THERAPEUTICS EX3 L(?) (ATRIAL FIBRILLATION) (MIRANDA)

Describe a supraventricular arrhythmia

Originates from ABOVE the bundle of His

Types of supraventricular arrhythmias? (four)

1. Afib

2. Aflutter

3. Paroxysmal supraventricular tachycardia

4. Autonomic atrial tachycardia

Describe a ventricular arrhythmia

Originates from BELOW the bundle of His

Types of ventricular arrhythmias? (three)

1. Premature ventricular complexes

2. Ventricular tachycardia

3. Ventricular fibrillation

Define atrial fibrillation

A supraventricular arrhythmia with uncoordinated atrial activation and consequently ineffective atrial contraction

Afib is defined by what kind of heartrate? Bpm?

Chaotic, rapid (300-500 bpm); irregular atrial rhythm

Conditions which predispose a person to Afib?

Advanced age

Smoking

Physical activity

Alcohol

Obesity

Height

Blood pressure (HTN)

Resting heart rate

Diabetes

Cardiovascular conditions which predispose a person to Afib?

HF

CAD

VHD

Cardiac surgery

Acute cases which can precipitate Afib?

Thyrotoxicosis

Surgery

Alcohol withdrawal

Sepsis

Excessive physical exertion

T/F: Afib is a progressive disease.

True

Describe AF Stage 2

Evidence of structural or electrical findings further predisposing a patient to AF

(atrial enlargement, frequent atrial ectopy)

Describe AF Stage 3

Has diagnosed AF

Paroxysmal, persistent, long-standing persistent, or successful AF ablation

Describe AF Stage 4

Permanent AF

Testing used to diagnose AF?

12-lead ECG (gold standard)

Holter/event monitor (paroxysmal)

Afib graph looks like what?

Extra spiky

Aflutter graph looks like what?

More squiggly in the middle

What are the FDA-cleared Direct to Consumer monitor types? (four)

Apple Watch

Fitbit sense

Samsung Galaxy Watch 3

Withings ScanWatch

Clinical characteristics of AF?

Palpitations, exertional fatigue, lightheadedness, exercise intolerance, dyspnea

Syncope is possible but uncommon

What are the 4As of AF management?

Access to All Aspects of Care for All

What does SOS stand for in AF management?

Stroke risk

Optimize (modifiable risk factors)

Symptom management

What does HEAD 2 TOES stand for in AF management?

Heart failure, exercise, arterial hypertension, diabetes, tobacco, obesity, ethanol, sleep

These are the most common/pertinent risk factors for AF

Primary prevention recommendations (LRFM) for management of AF?

Patients at increased risk of AF should receive comprehensive guideline-directed LRFM for AF, targeting obesity, physical inactivity, unhealthy alcohol consumption, smoking, diabetes, and hypertension.

What is the recommended percentage weight loss for secondary prevention in AF management?

Target of 10%

What is the recommended weekly physical fitness guideline for secondary prevention in AF management?

210 minutes/wk

Which risk score assessment do we prefer for assessing AF risk?

CHADS-VASc

T/F: For stroke management in Afib, we prefer DOACs over warfarin.

True

DOACs include? (four)

Apixaban

Dabigatran

Edoxaban

Rivaroxaban

T/F: ASA alone or with clopidogrel is an acceptable alternative to DOAC or warfarin in stroke management of AF.

False; only in the presence of another indication

Dosing for apixaban in Afib? Include adjusted dosing and why?

5 mg PO BID

2.5 mg PO BID if patient has any 2 of the following:

Age 80+

Body weight < or equal to 60

SCr > or equal to 1.5

Dabigatran (Pradaxa) dosing in Afib?

150 mg PO BID

Dabigatran (Pradaxa) dosing in Afib patients that have a CrCl of 15-30 mL/min?

75 mg PO BID

Contraindications associated with dabigatran?

Hypersensitivity, active pathological bleeding, mechanical heart valves

Edoxaban dosing in Afib?

60 mg PO daily

Edoxaban dosing in Afib for patients with a CrCl of 15-50 mL/min?

30 mg PO daily

Rivaroxaban dosing in Afib?

20 mg PO daily

With biggest meal

Rivaroxaban dosing in Afib for patients who have a CrCl of 15-50 mL/min?

15 mg PO daily

With biggest meal

What drug is responsible for the reversal of dabigatran?

Idarucizumab

What drug is responsible for the reversal of apixaban, rivaroxaban?

Andexanet alfa (Andexxa)

What drug is responsible for the reversal of acute major bleeding in patients receiving VKAs?

4-Factor PCC (Kcentra)

What drug is responsible for control and prevention of bleeding episodes, and is sometimes use off-label to reverse dabigatran-associated life-threatening bleeds?

Activated PCC

T/F: Most patients will need therapies to control HR, revert to SR, or maintain SR to limit symptoms or improve outcomes; most of these patients require a combination approach.

True

T/F: In older patients, we prefer rate control.

True

What are the three criteria we look for to determine that we prefer rate control over rhythm control?

If a patient is:

Older

Has a longer history of AF

Has fewer symptoms

We prefer rate control

What are the three criteria we look for to determine that we prefer rhythm control over rate control?

If a patient is:

Younger

Has a shorter history of AF

Has more symptoms

We prefer rhythm control

What is our goal HR in Afib patients without HF?

Less than 100-110 bpm

T/F: Non-DHP CCBs should be avoided in HFrEF.

True

Antiarrhythmic medications for rhythm control? (five)

Dofetilide

Donedarone

Flecainide

Propafenone

Sotalol

Non-pharm rhythm control options?

Cardioversion

Catheter ablation

Key features of pharmacological cardioversion?

Success rate varies with agent and duration of AF

No need for general anesthesia

Concerns with side effects/toxicity of AAD

Key features of direct current cardioversion (DCC)?

Associated with higher success rates

Treatment of choice for hemodynamic instability

Need for general anesthesia

T/F: Patients that undergo cardioversion need to be anticoagulated with UFH or LMWH.

True

When is pharmacological cardioversion a reasonable alternative?

For those who are hemodynamically stable, pharmacological cardioversion is a reasonable alternative to electrical cardioversion.

Pharmacological agents used for cardioversion? (four)

Ibutilide (if LVEF > or equal to 40%)

Amiodarone IV (longer to convert)

Flecainide, propafenone

Alternative: IV procainamide

When do we consider maintenance of sinus rhythm?

Reasonable for long-term therapy in those who are not candidates or decline catheter ablation, or prefer antiarrhythmics.

Pharmacological agents used for maintenance of sinus rhythm? (four)

Dofetilide, amiodarone (if LVEF < or equal to 40%)

Flecainide, propafenone (no previous MI, structural heart disease, ventricular scar or fibrosis)

Dronedarone

Alternative: Sotalol

Class Ia antiarrhythmics include? (three)

Disopyramine

Procainamide

Quinidine

Class Ib antiarrhythmics include? (two)

Lidocaine

Mexelitine

Class Ic antiarrhythmics include? (two)

Flecainide, propafenone

Class II antiarrhythmics include? (three)

Beta blockers

Metoprolol

Esmolol

Labetalol

Class III antiarrhythmics include? (five)

Amiodarone

Dronedarone

Dofetilide

Sotalol

Labetalol

Class IV antiarrhythmics include? (two)

CCBs

Verapamil

Diltiazem

T/F: Amiodarone has class I, II, III, and IV effects.

True

Side effects associated with amiodarone?

Photosensitivity

Blue-gray skin discoloration

Hypothyroidism

Elevation of 2x or greater in UNL

Tremors, ataxia, peripheral neuropathy, insomnia

Corneal micro deposits

Optic neuropathy

Indication of dofetilide?

Maintenance of NSR in patients with highly symptomatic AF

Dosing for dofetilide?

500 mcg po BID

Renally adjusted dosing for dofetilide in patients with CrCl 40-60 mL/min?

250 mcg po BID

Renally adjusted dosing for dofetilide in patients with a CrCl < 40 mL/min?

125 mcg BID

T/F: Dofetilide is contraindicated in patients with a CrCl of less than 20 mL/min.

True

Contraindications associated with dofetilide?

Congenital or acquired long QT syndrome, concurrent use with verapamil, cimetidine, HCTZ, trimethoprim, itraconazole, ketoconazole, prochlorperazine, megestrol

Adverse effects associated with dofetilide?

HA, dizziness, syncope, insomnia, QT prolongation

T/F: Prior to administration of dofetilide, previous AAD should be held for at least 3 half-lives.

True

T/F: During its initiation phase, dofetilide can potentially increase the risk of TdP.

True

Dronedarone (Multaq) dosing?

400 mg PO BID

US boxed warning for Multaq says what?

Increased risk of death, stroke, and HF

T/F: Multaq is used in the treatment of AF in patients with NYHA class III and/or IV, or patients who have had an episode of decompensated HF in the past 4 weeks.

False; explicitly not used for these.

Adverse effects associated with Multaq?

Abdominal pain

Bradycardia

N/V/D

QT prolongation

TdP

T/F: Multaq is hepatotoxic.

True

Dronedarone vs. Amiodarone: Approved Uses

Dronedarone is approved for the treatment of paroxysmal or persistent AFib or AFlu (not permanent)

It is not for ventricular arrhythmias

Amiodarone is approved for the treatment of supraventricular and ventricular tachyarrhythmias (VF, VT, AF, AFlu)

Dronedarone vs. Amiodarone: Half-life

The half-life of dronedarone is 15 hours.

The half-life of amiodarone is 40-100 days.

Ibutilide (Corvert) IV dosing

Cardioversion only

< 60 kg: 0.01 mg/kg over 10 min

> or equal to 60 kg: 1 mg over 10 min

Adverse effects associated with ibutilide (Corvert)

Nonsustained VT, QT prolongation, TdP

For how long after administration of Ibutilide (Corvert) should ECG monitoring be done?

At least 4 hours, or until QTc has returned to baseline

Treatment for Torsades de Pointes includes? (four)

1. Magnesium sulfate 1-2g IV over 1-2 min

2. Beta-blockers (long-term treatment)

3. Permanent pacing

4. Implantable cardioverter-defibrillator

Adverse effects associated with propafenone?

AFlu, bradycardia, dizziness, dyspnea, HF exacerbation, taste disturbances, VT, visual disturbances

Cardioversion dosing for propafenone?

> or equal to 70 kg, 600 mg x 1

< 70 kg, 450 mg x 1

Maintenance dosing for propafenone?

150 - 300 mg PO q8h

ER 225 - 425 mg PO q12h

Adverse effects associated with flecainide?

AFlu, AV block, dizziness, dyspnea, HF exacerbation, HA, QT prolongation, VT, visual disturbances

Antiarrhythmic drugs that prolong QT?

Class I (especially Class Ia and III??)

Antibiotics that prolong QT?

quinolones and macrolides

Azole antifungals that prolong QT?

Fluconazole, ketoconazole, itraconazole, voriconazole

Antidepressants that prolong QT?

TCAs, SSRIs, SNRIs, mirtazapine, trazodone

Antiemetic agents that prolong QT?

5-HT3 receptor antagonists

Droperidol

Phenothiazines

Antipsychotics that prolong QT?

Most of them I think

In hospital initiation of dofetilide requires patients do be in the hospital how long?

At least 3 days; must remain in hospital at least 12 hours after conversion (~5 doses)

What lab values do we monitor for dofetilide?

Mg

K

SCr

Guidelines for who should not receive dronedarone?

NYHA class III or IV, or in patients who have had an episode of decompensated HF in the past 4 wks

Adverse effects associated with dronedarone?

GI upset, bradycardia, inc. SCr, QTc prolongation

T/F: Ibutilide (Corvert) is only administered IV for cardioversion.

True

Adverse effects associated with ibutilide?

Non-sustained VT, QT prolongation, TdP

For how long must patients be in the hospital to be administered sotalol?

At least 3 days