Atrial slow conduction develops and dynamically expands during premature stimulation in an animal model of persistent atrial fibrillation

Slow conduction areas and conduction block in the atria are considered pro-arrhythmic conditions. Studies examining the size and distribution of slow conduction regions in the context of persistent atrial fibrillation (AF) may help to develop improved therapeutic strategies for patients with AF. In this work, we studied the differences of size and number in slow conduction areas between control and persistent AF goats and the influence of propagation direction on the development of these pathological conduction areas. Epicardial atrial electrical activations from the left atrial roof were optically mapped with physiological pacing cycle lengths and for the shortest captured cycle lengths. The recordings were converted to local activation times and conduction velocity measures. Regions with slow conduction velocity (less than 0 . 2 m s) were identified. The size of the connected regions and the number of non-connected regions were counted for propagation from different orthogonal directions. We found that regions of slow conduction significantly increases in our 15 persistent AF goat recordings in response to premature stimulation (24.4±4.3% increase to 36.6±4.4%, p < 0.001). This increase is driven by an increase of size from (3.70±0.89[mm2] to 6.36±0.91[mm2], p = 0.014) for already existing regions and not by generation of new slow conduction regions (11.6±1.8 vs. 13±1.9, p = 0.242). In 12 control goat recordings, no increase from baseline pacing to premature pacing was found. Similarly, size of the slow conduction areas and the count did not change significantly in control animals.

A homozygous SH3TC2 mutation in a Korean patient with Charcot–Marie–Tooth disease type 4C

Charcot–Marie–Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy associated with SH3TC2 mutations, resulting in slow conduction velocity via hypomyelination. The occurrence of CMT4C in demyelinating Charcot–Marie–Tooth (CMT) varies among ethnicities, and several variants have been reported as the founder mutation. In Korea, the incidence of CMT4C was calculated as approximately 2%, and all patients have compound heterozygous mutations, which is partly due to the prohibition of consanguineous marriage. Herein, we describe a 25-year-old male who presented a slowly progressive limb weakness and impaired vibration sensation. Whole-exome sequencing revealed homozygous variants c.929G>A of SH3TC2 after identifying negative multiplex ligation-dependent probe amplification results of PMP22. Based on our literature review, this is the first CMT4C patient with a homozygous variant with each allele inherited from both the parents.

Propagation Vectors Facilitate Differentiation between Conduction Block, Slow Conduction and Wavefront Collision

Background - Differentiation between conduction block, slow conduction, and wavefront collision can be difficult using activation mapping alone, often requiring differential pacing. Therefore, a real-time method for determination of complex patterns of conduction may be desired. We hereby report a novel algorithm for displaying propagation vectors, allowing differentiation between complex patterns of conduction and facilitating real-time detection of block during ablation. Methods - In 10 swine, a chronic transcaval ablation line with an intentional gap or complete block was created, simulating conduction block, slow conduction and wavefront collision. The line was mapped during atrial pacing using Carto 3 and a novel high-resolution array that includes 48 mini-electrodes (surface area-0.9mm 2 , spacing 2.4mm) distributed over 6 splines (Optrell™, Biosense Webster). Propagation vectors were created from unipolar waveforms of adjacent electrodes along and across splines that were acquired at single beats. In order to examine the utility of propagation vectors for detection conduction block during ablation, a cavotricuspid isthmus line (CTI) was created during coronary sinus pacing with the array positioned lateral to the line. Results - Propagation vectors detected the gap in all 6 interrupted ablation line, while activation maps only identified gap in 3/6 lines; in the remainder, activation maps alone could not differentiate between conduction block, slow conduction or wavefront collision. Propagation vectors accurately determined block in all 4 contiguous ablation line, while activation maps suggested conduction block or was indeterminant due to wavefront collision in 2/4 lines. CTI block was detected during ablation by abrupt reversal of propagation vectors from a lateral to a septal direction and acute reconnection was detected by reversal of the propagating vectors back to a lateral direction. Conclusions - Real-time propagation vectors enhance the ability of standard activation maps to differentiate between complex patterns of conduction, including determination of conduction block during ablation.

A Computational Study of the Electrophysiological Substrate in Patients Suffering From Atrial Fibrillation

In the context of cardiac electrophysiology, we propose a novel computational approach to highlight and explain the long-debated mechanisms behind atrial fibrillation (AF) and to reliably numerically predict its induction and sustainment. A key role is played, in this respect, by a new way of setting a parametrization of electrophysiological mathematical models based on conduction velocities; these latter are estimated from high-density mapping data, which provide a detailed characterization of patients' electrophysiological substrate during sinus rhythm. We integrate numerically approximated conduction velocities into a mathematical model consisting of a coupled system of partial and ordinary differential equations, formed by the monodomain equation and the Courtemanche-Ramirez-Nattel model. Our new model parametrization is then adopted to predict the formation and self-sustainment of localized reentries characterizing atrial fibrillation, by numerically simulating the onset of ectopic beats from the pulmonary veins. We investigate the paroxysmal and the persistent form of AF starting from electro-anatomical maps of two patients. The model's response to stimulation shows how substrate characteristics play a key role in inducing and sustaining these arrhythmias. Localized reentries are less frequent and less stable in case of paroxysmal AF, while they tend to anchor themselves in areas affected by severe slow conduction in case of persistent AF.

A novel ventricular map of electrograms duration as a method to identify areas of slow conduction during ablation of ventricular tachycardia

Funding Acknowledgements Type of funding sources: None. Background – Wave front inhomogeneous propagation is crucial for reentry circuit generation. Bipolar EGM duration is indicative of local conduction delay and may identify areas of low conduction as a functional substrate. This study aimed to create a map of EGM duration during the VT (VEDUM Map) to identify the area of the slowest conduction and to verify if RF delivery at this area allows to rapidly interrupt the VT. Methods – 24 high-density VTs maps (21 patients) were analyzed. Activation maps and voltage maps during SR were performed. An offline remap confirmed with MathLab software was customized to visualize the longest duration electrogram during VT. Results – All of the VTs were interrupted during the first RF delivery (mean time 7,3 ± 5,4 sec (range 3-25 sec)) at the area with the longest EGM duration (212 ± 47 ms (range 113-330 ms)). . In 9 pts (37,5%) the longest EGM was located at the entrance or exit area of the activation maps while in 5 pts (21%) the EGM covered the full diastolic phase. Finally, in 10 pts the longest EGM occurred in the mid-exit-diastolic phase. Conclusions - A novel Ventricular map of Electrograms DUration (VEDUM Map) is highly accurate in defining a conductive vulnerable zone of the VT circuit. The longest EGM duration within the isthmus is highly predictive of rapid VT termination. Quantitative variablesQualitative variablesMeanMedianStandard DeviationAge71738.40BMI26.624.54.02LV EDV16315442.7LV EDD61.2629.9LV EF38.7369.74VT cycle lenght (TCL)35537556.4EGM max. duration in VT21220847EGM max dur / TCL58.260.512Maximum EGM duration localization in CLProto = 12.5%Meso = 33.3%Tele = 25%Full = 20.8%Myocardium voltage characteristics in VEDUM EGMHealthy = 25%Transition = 20.8%Scar = 41.7%Critical Isthmus area12.3107.3VT Interruption during RFYes = 79.2%No = 20.8%Time (seconds) to interruption765Access typeEndo = 58.3%Epi = 29.2%Clinical and procedural dataAbstract Figure.

A new approach to atrial flutter ablation using functional substrate mapping with wavefront discontinuity during sinus rhythm

Funding Acknowledgements Type of funding sources: None. Background Ultra high-density (UHD) mapping allows accurate identification of local abnormal electrograms and low voltage within a small area range, allowing precise identification of reentry circuits. Areas with high isochronal density in a small area known as deceleration zones (DZ) are responsible for reentry. Purpose Identify the DZ and areas of low voltage in sinus rhythm (SR) and evaluate the feasibility of performing atrial flutter (AFL) ablation by targeting those zones. Methods We prospectively enrolled patients in SR referred for AFL ablation (either typical or atypical). An isochronal late activation mapping (ILAM) during SR with UHD catheter was performed, annotating latest deflection of local electrograms. DZ were defined as areas with &gt;3 isochrones within 1cm radius, prioritizing zones with maximal density. Atrial flutter was then induced and ILAM during flutter was performed for comparison. Voltage mapping was also assessed (0.1-0.5mV). Ablation targeted DZ in SR that displayed the higher voltage. DZ in SR were compared to DZ in AFL. Number of radiofrequency (RF) applications needed to terminate AFL were assessed. After AFL termination, complete line of the slow conduction zone was completed, and pulmonary vein isolation (PVI) was done in case of left AFL. Categorical variables are presented in absolute and relative values and median and interquartile range were used for numerical variables, as well t-student test for correlation of numerical variables. Results We studied 6 AFL (4 atypical, 66.7%) in 5 patients, 2 male (40%), median age 70 (64- 72). UHD ILAM in SR with 2195 points (1212-2865) and 2197 points (1356-3102) in AFL (p = 0.62). The UHD ILAM identified a median of (QR) DZ in SR, that colocalized with AFL isthmus and DZ in AFL in 100%. DZ were not always located in low voltage areas. Aiming at the higher voltage in the DZ terminated the AFL in all cases, with a median RF time of 38 (25-58) seconds and AFL was no longer inducible. However, according to protocol, the complete line of slow conduction zone was done, with a median RF time of 1049.5 (274-1194) seconds (p = 0,009). Conclusions Isochronal mapping in sinus rhythm with UHD catheters can display the functional substrate for reentry in AFL, allowing a substrate guided ablation in case of non-inducible AFL. Targeting the areas of high isochronal density, is effective in terminating AFL, obviating the need for extensive ablation. Abstract Figure.

Cardiac reparative therapy with adipose graft transposition procedure reduces slow conduction areas in a chronic myocardial infarction swine model

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Insituto de Salud Carlos III BACKGROUND Cardiac regenerative therapy is a promising treatment for patients with ischemic heart disease, but there are some concerns on the potential increased risk of arrhythmic events following specific cell therapies. Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting in transposing a vascularized adipose flap from the autologous pericardium and placing it over the epicardial scar area and has demonstrated to reduce infarct size and improve the left ventricular ejection fraction in preclinical and human studies. Specific electrophysiological properties of the scar, (i.e. slow conduction velocity (CV)) have been identified as key features of ventricular tachycardia (VT) isthmuses. PURPOSE To assess the effect of the AGTP on VT inducibility and the electrophysiological properties of the post-MI scar with ultra-high density (UHD) mapping. METHODS A left circumflex artery (first marginal branch) MI was induced in 10 Landrace X Large White pigs by delivering 1-3 coils. Two weeks post-MI, all subjects underwent baseline left ventricular endocardial UHD mapping during right ventricular pacing with 64-electrode basket mapping catheter, as well as electrophysiological study (EPS) to test for VT inducibility. Following the mapping, subjects were allocated 1:1 to AGTP or sham group. UHD mapping and EPS were repeated 30 days post-treatment (6 weeks after MI). Voltage and activation maps were analyzed off-line with self-customized Paraview-based software. Voltage cut-offs of 1.5 and 0.5mV (bipolar) defined normal tissue, border zone (BZ) and dense scar, respectively, and 6.7mV for unipolar. Conduction velocity (CV) was determined for every pair of contiguous points and areas of similar CV were quantified for every 0.2m/s steps (for up to 4 m/s). RESULTS There were no differences between groups with regard of dense scar, BZ an low unipolar voltage areas. The AGTP group had a significant reduction of the size of slow CV (&lt;0.2 m/s) areas, compared to the sham group in whom it increased (-4.1 ± 1.7 vs. +2.4 ± 1.6 mm2, p = 0.028)(Figure). There were no differences in the size of other ranges of CV. EPS did not induce VT in any subject at baseline, and only in 1 of the sham group at the follow-up EPS. CONCLUSIONS Cardiac reparative therapy with AGTP of post-MI scar reduced the size of slow conduction areas and could provide a protective effect against arrhythmic events in ischemic heart disease. Abstract Figure.