Naccarelli, Gerald V.

Introduction: Randomized trials have not demonstrated significant differences in stroke, heart failure or mortality between rhythm and rate control strategies for management of atrial fibrillation (AF). The comparative outcomes in contemporary clinical practice are not well described. The objective of this study was to evaluate outcomes in clinical practice with rhythm control versus rate control strategy. Methods: Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively compared with a strategy of rate control alone in a AF registry across various US practice settings. Unadjusted and adjusted (inverse-propensity weighted) outcomes were estimated. Results: The overall study population (n=6988) had a median age of 74 (25th, 75th percentile 65, 81) years, 56% were males, 77% had first detected or paroxysmal AF and 89% had CHA2DS2-VASc score ≥2. In unadjusted analyses, rhythm control was associated with lower all-cause death, cardiovascular death, first stroke/non-central nervous system systemic embolization/transient ischemic attack, or first major bleeding event (all p<0.05); however, rhythm control was associated with more cardiovascular hospitalizations (HR 1.24, 95% CI 1.10-1.39, p=0.0003; Figure). Conclusion: Among patients with AF in clinical practice, rhythm control was not superior to rate control strategy for outcomes of stroke, heart failure, or mortality, but was associated with more cardiovascular hospitalizations.

Background: The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) survey has recently been validated to measure the impact of atrial fibrillation on patients’ quality of life, but a clinically important difference (CID) in AFEQT score has not been defined. Knowing the CID is needed to interpret the meaningfulness of differences between treatments in clinical trials; or patient populations for quality assessment. Objectives: To calculate CID values in AFEQT in the ORBIT registry. Methods: ORBIT-AF is a US-based outpatient AF registry that measured disease-specific QoL with the AFEQT tool (score range= 0 (worst) to 100) at baseline and at 1 year follow-up. Two anchor-based methods were used to relate changes in AFEQT to clinically important differences in the more established European Heart Rhythm Association (EHRA) measure of functional status. Ranging from 1 (no symptoms) to 4 (disabling), a change of 1 EHRA class was defined as an important change in the anchor. Both the mean change and receiver operating characteristics (ROC) methods were then used to identify CIDs in AFEQT at 1 year follow-up. This was done for both improvement and worsening on the anchor. The mean change method defines a CID as the mean change in AFEQT score among patients with a 1 EHRA class change. The ROC method identifies a CID as the point on the ROC curve that best discriminates patients who experienced an important change in the anchor (≥ 1 EHRA class change) from those who experienced no change. Results: AFEQT was assessed in 2008 AF patients at baseline and 1347 patients at 1 year from 99 US sites participating in ORBIT-AF. CIDs and 95% confidence intervals (CI) corresponding to an improvement in EHRA for the mean change method were 5.4 (3.6, 7.2) AFEQT points and 1.9 (0.4, 9.3) AFEQT points for the ROC method. CIDs corresponding to worsening in EHRA for the mean change method were -4.2 (-6.9,-1.5) AFEQT points and -7.4 (-13.9,-4.6) AFEQT points for the ROC method. Conclusions: Changes in AFEQT as small as 2 points may be clinically relevant, although CIDs vary depending on the method of calculation. The variability suggests identifying a single universal CID to assess improvement in quality of life in AF patients may not be ideal and improvement may relate to the nature of a patient’s symptoms and their baseline level of activity.

Background: With increasing options for treating atrial fibrillation (AF), it is important to understand and quantify patient symptoms and quality of life (QoL), as improving symptoms and maximizing QoL are primary treatment goals. However, little is known about the factors associated with QoL. Methods: The Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) is a disease-specific QoL tool for AF, with domain and summary scores ranging from 0 (the worst health status) to 100. Using hierarchical pseudo-binomial regression, we evaluated factors associated with baseline AFEQT Summary and Subscale scores in the ORBIT AF registry. Adjusted associations were reported as odds ratios (OR) and 95% confidence intervals (CI). Results: AFEQT was assessed in 2,007 AF outpatients from 99 sites. Median age and interquartile range (IQR) was 76 (67-82); 43% were female; and the median CHA2DS2-VASC score was 4 (3-5). Median AFEQT summary score was 82 (67, 94). Median symptom score was 92 (78-100) and daily activity score was 77 (52-94). Female sex, younger age, new onset AF, higher heart rate, obstructive sleep apnea, and CAD were all associated with reduced QoL. (Table) Similar trends were seen for the symptoms subscale: female sex [OR 0.57 CI (0.48, 0.68)], younger age [OR 1.10 CI (1.06, 1.15)], and new onset AF [OR 0.55 CI (0.43, 0.70)] were associated with worse symptoms. Likewise, for the daily activities subscale, Other race [OR 0.54 CI (0.36-0.80)] and higher BMI [OR 0.98 CI (0.98-0.99)] were associated with decreased activity. Conclusions: In the largest community-based assessment of QoL in patients with AF, we found several patient factors to be associated with low QoL, including female sex, new onset AF, younger age, higher heart rate, and certain cardiopulmonary comorbidities. Understanding patient characteristics associated with worse QoL can be a foundation for eradicating disparities and tailoring treatment.

Background: Patients with sinus node dysfunction (SND) are at increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). Whether the presence of SND is also associated with worse outcomes among those with AF has not been well described. Methods: The ORBIT-AF registry enrolled patients with AF from a range of clinical practices across the US. SND was defined clinically, based on the presence of sinus bradycardia, severe sinus bradycardia, sinus arrest, sinoatrial exit block, or features of tachycardia-bradycardia syndrome. Descriptive statistics and multivariable logistic regression analysis were used to describe treatment patterns and outcomes for patients with and without SND and AF. Results: Overall, 1,710 (17.7%) patients had SND at enrollment. Patients with SND had lower left-ventricular ejection fractions, higher CHA 2 DS 2 -VASc risk scores, and more prior cerebrovascular events. Patients with SND had more severe symptoms (EHRA class IV: 17.5% vs. 13.9%; p=0.007) and poorer quality of life (median AFEQT 77.5 vs. 81.1; p=0.008) as compared to those without. SND patients were more frequently treated with oral anticoagulants (79.2% vs. 75.9%, p=0.004) and had more often received interventional therapy for AF (16.1% vs. 10.5%, p<0.0001). There were no differences in the current AF management strategy between patients with SND and those without [rate control (69.7% vs. 67.7%), rhythm control (30.0% vs. 32.0%); P=0.11]. After adjustment, significantly more patients with SND had progressed from paroxysmal AF at baseline to persistent or permanent AF at any follow-up or persistent AF at baseline to permanent AF at any follow-up than those without (OR 1.23, 95% CI 1.01-1.49, p=0.035). Conclusion: Sinus node dysfunction is associated worse symptoms, lower quality of life, and higher risk of progression to permanent AF. However, SND is not associated with increased risk of all-cause hospitalization, incident stroke, or all-cause death.

Introduction: Patient understanding of available therapies for atrial fibrillation (AF) is foundational to shared medical decision making and long term medication adherence. Yet, there is a paucity of data regarding the extent to which patients newly diagnosed with AF in routine community practice understand their options. Hypotheses: 1) Understanding of warfarin, novel oral anticoagulants (NOAC), rhythm control therapy, cardioversion and radio frequency ablation changes little from baseline to 6 months and 2) treatment rates at 6 months are associated with patient understanding of therapies at baseline. Methods: We analyzed survey data from SATELLITE, a substudy of new-onset AF patients enrolled at 56 US sites participating in the ORBIT-AF registry. Patients were surveyed at the baseline and 6 month follow up clinic visit using Likert scales. Agreement between time points was assessed with the McNemar test, and the relationship between understanding and treatment was assessed only for the subset not on treatment at baseline. Results: Of 1000 patients enrolled in SATELLITE, 506 had 6-month survey data (data collection is continuing). Among these, the median age was 69.0 years (IQR 63.0 - 76.0) and 93.7% (474 of 506) were white. There was evidence of improvement in the self-reported understanding of warfarin and NOACs from baseline to 6 months, but not for rhythm control, ablation or cardioversion. The proportion reporting high understanding improved significantly for warfarin (p<.0001) and NOACs (p<.0001) from 47% (223 of 474) and 51% (245 of 481) at baseline to 60% (284 of 474) and 69% (332 of 481) at 6 months respectively (Figure 1). Patients with high understanding of the benefits of ablation (p=0.0005) and options for ablation (p=0.0093) at baseline were more likely to have this therapy at the 6 month follow up (N=590), but improved understanding was not associated with increased use of warfarin/NOACs (N=83) or rhythm control (N=444). Conclusions: Patients with new-onset AF had improved self-reported understanding of some treatment options over the first 6-months from diagnosis; however, factors other than patient understanding may influence AF treatments received at 6 months. Patient understanding of AF treatments remains suboptimal at 6 months, and our results suggest a need for ongoing patient education.

Background Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion. Methods Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion. Results Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA. Conclusions Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking. Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type. Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients’ median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years). Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

Abstract Aims To determine the extent of shared decision-making (SDM), during selection of oral anticoagulant (OAC) and rhythm control treatments, in patients with newly diagnosed atrial fibrillation (AF). Methods and results We evaluated survey data from 1006 patients with new-onset AF enrolled at 56 US sites participating in the SATELLITE substudy of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT II). Patients completed surveys at enrolment and at 6-month follow-up. Patients were asked about who made their AF treatment decisions. Shared decision-making was classified as one that the patient felt was an autonomous decision or a shared decision with their healthcare provider (HCP). Approximately half of patients reported that their OAC treatment decisions were made entirely by their HCP. Compared with those reporting no SDM, patients reporting SDM for OAC were more often female (47.2% vs. 38.4%), while patients reporting SDM for rhythm control were more often male (62.2% vs. 57.6%). The most important factors cited by patients during decision-making for OAC were reducing stroke and bleeding risk, and their HCP’s recommendations. After adjustment, patients with self-reported understanding of OAC, and rhythm control options, had higher odds of having participated in SDM [odds ratio (OR) 2.54, confidence interval (CI): 1.75–3.68 and OR 2.36, CI: 1.50–3.71, both P ≤ 0.001, respectively]. Conclusion Shared decision-making is not widely implemented in contemporary AF practice. Patient understanding about available therapeutic options is associated with a more than a two-fold higher likelihood of SDM, and may be a potential target for future interventions.

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P <0.05 for each). Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Objective Non-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline. Methods We included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing. Results Among 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of −6.63 mL/min for NOACs and −6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year. Conclusions In the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.