Rate, Rhythm…

CJ Michaud, PharmD, BCCCP, BCPS

Clinical Pharmacist, Cardiothoracic Critical Care

Spectrum Health

Mark Colton, MSM, PA-C

Cardiac Electrophysiology

Director of APP Services, Cardiovascular Health

Spectrum Health

or Good Riddance

Atrial Fibrillation

Course Speaker Disclosure Information

CJ Michaud

Disclosures

None

Mark Colton

Disclosures

None

JAMA 2001; Circulation 2006

Atrial Fibrillation Increases with Age

Sample Case: Debbie• Debbie is a 67 year old F with PMH

of HTN who presents to PCP with several weeks of intermittent fatigue, palpitations and dyspnea on exertion. She shows you her apple watch…

Downer aka Rachel Dratch

Follow up ZIO monitor

confirms PAF

Audience Question - DebbieA 67yr old female with paroxysmal atrial fibrillation. She

suffers one episode a week lasting up to an hour. She

takes lisinopril for hypertension but otherwise very

healthy without any other medical history and takes no

other medications. What anticoagulant do you

recommend?(A) No changes

(B) Aspirin 81mg daily

(C) Aspirin 325mg daily

(D) Aspirin 81mg + Plavix 75mg daily

(E) Warfarin or Direct oral anticoagulant

Heart Rhythm 2015;12:e105–e113

151 General practitioners202 Cardiologists101 Electrophysiologists53 Neurologists

Debbie’s Initial AF Evaluation

1) Assess CHA2DS2-VASc and initiate anticoagulation to reduce CVA risk

2) Add rate control agent

3) Baseline Labs (CBC, CMP, Mg, TSH)

4) Refer to Cardiology/EP

∆

Assessing Anticoagulation Need

Annual Stroke Risk

0 points 1.9%

1 point 2.8%

2 points 4.0%

3 points 5.9%

4 points 8.5%

5 points 12.5%

6 points 18.2%

CHA2DS2-VASc• Oral anticoagulation recommended

if one or more non-sex risk factors• ≥ 1 for men• ≥ 2 for women

HAS-BLED• Score of ≥ 3 is considered high risk• Does not mean stopping OAC• Requires regular clinician review and

focused effort to reduce modifiable risk factors.

January CT, et al. J Am Coll Cardiol. 2019.

Anticoagulation to Prevent Stroke

• Trials that included bioprosthetic valves• ARISTOTLE (apixaban) n = 41

• ENGAGE AF-TIMI 48 (edoxaban) n = 191

Similar efficacy and safety outcomes versus warfarin

January CT, et al. 2019 AHA/ACC/HRS Focused Update. J Am Coll Cardiol. 2019.

Class I

- Antithrombotic therapy should be individualized based on shared

decision-making after discussion with patient.

- Calculate CHA2DS2-VASc score on all patients

- For men with a CHA2DS2-VASc score ≥ 2 and women with a

CHA2DS2-VASc score ≥ 3, oral anticoagulation is recommended**

- Direct oral anticoagulants are recommended over warfarin**

Lip GY, et al. Chest. 2018

Rate Control

• RACE II Trial: What is optimal heart rate? Strict (< 80 bpm) or lenient (<110 bpm)?

• N = 614; open-label randomization; treatment regimen per physician

• Primary endpoint• Composite of death from CV cause, HF hospitalization, stroke, systemic

embolism, bleeding, and life-threatening arrhythmic event.

Van Gelder IC, et al. NEJM 2010; 362: 1363-1373

Rate Control Agents

Images from: https://www.theafibclinic.com/atrial-fibrillation/what-is-atrial-fibrillation-afib/

So what is an AV Nodal Blocker?

Delays conduction through the AV node

- Increased refractoriness in phase 4- Reduces ventricular rate

Occasional unintended consequences:• AV Block• Bradycardia• Prolonged PR interval

Rate Control of Atrial Fibrillation

Beta Blockers

• Acute• Metoprolol: 2.5 – 10mg IVPush over 1-2 min; repeat q5min. Max 15mg

• Esmolol: 0.5mg/kg IVPush over 1 min; 50mcg/kg/min IV infusion; Max 200mcg/kg/min

• Propranolol: 1mg IVPush over 1 minute.

• Chronic• As rate controllers, beta blockers are accepted to have similar efficacy

• Systolic dysfunction, low EF, LV hypertrophy → metoprolol, carvedilol

• Pulmonary disease: avoid nonselectives (propranolol, carvedilol, labetalol, etc.)

• Contraindications?

Kotecha D, et al. BMJ Open 2017; 7e:015099

Calcium Channel Blockers• NON-dihydropyridines

• Diltiazem: 0.25mg/kg IVPush over 2 min; continuous infusion 5-15mg/hr.• PO: 30mg q6h starting dose; max 360-480 mg/day.

• Verapamil: IV form rarely indicated over diltiazem (0.15mg/kg bolus)

• PO: 40mg q8h starting dose; max 360 mg/day.

• Bind and inhibit L-type Ca2+ channels in myocytes and nodal tissue1) reduce firing rate of aberrant pacemaker cells2) AV nodal blocker – reduces conduction velocity, prolongs repolarization

• Contraindications: NYHF III or IV, hypotension• AEs (beyond cardiac): Headache, constipation

Kotecha D, et al. BMJ Open 2017; 7e:015099

Digoxin• Reduces HR through vagal inhibition of AV node.

• Not ideal to combat exercise-induced tachyarrhythmia

• Places in therapy• BB and/or CCB not achieving adequate rate control• Can’t use BB or CCB d/t ADHF or hypotension• HF symptoms where (+) inotropy is also desired

• IV Load: 0.25-0.5mg over 2-3 minutes, repeat q6h; max 1.5mg/24hr.

• PO Maintenance: 0.125 – 0.25mg daily

• T1/2: 36-48h in adults; 3-5 days if anuric!• Reduce regimens by about 50% during significant AKI

Kotecha D, et al. BMJ Open 2017; 7e:015099

Digoxin (and death)

• Large studies have been split on the mortality impact of chronic use

• Independently associated with higher mortality, regardless of HF

• Risk of desk independently related to serum concentration• Trough ≥ 1.2ng/mL: Hazard ratio increased 56% compared to non-digoxin users

Lopes RD, et al. J Am Coll Cardiol.2018; 71(10): 1063-74

Digoxin (and death)

37 trials through March, 2018

N = 825,061

Vamos M, et al. Am J. Cardiol 2019; 123(1): 69-74

Class IIa- Goal resting HR < 80bpm is reasonable for symptomatic AF

Class IIb- Goal resting HR < 110bpm for asymptomatic AF if LV

function remains normal

Class I- Control the ventricular rate using beta blockers or calcium

channel blockers

Lip GY, et al. Chest. 2018

∆

Update: Debbie

• CHA2Ds2-VASc of 3• Started on apixaban 5mg BID

• ZIO w/ 37% burden of AF with rates up to 154bpm. • Started on metoprolol succinate

50mg BID

• Baseline labs unremarkable

Atrial Fibrillation Clinic

• Complete history and physical examination

• Cardiac imaging and ischemic workup when appropriate• Transthoracic echocardiogram at minimum

• CBC, serum electrolytes, renal function, TSH• Troponin if ischemia is suspected

• Obstructive Sleep Apnea screening• STOP-BANG score to assess need for sleep study

Atrial Fibrillation Clinic• Evidence/Guideline based

protocols for comprehensive evaluation and management of atrial fibrillation

• Early access – 72hrs or less

• Standardized consistent treatment approach• Rate vs Rhythm

• Anticoagulation

• Risk factor investigation

Circulation. 2017;136:583–596

Modifiable AF Risk Factors

Circulation. 2017;136:583–596

Class I- For overweight and obese patients with AF, weight loss, combined

with risk factor modification, is recommended

Update: Debbie

• Stress echocardiogram normal

• Sleep Study normal

• TSH normal

• Initiated on flecainide 100mg BID in addition to current apixaban and metoprolol.

∆

1) Chemical cardioversion to sinus rhythm

2) Maintain sinus rhythm after electrical cardioversion

3) Reduce arrhythmia burden (frequency and duration of AF) and associated hospitalizations

Antiarrhythmic Drugs (AADs) can be used in three ways:

Average success rate ~50% in the first 90 minutes after drug administration.Less effective for AF duration > 7 days

Risk of recurrent AF after electrical cardioversion: 71-84% at 1 yearReduced to 30-50% when AAD is used.

Ming L, et al. Circulation. 2018; 138:1879-1896

Flecainide

Propafenone Amiodarone

Dronedarone

Sotalol

Verapamil

Diltiazem

Propranolol

Metoprolol

Dofetilide

Ibutilide

1C AADs: Flecainide and Propafenone

• Slow conduction velocity; reduce spontaneous automaticity

• WHO: those with no or minimal other heart disease• No structural heart disease

• These are (-) inotropes → no systolic dysfunction or ischemic disease

• Generally well tolerated• Flecainide: mild neuro AEs (tremor, headache)

• Propafenone: GI (nausea), QT prolongation (up to 25%)

Propafenone undergoes hepatic metabolism (CYP2D6), renal clearance, and is prone to drug interactions. - 2 major metabolites = ↑ BB/CCB activity

Ming L, et al. Circulation. 2018; 138:1879-1896

Class III AADsMedication

Na-ChannelBlockade?

K-ChannelBlockade?

Ca-ChannelBlockade?

BetaBlockade?

Alpha-Blockade?

Amiodarone X X X X X

Dronedarone X X X X X

Sotalol X X

Ibutilide X X

Dofetilide X

SotalolPrevents recurrence

100% renal clearance – caution!Increase QT

× LV hypertrophy, HF

+ CAD, acute MI

DofetilideNo negative inotropy

Used as chemical cardioverter ANDprevents recurrence

Renal clearanceIncrease QT

Inpatient EKG required to initiate (Tdp in 3.3%, most in 1st 3 days)

+ CAD, acute MI

+ Useful in these conditions × Avoid in these conditions

AmiodaroneMost effective at preventing recurrence

Very lipophilic → many AEsLung toxicity is cumulative dose related

++ Drug interactionsIncrease QT

+ CAD, acute MI, LV hypertrophy

IbutilideChemical cardioverter

Converts ~50% to normal sinus rhythmin about 30 min.

DronedaroneAMIO WITHOUT THE IODINEMuch fewer extracardiac AEs

No warfarin interaction!

× ADHF, reduced EF, HF

+ Young, no HF, need to avoid

amio toxicities

How to Choose?

Ming L, et al. Circulation. 2018; 138:1879-1896Gheorghe-Andrei D, et al. Europace. 20118; 20:731-732

Antiarrhythmic Drugs Have Modest Efficacy∆

• Recurrent Palpitations

• Repeat ZIO reveals paroxysmal atrial fibrillation with a 27% burden despite flecainide

• Next Steps?• Increase Flecainide

• Alternative AAD

• Abandon Rhythm control

• Pulmonary Vein Isolation

Update: Debbie

Pulmonary Vein Isolation is the Foundation of AF Ablation

N Engl J Med 1998;339:659-66

69 Foci Triggering AF in 45 Patients

Cryoballoon Pulmonary Vein Isolation

Voltage maps in Pulmonary Vein Isolation

Debbie AF Burden Following Cryo PVI

CRYO

Debbie, now 77, presents to the ED with intrascapular back pain. She has dynamic EKG changes and is taken for coronary angiography.

Audience Question72 yo F with known paroxysmal atrial fibrillation on apixaban presents with IWSTEMI and receives PCI to RCA. What is the best choice for anticoagulation at this time?

∆

(A) DOAC and aspirin 325mg

(B) DOAC and aspirin 81mg

(C) DOAC, aspirin 81mg and clopidogrel 75mg QD

(D) DOAC and clopidogrel 75mg QD

(E) Warfarin and clopidogrel 75mg QD

Dual vs. Triple Therapy

• AF patients who suffer acute coronary syndrome and require stenting are indicated for DAPT and oral anticoagulation (OAC).

Bleeding

Risk

Stent Thrombosis

AF Thrombosis

Future MACE

• European, ACCP, AHA/ACC/HRS guideline agreements:

• CHA2Ds2-VASc and HAS-BLED should be utilized

• Triple therapy significantly increases bleeding risk

• Duration of triple therapy should be minimized, disagree on duration target

• Clopidogrel should be P2Y12 inhibitor of choice in dual and triple therapy!

• DOACs (esp apixaban) may be preferable to warfarin

• For most patients, aspirin should be discontinued at discharge• High thrombosis-/ low bleeding-risk patients could continue for 1 month

Lip GY, et al. Chest. 2018January CT, et al. J Am Coll Cardiol. 2019

∆

Update: Debbie

• Debbie is discharged on apixaban 5mg BID and clopidogrel 75mg daily.

• Current medications:• Apixaban

• Clopidogrel

• Metoprolol Succinate

• Pantoprazole

• 8 months later, Debbie presents with fatigue, dyspnea on exertion, and melena.

• CBC reveals hemoglobin of 8 (baseline 12)

• Endoscopy reveals diffuse gastric AVMs. GI recommends against anticoagulation

LA Appendage Occlusion is Non-Inferior to Warfarin

Unable to titrate AVN agents

CKD rules out Sotalol/Tikosyn

Age prohibits repeat PVI

Amiodarone? AVN Ablation?

• Debbie (now 87) facetimes into your virtual EP clinic. She transmits her Apple Watch data which reveals 100% AF burden with average rates of 118bpm. BP marginal and she has CKDIII. Next steps?

Good Riddance – AV Node Ablation is a Last Resort

Class III

- AV node ablation should not be performed without a

pharmacologic trial to achieve ventricular rate control.

(Level of Evidence: C)

N Engl J Med 2010;362:1363-73

Debbie’s Journey Continues – Ours Ends…

• CHA2Ds2-VASc of 5• Watchman in place

• Coronary Artery Disease• PCI to RCA

• Permanent Atrial Fibrillation• AVN ablation with leadless pacemaker implantation

• Medications• Asa 81, BB, Statin