Development and Application of an Attribute-Based Taxonomy on the Benefits of Oral Anticoagulant Switching in Atrial Fibrillation: A Delphi Study.

INTRODUCTION: Patients with atrial fibrillation (AF) often switch between oral anticoagulants (OACs). It can be hard to know why a patient has switched outside of a clinical setting. Medication attribute comparisons can suggest benefits. Consensus on terms and definitions is required for inferring OAC switch benefits. The objectives of the study were to generate consensus on a taxonomy of the potential benefits of OAC switching in patients with AF and apply the taxonomy to real-world data. METHODS: Nine expert clinicians (seven clinical pharmacists, two cardiologists) with at least 3 years of clinical and research experience in AF participated in a Delphi process. The experts rated and commented on a proposed taxonomy on the potential benefits of OAC switching. After each Delphi round, ratings were analyzed with the RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness method. Median ratings, disagreement index, and comments were used to modify the taxonomy. The resulting taxonomy from the Delphi process was applied to a cohort of patients with AF who switched OACs in a population-based administrative health dataset from 1996 to 2019 in British Columbia, Canada. RESULTS: The taxonomy was finalized in two Delphi rounds, reaching consensus on five switch benefit categories: safety, effectiveness, convenience, economic considerations, and drug interactions. Safety benefit (a switch that could lower the risk of adverse drug events) had three subcategories: major bleeding, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding. Effectiveness benefit had four subcategories: stroke and systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), and all-cause mortality. Real-world OAC switches revealed that more OAC switches had convenience (72.6%) and drug interaction (63.0%) benefits compared to effectiveness (SSE 22.0%, ischemic stroke 11.1%, MI 3.1%, all-cause mortality 10.1%), safety (major bleeding 24.3%, GI bleeding 10.6%, ICH 48.5%), and economic benefits (12.1%). CONCLUSIONS: The Delphi-based taxonomy identified five criteria for the beneficial effects of OAC switching, aiding in characterizing real-world OAC switching.

Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

Left ventricle segment-specific motion assessment for cardiac-gated radiosurgery.

Purpose.Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery.Methods.CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments.Results.Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm2(controls) and 149-766 mm2(HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm2(controls) and 83-393 mm2(HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF).Conclusion.This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery.

Atrial fibrillation progression after cryoablation vs. radiofrequency ablation: the CIRCA-DOSE trial.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. METHODS: Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force-guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. RESULTS: At a median of 944.0 (interquartile range [IQR], 612.5-1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P = .03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P = .65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%-100.0%) with CRYO-4, and 99.1%% (IQR 87.0%-100.0%) with CRYO-2 (P = .38). CONCLUSIONS: Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up.

Assessment and management of asymptomatic atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia encountered in practice. It is currently estimated that AF affects approximately 2% of the general population; however, the true prevalence of AF is likely to be at least 3%-4% when asymptomatic AF is considered. For clinically apparent AF, the investigations and management are relatively well established. The identification of minimally symptomatic patients is challenging, and furthermore, the optimal management is less certain. Although there is some debate about the ideal treatment pathway for asymptomatic AF, in most cases, the investigations and comprehensive management follow the same recommendations as clinically apparent AF. In contrast, beyond risk factor optimisation, the ideal management of subclinical or device-detected AF remains undefined. The purpose of the current review is to discuss the assessment and management of asymptomatic AF.

Adherence to direct or vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a long-term observational study.

Our objectives were to measure long-term adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and to identify patient factors associated with adherence. Using linked, population-based administrative data from British Columbia, Canada, an incident cohort of adults prescribed OACs for AF was identified. We calculated the proportion of days covered (PDC) as a time-dependent covariate for each 90-day window from OAC initiation until the end of follow-up. Associations between patient attributes and adherence were assessed using generalized mixed effect linear regression models. 30,264 patients were included. Mean PDC was 0.69 (SD 0.28) over a median follow-up of 6.7 years. 54% of patients were non-adherent (PDC < 0.8). After controlling for confounders, factors positively associated with adherence were number of drug class switches, history of stroke or transient ischemic attack, history of vascular disease, time since initiation, and age. Age > 75 years at initiation, polypharmacy (among VKA users only), and receiving DOAC (vs. VKA) were negatively associated with adherence. PDC decreased over time for VKA users and increased for DOAC users. Over half of AF patients studied were, on average, nonadherent to OAC therapy and missed 32% of their doses. Several patient factors were associated with higher or lower adherence, and adherence to VKA declined during therapy while DOAC adherence increased slightly over time. To min im ize the risk stroke, adherence-supporting interventions are needed for all patients with AF, particularly those aged > 75 years, those with prior stroke or vascular disease, VKA users with polypharmacy, and DOAC recipients.

Trigger and Substrate Mapping and Ablation for Ventricular Fibrillation in the Structurally Normal Heart.

Sudden cardiac death (SCD) represents approximately 50% of all cardiovascular mortality in the United States. The majority of SCD occurs in individuals with structural heart disease; however, around 5% of individuals have no identifiable cause on autopsy. This proportion is even higher in those <40 years old, where SCD is particularly devastating. Ventricular fibrillation (VF) is often the terminal rhythm leading to SCD. Catheter ablation for VF has emerged as an effective tool to alter the natural history of this disease among high-risk individuals. Important advances have been made in the identification of several mechanisms involved in the initiation and maintenance of VF. Targeting the triggers of VF as well as the underlying substrate that perpetuates these lethal arrhythmias has the potential to eliminate further episodes. Although important gaps remain in our understanding of VF, catheter ablation has become an important option for individuals with refractory arrhythmias. This review outlines a contemporary approach to the mapping and ablation of VF in the structurally normal heart, specifically focusing on the following major conditions: idiopathic ventricular fibrillation, short-coupled ventricular fibrillation, and the J-wave syndromes-Brugada syndrome and early-repolarization syndrome.

PV Isolation Using a Spherical Array PFA Catheter: Preclinical Assessment and Comparison to Radiofrequency Ablation.

BACKGROUND: A multielectrode spherical array catheter capable of single-shot mapping and ablation has been introduced. OBJECTIVES: This study sought to compare the efficacy and safety of circumferential, linear, and focal ablation using either microsecond pulsed field (PF) and radiofrequency (RF) ablation in preclinical model. METHODS: Under general anesthesia, a 122 gold-plated multielectrode array was introduced into the left atrium. Twenty-nine canines underwent isolation of two pulmonary veins (PVs), with linear and focal left atrial ablation with both RF (n = 12) and PF (n = 17). PF was also delivered within the superior vena cava and atop the esophagus in three swine. Animals were sacrificed acutely (immediately for RF [6 of 12] and 3 days for PF [6 of 17]) and the remaining (n = 17) at 14 to 30 days. Detailed necropsy and histopathology were performed. RESULTS: All PVs were acutely (58 of 58) and durably (34 of 34) isolated and exhibited wide confluent lesions. Lesions were transmural for 97% to 100% of sections with depths of 2.5 to 3.4 mm and 2.5 to 3.5 mm in the acute and chronic cohorts, respectively. Linear and focal lesions displayed transmurality rates of 85% to 100% with depths of 3.5 millimeters to 4.2 millimeters in the acute cohort. In the chronic cohorts, linear lesions created with RF, PF+RF, and PF had no significant differences in depth (3.5 ± 1.8 mm, 4.0 ± 1.4 mm, and 3.9 ± 0.9 mm) or transmurality (83.3%, 100%, and 80%). Current of injury was seen on local unipolar electrogram immediately after PF and RF, and this occurred to a wider extent with PF. PF but not RF elicited bradycardia from ganglionated plexi stimulation. There were no instances of phrenic palsy, venous stenosis, esophageal damage, or thromboembolism. CONCLUSIONS: Circumferential, linear, and focal mapping and ablation can be achieved with this novel catheter using both PF and RF, with excellent efficacy and safety.

Patient experiences of implantable cardiac monitoring in hypertrophic cardiomyopathy: an exploratory study.

AIMS: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Insertable cardiac monitors (ICMs) are increasingly used in this population to provide closer monitoring, with the potential for notification systems. However, little is known regarding the psychological impact this information may have on patients. The Abbott Confirm Rx™ ICM has the capability of connecting to the patient's smartphone to enable active participation in their care, as well as two-way communication between the patient and their care providers. This study aimed to explore individuals' experiences of having a smartphone-enabled ICM to monitor for arrhythmias in HCM. METHODS AND RESULTS: Semi-structured interviews were conducted with 10 participants. Utilizing a grounded theory approach, the interview guide was modified based on emerging themes throughout the study. Reflexive thematic analysis was applied to categorize interview data into codes and overacting themes, with each interview independently coded by two study members. Analysis revealed three key themes: (i) psychological impact, (ii) educational needs, and (iii) technology expectations. Participants reported that receiving feedback from ICM transmissions resulted in improved symptom clarity, providing reassurance, and aiding implantable cardioverter defibrillator decision-making. Some participants reported uncertainty regarding when to send manual transmissions. Lastly, participants reported the app interface did not meet expectations with regard to the amount of data available for patients. CONCLUSION: Overall, utilizing a smartphone app to facilitate two-way communication of ICM transmissions was well accepted. Future directions include addressing gaps in educational needs and improvements in the patient interface with increased access to data.

Rhythms from Two Competing Periodic Sources Embedded in an Excitable Medium.

In an excitable medium, a stimulus generates a wave that propagates in space until it reaches the boundary or collides with another wave and annihilates. We study the dynamics generated by two periodic sources with different frequencies in excitable cardiac tissue culture using optogenetic techniques. The observed rhythms, which can be modeled using cellular automata and studied analytically, show unexpected regularities related to classic results in number theory. We apply the results to identify cardiac arrhythmias in people that are due to a putative mechanism of two competing pacemakers.

Correlation of unipolar electrogram modification with ablation index during pulmonary vein isolation: A pilot study.

BACKGROUND: Pulmonary vein isolation (PVI) using radiofrequency catheter ablation is a widely accepted therapy for drug-refractory atrial fibrillation patients. Elimination of the negative component of the local unipolar electrogram (UEGM) during PVI is a marker of transmural lesion formation. The ablation index (AI) can predict the quality of ablation lesion. Combining these two parameters could make PVI safer and efficient. The purpose of this pilot study was to examine the correlation between UEGM modification characteristics of the different target areas of left atrium and the associated AI values during PVI. METHODS: We analyzed 10 patients who underwent PVI using radiofrequency energy. The local electrophysiological properties and ablation parameters of 15 designated areas of interest in the left atria targeted by radiofrequency catheter ablation were collected. RESULTS: Out of the 10 patients, six were men (mean age 66 years) and 80% had paroxysmal AF. The mean time to achieve the UEGM modification in the posterior wall was shorter than that of the anterior wall (8.9 seconds vs. 11.1 s, respectively). The UEGM modification for every lesion was achieved at significantly lower AI values than conventional AIs (p < .001). CONCLUSION: During PVI, the AIs deduced according to the local UEGM modification are markedly shorter than those generally recommended AIs in contemporary practice. This indicates that conventionally recommended AIs could be safely reduced while ensuring the efficacy and quality of radiofrequency ablation during PVI. This approach would probably reduce to risk of collateral thermal injuries.

Healthcare utilization and quality of life for atrial fibrillation burden: the CIRCA-DOSE study.

AIMS: Atrial tachyarrhythmia recurrence ≥30 s remains the primary endpoint of clinical trials; however, this definition has not been correlated with clinical outcomes or pathophysiological processes. This study sought to determine the atrial tachyarrhythmia duration and burden associated with meaningful clinical outcomes. METHODS AND RESULTS: The time and duration of every atrial tachyarrhythmia episode recorded on implantable cardiac monitor were evaluated. Healthcare utilization and quality of life in the year following ablation were prospectively collected. Three hundred and forty-six patients provided 126 110 monitoring days. One-year freedom from recurrence increased with arrhythmia duration thresholds, from 52.6 (182/346) to 93.3% (323/346; P < 0.0001). Patients with atrial fibrillation (AF) recurrence limited to durations ≤1 h had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF recurrences lasting >1 h had a relative risk for emergency department consultation of 3.2 [95% confidence interval (CI) 2.0-5.3], hospitalization of 5.3 (95% CI 2.9-9.6), and repeat ablation of 27.1 (95% CI 10.5-71.0). Patients with AF burden of ≤0.1% had rates of healthcare utilization comparable with patients free of recurrence, while patients with AF burden of >0.1% had a relative risk for emergency department consultation of 2.4 (95% CI 1.9-3.9), hospitalization of 6.8 (95% CI 3.6-13.0), cardioversion of 9.1 (95% CI 3.3-25.6), and repeat ablation of 21.8 (95% CI 9.2-52.2). Compared with patients free of recurrence, the disease-specific quality of life was significantly impaired with AF episode durations >24 h, or AF burdens >0.1%. CONCLUSION: AF recurrence, as defined by 30 s of arrhythmia, lacks clinical relevance. AF episode durations >1 h or burdens >0.1% were associated with increased rates of healthcare utilization.

Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.

BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).