Association Between Oral Anticoagulant Adherence and Serious Clinical Outcomes in Patients With Atrial Fibrillation: A Long-Term Retrospective Cohort Study.

BACKGROUND: Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem. METHODS AND RESULTS: Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels. CONCLUSIONS: Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.

Long-term outcomes among out-of-hospital cardiac arrest survivors with reversible versus non-reversible causes.

BACKGROUND: Reversible cause of out-of-hospital cardiac arrest (OHCA) is vaguely defined in international guidelines as an identifiable transient or potentially correctable condition. Moreover, studies evaluating long-term outcomes of patients experiencing OHCA due to reversible and non-reversible causes are lacking. We aimed to determine differences in long-term outcomes in OHCA-survivors according to different etiology. METHODS: From the British Columbia Cardiac Arrest registry, adults with non-traumatic OHCA (2009-2016) surviving to hospital discharge were identified. Patients were categorized by OHCA etiology combining reversibility and underlying ischemic etiology. The primary outcome was a composite of all-cause mortality, recurrent OHCA, or re-hospitalization for sudden cardiac arrest or ventricular arrhythmias. Using the Kaplan-Meier method and multivariable Cox regression models, we compared the risk of the composite outcome according to different OHCA-etiology. RESULTS: Of 1,325 OHCA hospital-discharge survivors (median age 62.8, 77.9% male), 431 (32.5%) had reversible ischemic, 415 (31.3%) non-reversible ischemic, 99 (7.5%) reversible non-ischemic and 380 (28.7%) non-reversible non-ischemic etiology. At 3 years post-discharge, Kaplan-Meier event-free rate was highest in patients with a reversible ischemic etiology (91%, 95% CI 87-94%), and lowest in those with a reversible non-ischemic etiology (62%, 95% CI 51-72%). In multivariate analyses, compared to non-reversible non-ischemic cause, reversible ischemic cause was associated with a significantly lower hazard ratio (HR) (0.52, 95% confidence interval [CI], 0.33-0.81), reversible non-ischemic cause with a significantly higher HR (1.53, 95% CI, 1.03-2.32) and non-reversible ischemic cause with a non-significant HR 0.92 (95% CI, 0.64-1.33) for the composite outcome. CONCLUSIONS: The presence of a reversible ischemic cause is associated with long-term OHCA-outcomes.

The Diagnostic Utility of Holter Monitoring in Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Holter monitoring may raise suspicion of an underlying catecholaminergic polymorphic ventricular tachycardia (CPVT) diagnosis. Although not a primary investigation for CPVT, Holter monitoring is ubiquitously used as a diagnostic tool in the heart rhythm clinic. OBJECTIVES: The objective of this study was to explore Holter monitoring in CPVT diagnosis. METHODS: This retrospective cohort study analyzed off-therapy Holter monitoring from 13 ryanodine receptor 2-positive CPVT and 34 healthy patients from the Canadian Hearts in Rhythm Organization national registry. Using the Edwards method, the ratio of ambient-maximum heart rate during Holter monitoring was correlated with exertion level to separate premature ventricular contractions (PVCs) during periods of adrenergic and nonadrenergic stress. A receiver operating characteristic curve analysis determined the optimal threshold for isolating CPVT-induced PVCs during adrenergic states. RESULTS: PVC burden differed between groups (P = 0.001) but was within population norm, suggesting ambient PVCs are uncommon in CPVT. CPVT patients had higher PVC counts than healthy controls (P = 0.002), with a different distribution based on adrenergic state. The optimal threshold for separating PVCs into periods of adrenergic and nonadrenergic stress in CPVT patients was 76% of the maximum heart rate during the monitoring period. Compared with healthy controls, CPVT patients had a higher PVC count, limited to periods of adrenergic stress, defined by >76% maximum heart rate threshold (P = 0.002; area under the receiver operating characteristic curve: 0.84). Below this threshold, there was no significant PVC difference (P = 0.604). CONCLUSIONS: Holter monitor PVC counts alone are inadequate for CPVT diagnosis, owing to the adrenergic nature of the disease. Quantifying PVC prevalence at a heart rate threshold >76% identified CPVT with moderate sensitivity (69%) and high specificity (94%).

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.