Therapeutic potential of conduction system pacing as a method for improving cardiac output during ventricular tachycardia.

BACKGROUND: Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. METHODS: Study 1 aimed to improve the understanding of mechanisms of harm during VT (using pacing simulated VT). In 23 patients with left ventricular impairment, we recorded continuous ECG and beat-by-beat blood pressure measurements. We assessed the hemodynamic impact of heart rate and restoration of atrial and biventricular synchrony. Study 2 investigated novel pacing interventions during clinical VT by evaluating the hemodynamic effects of His bundle pacing at 5 bpm above the VT rate in 10 patients. RESULTS: In Study 1, at progressively higher rates of simulated VT, systolic blood pressure declined: at rates of 125, 160, and 190 bpm, -22.2%, -42.0%, and -58.7%, respectively (ANOVA p < 0.0001). Restoring atrial synchrony alone had only a modest beneficial effect on systolic blood pressure (+ 3.6% at 160 bpm, p = 0.2117), restoring biventricular synchrony alone had a greater effect (+ 9.1% at 160 bpm, p = 0.242), and simultaneously restoring both significantly increased systolic blood pressure (+ 31.6% at 160 bpm, p = 0.0003). In Study 2, the mean rate of clinical VT was 143 ± 21 bpm. His bundle pacing increased systolic blood pressure by + 14.2% (p = 0.0023). In 6 of 10 patients, VT terminated with His bundle pacing. CONCLUSIONS: Restoring atrial and biventricular synchrony improved hemodynamic function in simulated and clinical VT. Conduction system pacing could improve VT tolerability and treatment.

An Economic Evaluation of a Streamlined Day-Case Atrial Fibrillation Ablation Protocol and Conventional Cryoballoon Ablation versus Antiarrhythmic Drugs in a UK Paroxysmal Atrial Fibrillation Population.

BACKGROUND AND AIMS: Symptom control for atrial fibrillation can be achieved by catheter ablation or drug therapy. We assessed the cost effectiveness of a novel streamlined atrial fibrillation cryoballoon ablation protocol (AVATAR) compared with optimised antiarrhythmic drug (AAD) therapy and a conventional catheter ablation protocol, from a UK National Health Service (NHS) perspective. METHODS: Data from the AVATAR study were assessed to determine the cost effectiveness of the three protocols in a two-step process. In the first stage, statistical analysis of clinical efficacy outcomes was conducted considering either a three-way comparison (AVATAR vs. conventional ablation vs. optimised AAD therapies) or a two-way comparison (pooled ablation protocol data vs. optimised AAD therapies). In the second stage, models assessed the cost effectiveness of the protocols. Costs and some of the clinical inputs in the models were derived from within-trial cost analysis and published literature. The remaining inputs were derived from clinical experts. RESULTS: No significant differences between the ablation protocols were found for any of the clinical outcomes used in the model. Results of a within-trial cost analysis show that AVATAR is cost-saving (£1279 per patient) compared with the conventional ablation protocol. When compared with optimised AAD therapies, AVATAR (pooled conventional and AVATAR ablation protocols efficacy) was found to be more costly while offering improved clinical benefits. Over a lifetime time horizon, the incremental cost-effectiveness ratio of AVATAR was estimated as £21,046 per quality-adjusted life-year gained (95% credible interval £7086-£71,718). CONCLUSIONS: The AVATAR streamlined protocol is likely to be a cost-effective option versus both conventional ablation and optimised AAD therapy in the UK NHS healthcare setting.

Characterization of conduction system activation in the postinfarct ventricle using ripple mapping.

BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.

Machine learning-derived cycle length variability metrics predict spontaneously terminating ventricular tachycardia in implantable cardioverter defibrillator recipients.

Aims: Implantable cardioverter defibrillator (ICD) therapies have been associated with increased mortality and should be minimized when safe to do so. We hypothesized that machine learning-derived ventricular tachycardia (VT) cycle length (CL) variability metrics could be used to discriminate between sustained and spontaneously terminating VT. Methods and results: In this single-centre retrospective study, we analysed data from 69 VT episodes stored on ICDs from 27 patients (36 spontaneously terminating VT, 33 sustained VT). Several VT CL parameters including heart rate variability metrics were calculated. Additionally, a first order auto-regression model was fitted using the first 10 CLs. Using features derived from the first 10 CLs, a random forest classifier was used to predict VT termination. Sustained VT episodes had more stable CLs. Using data from the first 10 CLs only, there was greater CL variability in the spontaneously terminating episodes (mean of standard deviation of first 10 CLs: 20.1 ± 8.9 vs. 11.5 ± 7.8 ms, P < 0.0001). The auto-regression coefficient was significantly greater in spontaneously terminating episodes (mean auto-regression coefficient 0.39 ± 0.32 vs. 0.14 ± 0.39, P < 0.005). A random forest classifier with six features yielded an accuracy of 0.77 (95% confidence interval 0.67 to 0.87) for prediction of VT termination. Conclusion: Ventricular tachycardia CL variability and instability are associated with spontaneously terminating VT and can be used to predict spontaneous VT termination. Given the harmful effects of unnecessary ICD shocks, this machine learning model could be incorporated into ICD algorithms to defer therapies for episodes of VT that are likely to self-terminate.

RETRO-mapping: A novel algorithm automating wavefront categorization using activation mapping during persistent atrial fibrillation demonstrates a reduction in wavefront collisions following pulmonary vein isolation.

RETRO-mapping was developed to automate activation mapping of atrial fibrillation (AF). We used the algorithm to study the effect of pulmonary vein isolation (PVI) on the frequency of focal, planar, and colliding wavefronts in persistent AF. An AFocusII catheter was placed on the left atrial endocardium to record 3 s of AF at six sites pre and post-PVI in patients undergoing wide circumferential PVI for persistent AF. RETRO-mapping analyzed each segment in 2 ms time windows for evidence of focal, planar, and colliding waveforms and the automated categorizations manually validated. Ten patients were recruited. A total of 360 s of data in 120 segments of 3 s from 60 left atrial locations were analyzed. RETRO-map was highly effective at identifying focal waves and collisions during AF. PVI significantly reduced collision frequency but not focal and planar activation frequency. However, there was a significant reduction in the dispersion of activation directions. Larger studies may help determine factors associated with successful clinical outcome.

Catheter Ablation for Ventricular Tachycardia After MI: A Reconstructed Individual Patient Data Meta-analysis of Randomised Controlled Trials.

Background: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. Methods: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. Results: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41-0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67-1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. Conclusion: In patients with postinfarct VT, catheter ablation reduces mortality.

Left atrial appendage occlusion for atrial fibrillation and bleeding diathesis.

BACKGROUND: Patients with atrial fibrillation (AF) and likelihood of bleeding can undergo left atrial appendage occlusion (LAAO) as an alternative method of stroke prophylaxis. Short-term anti-thrombotic drugs are used postprocedure to offset the risk of device-related thrombus, evidence for this practice is limited. OBJECTIVES: To investigate optimal postimplant antithrombotic strategy in high bleeding-risk patients. METHODS: Patients with AF and high-risk for both stroke and bleeding undergoing LAAO were advised their perioperative drug therapy by a multidisciplinary physician panel. Those deemed to be at higher risk of bleeding from anti-thrombotic drugs were assigned to minimal treatment with no antithrombotics or Aspirin-alone. The remaining patients received standard care (STG) with a 12 week course of dual-antiplatelets or anticoagulation postimplant. We compared mortality, device-related thrombus, ischemic stroke, and bleeding events during the 90 days postimplant and long-term. Event-free survival was assessed using Kaplan-Meier survival analysis, with logrank testing for statistical significance. RESULTS: Seventy-five patients underwent LAAO of whom 63 patients (84%) had a prior serious bleeding event. The 42 patients on minimal treatment were older (74.3 ± 7.7 vs. 71.2 ± 7.2) with higher HASBLED score (3.6 ± 0.9 vs. 3.3 ± 1.2) than the 33 patients having standard care. There were no device-related thrombi or strokes in either group at 90 days postprocedure; STG had more bleeding events (5/33 vs. 0/42, p = 0.01) with associated deaths (3/33 vs. 0/42, p = 0.05). During long-term follow-up (median 2.2 years), all patients transitioned onto no antithrombotic drugs (43 patients [61%]) or a single-antiplatelet (29 patients [39%]). There was no evidence of early minimal treatment adversely affecting long-term outcomes. CONCLUSIONS: Short-term anti-thrombotic drugs may not be needed after LAAO implant in patients with high bleeding risk and could be harmful. Larger, prospective studies would be warranted to test these findings.

Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics.

AIMS: Left bundle branch pacing (LBBP) can deliver physiological left ventricular activation, but typically at the cost of delayed right ventricular (RV) activation. Right ventricular activation can be advanced through anodal capture, but there is uncertainty regarding the mechanism by which this is achieved, and it is not known whether this produces haemodynamic benefit. METHODS AND RESULTS: We recruited patients with LBBP leads in whom anodal capture eliminated the terminal R-wave in lead V1. Ventricular activation pattern, timing, and high-precision acute haemodynamic response were studied during LBBP with and without anodal capture. We recruited 21 patients with a mean age of 67 years, of whom 14 were males. We measured electrocardiogram timings and haemodynamics in all patients, and in 16, we also performed non-invasive mapping. Ventricular epicardial propagation maps demonstrated that RV septal myocardial capture, rather than right bundle capture, was the mechanism for earlier RV activation. With anodal capture, QRS duration and total ventricular activation times were shorter (116 ± 12 vs. 129 ± 14 ms, P < 0.01 and 83 ± 18 vs. 90 ± 15 ms, P = 0.01). This required higher outputs (3.6 ± 1.9 vs. 0.6 ± 0.2 V, P < 0.01) but without additional haemodynamic benefit (mean difference -0.2 ± 3.8 mmHg compared with pacing without anodal capture, P = 0.2). CONCLUSION: Left bundle branch pacing with anodal capture advances RV activation by stimulating the RV septal myocardium. However, this requires higher outputs and does not improve acute haemodynamics. Aiming for anodal capture may therefore not be necessary.

Septal scar as a barrier to left bundle branch area pacing.

BACKGROUND: The use of left bundle branch area pacing (LBBAP) for bradycardia pacing and cardiac resynchronization is increasing, but implants are not always successful. We prospectively studied consecutive patients to determine whether septal scar contributes to implant failure. METHODS: Patients scheduled for bradycardia pacing or cardiac resynchronization therapy were prospectively enrolled. Recruited patients underwent preprocedural scar assessment by cardiac MRI with late gadolinium enhancement imaging. LBBAP was attempted using a lumenless lead (Medtronic 3830) via a transeptal approach. RESULTS: Thirty-five patients were recruited: 29 male, mean age 68 years, 10 ischemic, and 16 non-ischemic cardiomyopathy. Pacing indication was bradycardia in 26% and cardiac resynchronization in 74%. The lead was successfully deployed to the left ventricular septum in 30/35 (86%) and unsuccessful in the remaining 5/35 (14%). Septal late gadolinium enhancement was significantly less extensive in patients where left septal lead deployment was successful, compared those where it was unsuccessful (median 8%, IQR 2%-18% vs. median 54%, IQR 53%-57%, p < .001). CONCLUSIONS: The presence of septal scar appears to make it more challenging to deploy a lead to the left ventricular septum via the transeptal route. Additional implant tools or alternative approaches may be required in patients with extensive septal scar.

Ripple AT Plus - isthmus-guided vs conventional ablation in the treatment of scar-related atrial tachycardia: study protocol for a randomised controlled trial.

BACKGROUND: Catheter ablation is routinely used to treat scar-related atrial tachycardia (s-AT). Conventional ablation often involves creating anatomical "lines" that transect myocardial tissue supporting reentry. This can be extensive, creating iatrogenic scar as a nidus for future reentry, and may account for arrhythmia recurrence. High-density mapping may identify "narrower isthmuses" requiring less ablation, with ripple mapping proven to be an effective approach in identifying. This trial explores whether ablation of narrower isthmuses in s-AT, defined using ripple mapping, results in greater freedom from arrhythmia recurrence compared to conventional ablation. METHODS: The Ripple-AT-Plus trial (registration ClinicalTrials.gov , NCT03915691) is a prospective, multicentre, single-blinded, randomised controlled trial with 12-month follow-up. Two hundred s-AT patients will be randomised in a 1:1 fashion to either "ripple mapping-guided isthmus ablation" vs conventional ablation on the CARTO3 ConfiDENSE system (Biosense Webster). The primary outcome will compare recurrence of any atrial arrhythmia. Multicentre data will be analysed over a secure web-based cloud-storage and analysis software (CARTONETTM). CONCLUSION: This is the first trial that considers long-term patient outcomes post s-AT ablation, and whether targeting narrower isthmuses in the era of high density is optimal.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Ventricular Conduction Stability Noninvasively Identifies an Arrhythmic Substrate in Survivors of Idiopathic Ventricular Fibrillation.

Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise-induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252-electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3-1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise-induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires further investigation as a testable manifestation of underlying myocardial abnormalities otherwise silent during routine testing.

Artificial intelligence-enabled electrocardiogram to distinguish atrioventricular re-entrant tachycardia from atrioventricular nodal re-entrant tachycardia.

Background: Accurately determining arrhythmia mechanism from a 12-lead electrocardiogram (ECG) of supraventricular tachycardia can be challenging. We hypothesized a convolutional neural network (CNN) can be trained to classify atrioventricular re-entrant tachycardia (AVRT) vs atrioventricular nodal re-entrant tachycardia (AVNRT) from the 12-lead ECG, when using findings from the invasive electrophysiology (EP) study as the gold standard. Methods: We trained a CNN on data from 124 patients undergoing EP studies with a final diagnosis of AVRT or AVNRT. A total of 4962 5-second 12-lead ECG segments were used for training. Each case was labeled AVRT or AVNRT based on the findings of the EP study. The model performance was evaluated against a hold-out test set of 31 patients and compared to an existing manual algorithm. Results: The model had an accuracy of 77.4% in distinguishing between AVRT and AVNRT. The area under the receiver operating characteristic curve was 0.80. In comparison, the existing manual algorithm achieved an accuracy of 67.7% on the same test set. Saliency mapping demonstrated the network used the expected sections of the ECGs for diagnoses; these were the QRS complexes that may contain retrograde P waves. Conclusion: We describe the first neural network trained to differentiate AVRT from AVNRT. Accurate diagnosis of arrhythmia mechanism from a 12-lead ECG could aid preprocedural counseling, consent, and procedure planning. The current accuracy from our neural network is modest but may be improved with a larger training dataset.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

Feasibility of mapping and ablating ectopy-triggering ganglionated plexus reproducibly in persistent atrial fibrillation.

BACKGROUND: Ablation of autonomic ectopy-triggering ganglionated plexuses (ET-GP) has been used to treat paroxysmal atrial fibrillation (AF). It is not known if ET-GP localisation is reproducible between different stimulators or whether ET-GP can be mapped and ablated in persistent AF. We tested the reproducibility of the left atrial ET-GP location using different high-frequency high-output stimulators in AF. In addition, we tested the feasibility of identifying ET-GP locations in persistent atrial fibrillation. METHODS: Nine patients undergoing clinically-indicated paroxysmal AF ablation received pacing-synchronised high-frequency stimulation (HFS), delivered in SR during the left atrial refractory period, to compare ET-GP localisation between a custom-built current-controlled stimulator (Tau20) and a voltage-controlled stimulator (Grass S88, SIU5). Two patients with persistent AF underwent cardioversion, left atrial ET-GP mapping with the Tau20 and ablation (Precision™, Tacticath™ [n = 1] or Carto™, SmartTouch™ [n = 1]). Pulmonary vein isolation (PVI) was not performed. Efficacy of ablation at ET-GP sites alone without PVI was assessed at 1 year. RESULTS: The mean output to identify ET-GP was 34 mA (n = 5). Reproducibility of response to synchronised HFS was 100% (Tau20 vs Grass S88; [n = 16] [kappa = 1, SE = 0.00, 95% CI 1 to 1)][Tau20 v Tau20; [n = 13] [kappa = 1, SE = 0, 95% CI 1 to 1]). Two patients with persistent AF had 10 and 7 ET-GP sites identified requiring 6 and 3 min of radiofrequency ablation respectively to abolish ET-GP response. Both patients were free from AF for > 365 days without anti-arrhythmics. CONCLUSIONS: ET-GP sites are identified at the same location by different stimulators. ET-GP ablation alone was able to prevent AF recurrence in persistent AF, and further studies would be warranted.

Evaluation of RETRO-Mapping for electrophysiological features including direction of plane activity during atrial fibrillation using multipolar catheters in humans.

INTRODUCTION: A quantifiable, automated standard of analyzing heart rhythm has long eluded cardiologists due, in part, to the limitations in technology and the ability to analyze large electrogram datasets. In this proof-of-concept study, we propose new measures to quantify plane activity in atrial fibrillation (AF) using our Representation of Electrical Tracking of Origin (RETRO)-Mapping software. METHODS: We recorded 30 s segments of electrograms at the lower posterior wall of the left atrium using a 20-pole double loop catheter (AFocusII). The data were analyzed with the custom RETRO-Mapping algorithm in MATLAB. Thirty second segments were analyzed for number of activation edges, conduction velocity (CV), cycle length (CL), activation edge direction, and wavefront direction. These features were compared across 34 613 plane edges in three types of AF: persistent AF treated with amiodarone (11 906 wavefronts), persistent AF without amiodarone (14 959 wavefronts), and paroxysmal AF (7748 wavefronts). Change in activation edge direction between subsequent frames and change in overall wavefront direction between subsequent wavefronts were analyzed. RESULTS: All activation edge directions were represented across the lower posterior wall. The median change in activation edge direction followed a linear pattern for all three types of AF with R2 = 0.932 for persistent AF treated without amiodarone, R2 = 0.942 for paroxysmal AF, and R2 = 0.958 for persistent AF treated with amiodarone. All medians and the standard deviation error bars remained below 45° (suggesting all activation edges were traveling within a 90° sector, a criterion for plane activity). The directions of approximately half of all wavefronts (56.1% for persistent without amiodarone, 51.8% for paroxysmal, 48.8% for persistent with amiodarone) were predictive of the directions of the subsequent wavefront. CONCLUSION: RETRO-Mapping can measure electrophysiological features of activation activity and this proof-of-concept study suggests that this can be extended to the detection of plane activity in three types of AF. Wavefront direction may have a role in future work for predicting plane activity. For this study, we focused more on the ability of the algorithm to detect plane activity and less the differences between the types of AF. Future work should be in validating these results with a larger data set and comparing with other types of activation such as rotational, collision, and focal. Ultimately, this work can be implemented in real-time for prediction of wavefronts during ablation procedures.

Comparison of methods for delivering cardiac resynchronization therapy: an acute electrical and haemodynamic within-patient comparison of left bundle branch area, His bundle, and biventricular pacing.

AIMS: Left bundle branch area pacing (LBBAP) is a promising method for delivering cardiac resynchronization therapy (CRT), but its relative physiological effectiveness compared with His bundle pacing (HBP) is unknown. We conducted a within-patient comparison of HBP, LBBAP, and biventricular pacing (BVP). METHODS AND RESULTS: Patients referred for CRT were recruited. We assessed electrical response using non-invasive mapping, and acute haemodynamic response using a high-precision haemodynamic protocol. Nineteen patients were recruited: 14 male, mean LVEF of 30%. Twelve had time for BVP measurements. All three modalities reduced total ventricular activation time (TVAT), (ΔTVATHBP -43 ± 14 ms and ΔTVATLBBAP -35 ± 20 ms vs. ΔTVATBVP -19 ± 30 ms, P = 0.03 and P = 0.1, respectively). HBP produced a significantly greater reduction in TVAT compared with LBBAP in all 19 patients (-46 ± 15 ms, -36 ± 17 ms, P = 0.03). His bundle pacing and LBBAP reduced left ventricular activation time (LVAT) more than BVP (ΔLVATHBP -43 ± 16 ms, P < 0.01 vs. BVP, ΔLVATLBBAP -45 ± 17 ms, P < 0.01 vs. BVP, ΔLVATBVP -13 ± 36 ms), with no difference between HBP and LBBAP (P = 0.65). Acute systolic blood pressure was increased by all three modalities. In the 12 with BVP, greater improvement was seen with HBP and LBBAP (6.4 ± 3.8 mmHg BVP, 8.1 ± 3.8 mmHg HBP, P = 0.02 vs. BVP and 8.4 ± 8.2 mmHg for LBBAP, P = 0.3 vs. BVP), with no difference between HBP and LBBAP (P = 0.8). CONCLUSION: HBP delivered better ventricular resynchronization than LBBAP because right ventricular activation was slower during LBBAP. But LBBAP was not inferior to HBP with respect to LV electrical resynchronization and acute haemodynamic response.

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.