Lecture 26-28 Atrial Fibrilation

Question 1

What is the general approach to managing Afib?

Answer 1

confirm diagnosis ⇒ stroke risk assessment ⇒ non-pharm options ⇒ pharm options: anticoagulation, rate and/or rhythm control ⇒ monitoring

Question 2

What is atrial fibrillation (AF), S&S?

Answer 2

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

Question 3

What is the pathophysiology/MOA of AF, how does it occur?

Answer 3

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

Question 4

Regarding risk fx for AF, what are conventional, emerging, and potential?

Answer 4

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

Question 5

What is non-pharm tx/recommendations for AF?

Answer 5

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

Question 6

What are some drugs that can induce AF

Answer 6

stimulants, alcohol, anti-cancer tx (Tyr-Kinase inhibitors, cyclophosphamide, doxorubicin), bisphosphonates

Question 7

How is AF diagnosed?

Answer 7

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

Question 8

What are possible screening mechanisms to detect/suspect AF?

Answer 8

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

Question 9

What are all the different classifications of AF?

Answer 9

Clinical Pattern: paroxysmal, persistent, ‘longstanding’ persistent, permanent

Structural: valvular, non-valvular

Pathophysiological: primary, secondary

Question 10

What are clinical pattern presentations/classifications of AF?

Answer 10

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

Question 11

What are structural presentations/classifications of AF?

Answer 11

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

Question 12

What are pathophysiological presentations/classifications of AF?

Answer 12

Primary: an established pathophysiological process (no precipitating cause)

Secondary: caused by a self-limited or acutely reversible precipitant (ex. sepsis, surgery, thyrotoxicosis)

Question 13

What are consequences of AF?

Answer 13

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

Question 14

What is atrial flutter (AFL)?

Answer 14

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

Question 15

What is the best way to determine whether an AF patient needs anticoagulation?

Answer 15

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)

Question 16

What is the CHADS2 risk score and the risk attributed to different scores?

Answer 16

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

Question 17

What is the CHA2DS2-VASc risk score and the risk attributed to different scores?

Answer 17

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%

Question 18

What is a CHADS-65 score used for?

Answer 18

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

Question 19

What is the HAS-BLED risk score and what is it used for?

Answer 19

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

Question 20

What are antithrombotic options for AF?

Answer 20

ASA, warfarin, ASA + clopidogrel, DOACs

Question 21

When ASA is used for tx of AF, what is the RRR for ischemic stroke, and rate of major bleeding?

Answer 21

19% RRR,, 1.1% major bleeding

Question 22

When warfarin is used for tx of AF, what is the target INR, RRR for all strokes, and rate of major bleeding?

Answer 22

target INR is 2-3

RRR for strokes = 64%

rate of major bleeding = 1.3%

Question 23

What is the study that compared ASA + clopidogrel against warfarin for AF tx (PICO as well)?

Answer 23

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

Question 24

What is the study that compared single antiplatelet vs dual antiplatelet tx for AF tx (PICO as well)?

Answer 24

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

Question 25

What is the study that compared dabigatran vs warfarin tx for AF (PICO, findings)?

Answer 25

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

Question 26

What is the study that compared rivaroxaban vs warfarin tx for AF (PICO, findings)?

Answer 26

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

Question 27

What is the study that compared apixaban vs warfarin tx for AF (PICO, findings)?

Answer 27

ARISTOTLE trial P: NVAF or AFL with CHADS2 >/= 1 I: apixaban 5 mg BID (2.5 mg BID used if >/= 2 of: >/= 80, weight /= 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

Question 28

What is the study that compared to edoxaban vs warfarin tx for AF (PICO, findings)?

Answer 28

ENGAGE AF-TIMI 48 trial P: NVAF with CHADS2 >/= 2 I: edoxaban 60 mg QD (30 mg if CrCl 30-50, weight

Question 29

When should DOACs be cautioned in AF tx?

Answer 29

caution when switching older/frail patients stable on VKA (warfarin), higher rate of events in people switching to DOACs rather than remaining on VKA

Question 30

When should we consider switching warfarin to a DOAC for AF tx?

Answer 30

mechanical valve replacement (RE-ALIGN, PROACT Xa) moderate-severe mitral stenosis (INVICTUS) antiphospholipid syndrome (TRAPS) left ventricular thrombus frail elderly pt (FRAIL-AF)

Question 31

What is the HR target for persistent or permanent AF?

Answer 31

resting HR less than 100 bpm

Question 32

What is the purpose of rate control meds in AF, why are they used?

Answer 32

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

Question 33

BBs for tx of AF (what do they do, which ones are preferred)

Answer 33

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

Question 34

Non-DHP CCBs for tx of AF

Answer 34

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

Question 35

Digoxin for tx of AF

Answer 35

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

Question 36

What is the Vaughan-Williams Classification System of antiarrhythmic drugs

Answer 36

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

Question 37

How are Class IC antiarrhythmic agents used in rhythm control in AF (drugs, MOA, dosing, safety/contra, PK)

Answer 37

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

Question 38

How are Class III antiarrhythmic agents used in rhythm control in AF (drugs, MOA, dosing, safety, PK, monitoring)

Answer 38

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

Question 39

What are some important principles guiding rate or rhythm control selection for AF?

Answer 39

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

Question 40

When should rhythm control be considered for an AF pt

Answer 40

within 1st year of AF, younger pt, arrhythmia-induced cardiomyopathy, frequent paroxysmal AD/difficult to rate control, pt preference

Question 41

What is the pill-in-pocket (PIP) approach in AF and when should it be used?

Answer 41

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

Question 42

Cardioversion for AF, when to use

Answer 42

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

Question 43

Catheter ablation for AF, when to use it

Answer 43

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

Question 44

What are the treatable risk factors of AF?

Answer 44

HEADTOES ⇒ HF, Exercise, Arterial HTN, DM, Tobacco, Obesity, Ethanol, Sleep