The rapid development of technologies, including blood pressure monitors enabled for atrial fibrillation screening has the potential to increase diagnosis and reduce the occurrence of cardio-embolic ischaemic stroke events
Atrial fibrillation (AF) is an important health problem that requires screening at the population level, given that a considerable proportion of patients are undiagnosed due to its asymptomatic clinical course. Recent technology development is effective at increasing AF screening and detection. AF screening procedures and technologies are required to be accurate enough to reduce the risks associated to unnecessary overdiagnosis and overtreatment, and accessible enough to be applied to high-risk populations without added risks and costs. Community pharmacists could play a key role in the battle against AF-related diseases.
The burden of AF in UK and worldwide
AF, the most common heart rhythm disorder, requires prompt diagnosis and management. Its presence is, in fact, closely associated with the occurrence of cardio-embolic ischaemic stroke, also known as one of the most feared and severe consequences of AF.
During AF, electrical and mechanical instability interfere with normal atrial function, predisposing the formation of blood clots of different sizes and shapes. Once detached from the atrial wall, emboli may became free to travel alongside the arterial system and get caught in peripheral arteries, causing tissue ischaemia and necrosis. For anatomic reasons, cerebral embolism during AF is three-times more frequent than embolism in other territories.1 Moreover, ischaemic stroke from AF is more deadly and disabling than strokes from other causes2.
Stroke risk in patients with AF is five times higher than in subjects with sinusal rhythm. Such risk is even increased in the presence of other diseases or clinical conditions, as it occurs in individuals with cardiac heart failure, hypertension, diabetes mellitus, vascular disease or previous athero-thrombotic events (Table 1). Age is a strong risk factor for both occurrence of AF and risk of stroke during AF. Anticoagulation is effective in normalising the risk of stroke associated with AF, although it is not free from serious adverse consequences such as cerebral or gastro-enteric haemorrhages. Pros and cons for anticoagulation should be carefully evaluated in each individual patient.3
AF prevalence in the worldwide population is projected to increase in the future due to ageing. The estimated number of individuals with AF globally was 33.5 million in 2010, and is predicted to increase by 40% on next two decades.4 In England, it is estimated that 1.4 million people have AF. This is equal to 2.5% of the population. Of these individuals, 2.8% of people are under 45 years, 16.6% are 45–65 years, and 80.5% >65 years. The peak in numbers occurs in the 80–84 age group5.
Clinical presentation and course of AF are heterogeneous: typical symptoms of AF are palpitations or the feeling of cardiac pulse irregularity. AF may be accompanied by a cohort of other symptoms different from palpitation, such as fatigue, chest pain, shortness of breath, lightheadedness, syncope or decreased exercise tolerance, most of which are common to other diseases. It is not infrequent that AF may occur asymptomatically; therefore its presence is discovered incidentally during an ECG exam, which is the gold standard for AF diagnosis, or hypothesised in the presence of irregular cardiac rhythm at pulse palpation. In the early phase of the disease, it is more frequent that AF may present as paroxysmal AF, corresponding to an arrhythmia which suddenly begins and spontaneously stops; in the later phase, AF tends to become more stable.
The rate of asymptomatic AF is approximately 33% of all episodes. In the UK, this corresponds to nearly 474.000 individuals. Subjects with asymptomatic AF are clearly at increased risk of stroke because they do not receive appropriate anticoagulation. It is estimated that one out of ten strokes occur in subjects with asymptomatic AF.6 Considering an approximately stroke rate from asymptomatic AF of over 20,000 per year in the UK, it has been estimated that screening for AF at the population level would save around 7000 strokes and 2000 premature deaths each year.7
Effective screening and why the pharmacy setting might be a good setting
According to the World Health Organization, a screening procedure is defined as the presumptive identification of unrecognised disease in an apparently healthy, asymptomatic, population by means of tests, examinations or other procedures that can be applied rapidly and easily to the target population. To be effective, a screening procedure must satisfy a series of criteria, summarised by Wilson and Junger in 1968 (Table 2):8 the condition to be screened should be an important health problem; there should be an accepted treatment for patients with recognised disease; facilities for diagnosis and treatment should be available; there should be a recognisable latent asymptomatic or early symptomatic stage; and the test should be suitable, acceptable and cost-effective to the population screened (the latter with reference to possible expenditures on medical care).8
Usually, screening for health diseases is performed at the primary or secondary healthcare level. In the UK, there are currently 11 screening programmes organised by the National Health Service, covering a range of different diseases ranging from aortic aneurysm, bowel, breast and cervical cancer, infectious diseases in pregnancy, newborn hearing and blood spot screening, to sickle cell and thalassaemia.
Pharmacies might provide an ideal setting to perform screening at the population level. Pharmacists are highly accessible and are often the first point of entry into the healthcare system. It has been estimated that nearly 90% of the general population visits a pharmacy at least once a year, and patients with chronic diseases, such as hypertension or diabetes mellitus, visit the community pharmacists five-times more frequently than their physicians.9 Moreover, banners and brochures in pharmacies could attract more attention to the programme, and staff can recommend the programme or distribute flyers to patients when they collect prescriptions.
Screening programmes delivered at the community pharmacies yet involve blood pressure assessment, serum cholesterol and capillary glucose test, enabling pharmacists to identify the global cardiovascular (CV) risk of an individual. This is made available by point-of-care hand-held testing systems and compact desktop analysers. Previous reports clearly showed that pharmacists are successful in performing screening for CV risk factors, providing evidence to support pharmacy’s role in health system.10
It should be highlighted that a screening test is not always 100% accurate, and will always require a confirmatory exam with the gold standard methodology. Screening tests could therefore provide false positive results when the screening is positive and the subsequent confirmatory exam is negative, and false negative results when the screening is negative in the presence of the pathological condition. The proportion of false positive and negative tests depends on the characteristics of the screening test and the prevalence of the disease in the population screened. The two main consequences of a relatively high rate of false positives and negatives are a false sense of security and late disease presentation on one hand, and inappropriate referral, unnecessary costs, and the consequences of being labelled with a serious health problem on the other. The role of the pharmacist is to make people aware of the possible pitfalls of the offered screening test, as well as the accessibility to pathways linking positive screening to disease confirmation and appropriate management and treatment.
How is AF screening currently performed at the population level?
AF screening is currently indicated by the National Institute for Health and Care Excellence (NICE) by pulse palpation to check for pulse irregularity, in people with atypical AF symptoms or in subjects at high AF and stroke risk, such as in individuals >65 years old. Although effective, the technique of pulse palpation to check for pulse irregularity was demonstrated to be rather inaccurate, being associated with nearly 20% of false negatives, and nearly 30% of false positives.11 Moreover, accuracy was quite different across studies, showing different ability to check for pulse irregularity, and the need of dedicated training. Single timepoint screening for AF could be ineffective even in the case whether arrhythmia is paroxysmal. Nevertheless, in people >65 years, AF screening by pulse palpation appears justified given the relatively high prevalence of asymptomatic AF.
Innovation in technology has produced a number of novel devices which improve feasibility of screening at the population level, and could be used to overcome the aforementioned limitations related to pulse palpation. The main methodologies developed for systematic AF screening are: handheld single-lead or smartphone-compatible ECG monitors; patch ECG monitors; plethysmographs via smartwatches; and modified blood pressure monitors to detect AF. Each of these types has its own strengths and limitations.
Handheld single-lead ECGs were launched on the market in 2013. The work on the principle of recording the electrical cardiac activity through a detector pad with metal electrodes upon which two fingers are usually placed. The detector pad may also be placed across the chest or engaged as a handlebar. The detector with electrodes is connected to an application or smartphone that processes the collected data. The single-lead ECG trace could thus be visualised in real time, analysed by dedicated software via proprietary algorithms, or stored and forwarded to healthcare professionals for remote evaluation. It is particularly suitable to detect arrhythmias in the presence of typical or atypical symptoms, or for the purpose of patient-activated single-point or repeated AF screening. Studies analysing the effectiveness of handheld single-lead ECGs in AF screening have shown high rates of sensitivity (nearly 98%) and specificity (91%). A landmark study conducted in Sweden in a population of individuals >75 years showed that single timepoint screening for AF with single-lead ECG was able to detect up to 1.5% of individuals with asymptomatic AF. If the measurement was repeated twice a day for 15 days, an additional 2.5% of undiagnosed AFs were detected. If the population was restricted to subjects aged 75 years or older with an additional stroke risk factor, this increased to 7.4%.12,13
These results also suggest that extending the observation period would inevitably result in greater effectiveness in detecting cases of paroxysmal AF. To this purpose, some extended-wear ECG patches have been developed, more or less with the same technological principles. The main disadvantage associated with this approach is skin irritation from electrodes and patches, leading to reduced patient compliance.
If the single-lead ECG trace has sufficient quality, a diagnosis of AF could be made. In this case, the positive screening in the presence of other stroke risk factors would ideally trigger the initiation of anticoagulation therapy without the need of confirmatory classical 12-lead ECG. It has not been tested to date, whether such approach is effective and safe in the long term in reducing deaths and disability associated with asymptomatic AF or, ultimately, if this approach would result in an unnecessary increased number of episodes of major haemorrhages in anticoagulated patients for whom such treatment was not indicated.
Finger photoplethysmography using smartphone cameras or wearable smartwatches (for example, AppleWatch) has recently raised increased attention as a solution to many problems related with the long-term evaluation of cardiac rhythm. This kind of wereable technology is attractive given the wide distribution of these products on the market, but often requires a noise-free trace for optimal performance. Such devices incorporate proprietary algorithms with variable techniques to assess cardiac rhythm and capture other personalised data, with the potential to extend accessibility of long-term AF screening to home settings, resource-poor settings, or difficult to reach populations. This approach was effective in detecting pulse irregularities in a case population of individuals >65 years old.14 However, this approach always requires prompt confirmation of AF through 12-lead ECG, and a higher than expected number of false positive results, as was shown in recent literature, would likely inevitably induce an increasing demand on health care services. Moreover, this approach tends to attract only relatively young participants, with very low AF detection rates, as compared to elderly population for whom digital technology is not yet familiar enough.
Some automated blood pressure (BP) monitors are equipped with algorithms enabling AF screening. Such an approach is, to date, probably the most inexpensive and easy to use screening procedure to be applied in different settings. Automated BP monitors detect variations in pulse regularity during BP measurement, using oscillometric technology. Different studies showed that such monitors offer high sensitivity and specificity (both >90%), and are clearly superior to pulse palpation.15,16
These devices can be used by health workers or patients, and provide single-timepoint or multiple patient-activated recordings, with the unique opportunity to screen for two clinical conditions (AF and high BP) that increase stroke risk without any extra effort. Because BP is routinely measured during healthcare visits, and BP measurement is often routinely offered in community pharmacies, this technique has the highest potential to screen for asymptomatic patients who otherwise would not be screened for AF. Moreover this approach may be complementary to pulse palpation, reducing the need for unnecessary ECG requested when the performer feels pulse irregularity. This technology has been recently implemented into 24-h automated BP monitors, which is the currently most accurate method for hypertension diagnosis and assessment. A recent study confirmed overall good accuracy in detecting AF episodes throughout the 24-h period, and an increased probability to detect paroxysmal AF episodes.17
Conclusions and future perspectives
AF is responsible for approximately one-third of all ischaemic strokes, with a considerable proportion related to unknown, untreated, AF. AF screening has been the subject of recent debate worldwide because of the increasing prevalence of AF with ageing and the opportunity to prevent strokes with appropriate anticoagulation. The rapid development of hand-held and wearable technologies, including BP monitors enabled for AF screening, smartphone apps, smartwatches and other devices, has the potential to change current knowledge about systematic AF screening.
There is ongoing research aimed at producing sufficient scientific evidence to confirm the health benefits of AF screening at the population level and in specific subgroups, in order to solve current fields of uncertainty, such as the overall benefit of AF screening in terms of stroke-associated morbidity and mortality reduction.
- A considerable proportion of patients with AF are undiagnosed due to its asymptomatic clinical course. The stroke risk in these patients is five times higher than in subjects with sinusal rhythm.
- Screening for AF is indicated in subjects at higher risk, such as in individuals >65 years old. This is currently performed through detection of pulse irregularity by pulse palpation.
- Innovation in technology has produced a number of novel devices which improve feasibility and effectiveness of screening for AF at the population level
- Pharmacies might provide an ideal setting to perform opportunistic AF screening at the population level, given that it has been estimated that nearly 90% of the general population visits a pharmacy at least once a year.
- AF screening through automated blood pressure monitors equipped with dedicated algorithms, is one of the most inexpensive and easy to use screening procedures.
- Chatterjee NA, Lubitz SA. Systemic embolic events (SEE) in atrial fibrillation: SEEing Embolic risk more clearly. Circulation. 2015;132:787–9.
- Bogiatzi C, Hackam DG, McLeod AI, Spence JD. Secular trends in ischemic stroke subtypes and stroke risk factors. Stroke 2014;45:3208–13.
- Gomez-Outes A et al. Causes of death in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2016;68:2508–21.
- Chugh SS et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014;129: 837–47.
- Public Health England. Atrial fibrillation prevalence estimates for local populations. www.gov.uk/government/publications/atrial-fibrillation-prevalence-estimates-for-local-populations (accessed June 2020).
- Freedman B, Potpara TS, Lip GY. Stroke prevention in atrial fibrillation. Lancet 2016;388: 806–17.
- Lane DA et al. Temporal trends in incidence, prevalence, and mortality of atrial fibrillation in primary care. J Am Heart Assoc 2017;6:pii: e005155.
- Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: WHO;1968. www.who.int/bulletin/volumes/86/4/07-050112BP.pdf (accessed June 2020).
- Shiu JR et al. Quantifying opportunities to affect diabetes management in the community. Can Pharm J 2006;139:37–8.
- Anderson C, Blenkinsopp A, Armstrong M. The contribution of community pharmacy to improving the public’s health: summary report of the literature review 1990–2007. 2009. Technical Report. Pharmacy Health Link, London.
- Hobbs FD et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess 2005;9:iii-iv, ix-x,1-74.
- Svennberg E et al. Mass screening for untreated atrial fibrillation: The STROKESTOP Study. Circulation 2015;131:2176–84.
- Engdahl J et al. Stepwise screening of atrial fibrillation in a 75-year-old population: implications for stroke prevention. Circulation 2013;127:930–7.
- Perez MV et al; Apple Heart Study Investigators. Stepwise screening of atrial fibrillation in a 75-year-old population: implications for stroke prevention. Large-scale assessment of a smartwatch to identify atrial fibrillation. N Engl J Med 2019;381:1909-17.
- Omboni S, Verberk WJ. Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community. BMJ Open 2016;6:e010745.
- Kabutoya T et al. Diagnostic accuracy of a new algorithm to detect atrial fibrillation in a home blood pressure monitor. J Clin Hypertens (Greenwich) 2017;19:1143–7.
- Kollias A et al. Atrial fibrillation detection during 24-hour ambulatory blood pressure monitoring: Comparison with 24-hour electrocardiography. Hypertension 2018;72:110–15.