When properly performed, vagal maneuvers can terminate SVT, so patient education on this maneuver may help to avoid a more prolonged tachycardia episode and reduce the need to seek medical attention. Vagal maneuvers should be performed with the patient in the supine position. Patients can be taught to perform a Valsalva maneuver by forcefully exhaling against a closed airway for 10 to 30 seconds, equivalent to at least 30 Another vagal maneuver based on the classic diving reflex consists of applying an ice-cold, wet towel to the face.85 IIa B-R Flecainide or propafenone is reasonable for ongoing management in patients without structural heart disease or ischemic heart disease who have symptomatic SVT and are not candidates for, or prefer not to undergo, catheter ablation.45,46,107 112 See Online Data Supplement 2. Several RCTs have demonstrated the efficacy of daily therapy with propafenone (450 mg/day to 900 mg/day) or flecainide (100 mg/day to 300 mg/day) to prevent recurrences of SVT in symptomatic patients.45,46,107 112 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 However, flecainide and propafenone have a risk of proarrhythmia in patients with structural heart disease or ischemic heart disease, so these drugs are contraindicated in these patient groups.113 These drugs, though often effective, have potential side effects and as such should be reserved for patients for whom beta blockers, diltiazem, or verapamil are ineffective or cannot be prescribed. I B-NR Synchronized cardioversion is recommended for acute treatment in patients with hemodynamically stable SVT 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 conversion 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 effective.87,96 Nevertheless, in rare instances, drugs may fail to successfully restore sinus rhythm, and cardioversion will be necessary. Synchronized cardioversion is inappropriate if the SVT is terminating and reinitiating spontaneously. IIa B-R 1. Intravenous diltiazem or verapamil can be effective for acute treatment in patients with hemodynamically stable SVT.87,89,92,97 See Online Data and 3. Intravenous diltiazem and verapamil have been shown to terminate SVT in 64% to 98% of patients. These drugs should be used only in hemodynamically stable patients. A slow infusion of either drug up to 20 minutes may lessen the potential for hypotension.97 It is important to ensure that tachycardia is not due to VT or pre-excited AF because patients with these rhythms who are given diltiazem or verapamil may become hemodynamically unstable or may have accelerated ventricular rate, which may lead to ventricular fibrillation. These agents are especially useful in patients who cannot tolerate beta blockers or experience recurrence after conversion with adenosine. Diltiazem and verapamil are not appropriate for patients with suspected systolic heart failure. IIa C-LD 2. Intravenous beta blockers are reasonable for acute treatment in patients with hemodynamically stable SVT.96 See Online Data Supplement 2. Evidence for the effectiveness of beta blockers in terminating SVT is limited. In a trial that compared esmolol with diltiazem, diltiazem was more effective in terminating SVT.96 Nonetheless, beta blockers have an excellent safety profile, so it is reasonable to use intravenous beta blockers to attempt to terminate SVT in hemodynamically stable patients. Recommendations for Acute Treatment of SVT of Unknown Mechanism (Continued) COR LOE Recommendations 2.5. Basic Principles of Electrophysiological Study, Mapping, and Ablation 2.5.1. Mapping With Multiple and Roving Electrodes An invasive EP study permits the precise diagnosis of the underlying arrhythmia mechanism and localization of the site of origin and provides definitive treatment if coupled with catheter ablation. There are standards that define the equip- ment and training of personnel for optimal performance of EP studies involve placement of multielectrode catheters in the heart at 1 sites in the atria, ventricles, or coronary sinus. Pacing and programmed electrical stimulation may be performed with or without pharmacological provoca- tion. Making a precise and correct diagnosis of the mechanism of SVT is the key to successful outcome, particularly when multiple arrhythmia mechanisms are possible; as such, appro- priate diagnostic maneuvers should be performed before pro- ceeding with ablation. By using diagnostic maneuvers during the EP study, the mechanism of SVT can be defined in most Complications of diagnostic EP studies are rare but can be life threatening.143 Cardiac mapping is performed during EP studies to iden- tify the site of origin of an arrhythmia or areas of critical conduction to allow targeting of ablation. Multiple techniques have been developed to characterize the temporal and spatial distribution of electrical activation.144 The simplest technique uses several multipole catheters plus a roving catheter that is sequentially positioned in different regions of interest and measures local activation time. Electroanatomic mapping sys- tems and specialized multielectrode catheters, such as circular or multispline catheters, can map simultaneously from mul- tiple sites and improve the speed and resolution of mapping. 2.5.2. Tools to Facilitate Ablation, Including 3-Dimensional Electroanatomic Mapping Several tools have been developed to facilitate arrhythmia mapping and ablation, including electroanatomic 3-dimen- sional mapping and magnetic navigation. Potential benefits of these technologies include more precise definition or localiza- tion of arrhythmia mechanism, spatial display of catheters and arrhythmia activation, reduction in fluoroscopy exposure for the patient and staff, and shortened procedure times, particu- larly for complex arrhythmias or anatomy.145 Disadvantages include higher cost, as well as additional training, support, and procedure preparation time. Several studies have dem- onstrated the advantages of electroanatomic mapping, with IIb B-R Sotalol may be reasonable for ongoing management in patients with symptomatic SVT who are not candidates for, or prefer not to undergo, catheter ablation.114 See Online Data Supplement 2. Sotalol is a class III antiarrhythmic agent with beta-blocker properties. Unlike flecainide and propafenone, it can be used in patients with structural heart disease or ischemic heart disease. One study randomized patients with reentrant SVT (AVNRT or AVRT) or other atrial tachyarrhythmias (eg, AF, atrial flutter, AT) to sotalol at a dose of 80 mg or 160 mg twice daily or placebo and found significant reductions in recurrence risk, including for patients with reentrant SVT, with no proarrhythmic adverse effects.114 Because of the potential for proarrhythmia, sotalol should be reserved for patients who are not candidates for catheter ablation and for whom beta blockers, diltiazem, or verapamil are ineffective or cannot be prescribed. IIb B-R Dofetilide may be reasonable for ongoing management in patients with symptomatic SVT who are not candidates for, or prefer not to undergo, catheter ablation and in whom beta blockers, diltiazem, flecainide, propafenone, or verapamil are ineffective or See Online Data Supplement 2. Dofetilide is a class III antiarrhythmic agent that, unlike sotalol, does not have beta-blocker properties. It may be reasonable in patients with structural heart disease or ischemic heart disease. In a trial of 122 patients randomized to dofetilide, propafenone, or placebo, the probability of remaining free of SVT after 6 months of treatment was 50% for dofetilide, 54% for propafenone, and 6% for placebo, with P<0.001 for either dofetilide or propafenone compared with placebo.107 Because of the potential for proarrhythmia, dofetilide should be reserved for patients who are not candidates for catheter ablation and for whom beta blockers, diltiazem, flecainide, verapamil, or propafenone are ineffective or cannot be prescribed. IIb C-LD Oral amiodarone may be considered for ongoing management in patients with symptomatic SVT who are not candidates for, or prefer not to undergo, catheter ablation and in whom beta blockers, diltiazem, dofetilide, flecainide, propafenone, sotalol, or verapamil are ineffective or contraindicated.115 See Online Data Supplement 2. Evidence for amiodarone for the ongoing management of SVT is limited. The drug was evaluated in a small retrospective study and was found to be effective in suppressing AVNRT during outpatient follow-up.115 Amiodarone is a second-line agent for patients who are not able to take beta blockers, diltiazem, dofetilide, flecainide, propafenone, sotalol, or verapamil given the toxicity and side effects that may develop with long-term amiodarone therapy. IIb C-LD Oral digoxin may be reasonable for ongoing management in patients with symptomatic SVT without pre-excitation who are not candidates for, or prefer not to undergo, catheter ablation.99 See Online Data Supplement 2. Evidence for the use of digoxin is limited. One small study randomized patients with SVT to digoxin (0.375 mg/day), propranolol (240 mg/day), and verapamil (480 mg/day), with 1 week of placebo washout between drug regimens.99 Overall, episodes and duration of SVT (ascertained by diary and weekly 24-h Holter) were 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, and in view of the risk of toxicity, digoxin should be reserved for patients who cannot take beta blockers, diltiazem, or verapamil or a class Ic agent (flecainide or propafenone) and must be used with caution in the presence of renal dysfunction. In some clinical studies, digoxin levels >1.2 ng/mL were associated with worse clinical outcomes, while levels <0.8 ng/mL were considered optimal; therefore, caution is advised.116 Recommendations for Ongoing Management of SVT of Unknown Mechanism (Continued) COR LOE Recommendations Page et al 2015 ACC/AHA/HRS SVT Guideline e519 success rates comparable to conventional approaches yet with significant reduction in fluoroscopy times.145 148 2.5.3. Mapping and Ablation With No or Minimal Radiation Fluoroscopy has historically been the primary imaging modal- ity used for EP studies. The use of ionizing radiation puts patient, operator, and laboratory staff at risk of the short- and long-term effects of radiation exposure. Attention to optimal fluoroscopic technique and adoption of radiation-reducing strategies can minimize radiation dose to the patient and oper- ator. The current standard is to use the as low as reasonably achievable (ALARA) principle on the assumption that there is no threshold below which ionizing radiation is free from harmful biological effect. Alternative imaging systems, such as electroanatomic mapping and intracardiac echocardiogra- phy, have led to the ability to perform SVT ablation with no or minimal fluoroscopy, with success and complication rates similar to standard techniques.147,149 152 Radiation exposure may be further reduced by using robotic or magnetic naviga- tion of catheters that use a 3-dimensional anatomic tracking system superimposed on traditional fluoroscopy imaging. A reduced- fluoroscopy approach is particularly important in pediatric patients and during pregnancy.153,154 2.5.4. Ablation Energy Sources Radiofrequency current is the most commonly used energy source for SVT ablation.155 Cryoablation is used as an alter- native to radiofrequency ablation to minimize injury to the AV node during ablation of specific arrhythmias, such as AVNRT, para-Hisian AT, and para-Hisian accessory path- ways, particularly in specific patient populations, such as children and young adults. Selection of the energy source Figure 4. Orthodromic atrioventricular reentrant tachycardia. Arrows point to the P waves, which are inscribed in the ST-segment after the QRS complex. The reentrant circuit involves anterograde conduction over the atrioventricular node, followed by retrograde conduction over an accessory pathway, which results in a retrograde P wave with short RP interval. Figure 5. Atrial tachycardia. Arrows point to the P wave, which is inscribed before the QRS complex. The focus of this atrial tachycardia was mapped during electrophysiological study to an area near the left inferior pulmonary vein. depends on operator experience, arrhythmia target location, and patient preference. Published trials, including a meta- analysis comparing radiofrequency ablation with cryoabla- tion for treatment of AVNRT, have shown a higher rate of recurrence with cryoablation but lower risk of permanent AV The rate of AVNRT recurrence with cryo- ablation depends on the size of the ablation electrode and the endpoint used.156,159 Ultimately, the choice of technol- ogy should be made on the basis of an informed discussion between the operator and the patient. 3. Sinus Tachyarrhythmias In normal individuals, the sinus rate at rest is generally between 50 bpm and 90 bpm, reflecting vagal tone.160 163 Sinus tachycardia refers to the circumstance in which the sinus rate exceeds 100 bpm. Sinus tachycardia may be appropriate in response to physiological stimuli or other exogenous factors or may be inappropriate when the heart rate exceeds what would be expected for physical activity or other circumstances. On the ECG, the P wave is upright in leads I, II, and aVF and is biphasic in lead V1. As the sinus rate increases, activation arises from more superior aspects of the right atrium, resulting in a larger-amplitude P wave in the inferior leads. Table 5. ECG Criteria to Differentiate VT From SVT in Wide-Complex Tachycardia Findings or Leads on ECG Assessed Interpretation QRS complex in leads V1-V6 Lack of any R-S complexes implies VT R-S interval (onset of R wave to nadir of S wave) >100 ms in any precordial lead implies VT QRS complex in aVR (Vereckei Presence of initial R wave implies VT Initial R or Q wave >40 ms implies VT Presence of a notch on the descending limb at the onset of a predominantly negative QRS implies VT AV dissociation* Presence of AV dissociation (with ventricular rate faster than atrial rate) or fusion complexes implies VT QRS complexes in precordial leads all positive or all negative (concordant) Implies VT QRS in tachycardia that is identical to sinus rhythm78 Suggests SVT R-wave peak time in lead II78 R-wave peak time 50 ms suggests VT *AV dissociation is also a component of the Brugada criteria.73 AV indicates atrioventricular; ECG, electrocardiogram; SVT, supraventricular tachycardia; and VT, ventricular tachycardia. Table 4. Differential Diagnosis of Wide QRS Complex Tachycardia Mechanism Ventricular tachycardia SVT with pre-existing bundle-branch block or intraventricular conduction defect SVT with aberrant conduction due to tachycardia (normal QRS when in sinus rhythm) SVT with wide QRS related to electrolyte or metabolic disorder SVT with conduction over an accessory pathway (pre-excitation) Paced rhythm Artifact SVT indicates supraventricular tachycardia. Figure 6. Permanent form of junctional reciprocating tachycardia (PJRT). Tachycardia starts after 2 beats of sinus rhythm. Arrows point to the P wave, which is inscribed before the QRS complex. The reentrant circuit involves anterograde conduction over the atrioventricular node, followed by retrograde conduction over a slowly conducting (or decremental) accessory pathway, usually located in the postero- septal region, to provide a retrograde P wave with long RP interval. This ECG does not exclude atypical AVNRT or a low septal atrial tachycardia, which can appear very similar to this ECG. AVNRT indicates atrioventricular nodal reentrant tachycardia; ECG, electrocardio- gram; and PJRT, permanent form of junctional reciprocating tachycardia. Page et al 2015 ACC/AHA/HRS SVT Guideline e521 3.1. Physiological Sinus Tachycardia Sinus tachycardia is regarded as physiological when it is the result of appropriate autonomic influences, such as in the set- ting of physical activity or emotional responses. Physiological sinus tachycardia may result from pathological causes, includ- ing infection with fever, dehydration, anemia, heart failure, and hyperthyroidism, in addition to exogenous substances, including caffeine, drugs with a beta-agonist effect (eg, alb- uterol, salmeterol), and illicit stimulant drugs (eg, amphet- amines, cocaine). In these cases, tachycardia is expected to resolve with correction of the underlying cause. 3.2. Inappropriate Sinus Tachycardia Inappropriate sinus tachycardia (IST) is defined as sinus tachycardia that is unexplained by physiological demands at rest, with minimal exertion, or during recovery from exercise. Crucial to this definition is the presence of associated, some- times debilitating, symptoms that include weakness, fatigue, lightheadedness, and uncomfortable sensations, such as heart racing. Patients with IST commonly show resting heart rates >100 bpm and average rates that are >90 bpm in a 24-hour The cause of IST is unclear, and mechanisms related to dysautonomia, neurohormonal dysregulation, and intrinsic sinus node hyperactivity have been proposed. It is important to distinguish IST from secondary causes of tachycardia, including hyperthyroidism, anemia, dehy- dration, pain, and use of exogenous substances and drugs of abuse. Anxiety is also an important trigger, and patients with IST may have associated anxiety disorders.160 Structural heart disease, such as cardiomyopathies, must also be excluded, though the development of a cardiomyopathy secondary to sinus tachycardia is extremely rare.164,165 IST must also be distinguished from other forms of tachycardia, including AT arising from the superior aspect of the crista terminalis and sinus node reentrant tachycardia (Section 4). It is also important to distinguish IST from postural ortho- static tachycardia syndrome, although overlap may be pres- ent within an individual. Patients with postural orthostatic tachycardia syndrome have predominant symptoms related to a change in posture, and treatment to suppress the sinus rate may lead to severe orthostatic hypotension. Thus, IST is a diagnosis of exclusion. 3.2.1. Acute Treatment There are no specific recommendations for acute treatment of IST. 3.2.2. Ongoing Management: Recommendations Because the prognosis of IST is generally benign, treatment is for symptom reduction and may not be necessary. Treatment Figure 7. Differential diagnosis for adult narrow QRS tachycar- dia. Patients with junctional tachycardia may mimic the pat- tern of slow-fast AVNRT and may show AV dissociation and/ or marked irregularity in the junctional rate. *RP refers to the interval from the onset of surface QRS to the onset of visible P wave (note that the 90-ms interval is defined from the surface as opposed to the 70-ms ventriculoatrial interval that is used for intracardiac diagnosis 80 ). AV indicates atrioventricu- lar; AVNRT, atrioventricular nodal reentrant tachycardia; AVRT, atrioventricular reentrant tachycardia; ECG, electrocardiogram; MAT, multifocal atrial tachycardia; and PJRT, permanent form of junctional reentrant tachycardia. Modified with permission from Blomstr m-Lundqvist et al.11 Figure 8. Acute treatment of regular SVT of unknown mechanism. 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; and SVT, supraventricular tachycardia. of IST is difficult, and it should be recognized that lowering the heart rate may not alleviate symptoms. Therapy with beta blockers or calcium channel blockers is often ineffective or not well tolerated because of cardiovascular side effects, such as hypotension. Exercise training may be of benefit, but the benefit is unproven. Ivabradine is an inhibitor of the I-funny or If chan- nel, which is responsible for normal automaticity of the sinus node; therefore, ivabradine reduces the sinus node pacemaker activity, which results in slowing of the heart rate. On the basis of the results of 2 large, randomized, pla- cebo-controlled trials, this drug was recently approved by the FDA for use in patients with systolic heart failure. In the BEAUTIFUL (Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Disease and Left-Ventricular Dysfunction) study,166 with coronary disease and a left ventricular ejection frac- tion <40% were randomized to ivabradine or placebo. In the SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine) trial,167 6558 patients with a left ventricular ejection fraction 35% were randomized to ivabradine or placebo. In both of these trials, therapy with ivabradine resulted in additional heart rate reductions of 6 to 8 bpm and proved to be generally safe. The drug has no other hemodynamic effects aside from lowering the heart rate. As such, it has been investigated for use to reduce the sinus rate and improve symptoms related to IST.168 176 Radiofrequency ablation to modify the sinus node can reduce the sinus rate, with acute procedural success rates reported in the range of 76% to 100% in nonrandomized Ablation is typically performed with 3-dimen- sional electroanatomic or noncontact mapping techniques targeting sites of early activation with isoproterenol infusion, with or without use of intracardiac ultrasound guided map- ping to image the crista terminalis. Nonetheless, symptoms commonly recur after several months, with IST recurrence in up to 27% and overall symptomatic recurrence (IST or non- IST AT) in 45% of patients.177,179,180,182 Complications can be significant and may include symptomatic sinus or junctional bradycardia necessitating pacemaker placement, phrenic nerve injury with paralysis of the right hemidiaphragm, and significant facial and upper-extremity swelling caused by narrowing of the superior vena cava/RA junction, which may rarely result in superior vena cava syndrome. In view of the modest benefit of this procedure and its potential for sig- nificant harm, sinus node modification should be considered only for patients who are highly symptomatic and cannot be adequately treated by medication, and then only after inform- ing the patient that the risks may outweigh the benefits of ablation. Even more aggressive surgical methods to ablate or denervate the sinus node have been described, further high- lighting the risks that highly symptomatic patients are willing to accept to find relief.184 Effective patient communication is key for these patients. Figure 9. Ongoing management of SVT of unknown mechanism. Colors correspond to Class of Recommendation in Table 1; drugs listed alpha- betically. *Clinical follow-up without treatment is also an option. EP indicates electrophysiological; pt, patient; SHD, structural heart disease (includ- ing ischemic heart disease); and SVT, supraven- tricular tachycardia. Page et al 2015 ACC/AHA/HRS SVT Guideline e523 4. Nonsinus Focal Atrial Tachycardia and MAT See Figure 10 for the algorithm for acute treatment of sus- pected focal atrial tachycardia (AT) and Figure 11 for the algorithm for ongoing management of focal AT. 4.1. Focal Atrial Tachycardia Focal AT is characterized as a fast rhythm from a discrete ori- gin, discharging at a rate that is generally regular, and con- ducting in a centrifugal manner throughout the atrial tissue. Focal AT represents approximately 3% to 17% of the patients referred for SVT ablation.49,122,186 The demographics of focal AT in the adult population will continue to change as SVTs are increasingly ablated at a younger age. Focal AT can be sustained or nonsustained. The atrial rate during focal AT is usually between 100 and 250 bpm.186 Presence and severity of symptoms during focal AT are vari- able among patients. Focal AT in the adult population is usu- ally associated with a benign prognosis, althoughAT-mediated cardiomyopathy has been reported in up to 10% of patients referred for ablation of incessant SVT.187,188 Nonsustained focal AT is common and often does not require treatment. The diagnosis of focal AT is suspected when the ECG criteria are met (Section 2). Algorithms have been devel- oped to estimate the origin of the focal AT from the P-wave morphology recorded on a standard 12-lead ECG.189,190 In general, a positive P wave in lead V1 and negative P waves in leads I and aVL are correlated to ATs arising from the left atrium. Positive P waves in leads II, III, and aVF suggest that the origin of AT is from the cranial portion of either atria. Shorter P-wave duration is correlated to AT arising from the paraseptal tissue versus the right or left atrial free wall.191 The precise location of the focal AT is ultimately confirmed by mapping during EP studies when successful ablation Focal AT has been localized to the crista terminalis, right or left atrial free wall or appendage, tricuspid or mitral annulus, paraseptal or paranodal areas, pulmonary veins, coronary sinus, and coronary cusps, but it originates more frequently from the right atrium than from the left atrium.197,198 The underlying mechanism of focal AT can be auto- matic, triggered activity, or microreentry, but methods to distinguish the mechanism through pharmacological testing or EP study are of modest value because of limited sensi- tivity and specificity.123,199,200 An automatic AT can be tran- siently suppressed by adenosine or by overdrive pacing and may be terminated by beta blockers, diltiazem, or verapamil. Whereas a triggered AT can be terminated by adenosine or overdrive pacing, its response to beta blockers, diltiazem, or verapamil may be variable. A microreentrant AT can be induced and terminated by programmed stimulation, but its response to adenosine, beta blockers, diltiazem, or vera- pamil may depend on the location of the microreentrant cir- cuit; the tachycardia can be terminated by these drugs if the microreentrant circuit involves tissue around the sinus node, Recommendations for Ongoing Management of IST COR LOE Recommendations I C-LD 1. Evaluation for and treatment of reversible causes are recommended in patients with suspected IST.160,185 See Online Data and 5. It is important to distinguish IST from physiological sinus tachycardia or focal AT from the high right atrium, which can have P-wave morphology similar to the sinus P wave. A careful history and physical examination, with further laboratory and imaging studies, are necessary to determine reversible causes of tachycardia, such as exogenous substances and drugs, infection, anemia, and hyperthyroidism. A focal AT would have sudden onset and termination, which would not be the case for IST. IIa B-R 1. Ivabradine is reasonable for ongoing management in patients with symptomatic IST.168 176 See Online Data and 5. In 1 small randomized crossover trial,168 ivabradine given at a dosage of 2.5 to 7.5 mg twice daily significantly reduced daytime heart rate from 98.4 11.2 at baseline to 84.7 9.0, compared with 98.6 11.1 on placebo (P<0.001), and improved exercise tolerance and symptoms in patients with IST. Similar findings have been observed in several additional nonrandomized observational studies.169 176 Furthermore, a significant number of patients in these studies reported complete resolution of symptoms, with persistent clinical benefit observed in some even after discontinuing the drug. In 1 observational study, ivabradine was more effective than metoprolol in reduction of the heart rate and amelioration of symptoms.170 The drug is well tolerated, with an excellent safety profile demonstrated in 2 large RCTs in patients with heart Ivabradine can cause phosphenes, an enhanced brightness in a portion of the visual field; this side effect, which is usually transient, was reported in 3% of patients taking the drug in the SHIFT trial.167 IIb C-LD 1. Beta blockers may be considered for ongoing management in patients with symptomatic IST.170,172 See Online Data and 5. Beta blockers are modestly effective in lowering the heart rate and improving symptoms that are due to IST. In a small nonrandomized observational cohort, metoprolol succinate titrated to a target of 95 mg daily lowered the heart rate over 4 weeks from a baseline.172 In a small nonrandomized study comparing metoprolol with ivabradine, both agents reduced heart rate compared with baseline and improved exercise Although effectiveness of beta blockers is modest and hypotension may limit dose, the overall safety of beta blockers warrants their use for treatment of symptomatic patients. IIb C-LD 2. The combination of beta blockers and ivabradine may be considered for ongoing management in patients with IST.172 See Online Data and 5. Some patients with IST may have particularly refractory symptoms, and single-drug efficacy may be limited. In a small observational study, the addition of ivabradine (7.5 mg twice daily) to metoprolol succinate (95 mg daily) reduced the heart rate from baseline to a greater extent than did metoprolol alone.172 On combination therapy, symptoms related to IST were resolved in all patients, and the combined therapy was well tolerated. In the SHIFT and BEAUTIFUL studies, the majority of patients were taking the combination of ivabradine and a beta blocker, which was well tolerated.166,167 Nevertheless, patients who are considered for combination therapy should be monitored closely for the possibility of excess bradycardia. Ivabradine can cause phosphenes, an enhanced brightness in a portion of the visual field; this side effect was reported in 3% of patients taking the drug in the SHIFT trial.167 Table 6. Acute Drug Therapy for SVT, Intravenous Administration* Drug Initial Dose Subsequent or Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions Nucleoside Adenosine 6-mg rapid IV bolus (injected into IV as proximal or as close to the heart as possible), administered over 1 2 s, followed by rapid saline flush If no result within 1 2 min, 12-mg rapid IV bolus; can repeat 12-mg dose 1 time. The safe use of 18-mg bolus doses has been Transient AV block, flushing, chest pain, hypotension, or dyspnea, AF can be initiated or cause decompensation in the presence of pre-excitation, PVCs/ventricular tachycardia, bronchospasm (rare), or coronary steal. Minor side effects are usually transient because of adenosine s very short half-life. AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Reactive airway disease Concomitant use of verapamil or digoxin WPW Beta blockers Esmolol 500-mcg/kg IV bolus over 1 min Infusion at 50 300 mcg/ kg/min, with repeat boluses between each dosing increase Hypotension, worsening HF, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF Hypotension Cardiogenic shock Reactive airway disease Renal dysfunction Drugs with SA and/or AV nodal blocking properties Metoprolol tartrate bolus over 2 min Can repeat 2.5- to 5.0- mg IV bolus in 10 min, up to 3 doses Hypotension, worsening HF, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF Hypotension Reactive airway disease Drugs with SA and/or AV nodal blocking properties Propranolol 1 mg IV over 1 min Can repeat 1 mg IV at 2-min intervals, up to 3 doses Hypotension, worsening HF, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Cardiogenic shock Reactive airway disease Decompensated HF Hypotension Hepatic or renal dysfunction Drugs with SA and/or AV nodal blocking properties Nondihydropyridine calcium channel antagonists Diltiazem 0.25-mg/kg IV bolus over 2 min Infusion at 5 10 mg/h, up to 15 mg/h Hypotension, worsening HF in patients with pre-existing ventricular dysfunction, bradycardia, abnormal liver function studies, acute hepatic injury (rare) AV block greater than first degree or SA node dysfunction (in absence of pacemaker) WPW with AF/atrial flutter Hypotension Decompensated systolic HF/LV dysfunction Drugs with SA and/or AV nodal blocking properties Hepatic or renal dysfunction Diltiazem is a substrate of CYP3A4 (major) and a moderate CYP3A4 inhibitor Apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, posaconazole, ranolazine, rifampin, simeprevir, voriconazole (Continued) Page et al 2015 ACC/AHA/HRS SVT Guideline e525 bolus over 2 min If no response, can give an additional 10 mg after first dose; then infusion at 0.005 mg/ kg/min Hypotension, worsening HF in patients with pre-existing ventricular dysfunction, pulmonary edema in patients with hypertrophic cardiomyopathy, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF/LV dysfunction Drugs with SA and/or AV nodal blocking properties Hypotension Cardiogenic shock WPW with AF/atrial flutter Hepatic or renal dysfunction Verapamil is a moderate CYP3A4 inhibitor and also inhibits P-glycoprotein Contraindicated with dofetilide Itraconazole, bosutinib, ceritinib, cilostazol, colchicine, cyclosporine, everolimus, dabigatran, edoxaban, flecainide, ibrutinib, ivabradine, olaparib, posaconazole, ranolazine, rivaroxaban, rifampin, silodosin, simeprevir, rivaroxaban, rifampin, simvastatin, topotecan, trabectedin, vincristine, voriconazole, grapefruit juice Cardiac glycosides Digoxin 0.25 0.5-mg IV bolus Can repeat 0.25-mg IV bolus, up to maximum dose of 1.0 mg over 24 h (ie, maximum loading dose 8 12 mcg/kg), given at 6 8-h intervals; maintenance dose based on patient s age, lean body weight, renal function, and concomitant drugs (IV 2.4 3.6 mcg/kg/d) Anorexia, nausea, vomiting, visual changes and cardiac arrhythmias if digoxin toxicity (associated with levels >2 ng/mL, although symptoms may also occur at lower levels) Renal dysfunction WPW with AF/atrial flutter AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Drugs with AV nodal-blocking properties Digoxin is a P-glycoprotein substrate Dronedarone (reduce dose by at least 50%), amiodarone (reduce dose by 30% 50%) Verapamil, clarithromycin, cyclosporine, erythromycin, flecainide, itraconazole, posaconazole, propafenone, voriconazole: Monitor digoxin levels A large retrospective study suggested an increased risk in mortality in patients who were treated with digoxin for newly diagnosed AF or atrial flutter; although the data were collected from a population that was different from SVT patients, digoxin should be used with caution.118 Class III antiarrhythmic agents Amiodarone 150 mg IV over Infusion at 1 mg/min (360 mg) over next 6 h; mg) over remaining 18 h Hypotension, bradycardia, phlebitis, QT prolongation, torsades de pointes (rare), increased INR Sinus or AV conduction disease (in absence of pacemaker) Inflammatory lung disease (acute) Hepatic dysfunction 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 (Continued) Table 6. Continued Drug Initial Dose Subsequent or Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions whereas microreentrant ATs from other locations generally will not be terminated by these drugs. Sinus node reentrant tachycardia is an uncommon type of focal AT that involves a microreentrant circuit in the region of the sinoatrial node, causing a P-wave morphology that is identical to that of sinus tachycardia (although this is not sinus tachycardia). Characteristics that distinguish sinus node reen- try from sinus tachycardia are an abrupt onset and termination and often a longer RP interval than that observed during nor- mal sinus rhythm. Sinus node reentry is characterized by par- oxysmal episodes of tachycardia, generally 100 bpm to 150 Confirmation of the reentrant mechanism requires an EP study. Induction of sinus node reentrant tachycardia during programmed stimulation, demonstration of entrain- ment, and localization of the tachycardia origin in the region of the sinus node are necessary to confirm the diagnosis. 4.1.1. Acute Treatment: Recommendations RCTs of drug therapy for comparative effectiveness in patients with focal AT in the acute setting are not avail- able. Many of the clinical outcomes are reported from small observational studies that included infants or pediatric The design or execution of these studies is frequently suboptimal because of the poorly defined inclu- sion criteria or variable clinical settings. Several studies included a mix of patients with congenital or postoperative AT, and some of these patients likely had macroreentrant AT. In many reports, the response to intravenous drug therapy was evaluated by EP study rather than in the clinical envi- In the clinical setting, if the diagnosis is uncertain, vagal maneuvers may be attempted to better iden- tify the mechanism of SVT. Digoxin has not been well studied for focalAT. Intravenous class Ic drugs (eg, flecainide, propafenone) may be moder- ately effective in treating focal AT in the acute setting, as reported in earlier, small observational studies, although intravenous forms of IC drugs are not available in the United States. In patients with an implanted cardiac pacing device, it may be possible to perform overdrive pacing through the device, although close monitoring is required to prevent any significant adverse effect, such as pacing-induced AF or other atrial arrhythmias. Equipment should be available to provide support for cardioversion of AF if needed. Ibutilide Contraindicated when QTc >440 ms ; 1 mg over kg); if <60 kg, then 0.01 mg/kg Can repeat 1 mg once, if the arrhythmia does not terminate within QT prolongation, torsades de pointes, AV block Prolonged QT interval History of torsades de pointes Avoid other QT interval prolonging drugs Concurrent administration of high-dose magnesium has been associated with enhanced efficacy and safety119,120 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 are not included in this list. For a more detailed list of drug drug interactions, clinicians should consult additional resources. If hypotension is a consideration, a slow infusion of diltiazem (2.5 mg/min) or verapamil (1 mg/min) for up to 20 minutes may lessen the potential for QTc calculation used the Bazett s Formula in most clinical studies. Patients should be observed with continuous ECG monitoring for at least 4 h after infusion or until QTc has returned to baseline. The infusion should be stopped as soon as the arrhythmia is terminated or in the event of sustained or nonsustained ventricular tachycardia or marked prolongation of QT or corrected QT interval. AF indicates atrial fibrillation; AV, atrioventricular; BID, twice daily; COR, Class of Recommendation; HF, heart failure; INR, international normalized ratio; IV, intravenous; LOE, Level of Evidence; LV, left ventricular; PVC, premature ventricular contraction; QTc, corrected QT interval; SA, sinoatrial; SVT, supraventricular tachycardia; and WPW, Wolff-Parkinson-White. Table 6. Continued Drug Initial Dose Subsequent or Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions Recommendations for Acute Treatment of Suspected Focal Atrial Tachycardia COR LOE Recommendations I C-LD Intravenous beta blockers, diltiazem, or verapamil is useful for acute treatment in hemodynamically stable patients with focal See Online Data Supplement 6. Intravenous beta blockers, diltiazem, or verapamil is recommended to treat focal AT. During EP study, propranolol or verapamil is moderately effective in either terminating the focal AT or slowing the ventricular rate in approximately 30% to 50% of the patients.204,205 Although these agents are relatively safe, close monitoring is recommended during intravenous drug therapy to evaluate for hypotension or bradycardia. I C-LD 2. Synchronized cardioversion is recommended for acute treatment in patients with hemodynamically unstable focal AT.94,208 See Online Data Supplement 6. Although minimum data are available on cardioversion of focal AT, synchronized cardioversion is a consideration in patients with drug- resistant arrhythmias associated with signs and symptoms of compromised hemodynamics. Termination of tachycardia is expected when a focal AT is of a microreentrant mechanism. Response of a triggered focal AT to cardioversion can be variable, whereas electrical cardioversion is not likely to be effective in focal AT with an automatic mechanism. In this latter case, antiarrhythmic drug therapy is usually required. Page et al 2015 ACC/AHA/HRS SVT Guideline e527 4.1.2. Ongoing Management: Recommendations IIa B-NR Adenosine can be useful in the acute setting to either restore sinus rhythm or diagnose the tachycardia mechanism in patients with suspected focal AT.123,200,207 See Online Data Supplement 6. Adenosine is usually effective in terminating focal AT of a triggered mechanism but is not expected to be effective in reentrant focal AT.207 Transient suppression can be observed in automatic focal AT. The observation of transient AV block with persistent AT can be helpful in making the diagnosis and differentiating focal AT from AVNRT and AVRT. IIb C-LD Intravenous amiodarone may be reasonable in the acute setting to either restore sinus rhythm or slow the ventricular rate in hemodynamically stable patients with focal AT.205,206 See Online Data Supplement 6. The therapeutic effect of intravenous amiodarone in the acute setting is likely mediated via blockade of the beta receptors or calcium channels. Amiodarone may be preferred in patients with reduced ventricular function or with a history of heart failure. IIb C-LD 2. Ibutilide may be reasonable in the acute setting to restore sinus rhythm in hemodynamically stable patients with focal AT.205,206 See Online Data Supplement 6. The effectiveness of ibutilide for treatment of focal AT is unclear. In 1 study, intravenous ibutilide terminated AT of single atrial morphology in 19 of 39 patients (38.8%), but the proportions of patients with focal AT and macroreentrant AT were not differentiated in this study cohort.206 Recommendations for Acute Treatment of Suspected Focal Atrial Tachycardia (Continued) COR LOE Recommendations Recommendations for Ongoing Management of Suspected Focal Atrial Tachycardia COR LOE Recommendations I B-NR 1. Catheter ablation is recommended in patients with symptomatic focal AT as an alternative to pharmacological therapy.122 126,188,191 196,206 See Online Data Supplement 6. A large number of nonrandomized cohort studies on focal AT ablation have accumulated in the past 2 decades. In a 2012 ablation registry provided by 74 voluntary medical centers in Spain, AT was found in 333 of 11042 of the ablation procedures performed.122 In experienced centers, when the AT can be induced in the laboratory, acute success rates above 90% to 95% have consistently been reported, with a complication rate of <1% to 2%.122,123,125,196 See Table 8 for a summary of ablation efficacy, complications, and rate of recurrence. Although uncommon, focal AT-mediated cardiomyopathy should be recognized in patients presenting with heart failure, reduced ventricular function, and persistent tachycardia. In a case control study of patients with AT, 10% of patients had evidence of cardiomyopathy.125 The tachycardia in patients with cardiomyopathy was incessant and slower than in the patients without cardiomyopathy (cycle lengths 502 ms and 402 ms, respectively). Normal ejection fraction was restored in 97% of patients after successful ablation.188 IIa C-LD 1. Oral beta blockers, diltiazem, or verapamil are reasonable for ongoing management in patients with symptomatic focal AT.123,204,205 See Online Data Supplement 6. Data on long-term drug therapy of focal AT are limited to observational studies, and some studies did not provide clear inclusion criteria, so results for AT were combined with those for other mechanisms of SVT. Nevertheless, these drugs are moderately effective, with a low incidence of significant adverse effects.123,204,205,209 214 IIa C-LD Flecainide or propafenone can be effective for ongoing management in patients without structural heart disease or ischemic heart disease who have focal AT.209 213 See Online Data Supplement 6. Small case series studies reported that focal AT suppression was achieved with flecainide in most patients.209,210 In infants and children, propafenone is moderately effective in focal AT suppression during follow-up.213 Flecainide and propafenone are generally tolerated by patients with focal AT. Combinations of a class Ic drug with a beta blocker, diltiazem, or verapamil may improve overall efficacy rates. IIb C-LD 1. Oral sotalol or amiodarone may be reasonable for ongoing management in patients with focal AT.188,211,215 219 See Online Data Supplement 6. Several studies reported moderate efficacies of oral sotalol or amiodarone in maintaining sinus rhythm in long-term treatment in Although most reports are in children, limited data suggest similar efficacy in adults.218 Because of the risk of proarrhythmia and other complications, before use of these drugs, a balance between anticipated benefit of focal AT suppression and potential adverse effects of these drugs should be carefully considered. 4.2. Multifocal Atrial Tachycardia MAT is defined as a rapid, irregular rhythm with at least 3 dis- tinct morphologies of P waves on the surface ECG. It may be difficult to distinguish MAT from AF on physical examination or even on a single ECG tracing, so a 12-lead ECG is indicated to confirm the diagnosis. On the ECG, the atrial rate is >100 bpm (or >90 bpm, as defined in at least 1 report220 ). Unlike AF, there is a distinct isoelectric period between P waves. The P-P, P-R, and R-R intervals are variable. The mechanism of MAT is not well established. Although it is assumed that the variability of P-wave morphology implies a multifocal ori- gin, there are very few mapping studies of MAT.221 Similarly, the variability of the P-R interval may relate to decremental conduction through the AV node, as opposed to the origin of the P wave. Occasional responsiveness to verapamil suggests a triggered mechanism, but data are limited.222 MAT is commonly associated with underlying conditions, including pulmonary disease, pulmonary hypertension, coro- nary disease, and valvular heart disease,223 as well as hypomag- nesemia and theophylline therapy.224 The first-line treatment is management of the underlying condition. Intravenous mag- nesium may also be helpful in patients with normal magne- Antiarrhythmic medications in general are not helpful in suppression of multifocal AT.226 Management often involves slowing conduction at the AV nodal level to control heart rate. Verapamil has been shown to have some efficacy in Table 7. Ongoing Drug Therapy for SVT, Oral Administration* Drug Initial Daily Dose(s) Maximum Total Daily Maintenance Dose Potential Adverse Effects Precautions (Exclude or Use With Caution) and Interactions Beta blockers Atenolol 25 50 mg QD 100 mg QD (reduced dosing in patients with severe renal dysfunction) Hypotension, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF Hypotension Reactive airway disease Severe renal dysfunction Drugs with SA and/or AV nodal blocking properties Metoprolol tartrate 25 mg BID 200 mg BID Hypotension, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF Hypotension Reactive airway disease Drugs with SA and/or AV nodal blocking properties Metoprolol succinate (long-acting) 50 mg QD 400 mg QD Hypotension, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF Hypotension Reactive airway disease Drugs with SA and/or AV nodal blocking properties Nadolol 40 mg QD 320 mg QD (reduced dosage with renal impairment) Hypotension, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Reactive airway disease Cardiogenic shock Decompensated HF Hypotension Renal dysfunction Drugs with SA and/or AV nodal blocking properties Propranolol 30 60 mg in divided or single dose with long- acting formulations 40 160 mg in divided or single dose with long-acting formulations Hypotension, worsening HF, bronchospasm, bradycardia AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Reactive airway disease Decompensated systolic HF Hypotension Drugs with SA and/or AV nodal blocking properties Nondihydropyridine calcium channel antagonists Diltiazem 120 mg daily in divided or single dose with long- acting formulations 360 mg daily in divided or single dose with long-acting formulations Hypotension, worsening HF in patients with pre-existing ventricular dysfunction, bradycardia, abnormal liver function studies, acute hepatic injury (rare) AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Hypotension Decompensated systolic HF/severe LV dysfunction WPW with AF/atrial flutter Drugs with SA and/or AV nodal blocking properties Diltiazem is a substrate of CYP3A4 (major) and a moderate CYP3A4 inhibitor Apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, ranolazine, rifampin, simeprevir (Continued) Page et al 2015 ACC/AHA/HRS SVT Guideline e529 Verapamil 120 mg daily in divided or single dose with long- acting formulations 480 mg daily in divided or single dose with long-acting formulations Hypotension, worsening HF in patients with pre-existing ventricular dysfunction, pulmonary edema in patients with hypertrophic cardiomyopathy, bradycardia, abnormal liver function studies AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Decompensated systolic HF/severe LV dysfunction Hypotension WPW with AF/atrial flutter Verapamil is a moderate CYP3A4 inhibitor and also inhibits P-glycoprotein Contraindicated with dofetilide Itraconazole, bosutinib, ceritinib, cilostazol, colchicine, cyclosporine, everolimus, dabigatran, edoxaban, flecainide, ibrutinib, ivabradine, olaparib, ranolazine, rivaroxaban, rifampin, silodosin, simeprevir, rivaroxaban, rifampin, simvastatin, topotecan, trabectedin, vincristine, grapefruit juice Cardiac glycosides Digoxin Loading: 0.5 mg, with mg doses administered at 6 8-h intervals until evidence of adequate effect (maximum dose 8 12 mcg/ kg over 24 h) 0.25 mg QD Maintenance: 0.125 0.25 mg QD, with dosing based on patient s age, lean body weight, and renal function and drug interactions; occasionally down to 0.0625 mg in cases of renal impairment (trough serum digoxin level 0.5 to Bradycardia, heart block, anorexia, nausea, vomiting, visual changes and cardiac arrhythmias in cases of digoxin toxicity (associated with levels >2 ng/mL, although symptoms may also occur at lower levels) Renal dysfunction WPW with AF/atrial flutter AV block greater than first degree or SA node dysfunction (in absence of pacemaker) Drugs with SA and/or AV nodal blocking properties Reduce dose by 30% 50% when administering with amiodarone and by 50% when administering with dronedarone Monitor digoxin concentrations with verapamil, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, flecainide Class Ic antiarrhythmic agents Flecainide 50 mg every 12 h 150 mg every 12 h (PR and QRS intervals should be monitored. 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. 