Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease: 3-Year Results From the STROKE AF Randomized Clinical Trial.

Importance: The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown. Objectives: To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD. Design, Setting, and Participants: This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded. Interventions: ICM monitoring vs site-specific usual care. Main Outcomes and Measures: The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee. Results: In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001). Conclusions and Relevance: Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Lower heart rates and beta-blockers are associated with new-onset atrial fibrillation.

Background: Lower heart rates (HRs) prolong diastole, which increases filling pressures and wall stress. As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers may increase the risk for AF due to suppression of resting HRs. Objective: Examine the relationships of HR, BNP, beta-blockers and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF. Methods: In REVEAL-AF, 383 subjects without a history of AF and a mean CHA2DS2VASC score of 4.4 ± 1.3 received an insertable cardiac monitor and were followed up to 30 months. In SPRINT, 7595 patients without prior history of AF and a mean CHA2DS2VASC score of 2.3 ± 1.2 were followed up to 60 months. Results: The median daytime HR in the REVEAL-AF cohort was 75bpm [IQR 68-83]. Subjects with below-median HRs had 2.4-fold higher BNP levels compared to subjects with above-median HRs (median BNP [IQR]: 62 pg/dl [37-112] vs. 26 pg/dl [13-53], p < 0.001). HRs <75bpm were associated with a higher incidence of AF: 37% vs. 27%, p < 0.05. This was validated in the SPRINT cohort after adjusting for AF risk factors. Both a HR < 75bpm and beta-blocker use were associated with a higher rate of AF: 1.9 vs 0.7% (p < 0.001) and 2.5% vs. 0.6% (p < 0.001), respectively. The hazard ratio for patients on beta-blockers to develop AF was 3.72 [CI 2.32, 5.96], p < 0.001. Conclusions: Lower HRs are associated with higher BNP levels and incident AF, mimicking the hemodynamic effects of diastolic dysfunction. Suppression of resting HR by beta-blockers could explain their association with incident AF.

Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the US.

BACKGROUND: Insertable cardiac monitors (ICMs) are a clinically effective means of detecting atrial fibrillation (AF) in high-risk patients, and guiding the initiation of non-vitamin K oral anticoagulants (NOACs). Their cost-effectiveness from a US clinical payer perspective is not yet known. The objective of this study was to evaluate the cost-effectiveness of ICMs compared to standard of care (SoC) for detecting AF in patients at high risk of stroke (CHADS2 ≥ 2), in the US. METHODS: Using patient data from the REVEAL AF trial (n = 393, average CHADS2 score = 2.9), a Markov model estimated the lifetime costs and benefits of detecting AF with an ICM or with SoC (specifically intermittent use of electrocardiograms and 24-h Holter monitors). Ischemic and hemorrhagic strokes, intra- and extra-cranial hemorrhages, and minor bleeds were modelled. Diagnostic and device costs, costs of treating stroke and bleeding events and medical therapy-specifically costs of NOACs were included. Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3% per annum, in line with standard practice in the US setting. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. RESULTS: Lifetime per-patient cost for ICM was $31,116 versus $25,330 for SoC. ICMs generated a total of 7.75 QALYs versus 7.59 for SoC, with 34 fewer strokes projected per 1000 patients. The model estimates a number needed to treat of 29 per stroke avoided. The incremental cost-effectiveness ratio was $35,528 per QALY gained. ICMs were cost-effective in 75% of PSA simulations, using a $50,000 per QALY threshold, and a 100% probability of being cost-effective at a WTP threshold of $150,000 per QALY. CONCLUSIONS: The use of ICMs to identify AF in a high-risk population is likely to be cost-effective in the US healthcare setting.

Predictors of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: A Prespecified Secondary Analysis of the STROKE AF Randomized Clinical Trial.

Importance: The Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial found that approximately 1 in 8 patients with recent ischemic stroke attributed to large- or small-vessel disease had poststroke atrial fibrillation (AF) detected by an insertable cardiac monitor (ICM) at 12 months. Identifying predictors of AF could be useful when considering an ICM in routine poststroke clinical care. Objective: To determine the association between commonly assessed risk factors and poststroke detection of new AF in the STROKE AF cohort monitored by ICM. Design, Setting, and Participants: This was a prespecified analysis of a randomized (1:1) clinical trial that enrolled patients between April 1, 2016, and July 12, 2019, with primary follow-up through 2020 and mean (SD) duration of 11.0 (3.0) months. Eligible patients were selected from 33 clinical research sites in the US. Patients had an index stroke attributed to large- or small-vessel disease and were 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor. A total of 496 patients were enrolled, and 492 were randomly assigned to study groups (3 did not meet inclusion criteria, and 1 withdrew consent). Patients in the ICM group had the index stroke within 10 days before insertion. Data were analyzed from October 8, 2021, to January 28, 2022. Interventions: ICM monitoring vs site-specific usual care (short-duration external cardiac monitoring). Main Outcomes and Measures: The ICM device automatically detects AF episodes 2 or more minutes in length; episodes were adjudicated by an expert committee. Cox regression multivariable modeling included all parameters identified in the univariate analysis having P values <.10. AF detection rates were calculated using Kaplan-Meier survival estimates. Results: The analysis included the 242 participants randomly assigned to the ICM group in the STROKE AF study. Among 242 patients monitored with ICM, 27 developed AF (mean [SD] age, 66.6 [9.3] years; 144 men [60.0%]; 96 [40.0%] women). Two patients had missing baseline data and exited the study early. Univariate predictors of AF detection included age (per 1-year increments: hazard ratio [HR], 1.05; 95% CI, 1.01-1.09; P = .02), CHA2DS2-VASc score (per point: HR, 1.54; 95% CI, 1.15-2.06; P = .004), chronic obstructive pulmonary disease (HR, 2.49; 95% CI, 0.86-7.20; P = .09), congestive heart failure (CHF; with preserved or reduced ejection fraction: HR, 6.64; 95% CI, 2.29-19.24; P < .001), left atrial enlargement (LAE; HR, 3.63; 95% CI, 1.55-8.47; P = .003), QRS duration (HR, 1.02; 95% CI, 1.00-1.04; P = .04), and kidney dysfunction (HR, 3.58; 95% CI, 1.35-9.46; P = .01). In multivariable modeling (n = 197), only CHF (HR, 5.06; 95% CI, 1.45-17.64; P = .05) and LAE (HR, 3.32; 1.34-8.19; P = .009) remained significant predictors of AF. At 12 months, patients with CHF and/or LAE (40 of 142 patients) had an AF detection rate of 23.4% vs 5.0% for patients with neither (HR, 5.1; 95% CI, 2.0-12.8; P < .001). Conclusions and Relevance: Among patients with ischemic stroke attributed to large- or small-vessel disease, CHF and LAE were associated with a significantly increased risk of poststroke AF detection. These patients may benefit most from the use of ICMs as part of a secondary stroke prevention strategy. However, the study was not powered for clinical predictors of AF, and therefore, other clinical characteristics may not have reached statistical significance. Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Longitudinal outcomes in cryptogenic stroke patients with and without long-term cardiac monitoring for atrial fibrillation.

Background: Guidelines recommend a confirmed diagnosis of atrial fibrillation (AF) to initiate oral anticoagulation in cryptogenic stroke (CS) patients. However, the intermittent nature of AF can make detection challenging with intermittent short-term cardiac monitoring. Objective: The purpose of this retrospective cohort study was to examine post-CS utilization of cardiac monitoring and associated clinical outcomes. Methods: Adults with incident hospitalization for CS were identified in the Optum® claims database and assessed for cardiac monitoring received poststroke. Patient were stratified into those with a long-term insertable cardiac monitor (ICM) vs external cardiac monitor (ECM) only. The timing of ICM placement poststroke was treated as a time-dependent covariate. The clinical outcomes of interest were time to AF diagnosis, oral anticoagulation usage, and all-cause mortality. Results: A total of 12,994 patients met selection criteria for the analysis, of whom 1949 (15%) received an ICM and 11,045 (85%) received ECM only. In those who had received an ECM as their first monitoring modality, only 4.4% moved on to receive an ICM for longer-term monitoring. Use of ECM before ICM was associated with a longer time to AF diagnosis (median 336 vs 194 days). Compared to those with ECM only, ICM patients had a significantly lower rate of death (hazard ratio [HR] 0.70; P = .004), and faster time to AF diagnosis (HR 1.50; P <.0001) and anticoagulation initiation (HR 1.57; P <.0001) during follow-up of up to 5 years after CS. Conclusion: In a real-world study of CS patients, prolonged cardiac monitoring was associated with higher rates of AF detection and treatment, and higher odds of survival.

Diagnostic sensitivity and cost per diagnosis of ambulatory cardiac monitoring strategies in unexplained syncope patients.

Diagnosing cardiac pauses that could produce syncopal episodes is important to guide appropriate therapy. However, the infrequent nature of these episodes can make detection challenging with conventional monitoring (CM) strategies with short-term ECG monitors. Insertable cardiac monitors (ICMs) continuously monitor for arrhythmias but present a higher up-front cost. It is not well understood whether these higher costs are offset by the costs of repeat evaluation in CM strategies. We simulated the likelihood of diagnostic success and cost-per-diagnosis of pause arrhythmias with CM strategies compared to ICM monitoring. ICM device data from syncope patients diagnosed with pause arrhythmias was utilized to simulate patient pathways and diagnostic success with CM. We assumed that detected true pause episodes (≥5 seconds) were symptomatic and prompted a hospital encounter and further evaluation with CM. Subsequent true pause episodes in yet-undiagnosed patients triggered additional rounds of CM. Costs of monitoring were accrued at each encounter and represent the U.S. payer perspective. Cost per diagnosed patient was calculated as the total costs accrued for all patients divided by the number of patients diagnosed, across 1,000 simulations. During a mean 505±333 days of monitoring ICM detected 2.4±2.7 pause events per patient, with an average of 109±94 days until the first event. CM was projected to diagnose between 13.8% (24-hour Holter) and 30.2% (two 30-day monitors) of the ICM-diagnosed patients. Total diagnostic costs per ICM-diagnosed patient averaged $7,847, whereas in the CM strategies average cost-per-diagnosis ranged from $12,950±2,589 with 24-hour Holter to $32,977±14,749 for two 30-day monitors. Relative to patients diagnosed with pause arrhythmias via ICM, CM strategies diagnose fewer patients and incur higher costs per diagnosed patient.

Impact of atrial fibrillation ablation on activity minutes in patients with cardiac implantable electronic devices.

BACKGROUND: Impaired quality of life due to atrial fibrillation (AF), which often includes decreased activity level, is an indication for ablation. However, the impact of ablation for AF on activity is poorly understood. OBJECTIVE: The purpose of this study was to assess the impact of ablation on activity minutes per day using continuous accelerometer data from cardiac implantable electronic devices (CIEDs). METHODS: Using the Optum® Health Record dataset (2007-2019) linked with the Medtronic CareLink® database, we identified patients who had a CIED with AF detection and accelerometer capabilities. Patients with a device that transmitted heart rhythm and activity data ≥3 months before and ≥12 months after ablation were included in analysis. The associations between ablation and activity minutes were assessed for each CIED type. RESULTS: Of 4297 eligible patients who underwent AF ablation, 409 (9.5%) (65% male; age 67.3 ± 9.8 years; 64% paroxysmal AF) were included in analysis. The average AF burden and activity minutes per day preablation were 30.9% ± 37.4% and 175 ± 99 minutes, respectively. After ablation, relative AF burden decreased by 75.1% ± 53.2% (P <.001). There was no change in activity minutes per day after ablation in the entire cohort (average change -0.10 ± 36.2 minutes; P = .96). There were also no clinically significant changes in activity minutes postablation in subgroups based on CIED, season of ablation, quartile of AF burden change, and quartile of age at the time of ablation. CONCLUSION: There were no clinically significant changes in activity minutes per day in patients with CIEDs after ablation for AF.

Healthcare utilization and clinical outcomes after ablation of atrial fibrillation in patients with and without insertable cardiac monitoring.

BACKGROUND: Compared with short-term electrocardiogram (ECG) monitors, insertable cardiac monitors (ICMs) have been shown to increase atrial fibrillation (AF) detection rates and the opportunity to treat recurrent AF in patients postablation. OBJECTIVE: To examine healthcare utilization and clinical outcomes following AF ablation, in patients with vs without ICM. METHODS: Retrospective analysis pooling Optum Clinformatics and Medicare Fee-for-service 5% Sample claims databases. Patients with an AF ablation between January 1, 2011, and March 31, 2018 who received an ICM implant within 1 year pre-/postablation were propensity score matched 1:3 to patients without ICM. Outcomes included AF-related healthcare utilization, medication use, and occurrence of composite severe cardiovascular events (stroke / transient ischemic attack, major bleeds, systemic embolism, AF- or heart failure-related hospitalization, or death). RESULTS: A total of 1000 ICM patients and 2998 non-ICM patients were included. During mean follow-up of 33 ± 16 months postablation, ICM patients experienced significantly fewer severe cardiovascular events (1.09 ± 2.22 vs 1.37 ± 4.19, P = .008) and associated costs ($20,757 vs $29,106, P = .0005). ICM patients had a greater number of AF-related clinic visits (16.8 vs 11.6 visits, P < .0001) and were more likely to receive a repeat ablation (38.7% vs 32.4%, P = .0003). Total all-cause costs during follow-up were not statistically different. Discontinuation of oral anticoagulation was higher in ICM patients at 1 year (44% vs 31%, P < .0001) and 2 years (73% vs 64%, P = .0012). CONCLUSION: A shift from acute, reactive care to routine outpatient management was observed in patients with long-term ECG monitoring. Results suggest closer patient management in patients with long-term monitoring after an AF ablation and an improvement in outcomes, at similar overall cost.

Ambulatory activity in stroke survivors associated with functional outcome and quality of life: An observational cohort study.

BACKGROUND: Physical activity is beneficial in stroke prevention and recovery. Understanding activity dynamics and its effect on outcome after stroke is important to improve recommendations and develop interventions. OBJECTIVES: We examined serial changes in daily ambulatory activity (AA) averaged over 1 week in people with subacute to chronic stroke and its association with functional outcome (modified Rankin scale [mRS]) and quality of life (EQ-5D-3L). METHODS: This observational study examined AA in stroke survivors with no to moderate disability (US National Institute of Stroke Scale [NIHSS] score) who were mostly community dwelling and had cryptogenic stroke based on data from the Continuous Cardiac Monitoring to Assess Atrial Fibrillation After Cryptogenic Stroke study. The participants underwent long-term AA monitoring by accelerometric activity data obtained from an insertable cardiac monitor without receiving any specific encouragement regarding physical activity. We analysed AA changes and assessed the association between baseline AA and mRS/EQ-5D-3L scores. A small group of participants had follow-up data for 2 years, which allowed for analysing long-term serial changes. RESULTS: We included 186 participants (mean [SD] age 61.3 [11.2] years, 67% male, mean 39 [28] days after stroke). AA increased during the subacute phase in individuals with mild (NIHSS score 1-4, P<0.001) and moderate (NIHSS score 5-10, P=0.013) disability but not in the non-impaired group. Baseline AA was inversely associated with NIHSS score (P<0.001) and was associated with mRS score (P=0.001) and weakly correlated with EQ-5D-3L score at 6 months (P=0.032, r=0.22). For the 45 participants with follow-up data (mean age 64.5 [9.7] years, 80% male, mean 34 [21] days after stroke), AA remained stable. CONCLUSION: AA increased in stroke survivors with impairments but remained stable in those whose symptoms had resolved. AA during the early subacute period was associated with mRS and EQ-5D-3L scores at 6 months. Insertable cardiac monitoring offers a feasible method for monitoring activity over prolonged periods in people after stroke. Its increased use may offer an opportunity to overcome the limited reliability and validity of many existing measures. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00924638).

Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke.

Importance: Understanding the temporal association between atrial fibrillation (AF) and ischemic stroke informs our understanding of the AF-stroke mechanism and treatment of paroxysmal AF. Objective: To define the temporal association between episodes of AF and stroke in patients with cardiac implantable electronic devices (CIEDs). Design, Setting, and Participants: In this case-crossover study, data from a large national electronic health record database were linked with a single-vendor database of heart rhythm records of patients with CIEDs capable of continuous heart rhythm monitoring. Patients with CIEDs who sustained an ischemic stroke who also had 120 days of continuous remote rhythm monitoring prestroke were included. Data were collected from January 2007 to March 2017, and data were analyzed from November 2019 to June 2020. Exposure: AF for 5.5 hours or more on any given day during days 1 to 30 vs days 91 to 120 prestroke. Main Outcomes and Measures: Odds ratio for stroke comparing AF during days 1 to 30 vs 91 to 120 prestroke. This analysis was planned prior to the study. Results: From 466 635 patients included in both the Optum electronic health record and CareLink databases, 891 patients with CIEDs and ischemic stroke with continuous monitoring in the 120 days prestroke were identified. Of 891 included patients, 575 (64.5%) were male, and the median (interquartile range) age was 76 (67-82) years. The vast majority of patients with stroke had either no AF meeting the threshold duration of 5.5 hours or more in both the case and control periods (682 of 891 [76.5%]) or AF of 5.5 hours or more in both periods (143 of 891 [16.0%]). For those not meeting the 5.5-hour AF threshold in either period, there was no or very little AF throughout the 120 days prestroke. A total of 66 patients had informative, discordant arrhythmic states, with 52 having AF of 5.5 hours or more in the case period vs 14 in the control period (odds ratio [OR], 3.71; 95% CI, 2.06-6.70). Stroke risk was increased most in days 1 to 5 following an AF episode (OR, 5.00; 95% CI, 2.62-9.55). AF greater than 23 hours on a given day was associated with the clearest increase in stroke risk (OR, 5.00; 95% CI, 2.08-12.01). Conclusions and Relevance: In this large cohort of patients with CIEDs and continuous rhythm monitoring prior to ischemic stroke, excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter. Our findings are consistent with the traditional view that AF is directly and transiently associated with ischemic stroke. These results provide support for trials of time-delimited anticoagulation for patients with infrequent multihour episodes of AF and rigorous, continuous rhythm monitoring.

Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype.

[Figure: see text].

Detection of Atrial Fibrillation After Central Retinal Artery Occlusion.

Background: Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO. Methods: We performed a retrospective, observational cohort study using data from the Optum deidentified electronic health record of 30.8 million people cross-referenced with the Medtronic CareLink database of 2.7 million people with cardiac monitoring devices in situ. We enrolled patients in 3 groups: (1) CRAO, (2) cerebral ischemic stroke, and (3) age-, sex-, and comorbidity-matched controls. The primary end point was the detection of new AF (defined as ≥2 minutes of AF detected on a cardiac monitoring device). Results: We reviewed 884 431 patient records in common between the two databases to identify 100 patients with CRAO, 6559 with ischemic stroke, and 1000 matched controls. After CRAO, the cumulative incidence of new AF at 2 years was 49.6% (95% CI, 37.4%­61.7%). Patients with CRAO had a higher rate of AF than controls (hazard ratio, 1.64 [95% CI, 1.17­2.31]) and a comparable rate to patients with stroke (hazard ratio, 1.01 [95% CI, 0.75­1.36]). CRAO was associated with a higher incidence of new stroke compared with matched controls (hazard ratio, 2.85 [95% CI, 1.29­6.29]). Conclusions: The rate of AF detection after CRAO is higher than that seen in age-, sex-, and comorbidity-matched controls and comparable to that seen after ischemic cerebral stroke. Paroxysmal AF should be considered as part of the differential etiology of CRAO, and those patients may benefit from long-term cardiac monitoring.

Effect of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: The STROKE-AF Randomized Clinical Trial.

Importance: Patients with ischemic stroke attributed to large- or small-vessel disease are not considered at high risk for atrial fibrillation (AF), and the AF incidence rate in this population is unknown. Objectives: To determine whether long-term cardiac monitoring is more effective than usual care for AF detection in patients with stroke attributed to large- or small-vessel disease through 12 months of follow-up. Design, Setting, and Participants: The STROKE-AF trial was a randomized (1:1), multicenter (33 sites in the US) clinical trial that enrolled 496 patients between April 2016 and July 2019, with primary end point follow-up through August 2020. Eligible patients were aged 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index stroke attributed to large- or small-vessel disease within 10 days prior to insertable cardiac monitor (ICM) insertion. Interventions: Patients randomized to the intervention group (n = 242) received ICM insertion within 10 days of the index stroke; patients in the control group (n = 250) received site-specific usual care consisting of external cardiac monitoring, such as 12-lead electrocardiograms, Holter monitoring, telemetry, or event recorders. Main Outcomes and Measures: Incident AF lasting more than 30 seconds through 12 months. Results: Among 492 patients who were randomized (mean [SD] age, 67.1 [9.4] years; 185 [37.6%] women), 417 (84.8%) completed 12 months of follow-up. The median (interquartile range) CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 5 (4-6). AF detection at 12 months was significantly higher in the ICM group vs the control group (27 patients [12.1%] vs 4 patients [1.8%]; hazard ratio, 7.4 [95% CI, 2.6-21.3]; P < .001). Among the 221 patients in the ICM group who received an ICM, 4 (1.8%) had ICM procedure-related adverse events (1 site infection, 2 incision site hemorrhages, and 1 implant site pain). Conclusions and Relevance: Among patients with stroke attributed to large- or small-vessel disease, monitoring with an ICM compared with usual care detected significantly more AF over 12 months. However, further research is needed to understand whether identifying AF in these patients is of clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Use of the HAVOC Score to Identify Patients at Highest Risk of Developing Atrial Fibrillation.

BACKGROUND: Recent studies using insertable cardiac monitors (ICMs) show a high incidence of atrial fibrillation (AF). Further identifying subsets of patients who could benefit most from ICMs is desirable. We evaluated whether the HAVOC risk score which predicts AF in patients with cryptogenic stroke also predicts AF detection by ICMs in those without recent stroke. METHODS: Participants were included from the prospective, industry-sponsored REVEAL AF study assessing AF incidence in patients with CHADS2 scores ≥3 or =2 with 1 or more additional AF risk factors, who had ICM data and were not receiving anti-arrhythmic drugs. Ischemic stroke occurring less than 1 year prior to enrollment or documented AF were exclusion criteria. AF was defined as an adjudicated ICM-detected episode ≥6 min in duration. HAVOC scores were calculated by assigning 4 points for congestive heart failure, 2 points for each of hypertension, age ≥75 years, valvular disease, and coronary artery disease, and 1 point for each of peripheral vascular disease and obesity (body mass index >30). Scores classified risk as low (0-4), intermediate (5-9), or high (10-14); corresponding AF detection rates were compared using the log-rank test. AF incidence rates in patients with and without a history of remote stroke at baseline were also compared. RESULTS: Among 391 participants, the mean age was 71.5 ± 9.8 years and 186 (47.6%) were women. In total, 130 (33.2%) developed AF over 18 months. Stratification by HAVOC risk score was: 95 (24%) low, 241 (62%) intermediate, and 55 (14%) high. At 18 months, AF incidence in patients with low HAVOC scores (19.5%) was lower than in those with intermediate (32.1%) or high (34.2%) scores. AF incidence was similar among those with (n = 78) versus without (n = 313) remote stroke (27.3% vs. 29.8%; median time from stroke to ICM insertion was 4.2 [2.2-8.2] years). CONCLUSIONS: The HAVOC risk score identified a subset of individuals at greatest risk of developing AF, while AF incidence rates were similar among those with and without remote stroke. The use of the HAVOC score could help identify those at greatest likelihood of manifesting AF during long-term monitoring.

Atrial fibrillation recurrence and spontaneous conversion to sinus rhythm after cardiac surgery: Insights from 426 patients with continuous rhythm monitoring.

INTRODUCTION: Cardiac surgery may influence occurrence and persistence of atrial fibrillation (AF). In patients with a history of cardiac surgery and postoperative pacemaker or implantable cardioverter defibrillator implantation we attempted to quantify AF characteristics and investigate factors that influence AF recurrence. METHODS: In 426 patients (319 male; age: 73 SD: 9 years) with a history of cardiac surgery (364 CABG; 69 mitral valve; 57 aortic valve and 59 combination procedures) the heart rhythm history (mean: 351 days SD: 54 days) was reconstructed and investigated for AF recurrence patterns. RESULTS: AF developed and subsequently recurred in 75% of patients (n = 320). The mean AF burden in these patients was 0.21 (21% of the total observed time spent in AF) and 4085 episodes of AF were observed and analyzed. AF episodes spontaneously terminated within 24 h (n = 2509), 48 h (n = 700), 72 h (n = 279), and 1 week (n = 31). The probability of spontaneous conversion to sinus rhythm (SR) decreased with time spent in AF and plateaued after approximately 7 days. Patient age, LVEF and presence of coronary artery disease significantly influenced the probability of spontaneous conversion to SR. Type of cardiac surgery also significantly influenced AF episode characteristics. CONCLUSION: AF episodes are common in patients with a history of cardiac surgery. Spontaneous conversion to SR diminishes with increasing time spent in AF and is influenced by AF characteristics and several patient-related factors. Continuous monitoring can provide detailed information about AF recurrence that may immensely improve our understanding and influence the clinical management of AF.

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

OBJECTIVE: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. METHODS: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. RESULTS: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). CONCLUSIONS: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

Relation of Antecedent Symptoms to the Likelihood of Detecting Subclinical Atrial Fibrillation With Inserted Cardiac Monitors.

Atrial fibrillation (AF) comes to attention clinically during an evaluation of symptoms, an evaluation of its adverse outcomes, or because of incidental detection during a routine examination or electrocardiogram. However, a notable number of additional individuals have AF that has not yet been clinically apparent or suspect-subclinical AF (SCAF). SCAF has been recognized during interrogation of pacemakers and defibrillators. More recently, SCAF has been demonstrated in prospective studies with long-term monitors-both external and implanted. The REVEAL AF trial enrolled a demographically "enriched" population that underwent monitoring for up to 3 years with an insertable cardiac monitor. SCAF was noted in 40% by 30 months. None of these patients had AF known before the study; however, some had nonspecific symptoms common to patients with known AF. The current study assessed whether patients with versus without such symptoms were more likely to have SCAF detected. We found that only palpitations had an association with AF detection when controlling for other baseline symptoms (hazard ratio 1.61 (95% confidence interval 1.12 to 2.32; p = 0.011). No other prescreening symptoms evaluated were associated with an increased likelihood of SCAF detection although patients without detected SCAF had an even higher frequency of symptoms than those with detected SCAF. Thus, REVEAL AF demonstrated that the presence of palpitations is associated with an increased likelihood of SCAF whereas other common symptoms are not; and, symptoms, per se, may more likely be consequent to associated disorders than they are a direct consequence of SCAF.

Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke.

Background: We assessed cost-effectiveness of insertable cardiac monitors (ICMs) in a US cryptogenic stroke population. Materials & methods: We modelled lifetime costs and quality-adjusted life years for three monitoring strategies post cryptogenic stroke: ICM starting immediately, ICM starting after Holter monitoring (delayed ICM) and standard of care involving intermittent ECG and Holter monitoring. Patient characteristics and detection efficacy were based on the CRYSTAL-AF trial. AF detection altered the modelled anticoagulation therapy and subsequent stroke and bleed risks. Results & conclusion: Immediate ICM was found to be cost-effective versus standard of care and cost-saving versus delayed ICM. Results were robust to sensitivity analyses. ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population.

Use of Oral Anticoagulation in a Real-World Population With Device Detected Atrial Fibrillation.

Background Guideline recommendations for oral anticoagulation (OAC) in patients with atrial fibrillation (AF) are based on CHA2DS2-VASc score alone. Patients with cardiac implantable electronic devices provide an opportunity to assess how the interaction between AF duration and CHA2DS2-VASc score influences OAC prescription rates. Methods and Results Data from the Optum de-identified Electronic Health Record data set were linked to the Medtronic CareLink database of cardiac implantable electronic devices. An index date was assigned as the later of 6 months after device implant or 1 year after Electronic Health Record data availability. Maximum daily AF duration (no AF, 6 minutes-23.5 hours, and >23.5 hours) was assessed for 6 months before index date. OAC prescription rates were computed as a function of both AF duration and CHA2DS2-VASc score. A total of 35 779 patients with CHA2DS2-VASc scores ≥1 were identified, including 27 198 not prescribed OAC. Overall OAC prescription rate among the 12 938 patients with device-detected AF >6 minutes was 36.7% and significantly higher in those with a maximum daily AF duration >23.5 hours (45.4%) compared with those with 6 minutes to 23.5 hours (28.7%). OAC prescription rates increased monotonically with both increasing AF duration and CHA2DS2-VASc score, reaching a maximum of 67.2% for patients with AF >23.5 hours and a CHA2DS2-VASc score ≥5. Conclusions Real-world prescription of OAC increased with both increasing duration of AF and CHA2DS2-VASc score. This highlights the need for further research into the role of AF duration, stroke risk, and the need for anticoagulation in patients with devices capable of long-term AF monitoring.

Atrial fibrillation ablation success defined by duration of recurrence on cardiac implantable electronic devices.

INTRODUCTION: Ablation for atrial fibrillation (AF) has emerged as an effective method of rhythm control. This exploratory analysis aimed to determine how various measures of recurrence would influence the definition of treatment success. METHODS: Using an electronic health record data set from January 2007 to June 2019 linked with Medtronic cardiac implantable electronic device (CIED) data, patients who underwent a first AF ablation procedure following CIED implantation were identified. Data were analyzed for recurrence of AF stratified by varying definitions of successful ablation. The performance of various simulated external AF monitoring strategies was assessed. RESULTS: A total of 665 patients were analyzed including 248 with paroxysmal AF (mean age: 66.2 ± 9.3 years, 73.0% male) and 417 patients with persistent AF (mean age: 67.3 ± 9.0 years, 73.6% male). Among patients with paroxysmal AF, survival free from recurrence at 1 year ranged from 28.2% to 72.1% (>6 min and >23 h thresholds, respectively) with an overall median percentage of time in AF reduction of 99.6%. Among patients with persistent AF, survival free from recurrence at 1 year ranged from 24.9% to 60.0% (>6 min and 7 consecutive days > 23 h thresholds, respectively) with an overall median percentage of time in AF reduction of 99.3%. A single 7-day monitoring strategy had a sensitivity of less than 50% for detecting AF greater than 6 min in patients with paroxysmal and persistent AF. CONCLUSION: In this real-world data set of AF patients with CIEDs undergoing catheter ablation, treatment success varied substantially with different definitions of minimally required AF duration and is significantly impacted by the method of recurrence detection.