Shared Decision Making in Cardiac Electrophysiology Procedures and Arrhythmia Management.

Shared decision making (SDM) has been advocated to improve patient care, patient decision acceptance, patient-provider communication, patient motivation, adherence, and patient reported outcomes. Documentation of SDM is endorsed in several society guidelines and is a condition of reimbursement for selected cardiovascular and cardiac arrhythmia procedures. However, many clinicians argue that SDM already occurs with clinical encounter discussions or the process of obtaining informed consent and note the additional imposed workload of using and documenting decision aids without validated tools or evidence that they improve clinical outcomes. In reality, SDM is a process and can be done without decision tools, although the process may be variable. Also, SDM advocates counter that the low-risk process of SDM need not be held to the high bar of demonstrating clinical benefit and that increasing the quality of decision making should be sufficient. Our review leverages a multidisciplinary group of experts in cardiology, cardiac electrophysiology, epidemiology, and SDM, as well as a patient advocate. Our goal is to examine and assess SDM methodology, tools, and available evidence on outcomes in patients with heart rhythm disorders to help determine the value of SDM, assess its possible impact on electrophysiological procedures and cardiac arrhythmia management, better inform regulatory requirements, and identify gaps in knowledge and future needs.

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

[Figure: see text].

Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death.

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

Machine Learning to Classify Intracardiac Electrical Patterns During Atrial Fibrillation: Machine Learning of Atrial Fibrillation.

BACKGROUND: Advances in ablation for atrial fibrillation (AF) continue to be hindered by ambiguities in mapping, even between experts. We hypothesized that convolutional neural networks (CNN) may enable objective analysis of intracardiac activation in AF, which could be applied clinically if CNN classifications could also be explained. METHODS: We performed panoramic recording of bi-atrial electrical signals in AF. We used the Hilbert-transform to produce 175 000 image grids in 35 patients, labeled for rotational activation by experts who showed consistency but with variability (kappa [κ]=0.79). In each patient, ablation terminated AF. A CNN was developed and trained on 100 000 AF image grids, validated on 25 000 grids, then tested on a separate 50 000 grids. RESULTS: In the separate test cohort (50 000 grids), CNN reproducibly classified AF image grids into those with/without rotational sites with 95.0% accuracy (CI, 94.8%-95.2%). This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, we applied gradient-weighted class activation mapping which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). CONCLUSIONS: CNNs improved the classification of intracardiac AF maps compared with other analyses and agreed with expert evaluation. Novel explainability analyses revealed that the CNN operated using a decision logic similar to rules used by experts, even though these rules were not provided in training. We thus describe a scaleable platform for robust comparisons of complex AF data from multiple systems, which may provide immediate clinical utility to guide ablation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02997254. Graphic Abstract: A graphic abstract is available for this article.

Noninvasive Assessment of Complexity of Atrial Fibrillation: Correlation With Contact Mapping and Impact of Ablation.

BACKGROUND: It is difficult to noninvasively phenotype atrial fibrillation (AF) in a way that reflects clinical end points such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging, calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. METHODS: Bi-atrial intracardiac electrograms of 47 patients with AF at ablation (30 persistent, 29 male, 63±9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and noninvasively tracked in 3-dimension using phase singularity. In a subset of 17 patients, sites of AF organization were targeted for ablation. RESULTS: Body surface mapping showed greater AF organization near intracardially detected drivers than elsewhere, both in phase singularity density (2.3±2.1 versus 1.9±1.6; P=0.02) and number of drivers (3.2±2.3 versus 2.7±1.7; P=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between noninvasive and invasive methods (r2=0.5; CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (P<0.01). CONCLUSIONS: AF complexity tracked noninvasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.

Mapping and Ablation of Rotational and Focal Drivers in Atrial Fibrillation.

Drivers are increasingly studied ablation targets for atrial fibrillation (AF). However, results from ablation remain controversial. First, outcomes vary between centers and patients. Second, it is unclear how best to perform driver ablation. Third, there is a lack of practical guidance on how to identify critical from secondary sites using different AF mapping methods. This article addresses each of these issues.

Online webinar training to analyse complex atrial fibrillation maps: A randomized trial.

BACKGROUND: Specific tools have been recently developed to map atrial fibrillation (AF) and help guide ablation. However, when used in clinical practice, panoramic AF maps generated from multipolar intracardiac electrograms have yielded conflicting results between centers, likely due to their complexity and steep learning curve, thus limiting the proper assessment of its clinical impact. OBJECTIVES: The main purpose of this trial was to assess the impact of online training on the identification of AF driver sites where ablation terminated persistent AF, through a standardized training program. Extending this concept to mobile health was defined as a secondary objective. METHODS: An online database of panoramic AF movies was generated from a multicenter registry of patients in whom targeted ablation terminated non-paroxysmal AF, using a freely available method (Kuklik et al-method A) and a commercial one (RhythmView-method B). Cardiology Fellows naive to AF mapping were enrolled and randomized to training vs no training (control). All participants evaluated an initial set of movies to identify sites of AF termination. Participants randomized to training evaluated a second set of movies in which they received feedback on their answers. Both groups re-evaluated the initial set to assess the impact of training. This concept was then migrated to a smartphone application (App). RESULTS: 12 individuals (median age of 30 years (IQR 28-32), 6 females) read 480 AF maps. Baseline identification of AF termination sites by ablation was poor (40%±12% vs 42%±11%, P = 0.78), but similar for both mapping methods (P = 0.68). Training improved accuracy for both methods A (P = 0.001) and B (p = 0.012); whereas controls showed no change in accuracy (P = NS). The Smartphone App accessed AF maps from multiple systems on the cloud to recreate this training environment. CONCLUSION: Digital online training improved interpretation of panoramic AF maps in previously inexperienced clinicians. Combining online clinical data, smartphone apps and other digital resources provides a powerful, scalable approach for training in novel techniques in electrophysiology.

Comparison of phase mapping and electrogram-based driver mapping for catheter ablation in atrial fibrillation.

INTRODUCTION: Adjunctive driver-guided ablation in addition to pulmonary vein isolation has been proposed as a strategy to improve procedural success and outcomes for various populations with atrial fibrillation (AF). First, this study aimed to evaluate the different mapping techniques for driver/rotor identification and second to evaluate the benefits of driver/rotor-guided ablation in patients with paroxysmal and persistent AF (PerAF). METHODS: We searched the electronic database in PubMed using the keywords "atrial fibrillation," "rotor," "rotational driver," "atrial fibrillation source," and "drivers" for both randomized controlled trials and observational controlled trials. Clinical studies reporting efficacy or safety outcomes of driver-guided ablation for paroxysmal AF or (PerAF) were identified. We performed subgroup analyses comparing different driver mapping methods in patients with PerAF. The odds ratios (ORs) with random effects were analyzed. RESULTS: Out of 175 published articles, seven met the inclusion criteria, of which two were randomized controlled trials, one was quasiexperimental study, and four observational studies (three case-controlled studies and one cross-sectional study). Overall, adjunctive driver-guided ablation was associated with higher rates of acute AF termination (OR: 4.62, 95% confidence interval [CI]: 2.12-10.08; P < 0.001), lower recurrence of any atrial arrhythmia (OR: 0.44, 95% CI: 0.30-0.065; P < 0.001), and comparable complication incidence. CONCLUSIONS: Adjunctive driver-guided catheter ablation suggested an increased freedom from AF/AT relative to conventional strategies, irrespective of the mapping techniques. Furthermore, phase mapping appears to be superior to electrogram-based driver mapping in PerAF ablation.

Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques.

BACKGROUND: Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods. METHODS: We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360±45 cycles using (1) a published phase method and (2) a commercial activation/phase method. RESULTS: Patients were 62.2±9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6±23.9% and 70.6±20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition. CONCLUSIONS: Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

Cost effectiveness of focal impulse and rotor modulation guided ablation added to pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Although ablation with focal impulse and rotor modulation (FIRM), as an adjunct to pulmonary vein isolation (PVI), has been shown to decrease atrial fibrillation (AF) recurrence, cost-effectiveness has not been assessed. OBJECTIVE: We aimed to evaluate the cost effectiveness of FIRM-guided ablation when added to PVI in a mixed AF population. METHODS AND RESULTS: We used a Markov model to estimate the costs, quality-adjusted survival, and cost effectiveness of adding FIRM ablation to PVI. AF recurrence rates were based on 3-year data from the CONFIRM trial. Model inputs for event probabilities and utilities were obtained from literature review. Costs were based on Medicare reimbursement, wholesale acquisition costs, and literature review. Three-year total costs FIRM+PVI versus PVI alone were $27,686 versus $26,924. QALYs were 2.338 versus 2.316, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $34,452 per QALY gained. Most of the cost (65-81%) was related to the index ablation procedure. Lower AF recurrence generated cost offsets of $4,266, primarily due to a reduced need for medications and repeat ablation. Probabilistic sensitivity analysis demonstrated ICER below $100,000/QALY in 74% of simulations. CONCLUSION: Based on data from the CONFIRM study, the addition of FIRM to PVI does have the potential to be cost-effective due to higher quality-adjusted life years and lower follow-up costs. Value is sensitive to the incremental reduction in AF recurrence, and FIRM may have the greatest economic value in patients with greater AF symptom severity. Results from ongoing randomized trials will provide further clarity.

Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation.

OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). INTRODUCTION: It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods. METHODS: We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. RESULTS: In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n  =  20) and focal (n  =  2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P < 0.001) with similar stability (P < 0.001). Vagal slowing was not observed at sites of AF termination. DISCUSSION: PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.

Electrocardiographic spatial loops indicate organization of atrial fibrillation minutes before ablation-related transitions to atrial tachycardia.

BACKGROUND: During ablation for atrial fibrillation (AF), it is challenging to anticipate transitions to organized tachycardia (AT). Defining indices of this transition may help to understand fibrillatory conduction and help track therapy. OBJECTIVE: To determine the timescale over which atrial fibrillation (AF) organizes en route to atrial tachycardia (AT) using the ECG referenced to intracardiac electrograms. METHODS: In 17 AF patients at ablation (58.7±9.6years; 53% persistent AF) we analyzed spatial loops of atrial activity on the ECG and intracardiac electrograms over successive timepoints. Loops were tracked at precisely 15, 10, 5, 3 and 1min prior to defined transitions of AF to AT. RESULTS: Organizational indices reliably quantified changes from AF to AT. Spatiotemporal AF organization on the ECG was identifiable at least 15min before AT was established (p=0.02). CONCLUSIONS: AF shows anticipatory global organization on the ECG minutes before AT is clinically evident. These results offer a foundation to establish when AF therapy is on an effective path, and for a quantitative classification separating AT from AF.

Organized Sources Are Spatially Conserved in Recurrent Compared to Pre-Ablation Atrial Fibrillation: Further Evidence for Non-Random Electrical Substrates.

INTRODUCTION: Recurrent atrial fibrillation (AF) after ablation is associated with reconnection of initially isolated pulmonary vein (PV) trigger sites. Substrates are often targeted in addition to PVI, but it is unclear how substrates progress over time. We studied if substrates in recurrent AF are conserved or have developed de novo from pre-ablation AF. METHODS AND RESULTS: Of 137 patients undergoing Focal Impulse and Rotor Mapping (FIRM) at their index procedure for AF, 29 consecutive patients (60 ± 8 years, 79% persistent) recurred and were also mapped at repeat procedure (21 ± 20 months later) using carefully placed 64-pole baskets and RhythmView(TM) (Topera, Menlo Park, CA, USA) to identify AF sources and disorganized zones. Compared to index AF, recurrent AF had a longer cycle length (177 ± 21 vs. 167 ± 19 milliseconds, P = 0.01). All patients (100%) had 1 or more conserved AF rotors between procedures with surrounding disorganization. The number of sources was similar for recurrent AF post-PVI versus index AF (3.2 ± 1.4 vs. 3.1 ± 1.0, P = 0.79), but was lower for recurrent AF after FIRM+PVI versus index AF (4.4 ± 1.4 vs. 2.9 ± 1.7, P = 0.03). Overall, 81% (61/75) of AF sources lay in conserved regions, while 19% (14/75) were detected de novo. CONCLUSION: Electrical propagation patterns for recurrent AF after unsuccessful ablation are similar in individual patients to their index AF. These data support temporospatial stability of AF substrates over 1-2 years. Trials should determine the relative benefit of adding substrate mapping and ablation to PVI for recurrent AF.

Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM).

Atrial fibrillation (AF) is the most common sustained arrhythmia and the most common indication for catheter ablation. However, despite substantial technical advances in mapping and energy delivery, ablation outcomes remain suboptimal. A major limitation to AF ablation is that the areas targeted for ablation are rarely of proven mechanistic importance, in sharp contrast to other arrhythmias in which ablation targets demonstrated mechanisms in each patient. Focal impulse and rotor modulation (FIRM) is a new approach to demonstrate the mechanisms that sustain AF ("substrates") in each patient that can be used to guide ablation then confirm elimination of each mechanism. FIRM mapping reveals that AF is sustained by 2-3 rotors and focal sources, with a greater number in patients with persistent than paroxysmal AF, lying within spatially reproducible 2.2 ± 1.4-cm(2) areas in diverse locations. This temporospatial reproducibility, now confirmed by several groups using various methods, changes the concepts regarding AF-sustaining mechanisms, enabling localized rather than widespread ablation. Mechanistically, the role of rotors and focal sources in sustaining AF has been demonstrated by the acute and chronic success of source (FIRM) ablation alone. Clinically, adding FIRM to conventional ablation substantially improves arrhythmia freedom compared with conventional ablation alone, and ongoing randomized trials are comparing FIRM-ablation with and without conventional ablation to conventional ablation alone. In conclusion, ablation of patient-specific AF-sustaining mechanisms (substrates), as exemplified by FIRM, may be central to substantially improving AF ablation outcomes.