Lecture 26-28 Atrial Fibrilation Flashcards
What is the general approach to managing Afib?
confirm diagnosis ⇒ stroke risk assessment ⇒ non-pharm options ⇒ pharm options: anticoagulation, rate and/or rhythm control ⇒ monitoring
What is atrial fibrillation (AF), S&S?
supraventricular tachyarrhythmia characterized by irregular atrial activation
most common sustained cardiac arrhythmia, roughly 1 million Canadians have it
S&S: low energy, fatigue, SOB, pulse faster than normal, pre-syncope or syncopal event, diaphoretic, can be asymptomatic
What is the pathophysiology/MOA of AF, how does it occur?
SA node is heart’s natural pacemaker, AV node receives signal
P wave on ECG marks start of cardiac cycle
‘trigger’ of rapid atrial firing results in disorganized contractions and can supersede normal sinus rhythm, atrial rate upwards of 400-600 bpm, ventricular response dependent on AV node to serve as filter
ventricular filling is passive from venous return and atrial kick aids in additional blood volume
myocardial fibrosis develops within atrial tissue with AF
Regarding risk fx for AF, what are conventional, emerging, and potential?
Conventional: age, male sex, HTN, HFrEF, valvular heart disease, overt thyroid disease, obstructive sleep apnea
Emerging: obesity, excessive alcohol, pre-HTN and increased pulse pressure, COPD, HFpEF, congenital heart disease, subclinical hyperthyroidism, CAD, morphometric
Potential: FHx, tobacco, left atrial dilatation, LV hypertrophy, inflammation, DM, pericardial fat, subclinical atherosclerosis, CKD, excessive endurance exercise, ECG
What is non-pharm tx/recommendations for AF?
Alcohol and Tobacco: limit to </= 1 drink per day, complete abstinence of both is target
Sleep Apnea: CPAP for moderate-severe, regular assessment
Exercise: moderate >/= 30 min a day x 3-5 days per week, resistance exercise 2-3 days x week, flexibility at least 10 min per day x 2 days per week in those >65
Weight Loss: target >/= 10% loss to BMI <27
Diabetes: target A1c </= 7%
BP: target </= 130/80 at rest and </= 200/100 at peak exercise
What are some drugs that can induce AF
stimulants, alcohol, anti-cancer tx (Tyr-Kinase inhibitors, cyclophosphamide, doxorubicin), bisphosphonates
How is AF diagnosed?
by ECG, characterized by irregular rhythm
ECG findings include absence of P waves (atrial rate range: 300-700 bpm), irregular intervals and narrow QRS complex
Holter Monitoring: normal sinus rhythm can be predominant rhythm with brief bouts of AF, ability for >/= 24 hour continuous ECG monitoring
Implantable Loop Recorders: for pt with RARE sx, can record for up to 3 years, minimally invasive procedure
What are possible screening mechanisms to detect/suspect AF?
Pulse-Based: irregular pulse detected using manual palpation, time efficient, cost effective and easy to perform, Accuracy ⇒ sensitivity 84-97%, specificity 69-75%,, Apple Watch has also shown ability to detect irregular rhythms
ECG: transthoracic ECG (TTE) recommended in all pt, identify LA size, LV hypertrophy or dysfxn, valvular heart disease, possible LAA thrombus
CXR: can assess for acute infection or signs of HF
Blood Work: CBC, coagulation profile, electrolytes, renal, thyroid, liver fxn tests
What are all the different classifications of AF?
Clinical Pattern: paroxysmal, persistent, ‘longstanding’ persistent, permanent
Structural: valvular, non-valvular
Pathophysiological: primary, secondary
What are clinical pattern presentations/classifications of AF?
Paroxysmal: continuous AF episode lasting > 30 seconds but terminating within 7 days of onset
Persistent: continuous AF episode lasting > 7 days but terminating within 1 year of onset
‘Longstanding’ Persistent: continuous AF >/= 1 year for which rhythm control is being pursued
Permanent: continuous AF for which therapeutic decision has been made to not pursue rhythm restoration
What are structural presentations/classifications of AF?
Valvular: AF in presence of any mechanical heart valve or in presence of moderate to severe mitral stenosis
Non-Valvular: AF without a mechanical heart valve or moderate-severe mitral stenosis
What are pathophysiological presentations/classifications of AF?
Primary: an established pathophysiological process (no precipitating cause)
Secondary: caused by a self-limited or acutely reversible precipitant (ex. sepsis, surgery, thyrotoxicosis)
What are consequences of AF?
Thrombosis: multiple re-entry loops cause disorganized atrial activity, ineffective atrial contraction leads to stasis of blood, potential thrombosis in left atria or left atrial appendage
Ventricular Response: impulses from atria are irregular and reach AV node (gatekeeper) at various times, impulses that pass through AV node cause ventricles to contract irregularly ⇒ increased rate up to 120-180 bpm (normal 60-100), can produce tachycardia-induced cardiomyopathy
Loss of Atrial Kick: atrial kick is the additional volume of blood into the ventricles before ventricular systole, atria contract in very rapid and irregular rhythm impairing emptying of blood into ventricles, atrial kick can account for up to 20% of CO
What is atrial flutter (AFL)?
closely related to AF and can co-exist
characterized by rapid irregular rhythm in atria with a regular or irregular ventricular rhythm - ventricular rate around 150 bpm
managed similarly to AF but often persistent instead of paroxysmal
What is the best way to determine whether an AF patient needs anticoagulation?
A: Presence of ‘Valvular’ AF ⇒ AF in presence of a mechanical heart valve or moderate-severe mitral stenosis (rheumatic or non-rheumatic) ⇒ anticoagulation recommended
B: Calculating Stroke Risk with CHADS2 or CHA2DS2-VASc ⇒ anticoagulation recommended for patients with an annual thromboembolic risk >/= 2%
C: Bleeding Risk Assessment with HAS-BLED- estimates 1 year risk of major bleeding (requiring hospitalization, decrease in Hgb > 2g/dL or requiring blood transfusion) for pt on OAC ⇒ score >/= 3 indicates increased risk of bleeding
D: select drug tx for stroke prevention based on IESC (cost/convenience)
What is the CHADS2 risk score and the risk attributed to different scores?
used to determine AF annual risk and if a patient need anticoagulation
C: Congestive HF = 1 point
H: Hypertension = 1 point
A: Age >/= 75 = 1 point
D: Diabetes = 1 point
S: Prior Stroke or TIA = 2 points
Scores: each percentage represents annual thromboembolic risk
0 = 1.9%
1 = 2.8%
2 = 4.0%
3 = 5.9%
4 = 8.5%
5 = 12.5%
6 = 18.2%
any pt with score above 2% is indicated for anticoagulation
What is the CHA2DS2-VASc risk score and the risk attributed to different scores?
used to determine AF annual risk and if a patients needs anticoagulation
C: Congestive HF = 1 point
H: Hypertension = 1 point
A: Age >/= 75 = 2 points
D: Diabetes = 1 point
S: Prior stroke or TIA = 2 points
V = vascular disease = 1 point
A: age > 65 but < 75 = 1 point
Sc: Sex Criteria - Female = 1 point
Scores: 0 = 0%
1 = 1.3%
2 = 2.2%
3 = 3.2%
4 = 4.0%
5 = 6.7%
6 = 9.8%
7 = 9.6%
8 = 6.7%
9 = 15.2%
anticoagulation recommended for patients with a risk >/= 2%
What is a CHADS-65 score used for?
used for rapid ID of patients who require OAC ⇒ NOT a risk estimate
if pt >/= 65 years ⇒ yes for OAC
if <65 but has: prior stroke or TIA OR HTN OR HF OR DM ⇒ yes for OAC
if no to all previous: coronary or PAD? ⇒ if yes then antiplatelet tx
if no to all then no antithrombotic needed
for OAC a DOAC is preferred over warfarin
What is the HAS-BLED risk score and what is it used for?
it estimates 1 year risk of major bleeding (requiring hospitalization, decrease in Hgb > 2g/dL or requiring blood transfusion) for pt on OAC ⇒ score >/= 3 indicates increased risk of bleeding
H: HTN (SBP > 160) = 1 point
A: Abnormal renal fxn (Cr > 200 micromol/L) or liver fxn (cirrhosis, bilirubin >2x upper normal, or AST/ALT/ALP > 3x upper normal) = 1 point
S: Stroke Hx = 1 point
B: Bleeding (major) or tendency (prior GI bleed, PUD, prior cerebral hemorrhage) = 1 point
L: Labile INR (unstable INR, time in therapeutic range <60%)
E: age > 65 = 1 point,, D: Drugs (antiplatelet, NSAIDs, anti-inflammatory meds, steroids), alcohol or drug abuse = 1 point
What are antithrombotic options for AF?
ASA, warfarin, ASA + clopidogrel, DOACs
When ASA is used for tx of AF, what is the RRR for ischemic stroke, and rate of major bleeding?
19% RRR,, 1.1% major bleeding
When warfarin is used for tx of AF, what is the target INR, RRR for all strokes, and rate of major bleeding?
target INR is 2-3
RRR for strokes = 64%
rate of major bleeding = 1.3%
What is the study that compared ASA + clopidogrel against warfarin for AF tx (PICO as well)?
ACTIVE-W trial,, P: non-valvular AF with > 1+ risk fx (>75, HTN, previous stroke/TIA, VTE, LVEF <45%, PAD or 55-74 years old + DM or CAD)
I: ASA 75-100 mg + clopidogrel 75 mg QD
C: Warfarin (INR 2-3)
O: stroke, non-CNS systemic embolism, MI or CV death
Findings: stopped prematurely due to support for OAC tx, similar rate of major bleeding
What is the study that compared single antiplatelet vs dual antiplatelet tx for AF tx (PICO as well)?
ACTIVE-A trial,, P: non-valvular AF or >/= 2 episodes within 6 months and 1+ risk fx (>75, HTN, previous stroke/TIA, VTE, LVEF <45%, PAD or 55-74 years old + DM or CAD)
I: ASA 75-100 mg QD + Clopidogrel 75 mg QD,, C: ASA 75-100 mg QD + placebo
O: major vascular event (stroke, non-CNS embolism, MI or vascular death)
Findings: risk of major bleeding higher in DAPT group, with DAPT being slightly more effective
What is the study that compared dabigatran vs warfarin tx for AF (PICO, findings)?
RE-LY trial
P: non valvular AF with: CHADS2 >/= 1 or 64-74 years old + DM, HTN, or CAD
I: dabigatran 110 mg BID or 150 mg BID
C: warfarin (INR 2-3)
O: stroke or systemic embolism at around 2 years
Findings: Dabigatran 150 mg BID is SUPERIOR to warfarin for stroke/SE and similar rates of major bleeding, while Dabigatran 110 mg BID is SIMILAR to warfarin for stroke/SE but lower rates of hemorrhage
also dabigatran 150 mg BID had sig lower ICH but had sig higher rate of GI bleeds
both doses of dabigatran had higher rates of MI than warfarin
What is the study that compared rivaroxaban vs warfarin tx for AF (PICO, findings)?
ROCKET-AF trial,, P: NVAF with CHADS2 >/= 2
I: rivaroxaban 20 mg QD (15 mg if CrCl 30-49)
C: warfarin (INR 2-3)
O: stroke/SE at around 2 years
Findings: rivaroxaban is NON-INFERIOR to warfarin for stroke/SE and with similar rates of major bleeding
rivaroxaban had sig lower rates of ICH but sig higher rates of GI bleeds
What is the study that compared apixaban vs warfarin tx for AF (PICO, findings)?
ARISTOTLE trial
P: NVAF or AFL with CHADS2 >/= 1
I: apixaban 5 mg BID (2.5 mg BID used if >/= 2 of: >/= 80, weight </= 60 kg, SCr >/= 133)
C: warfarin (INR 2-3)
O: stroke/SE at around 1.8 years
Findings: apixaban is SUPERIOR to warfarin for stroke/SE and SIGNIFICANTLY lower rates of major bleeding,, apixaban had sig lower rates of ICH, and similar rates for GI bleed
What is the study that compared to edoxaban vs warfarin tx for AF (PICO, findings)?
ENGAGE AF-TIMI 48 trial
P: NVAF with CHADS2 >/= 2
I: edoxaban 60 mg QD (30 mg if CrCl 30-50, weight </= 60 kg, or concomitant verapamil or quinidine)
C: warfarin (INR 2-3)
O: stroke/SE over around 2.8 years
Findings: edoxaban 30 mg and 60 mg are NON-INFERIOR to warfarin for stroke/SE and LOWER rates of major bleeding ⇒ still had higher rate of GI bleeds
When should DOACs be cautioned in AF tx?
caution when switching older/frail patients stable on VKA (warfarin), higher rate of events in people switching to DOACs rather than remaining on VKA
When should we consider switching warfarin to a DOAC for AF tx?
mechanical valve replacement (RE-ALIGN, PROACT Xa)
moderate-severe mitral stenosis (INVICTUS)
antiphospholipid syndrome (TRAPS)
left ventricular thrombus
frail elderly pt (FRAIL-AF)
What is the HR target for persistent or permanent AF?
resting HR less than 100 bpm
What is the purpose of rate control meds in AF, why are they used?
AV node is gatekeeper and determines which impulses travel through to ventricles
these drugs have negative dromotropic effects ⇒ slow AV node conduction
ex. BBs, non-DHP CCBs, digoxin all prolong refractory period
BBs for tx of AF (what do they do, which ones are preferred)
first line option for rate control in AF and preferred option in CAB or HF
net effect is to slow the HR, decrease AV node conduction and increase AV node refractory period
Drugs: the preferred options are BPAL ⇒ bisoprolol, propranolol, atenolol, labetalol
Non-DHP CCBs for tx of AF
first line option for rate control in AF
inhibits IC Ca2+ influx and more selective to L-type Ca2+ channels in heart ⇒ results in negative inotropic, chronotropic, and dromotropic effects
AVOID in HFrEF given no mortality benefit and negative inotropic effects
ex. verapamil, diltiazem
Digoxin for tx of AF
second line option for rate control in AF
POSITIVE inotropic effects via inhibition of myocardial Na-K ATPase, NEGATIVE chronotropic (HR) and dromotropic (conduction) effects via vagal activity
DIG trial found reductions in HF hospitalization in HFrEF population ⇒ consider if concomitant HR (LVEF </= 40%)
can consider when inadequate rate control OR sx management OR unable to tolerate other first line options
What is the Vaughan-Williams Classification System of antiarrhythmic drugs
Class I: Na+ Channel Blockers ⇒ Class Ia - (PQD) procainamide, quinidine, disopyramide,, Class Ib - lidocaine, mexiletine
Class Ic - flecainide, propafenone
Class II: BBs ⇒ propranolol, metoprolol, etc
Class III: K+ Channel Blockers ⇒ amiodarone, sotalol, dronedarone, dofetilide
Class IV: CCBs ⇒ diltiazem, verapamil
How are Class IC antiarrhythmic agents used in rhythm control in AF (drugs, MOA, dosing, safety/contra, PK)
Drugs: flecainide, propafenone
MOA: block Na+ channels in SA node to slow cardiac conduction
Dosing: Flecainide - 50-75 mg BID up to 150 mg BID
Propafenone - 150-300 mg TID
Safety: AVOID IN PT WITH HX OF MI WITH NON-NORMAL EF and OBSTRUCTIVE CAD, proarrhythmic effects or conduction disturbances, may prolong QTc
PK: Flecainide - great bioavailability, long t1/2 20 hrs and large Vd, metabolized by 2D6, concomitant use with BBs
Propafenone - variable bioavailability (<50%), t1/2 10 hrs, metabolized by 2D6, concomitant use with BBs
How are Class III antiarrhythmic agents used in rhythm control in AF (drugs, MOA, dosing, safety, PK, monitoring)
Drugs: amiodarone (may also be sotalol, dronedarone)
MOA: blocks K+ channels to prolong refractory period
Dosing: initial = varied dose loading, maintenance = 100-400 mg PO QD based on arrhythmia
Safety: pulmonary, hepatic, thyroid (hypo and hyper), ophthalmic toxicities
GI disturbances, can prolong QT but rarely causes TdP
PK: poor bioavailability and slow oral absorption, larger Vd and long t1/2 up to 3 months, available as IV and PO, inhibits CYP3A4 and others
Monitoring: baseline then Q3-6M thyroid fxn tests, baseline LFTs then Q6M, baseline then yearly ECG, annual eye exam, baseline CXR
What are some important principles guiding rate or rhythm control selection for AF?
safety of AADs: only associated with beneficial effect when started in pt with recent onset AF (< 1 year)
AADs associated with many AEs and selection is driven by safety and tolerability
Efficacy of AAD: long-term AAD may not completely suppress AF (ex. pt may still have sx and would continue to have risk of stroke), pt on both AAD and rate control need to receive anti-thrombotic tx stroke prevention tx
When should rhythm control be considered for an AF pt
within 1st year of AF, younger pt, arrhythmia-induced cardiomyopathy, frequent paroxysmal AD/difficult to rate control, pt preference
What is the pill-in-pocket (PIP) approach in AF and when should it be used?
it is a strategy to reduce ED visits/hospitalizations and minimize pill burden, first dose must be taken in a monitored setting
propafenone 600 mg (450 if <70 kg) or flecainide 300 mg (200 mg if <70 kg) - similar success rates, rapid acting agents
recommended to receive a BB or non-DHP CCB 30 minutes prior,, success defined as conversion to NSR within 6 hours without observable ADRs,,, When: infrequent episodes of AF, symptomatic and can recognize S&S, favourable anatomy, able to present to ED for 1st time
Cardioversion for AF, when to use
is a rhythm control tx, it carries a risk of thromboembolic complications due to possible embolization of pre-existing thrombus
can also promote new thrombus formation due to transient atrial dysfxn (‘stunning’)
90% initial success rate,, When: onset of AF <48 hours and anticoagulation is started
Catheter ablation for AF, when to use it
minimally invasive procedure using catheter tips to ‘do this’ to tissue
pulmonary vein isolation is most frequent target
> 70% success for paroxysmal AF
complications include hematuria, groin pain, pseudoaneurysm
anticoagulation recommended for 2-3 months after this then re-assessed with CHADS scoring
may require short-term antiarrhythmic tx (ex. 3 months)
When: symptomatic paroxysmal AF whose rhythm control is desired, antiarrhythmic drugs ineffective or contraindicated, HFrEF, AFL
What are the treatable risk factors of AF?
HEADTOES ⇒ HF, Exercise, Arterial HTN, DM, Tobacco, Obesity, Ethanol, Sleep
