CT scan with brain showing signs of strokeIntroduction
Criteria for screening a disease condition
Screening for persistent atrial fibrillation
Screening for paroxysmal AF
How much AF is relevant for stroke risk?
Cardiac monitoring for PAF in high risk groups for primary prevention of stroke
Conclusion
Key points
References

This is part 2 of a two-part article. 

Part 1 can be found here.

  

Introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia affecting about 2.4% of the UK population, with approximately half being undiagnosed. Public Health England (2015) estimates indicate an average GP surgery case burden of 174 (61 undiagnosed). There is a striking increase in prevalence with age, from <3% in the under 60s to >10% in the over 75s (see Figure 1).1

AF is a major risk factor for stroke, increasing the risk five-fold, and about one in five strokes is attributable to AF, increasing to one in two in older age groups. AF-related strokes are more severe, reflected on brain imaging as large cortical infarcts, with a high risk of death (one in four) and residual disability in the majority of survivors. Other complications include: non-stroke systemic embolism, cardiac failure, increased hospitalisation, reduced quality of life, and cognitive decline leading on to vascular dementia.

AF-related stroke satisfies standard criteria for screening,1 as summarised in Table 1. Given the significant societal implications, there needs to be a very good reason for us to “not undertake” screening programs for AF. The importance of prevention of AF-related stroke cannot be over-emphasised.2

 

Criteria for screening a disease condition

Jung et al set out objective criteria for considering the benefit of screening.2 Prevention of AF is already undertaken in various settings, and is one of the objectives of treating vascular risk factors like hypertension, diabetes and coronary artery disease. It is also one of the goals of lifestyle modification changes like smoking cessation, alcohol moderation and weight loss (in the context of obesity). Optimal targets should be targeted, including: blood pressure <130/80mmHg (<140/90 where age >75 years) and HbA1c <6.5%. Most risk factors for AF are monitored either in the primary care setting or in specialist clinics, though not necessarily with the primary aim of preventing AF. In addition, regular pulse checks tend to be part of routine practice enabling identification of persistent AF in high risk groups. Screening for persistent AF can usually be undertaken with pulse checks; whilst screening for paroxysmal AF may require longer periods of cardiac monitoring.

 

Screening for persistent atrial fibrillation

The initial focus should be on identifying persistent AF, which is easily detectable by a pulse examination and can be confirmed by an electrocardiogram (ECG), a universally available and inexpensive test. The majority of embolic complications (chiefly embolic stroke) are eminently preventable with a single intervention: anticoagulation (25 strokes prevented per 1000 people with no prior stroke or TIA; and 90 vascular events prevented, mostly strokes in those with a history of prior stroke or TIA, every year).3,4 This benefit far outweighs the increase in bleeding rates secondary to anticoagulation. In addition, many of the significant practical limitations of the traditional single option of warfarin have now been addressed by four new agents (direct oral anticoagulants: DOAC), all of which are approved by NICE.5 Thus, the only persistent contraindication to anticoagulation is an irremediable structural cause of bleeding. Other contraindications like active bleeding, recent bleeding, and history of remote bleeding are no longer considered absolute; and should be subject to a full review in light of details from prior medical history. In some cases, a structural cause for bleeding may need to be excluded (eg. upper GI endoscopy to confirm healing of previous ulcers).

TABLE 1. STUDIES INVESTIGATING SCREENING FOR PERSISTENT AF
Study Subjects Strategy Prevalence AF detection rate Comments
SAFE Study6,12 Over 65s in primary care UK Systematic ECG for all; opportunistic (pulse check, ECG if irregular) 7.2% Systematic screening 1.62%
Opportunistic 1.64%
Control 1.02%
 
SEARCH AF13 Age > 65 years
Australia
Pharmacist pulse palpation and iPhone single-lead ECG 6.7% New AF 1.5% New AF CHADSVASC ≥ 2: 100%
Started A/C: 60%
STROKESTOP14 Age 75-76
Sweden
Mass population screening
Handheld ECG for 2 weeks, twice recordings + symptom guided
9.3% 3% new AF
2% untreated known AF
Started A/C: 93% new AF
47% known AF


Whilst there are several guidelines elucidating the appropriate assessment and management of AF, there is virtually no formal guidance on AF screening. On the whole, there is uncertainty about the cost effectiveness of routine screening, and approaches targeted at high risk groups are likely to result in higher case-detection rates and consequently lower cost per case detected. There is no uniform agreement on the definition of “high risk” for screening programmes. A summary of AF detection rates in recent studies is presented in Table 1. Opportunistic pulse checks in older age groups alongside other interventions (eg. annual flu jab) have been demonstrated to be as effective as, but cheaper, than routine pulse checks6 and are recommended by European Guidelines.7,8 Whilst pulse checks may have significant time implications in primary care, especially if considering routine screening for all, novel devices can enable AF screening within the context of standard practice eg. automated AF detection algorithms incorporated into automated BP measurement devices, like WATCH BP Home.9 It is estimated that routine use of the WATCH BP device could prevent 221 strokes per year, equating to a net saving of £11.6 million annually. In addition, the advent of apps that can identify AF using single lead ECG (AliveCor10), or even beat-to-beat variation in facial skin colour (Cardiio Rhythm11) open up the possibility of self- screening for AF.

 

Screening for paroxysmal AF

Episodic or paroxysmal AF (PAF) may require repeated assessments and long-term cardiac monitoring, which can be costly. Cardiac monitoring is undertaken when there is a clinical suspicion of PAF based on the clinical presentation eg. episodic palpitations, dyspnoea or chest pain; syncope or pre- syncope, recurrent unexplained falls etc. In addition, there is growing evidence to support prolonged monitoring in the setting of cryptogenic stroke. Prolonged monitoring after cryptogenic stroke or TIA identifies a significant number of people with atrial fibrillation, as summarised in Table 2. Detection rates increase with duration of monitoring undertaken (see Table 3), though robust cost-effectiveness analysis to support the duration of optimal monitoring are not available at present.

TABLE 2. MAJOR STUDIES OF CARDIAC MONITORING FOR PAF DETECTION FOLLOWING CRYPTOGENIC STROKE
Study Subjects Strategy (comparator) AF detection Comments
Gaillard et al15 Cryptogenic stroke (MRI+) Transtelephonic EKG (random recordings; 1 per month) >32s AF: 9.2% A/C started: 100%
EMBRACE16 Cryptogenic stroke or TIA (<6 months) ELR (24h Holter) >30s AF: 16.1% (3.2%)
>2.5min AF: 9.9% (2.5%)
Doubling of A/C usage
CRYSTAL AF17 Age > 40 Cryptogenic stroke ICM (24h Holter) 6m: 8.9% (1.4%)
12m: 12.4% (2.0%)
ELR external loop recorder; ICM insertable cardiac monitor; m months; min minutes; s seconds

 

How much AF is relevant for stroke risk?

TABLE 3. RATE OF DETECTION OF AF FOR VARIOUS PERIODS OF MONITORING18
Duration of monitoring AF detection rate
Daily ECG x6 0.06%
24h monitoring 3.6%
24h monitoring x6 2%
7 day Holter x2 4%
72h monitoring 6.7%
7d monitoring 7.4%
30 day 14.3%
Implanted device 1 year 18.3%


There remains uncertainty about the prognostic value of brief periods of AF, and the question about how much duration of AF constitutes significant stroke risk has not yet been answered. Since prior stroke is the most potent risk factor for future stroke, clinical decisions tend be based on a history of prior stroke. In the setting of previous stroke, patients with brief periods of AF (>30 seconds) have intermediate stroke risk (between non-AF and persistent AF),19 and are generally deemed by stroke physicians to be adequate to recommend anticoagulation.20 For primary prevention, longer durations (>5-6 minutes) are felt to be relevant from observational studies as summarised in Table 4.

 

Cardiac monitoring for PAF in high risk groups for primary prevention of stroke

No study has explored the potential value of prolonged cardiac monitoring in the general population. It is unlikely that routine prolonged cardiac monitoring in the absence of a prior cryptogenic stroke or TIA will be cost effective.

TABLE 4. RECENT STUDIES OF CARDIAC MONITORING FOR PAF DETECTION FOR PRIMARY PREVENTION OF STROKE
Study Patient group Study duration AF rate AF Duration HR (outcome)
ASSERT21 Age ≥ 65years; hypertensives 3 months 10.1% > 6 minutes 2.5 (Ischaemic stroke or systemic embolism)
MOST22 Sinus node dysfunction 27 months 51.3% > 5 minutes 2.8 (death or nonfatal stroke)
TRENDS23 Indication for implantable cardiac monitor; CHADS2 ≥ 1 17 months 43% > 5.5 hours 2.2 (thromboembolism)


Conclusion

Incremental risk of AF detection in the crystal-AF study

AF portends a grave prognosis, substantially increasing stroke risk. In the presence of a potent intervention to reduce risk, a programme for screening is required. Population-based screening is not considered cost effective, thus targeted screening for AF is recommended as part of a comprehensive approach to stroke prevention in people with AF. It is crucial that identification of AF leads on to appropriate risk assessments to inform anticoagulation decisions. For persistent AF, pulse checks should be targeted at high risk groups perhaps in the context of other assessments (opportunistic). For paroxysmal AF, a structured approach to prolonged cardiac monitoring is required in the setting of previous stroke to reduce risk of recurrent stroke. The value of prolonged monitoring as screening in the general population is currently unclear.

 

Key points

  • There is significant potential for health benefits from screening for AF, however, systematic screening of the whole population is unlikely to be feasible or cost-effective, both for persistent and paroxysmal AF.
  • Targeted screening is recommended, focused on populations where presence of AF would identify significant risk of stroke and indicate anticoagulation. For persistent AF, target groups (all over 75s; and all with age 65-75 AND a risk factor, as incorporated in the CHADSVASC Score) should have a pulse rhythm check as part of annual health checks. For paroxysmal AF, target groups (history of cryptogenic stroke/TIA or symptoms suggestive of paroxysmal AF) should lead to prolonged cardiac monitoring, the duration of which remains unclear especially with respect to cost-efficacy.
  • The excuse of poor management of known AF is no longer a reason to “not screen”, but indicates the need to improve our response to identified AF. The availability of newer anticoagulants makes anticoagulation therapy more acceptable to users and clinicians alike, as they surmount most of the practical obstacles to warfarin therapy and monitoring.

 

James J, Fotherby M, Mistri AK
University Hospitals of Leicester NHS Trust

Conflict of interest: none declared


 

References

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4. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD001927. DOI: 10.1002/14651858.CD001927.pub2

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