Issue: August 2021
Source: Perez MV, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1901183.
Disclosures: Lubitz reports he received sponsored research support from Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer for VITAL-AF/GUARD-AF and IBM and consultant fees from Bayer, Blackstone Life Sciences, Bristol Myers Squibb and Pfizer. Perez reports he received grant funding from the NIH and Apple and consultant fees from Apple, Biotronik and Boston Scientific. Sandhu reports she received grants to support her research from Bristol Myers Squibb/Pfizer and Servier. Tarakji reports he received consultant fees from and was on the advisory board of AliveCor, Janssen Pharmaceuticals and Medtronic. Volgman reports she owns stock in Apple.
August 17, 2021
10 min read

Screening for asymptomatic AF brings potential benefits, many questions

Issue: August 2021
Source: Perez MV, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1901183.
Disclosures: Lubitz reports he received sponsored research support from Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer for VITAL-AF/GUARD-AF and IBM and consultant fees from Bayer, Blackstone Life Sciences, Bristol Myers Squibb and Pfizer. Perez reports he received grant funding from the NIH and Apple and consultant fees from Apple, Biotronik and Boston Scientific. Sandhu reports she received grants to support her research from Bristol Myers Squibb/Pfizer and Servier. Tarakji reports he received consultant fees from and was on the advisory board of AliveCor, Janssen Pharmaceuticals and Medtronic. Volgman reports she owns stock in Apple.
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Atrial fibrillation accounts for 454,000 hospitalizations and 158,000 deaths annually, according to the CDC. Many with AF have symptoms, but many do not, leading to the question of whether screening in asymptomatic individuals is needed.

Deciding who should be screened for AF among the asymptomatic patient population is a priority. But determining the exact number of asymptomatic AF patients is a challenge.

“Some estimates, taking into account the fact that we have more data for the higher-risk population and less data for the lower-risk population, are on the order of about 600,000 people in the U.S., but that’s a rough estimate,” Marco Perez, MD, associate professor of cardiovascular medicine at Stanford University Medical Center, told Cardiology Today.

The Apple Heart Study and other trials have demonstrated the feasibility of screening for AF in asymptomatic populations. However, questions remain about the best strategies to identify AF on a large scale with few false positives and false negatives.

In April, the U.S. Preventive Services Task Force reported that there was not enough evidence to make a recommendation regarding screening asymptomatic patients aged 50 years and older for AF. According to the USPSTF, more studies are needed to compare the pros and cons of screening for AF against usual care and to assess early AF treatment benefits.

Cardiology Today spoke with experts about the latest screening strategies for detecting and monitoring asymptomatic patients with AF, the role of wearable smart devices, the best candidates for loop recorders and the future of AF detection.

Evidence to date

There is evidence that mass screening for AF in selected subgroups may pay dividends. In the STROKESTOP study, a population-based AF screening program in adults aged 75 and 76 years living in two regions of Sweden, a previous diagnosis of AF was known in 9.3%, 3% had previously unknown AF detected during the study period and 0.5% had new AF detected on their first ECG.

The STROKESTOP results suggested that mass screening for AF identifies a significant proportion of participants with untreated AF, and initiation of prophylactic stroke treatment was highly successful in individuals with newly diagnosed AF; 3.7% of the screened population initiated oral anticoagulants.

The landmark Apple Heart Study, published in The New England Journal of Medicine in 2019, provided a solid foundation for large-scale pragmatic studies for AF detection.

“We learned a lot about how well the Apple Watch picked up an irregular pulse and how often it was confirmed to be AF on a subsequent monitor. There are still a lot of questions to be answered, but it is information that will be helpful for clinicians who have patients who present them with irregular pulses on devices like the Apple Watch,” Perez, an author of the Apple Heart Study, said.

Annabelle Santos Volgman

“The Apple Heart Study highlighted the feasibility of remote clinical trial enrollment, the interest that individuals have in being screened for AF and the validity of a particular photoplethysmography algorithm for detecting possible AF,” Steven Lubitz, MD, MPH, associate professor of medicine at Harvard Medical School and cardiac electrophysiologist at Massachusetts General Hospital, told Cardiology Today.

The role of smart devices

There has been rapid advancement in rhythm monitoring technology, including the use of wearable smart devices that have made the ability to diagnose people with asymptomatic AF easier, but some caveats must be considered.

“Whatever screening tool is used for AF has to have proper validation studies performed. If that screening tool is more pulse-based ... and you suspect AF, you need a confirmatory test to determine rhythm like a gold standard 12-lead ECG,” Roopinder Sandhu, MD, MPH, cardiac electrophysiologist and director of the Device Clinic in the Smidt Heart Institute at Cedars-Sinai, told Cardiology Today. “A lot of these screening tools are rhythm-based, so you get a tracing of the rhythm. Even then, it should be routine practice for physicians to review all tracings and confirm that AF is present, and if it’s not, but the suspicion for AF is still there, then additional heart rhythm monitoring is done. In practice, we are seeing more patients who pull out their phone during a visit and show us one of these strips.”

As wearable smart devices become even more ubiquitous — a survey taken in June 2019 found 21% of Americans use a smartwatch or fitness tracker — they could become part of the standard armamentarium used to identify AF.

“Wearable smart devices are increasingly common and enable detection of AF outside of a visit with a health care provider. I believe they will be important tools for identifying undiagnosed AF in the future,” Lubitz said.

Symptomatic patients stand to benefit from these devices because they give clinicians an on-demand ECG recording that is convenient and accessible.

“For asymptomatic patients, you can detect randomly for somebody who is actually in AF all the time, for example, but if you are looking for asymptomatic episodes for somebody who is not in AF all the time, this is where [intermittent ECGs] become less useful,” Khaldoun Tarakji, MD, MPH, associate section head of cardiac electrophysiology in the Heart and Vascular Institute at Cleveland Clinic, told Cardiology Today.

Subcutaneous loop recorders

Another challenge in AF is that patient symptoms can be intermittent. Some patients may have only a few episodes per year and the episodes could be long or short.

An implantable loop recorder is a remote heart recording device that is implanted underneath the skin of chest and records heart rhythm continuously for up to 3 years. It is used to detect causes of fainting, palpitations, very fast or slow heartbeats, as well as hidden rhythms that can cause strokes.

“The best example is somebody who passes out but only does so once a year; in that scenario, a loop recorder helps you identify the electrical reasons for them passing out,” Perez said.

An implantable loop recorder could be particularly advantageous, for instance, when there is a suspicion that a patient might be having an episode of AF or another heart rhythm that occurs rarely. In that case, with a loop recorder, those rare episodes would be detected.

“Patients who have infrequent symptoms are not detected by the usual 2- to 4-week time frame used with ECG monitors. [Implantable loop recorders] are excellent at detecting arrhythmias,” Cardiology Today Editorial Board Member Annabelle Santos Volgman, MD, McMullan-Eybel Endowed Chair for Excellence in Clinical Cardiology, vice chief for academic affairs and professor of medicine at Rush College of Medicine and medical director of the Rush Heart Center for Women, said in an interview.

Sandhu noted that an example of the usefulness of implantable loop recorders is in patients who have had an ischemic stroke with an inconclusive cause, but it is possible that that AF could be the underlying cause.

“If you don’t see any AF with just short-term cardiac monitoring, something prolonged like an implantable loop recorder that stays underneath the skin anywhere up to 3 years is a great way to monitor for AF,” Sandhu said.

Determination of benefit

The question of which patient populations would benefit from AF screening interventions is important, as the answer means patients not previously determined to be high risk for stroke may become candidates for preventive therapies such as oral anticoagulants.

Steven Lubitz

“Older individuals at elevated risk for stroke, who would be eligible for oral anticoagulation should AF be identified, are likely to benefit the most from AF screening interventions,” Lubitz said.

Some recent screening studies that have made an impact include the VITAL-AF, mSToPS and SCREEN-AF trials that determined certain methods of AF screening may be appropriate in certain populations and paved the way for additional research to address important questions about where AF screening is appropriate and how it should be carried out. VITAL-AF assessed whether point-of-care rhythm assessment with a single-lead ECG (AliveCor) in a primary care setting may increase newly diagnosed AF compared with a control group; there was no difference in the overall trial, but among older patients, the ECG group had more AF detection. In mSToPS, a wearable ECG monitor (Zio, iRhythm Technologies) conferred improved diagnosis of AF and use of guideline-recommended therapies. In SCREEN-AF, screening with wearable continuous ECG monitors was well tolerated, increased AF detection and sometimes prompted anticoagulant therapy among older individuals with hypertension.

“The VITAL-AF, mSToPS and SCREEN-AF studies provide important information on better defining those criteria. At present, there are guidelines that recommend that we do opportunistic AF screenings. For example, at the time of a medical encounter for anybody who is over the age of 65 or older. This of course is in an enriched population in whom identification of AF can change management,” Sandhu said.

Although the older population with risk factors for stroke are likely to benefit from screening interventions like those tested in VITAL-AF and mSToPS, there are a few caveats to be aware of.

“We don’t yet have good clinical evidence that a screening that leads to treatment such as blood thinners prevents strokes in these kinds of populations. When we talk about AF screening, there is more to it than just stroke,” Perez said.

Monitoring high-risk patients is warranted to detect AF, but there are risks that have to be taken into consideration.

Marco Perez

“The more you monitor high-risk individuals, the more AF you are going to pick up. We do know that detecting AF correlates with the risk of thromboembolism, but up until now we don’t know whether intervening and starting that patient on blood thinners will decrease that risk or not, because they carry the risk of bleeding. They are great studies to enhance our understanding about the prevalence of AF,” Tarakji said.

Tarakji noted that these screening interventions might become even more important when they are combined with a new wave of studies.

“These studies are not just looking at detection of AF using these devices, but they are also looking at outcomes,” he said. “Would intervention, in this case starting blood thinners, change the outcome or not? We are going to get a lot of knowledge about what to do for randomly detected episodes of asymptomatic AF. And that’s when these studies will become more relevant and more important.”

Pros and cons of screening

The USPSTF decision in April to not make a recommendation for AF screening in asymptomatic patients aged 50 years and older was driven in part by a lack of trials that reported on the benefits of anticoagulant therapy in screen-detected populations.

The USPSTF found no harm associated with the performance of ECG or use of portable or wearable rhythm monitoring devices, but the task force members wrote that abnormal test results could cause anxiety.

“Misinterpretation of a screening test result may lead to misdiagnosis and unnecessary treatment. In addition, ECG may detect other abnormalities (either true- or false-positive results) that can lead to further testing and treatments that have the potential for harm,” the USPSTF concluded.

Roopinder Sandhu

Although screening efforts show promise, one concern is that they could become too broad and result in more noise than providing clinicians with useful data.

“We have to gather all the data being produced by different studies all over the world and determine if detecting asymptomatic AF can actually lead to less strokes and deaths. We don’t want screening efforts to cause more harm by creating anxiety and unnecessary anticoagulation,” Volgman said in an interview.

Sandhu noted that screening the general population tends to include a lot of young healthy patients with low rates of detected AF.

“We want to be careful that we are targeting the right population,” Sandhu told Cardiology Today. “There has been a rapid explosion of technology to detect rhythm, and we want to be careful about the fact that this can also lead to physicians being inundated with data that exceeds their ability to manage.”

Appropriate guidelines are needed for who should undergo AF screening, how they should be managed and the care path that should be taken when dealing with the large amount of data being sent to physicians, Sandhu said.

In some cases, the benefit of screening depends on the screening method and the screening duration.

“In the ASSERT trial, when the participants were screened for the first 3 months, those who had even short episodes of AF were at risk of having a subsequent stroke,” Perez said in an interview. “However, in the same study, when the researchers expanded the search to 3.5 years, they found that it was only the long episodes of AF, not the short episodes of AF, that accounted for that increased risk of stroke. It points to the fact that we need to do careful studies to help us identify what kind of screening and what duration of screening is beneficial, and then the clinical studies to tell us if intervention based on those screening methods have benefits that outweigh the risks.”

Three large, randomized studies, ARTESIA, LOOP and NOAH, are underway to determine the value of anticoagulation in patients with detected AF.

The future of detection

Experts predict that over the next decade, AF detection will likely be conducted passively, utilizing wearables and other state-of-the-art technologies prescribed by physicians.

“I expect that we will have new tools for identifying individuals at highest risk for developing AF in whom to target for screening efforts,” Lubitz said.

In the future, Sandhu said, more data will become available on which populations to screen, with what device and what screening methodology is appropriate.

“More importantly, we will have a better idea of what is the clinical significance of screen-detected AF,” Sandhu said.

“The major paradigm shift has been that consumers now can purchase the devices directly without a clinician prescription and perform this monitoring on their own. What that means is that more and more people will be monitoring themselves for conditions like AF and the technologies to do so will become more pervasive,” Perez said.

Tarakji said he sees that as a positive.

“By combining the features of checking the pulse and intermittently checking the ECG when needed, you can do a lot with these devices. This is an exciting time, and we are lucky as a specialty in electrophysiology that these tools are available for us,” Tarakji said.

There are many avenues for future research.

“We need to understand whether AF screening prevents strokes and improves health outcomes, whether it is cost-effective and which approaches are most appropriate in which settings,” Lubitz said. “We need to determine how the health care system should deploy AF screening and how the health care enterprise should handle the voluminous data being generated from new technology. We need to identify the most efficient methods for predicting future risk of AF.”

Additionally, the newer devices are designed to be less invasive, more affordable and more accurate and will be used by consumers across a broader age spectrum. This is expected to lead to more interactions with the health care system, and raises questions for the future.

“We will have to start thinking about not whether we should be screening, but rather what to do with our patients who come in after they have done their own screening. What does that duration and burden mean? Does it increase your risk of stroke? Does oral anticoagulation benefit these patients? The answer to these questions will determine whether AF screening will become routine practice,” Perez said.