Ventricular tachycardia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Sara Zand, M.D.[2] Cafer Zorkun, M.D., Ph.D. [3], Avirup Guha, M.B.B.S.[4]

Overview

The mainstay of medical therapy in hemodynamic stable VT is suppression of tachyarrhythmia with antiarrhythmic medications such as amiodarone, sotalol, lidocaine, betablocker alongside with correction of hypokalemia, hypomagnesemia and hypocalcemia. In addition, treating the underlying causes of VT including ischemic heart disease or decompensated heart failure are warranted.

Medical Therapy

Common medications for treatment of VT include:[1]

Antiarrhythmic medications

[2]

Sodium channel blocker

Ranolazine

  • NO efficacy in reduction the fist VT, VF in high risk patients, but significant reduction of recurrent VT, VF requiring ICD implantation.[7]

Beta blocker

Amiodarone, sotalol

Calcium channel blocker



Arrhythmiac medication, class, dose Indication Receptor target Electrophysiologic effect Pharmacological characteristics Common advers effects
Acebutolol

PO 200–1200 mg daily, up to 600 mg bid

VT, PVC B1, mild internistic sympathetic activity Slowing sinus rate, increasing AV nodal refractoriness Prolonged haft life in renal impairment, metabolism: hepatic Bradycardia, hypotension, HF, AV block, Dizziness, fatigue, anxiety, impotence, hyperesthesia,hypoesthesia
Amiodarone (III)

IV:VF/pulseless VT arrest: 300 mg bolus, stable VT: 150-mg bolus then 1 mg/min x 6 h, then 0.5 mg/min x 18 h PO: 400 mg q 8 to 12 h for 1–2 wk, then 300–400 mg daily; reduce dose to 200 mg daily if possible

VT, VF, PVC INa, ICa, IKr, IK1, IKs, Ito, Beta receptor, Alpha receptor, nuclear T3

recepto

Slowed sinus rate, QRS prolongation, QTc prolongation, increased AV nodal refractoriness ,increased defibrilation threshold Metabolism: hepatic, half life: 26-107 days Hypotension, bradycardia, AV block, TdP, slowing VT below programmed ICD detection rate, increased defibrillation threshold, corneal microdeposits, thyroid abnormalities, ataxia, nausea, emesis, constipation, photosensitivity, skin discoloration, ataxia, dizziness, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis, pneumonitis
Atenolol (II)

PO: 25–100 mg qd or bid

VT, PVC, ARVC, LQTS Beta 1 Slowed sinus rate ,
increased AV nodal refractoriness
Metabolism: hepatic Bradycardia, hypotension, heart failure, AV block, dizziness, fatigue, depression, impotence
Bisoprolol (II)

PO: 2.5–10 mg once daily

VT, PVC Beta 1 receptor Slowed sinus rate, increased AV nodal refractoriness Metabolism: hepatic Chest pain, bradycardia, AV block, Fatigue, insomnia, diarrhea
Carvedilol (II)

PO: 3.125–25 mg q 12 h

VT, PVC Beta 1, Beta 2, Alpha Slowed sinus rate, increased AV nodal refractoriness Metabolism: hepatic Bradycardia, hypotension, AV block, edema, syncope, Hyperglycemia, dizziness, fatigue, diarrhea
Carvedilol (II)

PO: 3.125–25 mg q 12 h

VT, PVC Beta 1, Beta 2, Alpha Slowed sinus rate, increased AV nodal refractoriness Metabolism: hepatic Bradycardia, hypotension, AV block, edema, syncope, Hyperglycemia, dizziness, fatigue, diarrhea
Diltiazem (IV)

IV: 5–10 mg,qd: 15–30 min, Extended release: PO: 120–360 mg/da, PO: 3.125–25 mg q 12 h

RVOT VT, ideopathic left VT ICa-L Slowed sinus rate, slowed AV node conduction, PR prolongation Metabolism: hepatic Bradycardia, hypotension, AV block, edema, exacerbation of HF reduced EF, Headache, rash, constipation
Esmolol (II)

IV: 0.5 mg/kg bolus, 0.05 mg/kg/min

VT B1 Slowed sinus rate, increased AV node refractoriness Metabolism: RBC Bradycardia, hypotension, AV block, HF, dizziness, neusea
Flecainide (IC) PO: 50–200 mg q 12 h VT, PVC (in the absence of structural heart disease), CPVT INa, IKr, IKur Prolonged PR interval, prolonged QRS duration, increased defibrillation threshold Metabolism: RBC Sinus node dysfunction, AV block, drug-induced Brugada syndrome, monomorphic VT in patients with a myocardial scar, exacerbation of HFrEF
Lidocaine (IB)

IV: 1 mg/kg bolus, 1–3 mg/min, 1–1.5 mg/kg. Repeat 0.5–0.75 mg/kg bolus every 5–10 min (max cumulative dose 3 mg/kg), maintenance infusion: 1–4 mg/min or starting 0.5 mg/min

VT, VF INa Slightly shortening of QTc interval Metabolism: hepatic, prolonged half life in HF, liver disease, shock, severe renal disease Bradycardia, hemodynamic collapse, AV block, sinus arrest, delirium, psychosis, seizure, nausea, tinnitus, dyspnea, bronchospasm
Metoprolol (II) IV: 5 mg q 5 min up to 3 doses, PO: 25–100 mg Extended release qd or q 12 h VT, PVC B1 Slowed sinus rate, increased AV nodal refractoriness Metabolism: None, Excretion: urine Bradycardia, hypotension, AV block, dizziness, fatigue, diarrhea, depression, dyspnea
Metoprolol (II) IV: 5 mg q 5 min up to 3 doses, PO: 25–100 mg Extended release qd or q 12 h VT, PVC B1 Slowed sinus rate, increased AV nodal refractoriness Metabolism: None, Excretion: urine Bradycardia, hypotension, AV block, dizziness, fatigue, diarrhea, depression, dyspnea
Mexiletine (IB), PO: 150–300 mg q 8 h or q 12 h VT, PVC, VF, Long QT3 INa Slightly shortening of QTc interval Metabolism: hepatic HF, AV block, lightheaded, tremor, ataxia, paresthesias, nausea, blood dyscrasias
Nadolol (II)

PO: 40–320 mg daily

VT, PVC, LQTS, CPVT B1, B2 Slowed sinus rate, increased AV nodal refractoriness Metabolism: none, excretion: urine Bradycardia, hypotension, HF, AV block, edema, dizziness, cold extremities, bronchospasm
Procainamide (IA), IV: loading dose 10–17 mg/kg at 20–50 mg/min, maintenance dose: 1–4 mg/min, PO (SR preparation): 500–1250 mg q 6 h VT, PVC, LQTS, CPVT B1, B2 Slowed sinus rate, increased AV nodal refractoriness Metabolism: none, excretion: urine Bradycardia, hypotension, HF, AV block, edema, dizziness, cold extremities, bronchospasm
Propafenone (IC), PO: Immediate release 150–300 mg q 8 h, Extended release 225–425 mg q 12 h VT, PVC (in the absence of structural heart disease) INa, IKr, IKur, Beta receptor, Alpha recept Prolonged PR interval, prolonged QRS duration, increased defibrillation threshold Metabolism: hepatic HF, AV block, drug-induced Brugada syndrome, dizziness, fatigue, nausea, diarrhea, xerostomia, tremor, blurred vision
Propranolol (II), IV: 1–3 mg q 5 min to a total of 5 mg, PO: Immediate release 10–40 mg q 6 h; Extended release 60–160 mg q 12 h VT, PVC, Long QT syndrome Beta 1 , B2 , INa Slowed sinus rate, increased AV nodal refractoriness Metabolism: hepatic Bradycardia, hypotension, HF, AV block, sleep disorder, dizziness, nightmares, hyperglycemia, diarrhea, bronchospasm
Quinidine (IA), PO: sulfate salt 200–600 mg q 6 h to q 12 h, gluconate salt 324–648 mg q 8 h to q 12 h, IV: loading dose: 800 mg in 50 mL infused at 50 mg/min VT, VF, short QT syndrome, brugada INa, Ito, IKr, M, Alpha receptor QRS prolongation, QTc prolongation, increased defibrillation threshold Metabolism: hepatic Syncope, torsades de pointes, AV block, dizziness, diarrhea, nausea, esophagitis, emesis, tinnitus, blurred vision, rash, weakness, tremor, blood dyscrasias
Ranolazine (not classified), PO: 500–1000 mg q 12 h VT INa, IKr Slowed sinus rate, QTc prolongation Metabolism: hepatic Bradycardia, hypotension, headache, dizziness, syncope, nausea, dyspnea
Sotalol (III), IV: 75 mg q 12 h, PO: 80–120 mg q 12 h, may increase dose every 3 d; max 320 mg/d VT, VF, PVC B1, B2 IKr Slowed sinus rate, QTc prolongation, increased AV nodal refractoriness, decreased defibrillation threshold Metabolism: none Bradycardia, hypotension, HF, syncope, TdP, fatigue, dizziness, weakness, dyspnea, bronchitis, depression, nausea, diarrhea
Verapamil, IV: 2.5–5 mg q 15–30 min, sustained release PO: 240–480 mg/d RVOT VT, verapamil-sensitive idiopathic Left VT ICa-L Slowed sinus rate,PR prolongation, slowed AV nodal conduction Metabolism: hepatic Hypotension, edema, HF, AV block, bradycardia, exacerbation of HF reduced EF, headache, rash, gingival hyperplasia, constipation, dyspepsia

Electrolytes

Fatty acids, Lipids


Specific recommendation

Management of patients with Polymorphic Ventricular arrhythmia

 
 
 
Polymorphic Ventricular arrhythmia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Underlying etiology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute ischemia
 
External precipitating factors
 
Polymorphic Ventricular Arrhythmia triggered by unifocal PVC
 
Acquired long QT
 
 
 
 
 
 
 
Primary electrical disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approach to STEMI
 
Treatment of underlying condition (Class I)
 
Catheter ablation (Class IIa)
 
 
Remove precipitating factors (Class I)
  • Mg++/K+ i.v.(Class I)
  • Isoproterenol (Class I)
  • Pacing (Class I)
  •  
     
     
    Brugada, Early repolarization syndrome
     
    Idiopathic VF
     
    Long QT, CPVT
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Recurrent Ventricular arrhythmia
     
     
     
    Recurrent Ventricular arrhythmia
     
    Recurrent Ventricular arrhythmia
     
     
    Isoproterenol (Class IIa)
     
    Isoproterenol (Class IIa)
  • Quinidine (Class IIa)
  • Verapamil (Class IIa
  • Catheter ablation of PVC triggers (Class IIa)
  •  
    Beta-blocker (Class I)
  • Pacing (Class I)
  • Mg++/K+ i.v (Class I)
  • Antiarrhythmic drugs according to underlying disease (Class 2a)
  • Autonomic modulation (Class 2a)
  •  
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Deep sedation/ intubation (Class IIa)
     
    Deep sedation/ intubation (Class IIa)
  • Mechanical circulatory support (Class IIb)
  •  
    Deep sedation/ intubation (Class IIa)
  • Mechanical circulatory support (Class IIb)
  •  
     
    Recurrent ventricular arrhythmia
     
    Recurrent ventricular arrhythmia
     
    Recurrent ventricular arrhythmia
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Deep sedation/ intubation (Class IIa)
     
    Deep sedation/ intubation (Class IIa)
  • Mechanical circulatory support (Class IIb)
  •  
    Deep sedation/ intubation (Class IIa)
  • Mechanical circulatory support (Class IIb)
  •  
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    The above algorithm adopted from 2022 ESC Guideline[38]

    Management of sustained monomorphic ventricular tachycardia

    Recommendations for acute management of sustained VT
    DC cardiovertion (Class I, Level of Evidence B):

    DC cardioversion is recommended as the first-line therapy for hemodynamically not-tolerated sustained monomorphic ventricular tachycardia

    DC cardiovertion (Class I, Level of Evidence C) :

    DC cardioversion is recommended as the first-line treatment for patients presenting with tolerated sustained monomorphic VT when anesthetic/sedation risk is low

    Supraventricular tachycardia (Class IIa, Level of Evidence C)

    ❑ In patients presenting with a regular hemodynamically tolerated wide QRS complex tachycardia suspected for supraventricular tachycardia, administration of adenosine or vagal maneuvers should be considered

    Procainamide (Class IIa, Level of Evidence B)

    ❑In patients presenting with a hemodynamically tolerated sustained monomorphic VT and presence of structural heart disease, intravenous procainamide should be considered

    Flecainide, ajmaline, sotalol (Class IIb, Level of Evidence B)

    ❑In patients presenting with a hemodynamically tolerated sustained monomorphic VT in the absence of significant structural heart disease, flecainide, ajmaline, or sotalol may be considered

    Verapamil (Class III, Level of Evidence B)

    ❑Intravenous verapamil is not recommended in wide QRS complex tachycardia of unknown mechanism

    The above table adopted from 2022 ESC Guideline[38]

    Management of electrical storm

    Recommendations for management of electrical storm
    Sedation (Class I, Level of Evidence C):

    ❑ Mild to moderate sedation is recommended in patients with the electrical storm to reduce psychological distress and reduce sympathetic tone

    Strucrural heart disease (Class I, Level of Evidence B) :

    Antiarrhythmic therapy with beta-blockers (non-selective preferred) in combination with intravenous amiodarone is recommended in patients with structural heart disease and electrical storm unless contraindicated
    Catheter ablation is recommended in patients presenting with incessant VT or electrical storm due to sustained monomorphic VT refractory to antiarrhythmic drugs

    Torsades depointes (Class I, Level of Evidence C)

    ❑ Intravenous magnesium with supplementation of potassium is recommended in patients with TdP
    Isoproterenol or transvenous pacing to increase heart rate is recommended in patients with acquired LQT syndrome and recurrent TdP despite correction of precipitating conditions and magnesium

    Procainamide (Class IIa, Level of Evidence B)

    ❑In patients presenting with a hemodynamically tolerated sustained monomorphic VT and presence of structural heart disease, intravenous procainamide should be considered

    Intubation (Class IIa, Level of Evidence C)

    ❑Deep sedation/intubation should be considered in patients with an intractable electrical storm non-responsive drug treatment

    Catheter ablation should be considered in patients with recurrent episodes of VT/VF triggered by a similar PVC, refractory to medical treatment or coronary revascularization

    Quinidine (Class IIb, Level of Evidence C)

    Quinidine may be considered in patients with coronary artery disease and electrical storm due to recurrent VT refractory to other antiarrhythmic drugs

    Refractory electerical storm (Class IIb, Level of Evidence C)

    Autonomic modulation may be considered in patients with electrical storm refractory to medical therapy and in whom catheter ablation is ineffective or not possible
    Mechanical circulatory support may be considered in the management of drug-refractory electrical storm and [[cardiogenic shock]]

    The above table adopted from 2022 ESC Guideline[38]

    Recommendations for treatment with heart failure medication

    Class I
    "Optimal medical treatment including ACE-I/ARB/ ARNIs, mineralocorticoid receptor antagonist, beta-blockers, and SGLT2 inhibitors is indicated in all heart failure patients with reduced EF' (Level of Evidence A)"
    The above table adopted from 2022 ESC Guideline[38]

    Notes

    use of beta blockers lessened mortality rate.[50]

    • Prophylactic use of Higher dose amiodarone after MI increase mortality, whereas moderate dose amiodarone was not superior to placebo.[51]


     
     
     
     
     
     
     
     
     
     
    Sustained monomorphic VT
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Hemodynamic stability
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Stable
     
     
     
     
     
     
     
     
     
     
     
    Unstable
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    12-Lead ECG, history, physical exam
     
     
     
     
     
     
     
     
     
     
     
    Dirrect current cardioversion,ACLS
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Notifying disease causing VT
     
     
     
    Cardioversion(class1)
     
     
     
     
     
     
     
    VT termination
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Structural heart disease
     
     
     
    Intravenous procainamide (class2a)
     
     
     
     
     
    Yes, therapy of underlying heart disease
     
    NO, cardioversion (class1)
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    NO, Ideopathic VT
     
     
     
    Intravenous amiodarone or sotalole (class2b)
     
     
     
     
     
     
     
     
    VT termination
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Verapamil sensitive VT: Verapamil outflow tract VT: betablocker (class2a)
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Effective
     
    Non effective: cardioversion
     
     
     
     
     
     
     
     
    Yes,therapy of underlying heart disease
     
    NO, Sedation ,anesthesia, reassessing antiarrhythmic therapy, repeating cardioversion
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Therapy to prevent recurrence of VT
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    No VT termination
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Catheter ablation (class1)
     
     
    Catheter ablation (class1)
     
    Verapamil , betablocker (class2a)
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    The above algorithm adopted from 2017 AHA/ACC/HRS Guideline

    Comments




    Recommendations for treatment of recurrent ventricular tachycardia in ischemic heart disease
    Medications (Class I, Level of Evidence B):

    ❑ In patients with IHD and recurrent symptomatic ventricular tachycardia and frequent ICD shocks despite programming, betablocker, sotalol, amiodarone is recommended for supression of arrhythmia
    ❑ In patients with period MI and presence of VT storm refractory to amiodarone or other antiarrhythmic drugs, catheter ablation is recommended

    Catheter ablation (Class IIb, Level of Evidence C) :

    Catheter ablation can be the first line therapy for recurrent sustained monomorphic VT in IHD

    (Class III, Level of Evidence C)

    ❑ Class IC antiarrhythmic drugs (flecainide, propafenone ) is harmful for supression of ventricular tachycardia in patients with perior MI
    ❑ In patients with incessant VT/VF, after controlling tachyarrhythmia ICD should be implanted due to avoiding of repeated ICD shocks
    ❑ In patients with recurrent monomorphic VT , only revascularization is ineffective for preventing of tachyarrhythmia

    The above table adopted from 2017 AHA/ACC/HRS Guideline[2]

    Message

    Recommendations for treatment of recurrent ventricular tachycardia in non-ischemic heart disease
    Amiodarone, sotalol (Class IIa, Level of Evidence B):

    Amiodarone or sotalol is recommended in the presensence of recurrent ventricular arrhythmia and frequent ICD shocks despite optimal programming or beta blocker therapy

    Catheter ablation (Class IIa, Level of Evidence B) :

    ❑ In the setting of frequent ventricular arrhythmia despite optimal ICD programming or failed antiarrhythmic medications, catheter ablation is recommended

    The above table adopted from 2017 AHA/ACC/HRS Guideline[2]

    References

    1. 1.0 1.1 1.2 Bunch, T. Jared; Mahapatra, Srijoy; Murdock, David; Molden, Jamie; Weiss, J. Peter; May, Heidi T.; Bair, Tami L.; Mader, Katy M.; Crandall, Brian G.; Day, John D.; Osborn, Jeffrey S.; Muhlestein, Joseph B.; Lappe, Donald L.; Anderson, Jeffrey L. (2011). "Ranolazine Reduces Ventricular Tachycardia Burden and ICD Shocks in Patients with Drug-Refractory ICD Shocks". Pacing and Clinical Electrophysiology. 34 (12): 1600–1606. doi:10.1111/j.1540-8159.2011.03208.x. ISSN 0147-8389.
    2. 2.0 2.1 2.2 Al-Khatib, Sana M.; Stevenson, William G.; Ackerman, Michael J.; Bryant, William J.; Callans, David J.; Curtis, Anne B.; Deal, Barbara J.; Dickfeld, Timm; Field, Michael E.; Fonarow, Gregg C.; Gillis, Anne M.; Granger, Christopher B.; Hammill, Stephen C.; Hlatky, Mark A.; Joglar, José A.; Kay, G. Neal; Matlock, Daniel D.; Myerburg, Robert J.; Page, Richard L. (2018). "2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death". Circulation. 138 (13). doi:10.1161/CIR.0000000000000549. ISSN 0009-7322.
    3. Kudenchuk, Peter J.; Brown, Siobhan P.; Daya, Mohamud; Rea, Thomas; Nichol, Graham; Morrison, Laurie J.; Leroux, Brian; Vaillancourt, Christian; Wittwer, Lynn; Callaway, Clifton W.; Christenson, James; Egan, Debra; Ornato, Joseph P.; Weisfeldt, Myron L.; Stiell, Ian G.; Idris, Ahamed H.; Aufderheide, Tom P.; Dunford, James V.; Colella, M. Riccardo; Vilke, Gary M.; Brienza, Ashley M.; Desvigne-Nickens, Patrice; Gray, Pamela C.; Gray, Randal; Seals, Norman; Straight, Ron; Dorian, Paul (2016). "Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest". New England Journal of Medicine. 374 (18): 1711–1722. doi:10.1056/NEJMoa1514204. ISSN 0028-4793.
    4. Mazzanti, Andrea; Maragna, Riccardo; Faragli, Alessandro; Monteforte, Nicola; Bloise, Raffaella; Memmi, Mirella; Novelli, Valeria; Baiardi, Paola; Bagnardi, Vincenzo; Etheridge, Susan P.; Napolitano, Carlo; Priori, Silvia G. (2016). "Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3". Journal of the American College of Cardiology. 67 (9): 1053–1058. doi:10.1016/j.jacc.2015.12.033. ISSN 0735-1097.
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