is a biphasic relation between endo-epicardial coupling and BTR. While at high degrees of endo-epicardial connectivity, the BTR is limited by the endo-epicardial synchronicity, at low degrees of connectivity, it is limited by the number of endo-epicardial connections.
Permanent pulmonary vein isolation (PVI) remains an essential goal of ablation therapy in patients with atrial fibrillation. Aim of this study was the intra-individual comparison of unexcitability to pacing along the ablation line vs.... more
Permanent pulmonary vein isolation (PVI) remains an essential goal of ablation therapy in patients with atrial fibrillation. Aim of this study was the intra-individual comparison of unexcitability to pacing along the ablation line vs. dormant conduction (DC) as additional procedural endpoints. A total of 58 patients with paroxysmal atrial fibrillation (PAF) underwent PVI by circumferential ablation of ipsilateral pulmonary veins (PVs), followed by testing for DC by adenosine administration. Irrespective of the presence of DC, pacing along the ablation line for left atrium capture was performed and additional radio frequency (RF) energy applied if necessary. PVs with initial DC were re-tested after achieving unexcitability. PVI was achieved in 224 of 224 PVs. In 33 of 224 PVs (15%) DC was revealed. At 92 of 112 ablation lines (82%) sites of excitability were found. Three (9%) of the initial 33 PVs with DC showed further DC after achieving unexcitability at repeated testing. 32 of 33 assumed areas of unmasked PV-LA re-conduction as revealed by DC-testing showed a corresponding site of excitability on the ablation line. After a follow-up of 11.6±3.4 months 79% of patients were free of arrhythmia. Pacing for unexcitability can safely identify potential sites of DC and even sites that would have not been detected by testing for DC. Unexcitability therefore serves as a suitable and safe procedural endpoint not only for patients with contraindications to adenosine administration. Our data suggest that adenosine may be expendable when achieving unexcitability along the ablation line. This article is protected by copyright. All rights reserved.
... Frédéric Sacher, Martin Rotter, Mélèze Hocini, Li-Fern Hsu, Martin K. Stiles, Bobby John, Dennis H. Lau, ... Lancet 1989;1:175–9. 9 Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation... more
... Frédéric Sacher, Martin Rotter, Mélèze Hocini, Li-Fern Hsu, Martin K. Stiles, Bobby John, Dennis H. Lau, ... Lancet 1989;1:175–9. 9 Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) study. ...
The pathophysiological relevance of complex fractionated atrial electrograms (CFAE) in atrial fibrillation (AF) remains poorly understood. This work aims to comprehensively investigate how bipolar CFAE correlates with unipolar electrogram... more
The pathophysiological relevance of complex fractionated atrial electrograms (CFAE) in atrial fibrillation (AF) remains poorly understood. This work aims to comprehensively investigate how bipolar CFAE correlates with unipolar electrogram fractionation and the underlying electrophysiological substrate of AF. 10s unipolar AF electrograms were recorded using high-density electrode from the left atrium of 20 (10 persistent & 10 paroxysmal) AF patients undergoing cardiac surgery. Semi-automated bipolar CFAE algorithms: complex fractionated electrogram-mean (CFE-m), interval confidence interval (ICL), continuous electrical activity (CEA), average complex interval (ACI) & shortest complex interval (SCI) were evaluated against AF substrate complexity measures following fibrillation wave reconstruction derived from local unipolar activation time. The effect of inter-electrode spacing and electrode orientation on bipolar CFAE was also examined. All five semi-automated bipolar CFAE algorithms...
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SUMMARY Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with diverse clinical outcomes including sudden death, heart failure, and stroke. Depressed heart rate variability (HRV), a measure of cardiac autonomic... more
SUMMARY Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with diverse clinical outcomes including sudden death, heart failure, and stroke. Depressed heart rate variability (HRV), a measure of cardiac autonomic regulation, has been shown to predict mortality in patients with cardiovascular disease. Cardiac autonomic remodelling in animal models of HCM are not well characterised. This study analysed Gly203-Ser cardiac troponin-I transgenic (TG) male mice previously demonstrated to develop hallmarks of HCM by age 21 weeks. 33 mice aged 30 and 50 weeks underwent continuous electro-cardiogram (ECG) recording for 30 min under anaesthesia. TG mice demonstrated prolonged P-wave duration (P < 0.001) and PR intervals (P < 0.001) compared to controls. Additionally, TG mice demonstrated depressed standard deviation of RR intervals (SDRR; P < 0.01), coefficient of variation of RR intervals (CVRR; P < 0.001) and standard deviation of heart rate (SDHR; P < 0.001) compared to controls. Additionally, total power was significantly reduced in TG mice (P < 0.05). No significant age-related difference in either strain was observed in ECG or HRV parameters. Mice with HCM developed slowed atrial and atrioventricular conduction and depressed HRV. These changes were conserved with increasing age. This finding may be indicative of atrial and ventricular hypertrophy or dys-function, and perhaps an indication of worse clinical outcome in heart failure progression in HCM patients.
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