Optimalantiarrhythmic drug therapy for electricalstorm

Dan Sorajja,Thomas M.Munger,Win-Kuang Shen

Division of Cardiovascular Diseases,Mayo Clinic Arizona,Phoenix,AZ 85054,USA.

Optimalantiarrhythmic drug therapy for electricalstorm

Dan Sorajja?,Thomas M.Munger,Win-Kuang Shen

Division of Cardiovascular Diseases,Mayo Clinic Arizona,Phoenix,AZ 85054,USA.

Electrical storm,defined as 3 or more separate episodes of ventricular tachycardia or ventricular fibrillation within 24 hours,carries significant morbidity and mortality.These unstable ventricular arrhythmias have been described with a variety of conditions including ischemic heartdisease,structuralheartdisease,and genetic conditions.While implantable cardioverterdefibrillatorimplantation and ablation may be indicated and required,antiarrhythmic medication remains an importantadjunctive therapy for these persons.

antiarrhythmic medication,electrical storm,ventricular tachycardia,ventricular fibrillation

Introduction

Electricalstorm(ES),which is recurrentventricular tachycardia(VT)or ventricular fibrillation(VF),is a life-threatening arrhythmic event with significant morbidity and mortality[1-4].Definitions vary for ES, with prior studies using 2 episodes of ventricular tachyarrhythmias within 24 hours[5,6].More typically, the definition for ES includes 3 or more separate episodes of ventricular tachyarrhythmias,whether untreated or treated with anti-tachycardia pacing or shocks(Fig.1)[7-9].Hemodynamic instability is not required to be associated with ES.Patients can have palpitations,lightheadedness,and/orsyncope.Inappropriate implantable cardioverterdefibrillator(ICD)shocks are notconsidered as ES.Some definitions of ES use a time delineation between episodes,such asbeing atleast 5 minutes apart or having 2 episodes within 1 hour[1,10]. Incessant VT,which is defined as a recurrence ofventricular tachyarrhythmia within 5 minutes of termination ofa previousepisode,can be considered an ES[5,11].

Epidemiology of electrical storm

Ischemia or worsening ofheartfailure predominates as the etiology in adults,while congenitalheartdisease and primary electrical disease are more common in children,who have a significantly lower frequency of ES overall compared to adults[1,2,7,8,12-15].Common and uncommon causes of ES are listed in Table 1. Factors related to worsening coronary artery disease and heartfailure,such asage,male gender,and leftventricularejection fraction,are risk factors for ES[2].

Additional factors that can precipitate ES include medication change(particularly use of class I antiarrhythmic medications,worsening congestive heart failure,lower ejection fraction,psychologicalstress, and alcohol;however the majority of triggers remain unknown[3,16-18].It has been reported that one predictor of ES is the co-presence ofsustained ST-segmentelevation and abnormalQwavesin≥2 ECGleadsin patients with structuralheartdisease[19].VF itself may be the culpritas itresults in intracellular calcium overloadrepeatedly initiating fibrillation and ES[20].These ventricular tachyarrhythmias and associated recurrent ICD shocks lead to adrenergic activation and heartfailure in a worsening spiralfashion[21].

Table 1 Triggers of electrical storm

Circadian rhythm may play a role aswellasthere is a preponderance of ES during wintermonths(December, January,and February)and late afternoon similar to otherdata formyocardialinfarction and sudden cardiac death[15,17,22-25].

Substrates and mechanisms for ventricular tachyarrhythmias

Ventricular tachyarrhythmias can be grossly categorized based on electrocardiogram into 3 morphologies: monomorphic VT,polymorphic VT,and VF.Each of these is due to a pathophysiologic mechanism,in which a substrate is affected by a triggering event.

Monomorphic ventricular tachycardia

In monomorphic VT,the ventricularactivation morphology is the same on a beat-to-beatbasis,and most commonly is a reentrantelectricalwavefrontaround a fixed obstacle such as myocardialscar.Specific locationswithin the ventricleshave associated morphologies of ventricular tachyarrhythmias seen on electrocardiogram[26].Within or atthe border of these scar zones,slow conduction provides the necessary constructfor VT to sustain itself[27].Among episodes of ES,monomorphic VT comprises 77%ofthe cases[4].

Anotherform ofmonomorphic VT involvestriggered activity,usually in structurally normal hearts[28].These episodesof VT are usually self-limited,and uncommonly cause ES.Re-entry involving the His-Purkinje system in patients with cardiomyopathy or conduction system disease can resultin bundle-branch reentranttachycardia, usually with a leftbundle branch block morphology[29]. Another less common monomorphic VT is ventricular flutter,which isquite rapid with a cycle length ofapproximately 200 ms[30].

Polymorphic ventricular tachycardia

On a beat-to-beatbasis,polymorphic VT has varying amplitude and/orduration ofthe QRS complex,and this typeofventricularactivation includestorsadesde pointes. Polymorphic VT can occurin patients with normaland prolonged QT intervals during sinus rhythm[31].Among ES cases,polymorphic VT comprises 7%ofcases[4].

Polymorphic VT occurring with a normalQT interval usually involvesischemic heartdisease ornon-ischemic cardiomyopathy.During acute myocardialinfarctions, 2 to 4%of patients develop polymorphic VT,butthis arrhythmia ismore common with coronary vasospasm[32]. In non-ischemic cases,hypertrophic cardiomyopathy and acute myocarditis can presentwith polymorphic VT[31].In addition,catecholaminergic polymorphic VT may present with polymorphic VT or bidirectional tachycardia with alternating QRS morphologies[33].

In patientswith prolonged QT on electrocardiogram, there is a risk for torsades de pointes(‘‘twisting of the points’’),a form ofpolymorphic VT.The QT prolongation may be genetic ormay be acquired.With congenital cases of polymorphic VT,the mechanism often involves an adrenergic trigger,such as exercise[34].The types of clinicaltriggersare variable and have been correlated with different genotypes of congenital Long QT Syndrome. For acquired cases,electrolyte abnormalities such as hypokalemia and hypomagnesemia increase the QT interval,but drug therapy for a large number of medical conditions,with or withoutelectrolyte abnormalities, more frequently is the cause.A fulllistof drugs that cause or are implicated in acquired QT prolongation can be found on the website,‘www.qtdrugs.org’.The triggering mechanism isdue to early-afterdepolarization type premature ventricular complexes occurring during thelengthened repolarization ofthe ventricle[35].Ashortlong RR intervalsequence(giving the name‘‘pausedependent’’),precipitating polymorphic VT is common when the initiation of the tachycardia is recorded[36].QTprolongation normally occurs with bradycardia[37].The QT intervalcould be prolonged furtherwith the concomitantuse of class IIIantiarrhythmic agents due to the drug-mediated reverse use-dependence propertieswhich resultin blockade ofthe rapid componentofthe delayed rectifierpotassium current(responsible for phase 2 and 3 depolarization)[38].

A specific subtype of ventricular tachyarrhythmias that should be mentioned is bidirectional VT,which displays a beat-to-beatalternans in the QRS morphology and/or axis,most notable in the frontal plane leads. While commonly associated as one of the arrhythmia manifestations of digitalis toxicity,bidirectional VT can also be seen in catecholaminergic VT[39].

Ventricular fibrillation

The appearance of VF includes rapid,irregular, undulating waveforms(usually faster than 200 ms)that are more disorganized than polymorphic VT.As VF persists,the fibrillation slows with waveforms also developing decreased amplitude preceding asystole[40,41]. VF storm comprises 11%of ES cases[4].

The mostcommon etiology of VF,particularly with ES,is ischemia.While VF during the initial 24 to 48 hours of myocardial infarction does not increase mortality risk[42],when ES occurswith VF,the mortality rates are exceedingly high,between 85%and 97%,even with defibrillation[43,44].VF is also the most commonly recorded during sudden cardiac arrest[45].Less frequent causes of VF include congenitalchannelopathies such as Brugada syndrome and catecholaminergic polymorphic VT[46].While rare,VF can occur from atrial fibrillation with rapid ventricularresponse degenerating into VF in cases of Wolff-Parkinson-White[47].

Prognosis of electrical storm

Management of electrical storm

Fora more comprehensive guideline fortreatmentof ventricular arrhythmias,the joint reportfrom American College of Cardiology,American Heart Association, and the European Society of Cardiology should be reviewed[30].An algorithm for acute management of ES is suggested in Figure 2.Advanced cardiac life support(ACLS)[55]should be initiated.As partof ACLS, defibrillation of hemodynamically unstable and symptomatic patients is required.Unless contraindicated, amiodarone IV bolus and infusion should be given in combination withβ-blocker bolus,which should be eitherpropranololormetoprololbolus.Sedation can also be an effective measure to rapidly suppressthe catecholamine excess thatfrequently drives ES.Identifying the etiology,particularly reversible causessuch asischemia, medication effect,heartfailure,orelectrolyte abnormalities should be evaluated,and electrophysiology consultation should be sought[30].If there are specific known diagnosesoretiologiesforan episode ofES,those should be targeted fortherapy on an individualbasis.Asummary of pharmacologic and non-pharmacologic therapy for acute management of ES is presented in Table 2.A management algorithm based on QRS morphology of theventriculartachyarrhythmiaissuggested in Figure 3.

For long-term treatment,ICDs are indicated for secondary prevention of SCD unless contraindications are present,butonly after the ventriculararrhythmia is suppressed and controlled in the acute setting[56,57]. ICDs do not prevent the actual recurrence of the tachyarrhythmia which occurs in more than 50%of this patientpopulation during 1-2 years of follow up. While ablation has been shown to reduce the burden of VT[16,58],antiarrhythmic medication remains the first line of therapy in the acute setting of ES and often isneeded to be an adjuncttherapy to reduce the burden of these ventricular tachyarrhythmias long-term.As is the case with acute therapy of ES,long term therapy should target triggers and etiologies to preventrecurrence. Table 3 includes suggested options for long-term antiarrhythmic medications and treatmentto preventrecurrence of ventricular tachyarrhythmias and to reduce ICD shocks(Table 3).

Fig.2 Acute management algorithm for electrical storm.ACLS:Advanced cardiac life support.

Anti-arrhythmic drugs β-blockers

Episodes of ES frequently are due to significant increases in sympathetic tone,and ES causes further heightening of sympathetic tone due to hemodynamic duress.Frequently ischemia and prior infarction can resultin elevated sympathetic tone due to denervation of sympathetic-parasympathetic fibers[57].β-blockade of bothβ1-andβ2-receptors remains an important treatment,which can reduce the risk of recurrent VT and VF by more than 50%[59],likely by increasing the threshold required for fibrillation[60].For patients with ES with a recent myocardial infarction,the use of β-blockade dramatically decreases the risk of sudden death compared to class I anti-arrhythmic medications[61].This effect correlates to prior data from acute myocardial infarction patients in theβ-blocker Heart Attack Trialin whichβ-blockerreduced mortality largely from prevention of ventricular tachyarrhythmias[62].For channelopathies,such as catecholaminergic polymorphic VT,β-blockade also is the mainstay oftreatment[7].

The benefits ofβ-blockade are largely a class effect, but there are differences with selective versus nonselectiveβ-blockers.Much of the data for reduction in VF during acute myocardial infarction was thought to be due to theβ1 receptors[63].Furtherdata has shown that in heart failure and post-infarction patients,the totalpopulation ofβ-receptors decreases,mainly due to down-regulation oftheβ1 receptor,whileβ2 receptors are preserved and thereby make up alargerproportion of the receptor density[63,64].In practice,propanololhas been shown to suppress ES thatis refractory to metoprololaswellas amiodarone[65].The effectin increasing the threshold required forfibrillation islargerwith more potentβ-blockers as well as with non-selectiveβblockers antagonizing bothβ1-andβ2-receptors[60].

Table 2 Anti-arrhythmic medications and treatment for acute management of electrical storm

Amiodarone

Amiodarone has predominantly a Vaughan-Williams class IIIeffectofpotassium channelblockade resulting in lengthening ofthe cardiac action potential,leading to increased refractoriness of cardiac tissue.However, amiodarone also displays features of the other Vaughan William classes to a lesser degree,such as class I usedependentsodium channelblockade of inward sodium currents slowing the ventricularconduction,as wellas class IInon-competitive sympathetic blockade and class IV calcium channelblockade[66].The antiarrhythmic effects gradually build up due to slow distribution to tissue,and become maximal approximately 10 weeks after initiation[67].Recurrence of ventricular tachyarrhythmias during this loading phase does notpreclude long term effect and success of the medication to suppress these arrhythmias[66].

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The effectiveness of amiodarone has been seen in a number of studies on ventricular arrhythmias,and for this reason was chosen as the alternate therapy in the large secondary prevention trials,CIDS(Canadian Implantable Defibrillator Study),AVID(Antiarrythmics Versus Implantable Defibrillators),and CASH(Cardiac Arrest Study,Hamburg)[68-70].For acute controlof ES, amiodarone IV ata dose of 1 g per day is effective to suppress recurrent ventricular tachyarrhythmias[66].As a stand-alone medication,amiodarone effectively suppresses ventricular tachyarrhythmias in approximately 40%ofpatients within 24 hours of intravenous administration,even ifothermedicationsare unsuccessful[71,72]. In the OPTIC study(OptimalPharmacologicalTherapy in Cardioverter Defibrillator Patients),the use ofamiodarone combined withβ-blockers reduced the risk of ICD shock to 10.3%from 38.5%when onβ-blockers alone over the 1 year follow-up[73].Similar benefitwas seen in patients classified as receiving frequent ICD shocks(more than 10 ICD shocksperyear),with amiodarone plusβ-blockerhaving 1.4%incidence compared to 7.4%in patients onβ-blocker alone[73].In another cohortlooking in patients with prior ES,those patients on amiodarone had a recurrence ofES of12%compared to 53%in patients noton amiodarone over5-year follow-up[17].Using data from the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial(CAMIAT) and European Myocardial Infarct Amiodarone Trial (EMIAT),amiodarone in addition toβ-blockers had a statistically signification reduction in antiarrhythmic death compared to those notonβ-blocker,suggesting a separate butadditive effectofthe medications[74].In patients with out-of-hospitalarrestresistantto shocks and stillin VT or VF,thosepatientswho received amiodarone showed improved survivalto hospitaladmission (44%versus 34%with placebo)[75],and this benefitpersisted when compared to lidocaine(28%versus 15%)to be admitted to a hospital[76].

Table 3 Anti-arrhythmic medications and treatment for long-term treatment of electrical storm

Side effects from long term use of amiodarone are welldescribed.These include abnormalities seen in the thyroid,liver,lung,skin,and eye.In the CIDS trial, amiodarone-mediated side effects were reported in 82% of patients during 5.6 years of follow-up[77].Increased risk oftoxicity is associated with plasma concentrations＞2.5 mg/L[78].Torsade de pointes with amiodarone is low,estimated to be less than 0.5%of cases,but QT prolongation does occur secondary to the potassiumchannelblocking effects[66].The defibrillation threshold can increase and defibrillation threshold testing is recommended forpatients on amiodarone[79,80].Intolerances to the amiodarone result in discontinuation of the medication in 23.5%ofpatients within 1 yearofinitiation oftherapy[73].Bradycardia usually manifests 2 to 4 weeks afterinitiation in 2.4%ofpatients,and would be addressed by ICD implantation in these patients with ES.[56,66].

Sotalol

Sotalolisa Vaughan-Williamsclass IIIantiarrhythmic, blocking the rapid componentof the delayed rectifier potassium current,IKr,resulting in prolongation of repolarization and therefore the QT interval but also exerts class IInon-selectiveβ-blocking effect[81].These separate effects are due to the d-and l-isomers which have class III and class II effects,respectively.

In patients who presentwith sustained VT,sotalol intravenously was able to terminate the arrhythmia within 15 minutesin 75%ofpatients[82].The intravenous form of sotalolis notavailable in the United States.In the OPTIC study,oralsotalolhad a lowerrisk of ICD shock(24.3%)vsβ-blockers(38.5%)during a followup of12 months,butthiswasnotstatistically significant (p=0.055)due to smallsample size[73].In the group of patients who received frequent ICD shocks,the incidence among patients on sotalol was 2.3%,while patients onβ-blocker alone carried an incidence of 7.4%[73].In another study ofpatients with ICD forsecondary prevention of SCD,sotalol(at 80 to 160 mg twice perday)reduced the frequency ofshocksperyear from 3.89 peryearto 1.43 peryear,regardless ofejection fraction[83].In a double-blind study thatincluded patients with sustained VT induced by programmed electricalstimulation atbaseline,34%ofpatientsplaced on sotalol(160 mg twice a day)were unable to have VT induced after sotalolloading[84].Over the subsequent yearoffollow-up on 26 patients,1 patienthad sustained VT and another patients was feltto have arrhythmic death from VF[84].These accumulated data supportthe currentrecommendation thatsotalolcan be helpfulin the treatment for sustained ventricular tachyarrythmias unresponsive toβ-blockers[30].Of note,in the Survivalwith Oral D-sotalol(SWORD)trial,a primary sudden death prevention study using the d-isomer alone,there was a significant increase in mortality likely from arrhythmias[85].Most likely,theβ-blocking effect of the l-isomerhas a protective effect.

Long term side effects remain a limitation of the medication,as 18-37%of patients stop sotalolwithin 1 year[73,84].In follow-up monitoring,sotalolhas been implicated in 17%ofthe reported casesofdrug-induced polymorphic VT[85,86].In patientswith renaldysfunction, depressed leftventricularejection fraction,orsignificant heartfailure,sotalolshould be avoided with preference given to amiodarone andβ-blockers[30,73].

Quinidine

Quinidine is a class 1A antiarrhythmic medication blocking the fast inward sodium current in a usedependentmanner,butalso blocks multiple potassium curents including the Ito,IKr,and IKs[87].Quinidine has been associated with increased proarrhythmic effects and increased mortality[88,89].In approximately 1.5% patients per year,torsades des pointes occurs resulting in‘‘quinidine syncope’’[90].

However,quinidine has proven effective in Brugada syndrome patients with inducible sustained ventricular tachyarrhythmia during electrophysiological study.In these patients,quinidine was able to render ventricular tachyarrhythmias noninducible in 96%of patients[91]. With the 4 Brugada patients in this study who tolerated quinidine,the medication prevented initiation of VF over a follow-up of 80 months[91].For patients in ES due to Brugada syndrome,quinidine also shows the ability to terminate these episodes[92].Another patient cohort that may potentially benefitfrom quinidine is short QT syndrome.In these patients who tolerate quinidine,VF was rendered non-inducible atelectrophysiological study[93].On a similar spectrum,early repolarization or J-wave syndrome may benefit from use of quinidine[94,95].

The use of quinidine in VT suppression has decreased significantly because of the frequent side effects.The mostcommon intolerance to quinidine is diarrhea,occurring in patients usually within several days of starting therapy.Other known common side effects include the drugsˊanticholinergic effects, resulting in urinary hesitancy.More worrisome adverse effects include thrombocytopenia,lupus-like syndrome,and cinchonism[96].

Lidocaine and mexiletine

Lidocaine and mexiletine are class IB antiarrhythmic medications,which display the class-effect of use-dependence forboth fastand slow sodium channel blockade.Structurally,the two medications are close analogues with the main difference between them being availability ofan oralformulation formexiletine[90].Use ofmexiletine has shown an ability to suppress the burden ofventricular ectopy[97,98],butwith a trend toward increased mortality[30].The main use of lidocaine for ventricular tachyarrhythmias is with ischemia,during which the medication is able to reduce the incidence of VF by approximately one third[99].

In several guidelines,the use of lidocaine has been the preferred antiarrhythmic medication with VF after out-of-hospitalcardiac arrest[100-102].However,the effect of lidocaine in shock-resistantout-of-hospitalcardiac arrestwas inferiorand less likely to survive to hospital admission when compared to those patients who received amiodarone[76].Thisfinding issimilarto smaller studies which showed worse resuscitation rates with lidocaine[103,104].

These data supportthe currentrecommendations of using lidocaine for the suppression of ventricular arrhythmias in the setting of acute myocardialinfarction or ischemia[30,57].Mexiletine can also be used as adjunctive long-term therapy with amiodarone after ES.Lidocaine and mexiletine may benefitpatients with type 3 long QT syndrome to preventrecurrenttorsades de pointes due to their slow sodium channel blockade effect,thereby shortening the QT interval[30,105,106].

Side effects of lidocaine and mexiletine are dosedependentand resolve with discontinuation ordecrease in drug dosing.Centralnervous system toxicity generally manifests as drowsiness and tremor,butgeneralized seizuresmay also occur.Adverse cardiac effects include bradycardia and asystole[107-109].

Flecainide

This class IC antiarrhythmic medication blocks cardiac sodium channels in use-dependent fashion,but also blocksthe rapid componentofthe delayed rectifier potassium current,IKr,as well as ryanodine receptors (RyR2),which release calcium from cardiac sarcoplasmic reticulum[110].

In the landmark Cardiac Arrhythmia Suppression Trial(CAST),patients with priormyocardialinfarction with ventricular ectopy were placed on flecainide resulting in excess mortality predominantly due to an arrhythmia[111].Some of this has been attributed to low utilization ofβ-blockersconcomitantly(26%usage among flecainide users)[111].In patients withoutstructuralheartdisease orcoronary artery disease,flecainide can be a reasonable addition to concomitantβ-blocker or calcium channel blocker therapy for ventricularectopy[112].In patients with catecholaminergic polymorphic VT,flecainide can be combined withβ-blockade resulting in a decrease in risk of ES after ICD shocks[110,113].

The mostcommon non-cardiac adverse effectfrom flecainide is blurred vision and dizziness.The proarrhythmia effectswere described above,butothercardiac effects include decreased leftventricular inotropy and possible worsening ofheartfailure[114,115].

Other therapy-non-pharmacologic Sedation

With ES frequently due to adrenergic stimulation, sedation is able to reduce this sympathetic tone[116]. Propofol,a short-acting generalanesthetic agentmediating itseffectwith gamma-aminobutyric acid receptors (GABA),hasbeen shown to inhibitsympathetic activity, and suppress refractory ES[117,118].

Extracorporealmembrane oxygenation(ECMO)

While predominantly indicated forcardiogenic shock, venoarterial extracorporeal membrane oxygenation has been used to treat ES related for myocardialischemia[119], myocarditis[120],and Brugada syndrome[121].ECMO maintains tissue perfusion,unloads the left ventricle, preserves coronary circulation,and likely results in decrease of catecholamine release by the individual[122].

Overdrive pacing

In patients who continue to have ES despite other medications and treatments,overdrive pacing can successfully prevent the arrhythmias[16,123,124].The suppression can be a temporizing measure while awaiting revascularization for ischemia or electrophysiology study and attempted catheter ablation,as the ES may return once the pacing ceases[16,123].In cases ofdigitalis toxicity,QT prolongation,and pause-dependent ES, temporary rightventricularpacing can also be effective[30]. Rightventricularpacing alone may notbe able to suppress ES,and reportofbiventricularpacing and wellas triple-sitebiventricularpacing hasshown to be successful in treating ES[124,125].

Left stellate ganglionic blockade

In patients with recent myocardial infarction or ongoing ischemia,leftstellate ganglionic blockade when combined with amiodarone improved survivalcompared to class 1 antiarrhythmic therapy by ACLS guidelines in one smallcohort of ES[61].Unilateralsympathetic denervation in some cases may be insufficientand require bilateral surgical sympathetic denervation[126].In cases where surgicalapproach is notavailable,percutaneous blockade ofthe stellate ganglion with bupivacaine has residual block lasting severalweeks and prevent ES recurrence[127].

Other therapy for selected conditionspharmacologic

Isoproterenol

While adrenergic stimulation triggers orworsens ES in many patients,select populations may benefit from it.Brugada syndrome patients have increased risk of ES from VF;isoproterenolin these patients suppresses ES likely due to augmentation of L-type calcium current[46,128].

Potassium

With hypokalemia identified as a trigger of ES[5,50], the effectis likely due to QT prolongation.Potassium supplementation should be instituted for ventricular arrhythmias whetherfrom diuretic use orother causes, with a goallevelbeing greaterthan 4.5 to 5 mmol/L[30].

Magnesium

Hypomagnesemia has been implicated in polymorphic ventricular ES and other episodes of polymorphic VT[129,130].Magnesium likely exerts its antiarrhythmic effect by antagonizing the L-type calcium channel,which is responsible for generating early afterdepolarization type during the plateau phase ofventricularaction potentials[129].Magnesium supplementation is beneficial in hypomagnesemia due to diuretics and in cases of VT secondary to digoxin toxicity[57].

Conclusions

ES consists of frequent episodes of ventricular tachyarrhythmias,which carry significant morbidity and mortality.The most common cause is ischemia, butevaluation of these patients at presentation should include assessment of other potential substrates and triggers such as worsening heart failure,medications,and genetic conditions.Initial treatment should include ACLS and stabilizing measures.Many patients with ES willrequire more definitive therapy, such as revascularization or ablation with an electrophysiology study,butapplication of optimalmedical therapy remains an importantadjunctive therapy.Use ofβ-blocker and amiodarone are cornerstones of therapy,but tailoring the treatment and antiarrhythmic therapy for the underlying condition and trigger is necessary.

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?Corresponding author:Dan Sorajja,MD,Division of Cardiovascular Diseases,Mayo Clinic Arizona,5777 E Mayo Blvd,Phoenix,AZ 85054. Tel/Fax:(480)342-0239/(480)342-1606,E-mail:sorajja.dan@mayo.edu.

Received 14 November 2014,Accepted 05 December 2014,Epub 15 January 2015

The authors reported no conflict of interests.

?2015 by the Journal of Biomedical Research.All rights reserved.

10.7555/JBR.29.20140147