Feasibility Study to Improve Atrial Fibrillation Outcomes Using a Digital Application for Cardiovascular Risk Reduction: Precursor to a Multicenter Randomized Trial
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Stanford University

 
 
 
 
 
 
Feasibility Study to Improve Atrial Fibrillation Outcomes Using a Digital 
Application for Cardiovascular Risk Reduction: Precursor to a Multicenter 
Randomized Trial 
Study Protocol and Statistical Analysis Plan 
NCT04050982 
May 17, 2022 
 
 

 
 
Title Feasibility Study to Improve Atrial Fibrillation Outcomes using a Digital Application 
for Cardiovascular Risk Reduction: Precursor to a Multicenter Randomized Trial 
 
Purpose  
An effective intervention to support cardiovascular risk factor (CVRF) reduction in 
individuals with AF that can be easily provided with existing resources does not exist, 
despite the evidence that even though CVRF reduction has been shown to decrease AF 
symptom severity and burden.  The digital application, AF CARE, has been specifically 
designed to fill this critical need to support CVRF reduction in individuals with AF, and 
can be easily incorporated into the care delivered to individuals undergoing AF catheter 
ablation (CA), but its feasibility is unknown. Demonstrating that an available digital 
application can improve AF outcomes would be significantly impactful.   
The specific aims of this study are to: 1). Test the feasibility of AF CARE in terms 
of acceptability, demand, usage, adherence, and integration (1), and 2). Determine the 
efficacy of AF CARE based on the pre-post assessment of CVRF (LS7 and/or blood 
tests), AF knowledge, AF Symptom Severity and Burden (AFSS), and QOL assessment 
at baseline, 3, and 6 months in the AF CARE group compared to the usual care (UC) 
group to provide estimates of effect size.  
 
Background and Significance  
Atrial fibrillation (AF) is the most common cardiac arrhythmia disorder in the 
United States, contributing to a five-time greater risk of stroke and is independently 
associated with increased mortality (2,3).  Predictions of doubling the AF population is 
based on aging and increased prevalence of cardiovascular risk factors (4).  A predicted 
lifetime risk of AF rises from 20% to 33% with the addition of a single elevated CVRF 
(4,5,6).  Innovative interventions that promote the reduction of CVRF are needed to 
decrease AF symptom severity and burden. 
Current AF treatment guidelines include CVRF reduction, and when reduced in a 
randomized group, particularly weight loss, there was a significant reduction in AF 
burden and AF symptoms compared to those who received usual care (7,8).  A 
maintained weight loss of at least 10% contributed to the greatest reduction in AF 
symptoms and AF burden (9). While AF CA procedures significantly reduce AF 
symptom burden (10) and decrease AF associated mortality and morbidity (11), 
recurrences resulting in increased morbidity and mortality persist (12).  Altering the 
disease substrate with CVRF reduction and modifying the electrical substrate with CA 
procedures has shown an improvement in post-AF ablation outcomes, with less AF 
symptom severity/burden (13,14).  
Lifestyle modifications to reduce CVRFs are difficult. There is no consensus on 
which intervention for CVRF reduction is most effective (15), nor what delivery mode is 
most acceptable. The American Heart Association (AHA) Center for Health Technology 
and Innovation collaborated with the Stanford Center for Digital Health and PatientBond, 
a digital technology software company, to design a personalized digital application (app) 
that can be accessed via a smartphone, iPad, or personal computer (16).  This digital 
app, AF CARE, delivers patient-specific messages to promote behaviors that will reduce 

CVRF and improve AF knowledge, based on each individual’s responses to 12 
psychographic questions, 12 AHA Life’s Simple 7 (LS7) questions, and specific 
biometrics.  To date, the utility and effectiveness of AF CARE to reduce CVRF has not 
been tested.    
 
Research Design  
Phase I will be completed prior to randomization on 10 individuals with AF who will be 
asked to participate in interface testing of the digital platform for 1-3 months to identify 
potential programming modifications to enhance usage and adherence.   
Then, the primary aim of Phase II of this study will be to determine feasibility of utilizing 
AF CARE to provide lifestyle modification support to patients with AF. The secondary 
outcome will be to compare the CVRF, AF knowledge, AF Symptom Severity and 
Burden, and QOL between and within the UC group and the CARE AF group.   This 
feasibility study will use a prospective, RCT wait list design to allow for the 
determination of effect sizes to inform the power calculation for a multi-center trial, if 
found to be effective.  (Phase I).  
a. Sample: Sixty patients undergoing treatment for AF at Stanford Health Care. 
Inclusion: >18 years old, BMI > 28 kg/m2 AND one additional CVRF, access and 
willingness to engage in digital technology, has a valid email address and a cell 
phone number, and able to ambulate and speak/read English 
Exclusion: Class III/IV heart failure, MI or cardiac surgery in prior 3 months, severe 
renal/hepatic disease, active malignancy, current/recent (within 6 months) 
enrollment in weight loss program.  
b. Participants will be recruited when they are being followed for the 
management of their atrial fibrillation in the Stanford clinic..  
c. Procedure: Individuals meeting inclusion criteria, but not excluded, will be invited to 
participate. Once consented, demographics, biometrics and baseline measures will 
be collected. Both groups will be asked to enter initial responses into AF CARE and 
then will be randomized to either the digital platform AF CARE group and UC or Wait 
List Group. The UC wait list group will receive usual care for the first 3 months and 
then they will receive the digital platform (AF CARE) after 3 months of enrollment. 
Both groups will be appropriately referred for smoking cessation, behavioral 
medicine, endocrinology, and/or sleep clinic during initial and Month 3 visit, based on 
screening completed at that visit. Initial measures will be collected, and repeated at 
Month 3,  Month 6, and Month 12.   
Both AF CARE/UC  and Wait List 
Groups 
Initial Month 3 (CA) Month 6 
Month 12 
Medical History and Physical 
X 
X 
X 
X 
Demographics  
X 
 
 
 
Psychographic score  
X 
 
 
 
AHA Life’s Simple 7 
X 
X 
X 
X 
Biometrics- pt reported  
(BP, HR, RR, waist, BMI) 
X 
X 
X 
X 
Blood testing, if available:  
Lipid panel, Blood Sugar 
X 
 
X 
X 
6 Minute Walk Test 
X 
X 
X 
X 
Jessa AF Knowledge Questionnaire 
X 
X 
X 
X 
AF Symptom Severity Scale (AFSS) 
X 
X 
X 
X 

 
 
 
AF CARE GROUP: Patients will receive personalized messages twice 
weekly that will include behavior recommendations for CVRF reduction 
and AF education from the AHA library. Messages will be patient-specific 
based on the initially entered psychographic profile and data entered. 
Ongoing messages will include participant response requests and future 
messages elicited by AF CARE will be based on entered responses. 
During the protocol, 3 participant non-responses to communications will 
result in a message being sent to the research team to prompt a call to 
the participant to enforce the importance of the messaging. In addition, a 
participant posting a negative response (e.g.“I do not know how to get my 
medicine refilled”) will also result in a message being sent to the research 
team to determine if clinical follow-up is required.  
Wait List UC Group/AF CARE Group: Participants will be given a weight 
loss goal of 10% and other recommendations for CVRF reduction based 
on their initial LS7 assessment. They will be provided written educational 
materials to review independently on AF and AF CA treatment.  
Participants in this group will receive personalized messages twice 
weekly that will include behavior recommendations for CVRF reduction 
and AF education from the AHA library starting at 3 months following 
randomization. Measurable Outcomes: (See Table above).  
a.CVRF will be evaluated using the pre-post measures of the AHA Life’s Simple 7, 
along with patient reported blood pressure, BMI, blood tests (lipids and glucose), 
and 6-minute walk test.  
b.AF knowledge will be evaluated with the Jessa AF Knowledge Questionnaire 
c.AF Symptom Severity and Burden will be measured with the AF Symptom 
Severity Scale  
d. QOL will be measured with the AF Effect on Quality of Life Questionnaire, and 
the  Patient Health Questionnaire-9  
Data Analysis: Demographic data will be analyzed using descriptive statistics for 
continuous data and frequencies and percentages for categorical data.   
The feasibility of AF CARE will be determined by calculating acceptability, demand, 
AF CARE usage, adherence, and qualitative interview data analysis.  
Efficacy will be evaluated on CVRF, AF Knowledge, AF symptom severity and 
burden, and QOL using matched pair t-tests at baseline, 3 and 6, and 15 months to 
determine the differences between and within groups. This data will be used to 
calculate the sample size required in a future multicenter trial designed to achieve 
80% power to detect a change of 10% from baseline.  
d. Potential Pitfalls: Data integrity is an issue for self-reported measures in the usual 
care group. The level of usage with the AF CARE plan may be suboptimal or AF 
CARE may be ineffective in meeting study aims.  
Ambulatory Monitor (Zio patch)- if 
available 
X 
X 
X 
X 
AF Effect on Quality of Life (AFEQT) 
X 
X 
X 
X 
AF CARE Group -Access to AF 
CARE 
X------------------------------------------------ 
Wait List Access to AF CARE 
 
   X---------------------------------- 

e. Sustainability: Sustainability will be determined by participant engagement and 
efficacy. 
 
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