AS511 - WHI strong and healthy silent atrial fibrillation recording (WHISH-STAR) I (funded) and II (not funded)

Investigator Names and Contact Information

Marco Perez (mvperez@stanford.edu)

Introduction/Intent

Specific Aims

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and confers significant risk of morbidity and mortality despite available therapies. There are approximately 2.3 million people in the US currently afflicted, and this number is expected to rise 2.5-fold in the next 50 years.¹ Atrial fibrillation accounts for between 75,000 to 100,000 strokes per year, approximately 15% of all strokes nationally,² in addition to increased mortality after adjustment for numerous cardiovascular risk factors and comorbidities.³ AF has also been linked to increased risk of congestive heart failure, myocardial infarction⁴ , sudden cardiac death⁵, dementia and chronic kidney disease. Women comprise 60% of individuals with AF greater than age 75, and the clinical consequences of AF for women are of particular concern.⁶ Women with AF are more likely than men to develop stroke and MI, and have a higher overall mortality risk than men.^{2, 3, 7} Once AF is established, current treatment options have substantial risk and limited effectiveness at preventing AF-related complications. Therefore, novel primary preventive strategies are needed. BMI is a major risk factor for AF among women, and a recent small scale randomized trial demonstrated that a lifestyle weight loss intervention, which included low intensity exercise, resulted in a reduced burden of AF episodes⁸. We demonstrated that moderate degrees of PA (PA) were associated with a significant reduction in incident AF among women enrolled in the Women’s Health Initiative, even after adjustment for BMI ⁹. Therefore, interventions designed to increase physical activity might lower incident AF risk both through reductions in BMI and through independent mechanisms. One of the challenges faced when evaluating the effectiveness of interventions designed to reduce AF recurrence or prevent AF is that a sizable proportion of AF events are thought to be asymptomatic, and therefore, are not detected clinically. The significance of asymptomatic AF is not entirely clear, but it is well known that such patients can present with stroke as their first manifestation of AF. In patients with cryptogenic stroke, 12.2% of patients are found to have silent AF within one year on implantable monitoring¹⁰. Small, wearable patch monitors have been used to screen for AF with high compliance rates¹¹, however, screening of AF is not routinely recommended in part because the prevalence of silent AF and the efficacy of interventions based upon monitoring are not well known. In this application, we will take advantage of the NIH-funded WHI Strong & Healthy (WHISH) trial to test the effect of a physical activity intervention on incident AF in women. In the WHISH trial, women will be randomized to receive exercise instructions via an interactive voice response system and followed for several cardiovascular outcomes. By enrolling women from WHISH, we will take advantage of the established infrastructure of WHI and WHISH. Presence of AF and baseline risk factors were measured at baseline enrollment, and the women have been followed for several years for incident AF with review of hospitalized records, electrocardiograms and linkage to Centers for Medicare & Medicaid Services (CMS) data, as we have previously described^{12, 13}. We will also utilize this opportunity to add a monitoring component to the WHISH trial that will allow us to 1). Estimate the amount of silent asymptomatic AF that goes undetected by standard clinical monitoring in an elderly high-risk female population 2). Document the impact of our intervention on silent asymptomatic AF and electrocardiographic risk factors for AF 3). Explore whether monitoring for silent AF reduces rates of stroke or AF-related hospitalizations.

Specific Aim 1: To measure the effect of physical activity intervention on incident AF in the WHISH cohort. The WHISH trial will study over 51,807 women from WHI who have already consented to extended follow-up and will randomize half of them to consent for PA intervention. The women will be followed for incident atrial fibrillation, stroke and AF-related hospitalizations, and other cardiovascular endpoints using adjudicated chart reviews and Medicare linkage data. Hypothesis: Women randomized to tailored physical activity intervention will have lower rates of incident atrial fibrillation compared to controls receiving usual care.

Specific Aim 2: To compare rates of AF diagnosis in high-risk women randomized to screening with cardiac patch monitoring (CPM) to those in usual care. A randomly selected sample of 1100 women within the WHISH trial without baseline AF but with at least a 10-year Framingham risk of developing clinical AF of 12% will undergo 14-day cardiac patch monitor (CPM) screening at baseline, 6 months and 1 year. Hypothesis: Atrial fibrillation will be diagnosed at a significantly higher rate in the monitored group compared to those in usual clinical care.

Specific Aim 3: To measure the effect of screening for atrial fibrillation with cardiac patch monitors on rates of stroke and AF-related hospitalizations in high-risk women. Subjects with silent AF identified in Specific Aim 2 will be notified and encouraged to speak with their physicians regarding risks and benefits of stroke prophylaxis. Monitored women and controls will be followed for incident stroke for 4.5 years. Hypothesis: Women randomized to consent for cardiac patch monitoring will have lower rates of stroke or AFrelated hospitalizations than controls receiving usual care.