Clinical Cardiology

Atrial fibrillation

Mechanical prosthetic valve

Left atrial appendage thrombus

Left ventricular thrombus

Anterior wall MI

Endocarditis

Aortic sclerosis

Dilated cardiomyopathy

PFO /atrial septal aneurysm

Atrial flutter

Mitral stenosis

Aortic dissection

Atrial myxoma

Table 9-2

CHA2DS2-VASc score

Condition	Points
Age 65–74	1
Age ≥ 75	2
Female	1
CHF	1
HTN	1
Stroke/TIA/VTE history	2
Vascular disease	1
DM	1

Features of cardioembolic strokes

Sudden onset of symptoms that are maximal at onset
Multiple foci of ischemia in different vascular distributions on MRI
High risk of recurrence
Associated with increased morbidity and mortality

Paroxysmal, persistent, and permanent AF all appear to have similar risks for cardioembolic stroke (4.5 % annual risk of stroke overall)

Most emboli originate in left atrium and left atrial appendage (LAA)

LAA can have up to four lobes, all of which need to be properly visualized on transesophageal echo (TEE) to rule out thrombus

Strong correlation with LA dilation on echocardiography

Atrial “smoke” or spontaneous echo contrast in the left atrium: swirling echodensity seen on TEE, is a marker of stasis and increased thromboembolic risk

Prolonged cardiac monitoring is usually required for adequate workup after stroke

See EMBRACE trial below
Evaluation for AF after ischemic stroke
- Holter monitors, real-time continuous heart monitors, external loop recorders, implantable loop recorders are all options
- Event monitors
  
  Duration: 7–30 days
  
  Patient indicates when they have symptoms, which triggers recordings
  
  Operator-dependent (i.e., elderly, demented patients may have a hard time)
  
  Useful for infrequent, but symptomatic, events
  
  Asymptomatic events can be missed
- Continuous Telemetry Monitors
  
  Duration: 1–4 weeks
  
  Infrequent or transient symptoms
  
  Detection of symptomatic and asymptomatic episodes
  
  Continuous ECG recordings sent to data center, with physician-alert capabilities
- Loop Recorders
  
  Duration: >4 weeks
  
  Implantable device, has highest diagnostic yield
  
  MRI safe
  
  Combination of patient-activated and program-automated recording options

Timing of anticoagulation therapy following cardioembolic stroke

No guidelines on exactly when to start or resume anticoagulation following stroke
Most will wait at least 7–14 days following stroke to initiate anticoagulation
Smaller strokes and/or higher risk patients: can consider starting as early as 72 h post infarct
Main risk is hemorrhagic conversion of ischemic territory; therefore, many practitioners obtain noncontrast head CT prior to initiation to rule out clinically silent hemorrhage

Sick Sinus Syndrome

Unexplained bradycardia/sinus arrest without supraventricular tachycardia
Presence of supraventricular tachycardia leads to “tachy-brady syndrome”
Symptoms: syncope, palpitations, lightheadedness
Association with stroke, conversion into atrial fibrillation
Common indication for pacemaker
Antiplatelet therapy appropriate, anticoagulation if AF found

Treatment of Nonvalvular Atrial Fibrillation

Warfarin
- CHADS2VASc Score: validated scoring system used to identify patients who would benefit from anticoagulation (Table 9-2)
- Superior to aspirin for stroke prevention (See SPAF II trial below)
- Goal INR 2.5 (range 2–3)
- Leads to relative reduction in stroke risk by 60–70 % (absolute reduction in annual risk from 4.5 to 1.4 %)
- Risk of ischemic stroke rises rapidly if INR < 2
Newer anticoagulants are either noninferior to warfarin (rivaroxaban ) or have superior efficacy (dabigatran, apixaban) in lowering stroke risk, as well as having lower rates of intracerebral hemorrhage (ICH), fixed dosing with faster time to therapeutic effect, lack of regular lab testing, no dietary restrictions and fewer medication interactions; all require renal dose adjustments
- Drawbacks: limited proven reversal agents, no lab test for anticoagulant effect, cost
- Rivaroxaban : Factor Xa inhibitor
  
  See ROCKET-AF trial below
  
  Reversal agent is pending FDA approval
- Dabigatran : Direct thrombin inhibitor
  
  See RE-LY trial below
  
  Some in vitro data suggest that prothrombin complex concentrates may be effective for acute reversal
  
  Renally cleared, and dose is adjusted on creatinine clearance, not GFR
  
  Reversal agent: Idarucizumab, a monoclonal antibody specifically targeting dabigatran, was recently approved by the FDA
- Apixaban : Factor Xa inhibitor
  
  See ARISTOTLE and AVERROES trials below
Patients who may not tolerate full anticoagulation (high bleeding risk) may be placed on aspirin
- Leads to relative reduction in stroke risk by 17–20 % (absolute reduction in annual risk from 4.5 % to 3.3 %)
- Combination of Coumadin and aspirin not effective
- Antithrombotic therapy must be given in conjunction with rate/rhythm control
- Dual antiplatelet therapy with aspirin/clopidogrel : effective at reducing vascular events, but higher risk of hemorrhage (See ACTIVE-A trial below)

Notable Trials

EMBRACE (2014): Randomized trial comparing the ability of two modalities to detect atrial fibrillation in patients with recent, unexplained TIA or stroke. Patients were randomized to use either a 30-day event triggered recorder or a 24 h holter monitor. The study found that extended monitoring for 30 days had a much higher chance of detecting paroxysmal atrial fibrillation compared to 24 h monitoring, and led to a much higher rate of treatment with anticoagulation (Gladstone et al. 2014).

SPAF II (1994): Randomized trial comparing efficacy of warfarin (INR 2–4.5) versus aspirin 325 mg at reduction of stroke in patients with atrial fibrillation. The study evaluated two age groups (>75 and < 75). The study found that warfarin was more effective than aspirin in both age groups, with greater benefit in the older group. The study also found that younger patients with no other risk factors (hypertension , ischemic heart disease, prior thromboembolism) had low risk of stroke when treated with aspirin (Lancet, 1994).

RE-LY (2009): Randomized trial comparing efficacy and safety of dabigatran at two doses (110 mg or 150 mg twice daily) versus warfarin (INR 2–3) in patients with atrial fibrillation. Primary outcome was stroke or systemic embolism. Treatment with 110 mg twice daily had similar rates of the primary outcome compared to warfarin with lower rates of major hemorrhage. Treatment with 150 mg twice daily was associated with lower rates of stroke and similar rates of major hemorrhage compared to warfarin. Both doses had lower rates of intracranial hemorrhage compared to warfarin (Connolly et al. 2009).

ROCKET-AF (2011): Randomized trial comparing efficacy and safety of rivaroxaban versus warfarin (INR 2–3) in patients with atrial fibrillation. The study found that rivaroxaban was non-inferior to warfarin in preventing stroke and systemic thromboembolism. Rivaroxaban had lower rates of intracranial hemorrhage and fatal bleeding compared to warfarin (Patel et al. 2011).

ARISTOTLE (2011): Randomized trial comparing efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation. The study found that apixaban was superior to warfarin in preventing future stroke or systemic embolism, and caused fewer bleeding events compared to warfarin (Granger et al. 2011).

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