Transcript Risk Factors

‫الرجفان االذيني والخطورة الصمية‬
‫إعداد‬
‫د عمر القاسم‬
Established Patterns and Severity of Atrial Fibrillation
Patterns of Atrial Fibrillation
SAF Score*
SAF
Score
Newly
Diagnosed AF
Paroxysmal:
Self-terminating
<7d
Class 0
Persistent:
Sustained ≥7d
Permanent:
Decision to
continue
in AF
Impact on QOL**
Asymptomatic
1
Minimal effect on
QOL
2
Minor effect on QOL
3
Moderate effect on
QOL
4
Severe effect on
QOL
** QOL = quality of life
What are the symptoms of atrial
fibrillation?
Symptoms may be experienced on a regular basis, intermittently or
not at all:1,2
Fatigue, palpitations, dizziness, chest pains and breathlessness
Many people with atrial fibrillation lack any symptoms:1-3
More than half of episodes of atrial fibrillation are not felt by the
patient
Atrial fibrillation if present can be diagnosed using an
electrocardiogram4
Regular rhythm
P wave
Irregular rhythm
No P wave
Asymptomatic atrial fibrillation
Asymptomatic atrial fibrillation is a substantial problem for invidual health and for
the health care system:
it may cause stroke
it is frequent despite antiarrhythmic drug therapy or catheter or surgical
ablation
(it may cause cognitive dysfunction and dementia)
Mechanisms of AF
Extracardiac
Factors:
Hypertension
Obesity
Sleep apnea
Hyperthyroidism
Alcohol/drugs
Atrial Structural
Abnormalities:
Fibrosis
Dilation
Ischemia
Infiltration
Hypertrophy
Inflammation
Oxidative stress
AF
Atrial tachycardia
remodeling
Genetic Variants:
Channelopathy
Cardiomyopathy
RAAS activation
Atrial Electrical
Abnormalities:
↑Heterogeneity
↓Conduction
↓Action potential duration/refractoriness
↑Automaticity
Abnormal intracellular Ca++ handling
Autonomic
nervous system
activation
‫أسباب الرجفان األذيني‬
‫‪-1‬أمراض القلب الرثوية‬
‫‪ -2‬أمراض الشرايين التاجية‬
‫‪ -3‬ارتفاع ضغط الدم الشرياني‬
‫‪ -4‬زيادة نشاط الغدة الدرقية‬
‫‪ -5‬عيوب القلب الخلقية‬
‫‪-6‬اإلرتفاع العالي لحرارة الجسم ألي سبب التهاب جرثومي بكتيري أو‬
‫فيروسي‬
‫‪ -7‬التهاب عضلة القلب أوالتهاب غشاء التامور المغلف للقلب‬
‫‪ -8‬شرب المسكرات وتعاطي المخدرات‬
‫‪ -9‬بعد الجراحات القلبية واحتشاء العضلة القلبية‬
‫‪ -10‬غير معروف السبب عند ‪ %10‬من الحاالت ‪.‬‬
‫‪ -11‬األمراض الرئوية المزمنة‬
Risk Stratification in AF
Stroke Risk Factors
High-Risk Factors
Mitral stenosis
Prosthetic heart valve
History of stroke or TIA
Moderate-Risk Factors
Age >75 years►
Hypertension►
Diabetes mellitus►
Heart failure or ↓ LV function►
Less Validated Risk Factors
Age 65–75 years ►
Coronary artery disease ►
Female gender ►
Thyrotoxicosis ►
Atrial Fibrillation
Morbidity and Mortality
4- to 5-fold increased risk of stroke
Doubling of the risk for dementia
Tripling of risk for heart failure
40 to 90% increased risk for overall mortality
Risk of stroke in AF patients by age group
1.5% in 50 to 59 year age group
23.5% in 80 to 89 year age group
Benjamin EJ, et al. Circulation 2009;119:606-618
Priorities in the Management of AF
The Patient Care Pathway
Rhythm Control
Prevention of
Thromboembolism
Rate Control
Overview of AF Management
AF Detected
Assessment of
Thromboembolic
Risk (CHADS2)
Appropriate
Antithrombotic
Therapy
Detection and
Treatment of
Precipitating Causes
Management of
Arrhythmia
Rate
Control
Rhythm
Control
Strategy of rhythm-control for recent-onset AF/AFL
Clear onset <48 h or
Therapeutic OAC2 x 3 weeks
High-risk patients1 or Onset >48 h
or unknown or Inadequate OAC2
Rate-control
Hemodynamically
unstable
Urgent electrical
CV at 150-200J
Hemodynamically
stable
Pharmacological
or electrical CV at
150-200J
Antithrombotic therapy
No prior anticoagulation requiredInitiate OAC in ED if CHADS2 >1 or age >65Otherwise, initiate ASA if CAD or vascular d.Early follow-up to review long-term OAC1 High
Therapeutic OAC
for 3 weeks
before CV
Trans-esophageal
echocardiography
(TEE) guided CV3
Antithrombotic therapy
Initiate or continue OAC for >4 weeksEarly expert follow-up to review long-term OAC
risk of stroke (e.g. mechanical valve, rheumatic heart disease, recent stroke/TIA)
2 OAC = oral anticoagulant; N-OAC = Novel OAC (dabigatran, apixaban, rivaroxaban)
3 Immediate N-OAC preferred, but if N-OAC contraindicated use warfarin with heparin bridging
If Patient is Hemodynamically Stable
Goal is ventricular rate control (<100 bpm) and anticoagulation
Resting HR goal should be 60-85 bpm in symptomatic patient
Roughly 50% of patients with new onset AF will spontaneously convert
to NSR spontaneously within 48 hours of onset
Rate control or Rhythm control?
AFFIRM trial and RACE trial
No survival advantage in terms of stroke prevention rhythm control over rate
control rate control
Rate control agents
Calcium Channel Blockers
Beta blockers (caution in patients with reactive airway disease)
Digoxin
Amiodarone (for patients intolerant or unresponsive to other agents)
Indications for Urgent Direct Cardioversion
Hemodynamic Instability:
Patient with decompensated heart failure
Active ischemia: if symptomatic with angina or
evidence of ischemia/infarction on EKG
Evidence of organ hypoperfusion (altered mental
status, cold clammy skin, acute kidney injury)
Management of AF in the ED – Recommendations
Is Patient Stable?
Immediate Risk for
Stroke?
Low Risk
1. Clear onset <48 hours, or
2. Therapeutic OAC ≥ 3 wks
Pharmacological or
electrical CV at 150-200
J
(Immediate anticoagulation in ED
before CV not required) *
Antithrombotic therapy
Initiate OAC upon discharge from ED (or continue current OAC) if age ≥ 65 or
CHADS2 ≥ 1
Otherwise, initiate ASA if CAD or vascular disease
Early follow-up to review long-term OAC -
YES
NO
High Risk**
No therapeutic OAC ≥ 3 weeks and one of:
1. Onset >48 hours or unknown, or
2. Stroke/TIA <6 months or
3. Mechanical or rheumatic valve disease.
Rate-control
Therapeutic OAC for 3
Trans-esophageal
weeks before
echocardiography (TEE)
outpatient CV
guided CV
Antithrombotic therapy
- Continue OAC for ≥4
weeks after CV
- Early follow-up to review
long-term OAC
Antithrombotic therapy
Unstable – AF causing:
1. Hypotension, or
2. Cardiac ischemia, or
3. Pulmonary edema
Consider urgent
electrical CV if rate
control not effective
Antithrombotic therapy
- Initiate immediate OAC* in ED Initiate immediate OAC* in ED and and continue for ≥4 weeks continue for ≥4 weeks if any ‘high
risk’ ** features present
- Early follow-up to review
Early follow-up to review
long-term OAC
long-term OAC
a dose of OAC should be given just prior to cardioversion - either a novel direct oral anticoagulant (NOAC) or a dose of heparin or low molecular weight heparin * Immediate OAC =
with bridging to warfarin if a NOAC is contraindicated.
Emergency Management of AF
Overview of Rate Management
Rate Control Drug Choices
Heart Failure
CAD
No Heart Failure
or CAD
β-blockers
± Digoxin
β-blockers*
Calcium Channel
Blockers#
Combination Rx
β-blockers*
Calcium Channel
Blockers#
Digoxin†
Combination Rx
Drugs are listed in alphabetical order
*β-blockers preferred in CAD
# Non-dihydropyridine calcium channel blockers (diltiazem, verapamil)
†Digoxin may be considered as monotherapy only in particularly sedentary
individuals
Managing Rate Control - Recommended Drugs
ß-Blockers
Drug
Dose
Adverse Effects
Atenolol
50 - 150 mg p.o. daily
bradycardia, hypotension, fatigue,
depression
Bisoprolol
2.5 - 10 mg p.o. daily
as per atenolol
Metoprolol
25 mg - 200 mg p.o. bid
as per atenolol
20 - 160 mg p.o daily - bid
as per atenolol
80 - 240 mg p.o. tid
as per atenolol
Nadolol
Propranolol
Calcium Channel Blockers and Digoxin
Drug
Dose
Adverse Effects
Verapamil
120 - 480 mg p.o. daily
120 - 240 mg p.o. bid
bradycardia, hypotension, constipation
Diltiazem
120 - 480 mg p.o. daily
120 - 240 mg p.o. bid
bradycardia, hypotension, ankle swelling
Digoxin
0.0625 mg - 0.25 mg p.o. daily
bradycardia, nausea, vomiting,visual
disturbance
Overview of Rhythm Management
Rhythm Control Choices
Normal Systolic Function
No Hx of CHF
Dronedarone+
Flecainide*
Propafenone*
Sotalol#
Rhythm Control Choices
Hx of CHF or Left Ventricular
Systolic Dysfunction
EF > 35%
EF ≤ 35%
Amiodarone
Sotalol**
Amiodarone
Catheter
Ablation
Amiodarone
Catheter Ablation
Drugs are listed in alphabetical order
Dronedarone should be used with caution in combination with digoxin +
Class I agents should be AVOIDED in CAD and should be COMBINED •
with AV-nodal blocking agents
Sotalol should be used with caution in those at risk for torsades de #
pointes VT (e.g. female, age > 65 yr, taking diuretics)
** Sotalol should be used with caution with EF 35-40% and those at risk
for torsades de pointes VT (e.g. female, age > 65 yr, taking diuretics)
What is the link between atrial fibrillation and
?
stroke
People with atrial fibrillation are five times more likely
to have a stroke:1
20-30% of strokes are related to atrial fibrillation2
Up to three million people worldwide have an
atrial fibrillation-related stroke every year
– that is one person every 12 seconds!3-5
How do you measure the risk of
stroke?
CHADS2-Score: a simple index that is widely used to assess the risk of stroke
of a patient with atrial fibrillation. It can be used to guide antithrombotic
therapy
Congestive heart failure history - 1 point
Hypertension history - 1 point
Age > 75 years -1 point
Diabetes mellitus history -1 point
Stroke or TIA history - 2 points
The higher your CHADS2-Score, the higher your risk of having a stroke
This score has been expanded in 2010 by additional factors: female gender,
age between 65 and 74 years, presence of vascular disease: CHA2DS2VASc
1. Fuster V, Rydén LE, Cannom DS, et al. Circulation 2006; 114:700-52.
Stroke risk assessment with CHADS2
and CHA2DS2-VASc
Stroke risk assessment with CHADS2
and CHA2DS2-VASc
CHADS score
% AF popltn
0
low risk
16.3
1
moderate risk
26.7
2(+) high risk
57
Cowan C et al. Heart doi:10.1136/heartjnl-2012-303472
Optimizing Benefit and Reducing Risk
Hemorrhage
Thrombosis
HAS-BLED should be used to identify modifiable risk factors for bleeding
Score of ≥3 indicates need for regular clinical review
Patients with a higher HAS-BLED score also have a higher CHA2DS2-VASc score
There is net clinical benefit in anticoagulating CHA2DS2-VASc >0 whatever HAS-BLED score
Antithrombotic Therapy for Atrial Fibrillation
Risk Factor
No risk factors
CHADS2 = 0
One moderate risk factor
CHADS2 = 1
Any high risk factor or
>1 moderate risk factor
CHADS2 >2
or Mitral stenosis
Prosthetic valve
Recommended
Therapy
Aspirin, 81-325 mg qd
Aspirin, 81-325 mg/d or
Warfarin
(INR 2.0-3.0, target 2.5)
Warfarin
(INR 2.0-3.0, target 2.5)
Warfarin
(INR 2.5-3.5, target 3.0)
VKAs have a narrow therapeutic window
Adjusted odds ratios for ischaemic stroke and intracranial
bleeding in relation to intensity of anticoagulation
Odds ratio for event
20
15
10
Ischaemic
stroke
5
Target
INR
Intracranial
bleeding
1
1.0
2.0
3.0
4.0
5.0
6.0
International normalized ratio
7.0
8.0
Adapted from Wann et al. Circulation 2011;123;e269-e367
The Ideal Anticoagulant
Wide Therapeutic Margin
Safe Therapeutic
Range
Bleeding
Thrombosis
Thrombosis
Dose, Concentration, or Intensity of
Anticoagulation
The ACTIVE Trial
Clopidogrel + Aspirin
Atrial Fibrillation + Risk Factors
ACTIVE - W
Anticoagulation-eligible
VKA
(INR 2-3)
Clopidogrel
+ Aspirin
Open-label
Non-inferiority
n = 6,706
ACTIVE - A
OAC Contraindications or Unwilling
Aspirin
+ Placebo
Double-blind
Superiority
n = 7,554
Irbesartan, 300 mg/d vs. Placebo
n = 9,016
Risk Factors:
Age 75, hypertension, prior
stroke/TIA, LVEF<45%, PAD, age 55-74 +
CAD or diabetes
Clopidogrel
+ Aspirin
ACTIVE - I
Primary outcome: Stroke, systemic
embolism, MI or cardiovascular death
Antithrombotic Therapy for Atrial Fibrillation
Stroke Risk Reductions
Warfarin
Better
Antiplatelet Rx
Better
All patients
Warfarin vs.
Aspirin + Clopidogrel
Prior OAC
VKA-naïve
100%
50%
0
-50%
Coagulation pathway
TF
VKA
VII
VIIa
VKA
Initiation
IX
X
Propagatio
n
VKA
Inactive Factor
Xa
IXa
Active Factor
Direct Factor Xa inhibition
II
Rivaroxaban
Direct Factor IIa inhibition
Prothrombi
n
IIa
Dabigatran
Thrombin
Fibrinogen
Fibrin
Transformation
Catalysis
New Oral Anticoagulants for
Stroke Prevention in AF
Direct Inhibitors of Factor Xa
or Thrombin
Comparison of Features of New Oral
Anticoagulants in Advanced Stages of Development
Rivaroxaban
Apixaban
Dabigatran
Etexilate
Target
Xa
Xa
IIa
Molecular Weight
436
460
628
Prodrug
No
No
Yes
Bioavailability (%)
80
50
6
Time to peak (h)
3
3
2
Half-life (h)
9
9-14
12-17
Renal excretion
(%)
65
25
80
None
None
None
Features
Antidote
Prevention of Stroke in Patients with Chronic Kidney Disease (CKD) – Therapeutic
Choices
Therapeutic Choices in Patients with Chronic Kidney Disease and Stroke Risk Factors (CHADS2 ≥ 1)
GFR
Warfarin
Dabigatran
Rivaroxaban
Apixaban
GFR ≥ 60 mL/min
Dose adjusted for
INR 2.0-3.0
150 mg bid or
110 mg bid
20 mg daily
5 mg bid†
GFR 50-59
mL/min
Dose adjusted for
INR 2.0-3.0
150 mg bid or
110 mg bid
20 mg daily
5 mg bid†
GFR 30-49
mL/min
Dose adjusted for
INR 2.0-3.0
150 mg bid or
110 mg bid
15 mg daily
GFR 15-29
mL/min (not on
dialysis)
No RCT Data‡
No RCT Data§
No RCT Data¶
GFR < 15 mL/min
(on dialysis)
No RCT Data‡
No RCT Data¶
No RCT Data¶
5 mg bid
Consider 2.5 mg
bid†
5 mg bid (for GFR
> 25 mL/min only)
Consider 2.5 mg
bid†
No RCT Data
† Consider Apixaban 2.5 mg po bid if age ≥ 80 and body weight ≤ 60 kg.
‡ Dose adjusted warfarin has been used, but observational data regarding safety and efficacy is conflicting.
§ Modelling studies suggest that dabigatran 75 mg bid might be safe for patients with GFR 15-29 mL/min, but this has not been validated in a prospective cohort.
¶ No published studies support a dose for this level of renal function; product monographs suggest the drug is contraindicated for this level of renal function.
2
A guidelines based approach to AF
management
Days of withdrawal prior to high bleeding risk procedure
eGFR
ml/min/m2
apixaban
dabigatran
rivaroxaban
≥ 80
2-3
2-3
2-3
50 - 80
2-3
3
2-3
30 - 50
2-3
4
2-3
< 30*
2-3
5
2-3
2014 Focused Update CCS AF Guidelines Can J Cardiol (in press)
Percutaneous LAA Occlusion
The WATCHMAN® Device
Syed T, Halperin JL. Nature Clin Prac Cardiovasc Med 2007; 4:428
Holmes DR, et al. Lancet 2009; 374: 534
Rate vs Rhythm Control for Patients with Symptomatic
AF
SYMPTOMATIC AF
ATTEMPT RATE CONTROL
Beta-blocker
Calcium channel blocker
Special circumstances in
which to consider early
rhythm control:
Highly symptomatic
Multiple recurrences
Extreme impairment in QOL
Arrhythmia-induced
cardiomyopathy
YES
SYMPTOMS RESOLVE
NO
CONTINUE RATE
CONTROL
MODIFY RATE CONTROL - CONSIDER RHYTHM CONTROL
Paroxysmal AF
Low burden
recurrence
Pill in pocket
antiarrhythmic therapy
High burden recurrence
Maintenance
antiarrhythmic therapy
Catheter ablation
Persistent AF
Consider cardioversion
Symptoms
Symptoms
improve,
improve,
and patient
but AF recurs maintains sinus
rhythm
Symptoms
don’t change
in sinus
rhythm and
AF recurs
Observe. If AF
recurs, determine if symptomatic