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Author: Sandeep Devabhakthuni, PharmD, BCCP
Heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) often occur concomitantly, increasing the risk of stroke, hospitalization for HF, and all-cause mortality.1 Despite an increasing prevalence of AF in patients with HFrEF, there is no consensus on the best treatment approaches for this scenario.2 Existing rate and rhythm control strategies for AF present unique challenges in patients with HFrEF. In this blog, we’ll cover 3 clinical pearls for the acute management of AF in patients with HFrEF.
Clinical Pearl #1: Avoid non-dihydropyridine calcium channel blockers (non-DHP CCBs) for rate control
One of the major goals in acute management of AF is to control the ventricular rate by targeting a heart rate (HR) < 110 beats/min for those with preserved EF.2 In patients with HFrEF, rate control is often more lenient since these patients are usually able to tolerate HR in this range. Options for rate control in those with concomitant HFrEF are limited (Table 1). For example, although non-DHP CCBs are commonly used for this indication, diltiazem and verapamil are contraindicated in patients with left ventricular (LV) systolic dysfunction. The negative inotropic effects of these agents decrease cardiac output and have been shown to increase mortality in patients with HFrEF.3 The majority of the available literature on non-DHP CCBs focus on chronic management, in which patients are exposed to the long-term negative inotropic effect without the neurohormonal benefits that beta blockers provide.3-5
One study has compared the acute administration of non-DHP CCBs and beta blockers in patients with compensated HFrEF in AF with RVR presenting to an emergency department.6 This retrospective cohort demonstrated that intravenous administration of diltiazem for rate control in 48 patients with AF and HFrEF has similar efficacy compared to metoprolol in achieving heart rate < 100 beats/min within 30 min, without any hemodynamic compromise. While not statistically significant, the diltiazem group had numerically higher rates of adverse events compared to metoprolol.
This study did have significant limitations, including a single-center, retrospective design with incomplete medical record documentation, small sample size with no power calculation, and lack of formal treatment protocol. The majority of the patients had only NYHA Class I symptoms so findings likely cannot be extrapolated to more advanced patients. The investigators only looked at hemodynamic compromise within 30 minutes, which may have been too early to detect any problems with continued intravenous administration. Continued administration of a negative inotropic agent may increase risk of decompensation.
Prior small studies have investigated diltiazem for acute management of AF in HFrEF patients and demonstrated that intravenous administration is safe in the acute setting without any hemodynamic compromise.7-10 However, one retrospective study of 635 patients with HFrEF hospitalized with AF found a significantly higher frequency of acute kidney injury within 48 hours of starting diltiazem compared to those with preserved EF (10% vs. 3.6%, p=0.002).11 These conflicting findings highlight the need for randomized, controlled trials to evaluate safety of acute administration of non-DHP CCBs. Using non-DHP CCBs initially for rate control would present a challenge since switching to another medication would be needed for long-term control. Therefore, to avoid long-term deleterious effects, non-DHP CCBs are not recommended for acute management of AF in patients with HFrEF.
Clinical Pearl #2: Don’t titrate beta blockers too rapidly
Atrial fibrillation with RVR often presents concomitantly with acute decompensated heart failure, and the relationship between the two becomes critical. For acute management of AF in patients without LV dysfunction, beta blockers are often quickly uptitrated to achieve a goal heart rate < 110 beats/min.2,3 However, in patients with concomitant HFrEF, rapid titration can precipitate HF decompensation.12 While chronic administration of beta blockers in HFrEF is safe and improves outcomes, these medications must be slowly uptitrated for this indication.13,14 When beta blockers are titrated too quickly, their acute negative inotropic effects can trigger HF exacerbations. Intravenous administration of beta blockers should be avoided for similar reasons.13 As such, alternative rate control strategies like digoxin and amiodarone should be considered for acute management of AF in patients with HFrEF.3
Clinical Pearl #3: Use antiarrhythmics that are safe in patients with HFrEF
In patients who remain symptomatic despite adequate rate control, safe rhythm control strategies should be explored (Table 1). Although antiarrhythmic medications are often used to maintain sinus rhythm and prevent recurrent AF, several of these medications can worsen outcomes in patients with existing structural heart disease (i.e., prior MI, heart failure, significant left ventricular hypertrophy).3,14 Medications that have prominent sodium channel blocking effects (e.g., flecainide, propafenone) increase mortality in patients with MI from coronary artery disease.15 Also, flecainide, propafenone, and disopyramide are negative inotropes and should be avoided in patients with LV dysfunction.3,16,17 Although dronedarone lacks the iodine moieties of amiodarone and is associared with less adverse events, it increases mortality in patients with recently decompensated HF and depressed LV function.18 Dronedarone is not recommended in patients with HFrEF and those who had an episode of decompensated HF in the past 4 weeks, especially if they have depressed LV function.3, 19
Thus, pharmacologic options for rhythm control are limited; amiodarone and dofetilide are the only guideline-recommended antiarrhythmic medications for the treatment of AF in patients with HFrEF.3 Both amiodarone and dofetilide pose risks and are associated with multiple drug-drug interactions that should be monitored carefully. If these cannot be used, sotalol may be considered, as it has not been shown to increase risk of mortality in patients with compensated, non-advanced HFrEF.20 If sotalol is used in HFrEF, patients should be euvolemic without evidence of hemodynamic compromise.20.21
For those not responding or cannot tolerate antiarrhythmic therapy, nonpharmacologic cardioversion approaches should be considered. For those in whom the relationship between AF and symptoms of HF is less clear, a trial of electrical cardioversion can be performed to restore functional capacity.1 However, it has a limited role in the initial management of acute HF decompensation (in the absence of hemodynamic instability) until the patient is stabilized since early AF recurrence is common. Another option is catheter ablation, where there is growing evidence to support use in this population.22,23
Acute management of AF in patients with HFrEF presents many challenges when considering pharmacologic rate and rhythm control strategies. For rate control in patients with HFrEF, avoid use of non-DHP CCBs, which can exacerbate HF. Beta blockers should be used cautiously for acute management of AF in this patient population (if at all). If rhythm control is needed, it is important to utilize medications (e.g., amiodarone or dofetilide) that have been proven to be safe in patients with HFrEF. For those not responding or cannot tolerate antiarrhythmic therapy, there is an evolving role for catheter ablation for rhythm control of AF in patients with HFrEF.
Sandeep Devabhakthuni, PharmD, BCCP
- Verma A, Kalman JM, Callans DJ. Treatment of patients with atrial fibrillation and heart failure with reduced ejection fraction. Circulation. 2017;135:1547-63.
- Carlisle MA, Fudim M, DeVore AD, Piccini JP. Heart failure and atrial fibrillation, like fire and fury. JACC Heart Fail. 2019;7:447-56.
- January CT, Wann LLS, Alpert JS, et al. 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. J Am Coll Cardiol. 2014;64:e1-76.
- Page 2nd RL, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation 2016;134:e32-9.
- Moss AJ, Abrams J, Bigger T, et al. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med. 1988;319:385–92.
- Hirschy R, Ackerbauer KA, Peksa GD, O’Donnell EP, DeMott JM. Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction. Am J Emerg Med. 2019;37:80-84.
- Goldenberg IF, LewisWR, Dias VC, Heywood JT, PedersenWR. Intravenous diltiazem for the treatment of patients with atrial fibrillation or flutter and moderate to severe congestive heart failure. Am J Cardiol. 1994;74:884–9.
- Kulick DL, McIntosh N, Campese VM, et al. Central and renal hemodynamic effects and hormonal response to diltiazem in severe congestive heart failure. Am J Cardiol. 1987;59:1138–43.
- Walsh RW, Porter CB, Starling MR, O’Rourke RA. Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure. J Am Coll Cardiol. 1984;3:1044–50.
- Materne P, Legrand V, Vandormael M, Collignon P, Kulbertus HE. Hemodynamic effects of intravenous diltiazem with impaired left ventricular function. Am J Cardiol. 1984;54:733–7.
- Jandali MB. Safety of intravenous diltiazem in reduced ejection fraction heart failure with rapid atrial fibrillation. Clin Drug Investig. 2018;38:503-8.
- Waagstein F, Caidahl K, Wallentin I, Bergh CH, Hjalmarson A. Long-term beta blockade in dilated cardiomyopathy. Effects of short- and long-term metoprolol treatment followed by withdrawal and readministration of metoprolol. Circulation. 1989;80:551-563.
- Feeney ME, Rowe SLB, Mah ND, Barton CA, Ran R. Achieving ventricular rate control in patients taking chronic beta blocker therapy. Am J Emerg Med. 2018;36:110-113.
- Singh SN, Patrick J, Patrick J. Antiarrhythmic drugs. Curr Treat Options Cardiovasc Med. 2004;6:357-364.
- Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781–8.
- Kenedi PP. Clinical significance of the negative inotropic effect of disopyramide. J Int Med. Res. 1988;16:257-63.
- Santinelli V, Arnese M, Oppo I, et al. Effects of flecainide and propafenone on systolic performance in subjects with normal cardiac function. Chest. 1993;103:1068-73.
- Kober L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358:2678–87.
- Julian DG, Prescott RJ, Jackson FS, Szekely P. Controlled trial of sotalol for one year after myocardial infarction. Lancet. 1982;1:1142–47.
- Soyka LF, Wirtz C, Spangenberg RB. Clinical safety profile of sotalol in patients with arrhythmias. Am J Cardiol. 1990; 65:74A-81A.
- Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation. 1996; 94:2535-41.
- Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. 2018; 378:417-27.
- Turagam MK, Garg J, Whang W, et al. Catheter ablation of atrial fibrillation in patients with heart failure: a meta-analysis of randomized controlled trials. Ann Intern Med. 2019;170:41-50.
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