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Draft Research Plan

Atrial Fibrillation: Screening With Electrocardiography

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March 26, 2020

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This figure is the proposed analytic framework depicting the six key questions about screening with electrocardiography (ECG) for atrial fibrillation and the research approach that will guide the evidence review outlined in this research plan. In general, the figure illustrates the overarching question (key question 1):  whether screening asymptomatic adults ages 65 or older with ECG for atrial fibrillation leads to improved health outcomes. Health outcomes include all-cause mortality, stroke, and stroke-related morbidity and mortality. The framework starts on the left with the patient population of interest: asymptomatic adults ages 65 or older. Moving from left to right, the figure depicts the ability of screening with ECG to diagnose atrial fibrillation compared to usual care (key question 2), the diagnostic accuracy of selected screening tests (key question 3), and the potential harms of screening with ECG (key question 4). For older adults with screen-detected atrial fibrillation, whether treatment with anticoagulation or antiplatelet therapy improves health outcomes (key question 5) or results in harms (key question 6) completes the framework on the right.

Abbreviation: ECG=electrocardiography.

1.   Does screening for atrial fibrillation (AF) with electrocardiography (ECG) improve health outcomes (i.e., reduce all-cause mortality or reduce morbidity or mortality from stroke) in asymptomatic older adults? a.  Does improvement in health outcomes vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
2.   Does systematic screening for AF with ECG identify older adults with previously undiagnosed AF more effectively than usual care?
3.   What is the accuracy of selected screening tests for diagnosing AF in asymptomatic older adults?
4.   What are the harms of screening for AF with ECG in older adults?
      a.  Do the harms of screening vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
5.   What are the benefits of anticoagulation or antiplatelet therapy on health outcomes in asymptomatic, screen-detected older adults with AF?
       a.   Do the benefits of anticoagulation or antiplatelet therapy vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, race/ethnicity, or AF burden (i.e., number of episodes, duration of episodes, and proportion of time spent in AF)?
6.   What are the harms of anticoagulation or antiplatelet therapy in asymptomatic, screen-detected older adults with AF?
      a.  Do the harms of anticoagulation or antiplatelet therapy vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, race/ethnicity, or AF burden?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

1.   What is the prevalence of previously unrecognized or undiagnosed AF in asymptomatic adults? Does the prevalence vary by age, primary care vs. community setting, method of diagnosis (e.g., single ECG vs. ambulatory ECG monitoring), sex, or race/ethnicity

2.   What is the stroke risk for the following populations?
      ·  Asymptomatic older adults with previously unrecognized or undiagnosed AF
      ·  Older adults with paroxysmal vs. persistent AF
      ·  Older adults with paroxysmal AF who have a lower vs. higher AF burden

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions.  

  Include Exclude
Condition definition AF (paroxysmal or persistent) Other cardiac arrhythmias, non-arrhythmia–related cardiovascular disease (e.g., coronary heart disease, hypertension)
Populations KQs 1–4: Unselected or explicitly asymptomatic older adults (age ≥65 years); older adults selected for increased risk of nonvalvular AF (e.g., those with obesity, smoking, alcohol use, hypertension); and studies of mixed populations of asymptomatic and symptomatic persons are eligible if results are reported separately for asymptomatic persons or less than 10% of the sample is symptomatic
KQs 5, 6: Older adults with AF. To approximate screen-detected persons with AF, we will aim to stratify analyses based on whether participants are asymptomatic/screen detected vs. symptomatic (if possible); however, knowing that most studies enroll mixed populations or do not clearly enroll screen-detected or asymptomatic populations, we will not exclude studies based on whether participants were screen detected. To approximate “screening” vs. “disease management” populations, we will limit our analyses to studies of individuals not selected because of known heart disease, heart failure, and/or previous stroke or transient ischemic attack.
KQs 1–4: Symptomatic adults; adults with known (history of) AF; children, adolescents, and adults younger than age 65 years; adults at high(est) risk for AF (including but not limited to those with mitral valve disease or repair/replacement); and adults with history of stroke or transient ischemic attack
KQs 5, 6: Adults needing antiplatelet or anticoagulation medications for conditions other than AF; adults with AF and known heart disease, heart failure, and/or previous stroke or transient ischemic attack
Screening test or intervention KQs 1, 2, 4: Systematic screening using any approach (e.g., in-office, single 12-lead or less than 12-lead ECG, intermittent or continuous ambulatory ECG, intermittent or continuous ambulatory photoplethysmography), including commercially available technologies (e.g., smartwatches, smartphone applications, heart rhythm monitors) that are available directly to consumers

KQ 3: Single, in-office 12-lead or less than 12-lead ECG interpreted by primary care provider; intermittent ambulatory ECG; intermittent ambulatory photoplethysmography; two-stage screening tests involving a single initial test followed by a second test

KQs 5, 6: Medical treatment with antiplatelet agents (e.g., aspirin, clopidogrel, dipyridamole) or anticoagulants (e.g., apixaban, dabigatran, edoxaban, rivaroxaban, warfarin). Results will be stratified by type of medication.

KQs 1, 2, 4: Physical examination (including pulse palpation or heart auscultation), automated pulse or blood pressure measurement, pulse oximetry; two-stage approach in which a physical examination component or vital sign measurement is the initial test and only persons with irregular pulse receive ECG
KQ 3: Physical examination (including pulse palpation or heart auscultation), automated pulse or blood pressure measurement, pulse oximetry; two-stage approach in which a physical examination component or vital sign measurement is the initial test and only persons with irregular pulse receive ECG; single 12-lead ECG interpreted by cardiologist*; continuous ambulatory ECG monitoring.*
KQs 5, 6: Nonpharmacologic treatment to prevent stroke (e.g., implantable devices), treatment or management of AF for reasons other than prevention of stroke (e.g., rate or rhythm control, cardioversion, ablation), and combinations of treatment (e.g., aspirin plus warfarin)
Comparisons KQs 1, 2, 4: No screening, nonsystematic screening, usual care (which may include pulse palpation, automated blood pressure measurement, or cardiac auscultation during the course of a physical examination, or examination for another reason, with subsequent ECG if an irregular heart beat or pulse is noted)
KQ 3: For persistent AF, single 12-lead ECG interpreted by one or more cardiologists; for paroxysmal AF, continuous ambulatory ECG monitoring interpreted by one or more cardiologists
KQs 5, 6: Placebo, no treatment
KQ 1, 2, 4: No comparison, nonconcordant historical control
KQ 3: No reference standard, reference standard other than 12-lead ECG or continuous ambulatory ECG monitoring interpreted by one or more cardiologists
KQs 5, 6: Active treatment (i.e., other antiplatelet or anticoagulation medications)
Outcomes KQ 1: All-cause mortality, stroke, and stroke-related morbidity or mortality
KQ 2: Comparative diagnostic yield (i.e., number of persons diagnosed with AF in one group vs. another [unscreened/nonsystematically screened] group)
KQ 3: Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, false positives, false negatives, frequency of findings other than AF
KQ 4: Anxiety, labeling, harms of subsequent procedures or interventions initiated as a result of screening (e.g., subsequent ablation with complications), frequency of findings other than AF
KQ 5: All-cause mortality, cardioembolic stroke, and cardioembolic stroke–related morbidity or mortality
KQ 6: Any harms requiring unexpected or unwanted medical attention (e.g., hemorrhagic stroke, major bleeding, allergic reaction)
KQs 4, 6: Nonserious events (e.g., bleeding not requiring or resulting in medical attention)
Study designs KQ 1, 2, 4–6: RCTs and controlled clinical trials
KQ 3: Diagnostic test accuracy studies or systematic reviews of diagnostic test accuracy studies
KQ 4: Large prospective cohort studies are also eligible
KQ 5: Systematic reviews of relevant trials are also eligible
KQ 6: Systematic reviews of relevant trials and large prospective cohort studies are also eligible
All other designs, narrative reviews, case reports, case series, editorials, letters, cross-sectional studies, case-control studies, small prospective cohort studies, and retrospective cohort studies
Setting KQs 1–4: Studies performed in primary care or primary care–referable settings, community settings KQs 5, 6: Studies performed in primary care or specialty settings KQs 1–4: Studies performed in specialty settings (including the emergency department), studies of patients undergoing preoperative evaluation, and inpatient settings
KQs 5, 6: Studies conducted primarily in inpatient settings
Country Studies conducted in countries categorized as “Very High” on the 2018 Human Development Index (as defined by the United Nations Development Programme) Studies conducted in countries that are not categorized as “Very High” on the 2018 Human Development Index
Language English Non-English
Study quality Good or fair Poor (according to design-specific USPSTF criteria)

* 12-lead ECG and continuous ambulatory ECG interpreted by a cardiologist are excluded from KQ 3 (diagnostic accuracy) because these tests are considered the reference standard. 
Abbreviations: AF=atrial fibrillation; ECG=electrocardiography; KQ=key question; RCT=randomized, controlled trial; USPSTF=U.S. Preventive Services Task Force.  

The update will focus on screening with ECG in asymptomatic, older populations. We will not include studies of ECG testing in persons with symptoms or with known cardiovascular disease or screening in younger (age <65 years) persons. We will not review the diagnostic test accuracy of pulse palpation as an index test, either alone or as part of a two-step screening approach, when only persons who screen positive on the initial pulse assessment receive ECG, because the USPSTF considers pulse palpation a part of usual care.