Author: Courtney Cassella, MD (EM Resident Physician, Icahn School of Medicine at Mount Sinai) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Definitions

AF – Atrial fibrillation

Paroxysmal – Terminates spontaneously or with intervention within 7d

Persistent – Continuous >7d

Long-standing persistent – >12mo

Permanent – Persistent for which cardioversion has failed or has not been attempted

Nonvalvular – AF in absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair

BB – β-blocker

CCB – Nondihydropyridine Calcium Channel Blocker

Etiology/triggers

When a patient presents in new onset or rapid AF, a priority should be to identify and treat underlying disease or precipitating factors. The PIRATES mnemonic is a helpful reminder although it is not complete.

=>PIRATES mnemonic

Pulmonary disease (COPD, PE)

Ischemia (ACS)

Rheumatic heart disease (mitral stenosis)

Anemia (high output failure/tachycardia)/Atrial Myxoma

Thyrotoxicosis

Ethanol/Endocarditis

Sepsis/Sick Sinus Syndrome

=>Causes not included in the mnemonic:

Electrolyte abnormalities

Congestive heart failure

Medications/Drugs

Myocarditis/Pericarditis

High sympathetic tone states: sepsis, post-operative, hypovolemia

Acute Management

=>Rate versus Rhythm Control

The RACE1, 2 and AFFIRM3 studies demonstrate rhythm-control has no survival benefit over rate-control. It is prudent to purse rate control in the acute setting since it is contraindicated to cardiovert stable patients with AF >48 hours or unknown duration without anticoagulation. Therefore, for stable patients without pre-excitation, intravenous BB or CCB are recommended to slow rapid AF.4-12

=>β-Blocker (BB) versus Nondihydropyridine Calcium Channel Blocker (CCB)

Between a BB and CCB, which is the best medication? The decision often encompasses multiple factors including contraindications, physician comfort, home medications, pharmacodynamics, etc.

In regards to home medications, it may benefit patients to continue the same class of home medication. Mixing BB and CCB, although sometimes necessary for rate control, may act synergistically potentiating AV nodal blockade, bradycardia, and hypotension.13-15

β-Adrenergic Antagonist 16 β 1 (80% cardiac β receptors) receptor stimulation Increases inotropy and chronotropy β 2 receptor stimulation Increases inotropy, relaxation, and chronotropy Mediates bronchodilation Decreases systemic vascular resistance Mechanism: Blocks β -adrenergic stimulation β 1 selective antagonist – decrease inotropy and chronotropy Esmolol Shortest half life (T 1/2 8 minutes) No oral formulation Adverse reactions: dose dependent hypotension that resolves after 30 minutes of discontinuation 5 , 8 Metoprolol T 1/2 3-4 hours Oral formulation both short and long acting Atenolol T 1/2 5-9 hours Oral formulation Carvedilol Additional: Acebutolol, Betaxolol, Bisoprolol, Celiprolol, Nebivolol Contraindications : Active wheeze in reactive airway disease (asthma, COPD) – Although β 1-blockers are cardioselective, studies demonstrate they decrease FEV 1 and PEFR. Therefore BB should be used with caution in severe or active reactive airway disease. 17 , 18 Known II or III degree AV block – BB or CCB may cause II or III degree AV block in 15% of patients. 15



Non-dihydropyridine Calcium Channel Blocker 19 4 classes of CCBs, but nondihydropyridines have the greatest affinity for myocardial calcium channels Mechanism: Impedes calcium influx and channel recovery in the myocardium Inhibitory effect on SA and AV nodal tissue Nondihydropyridines Diltiazem Verapamil More potent negative inotrope > more profound side effect of hypotension 8 Contraindications : Decompensated heart failure as CCBs may lead to further hemodynamic compromise 4 , 20 , 21 (for more continue below) Known II or III degree AV block – BB or CCB may cause II or III degree AV block in 15% of patients. 15



Metoprolol and diltiazem are the most commonly used BB and CCBs given their oral formulation and relative hemodynamic stability. There are two prospective studies directly comparing metoprolol and diltiazem. Fromm et al found diltiazem may provide superior rate control compared to metoprolol with no adverse events noted (no episodes of hypotension or bradycardia).12 It is important to note the inclusion/exclusion criteria of the studies.

Inclusion: ventricular rate ≥120 bpm, SBP ≥90 mmHg

Exclusion: SBP <90mmHg, ventricular rate ≥220 bpm, QRS >0.100s, 2nd or 3rd AV block, STEMI, NYHA Class IV HF, active wheezing with history of asthma/COPD, anemia (hemoglobin <11 g/dL), pregnancy.

=>Amiodarone:

DO consider amiodarone in critically ill patients. DON’T use amiodarone in AF >48 h or unknown duration without anticoagulation.

In cases where BB or CCB fail to reduce the heart rate or induce hypotension, amiodarone may be a reasonable option. Although amiodarone is an anti-arrhythmic, it has AV nodal blocking properties. An AHA class IIa recommendation states amiodarone can be used for rate control in critically ill patients.4 (Three studies provide the basis for this recommendation6, 22, 23)

Class III antiarrhythmic Use in chemical cardioversion

Sodium and potassium channel blocking properties

β -blocking and calcium channel blocking properties => slows conduction through the AV node.

Considerations: Amiodarone is an anti-arrhythmic, therefore in cases of AF or flutter >48h of unknown duration there is a possibility of cardioversion and risk of stroke .

Pulmonary, hepatic, and thyroid toxicity

Clemo et al studied amiodarone for acute rate control in 33 ICU patients with hemodynamically destabilizing atrial tachycardia. This retrospective chart review targeted a cohort who failed conventional therapy including BB, CCB, digoxin, electrical cardioversion, and procainamide pharmacologic cardioversion. Amiodarone therapy was associated with a decrease in rate and increase in systolic blood pressure. Furthermore, there were no reported events of hypotension or bradycardia, possibly secondary to a lower loading dose of 2-3mg/kg. Of note, a significant amount of patients converted to sinus rhythm while on amiodarone infusion (29 at 24 hours, 20 at discharge).22

Table of Common Rate Control Agents via AHA/ACC/HRS Guidelines4

=>Goals of Rate Control: DO aim for ventricular rate less than 110 bpm.

Earlier guidelines recommend the goal heart rate to be less than 80 bpm. RACE II provided the basis for a lenient rate-control strategy by investigating a resting heart rate <110 bpm versus <80 bpm. RACE II found lenient-control was non-inferior to strict-control for composite death from cardiovascular causes, hospitalization for heart failure, stroke, systemic embolism, major bleeding, arrhythmic events (syncope, sustained VT, cardiac arrest, life-threatening adverse effects of drugs, implantation of pacemaker or ICD). 24

Asymptomatic/hemodynamically stable: <110 bpm

Symptomatic: Rate to point of asymptomatic

=>Electrical Cardioversion (Unstable AF): DO cardiovert unstable AF.

Patients with hemodynamic instability, ongoing ischemia, or worsening heart failure should undergo direct current cardioversion.4 If the choice is available, biphasic waveform devices have greater efficacy than monophasic.25, 26 In terms of the selection of energy level, Mittal et al provides a protocol for escalating shock energies on monophasic and biphasic devices with reported efficacy of each energy level.26 Some advocate starting at maximum energy to optimize success as studies have shown higher energy does not increase cardiac injury.27, 28

In regards to pad placement, a systematic review by Kirkland et al found no difference in anterolateral (right parasternal-left midaxillary) and anteroposterior (right parasternal-left infrascapular) pad placement in the success of cardioversion. However, a subgroup analysis indicated anterolateral placement might be more effective when using biphasic shocks.29

Managing Atrial Fibrillation Secondary to…

=>Sepsis: Do use BBs

AF is an independent predictor of mortality the critically ill, AF confers 31% mortality versus patients without AF at 17% mortality (P<0.001).30 A retrospective cohort by Walkey et al of 39,693 septic patients with AF analyzed practice patterns and mortality. CCBs were most commonly initiated in AF during sepsis (36%); however, BBs were associated with lower hospital mortality compared to CCB (RR 0.92), digoxin (R 0.79), and amiodarone (RR 0.64).31

=>Hyperthyroid: Do use BBs

BBs are recommended to control AF complicating thyrotoxicosis unless contraindicated (Level C).4 The rationale is two-fold, first hyperthyroidism is a state of increased β -adrenergic receptors thus BB reduce symptoms.32 Second, propranolol, atenolol, and metoprolol slowly decrease serum T3 concentrations by inhibiting the conversion from thyroxine (T4).33, 34

=>Heart Failure: Do use BBs

The AF-CHF study by Dydra et al compared rate versus rhythm control strategies in CHF. The study enrolled 1,376 patients with an EF <35% and recent history of AF, patients were randomized to rate control utilizing BB or rhythm control utilizing electrical cardioversion and amiodarone. Rhythm control was abandoned more frequently than rate control, 21% versus 9.1% respectively. The predominant reason to abandon rate control was worsening heart failure. Importantly, crossover from rhythm to rate control did not increase cardiovascular or all cause mortality.35 Although rate control is an acceptable strategy in CHF, BB therapy does not confer the same mortality benefit in AF as it does in sinus rhythm.36 Therefore, BB can be used in HF but does not need to be the only or first line agent.

The decrease in SVR, anti-ischemic effects, and LV relaxation of CCBs indicate theoretical benefit in CHF. However, the negative inotropic effect may impair left ventricular function.37 Furthermore, the MDPIT study by Goldstein et al showed post-MI patients on CCBs with early LV dysfunction (EF <40%) were found to have increased late onset heart failure.21 Although the evidence is not overwhelming, in cases of rapid AF and CHF, particularly decompensated HF, rate control with CCBs can be detrimental.

Briefly on Antithrombotic Therapy : DO anticoagulate.4,38

Patients with AF greater than 48 hours or less than 48 hours but high risk of stroke and no contraindications for anticoagulation should initiate anticoagulation as soon as possible before or immediately after cardioversion.4

Nonvalvular

Patients with nonvalvular AF, CHA 2 DS 2 -VASc is recommended for stroke risk assessment (Level B evidence). 4

AF, CHA DS -VASc is recommended for stroke risk assessment (Level B evidence). CHA 2 DS 2 -VASc 39 C ongestive Heart Failure H ypertension A ge >75 (2 points) D iabetes mellitus Prior S troke or TIA or Thromboembolism (2 points) V ascular disease – prior MI, PAD, aortic plaque A ge 65 to 74 years Female S ex

Scoring (% risk of stroke/year) 0 No therapy (0%/year) 1 Aspirin 325mg or oral anticoagulants (1.3%/year) ≥2 Oral Anticoagulants recommended (2.2%/year) Warfarin, Dabigatran, Rivaroxaban, Apixaban Anticoagulants Renal function should be assessed in NOACs (Direct thrombin or factor Xa inhibitors)



Valvular

Valve replacement – anticoagulation with warfarin INR 2 to 3 or 2.5 to 3.5 depending on tissue versus mechanical valve selection

Summary

Do Reverse/treat any underlying process (remember PIRATES) Use β1-selective BBs or non-dihydropyridine CCBs in rapid AF Use BB in patients with concurrent hyperthyroid Use CHA 2 DS 2 -VASc to risk stratify for stroke



Don’t Mix BB and CCB (if possible) Use a BB in severe asthma Use a CCB in decompensated HF Cardiovert stable AF with duration >48h or unknown duration if the patient isn’t on anticoagulation



References / Further Reading

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Circulation. 2014;130(23):2071-2104. Abrams J, Allen J, Allin D, Anderson J, Anderson S, Blanski L, et al. Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial. American heart journal. 1985;110(5):913-922. Delle Karth G, Geppert A, Neunteufl T, Priglinger U, Haumer M, Gschwandtner M, et al. Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Critical care medicine. 2001;29(6):1149-1153. Ellenbogen KA, Dias VC, Plumb VJ, Heywood JT, Mirvis DM. A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. Journal of the American College of Cardiology. 1991;18(4):891-897. Platia EV, Michelson EL, Porterfield JK, Das G. Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. The American journal of cardiology. 1989;63(13):925-929. Scheuermeyer FX, Grafstein E, Stenstrom R, Christenson J, Heslop C, Heilbron B, et al. Safety and efficiency of calcium channel blockers versus beta-blockers for rate control in patients with atrial fibrillation and no acute underlying medical illness. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine. 2013;20(3):222-230. Siu CW, Lau CP, Lee WL, Lam KF, Tse HF. Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation. Critical care medicine. 2009;37(7):2174-2179; quiz 2180. Demircan C, Cikriklar HI, Engindeniz Z, Cebicci H, Atar N, Guler V, et al. Comparison of the effectiveness of intravenous diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation. Emergency medicine journal: EMJ. 2005;22(6):411-414. 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