Patient selection, ventricular tachycardia substrate delineation and data transfer for stereotactic arrhythmia radioablation. A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) of the ESC and the Heart Rhythm Society (HRS).

Stereotactic arrythmia radioablation (STAR) is a novel, non-invasive and promising treatment option for ventricular arrythmias (VA). It has been applied in highly selected patients mainly as bail-out procedure, when (multiple) catheter-ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including etiology specific aspects, and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.

Characterizing cardiac contractile motion for noninvasive radioablation of ventricular tachycardia.

Background: Respiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored. Objective: We aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart. Methods: Patients with intracardiac leads or valves who underwent 4-dimensional cardiac computed tomography (CT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. The displacement of transvenous right atrial appendage, right ventricular (RV) implantable cardioverter-defibrillator, coronary sinus lead tips, and prosthetic cardiac devices across the cardiac cycle were measured in orthogonal 3-dimensional views on a maximal-intensity projection CT reconstruction. Results: A total of 31 preablation cardiac 4-dimensional cardiac CT scans were analyzed. The LV lead tip had significantly greater motion compared with the RV lead in the anterior-posterior direction (6.0 ± 2.2 mm vs 3.8 ± 1.7 mm; P = .01) and superior-inferior direction (4.4 ± 2.9 mm vs 3.5 ± 2.0 mm; P = .049). The prosthetic aortic valves had the least movement of all fiducials, specifically compared with the RV lead tip in the left-right direction (3.2 ± 1.2 mm vs 6.1 ± 3.8 mm, P = .04) and the LV lead tip in the anterior-posterior direction (3.8 ± 1.7 mm vs 6.0 ± 2.2 mm, P = .03). Conclusion: The degree of cardiac contractile motion varies significantly (1 mm to 15.2 mm) across different locations in the heart. The effect of contractile motion on the precision of radiotherapy should be assessed on a patient-specific basis.

Interobserver variability in target definition for stereotactic arrhythmia radioablation.

Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02-0.02 cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52-1.02 cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51-1.55 cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation.

Successful Noninvasive 12-Lead ECG Mapping-Guided Radiotherapy of Inaccessible Ventricular Tachycardia Substrate Due to Mechanical Valves.

In patients presenting with refractory ventricular tachycardia (VT) and aortic and mitral mechanical prosthetic valves, traditional catheter ablation is challenging. We describe a case in which a novel noninvasive computational electrocardiogram mapping algorithm localized VT sources originating from substrate near the mechanical valves, in which stereotactic ablative radiotherapy eliminated VT in 1.5-year follow-up. (Level of Difficulty: Advanced.).

Characteristics and outcomes of recurrent atrial fibrillation after prior failed pulmonary vein isolation.

BACKGROUND: The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized atrial arrhythmias (PAC, AT, macro-reentrant AFL) are possible contributors; however the prevalence and effect of their ablation on recurrent AF are unknown. We hypothesize that the identification and ablation of non-PV organized atrial arrhythmias were associated with less AF recurrence. METHODS: Patients who underwent repeat ablation for recurrent AF after prior PVI were retrospectively enrolled. The prevalence and characteristics of PV reconnections and non-PV organized atrial arrhythmias were identified. The outcomes of time to clinical AF recurrence, heart failure (HF) hospitalization, and mortality were analyzed in patients using multivariable adjusted Cox regression. RESULTS: In 74 patients with recurrent AF (age 66 ± 9 years, left atrial volume index 38 ± 10 ml/m2, 59% persistent AF), PV reconnections were found in 46 patients (61%), macro-reentrant atrial flutter in 27 patients (36%), and focal tachycardia in 12 patients (16%). Mapping and ablation of non-PV organized atrial arrhythmias were associated with a reduced recurrence of late clinical AF (adjusted HR 0.26, CI 0.08-0.85, p = 0.03) and the composite outcome of recurrence of late AF, HF hospitalization, and mortality (adjusted HR 0.38, CI 0.17-0.85, p = 0.02), with median follow-up of 1.6 (IQR 0.7-6.3) years. The presence of PV reconnections or empiric linear ablation was not associated with reduction in clinical AF or composite endpoints. CONCLUSION: The ablation of non-PV organized atrial arrhythmias resulted in a reduction of late clinical AF recurrence and composite outcome. In this challenging population, alternate mechanisms beyond PV reconnections need to be considered. Prospective studies are needed.

Computational ECG mapping and respiratory gating to optimize stereotactic ablative radiotherapy workflow for refractory ventricular tachycardia.

BACKGROUND: Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for refractory ventricular tachycardia (VT). However, the current workflow is complicated, and the precision and safety in patients with significant cardiorespiratory motion and VT targets near the stomach may be suboptimal. OBJECTIVE: We hypothesized that automated 12-lead electrocardiogram (ECG) mapping and respiratory-gated therapy may improve the ease and precision of SAbR planning and facilitate safe radiation delivery in patients with refractory VT. METHODS: Consecutive patients with refractory VT were studied at 2 hospitals. VT exit sites were localized using a 3-D computational ECG algorithm noninvasively and compared to available prior invasive mapping. Radiotherapy (25 Gy) was delivered at end-expiration when cardiac respiratory motion was ≥0.6 cm or targets were ≤2 cm from the stomach. RESULTS: In 6 patients (ejection fraction 29% ± 13%), 4.2 ± 2.3 VT morphologies per patient were mapped. Overall, 7 out of 7 computational ECG mappings (100%) colocalized to the identical cardiac segment when prior invasive electrophysiology study was available. Respiratory gating was associated with smaller planning target volumes compared to nongated volumes (71 ± 7 vs 153 ± 35 cc, P < .01). In 2 patients with inferior wall VT targets close to the stomach (6 mm proximity) or significant respiratory motion (22 mm excursion), no GI complications were observed at 9- and 12-month follow-up. Implantable cardioverter-defibrillator shocks decreased from 23 ± 12 shocks/patient to 0.67 ± 1.0 (P < .001) post-SAbR at 6.0 ± 4.9 months follow-up. CONCLUSIONS: A workflow including computational ECG mapping and protocol-guided respiratory gating is feasible, is safe, and may improve the ease of SAbR planning. Studies to validate this workflow in larger populations are required.

Effect of closed loop stimulation versus accelerometer on outcomes with cardiac resynchronization therapy: the CLASS trial.

PURPOSE: Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices. METHODS: A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-min walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: 1-week period of CLS and 1-week period of standard accelerometer (DDDR). RESULTS: Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 39 ± 8%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8 ± 123.9 vs 489.3 ± 164.9, p = 0.06). There were no differences between CLS and DDDR in 6MWD (293.1 ± 90.2 m vs 315.1 ± 95.5 m, p = 0.52), peak heart rate (HR) 110.7 ± 14.7 bpm vs 109.7 bpm ± 14.1, p = 0.67), or peak VO2 (12.3 ± 4.9 ml/kg/min vs 12.9 ± 5.9, p = 0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.98 ± 0.11 vs 1.0 ± 0.8, p = 0.35), VE/VCO2 slope also showed no difference between CLS and DDDR (35.8 ± 5.6 vs 35.4 ± 5.7, p = 0.65). Five patients (56%) preferred CLS programming (p = 1.0). CONCLUSIONS: In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2, and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02693262.

'They deserve a treat': the nature and antecedents of parental licensing surrounding children's physical activity.

OBJECTIVE: Little is known about parents' compensatory health beliefs (CHB) surrounding their children's engagement in physical activity (PA). Our aim was to provide evidence regarding the nature of, and factors underpinning, parents' PA-related compensatory beliefs for their children. DESIGN: A qualitative descriptive approach and thematic content analysis were employed. SETTING: Parents were recruited from community sport and PA programmes. PARTICIPANTS: Eighteen parents aged 32-52 years (mean age = 40·8 (sd 5·4) years; six males; twelve females). RESULTS: Analyses indicated that parents compensate through 'passive' or 'active' means. Among parents who compensated, most described their provision of 'treat' foods/drinks and a minority described allowing extended sedentary time to their children. Parents' reasons underpinning these beliefs related to their child's general physical/health status and psychological characteristics, and their own motivation and mood state. CONCLUSIONS: These findings provide the first evidence of unhealthy dietary and sedentary behaviour CHB that parents may hold regarding their children's involvement in PA.

Meta-analysis of the Usefulness of Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure With Preserved Ejection Fraction.

Catheter ablation improves clinical outcomes in atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, the role of catheter ablation in HF with a preserved ejection fraction (HFpEF) is less clear. We performed a literature search and systematic review of studies that compared AF recurrence at one year after catheter ablation of AF in patients with HFpEF versus those with HFrEF. Risk ratio (RR; where a RR <1.0 favors the HFpEF group) and mean difference (MD; where MD <0 favors the HFpEF group) 95% confidence intervals (CI) were measured for dichotomous and continuous variables, respectively. Six studies with a total of 1,505 patients were included, of which 764 (51%) had HFpEF and 741 (49%) had HFrEF. Patients with HFpEF experienced similar recurrence of AF 1 year after ablation on or off antiarrhythmic drugs compared with those with HFrEF (RR 1.01; 95% CI 0.76, 1.35). Fluoroscopy time was significantly shorter in the HFpEF group (MD -5.42; 95% CI -8.51, -2.34), but there was no significant difference in procedure time (MD 1.74; 95% CI -11.89, 15.37) or periprocedural adverse events between groups (RR 0.84; 95% CI 0.54,1.32). There was no significant difference in hospitalizations between groups (MD 1.18; 95% CI 0.90, 1.55), but HFpEF patients experienced significantly less mortality (MD 0.41; 95% CI 0.18, 0.94). In conclusion, based on the results of this meta-analysis, catheter ablation of AF in patients with HFpEF appears as safe and efficacious in maintaining sinus rhythm as in those with HFrEF.

P2Y12 inhibitors with oral anticoagulation for percutaneous coronary intervention with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the safety and efficacy of third-generation P2Y12 inhibitors versus clopidogrel in combination with oral anticoagulation (OAC) with or without aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: We performed a systematic review including both prospective and retrospective studies that compared dual and triple antithrombotic regimens for bleeding and major adverse cardiac events (MACE) in patients with AF undergoing PCI. We analysed rates of bleeding and MACE by P2Y12 inhibitor choice. Risk ratio (RR) 95% CIs were measured using the Mantel-Haenszel method. Where study heterogeneity was low (I2 <25%), we used the fixed effects model, otherwise the random effects model was used. RESULTS: A total of 22 014 patients were analysed from the seven studies included. Among patients treated with both OAC and P2Y12 inhibitor with or without aspirin, 90% (n=9708) were treated with clopidogrel, 8% (n=830) with ticagrelor, and 2% (n=191) with prasugrel. When compared with clopidogrel, use of ticagrelor (RR 1.36; 95% CI 1.18 to 1.57) and prasugrel (RR 2.11; 95% CI 1.34 to 3.30) were associated with increased rates of bleeding. Compared with clopidogrel, there were no significant differences in rates of MACE with ticagrelor (RR 1.03; 95% CI 0.65 to 1.62) or prasugrel (RR 1.49; 95% CI 0.69 to 3.24). CONCLUSION: Based on this meta-analysis, the use of clopidogrel is associated with a lower rate of bleeding compared with ticagrelor or prasugrel in patients with AF on OAC undergoing PCI.

Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF.

INTRODUCTION: Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease. METHODS AND RESULTS: In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications. CONCLUSIONS: Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation.

Mechanisms of human atrial fibrillation initiation: clinical and computational studies of repolarization restitution and activation latency.

BACKGROUND: Mechanisms of atrial fibrillation (AF) initiation are incompletely understood. We hypothesized that rate-dependent changes (restitution) in action potential duration (APD) and activation latency are central targets for clinical interventions that induce AF. We tested this hypothesis using clinical experiments and computer models. METHODS AND RESULTS: In 50 patients (20 persistent, 23 paroxysmal AF, 7 controls), we used monophasic action potential catheters to define left atrial APD restitution, activation latency, and AF incidence from premature extrastimuli. Isoproterenol (n=14), adenosine (n=10), or rapid pacing (n=36) was then initiated to determine impact on these parameters. Compared with baseline in AF patients, isoproterenol and rapid pacing decreased activation latency (64±14 versus 31±13 versus 24±14 ms; P<0.05), steepened maximum APD restitution slope (0.8±0.7 versus 1.7±0.5 versus 1.1±0.5; P<0.05), and increased AF incidence (12% versus 64% versus 84%; P<0.05). Conversely, adenosine shortened APD (P<0.05), yet increased activation latency (86±27 ms; P=0.002) so that maximum APD restitution slope did not steepen (1.0±0.5; P=NS), and AF incidence was unchanged (10%; P=NS). In controls, no intervention steepened APD restitution or initiated AF. Computational modeling revealed that isoproterenol steepened APD restitution by increased L-type calcium current and decreased activation latency via enhanced rapid delayed potassium reactifier current inactivation, whereas rapid pacing steepened APD restitution via increased cardiac inward potassium rectifier current. CONCLUSIONS: Steep APD restitution is a common pathway for AF initiation by isoproterenol and tachycardia via reduced activation latency that enables engagement of steep APD restitution at rapid rates. Modeling suggests that AF initiation from each intervention uses distinct ionic mechanisms. This insight may help design interventions to prevent AF.