May consider monitoring flecainide plasma levels, keeping trough plasma levels below 0.7 1.0 mcg/mL) Atrial flutter with 1:1 AV conduction , QT prolongation, torsades de pointes, worsening HF, bradycardia Sinus or AV conduction disease (in absence of pacemaker) Cardiogenic shock Avoid in structural heart disease (including ischemic heart disease) Atrial flutter (unless concomitant AV nodal therapy to avoid 1:1 conduction) Brugada syndrome Renal dysfunction Hepatic dysfunction QT-prolonging drugs Amiodarone, digoxin, ritonavir, saquinavir, tipranavir Propafenone 150 mg every 8 h (immediate release); 225 mg every 12 h (extended release) 300 mg every 8 h (immediate release); 425 mg every 12 h (extended release) (PR and QRS interval should be monitored. Consider dosage reduction with hepatic impairment) Atrial flutter with 1:1 AV conduction , QT prolongation, torsades de pointes, bradycardia, bronchospasm Sinus or AV conduction disease (in absence of pacemaker) Cardiogenic shock Hypotension Reactive airway disease Avoid in structural heart disease (including ischemic heart disease) Atrial flutter (unless concomitant AV nodal therapy to avoid 1:1 conduction) Brugada syndrome Hepatic dysfunction QT-prolonging drugs Drugs with SA and/or AV nodal blocking properties Amiodarone, ritonavir, saquinavir, tipranavir (Continued) Table 7. Continued Drug Initial Daily Dose(s) Maximum Total Daily Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions (Continued) Class III antiarrhythmic agents Amiodarone 400 600 mg QD in divided doses for 2 4 wk (loading dose); followed by 100 200 mg QD (maintenance dose) Up to 1200 mg QD may be considered in an inpatient monitoring setting (loading dose); up to 200 mg QD maintenance (to minimize long-term adverse effects) Bradycardia, QT prolongation, torsades de pointes (rare), gastrointestinal upset, constipation, hypothyroidism, hyperthyroidism, pulmonary fibrosis, hepatic toxicity, corneal deposits, optic neuritis, peripheral neuropathy, photosensitivity, adult respiratory distress syndrome after cardiac or noncardiac surgery (rare) Sinus or AV conduction disease (in absence of pacemaker) Inflammatory lung disease Hepatic dysfunction Hypothyroidism, hyperthyroidism Peripheral neuropathy Abnormal gait/ataxia Optic neuritis Drugs with SA and/or AV nodal blocking properties Amiodarone is a substrate of and inhibits P-glycoprotein and CYP2C9 (moderate), CYP2D6 (moderate), and CYP3A4 (weak); amiodarone is a substrate for CYP3A4 (major) and CYP2C8 (major); amiodarone is an inhibitor of OCT2 Reduce warfarin dose by 50%, and reduce digoxin dose by 30% 50% Agalsidase alfa, agalsidase beta, azithromycin, bosutinib, ceritinib, colchicine, dabigatran, edoxaban, flecainide, ivabradine, ledipasvir/sofosbuvir, lopinavir, lopinavir/ ritonavir, lovastatin, nelfinavir, pazopanib, propafenone, simvastatin, ritonavir, rivaroxaban, saquinavir, sofosbuvir, topotecan, vincristine, grapefruit juice Dofetilide 500 mcg every 12 h (if CrCl >60 mL/min) 250 mcg every 12 h (if CrCl 40 60 mL/min) 125 mcg every 12 h (if CrCl 20 to <40 mL/min) Not recommended if CrCl <20 mL/min Adjust dose for renal function, body size, and age Initiate for minimum of 3 d in a facility that can provide continuous ECG monitoring and cardiac resuscitation Contraindicated if the baseline QTc interval or QTc >440 ms or 500 ms in patients with ventricular conduction abnormalities Repeat ECG 2 3 h after administering the first dose to determine QTc; if the QTc increased by >15% compared with baseline or if QTc is >500 ms (550 ms in patients with ventricular conduction abnormalities), subsequent dosing should be down titrated by 50%; at 2 3 h after each subsequent dose, determine QTc (for in-hospital doses 2 5); if at any time after the second dose the QTc is >500 ms (550 ms in patients with ventricular conduction abnormalities), dofetilide should be discontinued QT prolongation, torsades de pointes Severe renal dysfunction (contraindicated if CrCl Prolonged QT History of torsades de pointes Concomitant use of hydrochlorothiazide, cimetidine, dolutegravir, itraconazole, ketoconazole, megestrol, trimethoprim, prochlorperazine trimethoprim/ sulfamethoxazole or verapamil, contraindicated Avoid other QT-prolonging drugs Sotalol 40 80 mg every 12 h (Patients initiated or reinitiated on sotalol should be placed in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring for a minimum of 3 d). Contraindicated if the QTc interval is >450 ms. CrCl should be calculated before dosing. If CrCl >60 mL/min, then dosing frequency is twice daily. If CrCl 40 60 mL/min, dosing interval is every 24 h. If CrCl <40 mL/min, should not be used.) 160 mg every 12 h (During initiation and titration, the QT interval should be monitored 2 4 h after each dose. If the QT interval prolongs to 500 ms, the dose must be reduced or the drug discontinued.) QT prolongation, torsades de pointes, bradycardia, bronchospasm Prolonged QT Renal dysfunction Hypokalemia Diuretic therapy Avoid other QT-prolonging drugs Sinus or AV nodal dysfunction (in absence of pacemaker) Decompensated systolic HF Cardiogenic shock Reactive airway disease Drugs with SA and/or AV nodal blocking properties Table 7. Continued Drug Initial Daily Dose(s) Maximum Total Daily Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions Page et al 2015 ACC/AHA/HRS SVT Guideline e531 patients with MAT who do not have ventricular dysfunction, sinus node dysfunction, or AV block227,228 ; although diltiazem has not been studied, it may provide a class effect with similar mechanism to verapamil. Beta blockers can be used with cau- tion to treat MAT in the absence of respiratory decompensa- tion, sinus node dysfunction, or AV block.229,230 Amiodarone has been reported to be useful in 1 report.231 Cardioversion is not useful in MAT.223 4.2.1. Acute Treatment: Recommendation 4.2.2. Ongoing Management: Recommendations 5.Atrioventricular Nodal Reentrant Tachycardia See Figure 12 for the algorithm for acute treatment of AVNRT and Figure 13 for the algorithm for ongoing management of AVNRT. AVNRT is the most common SVT. It is usually seen in young adults without structural heart disease or ischemic heart disease, and >60% of cases are observed in women.49 The ventricular rate is often 180 bpm to 200 bpm but ranges from 110 bpm to >250 bpm (and in rare cases, the rate can be Miscellaneous Ivabradine 5 mg BID 7.5 mg BID Phosphenes, AF Concomitant drugs that can exacerbate bradycardia Contraindicated in decompensated HF Contraindicated if BP <90/50 mmHg Contraindicated in severe hepatic impairment Hypertension Ivabradine is a substrate of CYP3A4 (major) Avoid use with concomitant strong CYP3A4 inhibitors (boceprevir, clarithromycin, indinavir, itraconazole, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, telaprevir, posaconazole, voriconazole) Avoid use with strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John s wort) Avoid use with diltiazem, verapamil, grapefruit juice Note: For this reference table, drugs are presented in alphabetical order within the drug classes, not by COR and LOE. *When 1 drug is used in combination with other drugs, appropriate dosing adjustments should be made with consideration of at least additive effects during dosage titration. All potential drug drug interactions and adverse reactions are not included in this list. For a more detailed list of drug interactions and adverse responses, clinicians should consult additional resources; for example, www.crediblemeds.org may be consulted for potential prolongation of the QT interval. QTc calculation used the Bazett s Formula in most clinical studies. Recommended given in conjunction with a beta blocker or nondihydropyridine calcium channel antagonist. AF indicates atrial fibrillation; AV, atrioventricular; BID, twice daily; BP, blood pressure; CrCl, creatinine clearance; ECG, electrocardiogram/electrocardiographic; HF, heart failure; INR, international normalized ratio; LV, left ventricular; QD, once daily; QID, 4 times a day; QTc, corrected QT interval; SA, sinoatrial; SVT, supraventricular tachycardia; TID, 3 times a day; and WPW, Wolff-Parkinson-White. Table 7. Continued Drug Initial Daily Dose(s) Maximum Total Daily Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions Recommendations for Ongoing Management of Multifocal Atrial Tachycardia COR LOE Recommendations IIa B-NR 1. Oral verapamil (Level of Evidence: B-NR) or diltiazem (Level of Evidence: C-LD) is reasonable for ongoing management in patients with recurrent symptomatic MAT.227,230 C-LD See Online Data Supplement 8. Long-term management of MAT frequently involves slowing of the ventricular response because arrhythmia termination is often not achievable. Verapamil has the advantage of not exacerbating pulmonary disease. Although it would be expected for diltiazem to have a similar effect, data on its use in patients with MAT are lacking. These drugs should not be used in patients with severe conduction abnormalities or sinus node dysfunction because those conditions can be exacerbated with these agents. Recommendations for Acute Treatment of Multifocal Atrial Tachycardia COR LOE Recommendation IIa C-LD 1. Intravenous metoprolol229 can be useful for acute treatment in patients with MAT. See Online Data Supplement 7. The mechanism of MAT can involve triggered activity, and treatment with intravenous verapamil can terminate the arrhythmia with moderate success. In 1 small study, intravenous verapamil converted MAT in 8 of 16 patients treated.233 Alternatively, intravenous verapamil may acutely slow the ventricular response to MAT. The major potential side effect is hypotension.233 The relatively cardioselective beta blocker metoprolol can also work by slowing the ventricular rate in MAT. Beta blockers are typically avoided in patients with severe underlying pulmonary disease, particularly those with bronchospasm; both beta blockers and verapamil are typically avoided in the presence of acute decompensated heart failure and/or hemodynamic instability. The anatomic substrate of AVNRT is dual AV nodal physiology (Table 3). AVNRT is often well tolerated and is rarely life threaten- ing. Patients will typically present with the sudden onset of palpitations and possibly with shortness of breath, dizziness, and neck pulsations. Syncope is a rare manifestation of AVNRT. AVNRT may occur spontaneously or on provocation with exertion, coffee, tea, or alcohol. 5.1. Acute Treatment: Recommendations IIa C-LD 2. Metoprolol is reasonable for ongoing management in patients with recurrent symptomatic MAT.226,229,230 See Online Data and 8. Beta blockers are typically avoided in the presence of acute decompensated heart failure or in patients with severe (particularly bronchospastic) pulmonary disease. However, metoprolol has been used in small studies in patients with serious pulmonary disease after correction of hypoxia or other signs of acute decompensation. In these studies, intravenous or oral metoprolol resulted in conversion to sinus rhythm or achieved rate control, and oral metoprolol was used for maintenance therapy.226,230 Beta blockers are generally avoided in patients with severe conduction abnormalities or sinus node dysfunction. Recommendations for Ongoing Management of Multifocal Atrial Tachycardia (Continued) COR LOE Recommendations Recommendations for Acute Treatment of AVNRT COR LOE Recommendations I B-R 1. Vagal maneuvers are recommended for acute treatment in patients with AVNRT.82 84,234,235 See Online Data Supplement 10. For acute conversion of AVNRT, vagal maneuvers, including Valsalva and carotid sinus massage, can be performed quickly and should be the first-line intervention to terminate SVT. These maneuvers should be performed with the patient in the supine position. There is no gold standard for proper Valsalva maneuver technique, but in general, the patient raises intrathoracic pressure by bearing down against a closed glottis for 10 to 30 seconds, equivalent to at least 30 mmHg to 40 mmHg.82,84 Carotid massage is performed after absence of bruit has been confirmed by auscultation, by applying steady pressure over the right or left carotid sinus for 5 to10 seconds.83,84 Another vagal maneuver based on the classic diving reflex consists of applying an ice-cold, wet towel to the face85 ; in a laboratory setting, facial immersion in water at 10 C (50 F) has proved effective in terminating tachycardia, as well.86 One study involving 148 patients with SVT demonstrated that Valsalva was more successful than carotid sinus massage, and switching from 1 technique to the other resulted in an overall success rate of 27.7%.82 The practice of applying pressure to the eyeball is potentially dangerous and has been abandoned. I B-R 2. Adenosine is recommended for acute treatment in patients with AVNRT.42,51,91,236 See Online Data and 10. Adenosine can be considered as both a therapeutic and diagnostic agent in narrow-complex tachyarrhythmias. It will acutely terminate AVNRT in approximately 95% of patients and will unmask atrial activity in arrhythmias, such as atrial flutter or AT.91,236 I B-NR Synchronized cardioversion should be performed for acute treatment in hemodynamically unstable patients with AVNRT when adenosine and vagal maneuvers do not terminate the tachycardia or are not feasible.94,208 See Online Data Supplement 10. Sinus rhythm must be promptly restored in patients with AVNRT who are hemodynamically unstable. The safety and effectiveness of cardioversion has been proven in patients with hemodynamically unstable SVT who had failed to convert with vagal maneuvers and intravenous pharmacological therapy.94 I B-NR Synchronized cardioversion is recommended for acute treatment in hemodynamically stable patients with AVNRT when pharmacological therapy does not terminate the tachycardia or is contraindicated.87,95 See Online Data and 9. Synchronized cardioversion is highly effective in terminating SVT (including AVRT and AVNRT).94 Most stable patients with SVT respond to pharmacological therapy, with success rates of 80% to 98% for agents such as verapamil, diltiazem, or adenosine. In some resistant cases, a second drug bolus or higher dose of initial drug agent is often effective.87,96 Nevertheless, in rare instances, drugs may fail to successfully restore sinus rhythm, necessitating synchronized cardioversion. IIa B-R Intravenous beta blockers, diltiazem, or verapamil are reasonable for acute treatment in hemodynamically stable patients with See Online Data Supplement 10. Intravenous diltiazem and verapamil are particularly effective in converting AVNRT to sinus rhythm. These drugs should be used only in hemodynamically stable patients. It is important to ensure the absence of VT or pre-excited AF, because patients with these rhythms may become hemodynamically unstable and develop ventricular fibrillation if administered diltiazem or verapamil. Diltiazem or verapamil should also be avoided in patients with suspected systolic heart failure. Evidence for the effectiveness of beta blockers to terminate AVNRT is limited. In a trial that compared esmolol with diltiazem, diltiazem was more effective in terminating SVT.237 Nonetheless, beta blockers have an excellent safety profile, so it is reasonable to use them to attempt to terminate SVT in hemodynamically stable patients. IIb C-LD 1. Oral beta blockers, diltiazem, or verapamil may be reasonable for acute treatment in hemodynamically stable patients with AVNRT.241,242 See Online Data Supplement 9. Overall, there are no data specifically studying the effect of oral beta-blocker monotherapy for the acute termination of AVNRT. However, 2 studies have demonstrated success with the combination of oral diltiazem and propranolol to terminate AVNRT or AVRT.241,242 Oral beta blockers have an excellent safety profile, and administration (particularly in patients without intravenous access) can be performed in conjunction with vagal maneuvers. IIb C-LD Intravenous amiodarone may be considered for acute treatment in hemodynamically stable patients with AVNRT when other therapies are ineffective or contraindicated.115 See Online Data Supplement 10. In a small cohort study, intravenous amiodarone was effective in terminating AVNRT.115 Long-term toxicity is not seen with intravenous amiodarone if given for a short period of time. Page et al 2015 ACC/AHA/HRS SVT Guideline e533 5.2. Ongoing Management: Recommendations Recommendations for Ongoing Management of AVNRT COR LOE Recommendations I B-R Oral verapamil or diltiazem is recommended for ongoing management in patients with AVNRT who are not candidates for, or prefer not to undergo, catheter ablation.98,99,243,244 See Online Data and 10. Both diltiazem and verapamil are well-tolerated and effective pharmacological alternatives to ablation for the ongoing treatment of patients When therapy with these agents is initiated, attention should be directed toward avoiding the potential for bradyarrhythmias and hypotension. Diltiazem and verapamil should also be avoided in patients with systolic heart failure. I B-NR 2. Catheter ablation of the slow pathway is recommended in patients with AVNRT.36,100 106,245 249 See Online Data and 10. Catheter ablation of AVNRT is regarded as first-line therapy for treatment of symptomatic AVNRT. It is potentially curative, and chronic pharmacological therapy is usually not needed after the procedure. Slow-pathway ablation (also called modification) is the preferred target during ablation of AVNRT. Large registry studies report the success rates of slow-pathway ablation to be >95%, with a <1% risk of AV block (Table 8).36,100 102,246 248 Cryoablation of AVNRT is an alternative to radiofrequency ablation. Recent systematic reviews and trials randomizing patients to radiofrequency ablation versus cryoablation suggest an equivalent acute success rate, with a lower rate of AV block but a higher rate of recurrence during I B-R Oral beta blockers are recommended for ongoing management in patients with AVNRT who are not candidates for, or prefer not to undergo, catheter ablation.99 See Online Data Supplement 9. Evidence for oral beta blockers is limited. One small study randomized patients with AVNRT and AVRT to digoxin (0.375 mg/day), propranolol (240 mg/day), or verapamil (480 mg/day), with 1 week of placebo washout between drug regimens.99 Episodes and duration of tachyarrhythmia (ascertained by diary and weekly 24-h Holter) were similar among the treatment groups, and all 3 medications were well tolerated. IIa B-R Flecainide or propafenone is reasonable for ongoing management in patients without structural heart disease or ischemic heart disease who have AVNRT and are not candidates for, or prefer not to undergo, catheter ablation and in whom beta blockers, diltiazem, or verapamil are ineffective or contraindicated.45,46,107 112,114,241,242,250,251 See Online Data and 10. In 1 RCT, the probability of 12 months of effective (defined as <2 attacks of arrhythmia) and safe treatment was 86% for propafenone and 93% for flecainide.109 Flecainide and propafenone have a risk of proarrhythmia in patients with structural heart disease or ischemic heart disease and are contraindicated in these patient groups. In 1 nonrandomized study, flecainide was evaluated as pill-in-the-pocket therapy along with diltiazem or propranolol.241,242 However, all patients were screened with EP studies, and only 5 patients were discharged on flecainide. As such, the merit of flecainide as pill in the pocket for outpatient therapy for AVNRT remains unclear. IIa B-NR Clinical follow-up without pharmacological therapy or ablation is reasonable for ongoing management in minimally symptomatic patients with AVNRT.244 See Online Data Supplement 10. In a prospective study of 93 adult patients with AVNRT who were followed for approximately 15 years, nearly half of minimally symptomatic patients who received no therapy (versus ablation or antiarrhythmic agents) improved over time and became asymptomatic.244 Patients with a confirmed or suspected diagnosis of AVNRT who choose not to undergo catheter ablation or take medications should be educated about when to seek medical attention and be taught how to perform vagal maneuvers. IIb B-R Oral sotalol or dofetilide may be reasonable for ongoing management in patients with AVNRT who are not candidates for, or prefer not to undergo, catheter ablation.107,114 See Online Data Supplement 9. Unlike flecainide and propafenone, sotalol and dofetilide can be used in patients with structural heart disease or coronary artery disease.113 Given the potential for significant QT prolongation and torsades de pointes, inpatient monitoring with serial ECGs is generally performed when these agents are initiated. Generally, these agents are reserved for patients who are unresponsive to, or are not candidates for, beta blockers, diltiazem, flecainide, propafenone, or verapamil. IIb B-R Oral digoxin or amiodarone may be reasonable for ongoing treatment of AVNRT in patients who are not candidates for, or prefer not to undergo, catheter ablation.99,115 See Online Data and 10. One small study randomized patients with unspecified PSVT to digoxin (0.375 mg/day), propranolol (240 mg/day), or verapamil (480 mg/ day), with 1 week of placebo washout.99 Episodes and duration of PSVT (ascertained by diary and weekly 24-h Holter) were largely similar, and all 3 medications were well tolerated.99 However, the dose of digoxin used was higher than that commonly used in clinical practice today. Amiodarone is effective in suppressing AVNRT during outpatient follow-up.115 Given the potential adverse effects of digoxin and amiodarone, these agents are generally reserved as third-line therapy for patients who are unresponsive to, or are not candidates for, beta blockers, diltiazem, verapamil, flecainide, or propafenone. IIb C-LD Self-administered ( pill-in-the-pocket ) acute doses of oral beta blockers, diltiazem, or verapamil may be reasonable for ongoing management in patients with infrequent, well-tolerated episodes of AVNRT.241,242 See Online Data Supplement 9. Two studies have demonstrated success with the combination of diltiazem and propranolol as a pill-in-the-pocket approach to acutely terminate PSVT caused by AVNRT, but the overall safety of self-administration of these medications remains unclear because episodes of syncope were observed.241,242 If oral therapy with empiric beta blockers, diltiazem, or verapamil fails to terminate the tachyarrhythmia, patients should seek medical attention. Figure 10. Acute treatment of suspected focal atrial tachycardia. Colors correspond to Class of Recommendation in Table 1; drugs listed alphabetically. *For rhythms that break or recur spontane- ously, synchronized cardioversion is not appropriate. IV indicates intravenous. 6. Manifest and Concealed Accessory Pathways Accessory pathways can be manifest or concealed; can con- duct in the anterograde direction, retrograde direction, or both; and can be associated with several different supraven- tricular arrhythmias. Some anterograde pathways may place patients at risk of SCD. Typically, pathways directly connect the atrium and ventricle, bypassing the normal conduction through the AV node and His Purkinje system. The pathways are considered manifest if they conduct in the anterograde direction, demonstrating pre-excitation with a delta wave on the ECG. Manifest pathways occur in 0.1% to 0.3% of the population and may conduct in both the anterograde and ret- rograde directions or, less commonly, only in the anterograde Concealed pathways conduct only in the retro- grade direction and therefore do not cause pre-excitation on the standard 12-lead ECG. The most common tachycardia associated with an accessory pathway is orthodromic AVRT, with a circuit that uses the AV node and His Purkinje system in the antero- grade direction, followed by conduction through the ventri- cle, retrograde conduction over the accessory pathway, and completion of the circuit by conduction through the atrium back into the AV node. Orthodromic AVRT accounts for approximately 90% to 95% of AVRT episodes in patients with a manifest accessory pathway. Pre-excited AVRT, including antidromic AVRT, accounts for 5% of the AVRT episodes in patients with a manifest pathway and involves conduction from the atrium to the ventricle via the acces- sory pathway, causing a pre-excited QRS complex. This is called antidromic AVRT tachycardia when the return reentrant conduction occurs retrogradely via the AV node. In rare cases of pre-excited AVRT, the return conduction occurs via a second accessory AV pathway. AF can occur in patients with accessory pathways, which may result in extremely rapid conduction to the ventricle over a manifest pathway, which increases the risk of inducing ventricular fibrillation and SCD. Other SVTs, such as AVNRT, AT, and atrial flutter, can also conduct rapidly over a manifest accessory pathway; in these instances, the pathway is con- sidered a bystander because it is not part of the tachy- cardia circuit. Most accessory pathways have conduction properties similar to the myocardium and do not demon- strate decremental conduction. A unique form of AVRT involves a concealed accessory pathway, usually located in the posteroseptal region, with retrograde decremental conduction properties resulting in a form of orthodromic reentrant tachycardia termed PJRT. This tachycardia has deeply inverted retrograde P waves in leads II, III, and aVF, with a long RP interval due to the location and decremental conduction properties of the accessory pathway (Figure 6). The incessant nature of PJRT may result in tachycardia- induced cardiomyopathy that usually resolves after suc- cessful treatment. Another unusual accessory pathway is the atriofascicular fiber (also called a Mahaim fiber) that connects the right atrium to a fascicle of the distal right bundle branch and has decremental anterograde conduction while not allowing conduction in the retrograde direction; this pathway can allow reentrant tachycardia with a cir- cuit that involves anterograde conduction over the acces- sory pathway with characteristic left bundle-branch block morphology and retrograde conduction through the AV node/His Purkinje system. Other rare accessory pathway connections that may participate in reentrant tachycardia are nodofascicular pathways (connecting the AV node to a fascicle) and nodoventricular pathways (connecting the AV node to the ventricular myocardium). Fasciculoventricular pathways, connecting a fascicle to the proximal right or left bundle branch, have also been described, although they have never been reported to participate in tachycardia. An EP study is necessary to establish the diagnosis of these rare accessory pathways. The diagnosis of WPW syndrome is reserved for patients who demonstrate ventricular pre-excitation on their resting ECG that participates in arrhythmias. Rapid anterograde accessory pathway conduction during AF can result in SCD in patients with a manifest acces- sory pathway, with a 10-year risk ranging from 0.15% Unfortunately, SCD may be the first pre- sentation of patients with undiagnosed WPW. Increased risk of SCD is associated with a history of symptomatic tachycardia, multiple accessory pathways, and a shortest pre-excited R-R interval of <250 ms during AF. The risk of SCD associated with WPW appears highest in the first Antiarrhythmic drug treatment of Page et al 2015 ACC/AHA/HRS SVT Guideline e535 patients with orthodromic AVRT can be directed at either the accessory pathway or the AV node, as both are key portions of the reentrant circuit. AV nodal blocking agents may be contraindicated in patients at risk of rapid con- duction down the accessory pathway during AF. Catheter ablation strategies target the accessory pathway, with high success rates. 6.1. Management of Patients With Symptomatic Manifest or Concealed Accessory Pathways See Figure 14 for the algorithm for acute treatment of ortho- dromic AVRT and Figure 15 for the algorithm for ongoing management of orthodromic AVRT. 6.1.1. Acute Treatment: Recommendations Recommendations for Acute Treatment of Orthodromic AVRT COR LOE Recommendations I B-R 1. Vagal maneuvers are recommended for acute treatment in patients with orthodromic AVRT.42,75,235,259 See Online Data and 12. For acute conversion of orthodromic AVRT, vagal maneuvers, including Valsalva and carotid sinus massage, can be performed quickly and should be the first-line intervention to terminate SVT. These maneuvers should be performed with the patient in the supine position. There is no gold standard for proper Valsalva maneuver technique, but in general, the patient raises intrathoracic pressure by bearing down against a closed glottis for 10 to 30 seconds, equivalent to at least 30 to 40 mm Hg.82,84 Carotid massage is performed after absence of bruit has been confirmed by auscultation, by applying steady pressure over the right or left carotid sinus for 5 to 10 Another vagal maneuver based on the classic diving reflex consists of applying an ice-cold, wet towel to the face85 ; in a laboratory setting, facial immersion in water at 10 C (50 F) has proved effective in terminating tachycardia, as well.86 One study involving 148 patients with SVT demonstrated that Valsalva was more successful than carotid sinus massage, and switching from 1 technique to the other resulted in an overall success rate of 27.7%.82 The practice of applying pressure to the eyeball is potentially dangerous and has been abandoned. I B-R 2. Adenosine is beneficial for acute treatment in patients with orthodromic AVRT.42,260,261 See Online Data and 12. Adenosine is effective for conversion of orthodromic AVRT in 90% to 95% of patients, with minor and brief (<1 min) side effects occurring in approximately 30% of patients.42,260,261 Patients often have atrial or ventricular premature complexes immediately after conversion that, on occasion, may induce further episodes of AVRT. In this situation, an antiarrhythmic drug may be required to prevent acute reinitiation of tachycardia. Because adenosine may precipitate AF that may then conduct rapidly to the ventricle and even cause ventricular fibrillation, electrical cardioversion should be available. I B-NR Synchronized cardioversion should be performed for acute treatment in hemodynamically unstable patients with AVRT if vagal maneuvers or adenosine are ineffective or not feasible.75,262,263 See Online Data Supplement 10. Synchronized cardioversion is highly effective in terminating AVRT.75 Cardioversion avoids complications associated with antiarrhythmic drug therapy and should be considered early in the management of hemodynamically unstable patients. Patients often have atrial or ventricular premature complexes immediately after cardioversion that, on occasion, may induce further episodes of AVRT. In this situation, an antiarrhythmic drug may be required to prevent acute reinitiation of tachycardia. I B-NR Synchronized cardioversion is recommended for acute treatment in hemodynamically stable patients with AVRT when pharmacological therapy is ineffective or contraindicated.87,95 See Online Data and 10. Synchronized cardioversion is highly effective in terminating SVT (including AVRT and AVNRT), and when the patient is stable, this is performed after adequate sedation or anesthesia.94 Most stable patients with SVT respond to pharmacological therapy, with success rates of 80% to 98% for agents such as verapamil, diltiazem, or adenosine. In some resistant cases, a second drug bolus or higher dose of initial drug agent might prove Nevertheless, in rare instances, drugs may fail to successfully restore sinus rhythm. I B-NR 5. Synchronized cardioversion should be performed for acute treatment in hemodynamically unstable patients with pre-excited AF.75,94 See Online Data Supplement 10. Synchronized cardioversion is highly effective in terminating pre-excited AF.75 When AF occurs in patients with ventricular pre-excitation, if the accessory pathway has a short refractory period, this may allow for rapid pre-excited AV conduction; the resulting fast, often irregular, broad- complex tachycardia is often unstable and may lead to ventricular fibrillation. It is therefore important to achieve early restoration of sinus rhythm in these patients. Patients often have atrial or ventricular premature complexes immediately after cardioversion that, on occasion, may induce AVRT or recurrent pre-excited AF. I C-LD or intravenous procainamide265 is beneficial for acute treatment in patients with pre-excited AF who are hemodynamically stable. See Online Data and 12. Small observational studies support the use of ibutilide or intravenous procainamide for the treatment of pre-excited AF in patients who are not Both medications can decrease ventricular rate by slowing conduction over the accessory pathway and have the additional benefit of possibly terminating AF.264,265 IIa B-R 1. Intravenous diltiazem, verapamil42,260,266,267 (Level of Evidence: B-R ), or beta blockers268 (Level of Evidence: C-LD) can be effective for acute treatment in patients with orthodromic AVRT who do not have pre-excitation on their resting ECG during sinus rhythm. C-LD See Online Data and 12. Intravenous diltiazem or verapamil effectively terminate approximately 90% to 95% of AVRT episodes in patients without pre-excitation on their resting sinus-rhythm ECG, with drug-induced hypotension occurring in approximately 3% of patients.42,260,266,267 Intravenous beta blockers have not been studied in clinical trials; however, clinical experience suggests they are useful for terminating AVRT, with a low risk of associated complications.268 6.1.2. Ongoing Management: Recommendations IIb B-R Intravenous beta blockers, diltiazem, or verapamil might be considered for acute treatment in patients with orthodromic AVRT who have pre-excitation on their resting ECG and have not responded to other therapies.42,266,267,269 See Online Data and 12. Intravenous beta blockers, diltiazem, and verapamil have a risk of enhancing conduction over the accessory pathway if the AVRT converts to AF during administration of the medication. Should the patient have a rapidly conducting manifest accessory pathway, further enhancing accessory-pathway conduction during AF by shortening the refractory period (digoxin) or decreasing BP and increasing catecholamines (diltiazem, beta blockers, verapamil) may place the patient at risk of AF degenerating into a malignant ventricular arrhythmia. The ability to promptly perform electrical cardioversion must be available should AF with rapid ventricular conduction occur. Before intravenous beta blockers, diltiazem, and verapamil were available, intravenous digoxin was commonly used for acute treatment of patients with orthodromic AVRT who had pre-excitation on their resting ECG270 ; this agent is rarely used now because other agents are available and digoxin may put patients at risk of ventricular fibrillation.271 III: Harm C-LD Intravenous digoxin, intravenous amiodarone, intravenous or oral beta blockers, diltiazem, and verapamil are potentially harmful for acute treatment in patients with pre-excited AF.269,271 275 See Online Data and 12. Patients with pre-excited AF should not receive intravenous digoxin, intravenous amiodarone, or intravenous/oral beta blockers, diltiazem, or verapamil because these medications may enhance conduction over the accessory pathway, increase the ventricular rate, and increase the risk of provoking a life-threatening ventricular arrhythmia.269,271 275 Digoxin increases the ventricular rate by shortening refractoriness of the accessory pathway, whereas amiodarone, beta blockers, diltiazem, and verapamil may increase the ventricular rate as a result of drug- induced hypotension with increased catecholamines. In addition, these medications may enhance conduction over the accessory pathway by slowing or blocking conduction through the AV node, preventing competitive concealed retrograde conduction into the accessory pathway. Recommendations for Acute Treatment of Orthodromic AVRT (Continued) COR LOE Recommendations Recommendations for Ongoing Management of Orthodromic AVRT COR LOE Recommendations I B-NR 1. Catheter ablation of the accessory pathway is recommended in patients with AVRT and/or pre-excited AF.103,254,276 282 See Online Data and 12. Several large series support the use of catheter ablation of the accessory pathway as first-line therapy in patients who have had AF and/or AVRT. These series report a success rate of approximately 93% to 95% and a 3% risk of major complications when patients are followed up (Table 8). AF in younger patients is usually associated with the accessory pathway and is unlikely to occur after ablation; in contrast, older patients may have recurrence of AF from causes unrelated to the accessory pathway.283,284 Catheter ablation is also effective for treating PJRT (Table 3) by ablating the concealed accessory pathway with a success rate of approximately 90%.283,284 Catheter ablation of an atriofascicular (Mahaim) pathway is successful in preventing reentrant tachycardia in approximately 70% to 100% of patients.285,286 I C-LD Oral beta blockers, diltiazem, or verapamil are indicated for ongoing management of AVRT in patients without pre- excitation on their resting ECG.46,287 See Online Data and 12. Observational studies and clinical experience confirm that beta blockers, diltiazem, and verapamil are effective for preventing recurrent tachycardia in approximately 50% of patients without pre-excitation on their resting ECG (concealed accessory pathway) and are associated with a favorable side effect profile.46,287 IIa B-R Oral flecainide or propafenone is reasonable for ongoing management in patients without structural heart disease or ischemic heart disease who have AVRT and/or pre-excited AF and are not candidates for, or prefer not to undergo, catheter See Online Data and 12. Flecainide and propafenone are beneficial for the treatment of AVRT by directly slowing or blocking conduction over the pathway. These drugs are effective in approximately 85% to 90% of patients, with 30% reporting an absence of tachycardia.45,108,109,112,288 Both drugs have a risk of proarrhythmia resulting in VT that is increased in patients with structural heart disease or ischemic heart disease; in such patients, these drugs are generally avoided. Side effects occur in up to 60% of patients, and approximately 20% discontinue the medications because of adverse effects.45,108,109,112,288 IIb B-R Oral dofetilide or sotalol may be reasonable for ongoing management in patients with AVRT and/or pre-excited AF who are not candidates for, or prefer not to undergo, catheter ablation.99,106 See Online Data Supplement 9. Unlike flecainide and propafenone, sotalol and dofetilide can be used in patients with structural heart disease or coronary artery disease.105 Given the potential for significant QT prolongation and torsades de pointes, inpatient monitoring with serial ECGs is generally performed when these agents are initiated. IIb C-LD Oral amiodarone may be considered for ongoing management in patients with AVRT and/or pre-excited AF who are not candidates for, or prefer not to undergo, catheter ablation and in whom beta blockers, diltiazem, flecainide, propafenone, and verapamil are ineffective or contraindicated.289,290 See Online Data and 12. Small observational studies support the use of amiodarone for preventing recurrent AVRT, but long-term efficacy has not been reported.289,290 Because of the important toxicity associated with long-term use of amiodarone, the drug is usually reserved for patients who are not candidates for catheter ablation and who have failed to respond to or have contraindications to other antiarrhythmic drugs. Page et al 2015 ACC/AHA/HRS SVT Guideline e537 6.2. Management of Asymptomatic Pre-Excitation 6.2.1. PICOTS Critical Questions See the ERC systematic review report, Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre- Excitation for the complete evidence review on the manage- ment of asymptomatic pre-excitation,9 and see Online Data Supplements 13, 14, and 15 for additional data on asymptomatic pre-excitation, which were reproduced directly from the ERC s systematic review. These recommendations have been designated with the notation SR to emphasize the rigor of support from the ERC s systematic review. PICOTS Question 1 did not provide adequate data for a recommendation; the other 3 PICOTS ques- tions are addressed in the recommendations in Section 6.2.2. As noted in Section 1.1, the recommendations in Section 6.3 are based on a separately commissioned systematic review of the available evidence, the results of which were used to frame our decision making. Full details are provided in the ERC s systematic review report.9 The following 4 questions were considered by the ERC: 1. What is the comparative predictive accuracy of inva- sive EP study (without catheter ablation of the acces- sory pathway) versus noninvasive testing for predicting arrhythmic events (including SCD) in patients with asymptomatic pre-excitation? 2. What is the usefulness of invasive EP study (without catheter ablation of the accessory pathway) versus no testing for predicting arrhythmic events (including SCD) in patients with asymptomatic pre-excitation? 3. What is the usefulness of invasive EP study (without catheter ablation of the accessory pathway) or noninva- sive EP study for predicting arrhythmic events (includ- ing SCD) in patients with asymptomatic pre-excitation? 4. What are the efficacy and effectiveness of invasive EP study with catheter ablation of the accessory pathway as appropriate versus noninvasive tests with treatment (including observation) or no testing/ablation as appro- priate for preventing arrhythmic events (including SCD) and improving outcomes in patients with asymptomatic pre-excitation? Figure 11. Ongoing management of focal atrial tachycardia. Colors correspond to Class of Recommendation in Table 1; drugs listed alpha- betically. Pt indicates patient; and SHD, structural heart disease (including ischemic heart disease). IIb C-LD Oral beta blockers, diltiazem, or verapamil may be reasonable for ongoing management of orthodromic AVRT in patients with pre- excitation on their resting ECG who are not candidates for, or prefer not to undergo, catheter ablation.46,287 See Online Data and 12. One RCT supports the use of verapamil for prevention of orthodromic AVRT in patients with pre-excitation on their resting ECG (manifest There are no RCTs supporting the use of oral beta blockers or diltiazem for prevention of recurrent AVRT, although clinical experience suggests the drugs are effective, with a favorable side effect profile.287 Patients with pre-excitation may develop AF during an episode of AVRT and be exposed to increased risk of rapid conduction over the accessory pathway while receiving beta blockers, diltiazem or verapamil, so these agents must be used with caution.269 The decision to treat with these agents should follow a discussion of risks with the patient. Although evidence of poor anterograde conduction via the accessory pathway may be reassuring, rapid conduction in AF has been described even in the setting of intermittent anterograde conduction.291 IIb C-LD Oral digoxin may be reasonable for ongoing management of orthodromic AVRT in patients without pre-excitation on their resting ECG who are not candidates for, or prefer not to undergo, catheter ablation.292 See Online Data Supplement 12. One small study reported the usefulness of oral digoxin in prevention of recurrent orthodromic AVRT in patients without pre-excitation on their resting ECG (concealed accessory pathway).293 Digoxin has been used clinically for many years, but the low efficacy indicates its use would be best limited to patients who are not candidates for catheter ablation or prefer pharmacological therapy and have failed to respond to other antiarrhythmic drugs. III: Harm C-LD Oral digoxin is potentially harmful for ongoing management in patients with AVRT or AF and pre-excitation on their resting ECG.271 See Online Data Supplement 12. Digoxin shortens the refractory period of the accessory pathway, such that AF may induce ventricular fibrillation.271 Even if AF has never been documented, AVRT may degenerate into AF. Thus, oral digoxin should not be used to treat patients with a manifest accessory pathway. Recommendations for Ongoing Management of Orthodromic AVRT (Continued) COR LOE Recommendations 6.2.2. Asymptomatic Patients With Pre-Excitation: Recommendations Recommendations for Management of Asymptomatic Patients With Pre-Excitation COR LOE Recommendations I B-NR SR 1. In asymptomatic patients with pre-excitation, the findings of abrupt loss of conduction over a manifest pathway during exercise testing in sinus rhythm294 297 (Level of Evidence: B-NR) SR or intermittent loss of pre-excitation during ECG or (Level of Evidence: C-LD) SR are useful to identify patients at low risk of rapid conduction over the pathway. C-LD SR See Online Data and 12. Noninvasive testing has been shown to identify patients at low risk of developing rapid conduction over the accessory pathway and life-threatening ventricular arrhythmias in response to AF. The noninvasive findings that identify a pathway not capable of maintaining rapid conduction during AF include intermittent loss of conduction over the accessory pathway on the resting ECG or during ambulatory monitoring, or abrupt loss of pre-excitation during exercise testing (Figure 16).294 297 The ECG should be evaluated closely to make certain the delta wave is truly absent, as accessory pathways, especially left lateral pathways, may demonstrate varying degrees of pre-excitation because of fusion between conduction over the accessory pathway and through the AV node. This may give the appearance of loss of pre-excitation if the subtle delta wave is not identified. Noninvasive tests have an approximately 90% positive predictive value and 30% negative predictive value for identifying pathways with life-threatening properties.294,295,297 IIa B-NR SR 1. An EP study is reasonable in asymptomatic patients with pre-excitation to risk-stratify for arrhythmic events.254,256,298 301 See Online Data Supplements 11 15. In the absence of symptoms, a clinical priority is identifying accessory pathways at increased risk of arrhythmic events, including rapid conduction during AF and development of life-threatening ventricular arrhythmias, with the most useful findings being the following: an R-R interval <250 ms between 2 pre-excited complexes during induced AF; the presence of multiple accessory pathways; the ability to induce sustained AVRT; the finding of AVRT precipitating pre-excited AF; and an accessory pathway refractory period <240 ms.254,256,298,299,301 Malignant arrhythmias correlate more with the EP properties of the accessory pathway than with the presence or absence of symptoms. This approach is supported by the low risk of complications observed in an EP study in which complication rates among 2169 patients ranged from 0.09% to 1% and included pneumothorax and access site complications.254 IIa B-NR SR Catheter ablation of the accessory pathway is reasonable in asymptomatic patients with pre-excitation if an EP study identifies a high risk of arrhythmic events, including rapidly conducting pre-excited AF.254,302,303 See Online Data Supplements 11 15. In a large prospective cohort study of 756 asymptomatic patients with close to 8 years of follow-up, 9% of patients developed malignant AF (shortest R-R interval 250 ms), and 2% developed ventricular fibrillation.254 Malignant arrhythmias correlated more with high-risk EP properties of the accessory pathway than with the presence or absence of symptoms. Ablation of the accessory pathway(s) in high-risk patients was also examined in 1 RCT that enrolled 76 patients, showing that arrhythmic events (defined as symptomatic SVT, AF, and ventricular fibrillation in this study) occurred in 7% of patients who underwent ablation versus 77% who did not undergo ablation.302 Another study that examined patients on the basis of whether an ablation was performed reported that none of the asymptomatic patients who had undergone ablation of the accessory pathway developed a malignant arrhythmia during 8 years of follow-up. The risk of complications with ablation ranged from 0.1% (complete heart block) to 0.9% (ablation-induced right bundle-branch block).254 The risks and benefits of proceeding with ablation of pathways found not to have high-risk characteristics should be discussed thoroughly with patients in advance of the EP procedure. IIa B-NR SR Catheter ablation of the accessory pathway is reasonable in asymptomatic patients if the presence of pre-excitation precludes specific employment (such as with pilots).103,254,276 282,302 304 See Online Data Supplements 11 15. Patients with asymptomatic pre-excitation whose job activities would place them or others at risk if a hemodynamically significant arrhythmia occurred (such as airline pilots) are potential candidates for catheter ablation. Catheter ablation is associated with a success rate of approximately 95% and a 3% risk of major complications when patients are followed up for 6 months to Other documents advise EP study in asymptomatic athletes who engage in moderate- or high-level IIa B-NR SR 4. Observation, without further evaluation or treatment, is reasonable in asymptomatic patients with pre-excitation.301,306 309 See Online Data Supplements 11 15. Most observational cohort studies suggest that the great majority of adult patients with asymptomatic pre-excitation who do not undergo an ablation of the accessory pathway have a benign course with few clinically significant arrhythmic events occurring over time. This supports the recommendation that observation without medical therapy or ablation is a reasonable alternative because the risk of SCD is small and is seen mainly in children.254,301,306 309 The choice to observe asymptomatic patients should be preceded by the patient being informed of the small risk of life-threatening arrhythmias developing in the absence of treatment, along with the success rate and complications associated with catheter ablation of the accessory pathway. Page et al 2015 ACC/AHA/HRS SVT Guideline e539 6.3. Risk Stratification of Symptomatic Patients With Manifest Accessory Pathways: Recommendations 7. Atrial Flutter See Figure 17 for a schematic depicting classification of atrial flutter/ATs; Figure 18 for the algorithm for acute treatment of atrial flutter; and Figure 19 for the algorithm for ongoing management of atrial flutter. 7.1. Cavotricuspid Isthmus Dependent Atrial Flutter Atrial flutter is a macroreentrant atrial arrhythmia character- ized by regular atrial rate and constant P-wave morphology. When the atrial flutter circuit involves the cavotricuspid isth- mus (CTI), it is labeled CTI-dependent atrial flutter. When CTI-dependent flutter involves a circuit that rotates around the tricuspid valve in a counterclockwise direction (up the septum and down the free wall), it is called typical ; less commonly, the CTI-dependent flutter circuit rotates in a clockwise direc- tion (sometimes called reverse typical ).203 Counterclockwise CTI-dependent atrial flutter is characterized electrocardio- graphically by dominant negative flutter waves in the inferior leads (so-called sawtooth waves ) and a positive P wave in lead V1 at atrial rates of 250 bpm to 350 bpm (Figure 17). Clockwise isthmus-dependent flutter shows the opposite pat- tern (ie, positive flutter waves in the inferior leads and wide, negative flutter waves in lead V1) (Figure 17). Although the atrial rates for flutter typically range from 250 bpm to 330 bpm, the rates may be slower in patients with severe atrial dis- ease or in patients taking antiarrhythmic agents or after unsuc- cessful catheter ablation.310 Atrial flutter can occur in clinical settings similar to those associated with AF, and atrial flutter can be triggered by AT or It is common for AF and atrial flutter to coexist in the same patient. After CTI ablation, 22% to 50% of patients have been reported to develop AF after a mean follow-up of 14 to 30 months, although 1 study reported a much higher rate ofAF devel- opment, with 82% of patients treated by catheter ablation for atrial flutter manifestingAF within 5 years.312 Risk factors for the mani- festing AF after atrial flutter ablation include prior AF, depressed left ventricular function, structural heart disease or ischemic heart disease, inducible AF, and increased LA size.121,312 316 Atrial flutter may result from antiarrhythmic therapy of AF, particularly when flecainide, propafenone, or amiodarone is used for treatment of AF.317,318 In those patients with atrial flutter resulting from antiarrhythmic therapy of AF, ablation of the CTI-dependent flutter may prevent recurrent flutter while antiarrhythmic therapy for AF is continued.318 Patients with atrial flutter are thought to have the same risk of thromboembolism as patients with AF; therefore, Figure 12. Acute treatment of AVNRT. Colors correspond to Class of Recommendation in Table 1; drugs listed alphabetically. *For rhythms that break or recur spontaneously, synchronized cardioversion is not appropriate. AVNRT indicates atrioventricular nodal reentrant tachycardia; and IV, intravenous. Recommendations for Management of Symptomatic Patients With Manifest Accessory Pathways COR LOE Recommendations I B-NR 1. In symptomatic patients with pre-excitation, the findings of abrupt loss of conduction over the pathway during exercise testing in (Level of Evidence: B-NR) or intermittent loss of pre-excitation during ECG or ambulatory monitoring297 (Level of Evidence: C-LD) are useful for identifying patients at low risk of developing rapid conduction over the pathway. C-LD See Online Data Supplements 11 15. An important consideration in the evaluation of patients with pre-excitation is determining risk of developing rapid conduction over the accessory pathway and life-threatening ventricular arrhythmias in response to AF. The noninvasive findings that identify a pathway incapable of maintaining rapid conduction during AF include intermittent loss of conduction over the accessory pathway on the resting ECG or during ambulatory monitoring or abrupt loss of pre-excitation during exercise testing.294 297 The ECG should be evaluated closely to make certain the delta wave is truly absent, as accessory pathways (especially left lateral pathways) may demonstrate varying degrees of pre-excitation because of fusion between conduction over the accessory pathway and through the AV node, which may give the appearance of loss of pre-excitation if the subtle delta wave is not identified. Noninvasive tests have an approximately 90% positive predictive value and 30% negative predictive value for identifying pathways with life- If noninvasive evaluation suggests that the accessory pathway conducts poorly in the anterograde direction, although risk of life-threatening events is likely lower, the EP study still may be useful because of patient symptoms. I B-NR 2. An EP study is useful in symptomatic patients with pre-excitation to risk-stratify for life-threatening arrhythmic events.254,256,298 300 See Online Data Supplements 11 15. Most symptomatic patients with accessory pathways undergo catheter ablation, but in some instances, EP studies are performed to identify whether the patient is at increased risk of rapid conduction down the accessory pathway during AF and development of life-threatening ventricular arrhythmias. The most useful findings for risk stratification are an R-R interval <250 ms between 2 pre-excited complexes during induced AF; the presence of multiple accessory pathways; the finding of AVRT precipitating pre-excited AF; and an accessory pathway refractory period <240 ms.254,256,298 300 recommendations for anticoagulation mirror those for patients Similarly, the recommendations for anticoag- ulation with regard to either pharmacological or electrical car- dioversion of patients with atrial flutter are the same as those for patients with AF, as discussed in the 2014 AF guideline 7.2. Non Isthmus-Dependent Atrial Flutters Non isthmus-dependent atrial flutter or atypical flutter describes macroreentrant ATs that are not dependent on conduction through the CTI. A variety of circuits have been described, including a path around the mitral annulus (perimi- tral flutter), re-entry involving the left atrial roof, and re-entry around regions of scarring in the right or left atrium. Non isthmus-dependent atrial flutters often occur in patients with atrial scarring from prior heart surgery or ablation but also may occur in any form of heart disease or may be idiopathic.134,140,319 Non isthmus-dependent atrial flutters can coexist with CTI- dependent flutter or involve the presence of multiple atrial re- The reentrant circuits are classified as either macroreentrant AT (large; often several centimeters or longer in diameter) or microreentrant AT ( 2 cm in diameter), which may be indistinguishable from focal AT.321 In the presence of substantial atrial disease, prior surgery, or prior radiofrequency catheter ablation, the ECG flutter- wave morphology is not a reliable predictor of whether the flutter circuit involves the CTI. Although an ECG with a typical flutter appearance has good predictive value for CTI- dependent flutter in a patient who has not undergone prior catheter ablation of AF, the ECG appearance is less useful in predicting the flutter circuit in a patient who has previously undergone AF ablation.322 325 The presence of a positive or biphasic (but dominantly positive) deflection in V1, accom- panied by deflections in other leads inconsistent with typical counterclockwise atrial flutter, suggests the presence of an atypical flutter (Figure 17). Definitive diagnosis requires EP study and intracardiac mapping.326 Catheter ablation of non CTI-dependent flutter requires more extensive mapping than does ablation of CTI-dependent flutter, and success rates are lower (Table 8). The location of the circuit determines ablation approach and risks. The substrate for macroreentrant atrial arrhythmias after cardiac surgery is atrial scarring from atriotomy inci- sions and cannulation sites and from the underlying myo- pathic process of the valve disease itself; this is sometimes referred to as incisional atrial reentrant tachycardia. The location of the reentrant circuit depends on the type of surgi- cal approach, and common populations include patients who have undergone mitral valve surgery or have a repaired atrial These arrhythmias are also common after surgical or catheter ablation for AF.331,332 Both single- and dual-loop circuits, as well as focal ATs, can be present. It is useful to review the procedural notes to identify the location of atrial incisions or prior ablation that can assist with future mapping and ablation. The development of a microreentrant or macroreentrant left AT after AF ablation occurs in approximately 5% of This is less frequent if ablation is limited to pulmonary vein isolation. On the other hand, these arrhythmias Figure 13. Ongoing management of AVNRT. Colors correspond to Class of Recommendation in Table 1; drugs listed alphabetically. AVNRT indi- cates atrioventricular nodal reentrant tachycardia; pt, patient; and SHD, structural heart disease (including ischemic heart disease). Page et al 2015 ACC/AHA/HRS SVT Guideline e541 are more common in patients with longer-duration persistent AF or more dilated left atria or when linear ablation lesions Non reentrant focal arrhythmias often origi- nate at lesion edges or reconnected segments of prior isolated Reisolation of the pulmonary vein and ablation of any nonpulmonary vein foci are often effective in treating these arrhythmias. Detailed activation and entrain- ment mapping of the tachycardia during a second procedure result in effective ablation in approximately 90% of patients.335 Although right atrial CTI-dependent flutter may also occur, most of the tachycardias originate in the left atrium. As with all types of atrial flutter, it may be very difficult to achieve rate control in patients with post AF ablation non CTI-dependent flutter (far more so than in patients with preablation AF). When the ventricular response cannot be controlled with common rate-control medications, attempts at restoration of sinus rhythm with pharmacological therapy and cardioversion are often required. Many of the atrial flut- ters that are observed during the first 3 months after catheter ablation or after cardiac surgery will not recur later on. For this reason, it is advised that attempts at ablation of atrial flut- ter after AF ablation be deferred until after the 3-month wait- Rarely, pharmacological therapy and attempts at rhythm control with antiarrhythmic drug therapy fail to adequately control atrial flutter during the 3 months after AF ablation. In this situation, early repeat ablation is warranted. 7.3. Acute Treatment: Recommendations Recommendations for Acute Treatment of Atrial Flutter COR LOE Recommendations I A 1. Oral dofetilide or intravenous ibutilide is useful for acute pharmacological cardioversion in patients with atrial flutter.119,340 346 See Online Data and 17. Pharmacological cardioversion of atrial flutter is generally less effective than synchronized cardioversion and carries the potential risk of proarrhythmia but can be an option when sedation is not available or not well tolerated or when indicated by patient preference. Intravenous ibutilide converts atrial flutter to sinus rhythm in approximately 60% of cases.342 The major risk is torsades de pointes, which is more likely to occur in patients with reduced left ventricular ejection fraction. Patients receiving ibutilide should undergo continuous ECG monitoring during administration and for at least 4 hours after completion of dosing. Pretreatment with magnesium can increase the efficacy and reduce the risk of torsades de pointes.119 Anticoagulation issues for chemical cardioversion are the same as those for electrical cardioversion of atrial flutter.10 I B-R Intravenous or oral beta blockers, diltiazem, or verapamil are useful for acute rate control in patients with atrial flutter who are See Online Data and 17. It is often more difficult to achieve rate control for atrial flutter than for AF. Nonetheless, effective rate control may be achieved with beta blockers, diltiazem, or verapamil in patients with atrial flutter through a direct effect on the AV node. Hypotension is the main adverse effect. Intravenous diltiazem is the preferred intravenous calcium channel blocker for acute rate control because of its safety and Diltiazem and verapamil should be avoided in patients with advanced heart failure and in patients with heart block or sinus node dysfunction in the absence of pacemaker therapy. Verapamil and diltiazem also should not be used in patients with known pre- excitation. The heart rate control achieved with beta blockers is similar to that seen with verapamil and diltiazem. The rate-slowing effect of beta blockers is largely related to reduction of sympathetic tone. Esmolol is generally the preferred intravenous beta blocker because of its rapid onset.353 Care should be used in administering beta blockers for rate control in atrial flutter patients with decompensated heart failure or reactive airway disease.355 I B-NR Elective synchronized cardioversion is indicated in stable patients with well-tolerated atrial flutter when a rhythm-control strategy is being pursued.356 358 See Online Data and 17. Heart rates can be difficult to control in atrial flutter. Cardioversion for atrial flutter can be successful at lower energy levels than for AF.356 Anticoagulation issues for cardioversion are the same as those for patients with AF and are addressed in the 2014 AF guideline.10 Restoration of sinus rhythm is favored to avoid development of tachycardia-mediated cardiomyopathy, which is associated with a rapid ventricular response in atrial flutter. I B-NR Synchronized cardioversion is recommended for acute treatment of patients with atrial flutter who are hemodynamically unstable and do not respond to pharmacological therapies.75,208,356,359 See Online Data and 17. The ventricular rate in atrial flutter can be difficult to control with pharmacological therapy. In patients with any signs or symptoms of hemodynamic compromise attributed to atrial flutter, synchronized cardioversion (with appropriate considerations with regard to anticoagulation) should be pursued without delay. I C-LD Rapid atrial pacing is useful for acute conversion of atrial flutter in patients who have pacing wires in place as part of a permanent pacemaker or implantable cardioverter-defibrillator or for temporary atrial pacing after cardiac surgery.360 364 See Online Data and 17. Atrial pacing is effective at terminating flutter in >50% of cases.364 Atrial pacing is more commonly applied in situations in which atrial wires are already in place, such as in the postoperative setting or in patients with programmable cardiac implanted electrical devices. A temporary pacing wire may also be placed and atrial pacing for termination of atrial flutter can be useful when sedation is contraindicated, or in the setting of digitalis toxicity, in which DC cardioversion is contraindicated. Pace-termination is performed by pacing the atrium at a rate starting approximately 5% to 10% above the atrial flutter rate to achieve atrial entrainment and by maintaining pacing for 15 seconds, with repeated attempts at incrementally faster rates (reducing the pacing cycle length by 5 to 10 ms until normal sinus rhythm or AF occurs.364 When AF is precipitated, this is often more easily rate-controlled and may subsequently revert to sinus rhythm. Recommendations for anticoagulation with regard to pace-termination of atrial flutter are the same as those for chemical or electrical conversion of AF. 7.4. Ongoing Management: Recommendations I B-NR Acute antithrombotic therapy is recommended in patients with atrial flutter to align with recommended antithrombotic therapy for patients with AF.365 See Online Data and 17. The risk of stroke associated with AF is well established, and several RCTs have demonstrated the efficacy of anticoagulation for stroke prevention in patients with additional risk factors.366 Anticoagulation has also been shown to prevent stroke when administered during the weeks immediately before and after cardioversion.367 Whether atrial flutter carries a risk of stroke similar to that in patients with AF has been debated in the past but is now supported by limited evidence from mechanistic, observational, and prospective studies that include patients primarily with atrial flutter.365 369 Several reports have suggested that the risk of stroke in patients with atrial flutter is mitigated by anticoagulation. Meta-analysis of 13 studies of patients undergoing cardioversion of atrial flutter reported short-term stroke risks ranging from 0% to 7%, and the thromboembolism rate in patients with sustained flutter Other studies have reported similar risk and effectiveness of anticoagulation.369 Therefore, on the basis of the available data, recommendations for antithrombotic therapy for patients with atrial flutter are similar to those for patients with AF.10 IIa B-R Intravenous amiodarone can be useful for acute control of the ventricular rate (in the absence of pre-excitation) in patients with atrial flutter and systolic heart failure, when beta blockers are contraindicated or See Online Data and 17. 