Mass Screening for AF With Only the Use of a Smartphone: The DIGITAL-AF Trial

Introduction

The United States Preventive Services Task Force has concluded that there is insufficient evidence to determine whether benefits of electrocardiogram (ECG) screening for previously undiagnosed atrial fibrillation (AF) outweigh the harms in asymptomatic individuals.1 This is not a recommendation against screening but reflects a lack of conclusive evidence in support. In contrast, European Society of Cardiology guidelines recommend opportunistic AF screening by pulse taking or ECG in individuals >65 years of age (Class I, Level of Evidence B).2 Indeed, systematic ECG screening has no higher diagnostic yield when compared with opportunistic screening by pulse palpation.3 Moreover, the former is costly and cumbersome to organize in clinical practice.

Smartphone Based Screening for AF

Recent innovations in AF screening strategies have the potential to increase screening coverage at relatively low cost and efforts. Smartphone based AF screening is attractive in this respect because the use of smartphones is likely to become—if it isn't already—ubiquitous. The REHEARSE AF (Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation) study has demonstrated the feasibility of acquiring an ECG by using a dedicated monitor connected to a Wi-Fi enabled iPod (iECG).4 In REHEARSE AF, the investigators followed 1,001 individuals from a total of 5,846 invited to participate. Five hundred participants were randomized to iECG screening twice weekly, with the others serving as a control group who received routine clinical care. During 12 month follow up, 60,440 iECGs were obtained, leading to 19 new AF diagnoses. Compared with controls, iECG screening increased AF detection significantly with a factor of 3.9 (p = 0.007).

Photo Plethysmography Through a Smartphone Camera

Smartphone applications using photo-plethysmography (PPG) technology through the phone's built in camera allow cardiac rhythm discrimination without the use of additional hardware (Figure 1), making technology even more readily accessible and cheaper.5-7 PPG and iECG, both acquired through a smartphone, have been compared against each other, finding similar diagnostic accuracy with somewhat lower positive and higher negative predictive values for PPG.6, 7 Small studies on PPG based AF screening have demonstrated excellent sensitivity (87 100%) with an acceptable specificity (90 97%) against the 12 lead ECG as the gold standard.6, 8-16

Figure 1

Figure 1

The DIGITAL AF study

Study Aim

The DIGITAL AF study was set up to assess the feasibility of mass screening for AF through a smartphone based algorithm using PPG technology by a CE-approved application that was recently granted market clearance by the United States Food and Drug Administration (FDA), making it the first FDA-approved mobile application to detect heart rhythm disorders.7

Study Design

Through a local newspaper article in layman's press, information on AF and the potential value of screening was provided. Readers were invited to participate in a screening program by making use of the cameras in their smartphones. A QR code was provided to give free access to the screening application for a 7 day period. Study participants were instructed to assess their heart rhythm twice daily, as well as in case of any symptoms.

Study Results

Within 48 hours after publication of the newspaper article, 12,328 individuals registered for voluntarily participation in the AF screening program and completed at least 1 measurement with a PPG signal of sufficient quality for analysis. With the local community served by the newspaper as denominator, screening coverage of the overall population was 1.43%. Among study participants, 1,179 (10%) adhered strictly to the recommended 2 measurements per day. Premature drop out from screening, defined as compliance with the screening protocol on day 1 but no measurements on day 7, was observed in 3,328 (27%). AF was detected by the application's algorithm and confirmed by offline analysis of the corresponding raw PPG signals in 136 participants, for an overall prevalence of 1.1%. The prevalence of AF increased from 0.1% in individuals <40 years to 11.1% in individuals ≥80 years (Figure 2). The cumulative diagnostic yield for AF increased from 0.4% with a single heart rhythm assessment to 1.4% with screening during the entire 7-day screening period (Figure 3).

Figure 2

Figure 2

Figure 3

Figure 3

Photo-Plethysmography Signal Quality

Measurements by study participants generated 120,446 unique PPG traces of 60 seconds duration. PPG signal quality was sufficient for analysis in 110,713 cases (92%). The frequency of measurements with insufficient quality for analysis decreased significantly during the screening period, from 17% on day 1 to 2% on day 7 (p < 0.001), indicating a steep learning curve.

Clinical Implications

The DIGITAL AF study represents one of the largest population screening efforts for AF that has ever been performed. What stands out even more than the 12,328 individuals screened, however, is the short period of enrollment (48 hours) and the fact that subjects were allowed an unlimited amount of heart rhythm assessments at any time of the day. Such flexibility and limited logistic efforts are major benefits of smartphone based PPG screening for AF. Yet it should be noted that the study does not provide insight into the number of people and amount of time needed to review the offline PPG traces for confirmatory analysis. Secondly, the DIGITAL AF study suggests an increasing diagnostic yield for AF with repeated heart rhythm assessments up to 7 days. This again underlines the limitations of conventional tools for AF screening like the 12 lead ECG as well as Holter monitor registrations that are usually shorter in time.

Because AF screening through smartphone based PPG technology may play an important role in future clinical practice, some important questions regarding therapeutic consequences should be considered. Importantly, all pivotal randomised clinical trials showing benefits of oral anticoagulation in AF patients at high thromboembolic risk have made the AF diagnosis conventionally through 12 lead ECG.17-21 With smartphone based AF screening, there is a potentially earlier diagnosis when the AF burden is lower. Although it has been found that AF episodes as short as 6 minutes might be associated with a higher thromboembolic risk, ongoing randomised clinical trials are still sorting out just how much AF burden is needed for patients to benefit from anticoagulation.22 Another important question is whether more intensive AF screening should lead to earlier referral for AF ablation procedures in selected populations when those have shown promise to improve clinical outcomes.23 Large, randomised clinical trials are urgently needed to address these questions. Finally, smartphone based AF screening has a potential impact on patient awareness for the disease, which could lead to better education and more extensive follow up. This has the potential to improve clinical outcomes, although cost efficiency should be studied further.

Conclusions

Mass screening for AF using only a smartphone with dedicated application based on PPG technology is feasible at low cost and logistic efforts. Future studies should investigate whether employment of such screening program may benefit the general population or groups at high risk for thromboembolic stroke.

References

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Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Arrhythmias, Cardiac, Algorithms, Atrial Fibrillation, Control Groups, Electrocardiography, Electrocardiography, Ambulatory, Follow-Up Studies, Heart Rate, Mass Screening, Mobile Applications, Palpation, Plethysmography, Stroke, Thromboembolism, United States Food and Drug Administration


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