4/10/2015
Cryptogenic stroke
Getting to the heart of the matter
Santosh Oommen, MD, FACC
New Mexico Heart Institute
Current Concepts Course 2015
Disclosures
• I have not managed to accrue any financial
disclosures since last year.
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4/10/2015
From theheart.org
AF and embolic stroke
• Approximately 1 in 6 cerebrovascular accidents
(CVA’s) are secondary to known atrial fibrillation –
proportion increases to 1 in 4 in patients age 80+.
• This remains an opportunity for intervention in the
medical field, given the known ability of
anticoagulation to reduce stroke risk by ~65% (vs.
aspirin, which provides a ~25% risk reduction.)
• But what about the proportion of CVA patients
whose stroke etiology is unknown?
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4/10/2015
From theheart.org
AF and cryptogenic stroke
• The current stroke guidelines give a Class I-A
indication to antiplatelet agents for treatment in
cryptogenic ischemic stroke. Anticoagulation is
not recommended unless atrial fibrillation is
documented.
• However, as atrial fibrillation can be both
paroxysmal and asymptomatic, a proportion of
cryptogenic stroke is likely due to AF that has not
been captured on initial evaluation.
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4/10/2015
How is cryptogenic stroke defined?
• Could be operationally defined as any ischemic
CVA that does not have a reasonably clear
etiology despite evaluation including:
– ECG
– 24 hour telemetry
– Echocardiogram with bubble study
– Transesophageal echocardiogram
– CT or MR intracranial and extracranial vessel imaging
– Hypercoagulable evaluation for patients age <55
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4/10/2015
EMBRACE trial NEJM June 2014
• 572 patients (June 2009 to March 2012)
• Age 55 or older with ischemic CVA or TIA in the prior
6 months
• Etiology not clear after ECG, telemetry/holter for 24
hours, neurovascular imaging, and echocardiogram
• Exclusion criteria: No known AF history or
intracardiac device already present.
EMBRACE trial NEJM June 2014
• Randomized 1:1 to a single repeat round of 24 hour
holter (control arm) vs. a 30-day event recorder.
• AF episodes adjudicated centrally by evaluators
blinded to pts’ clinical and demographic
characteristics.
• Primary outcome: Detection of 30 seconds or more
of AF/AFl within 90 days post-randomization
• Secondary outcomes: Included use of oral
anticoagulants at 90 days post-randomization.
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4/10/2015
EMBRACE trial NEJM June 2014
• Primary outcome noted in 16.1% in the intervention
group and 3.2% in the control group (p<0.001)
• Interestingly, half of AF episodes detected in first
week of wearing monitor, and ~75% in the first two
weeks.
• Statistically more likely to pick up AF if monitor worn
within less than 3 months from index event vs greater
than 3 months ( 18.5% vs 9.0%, p=0.049).
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• 13.6% of intervention group vs 4.7% of the control
group were switched to oral anticoagulation
(p<0.001.)
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4/10/2015
CRYSTAL AF Trial NEJM June 2014
• 441 pts (June 2009 – April 2012)
• Age 40 or older with ischemic CVA or TIA in 90 days
prior to enrollment
• Etiology not clear after ECG, at least 24 hours of
telemetry or Holter, echocardiogram, TEE, CTA or
MRA, and screening for thrombophilia (if less than 55
years old.)
• No known history of AF/AFl or implanted cardiac
pacemaker or defibrillator
CRYSTAL AF Trial NEJM June 2014
• Randomized 1:1 to either ECG’s at office visits or
insertion of a Reveal XT (Medtronic) implantable loop
recorder.
• Primary endpoint: Time to first detection of AF at 6
months of follow-up
• Secondary endpoints: Time to first detection of AF at
12 months of follow-up, recurrent ischemic CVA or
TIA, and change to oral anticoagulation.
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4/10/2015
No significant differences in Table 1 characteristics
No significant differences in Table 1 characteristics
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4/10/2015
• The primary endpoint, detection of AF at 6 months,
was met in 8.9% (19 pts) in the intervention group,
and 1.4% (3 pts) in the control group.
• AF episodes were asymptomatic in 74% of the
intervention group, 33% in the control group.
• Rate of anticoagulant use was 10.1% vs 4.6% in the
intervention vs control group at 6 months (p=0.04)
• Rate of recurrent ischemic stroke/TIA was 5.2% vs
8.6% in the intervention vs control group at 6 months
AF detected in 12.4% vs 2.0% at 12
months (p<0.001)
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4/10/2015
AF detected in 30% vs 3% of pts at 36
months (p<0.001).
Other Fun Facts
• At 12 months, the median value for max time in AF in
a 24 hour period was 11.2 hours.
• The overall findings held across age, gender, ethnicity,
and CHADS score.
• In terms of complications, 2.4% of patients had
devices removed due to infection or erosion. (Oral
antibiotics were presumably used in these cases.)
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4/10/2015
You may have noticed…
• There is a difference between the EMBRACE (event
monitor) and CRYSTAL-AF (implantable cardiac
monitor) studies in terms of detection of AF…
• The detection of AF seems significantly higher in the
EMBRACE trial (16.1% at 30 days) vs CRYSTAL-AF
(8.9% at 6 months).
• Main reason? Mean age in EMBRACE: 73 yo. In
CRYSTAL-AF: 61 yo.
Just to get a visual
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4/10/2015
Conclusions:
• The longer you monitor patients with cryptogenic
stroke, the more AF you will find.
• This can be expected to change management
from antiplatelet to anticoagulant therapy in a
significant subset of patients, quite possibly
reducing further morbidity and mortality.
Conclusions:
• We have ever increasing options for stroke risk
reduction in atrial fibrillation, both
pharmacological (novel oral anticoagulants) and
non-pharmacological (i.e. Watchman, ?AF
ablation?).
• Question: Is longer term screening for atrial
fibrillation in cryptogenic stroke patients
ultimately an avenue we can afford NOT to
pursue?
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4/10/2015
Thank You!
Santosh Oommen, MD, FACC
New Mexico Heart Institute
Current Concepts Course 2015
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