Atrial fibrillation rate control

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Atrial fibrillation with rapid ventricular rate is a common finding in many hospitalized patients. The ventricular rate may be increased up to 150-170. It is essential to bring the ventricular rate down to less than 110 because a rapid ventricular response can cause hemodynamic instabilities and tachycardia mediated cardiomyopathies (heart failure). AF can cause disabling and annoying symptoms. Palpitations, angina, lassitude (weariness), and decreased exercise tolerance are related to rapid heart rate and inefficient cardiac output caused by AF. This can significantly increase mortality and morbidity, which can be prevented by early and adequate treatment of the AF.

Rate Control

Rate Control versus Rhythm Control

There are two ways to approach symptoms: rate control and rhythm control.

  • Rate control treatments seek to reduce the heart rate to normal while allowing the patient to remain in AF. A goal of < 110bpm (lenient rate control) is usually targeted, since patients do not seem to do any better with stricter control[1].
  • Rhythm control seeks to restore the normal heart rhythm, called normal sinus rhythm. Options for rhythm control include anti-arrhythmic medications (flecainide, amiodarone, sotalol, and others), catheter-based ablation procedures, and surgical ablation procedures.
  • Rate control with anticoagulation was found to be non-inferior to rhythm control in terms of mortality outcomes in the AFFIRM Trial.[2]
  • AFFIRM also showed no reduction in risk of stroke with rhythm control strategy compared to rate control with anticoagulation.[2]
  • Based on this evidence, a rhythm control strategy is no longer pursued in most AF patients, since the anti-arrhythmic drugs can have serious side effects and catheter or surgical ablation procedures have risks as well.
  • Rhythm control may be desired when the patient is significantly symptomatic despite rate control, or if the patients cannot tolerate rate control medications.

Pharmacologic Rate Control

Mechanism of Action

  • Rate control is achieved with medications that work by increasing the degree of block at the AV node, effectively decreasing the number of impulses that conduct to the ventricles. This can be accomplished with:
  • Calcium channel blockers (diltiazem or verapamil) block the influx of calcium and reduce the upstroke of the action potential.
  • Beta blockers (preferably the cardioselective beta blockers such as metoprolol, atenolol, bisoprolol) slow conduction by decreasing sympathetic tone.
  • Cardiac glycosides (i.e. digoxin) are vagomimetics and slow conduction by increasing parasympathetic effects on the node.
  • Amiodarone is a class III anti-arrhythmic drug which also has AV node blocking effects. Amiodarone can be used for rate control when other agents are contraindicated or ineffective. The classic situation where amiodarone would be used is when a patient is hypotensive (often septic), but also in AF with rapid ventricular response. Beta-blockers and calcium channel blockers are not ideal due to negative inotropic effects. Amiodarone has less negative inotropy and is preferred for this situation.

Beta Blockers

Acute Beta Blocker Therapy
  • Intravenous beta blocker like metoprolol and esmolol.
  • Useful when atrial fibrillation is secondary to high adrenergic tone like in post operative situations.
Metoprolol
  • Dose 2.5-5 mg over 2 minutes.
  • Route - Intravenous.
  • Maximum dose 15 mg.
  • Doses can be repeated over 5 minutes interval.
Esmolol
  • Short duration of action (10-20 min).
  • Metabolized by RBC esterases.
  • Advantage - It can be used in conditions where patient's response and tolerance to beta blocker is uncertain. If there is a concern that beta-blockade may cause decompensated heart failure, hypotension, or bradycardia, the short half-life of esmolol permits a therapeutic trial to check the patient's response. Based on that the patient are started on other long acting beta blockers.
  • Doses
    • Infusion at rate of 50 µg/kg per min, with an increase in the rate of administration by 50 µg/kg per min every 30 minutes.
    • Some hospitals prefer starting with a bolus of 0.5 mg/kg over one minute, followed by infusion of 50 µg/kg per min. Monitor for four minutes. In case of inadequate response, another bolus is given followed by an infusion of 100 µg/kg per min. Wait for 4 minutes. In case of inadequate response a third bolus can be given followed by an infusion at 150 µg/kg per min rate. The maximum infusion that can be given is 200 µg/kg per min.

Chronic Beta Blocker Therapy

  • Oral beta blockers are preferred for treatment of chronic atrial fibrillation.
  • Commonly used agents are Atenolol or metoprolol
  • Atenolol dose - 25 mg per day. Maximum dose permitted is 200 mg per day.
  • Metoprolol dose - 25mg to 200mg of short acting (metoprolol tartrate) twice a day or 50mg to 400mg of long acting (metoprolol succinate) daily. Metoprolol succinate is the preferred form due to convenience.
  • Carvedilol or metoprolol succinate should be used in patients with chronic heart failure with reduced ejection fraction, since these agents are also indicated for heart failure with reduced ejection fraction.
Side Effects of Beta Blocker Therapy

Calcium Channel Blockers

  • Nondihydropyridine calcium channel blockers verapamil and diltiazem (Cardizem) are commonly used.
  • Diltiazem is common used as a drip for acute rate control when patients present with rapid ventricular response
    • Dose 15-20mg once, then start drip at 10mg/minute
  • Diltiazem can be transitioned from a drip to a short acting oral form (given 4x daily), then a long acting form (given daily)
    • Immediate release diltiazem is usually dose 30-120mg every 6 hours
    • Long-acting diltiazem is usually dose 120-480mg daily
  • Verapamil is less commonly used, but is also available as both PO and IV formulations

Digoxin

  • Cardiac glycoside with positive inotropic and AV nodal blocking properties (increases vagal tone at the AV node)
  • Can be useful in patients with heart failure since it is the only positive inotrope that blocks the AV node. Beta-blockers and calcium channel blockers are negative inotropes.
  • Less favored than beta-blockers or calcium channel blockers due to narrow therapeutic index and concerns about increased mortality in AF patients treated with digoxin in the TREAT-AF study [3]

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)[4]

Rate Control

Class I
"1. Control of the ventricular rate using a beta blocker or nondihydropyridine calcium channel antagonist is recommended for patients with paroxysmal, persistent, or permanent AF. (Level of Evidence: B) "
"2. Intravenous administration of a beta blocker or nondihydropyridine calcium channel blocker is recommended to slow the ventricular heart rate in the acute setting in patients without pre-excitation. In hemodynamically unstable patients, electrical cardioversion is indicated. (Level of Evidence: B) "
"3. In patients who experience AF-related symptoms during activity, the adequacy of heart rate control should be assessed during exertion, adjusting pharmacological treatment as necessary to keep the ventricular rate within the physiological range. (Level of Evidence: C) "
Class III: Harm
"1. AV nodal ablation with permanent ventricular pacing should not be performed to improve rate control without prior attempts to achieve rate control with medications. (Level of Evidence: C)"
"2. Nondihydropyridine calcium channel antagonists should not be used in patients with decompensated HF as these may lead to further hemodynamic compromise. (Level of Evidence: C)"
"3. In patients with pre-excitation and AF, digoxin, nondihydropyridine calcium channel antagonists, or intravenous amiodarone should not be administered as they may increase the ventricular response and may result in ventricular fibrillation. (Level of Evidence: B)"
"4. Dronedarone should not be used to control the ventricular rate in patients with permanent AF as it increases the risk of the combined endpoint of stroke, MI, systemic embolism, or cardiovascular death. (Level of Evidence: B)"
Class IIa
"1. A heart rate control (resting heart rate <80 bpm) strategy is reasonable for symptomatic management of AF. (Level of Evidence: B)"
"2. Intravenous amiodarone can be useful for rate control in critically ill patients without pre-excitation. (Level of Evidence: B)"
"3. AV nodal ablation with permanent ventricular pacing is reasonable to control the heart rate when pharmacological therapy is inadequate and rhythm control is not achievable. (Level of Evidence: B)"
Class IIb
"1. A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and LV systolic function is preserved. (Level of Evidence: B)"
"2. Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated. (Level of Evidence: C)"

Sources

References

  1. Isabelle C. Van Gelder, M.D., Hessel F. Groenveld, M.D., Harry J.G.M. Crijns, M.D., Ype S. Tuininga, M.D., Jan G.P. Tijssen, Ph.D., A. Marco Alings, M.D., Hans L. Hillege, M.D., Johanna A. Bergsma-Kadijk, M.Sc., Jan H. Cornel, M.D., Otto Kamp, M.D., Raymond Tukkie, M.D., Hans A. Bosker, M.D., Dirk J. Van Veldhuisen, M.D., and Maarten P. Van den Berg, M.D., for the RACE II Investigators* Lenient versus Strict Rate Control in Patients with Atrial Fibrillation. NEJM 2010; 362:1363-1373 April 15, 2010DOI: 10.1056/NEJMoa1001337
  2. 2.0 2.1 Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD (2002). "A comparison of rate control and rhythm control in patients with atrial fibrillation". N Engl J Med. 347 (23): 1825–33. PMID 12466506
  3. Mintu P. Turakhia, MD, MAS∗; Pasquale Santangeli, MD†; Wolfgang C. Winkelmayer, MD, MPH, ScD§; Xiangyan Xu, MS∗; Aditya J. Ullal, BA∗; Claire T. Than, MPH∗; Susan Schmitt, PhD∗; Tyson H. Holmes, PhD‖; Susan M. Frayne, MD, MPH∗; Ciaran S. Phibbs, PhD∗; Felix Yang, MD∗∗; Donald D. Hoang, BA∗; P. Michael Ho, MD, PhD††; Paul A. Heidenreich, MD, MS. Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial FibrillationFindings From the TREAT-AF Study. JACC 2014;64(7):660-668.
  4. 4.0 4.1 January, C. T.; Wann, L. S.; Alpert, J. S.; Calkins, H.; Cleveland, J. C.; Cigarroa, J. E.; Conti, J. B.; Ellinor, P. T.; Ezekowitz, M. D.; Field, M. E.; Murray, K. T.; Sacco, R. L.; Stevenson, W. G.; Tchou, P. J.; Tracy, C. M.; Yancy, C. W. (2014). "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". Circulation. doi:10.1161/CIR.0000000000000041. ISSN 0009-7322.
  5. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2011) 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123 (10):e269-367. DOI:10.1161/CIR.0b013e318214876d PMID: 21382897
  6. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA; et al. (2011). "2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Heart Rhythm. 8 (1): 157–76. doi:10.1016/j.hrthm.2010.11.047. PMID 21182985.


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