{"id":128979,"date":"2023-01-09T17:12:50","date_gmt":"2023-01-09T17:12:50","guid":{"rendered":"https:\/\/ccs.ca\/?post_type=guideline&p=128979"},"modified":"2023-04-19T07:53:33","modified_gmt":"2023-04-19T07:53:33","slug":"chapter-9-arrhythmia-management","status":"publish","type":"guideline","link":"https:\/\/ccs.ca\/guideline\/2020-atrial-fibrillation\/chapter-9-arrhythmia-management\/","title":{"rendered":"9. Arrhythmia Management"},"content":{"rendered":"\n
The acute management of AF is centred on the following domains:<\/p>\n\n\n\n
1. Determination if AF is the primary concern (\u201cprimary AF\u201d) or secondary to another acute medical illness (\u201csecondary AF\u201d). AF in the setting of critical illness has been associated with an increased risk of death (see section 11.5).[505]<\/a>,[506]<\/a><\/sup> Unfortunately, there is a paucity of high-quality evidence on whether or how to treat AF patients in the setting of critical illness,[507]<\/a>,[508]<\/a><\/sup> and there is a wide variety of reported approaches to AF management in this setting.[509]<\/a><\/sup> In the ED setting, results of a retrospective study suggested that rate and rhythm control efforts in patients with AF secondary to acute medical illness (predominantly sepsis and acute HF) might be associated with higher rates of adverse events.[510]<\/a><\/sup> Recommendation<\/p> 70. We recommend that the management of patients who present with recent-onset AF due to a reversible or secondary cause should be directed at the primary illness (Strong Recommendation; Low-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> AF in the acute care environment can be secondary to a primary cardiac pathology or can occur secondary to a specific precipitating event, such as infection, surgery, or thyroid disease.<\/p>\n 71. We recommend immediate electrical cardioversion for patients whose recent-onset AF is the direct cause of instability with hypotension, ACS, or pulmonary edema (Strong Recommendation; Low-Quality Evidence).<\/p>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a high value on immediately addressing instability by attempting cardioversion and a lower value on reducing the risk of cardioversion-associated stroke with a period of anticoagulation before cardioversion.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Therapeutic anticoagulation should be initiated as soon as possible, ideally prior to cardioversion if time allows.<\/p>\n 72. We suggest that a rhythm control strategy be considered for most stable patients with recent-onset AF (Weak Recommendation; Moderate-Quality Evidence).<\/p>\n<\/div>\n\n\n Values and Preferences<\/p> In patients with established AF multiple RCTs have shown no significant difference in cardiovascular outcomes between patients treated with a strategy with rate control vs rhythm control, recognizing that most of these trials did not specifically address recentonset AF. In patients with newly diagnosed AF (ie, within a year) an initial strategy of rhythm control has been associated with reduced cardiovascular death and reduced rates of stroke.<\/p>\n 73. In patients with AF and manifest pre-excitation we recommend against acute rate control (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> See section 11.8 for the management of patients with AF and pre-excitation.<\/p>\n 74. We recommend that patients who present with AF in the acute care setting have their need for long-term antithrombotic therapy be determined using the CCS Algorithm (CHADS-65) (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> See section 8.4.1 for the recommendations regarding OAC in the context of cardioversion.<\/p>\n<\/div>\n\n\n\n In the setting of recent onset AF, the rate control agent and the formulation chosen will be influenced by clinical circumstance (eg, the presence of HF or hypotension) and patient comorbidities (eg, known LV dysfunction, reactive airways disease, hypotension, history of MI, or angina; Supplemental Table S10). Options include oral or I.V. \u03b2-blockers, oral or I.V. nondihydropyridine calcium channel blockers (ND-CCBs), I.V. digoxin, and I.V. amiodarone (recognizing that the latter is also a rhythm control agent). I.V. rate control agents might be initially considered, however if the patient is hemodynamically stable oral agents might be preferred. If an I.V. agent is used as the initial therapy, it is important to coadminister an oral rate control agent as soon as possible to maintain rate control\/avoid rebound tachycardia as the I.V. formulation wears off.[520]<\/a><\/sup> In patients without contraindications, \u03b2-blockers and calcium channel blockers (CCBs) are considered first-line agents for rate control. Only two small RCTs totalling 92 patients have compared I.V. \u03b2-blockers with CCBs in patients with recent-onset AF (one of which also included AFL), both showed that I.V. diltiazem was more effective at controlling the heart rate (< 100 beats per minute [bpm]) at 20-30 minutes compared with I.V. metoprolol (RR, 1.8; 95% CI, 1.2- 2.6).[521]<\/a>–[523]<\/a><\/sup> A retrospective study of 110 AF patients showed similar results at 60 minutes, although the success rate with diltiazem in that study (57%) was lower than those reported in the RCTs (90%-95%).[521]<\/a>,[522]<\/a>,[524]<\/a><\/sup> In patients with ACS who require acute rate control, \u03b2-blockers are the agent of choice. Digoxin or amiodarone might be considered for acute rate control in the setting of decompensated HF, known significant LV systolic dysfunction (defined as LVEF \u2264 40%), or mild hypotension.[7]<\/a><\/sup> However, it is important to recall that I.V. formulations of amiodarone can lower BP.[525]<\/a><\/sup> Moreover, in this population the selective use of I.V. CCBs (and \u03b2-blockers) has been safely and successfully used in several randomized and nonrandomized studies, often with an improvement in BP when the recent-onset AF is rate controlled. Jandali performed a retrospective cohort study on the use of I.V. diltiazem in 162 patients with LV systolic dysfunction (LVEF \u2264 50%; with 52 having an LVEF \u2264 30%), and compared them with 473 patients with preserved LVEF (\u2265 50%).[526]<\/a><\/sup> There was no difference in the rates of hypotension, intensive care unit (ICU) transfer, or mortality between the patients with LVEF \u2265 50% vs those with LVEF < 50%, or those with LVEF \u2265 30% vs those with LVEF < 30%. Hirschy et al. performed a retrospective cohort study on the use of I.V. metoprolol (14 patients) and I.V. diltiazem (34 patients) in patients with known LV systolic dysfunction (mean LVEF 23% [15-35] vs 25% [15-30], respectively). Successful rate control within 30 minutes occurred in 62% of the metoprolol group and 50% of the diltiazem group (P \u00bc 0.49), with no difference in complications or worsening HF.[527]<\/a><\/sup> Goldenberg et al. performed a small double-blind RCT of 37 AF patients with reduced ejection fraction (EF; LVEF 36% \u00b1 14%) and symptomatic HF (New York Heart Association [NYHA] class III [62%] and IV [38%]), in whom the cautious use of I.V. diltiazem resulted in therapeutic response (97%) with self-limited hypotension in 11%, and no patients experiencing worsening of HF.[528]<\/a><\/sup> Although these studies have shown that the use of I.V. CCBs for rate control in highly selected patients can be safe, caution must be used because of the risk of precipitating cardiac decompensation.<\/p>\n\n\n Recommendation<\/p> 75. We recommend that either \u03b2-blockers or ND-CCBs (diltiazem or verapamil) be first-line agents for AF rate control in patients without significant LV dysfunction (eg, patients with an LVEF > 40%) (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Practical Tip<\/p> Use caution when administering I.V. formulations of \u03b2-blockers or ND-CCBs (verapamil and diltiazem) because of the risk of precipitating hypotension.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> The selection of a \u03b2-blocker or NDCCB for rate control of AF should be on the basis of patient comorbidities, contraindications, and side effect profile.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Oral formulations should be introduced as soon as possible because of the need for ongoing control of ventricular rate.<\/p>\n 76. We recommend evidence-based \u03b2-blockers (bisoprolol, carvedilol, metoprolol) be first-line agents for rate control of hemodynamically stable AF in the acute care setting in patients with significant LV dysfunction (LVEF \u2264 40%) (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n 77. We suggest I.V. amiodarone or I.V. digoxin be considered for acute rate control in patients with significant LV dysfunction (LVEF \u2264 40%), decompensated HF, or hypotension, when immediate electrical cardioversion is not indicated (Weak Recommendation; Moderate-Quality Evidence).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Use caution when administering I.V. amiodarone for rate control because of the possibility of hypotension and\/or conversion to sinus rhythm, and the subsequent risk of stroke in patients who are not adequately anticoagulated.<\/p>\n<\/div>\n\n\n\n There have been no RCTs that specifically examined rate control targets in the acute care setting,[529]<\/a><\/sup> nor in patients with paroxysmal AF.[530]<\/a><\/sup><\/p>\n\n\n Recommendation<\/p> 78. We recommend titrating rate-controlling agents to achieve a heart rate target of \u2264 100 bpm at rest for patients who present with a primary diagnosis of AF in the acute care setting (Strong Recommendation; Low-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Practical Tip<\/p> There is no evidence to support a specific heart rate target in acutely ill patients with AF secondary to a reversible or secondary cause. Treatment targets should be individualized in this patient population after consideration of the risk\/benefits of pharmacological rate control.<\/p>\n<\/div>\n\n\n\n For stable patients with recent-onset AF who are eligible for cardioversion, the choice to pursue sinus rhythm restoration should be made on the basis of patient symptoms and goals of care, recognizing that early rhythm control has been associated with a lower risk of stroke and cardiovascular death.[515]<\/sup><\/a> Because cardioversion increases the risk of systemic embolism, it is important to start appropriate anticoagulation as soon as time allows for all patients (see section 8.4.1).[339]<\/a><\/sup> For patients with recent-onset AF who are eligible for cardioversion, rhythm control is preferred and can be established via either pharmacological or electrical cardioversion. In general, electrical cardioversion is more effective than pharmacological cardioversion, especially for more prolonged AF episode durations.[363]<\/a>,[531]<\/a>–[534]<\/a> <\/sup>Pharmacological cardioversion has the advantage of being immediately feasible in a nonfasting patient, as well as avoiding the delays and risks associated with procedural sedation. However, most pharmacological agents have cautions or contraindications that limiting their use in patients with significant cardiac comorbidities, and their use requires a monitored bed, access to a crash cart, and a dedicated nurse to monitor for potential complications.<\/p>\n\n\n Recommendation<\/p> 79. We recommend that synchronized direct current or pharmacologic cardioversion may be used for sinus rhythm restoration in hemodynamically stable patients with recent-onset AF (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Practical Tip<\/p> In treatment environments in which procedural sedation is readily available, DCCV might be the preferred initial means to restore sinus rhythm, because it is more than 90% effective in the acute care environment and reduces ED length of stay.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> A strategy of pharmacological conversion followed by DCCV (if necessary) might be preferred in environments in which procedural sedation is not readily available, because pharmacological conversion might avert the need for DCCV in approximately half of the treated patients.<\/p>\n<\/div>\n\n\n\n Antiarrhythmic medication selection is typically dictated by the patient\u2019s comorbidities as well as physician preference. Characteristics, indications, contraindications, and monitoring details of antiarrhythmic medications used for acute pharmacological cardioversion are presented in Supplemental Table S11.<\/p>\n\n\n Recommendation<\/p> 80. We recommend that the choice of antiarrhythmic drug used for acute pharmacological cardioversion be defined according to patient characteristics (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> The choice of medication in patients without any contraindications will depend on physician experience, duration of AF, and considerations unique to the practice setting (See Supplemental Table S11).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> All patients require monitoring after cardioversion, the length of which is dependent on the method of conversion. A general guideline is to observe patients for a duration of time that is equal to half of the medication\u2019s therapeutic half-life.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> If the patient\u2019s history is unknown, electrical cardioversion should be used in preference to pharmacological cardioversion.<\/p>\n<\/div>\n\n\n\n Procainamide, a class Ia agent, is the most common I.V. medication used for cardioversion of recent-onset AF in the Canadian ED setting.[535]<\/a><\/sup> Although procainamide can be administered as a 1-g bolus over 30 minutes followed by an infusion of 2 mg\/min or a dose of 15-18 mg\/kg administered over 60 minutes, most clinical evidence (including safety outcomes) was derived on the basis of a single infusion of 1 g over 60 minutes.[531]<\/a>,[536]<\/a>–[538]<\/a><\/sup> Procainamide is more effective for the conversion of recent-onset AF (50%-60% conversion) than for AFL (30% conversion).[531]<\/a>,[536]<\/a>–[538]<\/a><\/sup> The most common side effect is hypotension (approximately 5%), although premature ventricular contractions, runs of ventricular tachycardia and QRS widening might occur.[531]<\/a>,[536]<\/a>,[537]<\/a><\/sup> This medication, like all drugs with class I (Na+<\/sup> channel-blocking) action, should be avoided in patients with Brugada syndrome.[539]<\/a><\/sup><\/p>\n\n\n\n Ibutilide is an I.V. class III agent that has been shown to effectively terminate AFL (50%-75%) and AF (30%-50%), with cardioversion typically occurring within 30-60 minutes.[540]<\/a>–[546]<\/a> <\/sup>However, widespread clinical uptake has been limited by a significant risk of torsades de pointes (TdP) and ventricular tachycardia (most frequently nonsustained), each of which occurs in approximately 2%-3% of patients.[540]<\/a>–[548]<\/a><\/sup> Consequently, ibutilide should not be used in patients with a prolonged QTc (> 440 ms), a history of HF (typically defined as clinically symptomatic or NYHA classification > II), or reduced EF, signs of an ACS, and\/or low serum potassium or magnesium levels.[540]<\/a>–[545]<\/a>,[547]<\/a><\/sup> Periprocedural I.V. magnesium (typically given pre- and post treatment) appears to improve ibutilide cardioversion rates, with higher doses (eg, 4 g total) more effective than lower doses (1-3 g total).[549]<\/a>,[550]<\/a><\/sup> Patients must be observed with continuous ECG monitoring for a minimum of 4 hours after ibutilide administration.<\/p>\n\n\n\n Vernakalant is an atrial-selective antiarrhythmic approved for conversion of AF. In patients treated within 48 hours of AF onset, randomized trials report a conversion rate at 90 minutes ranging from 52% to 69%, which is not significantly better than other active agents (combined comparator of ibutilide and amiodarone).[544]<\/a>,[545]<\/a>,[551]<\/a>–[553]<\/a><\/sup> However, the median time to cardioversion of 10-12 minutes is shorter than the next fastest pharmacological agent (ibutilide, median time to conversion 26 minutes). The major side effects are hypotension and bradycardia after cardioversion.[551]<\/a>,[554]<\/a>,[555]<\/a><\/sup> Transient but fairly common side effects include dysgeusia, paresthesia, and nausea.[544]<\/a>,[551]<\/a>,[554]<\/a>,[555]<\/a><\/sup> Vernakalant is not effective for the conversion of AFL; and should be avoided in patients with hypotension, severe HF (NYHA classification III\/IV), bradycardia, recent ACS, or severe aortic stenosis.[552]<\/a>,[555]<\/a>,[556]<\/a><\/sup><\/p>\n\n\n\n With the exception of patients with structural heart disease, amiodarone is not recommended for acute rhythm control because of a delay in conversion (approximately 8 hours).[525]<\/a>,[532]<\/a>,[557]<\/a><\/sup> The most common adverse drug reactions with I.V. administration are phlebitis, hypotension, and bradycardia.[525]<\/a>,[532]<\/a><\/sup> Although there is potential for prolongation of the QT interval, the incidence of TdP is rare.[532]<\/a>,[557]<\/a><\/sup><\/p>\n\n\n\n I.V. flecainide and propafenone are superior to placebo but are not currently available in Canada for acute care cardioversion.[525]<\/a>,[558]<\/a><\/sup> The oral formulations, however, have similar, if slightly delayed, efficacy as their I.V. counterparts.[558]<\/a>,[559]<\/a><\/sup> Three hours after administration of a single dose of oral flecainide, between 57% and 68% of patients will convert.[532]<\/a><\/sup> Success rates with oral propafenone are similar.[532]<\/a>,[559]<\/a><\/sup> Although the time to cardioversion (approximately 2-6 hours) is longer than with I.V. formulations, the major clinical benefit is that patients are able to treat their AF episodes at home (\u201cpill-in-the-pocket\u201d), which reduces the need to visit the ED for recurrences. A key caveat to this approach is that the first treatment attempt must be administered in a monitored environment, to verify efficacy and exclude treatment-related adverse reactions.[557]<\/a>,[560]<\/a>–[563]<\/a><\/sup> A \u03b2-blocker or ND-CCB should be given \u2265 30 minutes before administration of a class Ic antiarrhythmic to prevent the risk of 1:1 AV conduction during AFL. One study suggests that rare adverse events can occur even after successful use in a monitored environment[563]<\/a><\/sup>; therefore, clear instructions must be given to these patients about when to seek emergency care (Supplemental Table S12). It is important to note that flecainide and propafenone should not be used in patients with structural heart disease, including a history of ischemic heart disease.<\/p>\n\n\n\n In patients with hemodynamically stable recent-onset AF in whom sinus rhythm restoration is desired, there is a wealth of observational data supporting the safety and efficacy (approximately 90%) of direct-current cardioversion (DCCV).[363]<\/a>,[531]<\/a>,[533]<\/a>,[535]<\/a>,[564]<\/a>–[567]<\/a><\/sup> Since the late 1990s patient sedation and cardioversion have typically been performed by emergency physicians in the Canadian ED setting.[531]<\/a>,[535]<\/a>,[565]<\/a><\/sup> Adverse events attributable to DCCV such as bradyarrhythmia, acute HF, and skin burns are rare.[533]<\/a>,[566]<\/a>,[567]<\/a><\/sup> The time to patient discharge using DCCV is shorter than when using pharmacological cardioversion.[534]<\/a>,[568]<\/a><\/sup> Importantly, AF patients who receive DCCV in the ED rate their care as more effective compared with those who receive only rate control, however, their QOL scores at 30 days were not different than those treated with only rate control.[569]<\/a><\/sup> Biphasic shocks are preferred over monophasic because less energy is required.[570]<\/a><\/sup> Pad placement (anterolateral vs anteroposterior) does not seem to influence cardioversion efficacy.[538]<\/a>,[571]<\/a> <\/sup>In obese patients, using paddles and applying force might improve success rates with DCCV over adhesive pads.[572]<\/a>,[573]<\/a><\/sup> Pretreatment with antiarrhythmic drugs (eg, ibutilide and amiodarone) has been shown to improve the effectiveness of DCCV.[363]<\/a>,[574]<\/a><\/sup><\/p>\n\n\n Recommendation<\/p> 81. We recommend at least a 150-J biphasic waveform as the initial energy setting for DCCV (Strong Recommendation; Low-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a high value on the avoidance of repeated shocks after ineffective attempts at low-energy cardioversion.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Electrical cardioversion should ideally be performed with one trained operator managing the sedation and airway and a second trained operator managing the synchronized DCCV. Atropine and pacing capability must be immediately available in case of prolonged sinus pause after cardioversion.<\/p>\n 82. We suggest antiarrhythmic drug therapy be considered to enhance the efficacy of electrical cardioversion and the maintenance of sinus rhythm, particularly in patients with persistent and long-standing persistent AF (Weak Recommendation; Low-Quality Evidence).<\/p>\n 83. We suggest that the use of antiarrhythmic drug therapy after sinus rhythm restoration be on the basis of the estimated probability of AF recurrence (Weak Recommendation; Low-Quality Evidence).<\/p>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a high value on minimizing the risk of infrequent but serious side effects associated with long-term antiarrhythmic drugs. A high value is also placed on the appropriate use of speciality care to make patient-specific decisions to minimize these risks.<\/p>\n<\/div>\n\n\n\n Pharmacotherapy for long-term AF rate control revolves around agents with negative dromotropic properties such as \u03b2-blockers and ND-CCBs (verapamil and diltiazem). The choice of a specific rate-controlling regimen should be on the basis of patient\u2019s characteristics and the drug\u2019s efficacy\/side effect profile (Supplemental Table S10; Fig. 18).[575]<\/a><\/sup> In patients without significant LV dysfunction (LVEF > 40%), \u03b2-blockers and ND-CCBs are first-line options. There are no randomized long-term data to support choosing a \u03b2-blocker over an ND-CCB. Several retrospective studies of AF patients have shown conflicting results when rates of hospital admission after using \u03b2-blockers vs CCBs were compared: one showed no difference whereas another showed that use of CCBs was associated with a higher rate of hospitalization compared with use of \u03b2-blockers.[520]<\/a>,[576]<\/a><\/sup> In the longer-term, \u03b2-blockers might be more effective at slowing ventricular rates at rest and during exercise, however, their use is associated with a higher risk of adverse effects, notably fatigue and exercise intolerance.[577]<\/a>–[580]<\/a><\/sup> Moreover, there is emerging evidence suggesting that CCBs might have favourable dose-response characteristics for AF rate control vs \u03b2-blockers, such that they might be preferred in patients with a preserved LVEF and without another indication for a \u03b2-blocker.[522]<\/a>,[580]<\/a>–[582]<\/a><\/sup> Specific patient characteristics might favour the use of one pharmacological class (eg, ND-CCBs with hypertension or reactive airway disease, vs \u03b2-blockers with CAD). Caution should be used when \u03b2-blockers are used with ND-CCBs. In patients with significant LV systolic dysfunction (LVEF \u2264 40%), maximally tolerated doses of evidence-based \u03b2-blockers (extended-release metoprolol succinate, bisoprolol, carvedilol) remain first-line therapy for rate control, although the benefits of adrenergic blockade, in addition to that provided by the control of the ventricular response rate, are uncertain.[583]<\/a>–[588]<\/a><\/sup><\/p>\n\n\n\n Recommendation<\/p> 84. We recommend \u03b2-blockers or ND-CCBs (diltiazem or verapamil) be first-line agents for rate control of AF in patients without significant LV dysfunction (LVEF > 40%) (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a high value on the extensive clinical experience and record of safety and efficacy of \u03b2-blockers and ND-CCBs (verapamil and diltiazem) for AF rate control.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> The choice of specific rate-controlling agents should be guided by the patient\u2019s characteristics and the drug efficacy\/side effect profile.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> ND-CCBs (verapamil and diltiazem) have favourable pharmacological properties for rate control and might be the preferred choice in patients without a compelling indication for \u03b2-blocker usage.<\/p>\n 85. We recommend evidence-based \u03b2-blockers (bisoprolol, carvedilol, metoprolol) be first-line agents for rate control of AF in patients with significant LV dysfunction (LVEF \u2264 40%) (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n 86. We recommend against rate control as a treatment strategy in patients with AF and who manifest preexcitation (Strong Recommendation; Moderate-Quality Evidence).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> See section 11.8 for the management of patients with AF and pre-excitation.<\/p>\n 87. We suggest combination therapy (eg, a \u03b2-blocker with a ND-CCB) in patients who do not achieve satisfactory symptom or heart rate control with monotherapy (Weak Recommendation; Low-Quality Evidence).<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Combination therapy should be used with caution in patients at risk of significant bradycardia\/AV block (eg, patients with resting sinus bradycardia or with significant conduction disease). These patients might require pacemaker implantation to facilitate pharmacological rate control.<\/p>\n<\/div>\n\n\n\n Monotherapy with digoxin is generally ineffective in younger patients because of its inability to control ventricular rate during exertion or stress. Moreover, digoxin has a narrow therapeutic window, with observational evidence suggesting potential harmful effects when used for ventricular rate control.[589]<\/a>–[592]<\/a><\/sup> However, a recent meta-analysis of 28 trials of digoxin for AF rate control showed no increase in all-cause mortality vs control intervention (RR, 0.82; 95% CI, 0.24-11.5).[593]<\/a><\/sup> As such, digoxin remains a reasonable choice for selected older or sedentary patients with HF and for those with inadequate rate control while receiving maximally tolerated doses of a \u03b2-blocker\/ND-CCB. Although there is no direct evidence to support digoxin concentration monitoring for AF rate control, it might be reasonable to monitor patients at risk of digoxin-related adverse events (eg, female sex with low body weight and impaired renal function), at the clinician\u2019s discretion, aiming for trough levels between 0.5 and 0.9 ng\/mL.[594]<\/a><\/sup> Furthermore, it is important to note that coadministration of ND-CCBs and amiodarone will decrease digoxin clearance, resulting in a propensity toward toxicity.<\/p>\n\n\n Recommendation<\/p> 88. We suggest that digoxin be considered as a monotherapy in older or sedentary individuals with permanent AF; or those with side effects or contraindications to first-line agents; or in addition to first-line agents in those who fail to achieve satisfactory symptom or heart rate control (Weak Recommendation; Low-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a lesser value on observational cohort studies in which adverse outcomes from digoxin have been reported.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Digoxin is relatively ineffective for heart rate control in younger patients during activity but might be useful in older or sedentary individuals with HF, particularly in combination therapy.<\/p>\n<\/div>\n\n\n Practical Tip<\/p> Therapeutic drug monitoring might be useful in adjusting digoxin dose, particularly in patients at risk of digoxin-related adverse events (eg, female sex with low body weight and impaired renal function). In patients with HF with reduced EF (HFrEF) trough levels between 0.5 and 0.9 ng\/mL were associated with a significant decrease in all cause mortality and hospitalizations compared with levels \u2265 1.0 ng\/mL, however, the optimal trough level for AF patients is unknown.<\/p>\n<\/div>\n\n\n\n Amiodarone is a class III antiarrhythmic with complex pharmacological properties and potential serious adverse effects. However, selected patients such as the critically ill or those with side effects from, or contraindication to, first-line agents might benefit from amiodarone for rate control after careful consideration of alternative agents, alternative approaches (eg, transition to rhythm control), and risk\/benefits of continued amiodarone therapy.[595]<\/a>,[596]<\/a><\/sup><\/p>\n\n\n Recommendation<\/p> <\/p>\n 89. We recommend that amiodarone be used for AF rate control only in highly-selected patients such as the critically ill or those with significant side effects from or contraindication to first-line agents after careful consideration of alternative agents and risk\/benefits of amiodarone therapy (Strong Recommendation; Low-Quality Evidence).<\/p>\n <\/p>\n Dronedarone should not be used for AF rate control because it was associated with excess HF, stroke, and cardiovascular death in the P<\/strong>ermanent A<\/strong>trial Fibrilla<\/strong>tion Outcome S<\/strong>tudy Using Dronedarone on Top of Standard Therapy (PALLAS) trial.[597]<\/a><\/sup><\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Recommendation<\/p> 90. We recommend dronedarone not be used for AF rate control or in patients with HF (Strong Recommendation; High-Quality Evidence).<\/p>\n <\/div>\n <\/div>\n<\/div>\n\n\n Values and Preferences<\/p> This recommendation places a high value on randomized controlled trial data that have shown that the use of dronedarone resulted in excess of cardiovascular death, and unplanned cardiovascular hospitalization.<\/p>\n<\/div>\n\n\n\n The goals of ventricular rate control are the reduction of AF-related symptoms and the prevention of adverse cardiovascular events, rather than the achievement of a specific heart rate target. It is known that overly aggressive rate control is associated with adverse outcomes (eg, risk of symptomatic bradycardia with subsequent pacemaker implantation) and increased frequency of medical encounters. Conversely, overly lenient rate control might lead to HF (eg, tachycardia-mediated cardiomyopathy). In addition, specific populations might need stricter HR targets (eg, patients with cardiac resynchronization therapy [CRT], HF, tachycardia-mediated cardiomyopathy, mitral stenosis, stable angina), whereas others might do well with a more lenient target. As such, the intensity of AF rate control beyond the target HR of \u2264 100 bpm should be individualized on the basis of clinical characteristics and coexisting cardiovascular diagnoses. Most of the evidence to guide clinical decision-making for ventricular rate control targets has been acquired in patients with preserved LVEF.[512]<\/a>–[514]<\/a>,[598]<\/a><\/sup> Previous guidelines have recommended heart rate targets of < 80 bpm at rest and < 110 bpm with exercise, because these targets were used in the A<\/strong>trial F<\/strong>ibrillation F<\/strong>ollow-up I<\/strong>nvestigation of R<\/strong>hythm M<\/strong>anagement (AFFIRM) study.[512]<\/sup> However, retrospective analyses of the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) and AFFIRM studies suggested that cardiovascular morbidity, mortality, and QOL did not differ between those achieving or not achieving the prespecified heart rate target (but still maintaining a resting heart rate < 100 bpm).[599]<\/a><\/sup> The prospective randomized Ratecontrol Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient Versus Strict Rate-control-II (RACE-II) trial598 showed that lenient rate control (resting heart rate target < 110 bpm) was noninferior to strict rate control (resting heart rate target < 80 bpm, < 110 bpm with exercise), with fewer medications, lower medication doses, fewer adverse events, and reduced health care utilization. However, it is important to recognize that the mean heart rates achieved were 76 \u00b1 14 bpm in the strict group and 85 \u00b1 14 bpm in the lenient group, with very few of those patients randomized to lenient rate control having resting heart rate of > 100 bpm.[600]<\/a><\/sup> As such, there remain some questions as to the ideal heart rate target. A recent analysis of the O<\/strong>utcomes R<\/strong>egistry for B<\/strong>etter I<\/strong>nformed T<\/strong>reatment of A<\/strong>trial F<\/strong>ibrillation (ORBITAF) registry and a retrospective analysis of the AFFIRM and A<\/strong>trial F<\/strong>ibrillation and C<\/strong>ongestive H<\/strong>eart
2. Determination of hemodynamic stability, defined as AF causing hypotension, ACS, or pulmonary edema. Acute unstable AF should be treated with synchronized direct current cardioversion (DCCV), however, instability solely due to AF is rare, therefore, an underlying precipitant should also be aggressively sought and managed.[511]<\/a><\/sup>
3. Determination of an arrhythmia management strategy, defined as rate vs rhythm control. In patients with established AF multiple RCTs have shown no significant difference in cardiovascular outcomes between patients treated with a strategy with rate control vs rhythm control.[512]<\/a>–[514]<\/a><\/sup> In patients with newly diagnosed AF (ie, within a year) an initial strategy of rhythm control has been associated with reduced cardiovascular death and reduced rates of stroke.[515]<\/a><\/sup>
4. Determination of the need for hospitalization. Most patients with AF can be safely discharged home after acute management. However, hospitalization might be required for highly symptomatic patients with AF in association with acute medical illness or complex medical conditions, in highly symptomatic patients in whom adequate rate control cannot be achieved, or in those who require monitoring or ancillary investigations not readily available in the outpatient setting.
5. Determination of the need for OAC. There is evidence that OAC prescription in the ED results in improved longterm use.[364]<\/a>,[516]<\/a>,[517]<\/a><\/sup> As such, it is of paramount importance that OAC be initiated as soon as time allows in patients who undergo cardioversion for new-onset AF (see section 8.4.1), as well as in patients at risk of stroke (see the \u201cCCS algorithm\u201d in Fig. 8) whether or not attempts at rhythm control are made.
6. Early follow-up. Patients discharged from the ED with AF benefit from early follow-up. Ideally this should occur within a week of discharge, because early follow-up has been associated with lower rates of readmission and death.[518]<\/a><\/sup> In addition, cardiology assessment within 3 months of hospital discharge for new-onset AF has been associated with lower rates of death, stroke, and major bleeding.[519]<\/a><\/sup>
A general overview of rate and rhythm management of AF is provided in Figure 16, and the approach to the management of AF in the acute care setting is provided in Figure 17.<\/p>\n\n\n9.1.1 Acute rate control<\/h3>\n\n\n\n
9.1.1.1 Acute rate control targets<\/h4>\n\n\n\n
<\/figure>\n\n\n\n
9.1.2 Acute rhythm control <\/h3>\n\n\n\n
9.1.2.1 Pharmacologic cardioversion<\/h4>\n\n\n\n
<\/figure>\n\n\n\n
9.1.2.1.1 Procainamide<\/h5>\n\n\n\n
9.1.2.1.2 Ibutilide<\/h5>\n\n\n\n
9.1.2.1.3 Vernakalant<\/h5>\n\n\n\n
9.1.2.1.4 Amiodarone<\/h5>\n\n\n\n
9.1.2.1.5 Flecainide and propafenone<\/h5>\n\n\n\n
9.1.2.2 Electrical cardioversion<\/h4>\n\n\n\n
9.2 Long-term rate control<\/h2>\n\n\n\n
9.2.1 Agents<\/h3>\n\n\n\n
<\/figure>\n\n\n
9.2.2 Targets<\/h3>\n\n\n\n