Atrial Fibrillation Screening With Photo-plethysmography Through a Smartphone Camera

Frederik H. Verbrugge; Tine Proesmans; Johan Vijgen; Wilfried Mullens; Maximo Rivero-Ayerza; Hugo Van Herendael; Pieter Vandervoort; Dieter Nuyens

Disclosures

Europace. 2019;21(8):1167-1175. 

In This Article

Discussion

This study represents one of the largest population screening efforts for AF making use of a non-conventional screening method (i.e. other than 12-lead ECG, Holter registration, or implantable loop recorder). By making use of PPG technology through a smartphone camera by a dedicated, CE approved application, 12 328 individuals were screened during a 7-day period. Importantly, participants were actively and voluntarily involved in their measurements and it was possible for them to choose the moments of heart rhythm assessment and repeat them an unlimited amount of times. Furthermore, it was possible to register potential symptoms at the same time through the application. The screening technique was simple and required only the use of a smartphone. As a result, 120 446 unique PPG traces were obtained with acceptable quality for analysis in >90%. A possible diagnosis of AF was made in 136 patients (1.1%). One hundred out of 136 patients (74%) had a confirmed AF diagnosis.

The current study provides some important insights regarding AF screening. Firstly, after publication of a single advertising article in a local newspaper, 1.43% of the overall population could be screened by just providing free access to a smartphone-based screening programme. Screening coverage went up to 2.5% in age categories most relevant for screening. Presumably, more extensive advertisement efforts through diverse media could be exploited to further increase this number with relatively low cost and logistic efforts. Secondly, data from this study strongly suggest that more intensive screening for AF is associated with a substantially higher diagnostic yield. Indeed, participants adhering strictly to the recommended screening frequency of two heart rhythm assessments per day had almost a doubling of their chance to be detected with possible AF. In addition, the cumulative diagnostic yield for possible AF increased continuously from 0.4% with a single heart rhythm assessment to 1.4% with screening during a 7-day period. Importantly, a continuous increase in diagnostic yield is expected with longer screening periods, even beyond 7 days. Thirdly, in the majority of cases where possible AF was detected, there were no specific symptoms and general well-being was similar compared to individuals with a normal regular heart rhythm. This indicates that the screening strategy as outlined in this manuscript is particularly interesting to potentially detect silent, subclinical AF, which is associated with more frequent complications.[14] Fourthly, this study provides convincing evidence that the build-in camera of a smartphone can be used to obtain reliable PPG signals in a broad population, also including elderly who might be less familiar with smartphone handling. The frequency of measurements with insufficient PPG signal quality quickly fell from 17% to 6% after 1 day use of the smartphone application and further to 2% after 7 days, indicating a fast learning curve among participant. Fifthly, results of this study suggest the importance of secondary offline analysis of divergent raw PPG signals, both to consider alternative arrhythmia diagnoses and avoid false positive detection of AF. Finally, all screening-positive participants that provided outcome data were confirmed on ECG after consulting a medical professional.

Two previous studies have used smartphone-based PPG technology to screen for AF, albeit through a different smartphone application, and have validated findings against an accepted gold standard. McManus et al.[7] obtained 219 PPG traces from 98 participants with AF, 15 with premature atrial beats, and 15 with premature ventricular beats. They found 97% sensitivity and 93.5% specificity for detecting AF by comparing to a 12-lead ECG or 3-lead telemetry. Krivoshei et al.[9] compared 5-min PPG signals between 40 patients with AF and 40 individuals in sinus rhythm and found a somewhat lower sensitivity of 87.5% with a specificity of 95%. More recently, Proesmans et al.[15] validated the FibriCheck application in a primary care convenience sample of 223 patients, of whom 102 were in AF. They reported a sensitivity of 96% and a specificity of 97% for the detection of AF compared to 12-lead ECG.

Alternatively, by adding an additional piece of hardware (i.e. electrode) to a smartphone, acquisition of a single-lead ECG is possible. Such an approach was tested in the Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation (REHEARSE-AF) study.[16] In this study, 1001 individuals aged >65 years without a known history of AF or cardiac pacing and with a CHA2DS2-VASc score ≥2 not receiving anticoagulation therapy were recruited and randomized towards smartphone-based single-lead ECG screening twice weekly over 12 months vs. usual care. With smartphone-based AF screening, the diagnostic yield for AF was significantly higher {hazard ratio [95% confidence interval (CI)] = 3.9 (1.4–10.4); P = 0.007} at a cost of $10 780 per AF diagnosis. Photo-plethysmography technology and single-lead ECG, both acquired through a smartphone, have been compared against each other, finding similar diagnostic accuracy with a somewhat lower positive predictive value and higher negative predictive value for PPG.[6,12] The main benefit of PPG technology over single-lead ECG is that no additional hardware is needed, making the technology cheaper and more readily accessible. Indeed, the current study screened more than 10 times the number of patients recruited in REHEARSE-AF with the smartphone application software and the company's medical technician services as the only potential costs (estimated as €1278 per AF diagnosis; market price provided by the company with data not presented in the Results section). Moreover, recruitment in this study was very fast (within 48 h) with an unlimited amount of heart rhythm assessments for every subscriber, again indicating the low threshold for screening and absence of significant logistic barriers impeding screening uptake.

Clinical Implications

As AF screening through non-conventional screening methods like smartphone-based PPG technology is likely to play a more important role in future clinical practice, some important questions regarding implementation and therapeutic consequences arise. Importantly, all pivotal randomized clinical trials showing benefits of oral anticoagulation in AF patients at high stroke risk have made the AF diagnosis conventionally through 12-lead ECG.[17–19] With smartphone-based AF screening, there is a potentially earlier diagnosis of AF when its burden is lower. Although it has been found that AF episodes as short as 6 min might be associated with a higher thrombo-embolic risk, ongoing randomized clinical trials are still sorting out just how much AF burden is needed for patients to benefit from anticoagulation.[20] A second important question is whether more intensive AF screening should lead to earlier referral for AF ablation procedures in selected populations where those have shown promise to improve clinical outcomes.[21] Large, randomized clinical trials are urgently needed to address these questions. Thirdly, smartphone-based applications to screen for AF have 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. In this respect, the screening strategy used in the current study is particularly attractive as there is a low burden for both patients and physicians. The former has an easy screening tool at his/her disposal, with stringent quality checks of PPG signals provided by medical technicians of the company and with feedback going directly to the user of the application. The latter gets only involved when there is a potential concern of a relevant heart rhythm disorder. In this scenario, there is thus no need for the physician to review the irregular measurements. Finally, there may be an important role for smartphone-based AF screening in particular patients' populations. In patients with embolic stroke of undetermined source, serial ECG and Holter screening have important logistic limitations and implantable loop recorders have greater costs. Additionally, smartphone-based heart rhythm assessment could be interesting during the follow-up of patients with known AF and after ablation procedures, to quantitatively assess its burden and correlate it with symptoms, especially when the latter are atypical.

Study Limitations

The results of this study should be interpreted in the light of some methodological limitations. Firstly, heart rhythm assessments in the current study were 1 min snapshots. The duration of possible AF episodes could therefore not be quantified and, consequently, there is no prove for long-standing episodes of AF. Secondly, as the screening method implied the use of a smartphone, selection bias might have occurred. Results of the current study may not be applicable to individuals not used to handle a smartphone. Indeed, a lower screening uptake was found in persons above the age of 70 years, potentially for this reason. Yet, as current generations in whom smartphone use is ubiquitous grow older, this should not have a major impact on the external validity of this study. Further, inherent to the study design that relied on a newspaper article to convince people to participate to a screening programme, patients already diagnosed with AF could have been particularly attracted by this concept to monitor their disease. This could have inflated the population prevalence of AF found in this study. Thirdly, the large bunch of normal PPG signals found with screening were not manually revisited to confirm the diagnosis of a normal regular rhythm, creating the theoretical possibility of missed AF diagnoses. Yet, it has been demonstrated that PPG-based screening for AF has a very high negative predictive value >99%.[6] Moreover, as there was no limitation for the number of heart rhythm assessments per individual, AF would presumably be detected with subsequent measurements. Fourthly, although every abnormal PPG signal was analysed offline by experienced technicians under supervision of a cardiologist, a 12-lead ECG was not available as gold standard comparison to confirm the diagnosis of AF. Fifthly, as study participants were identified by their smartphone use, the possibility exists that some measurements have been carried out by other persons than the owner of the smartphone him/herself. Finally, no follow-up data were available on therapeutic interventions and outcome in participants with possible AF. Whether participants with screening-detected subclinical AF are eligible for stroke prevention with oral anticoagulation remains to be answered.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....