Pacing Interval Research Articles

The effect of fixed and functional remodelling on conduction velocity, wavefront propagation, and rotational activity formation in atrial fibrillation.

Pathophysiology of atrial fibrillation (AF) remains unclear. Interactions between scar and conduction velocity (CV) and their impact on wavefront propagation in sinus rhythm (SR) and rotational activity burden in AF were evaluated. Local activation times (LATs) and voltage data were obtained from patients undergoing ablation for persistent AF. Omnipolar voltage (OV) and bipolar voltage (BV) data were obtained during AF and SR at pacing intervals of 600 and 250 ms. Local activation times were used to determine CV dynamics and their relationship to the underlying voltage and pivot points in SR. Computational modelling studies were performed to evaluate the impact of CVs and fibrosis on rotational activity burden in AF. Data from 60 patients with a total of 2 768 400 LAT and voltage points were analysed (46 140 ± 5689 points/patient). Voltage determined CV dynamics. Enhanced CV heterogeneity sites were predominantly mapped to low-voltage zones (LVZs) (0.2-0.49 mV) (128/168, 76.2%) rather than LVZs (<0.2 mV) and frequently co-located to pivot points (151/168, 89.9%). Atrial fibrillation OV maps correlated better with SR BV 250 ms than 600 ms maps, thereby representing fixed and functional remodelling. Sinus rhythm maps at 250 ms compared with 600 ms harboured a greater number of pivot points. Increased CV slowing and functional remodelling on computational models resulted in a greater rotational activity burden. Conduction velocity dynamics are impacted by the degree of scar. Conduction velocity heterogeneity and functional remodelling impacts wavefront propagation in SR and rotational activity burden in AF. This study provides insight into the pathophysiology of AF and identifies potential novel ablation targets.

Autonomic modulation impacts conduction velocity dynamics and wavefront propagation in the left atrium.

Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated. Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified. Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.

Effects of different types of fibrotic remodelling in areas of low voltage on atrial fibrillation dynamics: an in-silico study

Abstract Background Personalized computational models include the effects of personalised anatomy and atrial fibrillation (AF) remodelling in a framework that can be used to investigate patient-specific AF mechanisms and test treatment response, but modelling fibrosis remains an unresolved matter. The interpretation of regions exhibiting low voltage in electroanatomic mapping data at different pacing rates also remain unclear. However, these occurrences are correlated with fibrotic remodelling. We aimed to use patient-specific simulations to investigate the effects of fibrosis type on AF properties by modelling conduction velocity slowing, changes in ionic channels, and replacement fibrosis, incorporated in regions of low voltage identified through omnipolar mapping at different pacing rates. Methods Local activation times (LATs) voltage and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were collected in sinus rhythm with coronary sinus pacing at pacing interval (PIs) of 250ms and 600ms. For a total of 10 cases, personalised anatomical models were constructed for electrophysiology simulations, and analysed using an automated pipeline in python. For conductivity models, areas with peak omnipolar voltage (OV) below 0.5mV were assigned low conduction velocity. To incorporate ionic changes, the ionic properties were altered in fibrotic regions (peak OV &amp;lt; 0.5mV). In the simulations where replacement fibrosis was included through a probabilistic percolation method, percolation was modelled by using random number generator to probabilistically remove elements of low voltage. Pulmonary vein isolation was simulated in each model after 5s of AF, and wavefront propagation patterns were analysed to quantify the number of rotational areas or areas of wavefront break-up in 7 anatomical segments. Results The models with conductivity fibrotic remodelling demonstrated rotational drivers in more than two LA anatomical segments for both CS250ms pacing rate and CS600ms pacing rate across all 10 cases. The anterior wall exhibited the largest degree of rotational activity in 7 out of 10 cases for CS250ms pacing rate and in 9 out of 10 cases for CS600ms pacing rate (Figure A). The combination of percolation and conductivity remodelling also exhibited rotational activity on the anterior wall in 9 out of 10 cases at CS250ms pacing rate, and 7 out of 10 cases for CS600ms pacing rate. For the simulations where replacement fibrosis was included (percolation), both the roof and anterior wall exhibited the largest degree of rotational activity in 5 out of 10 cases at CS250ms pacing rate; while at CS600ms pacing rate, the posterior walled exhibited the majority of rotational activity in 7 cases (Figure B). All fibrosis models containing ionic changes terminated in more than half of the 10 cases for both pacing rates (CS250ms and 600). Conclusion The impact of low voltage on fibrotic remodelling causes complex effects on AF dynamics.

Peak frequency can be effectively used to characterize atrial remodelling in atrial fibrillation

Abstract Introduction Characterizing atrial fibrillation (AF) substrate can guide ablation strategies, particularly as current efficacy leaves room for substantial improvement. Low voltage zones (LVZs) correlate with atrial fibrosis and scar and can independently predict AF recurrence. Ablation of these zones improves freedom from arrhythmia, but the chaotic nature of atrial excitation frequently results in overestimation of LVZs limiting accurate substrate identification. Purpose While omnipolar voltage (OV) mapping has emerged to address this issue by closely correlating with sinus rhythm (SR) voltage maps, our study builds upon this by investigating a novel parameter, peak frequency (PF), to further refine AF substrate characterization. Methods Patients undergoing catheter ablation for persistent AF were enrolled. OV maps and PF maps were created during AF while bipolar voltage (BV) maps were created in SR with atrial pacing at pacing intervals (PIs) of 600ms and 250ms. Areas were classified as fixed scar (consistent LVZs across all maps), functional remodelling (LVZs in AF OV and SR BV 250ms maps) and non-LVZs (normal voltage across all maps). PF was assessed in these areas and defined as the highest frequency detected in the electrogram. Results Among 20 patients, the average voltage in AF OV maps differed significantly from SR BV 600ms (0.49±0.76mV in AF OV vs. 1.12±0.97mV SR BV 600ms, p&amp;lt;0.001) but not SR BV 250ms maps (0.49±0.76mV in AF OV vs. 0.52±0.84mV SR BV 250ms, p=0.10). Comparing co-registered points, there was a significant difference between AF OV and SR BV 600ms maps (0.21±0.09mV, p&amp;lt;0.001) but not between AF OV and SR BV 250ms maps (0.06±0.04mV, p=0.10). These findings were also consistent with regards to the proportion of LA area occupied by LVZs (42.4±8.2% AF OV, 24.3±7.4% SR BV 600ms and 39.4±6.7% SR BV 250ms; p=0.001). AF OV maps thereby correlated better with SR BV 250ms maps hence representing both fixed scar and functional remodelling. PF values ≥244Hz were predictive of non-LVZs (OR 3.91, 95% CI 3.77-4.07,) with an AUC of 0.71. A PF of ≤214Hz was predictive of fixed scar (OR 17.67, 95% CI 16.82-18.56, p&amp;lt;0.001) with an AUC of 0.90. A PF between 215-236Hz was predictive of functional remodelling (OR 2.83, 95% CI 2.71-2.95, p&amp;lt;0.001) with an AUC of 0.60. The majority of LVZs identified exclusively in AF OV maps exhibited PFs akin to those in non-LVZs highlighting the ability of PF to pinpoint potential overestimations in LVZs. Conclusions PF mapping can effectively discern between areas of fixed scar, functional remodelling, and potential overestimation of LVZs. PF may enhance substrate characterization in AF utilising data solely from electrograms.Trial Design and Zone AssignmentPeak Frequency and Voltage Zones

Selective and non-selective right bundle pacing for the diagnosis of bundle branch reentry ventricular tachycardia.

Bundle branch reentry ventricular tachycardia (BBRVT) can be seen in patients with conduction disease. In this report, we describe the use of conduction system pacing for its diagnosis. BBRVT was induced in two patients with infra-nodal conduction disease. Bundle branch reentry ventricular tachycardia with a left bundle branch block morphology was observed in the first patient (type A), whereas the second patient had a right bundle branch block morphology (type C).The diagnosis of BBRVT was confirmed in both patients by ventriculo-atrial dissociation, and the interdependence of the conduction system and the ventricular tachycardia cycle length variations.Selective and non-selective RB pacing was observed in the two patients during apical right ventricular pacing for entrainment of BBRVT with evidence of manifest entrainment with non-selective RB capture in the first patient, and concealed entrainment by selective RB capture in the second patient. Other criteria for entrainment including a short post-pacing interval at the right bundle pacing site were noted. Right bundle pacing is feasible in patients with BBRVT and may be a helpful manoeuver for the diagnosis of BBRVT.

PO-02-172 CONDUCTION VELOCITY AND CONDUCTION VELOCITY DYNAMICS IN THE LEFT ATRIUM ARE IMPACTED BY STRUCTURAL AND AUTONOMIC MODULATION AND SITES OF CONDUCTION VELOCITY HETEROGENEITY CORRELATE TO RE-ENTRY ACTIVITY IN ATRIAL FIBRILLATION

Structural and autonomic remodelling is proposed to drive atrial fibrillation (AF). Conduction velocity (CV) heterogeneity predisposes cardiac tissue to re-entry mechanisms. The impact of structural and autonomic remodelling on CV dynamics and re-entry formation is unclear. Evaluate the impact structural and autonomic modulation has on CV dynamics and re-entry activity in AF. Local activation times (LATs), voltage and geometry data were obtained from 20 patients undergoing catheter ablation for persistent AF. LATs were obtained at 3 pacing intervals (PI) (600, 400 and 250ms) with pacing from two pacing sites. LATs were used to determine CV dynamics and their relationship to voltage using an automated algorithm. Relationship between sites of enhanced CV heterogeneity defined as rate dependent CV slowing (RDCV) sites (sites exhibiting CV difference (CVd) between PI=600ms and PI=250ms of ≥20% of the mean CVd seen between these PIs for that voltage zone) and re-entry activity in AF was evaluated. Re-entry activity was identified using an automated algorithm and defined as ≥1.5 rotations of 360 degrees. The impact of autonomic modulation on CV dynamics both pharmacologically and with ganglionated plexi stimulation was assessed. A total of 512,082 LAT and voltage points were analysed. Voltage impacts CV (1.36±0.98 nLVZ ≥0.5mV, 1.05±1.03 LVZ 0.2-0.49mV and 0.58±0.37 vLVZ <0.2mV) (Figure 1A-B) and CV dynamics, whereby at nLVZ the curves are steeper (0.03±0.02ms CVd PI 600-400ms, 0.54±1.1ms CVd PI 400-250ms), broader at LVZ (0.16±0.09ms CVd PI 600-400ms, 0.23±1.1ms CVd PI 400-250ms) and flat at vLVZ (0.04±0.01ms CVd PI 600-400ms, 0.05±0.02ms CVd PI 400-250ms) (Figure 1C). Per patient, 5.6±1.1 RDCV sites and 3.4±1.3 sites of re-entry activity were identified. Of the RDCV sites, 72.3% (81/112) correlated to 94.1% (64/68) of re-entry activity sites which were mainly confined to LVZs (59/68, 86.8%). Autonomic modulation affected the CV dynamic curves through increasing rate dependency slowing (Figure 1D). The number of RDCV sites identified were enhanced following autonomic modulation (3.4±1.2 increase per patient). CVs and CV dynamics are impacted by structural remodelling and are influenced by autonomic modulation which enhances CV heterogeneity. CV heterogeneity sites correlate to re-entry activity in AF. Assessment of CV dynamics and heterogenity may help to determine the mechanistic importance of LVZs.

PO-04-186 ASSESSING PROXIMITY TO THE VENTRICULAR TACHYCARDIA CIRCUIT EARLY IN THE PACING TRAIN: NUMBER NEEDED TO RESET

When ventricular tachycardia (VT) continues after entrainment the post pacing interval (PPI) can be used to assess proximity to the circuit. It is not known if the initial beats of a pacing train can be used to assess reentry circuit proximity, which could be useful when pacing terminates or alters VT. We hypothesized that the number of stimuli with local electrogram(EGM) capture needed to reset (NNR) VT may provide an indication of proximity to the reentry circuit as has been shown in atrial flutter. During stable scar-related VT, pacing trains 10 – 40ms faster than the VT cycle length with the first stimulus synchronized to a ventricular electrogram were delivered. We included sites with stable VT cycle length(TCL) and without perturbation of VT post pacing to allow comparison with the PPI-TCL. Of 102 trains at 92 sites in 28 VTs in 17 patients the first capturing stimulus was earlier than 30 ms in prematurity relative to local activation, such that NNR could be artificially short. NNR was analyzed in the remaining 23 trains at 21sites in 10 VTs (457ms +/- 85ms CL). The PPI-TCL ranged from 0-100ms and the NNR ranged from 1-6. PPI-TCL was correlated with NNR (r=0.67, p=0.006) (figure). When the first or second stimulus reset VT (NNR = 1 or 2) the PPI-TCL was < 30ms and 3-6 with a PPI-TCL of >30ms. The NNR provides an indication to the proximity to the circuit with NNR <2 indicating a PPI-TCL of <30ms that can potentially be applied if pacing terminates VT. Application of NNR requires attention to synchronization of the pacing train that is not straight forward in areas of fractionated electrograms.

Antitachycardic Therapy of ICD in Patients with Multiple Morphologies of Monomorphous Ventricular Tachycardia Refractory to Therapy

The article presents a description of a clinical case of a patient with structural myocardial pathology (postinfarction cardiosclerosis) with recurrent paroxysmal sustained monomorphic ventricular tachycardia (VT) refractory to the nominal recommended ICD (implantable cardioverter defibrillator) settings; as well as discusses the shortcomings of existing standard algorithms for antitachycardia pacing (ATP) of implantable cardioverter defibrillators and potential ways to increase its efficiency. The refractoriness of recurrent paroxysms of ventricular tachycardia to ATP therapy increases the risk of repeated ICD shocks.&#x0D; Despite the existence of universal recommendations for ICD programming and ATP therapy, there is a need in clinical practice for individualized ATP programming in patients refractory to nominal settings. Increasing the number of ATP series and changing algorithms enables to increase the efficiency of ATP up to 8089%. Refractoriness to standard ATP settings may be also overcome by using alternative ATP pacing algorithms (Ramp, Burst-plus, or Ramp-plus instead of Burst), changing the pacing interval, ATP sequence duration, pacing type, and even adding 12 extra stimuli, as well as using data from the previous intracardiac electrophysiological heart test.&#x0D; The presented clinical case of a patient with postinfarction cardiosclerosis and paroxysmal stable monomorphic VT (SM-VT) of several morphologies demonstrates that the arrhythmogenic substrate after myocardial infarction changes for a long time without new stenoses in large coronary arteries and without new episodes of acute coronary syndrome, as well as generates several different morphologies of VT from one scar (with different heart rates) and the effect on hemodynamics. The efficiency of early ATP pacing may differ for VT of various morphologies, which makes it reasonable to use alternative pacing algorithms (in addition to the standard Burst sequences recommended by the 2019 Consensus on ICD programming) and testing possible ATP algorithms during ablation of monomorphic VT, including during preventive VT ablation before ICD implantation.

E/e’ Ratio Predicts the Atrial Pacing-Induced Left Atrial Pressure Response in Patients with Preserved Ejection Fraction

Background and Objectives: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Materials and Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n = 204, AF group) or supraventricular tachycardia (n = 34, control group) were analyzed (male n = 183, 54 ± 12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e' (≥ 8) than in those with a low E/e' (<8). LAPR at a pacing interval of 400 ms and E/e' were positively correlated (r = 0.373, p < 0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

An iterated map model with CaMKII feedback in modeling the force frequency relationship of a cardiac cell

Experiment data on isolated rat hearts shows that the transient behaviors after switching pacing intervals are very complicated with increasing, decreasing, and rebound of the contraction force. The strength of contraction in the heart muscle is strongly related to intracellular free Ca2+ mediated by an action potential. This behavior can be explained by calcium cycling inside the excitable cardiac myocytes coupled with their action potential. The previous and recently proposed models can only explain a short period of time after changing the pacing frequency. Our aim is to develop a simple feedback model based on the role of the enzyme CaMKII to describe the whole dynamic picture captured from experiments.

The jugular approach for leadless pacing: A novel and safe alternative.

To evaluate safety of leadless pacemaker implantation through the internal jugular vein in a larger cohort with longer follow-up. Moreover, feasibility of non-apical pacing as well as relation between pacing site and QRS duration were assessed. Eighty Two consecutive patients, who received a leadless pacemaker though the internal jugular vein, were included. Electrical parameters were measured at regular follow-up and any complications were registered. Paced QRS interval was compared for three pacing sites, RVOT, RV mid septum, and RV apical septum. In all patients, the leadless pacemaker was implanted successfully. In 69 patients, the device was implanted in a non-apical position. In 71% of cases, the device could be deployed at first attempt. The median fluoroscopy time was 4.4 min (range 0.9-51) The paced QRS interval was significantly narrower for non-apical pacing sites compared to apical pacing si 156 vs. 179ms. p=.04, respectively. During mean follow-up of 16 months (range 0-43 months), electrical parameters remained stable. Two complications occurred, which could be resolved during the implant procedure. There were no access site related complications. The jugular approach for leadless pacemaker implantation is feasible and may avoid vascular complications. It facilitates non-apical positioning of leadless pacemakers leading to a narrower paced QRS interval. The jugular approach allows for immediate post procedural ambulation.

Astronomically controlled aridity in the Sahara since at least 11 million years ago

The Sahara is the largest hot desert on Earth. Yet the timing of its inception and its response to climatic forcing is debated, leading to uncertainty over the causes and consequences of regional aridity. Here we present detailed records of terrestrial inputs from Africa to North Atlantic deep-sea sediments, documenting a long and sustained history of astronomically paced oscillations between a humid and arid Sahara from over 11 million years ago. We show that intervals of strong dust emissions from the heart of the continent predate both the intensification of Northern Hemisphere glaciation and the oldest land-based evidence for a Saharan desert by millions of years. We find no simple long-term gradational transition towards an increasingly arid climate state in northern Africa, suggesting that aridity was not the primary driver of gradual Neogene expansion of African savannah C4 grasslands. Instead, insolation-driven wet–dry shifts in Saharan climate were common over the past 11 Myr, and we identify three distinct stages in the sensitivity of this relationship. Our data provide context for evolutionary outcomes on Africa; for example, we find that astronomically paced arid intervals predate the oldest fossil evidence of hominid bipedalism by at least 4 Myr. Pulses of Saharan dust have been entering the North Atlantic since at least 11 Ma, a result of astronomically paced cycles between arid and humid conditions in northern Africa, according to a terrigenous input record from an ocean core off west Africa.

Cardiac Resynchronization Therapy Response Is Equalized in Men and Women byElectricalOptimization: PR Matters.

This study hypothesized that the shorter intrinsic PR interval observed in women allows a greater degree of fusion with intrinsic conduction, achieving a shorter QRS interval duration and, thus, a better response. Women benefit more from cardiac resynchronization therapy (CRT) than men. However, the reason for this difference remains elusive. A cohort of 180 patients included in the BEST (Fusion based optimization in resynchronization therapy [ECG Optimization of CRT: Evaluation of Mid-Term Response]; NCT01439529) study were retrospectively analyzed. Patients were initially randomized to either nonoptimized CRT (NON-OPT group; n=89) or electrocardiographically optimized CRT based on the fusion-optimized intervals (FOI) method (FOI group; n=91). Echocardiographic response was defined as a >15% decrease in left ventricular end-systolic volume at the 12-month follow-up. The basal PR interval was shorter in women as compared to men. In the NON-OPT group, CRT resulted in a shorter paced QRS interval in women than in men (134 ± 21ms vs. 151 ± 21ms, respectively; p=0.003, 95% confidence interval [CI]: -27 to -5.6) and better response in women than in men: 70.4% vs. 46.4%, respectively (odds ratio: 0.37; p=0.04; 95%CI: 0.14 to 0.97). There were no differences in paced QRS interval duration (126 ± 13ms vs. 129 ± 17ms; p=0.47) or response between women and men in the FOI group (68% vs. 70.5%; odds ratio: 1.12; p=0.82; 95%CI: 0.41 to 3.07). FOI extended the atrioventricular interval to obtain the best fusion; the atrioventricular intervals tended to require greater extension in men than in women (22 ± 33ms vs. 8 ± 28ms, respectively; p=0.07). Women had a shorter PR interval, which was associated with a shorter QRS interval and better response to CRT. The difference in QRS interval duration and response between men and women did not persist when CRT wasoptimized using fusion with intrinsic conduction (FOI programming).

B-PO02-176 ENTRAINMENT OF IDIOPATHIC LEFT VENTRICULAR TACHYCARDIA FROM LEFT VENTRICULAR SEPTUM INDICATED NEGATIVE PARTICIPATION OF DISTAL LEFT POSTERIOR FASCICLE

As a macro-reentrant tachycardia, the circuit of idiopathic left ventricular tachycardia (ILVT) is mainly described by activation mapping. Evidence from entrainment in left ventricle (LV) is limited. To investigate the reentrant circuit ILVT by entrainment at LV septum. In 4 patients with ILVT from left posterior fascicle (LPF) area, a decapolar catheter placed at LV septum was used to delineate activation pattern of Purkinje potentials (PP) during tachycardia. Entrainment was performed using multiple pairs of electrodes where PPs were recorded. The tachycardia cycle length (TCL), QRS pattern, electrogram sequences and post pacing intervals (PPI) were analyzed. PPIs were measured from both stimulus to return PP (PPI1) and ventricular electrogram (PPI2), respectively. P1 potentials was recorded in 3/4 patients. 18 bursts of entrainment were performed. QRS during overdrive was always slightly different from tachycardia QRS in morphology, but sequence of P2 suggested concealed fusion when entraining earliest P2, or P1-P2 fusion site(n=4). PPI1-TCL here was significantly shorter than PPI2-TCL (6±6.7ms vs. 33.8±6.7ms P<0.01) and PPI1-TCL at the next distal bipole (n=4, 6±6.7ms vs. 36.3±15.6ms, P<0.01), although their P2 timing difference were all less than 15ms. Ablation at sites with shortest PPI1 eliminated all ILVTs. Overdrive from earliest P2 site during ILVT demonstrated entrainment with concealed fusion in fascicles. PPI was significantly longer at the sites distal to earliest P2, indicating distal LPF was the "inner bystander" of the circuit, which may solely involve Purkinje network in the vicinity of LPF.

Cardiac resynchronization therapy in patients with heart failure and narrow QRS complexes (≤ 130ms): role of speckle tracking echocardiography and different interventricular (VV) pacing intervals.

Response to cardiac resynchronization therapy (CRT) in patients with heart failure with reduced ejection fraction (HFrEF) depends on the degree of correction of interventricular (VV) electromechanical dyssynchrony between the left and right ventricles (LV, RV). Wide (> 130ms [ms]) QRS interval is used as a qualifying ECG parameter for CRT device implantation. In this study, we aimed to evaluate myocardial strain (S) and myocardial strain patterns (SP) and strain rate (SR) by speckle tracking echocardiography (STE) and mechanical characteristics at different VV intervals in acute settings and long-term outcome from "sequential LV-RV" pacing programming in patients with narrow (< 130ms) and wide (> 130ms) QRS complexes as a basis for extending CRT in select patients with narrow QRS. From a previously established cohort of patients who had undergone CRT device implantation, we identified patients with narrow (< 130ms) and wide (> 130ms) QRS complexes, groups A and B respectively. In all patients, we assessed myocardial SP and SR by STE, and mechanical characteristics at VV intervals: "LV Off," "VV0," "VV60," and "RV Off" to provide "RV-only," "simultaneous BiV," "sequential LV-RV," and "LV-only" pacing in the acute settings, and subsequently long-term clinical outcomes with CRT devices programmed to VV60. We compared acute STE characteristics and long-term clinical outcomes between the groups. The study cohort comprised 271 patients (age 69.2 ± 10.3years [mean ± SD], male-60%). Group A (n = 69) and group B (n = 202) were well matched for the clinical variables, including distribution of patients with ischemic versus non-ischemic cardiomyopathies. QRS width and left ventricular ejection fraction (LVEF) in groups A and B were 120.1 ± 12.3ms and 152.1 ± 12.9ms (p < 0.05), and 22.3 ± 9.4%, and 23.3 ± 10.2% (p = not significant [NS]). With VV0, VV60, and LV-only timings, corresponding LVEF rates in the acute settings were 31.45 ± 10.9%, 40.08 ± 8.3%, and 44.32 ± 7.98% (p < 0.01) in group A, and 38.94 ± 8.5%, 46.91 ± 7.33%, and 49.9 ± 8.94% (p < 0.01) in group B, and accounted for similar incremental percentage increase in LVEF compared to baseline in group A (43.2 ± 51.7%, 80.9 ± 61.4%, and 93.4 ± 65.6% respectively) and group B (67.3 ± 82.0%, 100.6 ± 94.3%, and 112.9 ± 95.7% respectively) (p = NS). Abnormal SP and SR were consistently observed with RV pacing that improved with VV60 and LV-only pacing in both groups. Strain scores at different VV timings were similar between the groups (p = NS). At 1-year follow-up, LVEF improved from 22.4 ± 8.0% to 39.8 ± 11.5% (p ≤ 0.001) for the total cohort with similar increments observed in both groups (p = NS). There were fewer NYHA III-IV class patients at 1year in both groups. Comparable myocardial SP and SR characteristics and LVEF improvement with VV60 and LV-only pacing in the acute setting and long-term outcome of CRT by "sequential LV-RV" pacing seen in patients with both narrow and wide QRS duration suggest that CRT device implantation may be justified in select patients with HFrEF and narrow QRS duration (< 130ms) who have demonstrable dyssynchrony and abnormal myocardial SP and SR characteristics.

Left bundle branch pacing: efficacy and safety compared to right ventricular outflow tract pacing

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with preserved left ventricular ejection fraction (LVEF) and atrioventricular block (AVB) who are anticipated for high-burden of right ventricular (RV) pacing possess a risk to develop pacing-induced cardiomyopathy and adverse clinical outcomes. Left bundle branch pacing (LBBP) has recently emerged as a mode of conduction system pacing in the quest for physiological pacing. Purpose The aim of our study was to assess LBBP feasibility and safety compared to right ventricular outflow tract pacing (RVOTP). Methods Single centre randomized clinical trial to investigate acute success, feasibility and safety of LBBP versus RVOTP. May to October 2020. Patients with pacemaker indication and preserved LVEF were randomized 1:1 and followed up 3 months. Success was defined in LBBP group as a paced ECG &amp;lt; 120ms or with a 20% length reduction from the basal ECG. Results 120 patients were randomized, 60 in each group, 61% males. The mean age was 77,9 ± 9 years and third-degree AVB was the main pacing indication. The procedure was successful in 95% of the cases in both groups (p = 1). The paced QRS interval was narrower in the LBBP group compared to the RVOT group (99 ± 2 ms vs 113,6 ± 11,7 ms, p &amp;lt; 0,001). Lower fluoroscopy times were achieved in LBBP group (3.1 ± 2.1 min vs 4.3 ± 3.4, p = 0,035) and also longer procedure times in LBBP group (68,9 ± 36,9 min vs 44,3 ± 18,7 min, p &amp;lt; 0,001). No complications were achieved and no difference in ventricular lead dislocation was found between both groups (1.6% vs 1.6%)(p = 1). Conclusions LBBP is feasible, safe and provides a narrower paced QRS compared to RVOTP. LBBP required lower fluoroscopy times but longer procedure times compared to RVOTP. LBBP (n = 60) RVOTP (n = 60) p Age (mean ± SD) 76,7 ± 9 79,7 ± 8 0,067 Male gender 62 (37) 60 (36) 1 Successful procedure 95 (57) 95 (57) 1 Basal left bundle branch block 15 (9) 13 (8) Basal QRS duration (mean ± SD) 112,6 ± 29,6 109,9 ± 25,8 0,59 Pacing QRS duration (min)(mean ± SD) 99 ± 2 139,6 ± 11,7 &amp;lt; 0,001 Procedure time (min) (mean ± SD) 68,9 ± 36,9 44,3 ± 18,7 &amp;lt; 0,001 Fuoroscopy time (min)(mean ± SD) 3.1 ± 2.1 4.3 ± 3.4 0,035 R wave (mV)(mean ± SD) 9,9 ± 5,7 9,9 ± 5 0,98 Right ventricle pacing threshold (V)(mean ± SD) 0,67 ± 0,3 0,58 ± 0,24 0,08 Ventricular lead dislocation 1.6 (1) 1.6 (1) 1

The role of marshall bundle epicardial connections in atrial tachycardias after atrial fibrillation ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial tachycardias (ATs) are often seen in the context of AF ablation. Objectives We evaluated the role of the Marshall bundle (MB) network in left atrial (LA) ATs using high-density high-spatial resolution 3D mapping. Methods 199 post-AF ablation LA tachycardias were mapped in 140 consecutive patients (112 (80%) males, mean age: 61.8 years); 133 (66.8%) were macro-reentrant and 66 (33.2%) were scar-related re-entry. MB-dependent perimitral AT (PMAT) was diagnosed where the difference between the post pacing interval and the tachycardia cycle length (PPI-TCL) was &amp;lt;20ms in parts of the expected MB-dependent perimitral circuit (within the VOM, the ridge between the left pulmonary veins and LA appendage (LAA), the anterior LA and between 6- and 11-o’clock of the mitral annulus) and the PPI-TCL was &amp;gt;20ms in areas bypassed by the VOM (the distal coronary sinus (CS), the posterior LA and the mitral isthmus). MB-related re-entry was diagnosed by PPI-TCL &amp;lt;20ms at the left lateral ridge, posterior base of LAA, inferolateral LA or VOM ostium; and PPI-TCL &amp;gt;20ms in the septal annulus. Typically, in MB-dependent localized re-entry, the earliest activation was found along the MB-LA endocardial connection or MB-CS epicardial connection. Results The MB network was found to participate in 60 (30.2%) re-entrant ATs, 31 PMATs and 29 localized re-entries. High-frequency multiphasic fragmented electrograms with long duration were often recorded endocardially or epicardially at the MB-LA or MB-CS connections. The amplitude and duration of these signals were 0.5 ± 0.79 mV and 65 ± 40 ms for MB-PMATs and 0.26 ± 0.28mV and 122 ± 67 ms for MB-localized re-entries. Unipolar EGMs at the site of endocardial-epicardial breakthrough had a rS pattern in all MB-related ATs. Of 60 MB-related ATs, 49 (81.6%) terminated with RF ablation, 44 (73.3%) at the MB-LA junction and 5 (8.3%) at the MB-CS junction, while 9 (15%) terminated after 2.5-5 cc of alcohol infusion inside the vein of Marshall (VOM). Of the 31 MB-related macroreentrant ATs, 17 (54.8%) terminated at the MB-LA junction, 5 (16.1%) at the MB-CS junction and 7 (22.6%) with alcohol infusion inside the VOM. Two macroreentries (6.5%) using the MB did not terminate with RF energy either endocardially at the MB-LA junction or epicardially at the MB-CS junction, and we were unable to identify or cannulate the VOM for ethanol infusion. Of the 29 localized re-entrant ATs using the MB, 27 (93.1%) terminated at the MB-LA junction, none terminated at the MB-CS junction and 2 (6.9%) terminated after alcohol infusion. After a mean follow up of 12 months, only 4 patients (6.7%) had AT recurrence. Conclusions MB re-entrant ATs accounted for up to 29% of the left ATs after AF ablation. Ablation of the MB-LA or CS-MB connections or alcohol infusion inside the VOM is required to treat these arrhythmias. Abstract Figure.

Dynamic comparisons of epicardial electrograms between the left atrium and pulmonary veins in atrial fibrillation in goat model

Objective: To compare epicardial electrograms between the left atrium (LA) and pulmonary veins (PVs) dynamically at development of persistent atrial fibrillation(AF) in goats PVs. Methods: Ten female goats were instrumented with electrodes at the LA and left side PV. Sustained AF (＞24 h) was induced in the goat by rapid intermittent left atrial pacing for(9.5±2.3)days at a pacing interval of 20 ms for 1 s with a maximum output of 6.0 V, followed by a 2-s period without pacing. Characteristics of PVs and LA epicardial electrograms were analyzed in the development of AF. Results: With prolonged stimulation, the duration of AF was prolonged, complex fractionated atrial electrograms(CFAEs) in LA and was increased gradually, PVs had more CFAEs than LA all the time. When induced AF lasted for more than 24 h, CFAEs in PVs became sustained approximately (2.7%±3.6% vs 92.6%±6.4%, at onset of AF vs AF lasted for more than 24 h, P＜0.05), and the ratio of CFAEs in PVs was more than that in LA (92.6%±6.4% vs 72.8%±5.3%, P＜0.05). Conclusion: The epicardial CFAEs are in specific area, which increase along with electrical remodeling. The epicardial CFAEs may play an important role in the maintenance of AF in this model.

Optimizing single-chamber pacing in dogs Part 1: Rate determinations, rate interventions and hysteresis

Determining ideal pacing rates to meet physiological needs and optimizing programming to prevent unnecessary right ventricular pacing in dogs requires an understanding of heart rate profiles and applicable pacing technology. The heart rate and rhythm of the dog is complex necessitating investigation of rate requirements of activity and circadian influences. Overlaying this information are a multiplicity of other factors such as age, breed, temperament, cardiovascular disease and underlining rhythm disorders that contribute to the difficulty in making general conclusions. However, all such information permits better implementation of programming options with the goal of better outcomes. In this review (Part 1 of a two-part review) instantaneous heart rate, rolling average heart rate, simple average heart rate, heart rate tachograms, RR interval tachograms (2D, 3D and dynamic), and Poincaré plots (2D, 3D and dynamic) are discussed as they apply to decisions in the determination and examination of pacing rates for dogs programmed in the VVI pacing mode (Ventricular paced, Ventricular sensed, Inhibited pacing). The applicable pacing operations available for three pacemaker companies are reviewed (Abbott, Biotronik/Dextronix, and Medtronic). The programmable options considered include: slowest pacing rate without additional features to extend the pacing interval, sleep/rest rate preferences, hysteresis to lengthen pacing interval following intrinsic beats, and intermittent increases in pacing following abrupt loss of intrinsic rhythm. Recommendations are suggested for follow-up of individual dogs with examination of pacing statistics and Holter monitoring.

A novel trigger-substrate mechanism based on clinically concealed repolarization abnormalities underlies idiopathic ventricular fibrillation

Abstract Background Sudden cardiac arrest (SCA) is most often due to ventricular fibrillation (VF). When no cause is found during diagnostic follow-up, fibrillation is classified as idiopathic (iVF). We hypothesize that a critical functional substrate-trigger interaction underlies iVF. Purpose To study electrophysiological triggers and substrate for iVF in a clinical cohort; and seek mechanistic explanations in explanted pig hearts and computer models mimicking trigger-substrate interactions. Methods Repolarization time (RT) isochrones on the epicardium were studied with electrocardiographic imaging (ECGI) in patients with iVF, patients with frequent monomorphic premature ventricular complexes (fmPVC) but no structural disease or SCA, and controls without cardiovascular disease. RT gradients were created in explanted, Langendorff-perfused pig hearts by local infusion of dofetilide (“dof”, 250 nM, delaying RT) and pinacidil (“pin”, 30 μM, shortening RT) in adjacent regions of the heart. Arrhythmia inducibility was tested by programmed stimulation (8 atrial stimuli [S1] followed by one ventricular stimulus [S2] paced at regions of early or late RT). A computational ventricular monodomain model was used to study the location-dependency of trigger-substrate interaction; RT gradients were created by local changes in potassium channel conductance. Results Although QTc values were similar, iVF survivors (n=11) displayed significantly steeper RT gradients than controls (n=10) or fmPVC individuals (n=7): 269±111 vs 179±40 vs 171±76 ms/cm respectively (panel A). Unipolar electrograms (EGMs) at the gradients displayed a change in polarity of the local T wave (B). In iVF, PVCs originated more often from regions with early RT than in fmPVC individuals (yellow circles in A; 64% vs 14%). In the explanted hearts (C), drug infusion resulted in similar RT gradients and polarity changes of EGM T waves (D-E). VF inducibility by pacing of the early RT region (D) increased significantly with steeper RT gradients (baseline: 3/6 hearts inducible, dof+pin: 3/3). Pacing of late RT regions (E) did not induce arrhythmias in baseline (0/6) nor with RT gradients (0/3). For similar pacing intervals at the early RT region, the 12-lead ECG R-on-T morphology was similar but VF only occurred in the presence of RT gradients (F). In the computer model, the number of inducible pacing intervals critically depended on the stimulus location (G). Conclusion Combined, these results demonstrate that R-on-T superposition per se is insufficient to explain arrhythmogenesis. Rather, not only the temporal coupling interval but also the spatial origin of PVCs in relationship to the degree of local repolarization abnormalities are critical elements. In iVF, a substrate of RT gradients (panel H1) with triggers from early RT regions (H2) precipitate reentry (H3). Noninvasive ECGI can uncover these substrate and trigger characteristics in (at least a subset of) iVF survivors. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Scientific Research Veni grant TTW 16772, French National Research Agency (ANR-10-IAHU04-LIRYC)