Current perspectives on wearable rhythm recordings for clinical decision-making: the wEHRAbles 2 survey.

Novel wearable devices for heart rhythm analysis using either photoplethysmography (PPG) or electrocardiogram (ECG) are in daily clinical practice. This survey aimed to assess impact of these technologies on physicians' clinical decision-making and to define, how data from these devices should be presented and integrated into clinical practice. The online survey included 22 questions, focusing on the diagnosis of atrial fibrillation (AF) based on wearable rhythm device recordings, suitable indications for wearable rhythm devices, data presentation and processing, reimbursement, and future perspectives. A total of 539 respondents {median age 38 [interquartile range (IQR) 34-46] years, 29% female} from 51 countries world-wide completed the survey. Whilst most respondents would diagnose AF (83%), fewer would initiate oral anticoagulation therapy based on a single-lead ECG tracing. Significantly fewer still (27%) would make the diagnosis based on PPG-based tracing. Wearable ECG technology is acceptable for the majority of respondents for screening, diagnostics, monitoring, and follow-up of arrhythmia patients, while respondents were more reluctant to use PPG technology for these indications. Most respondents (74%) would advocate systematic screening for AF using wearable rhythm devices, starting at patients' median age of 60 (IQR 50-65) years. Thirty-six percent of respondents stated that there is no reimbursement for diagnostics involving wearable rhythm devices in their countries. Most respondents (56.4%) believe that costs of wearable rhythm devices should be shared between patients and insurances. Wearable single- or multiple-lead ECG technology is accepted for multiple indications in current clinical practice and triggers AF diagnosis and treatment. The unmet needs that call for action are reimbursement plans and integration of wearable rhythm device data into patient's files and hospital information systems.

Spectral characterization and impact of stepwise ablation protocol including LAA electrical isolation on persistent AF.

OBJECTIVES: To study how left atrial appendage electrical isolation (LAAEI) impacts atrial dominant frequency (DF) in patients with long-standing persistent atrial fibrillation (LSPAF). BACKGROUND: LAAEI is associated with a high probability of freedom from atrial fibrillation (AF) and spectral analysis may identify high-frequency sources. How LAAEI impacts the AF dynamics and the subgroup of LSPAF patients in whom LAAEI would be most beneficial, is unclear. METHODS: Twenty patients with LSPAF were included in the study. Fast Fourier transforms (FFT) were performed on atrial electrograms recorded from 13 sites in the LA and RA. The highest peak frequency was defined as DF. RESULTS: There was no significant difference in DF between atrial sites except for at the superior vena cava which had the lowest DF at baseline. Stepwise ablation consisting of circumferential pulmonary vein isolation and a linear ablation set of mitral isthmus and roof significantly reduced the DF within the coronary sinus (CS) (5.93 ± 0.98 Hz vs. 5.09 ± 0.72 Hz, p < .05) and the LA posterior wall (LApos) (6.26 ± 0.92 Hz vs. 5.43 ± 0.98 Hz, p < .01). LAAEI preferentially further decreased the DF at the LApos (p < .01), but not at the CS. In cases where there was < 13.6% reduction in the DF of the LApos following the stepwise ablation, the addition of LAAEI was associated with an increased restoration of sinus rhythm (55%, p < .05). CONCLUSION: LAAEI in addition to stepwise ablation results in further reduction of the DF in the LApos, which is associated with acute termination of AF and favorable ablation outcome.

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.

Mechanistically based mapping of human cardiac fibrillation.

The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper 'On dynamic equilibrium in the heart', Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms - sources in preferred cardiac regions or spatially diffuse self-sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non-uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non-coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation.

New Mechanism-based Approaches to Ablating Persistent AF: Will Drug Therapy Soon Be Obsolete?

Persistent atrial fibrillation (AF) represents a major public health and medical challenge. The progressive nature of the disease, high morbidity, and increasing health-economic costs ensure that it remains at the forefront of novel research into mechanisms and potential therapies. These are largely divided into pharmacological (drugs) and electrical (ablation) with patients often going from former to latter. AF ablation has improved sufficiently to be offered as first line for paroxysmal AF, but whether drug therapy will or be relegated. In this review, we shall outline the progress in mechanistic understanding of AF that may allow results from ablation to diverge dramatically from drug therapy and identify populations in whom drug therapy may become less relevant. We end by looking ahead to future developments that we hope will spur on therapeutic efficacy in both fields.

Rotor mapping and ablation to treat atrial fibrillation.

PURPOSE OF REVIEW: Rotors have long been postulated to drive atrial fibrillation, but evidence has been limited to animal models. This changed recently with the demonstration using focal impulse and rotor modulation (FIRM) mapping that rotors act as human atrial fibrillation sources. This mechanistic approach to diagnosing the causes of atrial fibrillation in individual patients has been supported by substantially improved outcomes from FIRM-guided ablation, resulting in increased attention to rotors as therapeutic targets. RECENT FINDINGS: In this review, we outline the pathophysiology of rotors in animal and in-silico studies of fibrillation, and how this motivated FIRM mapping in humans. We highlight the characteristics of rotors in human atrial fibrillation, now validated by several techniques, with discussion on similar and discrepant findings between techniques. The interventional approaches to eliminate atrial fibrillation rotors are explained and the ablation results in latest studies using FIRM are discussed. SUMMARY: We propose that mapping localized sources for human atrial fibrillation, specifically rotors, is moving the field towards a unifying hypothesis that explains several otherwise contradictory observations in atrial fibrillation management. We conclude by suggesting areas of potential research that may reveal more about these critical sites and how these may lead to better and novel treatments for atrial fibrillation.

Repeat ablation of atrial fibrillation using electrogram dispersion to identify additional areas of mechanistic significance.

Background: Electrogram dispersion identifies putative atrial fibrillation (AF) drivers in first time ablation procedures, with high acute termination rates and long-term outcomes akin to extensive ablation approaches. Its use in a population that had undergone repeat ablation is unknown, particularly where the pulmonary veins are already isolated. Objective: This purpose of this study was to assess electrogram dispersion mapping during repeat ablation procedures for persistent AF. Methods: One hundred sixty-seven patients from the United Kingdom and Denmark, all with persistent AF recurrence after prior ablation procedure(s), were mapped using a five splined catheter for electrogram dispersion before ablation. Areas were manually tagged on biatrial electroanatomic maps and ablated once pulmonary vein isolation was confirmed or reisolated if required. All patients had 12-month continuous monitoring, with most of the cohort having follow-up beyond 24 months. Results: Of the 167 patients [53 (32%) female; mean age 66 ± 8 years; mean left atrial (LA) diameter 4.8 cm; mean ejection fraction 53%], 108 had pulmonary veins already isolated. Dispersion sites occurred in both atria (3.2 LA, 1.4 right atrium). Acute termination to sinus rhythm occurred in 71 (42%) of the cohort patients, with a further 73 (44%) terminating to atrial tachycardia/flutter. At 12-month follow-up, 95% of patients were free of AF, with 74% overall freedom from all atrial arrhythmias. Heart failure and severely enlarged LA predicted recurrence, and termination to sinus improved freedom from all atrial arrhythmias. Conclusion: Dispersion mapping is a promising approach at repeat ablation procedures for persistent AF, with high acute termination rates and good clinical outcomes. Further prospective randomized trials are needed to evaluate this approach in a population that had undergone repeat ablation.

Atrial fibrillation mechanisms before and after pulmonary vein isolation characterized by noncontact charge density mapping.

BACKGROUND: The interaction of the pulmonary vein (PV) and putative nonpulmonary triggers of atrial fibrillation (AF) remains unclear and has yet to translate into patient-tailored ablation strategies. OBJECTIVE: The purpose of this study was to use noncontact mapping to detail the global conduction patterns in paroxysmal and persistent AF and how they are modified during PV ablation. METHODS: Forty patients during AF ablation underwent mapping using a noncontact catheter (AcQMap, Acutus Medical, Inc., Carlsbad, CA) before and after PV isolation (PVI). Propagation history maps were analyzed postprocedure for each patient to categorize conduction patterns into focal, organized reentrant, and disorganized patterns (F-Patterns, O-Patterns, and D-Patterns, respectively). RESULTS: Activation patterns identified by using a noncontact mapping system can be subclassified from 3 main patterns into subtypes (macroreentrant and localized reentrant [MR and LR] subtypes and disorganized 1 and disorganized 2 [D1 and D2] subtypes). Persistent AF demonstrated more D-Patterns and less O-Patterns and F-Patterns than did paroxysmal AF. In addition, patients with PAF inducible after PVI demonstrated a higher region number and higher prevalence of MR subtypes than did those noninducible. PVs remained the critical region and included almost one-third of all patterns across any AF types. PVI was effective to eliminate PV-related functional phenotypes and affected recurrence with other patterns. CONCLUSION: Activation patterns identified using AcQMap can be classified into 3 main patterns (F-Patterns, O-Patterns, and D-Patterns) as well as subtypes (MR and LR subtypes and D1 and D2 subtypes). PerAF was different from PAF in demonstrating a higher region number and higher prevalence of D-Patterns but a lower region number and lower prevalence of O-Patterns and F-Patterns.

Novel aggregated multiposition noncontact mapping of atrial tachycardia in humans: From computational modeling to clinical validation.

BACKGROUND: A novel aggregated multiposition noncontact mapping (AMP-NCM) algorithm is proposed to diagnose cardiac arrhythmias. OBJECTIVE: The purpose of this study was to computationally determine an accuracy threshold and to compare the accuracy and clinical utility of AMP-NCM to gold standard contact mapping. METHODS: In a cellular automata model, the number of catheter positions and chamber coverage were varied to establish accuracy requirements for clinically relevant AMP-NCM. This guided the clinical study protocol. In a prospective cohort of patients with atrial tachycardia (AT), noncontact mapping (NCM) recordings from a single position (SP) and multiple positions were compared to contact mapping with a high-density multipolar catheter using morphology and timing differences of reconstructed signals. Identification of AT mechanisms and ablation targets using both AMP-NCM and contact mapping were randomly evaluated by 5 blinded reviewers. RESULTS: AMP-NCM accuracy was asymptotic at 60 catheter positions in computational modeling. Twenty patients (age 65 ± 12 years; 19 male) with 26 ATs (5 focal, 21 reentrant) were studied. Morphologic correlation of signals derived from AMP-NCM was significantly better than those from SP-NCM compared to contact signals (median 0.93 vs 0.76; P <.001). AMP-NCM generated maps more rapidly than contact mapping (3 ± 1 minutes vs 13 ± 6 minutes; P <.001) and correctly diagnosed AT mechanisms in 25 of 26 maps (96%). Overall, 80% of arrhythmia mechanisms were correctly identified using AMP-NCM by blinded reviewers. CONCLUSION: Once 60 catheter positions were achieved, AMP-NCM successfully diagnosed mechanisms of AT and identified treatment sites equal to gold standard contact mapping in 3 minutes of procedural time.

Individualized ablation strategy to treat persistent atrial fibrillation: Core-to-boundary approach guided by charge-density mapping.

BACKGROUND: Noncontact charge-density mapping allows rapid real-time global mapping of atrial fibrillation (AF), offering the opportunity for a personalized ablation strategy. OBJECTIVE: The purpose of this study was to compare the 2-year outcome of an individualized strategy consisting of pulmonary vein isolation (PVI) plus core-to-boundary ablation (targeting the conduction pattern core with an extension to the nearest nonconducting boundary) guided by charge-density mapping, with an empirical PVI plus posterior wall electrical isolation (PWI) strategy. METHODS: Forty patients (age 62 ± 12 years; 29 male) with persistent AF (10 ± 5 months) prospectively underwent charge-density mapping-guided PVI, followed by core-to-boundary stepwise ablation until termination of AF or depletion of identified cores. Freedom from AF/atrial tachycardia (AT) at 24 months was compared with a propensity score-matched control group of 80 patients with empirical PVI + PWI guided by conventional contact mapping. RESULTS: Acute AF termination occurred in 8 of 40 patients after charge-density mapping-guided PVI alone and in 21 of the remaining 32 patients after core-to-boundary ablation in the study cohort, compared with 8 of 80 (10%) in the control cohort (P <.001). On average, 2.2 ± 0.6 cores were ablated post-PVI before acute AF termination. At 24 months, freedom from AF/AT after a single procedure was 68% in the study group vs 46% in the control group (P = .043). CONCLUSION: An individualized ablation strategy consisting of PVI plus core-to-boundary ablation guided by noncontact charge-density mapping is a feasible and effective strategy for treating persistent AF, with a favorable 24-month outcome.

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.

Catheter Ablation of Atrial Fibrillation in Patients With Functional Mitral Regurgitation and Left Ventricular Systolic Dysfunction.

Background: The efficacy of catheter ablation for atrial fibrillation (AF) in patients with functional mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction (LVSD) is not known. The aim of the study is to determine the efficacy of catheter ablation for AF in patients with functional MR and LVSD, and to validate its effects on the severity of MR and cardiac reverse remodeling. Methods: We performed a retrospective study of 54 patients with functional MR who underwent AF ablation, including 21 (38.9%) with LVSD and 33 (61.1%) with normal LV systolic function (LVF). The primary outcomes evaluated were freedom from recurrent atrial tachyarrhythmia (ATa), severity of MR, and left atrial (LA) and LV remodeling. Results: During a mean follow-up of 20.7 ± 16.8 months, freedom from recurrent ATa was not significantly different between patients with LVSD and those with normal LVF after the first ablation (P = 0.301) and after multiple ablations (P = 0.728). Multivariable predictors of recurrent ATa were AF duration [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01-1.25; P = 0.039), previous stroke (HR 5.28, 95% CI 1.46-19.14; P = 0.011), and estimated glomerular filtration rate (HR 0.97, 95% CI 0.95-0.99; P = 0.012). Compared with baseline, there was a significant reduction in severity of MR (P = 0.007), LA size (P < 0.001) and LV end-systolic dimension (P = 0.008), and improvement in the LV ejection fraction (P = 0.001) after restoring sinus rhythm in patients with LVSD. Conclusion: Catheter ablation is a valid option for the treatment of AF in patients with functional MR and LVSD, even though multiple procedures may be required.

Oral Anticoagulants in Patients With Atrial Fibrillation and End-Stage Renal Disease.

The role of oral anticoagulants (OAC) in atrial fibrillation (AF) is well established. However, none of the randomized controlled trials included patients with end-stage renal disease (ESRD) leaving a lack of evidence in this large, challenging and unique patient group. Patients on hemodialysis (HD) with AF have additional risk factors for stroke due to vascular comorbidities, HD treatment, age, and diabetes. Conversely, they are also at increased risk of major bleeding due to uremic platelet impairment. Anticoagulants increase bleeding risk in patients with ESRD and HD up to 10-fold compared with non chronic kidney disease (CKD) patients on warfarin. There are conflicting data and recommendations regarding use of OACs in ESRD which will be reviewed in this article. We conclude by proposing a modified strategy for OAC use in ESRD based on the latest evidence.

The Enduring Value of the Physical Examination.

This article focuses exclusively on physical examination (PE) in the context of clinical medicine, that is, the interaction between a health care provider and patient. In essence, there is not only benefit (value) to PE but also that it will last (endure) for some time. Both "enduring" and "value" are explored in more depth with respect to the future integration of PE into the clinical assessment of a patient and how its value extends well beyond current diagnostic/cost-based metrics.

Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/Physiological Study.

Atrial fibrillation is the most common rhythm disorder of the heart associated with a rapid and irregular beating of the upper chambers. Activation mapping remains the gold standard to diagnose and interpret atrial fibrillation. However, fibrillatory activation maps are highly sensitive to far-field effects, and often disagree with other optical mapping modalities. Here we show that computational modeling can identify spurious non-local components of atrial fibrillation electrograms and improve activation mapping. We motivate our approach with a cohort of patients with potential drivers of persistent atrial fibrillation. In a computational study using a monodomain Maleckar model, we demonstrate that in organized rhythms, electrograms successfully track local activation, whereas in atrial fibrillation, electrograms are sensitive to spiral wave distance and number, spiral tip trajectories, and effects of fibrosis. In a clinical study, we analyzed n = 15 patients with persistent atrial fibrillation that was terminated by limited ablation. In five cases, traditional activation maps revealed a spiral wave at sites of termination; in ten cases, electrogram timings were ambiguous and activation maps showed incomplete reentry. By adjusting electrogram timing through computational modeling, we found rotational activation, which was undetectable with conventional methods. Our results demonstrate that computational modeling can identify non-local deflections to improve activation mapping and explain how and where ablation can terminate persistent atrial fibrillation. Our hybrid computational/physiological approach has the potential to optimize map-guided ablation and improve ablation therapy in atrial fibrillation.

Early Diagnosis of Defibrillation Lead Dislodgement.

OBJECTIVES: This study sought to develop and evaluate an algorithm for early diagnosis of dislodged implantable cardioverter-defibrillator (ICD) leads. BACKGROUND: Dislodged defibrillation leads may sense atrial and ventricular electrograms (EGMs), triggering shocks in the vulnerable period that induce ventricular fibrillation (VF). METHODS: We developed a 2-step algorithm by using experimental lead dislodgements (LDs) at ICD implantation and a control dataset of newly implanted, in situ leads. Step 1 consisted of an alert triggered by abrupt decrease in R-wave amplitude and increase in pacing threshold. Step 2 withheld therapy based on ventricular EGM evidence of LD identified from experimental LD behavior. We estimated the algorithm's performance using a registry dataset of 3,624 new implantations and an atrial dislodgement dataset of 14 LDs at the atrium. RESULTS: In the registry dataset, the algorithm identified 20 of 21 radiographic LDs (95%) at a median of 11 days before clinical diagnosis. Step 1 had positive predictive values of 57% for radiographic LD and 77% for surgical revision. The false positive rate was 0.4% after step 1 and ≤0.2% after step 2. In the atrial dislodgement dataset, step 1 identified all 14 LDs; step 2 would have prevented inappropriate therapy in all 7 patients with stored EGMs at LD, including 2 patients with fatal, shock-induced VF. CONCLUSIONS: An ICD algorithm can facilitate early diagnosis of defibrillation LD. Additional data are needed to determine the safety of withholding shocks based on EGM evidence of LD.