Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Progress in atrial fibrillation ablation during 25 years of Europace journal.

The first edition of Europace journal in 1999 came right around the time of the landmark publication of the electrophysiologists from Bordeaux, establishing how elimination of ectopic activity from the pulmonary veins (PVs) resulted in a marked reduction of atrial fibrillation (AF). The past 25 years have seen an incredible surge in scientific interest to develop new catheters and energy sources to optimize durability and safety of ablation, as well as study the mechanisms for AF and devise ablation strategies. While ablation in the beginning was performed with classic 4 mm tip catheters that emitted radiofrequency (RF) energy to create tissue lesions, this evolved to using irrigation and contact force (CF) measurement while increasing power. Also, so-called single-shot devices were developed with balloons and arrays to create larger contiguous lesions, and energy sources changed from RF current to cryogenic ablation and more recently pulsed field ablation with electrical current. Although PV ablation has remained the basis for every AF ablation, it was soon recognized that this was not enough to cure all patients, especially those with non-paroxysmal AF. Standardized approaches for additional ablation targets have been used but have not been satisfactory in all patients so far. This led to highly technical mapping systems that are meant to unravel the drivers for the maintenance of AF. In the following sections, the development of energies, strategies, and tools is described with a focus on the contribution of Europace to publish the outcomes of studies that were done during the past 25 years.

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria.

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1 ) and Na+ /K+ pump (INaK ) densities (IK1 0.11 ± 0.03 vs. 0.07 ± 0.03 S mF-1 ; INaK 0.68 ± 0.15 vs. 0.38 ± 26 S mF-1 ; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12 ± 0.02 S mF-1 ) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL , density 0.08 ± 0.03 S mF-1 ). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa ), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13 ± 0.05 S mF-1 ). For short refractoriness, atria with high INa (median density 8.92 ± 2.59 S mF-1 ) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33 ± 1.41 S mF-1 ). In silico drug trials in 800 human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics. KEY POINTS: Atrial fibrillation (AF) maintenance is facilitated by small L-type Ca2+ current (ICaL ) and large inward rectifier K+ current (IK1 ) and Na+ /K+ pump. In severely remodelled left atrium, with low voltage areas (LVA) covering more than 40% of the posterior wall, sustained AF requires higher IK1 and rotors localize in healthy right atrium. For lower LVA extensions, rotors can also anchor to LVA, if the atria present short refractoriness (low ICaL ) Vernakalant is effective in atria presenting long refractoriness (high ICaL ). For short refractoriness, atria with fast Na+ current (INa ) up-regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low INa . The inward currents (ICaL and INa ) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.

Real-world clinical outcomes with a next-generation left atrial appendage closure device: the FLXibility Post-Approval Study.

AIMS: The FLXibility Post-Approval Study collected data on unselected patients implanted with a WATCHMAN FLX in a commercial clinical setting. METHODS AND RESULTS: Patients were implanted with a WATCHMAN FLX per local standard of care, with a subsequent first follow-up visit from 45 to 120 days post-implant and a final follow-up at 1-year post-procedure. A Clinical Event Committee adjudicated all major adverse events and TEE/CT imaging results were adjudicated by a core laboratory. Among 300 patients enrolled at 17 centres in Europe, the mean age was 74.6 ± 8.0 years, mean CHA2DS2-VASc score was 4.3 ± 1.6, and 62.1% were male. The device was successfully implanted in 99.0% (297/300) of patients. The post-implant medication regimen was DAPT for 87.3% (262/300). At first follow-up, core-lab adjudicated complete seal was 88.2% (149/169), 9.5% (16/169) had leak <3 mm, 2.4 (4/169) had leak ≥3 mm to ≤5 mm, and 0% had >5 mm leak. At 1 year, 93.3% (280/300) had final follow-up; 60.5% of patients were on a single antiplatelet medication, 21.4% were on DAPT, 5.6% were on direct oral anticoagulation, and 12.1% were not taking any antiplatelet/anticoagulation medication. Adverse event rates through 1 year were: all-cause death 10.8% (32/295); CV/unexplained death 5.1% (15/295); disabling and non-disabling stroke each 1.0% (3/295, all non-fatal); pericardial effusion requiring surgery or pericardiocentesis 1.0% (3/295); and device-related thrombus 2.4% (7/295). CONCLUSION: The WATCHMAN FLX device had excellent procedural success rates, high LAA seal rates, and low rates of thromboembolic events in everyday clinical practice.

Reducing the electrogram review burden imposed by insertable cardiac monitors.

BACKGROUND: Insertable cardiac monitors (ICMs) are essential for ambulatory arrhythmia diagnosis. However, definitive diagnoses still require time-consuming, manual adjudication of electrograms (EGMs). OBJECTIVE: To evaluate the clinical impact of selecting only key EGMs for review. METHODS: Retrospective analyses of randomly selected Abbott Confirm Rx™ devices with ≥90 days of remote transmission history were performed, with each EGM adjudicated as true or false positive (TP, FP). For each device, up to 3 "key EGMs" per arrhythmia type per day were prioritized for review based on ventricular rate and episode duration. The reduction in EGMs and TP days (patient-days with at least one TP EGM), and any diagnostic delay (from the first TP), were calculated versus reviewing all EGMs. RESULTS: In 1000 ICMs over a median duration of 8.1 months, at least one atrial fibrillation (AF), tachycardia, bradycardia, or pause EGM was transmitted by 424, 343, 190, and 325 devices, respectively, with a total of 95 716 EGMs. Approximately 90% of episodes were contributed by 25% of patients. Key EGM selection reduced EGM review burden by 43%, 66%, 77%, and 50% (55% overall), while reducing TP days by 0.8%, 2.1%, 0.2%, and 0.0%, respectively. Despite reviewing fewer EGMs, 99% of devices with a TP EGM were ultimately diagnosed on the same day versus reviewing all EGMs. CONCLUSION: Key EGM selection reduced the EGM review substantially with no delay-to-diagnosis in 99% of patients exhibiting true arrhythmias. Implementing these rules in the Abbott patient care network may accelerate clinical workflow without compromising diagnostic timelines.

Real-world evidence in a national health service: results of the UK CardioMEMS HF System Post-Market Study.

AIMS: The CardioMEMS HF System Post-Market Study (COAST) was designed to evaluate the safety, effectiveness, and feasibility of haemodynamic-guided heart failure (HF) management using a small sensor implanted in the pulmonary artery of New York Heart Association (NYHA) Class III HF patients in the UK, Europe, and Australia. METHODS AND RESULTS: COAST is a prospective, international, multicentre, open-label clinical study (NCT02954341). The primary clinical endpoint compares annualized HF hospitalization rates after 1 year of haemodynamic-guided management vs. the year prior to sensor implantation in patients with NYHA Class III symptoms and a previous HF hospitalization. The primary safety endpoints assess freedom from device/system-related complications and pressure sensor failure after 2 years. Results from the first 100 patients implanted at 14 out of the 15 participating centres in the UK are reported here. At baseline, all patients were in NYHA Class III, 70% were male, mean age was 69 ± 12 years, and 39% had an aetiology of ischaemic cardiomyopathy. The annualized HF hospitalization rate after 12 months was 82% lower [95% confidence interval 72-88%] than the previous 12 months (0.27 vs. 1.52 events/patient-year, respectively, P < 0.0001). Freedom from device/system-related complications and pressure sensor failure at 2 years was 100% and 99%, respectively. CONCLUSIONS: Remote haemodynamic-guided HF management, using frequent assessment of pulmonary artery pressures, was successfully implemented at 14 specialist centres in the UK. Haemodynamic-guided HF management was safe and significantly reduced hospitalization in a group of high-risk patients. These results support implementation of this innovative remote management strategy to improve outcome for patients with symptomatic HF. Clinical registration number: ClinicalTrials.gov identifier: NCT02954341.

An active fixation quadripolar left ventricular lead for cardiac resynchronization therapy with reduced postoperative complication rates.

BACKGROUND: The rate of left ventricular (LV) lead displacement after cardiac resynchronization therapy (CRT) remains high despite improvements in lead technology. In 2017, a novel quadripolar lead with active fixation technology became available in the UK. METHODS: This was a retrospective, observational study analyzing device complications in 476 consecutive patients undergoing successful first-time implantation of a CRT device at a tertiary center from 2017 to 2020. RESULTS: Both active (n = 135) and passive fixation (n = 341) quadripolar leads had similar success rates for implantation (99.3% vs. 98.8%, p = 1.00), although the pacing threshold (0.89 [0.60-1.25] vs. 1.00 [0.70-1.60] V, p = .01) and lead impedance (632 [552-794] vs. 730 [636-862] Ohms, p < .0001) were significantly lower for the active fixation lead. Patients receiving an active fixation lead had a reduced incidence of lead displacement at 6 months (0.74% vs. 4.69%, p = .036). There was no significant difference in the rate of right atrial (RA) and right ventricular (RV) lead displacement between the two groups (RA: 1.48% vs. 1.17%, p = .68; RV: 2.22% vs. 1.76%, p = .72). Reprogramming the LV lead after displacement was unsuccessful in most cases (successful reprogramming: Active fix = 0/1, Passive fix = 1/16) therefore nearly all patients required a repeat procedure. As a result, the rate of intervention within 6 months for lead displacement was significantly lower when patients were implanted with the active fixation lead (0.74% vs. 4.40%, p = .049). CONCLUSION: The novel active fixation lead in our study has a lower incidence of lead displacement and re-intervention compared to conventional quadripolar leads for CRT.

INtra-procedural ultraSound Imaging for DEtermination of atrial wall thickness and acute tissue changes after isolation of the pulmonary veins with radiofrequency, cryoballoon or laser balloon energy: the INSIDE PVs study.

Preliminary data in human suggest that both Intracardiac echocardiography (ICE) and Intravascular ultrasound (IVUS) can be used for real-time information on the left atrial (LA) wall thickness and on the acute tissue changes produced by energy delivery. This pilot study was conducted to compare ICE and IVUS for real-time LA wall imaging and assessment of acute tissue changes produced by radiofrequency (RF), cryo and laser catheter ablation. Patients scheduled for RF, cryoballoon or laser balloon Pulmonary Vein Isolation (PVI) catheter ablation were enrolled. Each pulmonary vein (PV) was imaged before and immediately after ablation with either ICE or IVUS. The performance of ICE and IVUS for imaging were compared. Pre- and post-ablation measurements (lumen and vessel diameters, areas and sphericity indexes, wall thickness and muscular sleeve thickness) were taken at the level of each PV ostium. A total of 48 PVs in 12 patients were imaged before and after ablation. Both ICE and IVUS showed acute tissue changes. Compared to IVUS, ICE showed higher imaging quality and inter-observer reproducibility of the PV measurements obtained. Acute wall thickening suggestive of oedema was observed after RF treatment (p = 0.003) and laser treatment (p = 0.003) but not after cryoablation (p = 0.69). Our pilot study suggests that ICE might be preferable to IVUS for LA wall thickness imaging at the LA-PV junctions during ablation. Ablation causes acute wall thickening when using RF or laser energy, but not cryoenergy delivery. Larger studies are needed to confirm these preliminary findings.

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt.

BACKGROUND: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. OBJECTIVE: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. METHODS: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. RESULTS: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire-guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002). CONCLUSIONS: AHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling.

Electrical synchronization achieved by multipoint pacing combined with dynamic atrioventricular delay.

PURPOSE: Multipoint pacing (MPP) improves left ventricular (LV) electrical synchrony in cardiac resynchronization therapy (CRT). SyncAV automatically adjusts atrioventricular delay (AVD) according to intrinsic AV intervals and may further improve synchrony. Their combination has not been assessed. The objective was to evaluate the improvement in electrical synchrony achieved by SyncAV combined with MPP in an international, multicenter study. METHODS: Patients with LBBB undergoing CRT implant with a quadripolar lead (Abbott Quartet™) were prospectively enrolled. QRS duration (QRSd) was measured by blinded observers from 12-lead ECG during: intrinsic conduction, BiV pacing (conventional biventricular pacing, nominal static AVD), MPP (2 LV cathodes maximally spaced, nominal static AVD), BiV + SyncAV, and MPP + SyncAV. All SyncAV offsets were individualized for each patient to yield the narrowest QRSd during BiV pacing. QRSd changes were compared by ANOVA and post hoc Tukey-Kramer tests. RESULTS: One hundred and three patients were enrolled (65.7 ± 12.1 years, 67% male, 37% ischemic, EF 26.4 ± 6.5%, PR 190.3 ± 39.1 ms). Relative to intrinsic conduction (QRSd of 165 ± 16 ms), BiV reduced QRSd by 11.9% to 145 ± 18 ms (P < 0.001 vs intrinsic), and MPP reduced QRSd by 13.3% to 142 ± 19 ms (P < 0.001 vs intrinsic). However, enabling SyncAV with a patient-optimized offset nearly doubled this QRSd reduction. BiV + SyncAV reduced QRSd by 22.0% to 128 ± 13 ms (P < 0.001 vs BiV), while MPP + SyncAV reduced QRSd further by 25.6% to 122 ± 14 ms (P < 0.05 vs BiV + SyncAV). CONCLUSION: SyncAV can significantly improve acute electrical synchrony beyond conventional CRT, with further improvement achieved by superimposing MPP.

Subcutaneous or Transvenous Defibrillator Therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).

Rationale and design of the PRAETORIAN-DFT trial: A prospective randomized CompArative trial of SubcutanEous ImplanTable CardiOverter-DefibrillatoR ImplANtation with and without DeFibrillation testing.

In transvenous implantable cardioverter-defibrillator (TV-ICD) implants, routine defibrillation testing (DFT) does not improve shock efficacy or reduce arrhythmic death but patients are exposed to the risk of complications related to DFT. The conversion rate of DFT in subcutaneous ICD (S-ICD) is high and first shock efficacy is similar to TV-ICD efficacy rates. STUDY DESIGN: The PRAETORIAN-DFT trial is an investigator-initiated, randomized, controlled, multicenter, prospective two-arm trial designed to demonstrate non-inferiority of omitting DFT in patients undergoing S-ICD implantation in which the S-ICD system components are optimally positioned. Positioning of the S-ICD will be assessed with the PRAETORIAN score. The PRAETORIAN score is developed to systematically evaluate implant position of the S-ICD system components which determine the defibrillation threshold on post-operative chest X-ray. A total of 965 patients, scheduled to undergo a de novo S-ICD implantation without contra-indications for either DFT strategy, will be randomized to either standard of care S-ICD implantation with DFT, or S-ICD implantation without DFT but with evaluation of the implant position using the PRAETORIAN score. The study is powered to claim non-inferiority of S-ICD implantation without DFT in de novo S-ICD patients in respect to the primary endpoint of first shock efficacy in spontaneous arrhythmia episodes. Patients with a high PRAETORIAN score (≥90) in the interventional arm of this study will undergo DFT according to the same DFT protocol as in the control arm. CONCLUSION: The PRAETORIAN-DFT trial is a randomized trial that aims to gain scientific evidence to safely omit a routine DFT after S-ICD implantation in patients with correct device positioning.

Multicenter Randomized Controlled Crossover Trial Comparing Hemodynamic Optimization Against Echocardiographic Optimization of AV and VV Delay of Cardiac Resynchronization Therapy: The BRAVO Trial.

OBJECTIVES: BRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method. BACKGROUND: Cardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform. METHODS: This study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro-B-type natriuretic peptide. RESULTS: A total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro-B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms. CONCLUSIONS: Optimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829).

Myocardial Perfusion Is Impaired and Relates to Cardiac Dysfunction in Patients With Atrial Fibrillation Both Before and After Successful Catheter Ablation.

Background Atrial fibrillation ( AF ) is associated with myocardial infarction, and patients with AF and no obstructive coronary artery disease can present with symptoms and evidence of cardiac ischemia. We hypothesized that microvascular coronary dysfunction underlies these observations. Methods and Results Myocardial blood flow ( MBF ) at baseline and during adenosine stress and left ventricular and left atrial function were evaluated by magnetic resonance in 49 patients with AF (25 paroxysmal, 24 persistent) with no history of epicardial coronary artery disease or diabetes mellitus, before and 6 to 9 months after ablation. Findings were compared with those obtained in matched controls in sinus rhythm (n=25). Before ablation, patients with AF had impaired left atrial function and left ventricular ejection fraction and strain indices (all P<0.05 versus controls). MBF was impaired in patients both under baseline conditions (1.21±0.24 mL/min per g·[mm Hg·bpm/104]-1 versus 1.34±0.28 mL/min per g·[mm Hg·bpm/104]-1 in controls, P=0.044) and during adenosine stress (2.29±0.48 mL/min per g versus 2.73±0.37 mL/min per g in controls, P<0.001). Under baseline conditions, MBF correlated with left ventricular strain and left atrial function (all P≤0.001), so that cardiac function was most impaired in patients with the lowest MBF . Baseline and stress MBF remained unchanged postablation (both P=ns), and baseline MBF showed similar correlations with functional indices to those present preablation (all P≤0.001). Conclusions Baseline and stress MBF are significantly impaired in patients with AF but no epicardial coronary artery disease. Reduction in MBF is proportional to severity of left ventricular and left atrial dysfunction, even after successful ablation. Coronary microvascular dysfunction may be a relevant pathophysiological mechanism in patients with a history of AF .

Guidance for Optimal Site Selection of a Leadless Left Ventricular Endocardial Electrode Improves Acute Hemodynamic Response and Chronic Remodeling.

OBJECTIVES: This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LVENDO) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response. BACKGROUND: Biventricular endocardial (BiVENDO) pacing may offer a potential benefit over standard CRT; however, the optimal LVENDO pacing site is highly variable. Indiscriminately delivered BiVENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%. METHODS: Registry of centers implanting a wireless, LVENDO pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California); John Radcliffe Hospital (Oxford, United Kingdom), Guy's and St. Thomas' Hospital (London, United Kingdom), and The James Cook University Hospital (Middlesbrough, United Kingdom). Centers used a combination of preprocedural imaging and electroanatomical mapping the identify the optimal LVENDO site. RESULTS: A total of 26 patients across the 3 centers underwent a guided implant. Patients were predominantly male with a mean age of 68.8 ± 8.4 years, the mean LV ejection fraction was 34.2 ± 7.8%. The mean QRS duration was 163.8 ± 26.7 ms, and 30.8% of patients had an ischemic etiology. It proved technically feasible to selectively target and deploy the pacing electrode in a chosen endocardial segment in almost all cases, with a similar complication rate to that observed during indiscriminate BiVENDO. Ninety percent of patients met the definition of echocardiographic responder. Reverse remodeling was observed in 71%. CONCLUSIONS: Guided endocardial implants were associated with a higher degree of chronic LV remodeling compared with historical nonguided approaches.

Thrombo-embolic events in left ventricular endocardial pacing: long-term outcomes from a multicentre UK registry.

Aims: Endocardial left ventricular (LV) pacing is a viable alternative in patients with failed coronary sinus (CS) lead implantation. However, long-term thrombo-embolic risk remains unknown. Much of the data have come from a small number of centres. We examined the safety and efficacy of endocardial LV pacing to determine the long-term thrombo-embolic risk. Methods and results: Registries from four UK centres were combined to include 68 patients with endocardial leads with a mean follow-up of 20 months. These were compared to a matched 1:2 control group with conventional CS leads. Medical records were reviewed, and patients contacted for follow-up. Ischaemic stroke occurred in four patients (6%) in the endocardial arm providing an annual event rate (AER) of 3.6% over a 20 month follow-up; compared to 9 patients (6.6%) amongst controls with an AER of 3.4% over a 23-month follow-up. Regression analyses showed a significant association between sub-therapeutic international normalized ratio and stroke (P = 0.0001) in the endocardial arm. There was no association between lead material and mode of delivery (transatrial/transventricular) and stroke. Mortality rate was 12 and 15 per 100 patient years in the endocardial and control arm respectively with end-stage heart failure being the commonest cause. Conclusion: Endocardial LV lead in heart failure patients has a good success rate at 1.6 year follow-up. However, it is associated with a thrombo-embolic risk (which is not different from conventional CS leads) attributable to sub-therapeutic anticoagulation. Randomized control trials and studies on non-vitamin K antagonist oral anticoagulants are required to ascertain the potential of widespread clinical application of this therapeutic modality.