Researchers from the Stanford University School of Medicine have presented preliminary results of the Apple Heart Study, an unprecedented virtual study with over 400,000 enrolled participants. The researchers reported that wearable technology can safely identify heart rate irregularities that subsequent testing confirmed to be atrial fibrillation, a leading cause of stroke and hospitalisation in the US.
The study was launched with sponsorship by Apple in November 2017 to determine whether a mobile app that uses data from a heart-rate pulse sensor on the Apple Watch can identify atrial fibrillation. The condition often remains hidden because many people don’t experience symptoms.
Key findings from the study include: overall, only 0.5% of participants received irregular pulse notifications, an important finding given concerns about potential over-notification; comparisons between irregular pulse-detection on Apple Watch and simultaneous electrocardiography (ECG) patch recordings showed the pulse detection algorithm (indicating a positive tachogram reading) has a 71% positive predictive value; 84% of the time, participants who received irregular pulse notifications were found to be in atrial fibrillation at the time of the notification; one-third (34%) of the participants who received irregular pulse notifications and followed up by using an ECG patch over a week later were found to have atrial fibrillation. Since atrial fibrillation is an intermittent condition, it’s not surprising for it to go undetected in subsequent ECG patch monitoring; and 57% of those who received irregular pulse notifications sought medical attention.
“The results of the Apple Heart Study highlight the potential role that innovative digital technology can play in creating more predictive and preventive health care,” said Dr Lloyd Minor, dean of the Stanford School of Medicine. “Atrial fibrillation is just the beginning, as this study opens the door to further research into wearable technologies and how they might be used to prevent disease before it strikes – a key goal of precision health.”
For the study, each participant was required to have an Apple Watch (series 1, 2 or 3) and an iPhone. The most recent Apple Watch, which features a built-in ECG, wasn’t part of the study, as it was released after the study’s launch. The Apple Heart Study app intermittently checked the heart-rate pulse sensor for measurements of an irregular pulse. If an irregular pulse was detected, the participant received a notification and was asked to schedule a telemedicine consultation with a doctor involved in the study through American Well. Participants were then sent ambulatory ECG patches through bio-telemetry, which recorded the electrical rhythm of their hearts for up to a week.
The Stanford principal investigators were Dr Mintu Turakhia, associate professor of cardiovascular medicine, and Dr Marco Perez, associate professor of cardiovascular medicine, and the study chair was Dr Kenneth Mahaffey, professor of cardiovascular medicine.
“The study’s findings have the potential to help patients and clinicians understand how devices like the Apple Watch can play a role in detecting conditions such as atrial fibrillation, a deadly and often undiagnosed disease,” said Turakhia. “The virtual design of this study also provides a strong foundation upon which future research can be conducted to explore the health implications of wearable technology.”
“The performance and accuracy we observed in this study provides important information as we seek to understand the potential impact of wearable technology on the health system,” said Perez. “Further research will help people make more informed health decisions.”
Researchers from the Lankenau Heart Institute, Jefferson Medical College, the University of Colorado School of Medicine, Cooper Medical School of Rowan University, StopAfib.org, the American Foundation for Women’s Health, and Duke University also contributed to the study.
The Apple Watch and corresponding Heart Study app uses photoplethysmography to intermittently measure blood flow activity and detect subtle changes that might indicate an irregular heartbeat. A tachogram is then created and is analysed by an algorithm.
A total of 419,297 people self-enrolled in the study. Participants could not have AFib or be taking anticoagulants and were required to have an Apple Watch and compatible iPhone. They were given information about the study when they downloaded the Heart Study app. Detection of five of six repeat tachograms of an irregular pulse within a 48-hour period triggered a notification to be sent via the app. Participants receiving a notification were prompted to contact the study doctor through the app for a video consultation to determine if the participant should wear an ECG patch. The patch was worn for up to seven days.
The primary endpoints were AFib >30 seconds on ECG patch and simultaneous AFib on ECG patch and tachogram.
A pulse notification was received by 2,161 participants (0.52%). Notification rates were most frequent in participants over age 65 (slightly >3.0%) and lowest among those under 40 (0.16%). Patches were sent to 658 participants and 450 were returned and included in the analysis. AFib was identified in 34% of those who received a notification and wore the ECG patch.
“AFib can come and go, particularly early on in the course of the disease. It’s not surprising for it to go undetected in subsequent ECG patch monitoring. So while only 34% of people who were still having AFib on the ambulatory ECG, that doesn’t mean that 66% didn’t have AFib. It just means that AFib may not have been there at the time,” Turakhia said. “These parameters help us understand how we, as clinicians, should think about these notifications.”
The positive predictive value (PPV) for the tachogram was 71% and the PPV for notification was 84%. About half of participants receiving an irregular pulse notification contacted a study doctor. Subsequent surveys showed that 57% of participants who received an alert sought medical care outside of the study regardless of whether they had been seen virtually by a study doctor. “This is encouraging because it tracks with our understanding of AFib as being more common as you get older,” Turakhia said, adding that the overall study population represented a striking cross section of cardiovascular risk.
The study had several limitations, including reliance on self-reported data from participants and the potential for a high number of false positive heart rhythms that could then lead to further unnecessary tests and undue anxiety for patients. Additionally, the target enrolment of 500,000 participants, with 75,000 aged 65 or older, was not reached.
ACC.org editor-in-chief Dr Kim A Eagle also noted that while the watch and corresponding app “offers promise,” its accuracy is still far short of more traditional and currently used monitoring techniques. “This is just a glimpse of the future, but we have a ways to go,” he said.
Turakhia said the trial does represent “a paradigm shift” for how clinical studies can be conducted. “We don’t have to bring people into a brick and mortar clinic and give the study intervention,” he said.
However, what the Apple Heart Study won’t do — what it can’t do — is provide any insight into the device’s real overall effects on health, writes Larry Husten in Stat News. He says this is because the study was not a randomised controlled trial, the gold standard of medical research. Instead, it is a purely observational study designed to see whether the Apple Watch’s heart pulse monitor can identify people who have a-fib.
But because the study does not contain a control arm, it can’t say what might have happened to a similar group of 400,000 people who did not use the Apple Watch.
Husten writes that the study will therefore be a rich source of anecdotes but, as good scientists know, anecdotes aren’t data. He says that some people will inevitably argue that saving the life of a young girl, as related by the Apple CEO, is proof the watch can contribute to our health. But that assumption may not hold up if the cost of the benefit means harm to many other healthy people.
Husten points out that when evaluating a new drug or device, it is a cardinal rule that the benefits must be weighed against the risks. With some drugs and devices, the risks are obvious. In others, such as with something as apparently benign as the Apple Watch, the risks may be less immediately apparent. Nevertheless, they can be real and potentially significant.
He says in the report that to understand these potential harms, it’s important to recognise that no medical test is perfect. There are always false negatives, in which the device fails to detect a real problem, and false positives, in which it wrongly detects a problem that doesn’t exist.
Harm occurs from these in several ways. One is when people who have atrial fibrillation don’t consult a doctor about symptoms such as heart palpitations or shortness of breath because they feel falsely reassured by the absence of any alert from their Apple Watch.
Husten writes that the study provides no evidence about the true rate of false negatives in the study population because the researchers did not independently monitor people in whom the device did not detect A-fib. He says a far more common problem will be false positives, in which the watch delivers an alert to people who do not have A-fib.
He writes: “Imagine the impact of such an alert on a perfectly healthy person who suddenly believes he or she might have a heart rhythm disorder. Then imagine the impact on a health care system as thousands of young, healthy people suddenly want to schedule appointments with cardiologists. Is this really the best use of time for those seeking care or those providing it? Can our already overburdened health care system absorb this sort of influx? What will happen to the underserved sick and elderly people who really do need the services of a cardiologist?
“You may think it’s a mistake to focus on false positives and false negatives because the watch is highly accurate at detecting A-fib. But experts who have looked at this issue already know that there will be a large number of false positive alarms, far more than the number of accurate positive alarms. Venkatesh Murthy, a cardiologist at the University of Michigan who has studied this issue, told me that more than 90% of irregular rhythm alerts in younger and middle aged users will be false alarms.
“Even if the Apple Watch does work correctly, it is by no means clear it will generate benefits to the public’s health. Most episodes of A-fib are not harmful. There has been an enormous amount of research on people with A-fib who enter the health care system through conventional means – most often by going to a doctor about their symptoms or by having the problem diagnosed during a physical examination. The medical community has a fairly good idea about which of these patients are most likely to benefit from further treatment, although I must acknowledge that there is some controversy even here.
“But the medical community has no idea how to respond appropriately or efficiently to the large number of people who will be identified as having A-fib by the Apple Watch alone. Most of these people – young and tech-savvy – will almost certainly be at low risk for a stroke or other harmful consequence of A-fib. It is entirely possible that the vast majority would do fine until their heart problem was identified by traditional means.”
Husten writes that it is also possible that the harms of the treatments they are offered could outweigh any reduction in stroke risk. In fact, the blood-thinning drugs used to prevent stroke in people with A-fib can make it difficult to stop bleeding and can even lead to an uncommon but serious kind of stroke caused by bleeding into the brain.
Husten writes that there no evidence yet that treating people for A-fib that’s first detected by an Apple Watch will result in a net benefit when strokes averted are balanced against excessive bleeding and complications from procedures for a-fib like catheter ablation or the implantation of a Watchman device. And the Apple Heart Study will not provide this proof.
Husten writes: “There’s a lot of enthusiasm out there for new, high-tech devices like the Apple Watch, but it is extremely difficult to find thoughtful perspectives on the complex medical issues they raise. We are in the middle of an overwhelming rush to embrace new technology and make health data available to everyone. This movement is fuelled by Apple and other technology companies that are starting to spread some of their enormous wealth in the medical community, laying the groundwork for their expansion into this field.
“Unfortunately, the immediate response to this new study is likely to be even more irrational exuberance and premature implementation of a potentially harmful technology before there is any evidence showing that the Apple Watch actually improves human health.”
Even among those flagged, the watch’s diagnosis was “not perfect”, said Dr Richard Kovacs of the American College of Cardiology, who was not involved with the study. And, The Guardian reports, other cardiac experts said the study suggests screening with wearable technology might be technically feasible eventually, but needs lots more research.
“I would not advise this to the overall general population,” said Dr Valentin Fuster, director of Mount Sinai Heart in New York and a former American Heart Association president, who was not involved with the study. Instead, he said, he would like to see it tested in seniors with risk factors such as high blood pressure.