The Apple Heart Study was a prospective, single-group study that was based on a siteless, pragmatic design. Of the 419,297 participants enrolled, only 0.52% received an irregular pulse notification, and among those with an initial notification who returned an ECG patch, 84% (95% CI, 76 to 92) of their subsequent notifications were confirmed to be atrial fibrillation. Of participants 65 years of age and older, 3.2% received notifications. These estimates may help providers better understand the implications of irregular pulse notifications when patients present for clinical care.

The overall yield of atrial fibrillation on an ECG patch was 34% among those who received notifications. This finding is clinically relevant because these participants had a relatively high burden of atrial fibrillation, with a majority of episodes lasting more than 1 hour. The absence of atrial fibrillation on a subsequent ECG patch does not imply that the initial notification was a false positive. Rather, atrial fibrillation may have been paroxysmal and infrequent, which is the most common pattern in early-stage atrial fibrillation. The index atrial fibrillation episode may have ended by the time the ECG patch was worn, which was, on average, 13 days after the initial notification.

Although the percentage of participants younger than 40 years of age who received notifications (0.16%) was low, the atrial fibrillation yield on ECG patch monitoring in this group was also lower (18%) than in other age groups. This may be a reflection of the paroxysmal nature of atrial fibrillation at the earlier stages of disease, but further studies are needed to better understand the public health implications of identifying irregular pulse in persons younger than 40 years of age.

The positive predictive value of an individual tachogram was 0.71 (97.5% CI, 0.69 to 0.74) and the positive predictive value of an irregular pulse notification was 0.84 (95% CI, 0.76 to 0.92), which suggests that algorithms that rely on confirmation of multiple irregular tachograms before triggering a notification improve accuracy. Many of the irregular tachograms not adjudicated as atrial fibrillation were instead concordant with rhythms that may warrant further clinical attention and require additional study. The positive predictive values were measured for participants who had already received an irregular pulse notification and are therefore only an estimate of the positive predictive value of an initial notification in the overall cohort.

This study also provides insight into the way digital alerts result in engagement with the health care system. That 76% of notified participants who returned a survey contacted either the telemedicine provider or a nonstudy provider suggests that many actively sought medical attention. The remaining may have ignored the notification because they knew they had atrial fibrillation, were asymptomatic, did not trust the notification, or did not feel that the notification, even if true, required follow-up.

There are several limitations to the study. Participants did not initiate contact with the study provider after notification and fewer returned ECG patches (450 of 2161 notified) than anticipated. As a result, the targeted statistical precision for estimating the yield of atrial fibrillation on patch monitoring, which was one of our primary end points, was not met. The reported confidence intervals appropriately reflect the uncertainty of our key quantities of interest among participants who returned their ECG patches; however, the generalizability of these estimates to participants who did not return ECG patches remains uncertain. Nevertheless, no qualitative differences were observed between those notified and excluded from the analysis and those notified who provided ECG patches with data that could be analyzed. The study was not designed to assess the algorithm as a screening tool or to measure sensitivity, specificity, or false positive results. The algorithm was designed to minimize false positive findings,3 and the low incidence of notifications reflects this intent. Furthermore, the algorithm was not designed to detect short episodes of atrial fibrillation, and participants with a low burden of atrial fibrillation could have been missed. The study objective was not to address the use of the Apple Watch as a population screening tool. Patients using this technology should be aware that the absence of an irregular pulse notification does not exclude possible arrhythmias. Conversely, notification based on an irregular pulse from a photoplethysmography signal should not be used for a definitive diagnosis of atrial fibrillation. Since rhythm-detection technologies are rapidly evolving, additional studies using features such as wearable ECG monitoring devices will need to be performed as the technology becomes available. Nevertheless, uncertainty remains about the benefits of diagnosing and treating asymptomatic atrial fibrillation, particularly in persons whose episodes of atrial fibrillation are of 6 hours’ duration or less.

There was no direct physical contact with participants from the time of enrollment and consent to interaction with the telemedicine provider and ECG patch monitoring. Although our siteless, pragmatic study design allowed us to enroll more than 400,000 participants in 8 months, we relied on the participants’ assessments regarding their eligibility for inclusion and regarding outcomes. Substantial loss to follow-up results in uncertain validity and generalizability inherent to this design. At enrollment, persons with previous atrial fibrillation were asked not to participate, but several participants who received notifications later reported a history of atrial fibrillation. Although we mitigated this misclassification by verifying enrollment criteria at the study visit, this kind of misclassification illustrates the challenges of relying on the participants themselves to assess enrollment eligibility and outcomes. In the future, studies may be able to leverage health record data directly from smartphones. As the number of app-based studies grows, development of methods to maximize engagement and the accuracy of data reported by participants is an important area of investigation. Although the participants we enrolled were geographically, racially, and ethnically diverse, the cohort was skewed toward a younger demographic, reflective of smartwatch owners. Studies using similar designs will need to consider these factors to ensure that all affected age and socioeconomic groups are represented.

We found that the probability that a participant was notified of an irregular pulse was low, but among participants who were notified of an irregular pulse, more than one third had atrial fibrillation identified on a subsequently worn ECG patch monitor, and among those notified who returned an ECG patch, positive notifications were concordant with atrial fibrillation 84% (95% CI, 76 to 92) of the time. We believe that these data support the ability of the algorithm to correctly identify atrial fibrillation in users whom it notifies of irregular pulses. Rigorous investigation of this technology and of its use in a clinical setting is needed, including the ways this technology can guide further evaluation and treatment to improve clinical outcomes. Finally, this study provides a foundation on which further research in digital health can be conducted.