Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Postinfarct ventricular tachycardia substrate: Characterization and ablation of conduction channels using ripple mapping.

BACKGROUND: Conduction channels have been demonstrated within the postinfarct scar and seem to be co-located with the isthmus of ventricular tachycardia (VT). Mapping the local scar potentials (SPs) that define the conduction channels is often hindered by large far-field electrograms generated by healthy myocardium. OBJECTIVE: The purpose of this study was to map conduction channel using ripple mapping to categorize SPs temporally and anatomically. We tested the hypothesis that ablation of early SPs would eliminate the latest SPs without direct ablation. METHODS: Ripple maps of postinfarct scar were collected using the PentaRay (Biosense Webster) during normal rhythm. Maps were reviewed in reverse, and clusters of SPs were color-coded on the geometry, by timing, into early, intermediate, late, and terminal. Ablation was delivered sequentially from clusters of early SPs, checking for loss of terminal SPs as the endpoint. RESULTS: The protocol was performed in 11 patients. Mean mapping time was 65 ± 23 minutes, and a mean 3050 ± 1839 points was collected. SP timing ranged from 98.1 ± 60.5 ms to 214.8 ± 89.8 ms post QRS peak. Earliest SPs were present at the border, occupying 16.4% of scar, whereas latest SPs occupied 4.8% at the opposing border or core. Analysis took 15 ± 10 minutes to locate channels and identify ablation targets. It was possible to eliminate latest SPs in all patients without direct ablation (mean ablation time 16.3 ± 11.1 minutes). No VT recurrence was recorded (mean follow-up 10.1 ± 7.4 months). CONCLUSION: Conduction channels can be located using ripple mapping to analyze SPs. Ablation at channel entrances can eliminate the latest SPs and is associated with good medium-term results.

Quantification of Electromechanical Coupling to Prevent Inappropriate Implantable Cardioverter-Defibrillator Shocks.

OBJECTIVES: This study sought to test specialized processing of laser Doppler signals for discriminating ventricular fibrillation (VF) from common causes of inappropriate therapies. BACKGROUND: Inappropriate implantable cardioverter-defibrillator (ICD) therapies remain a clinically important problem associated with morbidity and mortality. Tissue perfusion biomarkers, implemented to assist automated diagnosis of VF, sometimes mistake artifacts and random noise for perfusion, which could lead to shocks being inappropriately withheld. METHODS: The study tested a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring as a method for assessing circulatory status. Fifty patients undergoing VF induction during ICD implantation were recruited. Noninvasive laser Doppler and continuous electrograms were recorded during both sinus rhythm and VF. Two additional scenarios that might have led to inappropriate shocks were simulated for each patient: ventricular lead fracture and T-wave oversensing. The laser Doppler was analyzed using 3 methods for reducing noise: 1) running mean; 2) oscillatory height; and 3) a novel quantification of electromechanical coupling which gates laser Doppler relative to electrograms. In addition, the algorithm was tested during exercise-induced sinus tachycardia. RESULTS: Only the electromechanical coupling algorithm found a clear perfusion cut off between sinus rhythm and VF (sensitivity and specificity of 100%). Sensitivity and specificity remained at 100% during simulated lead fracture and electrogram oversensing. (Area under the curve running mean: 0.91; oscillatory height: 0.86; electromechanical coupling: 1.00). Sinus tachycardia did not cause false positive results. CONCLUSIONS: Quantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artifacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.

Evaluation of a new algorithm for tracking activation during atrial fibrillation using multipolar catheters in humans.

BACKGROUND: Conventional mapping techniques during atrial fibrillation (AF) are difficult to apply because of cycle length irregularity. Mapping studies are usually restricted to short durations of AF in limited regions because of the laborious manual annotation of local activation time (LAT). The purpose of this study was to test an automated algorithm to map activation during AF, with comparable accuracy to manual annotation. METHODS: Left atrial (LA) mapping was performed using a 20-pole double loop catheter (AFocusII) in 30-second data segments from 16 patients. The new algorithm (RETRO-Mapping) was designed to detect wavefront propagation between electrodes, and display activating wavefronts on a two-dimensional representation of the catheter. Activation patterns were validated against their bipolar electrograms and with isochronal maps. The mapping protocol was approved by the research ethics committee (13/LO1169 and 14/LO1367). RESULTS: During AF, uniform wavefront activation direction (mean ± SD, degrees) from manually constructed isochronal maps was comparable to RETRO-Propagation Map (RETRO-PM) and RETRO-Automated Direction (RETRO-AD): 1 ± 6.9 for RETRO-PM; and 2 ± 6.6 for RETRO-AD. There was no significant difference in activation direction assigned to 1373 uniform wavefronts during AF when comparing RETRO-PM with RETRO-AD (Bland-Altman mean difference: -0.1 degrees; limits of agreement: -8.0 to 8.3; 95% CI -0.4 to 0.2; (r = 0.01) R2 = < 0.005; P = .77). CONCLUSION: We have developed and validated a new technique to map activation during AF. This technique shows comparable accuracy to that of conventional isochronal mapping with careful manual adjustment of LAT.

Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation.

BACKGROUND: Bipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance. OBJECTIVE: The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than VSR. METHODS: AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map). After cardioversion, VSR was mapped (557 ± 326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients. RESULTS: The time course of VmAF was assessed from 1-40 AF cycles (∼8 seconds) at 1113 locations. VmAF stabilized with sampling >4 seconds (mean voltage error 0.05 mV). Paired point analysis of VmAF from segments acquired 30 seconds apart (3667 sites; 15 patients) showed strong correlation (r = 0.95; P <.001). Delayed enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33% ± 13%. VmAF distributions were (median [IQR]) 0.21 [0.14-0.35] mV in DE vs 0.52 [0.34-0.77] mV in non-DE regions. VSR distributions were 1.34 [0.65-2.48] mV in DE vs 2.37 [1.27-3.97] mV in non-DE. VmAF threshold of 0.35 mV yielded sensitivity of 75% and specificity of 79% in detecting MRI-DE compared with 63% and 67%, respectively, for VSR (1.8-mV threshold). CONCLUSION: The correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.

Analytical approaches for myocardial fibrillation signals.

Atrial and ventricular fibrillation are complex arrhythmias, and their underlying mechanisms remain widely debated and incompletely understood. This is partly because the electrical signals recorded during myocardial fibrillation are themselves complex and difficult to interpret with simple analytical tools. There are currently a number of analytical approaches to handle fibrillation data. Some of these techniques focus on mapping putative drivers of myocardial fibrillation, such as dominant frequency, organizational index, Shannon entropy and phase mapping. Other techniques focus on mapping the underlying myocardial substrate sustaining fibrillation, such as voltage mapping and complex fractionated electrogram mapping. In this review, we discuss these techniques, their application and their limitations, with reference to our experimental and clinical data. We also describe novel tools including a new algorithm to map microreentrant circuits sustaining fibrillation.

Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

BACKGROUND: Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. METHODS: We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. RESULTS: Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). CONCLUSIONS: The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach.

Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial Fibrillation.

BACKGROUND: Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF. METHODS AND RESULTS: Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism. The effects of different data types (action potentials and unipolar or bipolar electrograms) and rotor stability on resolution requirements were investigated. We also determined the ability of clinically used endocardial catheters to identify AF mechanisms using clinically recorded and simulated data. The spatial resolution required for correct identification of rotors and focal sources is a linear function of spatial wavelength (the distance between wavefronts) of the arrhythmia. Rotor localization errors are larger for electrogram data than for action potential data. Stationary rotors are more reliably identified compared with meandering trajectories, for any given spatial resolution. All clinical high-resolution multipolar catheters are of sufficient resolution to accurately detect and track rotors when placed over the rotor core although the low-resolution basket catheter is prone to false detections and may incorrectly identify rotors that are not present. CONCLUSIONS: The spatial resolution of AF data can significantly affect the interpretation of the underlying AF mechanism. Therefore, the interpretation of human AF data must be taken in the context of the spatial resolution of the recordings.

A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to Guide Substrate Ablation for Ventricular Tachycardia.

BACKGROUND: Post-infarct ventricular tachycardia is associated with channels of surviving myocardium within scar characterized by fractionated and low-amplitude signals usually occurring late during sinus rhythm. Conventional automated algorithms for 3-dimensional electro-anatomic mapping cannot differentiate the delayed local signal of conduction within the scar from the initial far-field signal generated by surrounding healthy tissue. Ripple mapping displays every deflection of an electrogram, thereby providing fully informative activation sequences. We prospectively used CARTO-based ripple maps to identify conducting channels as a target for ablation. METHODS AND RESULTS: High-density bipolar left ventricular endocardial electrograms were collected using CARTO3v4 in sinus rhythm or ventricular pacing and reviewed for ripple mapping conducting channel identification. Fifteen consecutive patients (median age 68 years, left ventricular ejection fraction 30%) were studied (6 month preprocedural implantable cardioverter defibrillator therapies: median 19 ATP events [Q1-Q3=4-93] and 1 shock [Q1-Q3=0-3]). Scar (<1.5 mV) occupied a median 29% of the total surface area (median 540 points collected within scar). A median of 2 ripple mapping conducting channels were seen within each scar (length 60 mm; initial component 0.44 mV; delayed component 0.20 mV; conduction 55 cm/s). Ablation was performed along all identified ripple mapping conducting channels (median 18 lesions) and any presumed interconnected late-activating sites (median 6 lesions; Q1-Q3=2-12). The diastolic isthmus in ventricular tachycardia was mapped in 3 patients and colocated within the ripple mapping conducting channels identified. Ventricular tachycardia was noninducible in 85% of patients post ablation, and 71% remain free of ventricular tachycardia recurrence at 6-month median follow-up. CONCLUSIONS: Ripple mapping can be used to identify conduction channels within scar to guide functional substrate ablation.

A Prospective Study of Ripple Mapping in Atrial Tachycardias: A Novel Approach to Interpreting Activation in Low-Voltage Areas.

BACKGROUND: Post ablation atrial tachycardias are characterized by low-voltage signals that challenge current mapping methods. Ripple mapping (RM) displays every electrogram deflection as a bar moving from the cardiac surface, resulting in the impression of propagating wavefronts when a series of bars move consecutively. RM displays fractionated signals in their entirety thereby helping to identify propagating activation in low-voltage areas from nonconducting tissue. We prospectively used RM to study tachycardia activation in the previously ablated left atrium. METHODS AND RESULTS: Patients referred for atrial tachycardia ablation underwent dense electroanatomic point collection using CARTO3v4. RM was played over a bipolar voltage map and used to determine the voltage "activation threshold" that differentiated functional low voltage from nonconducting areas for each map. Ablation was guided by RM, but operators could perform entrainment or review the isochronal activation map for diagnostic uncertainty. Twenty patients were studied. Median RM determined activation threshold was 0.3 mV (0.19-0.33), with nonconducting tissue covering 33±9% of the mapped surface. All tachycardias crossed an isthmus (median, 0.52 mV, 13 mm) bordered by nonconducting tissue (70%) or had a breakout source (median, 0.35 mV) moving away from nonconducting tissue (30%). In reentrant circuits (14/20) the path length was measured (87-202 mm), with 9 of 14 also supporting a bystander circuit (path lengths, 147-234 mm). In breakout tachycardias, splitting of wavefronts resulted in 2 to 4 incomplete circuits. RM-guided ablation interrupted the tachycardia in 19 of 20 cases with the first ablation set. CONCLUSIONS: RM helps to define activation through low-voltage regions and aids ablation of atrial tachycardias.

No Benefit of Complex Fractionated Atrial Electrogram Ablation in Addition to Circumferential Pulmonary Vein Ablation and Linear Ablation: Benefit of Complex Ablation Study.

BACKGROUND: The optimal ablation strategy for persistent atrial fibrillation (AF) remains unclear. METHODS AND RESULTS: This multicentre randomized study compared circumferential pulmonary vein ablation+linear ablation (control arm) versus circumferential pulmonary vein ablation+linear ablation+complex fractionated atrial electrogram (CFAE) ablation (CFAE arm) in patients with persistent AF. Circumferential pulmonary vein ablation was performed followed by roof and mitral isthmus ablation, before CFAE ablation in the CFAE arm. Ablation strategy was maintained at the first redo procedure. Sixty-five patients were recruited in each arm. The mean age was 61±10 years, 75% were men, median AF duration was 2 years, 42% had long-lasting persistent AF, 68% had associated cardiovascular disease, mean left atrial dimension was 46±6 mm, and median CHA2DS2-VASc score was 2. Ablation and procedure times were significantly longer in the CFAE arm (70±20 versus 55±17; 201±35 versus 152±45 minutes; P<0.005). After a mean follow-up of 35±5 months, single-procedural success off antiarrhythmic drugs at 12 months (CFAE: 30/65 [46%] versus control: 37/65 [57%]; P=0.29) and multiprocedural success (CFAE: 51/65 [78%] versus control: 52/65 [80%]; P=1.0) were not significantly different. At the first redo procedure, patients in the CFAE arm had a higher incidence of organized atrial tachycardia/flutter (24/33 [73%] versus 11/31 [35%]; P=0.005) and gap-related macro-re-entrant flutter (8/33[24%] versus 1/31[3%]; P=0.03). Early recurrence of atrial arrhythmia was an independent predictor of late recurrence. CONCLUSIONS: CFAE ablation did not confer incremental benefit when performed in addition to circumferential pulmonary vein ablation and linear ablation. It was associated with a higher incidence of gap-related flutter. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01711047.

A diagnostic algorithm to optimize data collection and interpretation of Ripple Maps in atrial tachycardias.

BACKGROUND: Ripple Mapping (RM) is designed to overcome the limitations of existing isochronal 3D mapping systems by representing the intracardiac electrogram as a dynamic bar on a surface bipolar voltage map that changes in height according to the electrogram voltage-time relationship, relative to a fiduciary point. OBJECTIVE: We tested the hypothesis that standard approaches to atrial tachycardia CARTO™ activation maps were inadequate for RM creation and interpretation. From the results, we aimed to develop an algorithm to optimize RMs for future prospective testing on a clinical RM platform. METHODS: CARTO-XP™ activation maps from atrial tachycardia ablations were reviewed by two blinded assessors on an off-line RM workstation. Ripple Maps were graded according to a diagnostic confidence scale (Grade I - high confidence with clear pattern of activation through to Grade IV - non-diagnostic). The RM-based diagnoses were corroborated against the clinical diagnoses. RESULTS: 43 RMs from 14 patients were classified as Grade I (5 [11.5%]); Grade II (17 [39.5%]); Grade III (9 [21%]) and Grade IV (12 [28%]). Causes of low gradings/errors included the following: insufficient chamber point density; window-of-interest<100% of cycle length (CL); <95% tachycardia CL mapped; variability of CL and/or unstable fiducial reference marker; and suboptimal bar height and scar settings. CONCLUSIONS: A data collection and map interpretation algorithm has been developed to optimize Ripple Maps in atrial tachycardias. This algorithm requires prospective testing on a real-time clinical platform.

An automated algorithm for determining conduction velocity, wavefront direction and origin of focal cardiac arrhythmias using a multipolar catheter.

Determining locations of focal arrhythmia sources and quantifying myocardial conduction velocity (CV) are two major challenges in clinical catheter ablation cases. CV, wave-front direction and focal source location can be estimated from multipolar catheter data, but currently available methods are time-consuming, limited to specific electrode configurations, and can be inaccurate. We developed automated algorithms to rapidly identify CV from multipolar catheter data with any arrangement of electrodes, whilst providing estimates of wavefront direction and focal source position, which can guide the catheter towards a focal arrhythmic source. We validated our methods using simulations on realistic human left atrial geometry. We subsequently applied them to clinically-acquired intracardiac electrogram data, where CV and wavefront direction were accurately determined in all cases, whilst focal source locations were correctly identified in 2/3 cases. Our novel automated algorithms can potentially be used to guide ablation of focal arrhythmias in real-time in cardiac catheter laboratories.

Mitral isthmus ablation using steerable sheath and high ablation power: a single center experience.

BACKGROUND: Mitral isthmus ablation is challenging. The use of steerable sheath and high ablation power may improve success rate. METHODS: This single-center, prospective study enrolled 200 patients who underwent ablation for atrial fibrillation (AF), including mitral isthmus ablation. Mitral isthmus ablation was performed using an irrigated ablation catheter via a steerable sheath (endocardium: maximum power: 40/50 W limited to annular end, maximum temperature: 48 °C; coronary sinus [CS]: maximum power: 25/30 W, maximum temperature: 48 °C). Endpoint was bidirectional mitral isthmus block. RESULTS: Mitral isthmus block was acutely achieved in 182/200 patients (91%). Sixty-nine percent of patients required CS ablation. Mean total ablation time was 13 ± 6 minutes. There was 1 case of acute circumflex artery occlusion. Mean left atrium (LA) diameter was significantly bigger in patients with unsuccessful mitral isthmus ablation (49 ± 4 mm vs. 43 ± 6 mm; P = 0.0007). In redo procedures, the incidence of reconduction at the mitral isthmus, roof and cavotricuspid isthmus was 44%, 37%, and 29%, respectively. Overall incidence of perimitral flutter was 9%. Prior complex fractionated atrial electrogram ablation was a predictor for microreentrant atrial tachycardia (AT) whereas gaps in linear lesions predicted macroreentrant flutters. After a mean follow-up of 20 ± 9 months, 73% of patients remained free from AF or AT. CONCLUSION: We reported on a series of mitral isthmus ablation using steerable sheath and high ablation power (50 W). Larger LA diameter was a predictor of failure to achieve mitral isthmus block. The mitral isthmus had a moderately high incidence of re-conduction but was only associated with a relatively low incidence of perimitral flutter.