Effect of drugs on AV function in AF Various drugs can slow conduction through the atrioventricular node in atrial fibrillation by altering its physiology. The calcium (Ca++) channel blockers, primarily diltiazem and verapamil, block the influx of calcium and therefore slow conduction by reducing the upstroke of the action potential; digoxin, carotid massage, Valsalva maneuver, and edrophonium are vagotonic and slow conduction by increasing parasympathetic effects on the node; beta blockers slow conduction by offsetting sympathetic inputs; and adenosine slows conduction only transiently by increasing potassium conduction and decreasing calcium influx. Graphic 51932 Version 1.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 25/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate [2,3] Six-minute walk test technique Flat, straight corridor 30 m (100 feet) in length Turnaround points marked with a cone Patient should wear comfortable clothes and shoes Patient rests in chair for at least 10 minutes prior to test (ie, no warm-up period) Heart rate and pulse oxygen saturation (SpO ) should be monitored throughout the test 2 If the patient is using supplemental oxygen, record the flow rate and type of device [1] Have patient stand and rate baseline dyspnea and overall fatigue using Borg scale* Set lap counter to zero and timer to six minutes Instruct the patient: Remember that the object is to walk AS FAR AS POSSIBLE for 6 minutes, but don't run or jog. Pivot briskly around the cone. Standardized encouragement statements should be provided at one minute intervals, such as "You are doing well. You have _ minutes to go" and "Keep up the good work. You have _ minutes to go." At the end of the test, mark the spot where the patient stopped on the floor If using a pulse oximeter, measure the pulse rate and SpO and record 2 [1] After the test record the Borg* dyspnea and fatigue levels Ask, "What, if anything, kept you from walking farther?" Calculate the distance walked and record Refer to UpToDate table on the modified Borg Scale. Reference: 1. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982; 14:377. 2. American Thoracic Society. ATS statement: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166:111. 3. Holland AE, Spruit MA, Troosters T, et al. An o cial European Respiratory Society/American Thoracic Society technical standard: eld walking tests in chronic respiratory disease. Eur Respir J 2014; 44:1428. Graphic 90285 Version 4.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 26/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate Medications and doses for ventricular rate control in adult patients with atrial fibrillation Medication IV dosing Oral dosing* Notes Diltiazem Bolus dosing: IR: 30 mg 4 times daily; increase as needed to IV regimen usually controls the ventricular First bolus: 0.25 achieve ventricular rate control; usual dose: 120 mg/kg (average adult dose: 20 mg) rate within 4 to 5 minutes. to 480 mg/day in 3 or 4 administered over 2 Some experts use a lower bolus dose of 5 divided doses. minutes; if dose is tolerated but does to 15 mg if there is concern for ER: 120 mg once daily or in 2 divided doses not produce desired response (ie, 20% hypotension. depending on formulation ; increase as reduction in baseline heart rate or heart rate 100 beats/min) within 15 minutes, administer a second needed to achieve ventricular rate control; usual dose: 120 to 480 mg/day. bolus. Second bolus: 0.35 mg/kg (average adult dose: 25 mg) administered over 2 minutes. In those who respond to the first or second bolus, initiate a continuous infusion at 5 to 10 mg/hour. May increase in 5 mg/hour increments as needed to a maximum of 15 mg/hour. Esmolol Rapid titration with bolus Not available as oral Due to short half-life, doses: preparation. useful when uncertain if patient will become 500 mcg/kg loading dose administered over 1 minute, hypotensive with a beta blocker. followed by a continuous infusion of 50 mcg/kg/minute. Reassess after 4 minutes. https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 27/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate If response is inadequate, administer a second bolus of 500 mcg/kg and increase infusion to 100 mcg/kg/minute. Reassess after 4 minutes. If response is inadequate, administer a third and final bolus of 500 mcg/kg and increase infusion to 150 mcg/kg/minute. Reassess after 4 minutes. If response is inadequate, may increase infusion to a maximum of 200 mcg/kg/minute. OR Slow titration without bolus doses: Initiate continuous infusion at 50 mcg/kg/minute; if needed based on clinical response, may increase in 50 mcg/kg/minute increments at 30- minute intervals to a maximum of 200 mcg/kg/minute. Verapamil Bolus dosing: 5 to 10 mg administered over 2 to 3 IR: 40 mg 3 to 4 times daily; increase as needed Rate control is often achieved with 1 or 2 minutes; may repeat every 15 to 30 minutes as to achieve ventricular rate control; maximum dose: bolus doses. With IV administration, needed and tolerated. 480 mg/day in 3 to 4 divided doses. onset of effect on AV node is within 2 Once rate control is achieved with bolus doses, minutes and peak https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 28/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate initiate a continuous infusion at 5 mg/hour; ER : 120 or 180 mg once daily; increase as needed effect is in 10 to 15 minutes. titrate based on clinical to achieve ventricular rate Control of the ventricular response is response to a maximum of 20 mg/hour. control; maximum dose: 480 mg/day in 1 to 2 lost in approximately divided doses. 90 minutes if repeated boluses or a maintenance infusion are not given. Metoprolol Bolus dosing: 2.5 to 5 mg IR (metoprolol tartrate): administered over 2 minutes; may repeat at 5- 25 mg twice daily; increase dose gradually minute intervals up to a (eg, by 12.5 mg every 6 total dose of 15 mg. hours) as needed and tolerated to achieve While subsequent doses can be given intravenously, ventricular rate control; maximum dose: 100 mg the optimal regimen is not well defined, and oral twice daily. administration is ER (metoprolol succinate): preferable. 50 mg once daily; increase dose gradually as tolerated to achieve ventricular rate control; maximum dose: 400 mg once daily. Propranolol Bolus dosing: 1 mg IR: 10 mg 3 to 4 times administered over 1 minute; may repeat at 2- daily; increase dose gradually as tolerated to minute intervals for up to 3 achieve ventricular rate doses. control; maximum dose: 40 mg 3 to 4 times daily. ER: 60 mg once daily; increase as needed to achieve ventricular rate control up to 160 mg once daily. Digoxin TDD: 0.25 to 0.5 mg administered over several TDD: 0.5 mg once, followed by 0.25 mg every May use as add-on therapy in patients who minutes, followed by 0.25 mg every 6 hours for a 6 hours for a total loading dose of 0.75 to 1.5 mg. do not adequately respond to a calcium total loading dose of 0.75 to 1.5 mg. channel blocker and/or beta blocker; not Maintenance dose (for use after administration of IV or oral TDD): 0.125 generally used as monotherapy. to 0.25 mg once daily. https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 29/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate Amiodarone Loading dose: 150 mg over 10 minutes followed by 1 mg/minute for 6 hours, Following IV infusion, administer 400 to 1200 May use in select patients requiring mg/day in divided doses urgent therapy who are intolerant of other then 0.5 mg/minute for 18 hours; may administer to complete a total (IV plus oral) loading dose of preferred agents (ie, repeat boluses of 150 mg over 10 minutes as needed, not to exceed 6 to 8 additional bolus doses approximately 10 grams. Consider overlapping IV calcium channel blockers, beta blockers, and oral therapy for 24 to 48 hours. digoxin). Due to small chance of per 24 hours. cardioversion, careful attention to Usual maintenance dose: 100 to 200 mg once daily. anticoagulation is necessary. This table shows doses of drugs that can be used for ventricular rate control in adult patients with atrial fibrillation who do not have heart failure. It should be used in conjunction with UpToDate content on control of ventricular rate in patients with atrial fibrillation. When initiating or altering therapy, use of a drug interactions database, such as Lexicomp drug interactions, is advised. IV: intravenous; IR: immediate-release; ER: extended-release; AV: atrioventricular; TDD: total digitalizing dose. Oral dosing in this table is initial dosing for patients requiring nonurgent therapy, unless otherwise noted. For patients transitioning from IV to oral therapy, UpToDate authors typically convert the total daily dose of the IV medication to an equivalent divided or long-acting oral dose of a medication in the same class. Refer to UpToDate topic on control of ventricular rate in patients with atrial fibrillation for discussion. Diltiazem extended-release is available in 12- and 24-hour formulations. Refer to a drug information reference, such as Lexicomp drug information included with UpToDate, or local product information for dosing details. Verapamil ER delayed-onset capsules (ie, Verelan PM and generics) are not interchangeable with other ER formulations and are intended for management of hypertension. Digoxin has a narrow therapeutic window and can cause significant toxicity. Individual patient characteristics (eg, kidney function, body habitus, concomitant medications) should be carefully considered when determining loading and maintenance dosing regimens. Dosing in this table does not account for dose adjustments. For discussion of dosing and monitoring, refer to UpToDate content on treatment with digoxin. Amiodarone use is associated with a relatively high incidence of adverse effects. Refer to related UpToDate content for discussion, including monitoring. Graphic 141646 Version 2.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 30/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate Dose response to diltiazem for rate control in atrial fibrillation Kaplan-Meier analysis of the percentage of patients maintaining a therapeutic rate control response to each dose level of intravenous diltiazem infusion in patients who initially responded to bolus diltiazem. Maintenance of rate control was greater at doses of 10 to 15 mg/h. Data from Ellenbogen KA, Dias VC, Cardello FP, et al. Am J Cardiol 1995; 75:45. Graphic 80630 Version 3.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 31/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate Efficacy of amiodarone in rate control for atrial fibrillation Effect of intravenous placebo, amiodarone, and flecainide on the ventricular response to atrial fibrillation in patients who failed to revert to sinus rhythm after the initiation of therapy. Amiodarone slowed the ventricular response, an effect that was not seen with flecainide or placebo. Although flecainide was less effective for rate control, it was associated with earlier reversion to sinus rhythm than amiodarone or placebo. Note that the time scale is nonlinear. Data from Donovan KD, Power BM, Hockings GE, et al. Am J Cardiol 1995; 75:693. Graphic 81119 Version 3.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 32/33 7/5/23, 9:14 AM Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy - UpToDate Contributor Disclosures Rachel Kaplan, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/control-of-ventricular-rate-in-patients-with-atrial-fibrillation-who-do-not-have-heart-failure-pharmacologic-therapy/ 33/33