REVIEW

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp

Cardiological Aspects of Stroke Prevention Marc Fisher, MD; Mark McAllister, MD

Many cardiac disorders and their treatment are associated with an increased risk for ischemic or hemorrhagic stroke, so it is important for cardiologists to be aware of recent advances in the field of stroke prevention. Atrial fibrillation (AF) is the most common cardiac disorder associated with a substantial risk for ischemic stroke (IS). The availability of implantable cardiac monitoring devices has substantially increased the detection rate of occult AF after IS. The 4 new oral anticoagulants have advantages when compared with warfarin, the standard therapy in AF to prevent IS, demonstrating a reduced risk for IS or intracerebral hemorrhage. Patients with cardiomyopathy, cardiac valve replacement, recent myocardial infarction, larger aortic arch atheroma and patent foramen ovale all have some level of increased risk for IS. The best approach for IS prevention in these disorders remains unsettled and varying approaches are recommended.   (Circ J 2015; 79: 271 – 277) Key Words: Antithrombotic therapy; Cardiac disorders; Prevention; Stroke

I

schemic stroke (IS) is an untoward consequence of many cardiology disorders and intracerebral hemorrhage is a feared side effect of therapies used to prevent IS. It is incumbent on cardiologists to be aware of the IS risks associated with disorders they commonly encounter and to choose the safest and most effective therapies to prevent IS. This review will focus on the most common cardiology disorder associated with a substantial IS risk, atrial fibrillation (AF) (Table 1). Cardiac conditions for which anticoagulation is indicated are cardiomyopathy, valvular heart disease, recent myocardial infarction (MI), aortic arch disease and patent foramen ovale (PFO). For each condition the risk of IS will be provided, and data about therapeutic approaches to IS prevention surveyed together with the risks of side effects associated with these therapies, with the intention of enabling cardiologists to approach the management of these patients rationally and decisively.

AF The risk of IS in AF patients is substantial and several risk stratification scores based on age, sex, and the presence of concomitant disorders have been developed. The most widely used risk score is the CHADS2 score, where C stands for congestive heart failure, H for hypertension, A for age ≥75 years, D for diabetes and S for prior stroke or transient ischemic attack (TIA).1 Each component when present is given a score of 1, except for prior stroke/TIA, which is scored 2 (Table 2). The annual risk of IS is 1.9% for a score of 0, 2.8% for a score of 1, 4.0% for a score of 2, 5.9% for a score of 3, 8.5% for a score of 4, 12.5% for a score of 5 and 18.2% for a score of 6. The IS risk with the CHADS2 score has been validated in many different studies and populations.2,3 A similar but enhanced

risk score, known as the CHA2DS2-VASC, may increase IS risk prediction.4 In this score an additional point is given for age of 65–74 and age ≥75 years is scored 2. Female sex and vascular disease other than prior IS or TIA are each scored 1. The IS risk with a lower score is less than with the CHADS2 score. Both scores may underestimate the risk of subsequent stroke in IS and TIA patients without other risk factors. Another important risk stratification in AF patients is the risk for bleeding if oral anticoagulation is initiated. The HAS-BLED is a score that predicts bleeding risk (Table 2) and has been validated in a large cohort of AF patients treated with warfarin.5 Both the IS risk score and the bleeding risk score should be considered when making decisions about oral anticoagulation therapy. The pathophysiological relationship of AF and IS is relatively obvious when patients are known to have AF prior to IS onset or the arrhythmia is observed at presentation to the hospital or shortly thereafter. However, it must be acknowledged that AF in IS patients does not necessarily imply that AF was the source of the IS. Patients may have alternative etiology for their stroke, such as large vessel atherosclerosis or small vessel disease in penetrating intracranial arteries.6 In AF patients who have stenosis or occlusion in a vessel supplying the territory involved with the infarct it can be problematic to determine if the local vascular disease was the cause or the AF. In patients with lacunar stroke that is typically ascribed to small vessel atherosclerosis concomitant AF is likely not the cause of IS and is an incidental finding. It must be acknowledged that lacunar stroke may in unusual circumstances be caused by AF, especially in patients under 75 years of age without known vascular risk factors. IS patients without known AF and who have no readily identifiable source for their stroke, which includes head and neck vessel imaging and evaluation for a

Received December 9, 2014; accepted December 10, 2014; released online January 7, 2015 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Mailing address:  Marc Fisher, MD, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.   E-mail: [email protected] ISSN-1346-9843  doi: 10.1253/circj.CJ-14-1342 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected] Circulation Journal  Vol.79, February 2015

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FISHER M et al.

Table 1.  Overview of Cardiac Conditions and Anticoagulation Indicated

Unclear whether indicated

Not indicated

 itral stenosis and history of embolism, AF, M or LA thrombus

Cardiomyopathy

Mitral regurgitation

Mechanical valves

Mitral stenosis and enlarged LA

Aortic valve disease

AF and elevated risk scores

MI with LV thrombus or apical hypokinesis

Bioprosthetic valves >3 months after surgery

Aortic arch disease and embolism

Bacterial endocarditis

PFO-related stroke AF, atrial fibrillation; LA, left atrium; MI, myocardial infarction; LV, left ventricle.

Table 2.  Components of the CHADS2, CHA2DS2-VASC and HAS-BLED Scores (Points) CHA2DS2-VASC

CHADS2

HAS-BLED

CHF (1)

CHF (1)

Hypertension (1)

Hypertension (1)

Hypertension (1)

Abnormal renal/liver function (1–2)

Age ≥75 (1)

Age ≥75 (2)

Prior stroke (1)

Diabetes (1)

Diabetes (1)

Bleeding history (1)

Prior stroke (2)

Prior stroke (2)

Labile INR (1)

Other vascular disease (1)

Age >65 (1)

Age 65–74 (1)

Drugs and/or ETOH (1–2)

Female sex (1) CHF, congestive heart failure; ETOH, alcohol; INR, international normalized ratio.

cardiac source of embolization, are said to have cryptogenic stroke.7 Such cryptogenic stroke patients with a stroke in a large vessel territory and no obvious source are presumed in many cases to have undetected AF. To determine if AF is present in cryptogenic IS patients, various approaches have been used. Initially, cardiac rhythm is monitored for ≥24 h during the hospitalization, as suggested by current management guidelines.8 This rhythm monitoring approach leads to AF detection in approximately 6% of unselected patients and 13% in patients selected for a higher risk of AF detection.9 The yield increases with the length of monitoring. External loop recorders used for up to 7 days and re-applied 3–6 months later increased the yield of previously unknown AF to 14%.10 The heterogeneity and selection bias in the studies analyzed makes generalization of the results of this meta-analysis problematic. Recently, 2 randomized trials were reported that evaluated AF detection in cryptogenic stroke patients undergoing prolonged ECG monitoring vs. short-term monitoring. In the 30-day Cardiac Event Monitoring Belt for Recording Atrial Fibrillation After a Cardiac Ischemic Event (EMBRACE) study,11 572 patient with cryptogenic stroke were randomly assigned to 24-h monitoring or a 30-day event triggered monitor. The mean age of the patients was 70 years and monitoring began on average 75 days after the index stroke. AF lasting ≥30 s was detected in 16.1% of the 30-day event monitor group and 3.2% of the 24-h monitoring group. The Cryptogenic Stroke and Underlying AF (CRYSTAL AF) trial compared the time to detection of AF in 441 IS or TIA patients determined to be cryptogenic after an extensive baseline evaluation for potential sources with 2 cardiac rhythm monitoring strategies.12 The control group had ECG monitoring performed at the discretion of the investigator and the other group had an implantable cardiac monitoring device. The mean time to randomization was 38 days from the ischemic event and the mean age of the patients included was 61.5 years. AF at 6 months was detected in 8.9% of the patients assigned to the inserted cardiac monitor and in 1.4% of the control group, and at 12 months the rates

were 12.4% and 2.0%, respectively. The median time to AF detection was 84 and 55 days, respectively, in the 2 groups and most of the detected AF episodes were asymptomatic. The median duration of the detected AF episodes was 4.3 min. The higher rates of AF detection with the implantable device led to an increase in the initiation of oral anticoagulation. The low rate of AF detection in the control group of the CRYSTAL AF trial as compared with the EMBRACE trial may reflect the age difference of the subjects in the 2 studies or other uncertain factors. Our personal experience with 30-day event monitors in cryptogenic IS and TIA patients had a much lower yield than observed in the EMBRACE trial and has led to use of implantable cardiac monitors for AF detection in cryptogenic patients deemed to be likely to have AF as the source of their ischemic event. An important question raised by increasing detection of AF by better monitoring is what duration of AF is clinically meaningful. It has been suggested that

Cardiological aspects of stroke prevention.

Many cardiac disorders and their treatment are associated with an increased risk for ischemic or hemorrhagic stroke, so it is important for cardiologi...
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