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Current and Emerging Antiarrhythmic Drug Therapy for Ventricular Tachycardia

Current and Emerging Antiarrhythmic Drug Therapy for Ventricular Tachycardia Ventricular arrhythmias, including ventricular fibrillation (VF) and sustained ventricular tachycardia (VT), are the principal causes of sudden cardiac death in patients with structural heart disease. While coronary artery disease is the predominant substrate associated with the development of VT, these arrhythmias are known to occur in a variety of disorders, including dilated cardiomyopathy, valvular and congenital heart disease, and cardiac ion channelopathies such as the long QT syndrome. In a minority of patients, VT occurs in the absence of structural heart disease. Despite the established mortality benefit of the implantable cardioverter defibrillator (ICD) in patients at risk of lethal arrhythmias, recurrent VT/VF events continue to be a source of morbidity and impaired quality of life in such patients. Antiarrhythmic therapy is indicated in select patients to treat symptomatic VT episodes, to reduce the incidence of ICD shocks, and potentially to improve quality of life and reduce hospitalizations related to cardiac arrhythmia. The primary adverse effects of antiarrhythmic medications are related to both cardiac and extracardiac toxicity, including the risk of proarrhythmia. Current drug therapy for ventricular arrhythmia has been limited by suboptimal efficacy in many patients, resulting in recurrent VT/VF events, and by drug toxicity or intolerance leading to discontinuation in a large percentage of patients. Amiodarone and sotalol are the principal agents used in the chronic treatment of VT. In addition, dronedarone and dofetilide, agents approved for the treatment of atrial fibrillation, and ranolazine, an antianginal agent, have been demonstrated to be protective against ventricular arrhythmia in small clinical studies. Finally, advances in basic electrophysiology have uncovered new molecular targets for the treatment of ventricular arrhythmia, and pharmacologic agents directed at these targets may emerge as promising VT treatments in the future. The roles of these current and emerging therapies for the treatment of VT in humans will be summarized in this review. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cardiology and Therapy Springer Journals

Current and Emerging Antiarrhythmic Drug Therapy for Ventricular Tachycardia

Williams, Eric; Viswanathan, Mohan
Cardiology and Therapy , Volume 2 (1) – Feb 20, 2013
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20 pages

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Publisher
Springer Journals
Copyright
Copyright © 2013 by The Author(s)
Subject
Medicine & Public Health; Internal Medicine; Cardiology
ISSN
2193-8261
eISSN
2193-6544
DOI
10.1007/s40119-013-0012-5
pmid
25135287
Publisher site
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Abstract

Ventricular arrhythmias, including ventricular fibrillation (VF) and sustained ventricular tachycardia (VT), are the principal causes of sudden cardiac death in patients with structural heart disease. While coronary artery disease is the predominant substrate associated with the development of VT, these arrhythmias are known to occur in a variety of disorders, including dilated cardiomyopathy, valvular and congenital heart disease, and cardiac ion channelopathies such as the long QT syndrome. In a minority of patients, VT occurs in the absence of structural heart disease. Despite the established mortality benefit of the implantable cardioverter defibrillator (ICD) in patients at risk of lethal arrhythmias, recurrent VT/VF events continue to be a source of morbidity and impaired quality of life in such patients. Antiarrhythmic therapy is indicated in select patients to treat symptomatic VT episodes, to reduce the incidence of ICD shocks, and potentially to improve quality of life and reduce hospitalizations related to cardiac arrhythmia. The primary adverse effects of antiarrhythmic medications are related to both cardiac and extracardiac toxicity, including the risk of proarrhythmia. Current drug therapy for ventricular arrhythmia has been limited by suboptimal efficacy in many patients, resulting in recurrent VT/VF events, and by drug toxicity or intolerance leading to discontinuation in a large percentage of patients. Amiodarone and sotalol are the principal agents used in the chronic treatment of VT. In addition, dronedarone and dofetilide, agents approved for the treatment of atrial fibrillation, and ranolazine, an antianginal agent, have been demonstrated to be protective against ventricular arrhythmia in small clinical studies. Finally, advances in basic electrophysiology have uncovered new molecular targets for the treatment of ventricular arrhythmia, and pharmacologic agents directed at these targets may emerge as promising VT treatments in the future. The roles of these current and emerging therapies for the treatment of VT in humans will be summarized in this review.

Journal

Cardiology and Therapy – Springer Journals

Published: Feb 20, 2013

References

  • Executive summary: heart disease and stroke statistics—2012 update: a report from the American Heart Association
    Roger, VL; Go, AS; Lloyd-Jones, DM
  • Frequency of sudden cardiac death and profiles of risk
    Myerburg, RJ; Interian, A; Mitrani, RM; Kessler, KM; Castellanos, A
  • Catheter ablation of cardiac arrhythmias
    Wilber, DJ
  • EHRA/HRS expert consensus on catheter ablation of ventricular arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA)
    Aliot, EM; Stevenson, WG; Almendral-Garrote, JM
  • New drugs vs. old concepts: a fresh look at antiarrhythmics
    Thireau, J; Pasquie, JL; Martel, E; Guennec, JY; Richard, S
  • Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation
    Bakker, JM; Capelle, FJ; Janse, MJ
  • Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart
    Pogwizd, SM; Hoyt, RH; Saffitz, JE
  • Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes
    Al-Khatib, SM; Granger, CB; Huang, Y
  • Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators
    Newby, KH; Thompson, T; Stebbins, A
  • Task Force on Sudden Cardiac Death of the European Society of Cardiology
    Priori, SG; Aliot, E; Blomstrom-Lundqvist, C
  • Long-term reproducibility and significance of provokable ventricular arrhythmias after myocardial infarction
    Roy, D; Marchand, E; Theroux, P
  • Cardiac electrophysiology: from cell to bedside
    Callans, DJ; Josephson, ME
  • 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society
    Epstein, AE; Dimarco, JP; Ellenbogen, KA
  • Prediction of sudden cardiac death: next steps in pursuit of effective methodology
    Stecker, EC; Chugh, SS
  • Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction
    Hohnloser, SH; Kuck, KH; Dorian, P
  • Electrical storm presages nonsudden death: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial
    Exner, DV; Pinski, SL; Wyse, DG
  • Should catheter ablation be the preferred therapy for reducing ICD shocks?: ventricular tachycardia ablation versus drugs for preventing ICD shocks: role of adjuvant antiarrhythmic drug therapy
    Patel, C; Yan, G-X; Kocovic, D; Kowey, PR
  • Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial
    Connolly, SJ; Dorian, P; Roberts, RS
  • A classification of antiarrhythmic actions reassessed after a decade of new drugs
    Vaughan Williams, EM
  • Cardiac electrophysiology: from cell to bedside
    Gillis, AM
  • Cardiac electrophysiology: from cell to bedside
    Smith, TW; Cain, ME
  • Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) study
    Singh, S; Zoble, RG; Yellen, L
  • Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group
    Torp-Pedersen, C; Moller, M; Bloch-Thomsen, PE
  • Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial
    Kober, L; Bloch-Thomsen, PE; Moller, M
  • Effect of dronedarone on cardiovascular events in atrial fibrillation
    Hohnloser, SH; Crijns, HJGM; Eickels, M
  • Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter
    Singh, BN; Connolly, SJ; Crijns, HJ
  • A focus on antiarrhythmic properties of ranolazine
    Vizzardi, E; D’Aloia, A; Quinzani, F
  • Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial
    Scirica, BM; Morrow, DA; Hod, H
  • a randomised trial
  • Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial
    Chen, ZM; Pan, HC; Chen, YP
  • Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group
    Pacifico, A; Hohnloser, SH; Williams, JH
  • Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival with oral d-sotalol
    Waldo, AL; Camm, AJ; de Ruyter, H
  • Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators
    Boutitie, F; Boissel, JP; Connolly, SJ
  • Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial
    Echt, DS; Liebson, PR; Mitchell, LB
  • Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator
    Dorian, P; Borggrefe, M; Al-Khalidi, HR
  • New pharmacological agents for arrhythmias
    Mason, PK; DiMarco, JP
  • Effects of initiating carvedilol in patients with severe chronic heart failure: results from the COPERNICUS Study
    Krum, H; Roecker, EB; Mohacsi, P
  • A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias
    Ryden, L; Ariniego, R; Arnman, K
  • Mechanisms and clinical management of inherited channelopathies: long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome
    Kaufman, ES
  • Adjunctive drug therapy of acute myocardial infarction—evidence from clinical trials
    Hennekens, CH; Albert, CM; Godfried, SL; Gaziano, JM; Buring, JE
  • Role of antiarrhythmic drugs in patients with implantable cardioverter defibrillators
    Herendael, H; Pinter, A; Ahmad, K
  • Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death
    Sim, I; McDonald, KM; Lavori, PW; Norbutas, CM; Hlatky, MA
  • Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure
    Bardy, GH; Lee, KL; Mark, DB
  • Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT, Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators
    Cairns, JA; Connolly, SJ; Roberts, R; Gent, M
  • Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators
    Julian, DG; Camm, AJ; Frangin, G
  • The side effect profile of class III antiarrhythmic drugs: focus on d,l-sotalol
    MacNeil, DJ
  • A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators
    Mason, JW
  • Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study)
  • Prophylactic lidocaine use in acute myocardial infarction: incidence and outcomes from two international trials. The GUSTO-I and GUSTO-IIb Investigators
    Alexander, JH; Granger, CB; Sadowski, Z
  • Increased mortality after dronedarone therapy for severe heart failure
    Kober, L; Torp-Pedersen, C; McMurray, JJV
  • Dronedarone for recurrent ventricular tachycardia: a real alternative?
    Exposito, V; Rodriguez-Entem, F; Gonzalez-Enriquez, S; Olalla, JJ
  • A patient with recurrent atrial fibrillation and monomorphic ventricular tachycardia treated successfully with dronedarone
    Fink, A; Duray, GZ; Hohnloser, SH
  • Suppression of ventricular tachycardia with dronedarone: a case report
    Shaaraoui, M; Freudenberger, R; Levin, V; Marchlinski, FE
  • Dronedarone in high-risk permanent atrial fibrillation
    Connolly, SJ; Camm, AJ; Halperin, JL
  • Voltage- and time-dependent block of the delayed K + current in cardiac myocytes by dofetilide
    Carmeliet, E
  • A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease
    Boriani, G; Lubinski, A; Capucci, A
  • Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies
    Baquero, GA; Banchs, JE; Depalma, S
  • Effect of ranolazine on ventricular repolarization in class III antiarrhythmic drug-treated rabbits
    Frommeyer, G; Kaiser, D; Uphaus, T
  • Low doses of ranolazine and dronedarone in combination exert potent protection against atrial fibrillation and vulnerability to ventricular arrhythmias during acute myocardial ischemia
    Verrier, RL; Pagotto, VP; Kanas, AF
  • Suppression of non-sustained ventricular tachycardia with ranolazine: a case report
    Kaliebe, JW; Murdock, DK
  • Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks
    Bunch, TJ; Mahapatra, S; Murdock, D
  • Synergistic electrophysiologic and antiarrhythmic effects of the combination of ranolazine and chronic amiodarone in canine atria
    Sicouri, S; Burashnikov, A; Belardinelli, L; Antzelevitch, C
  • Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification
    Camm, AJ; Pratt, CM; Schwartz, PJ
  • Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study
    Kowey, PR; Crijns, HJ; Aliot, EM
  • Celivarone in patients with an implantable cardioverter-defibrillator: adjunctive therapy for the reduction of ventricular arrhythmia-triggered implantable cardioverter-defibrillator interventions
    Gojkovic, O; Aliot, EM; Capucci, A
  • Flecainide suppresses defibrillator-induced storming in catecholaminergic polymorphic ventricular tachycardia
    Hong, RA; Rivera, KK; Jittirat, A; Choi, JJ
  • JTV519 (K201) reduces sarcoplasmic reticulum Ca(2)(+) leak and improves diastolic function in vitro in murine and human non-failing myocardium
    Sacherer, M; Sedej, S; Wakula, P
  • CaMKII inhibition rescues proarrhythmic phenotypes in the model of human ankyrin-B syndrome
    Degrande, S; Nixon, D; Koval, O
  • Drug development for treatment of cardiac arrhythmias: targeting the gap junctions
    Wit, AL; Duffy, HS
  • Maintenance of intercellular coupling by the antiarrhythmic peptide rotigaptide suppresses arrhythmogenic discordant alternans
    Kjolbye, AL; Dikshteyn, M; Eloff, BC; Deschenes, I; Rosenbaum, DS
  • Targeting calcium handling in arrhythmias
    Antoons, G; Sipido, KR
  • The cardiac sarcolemmal ATP-sensitive potassium channel as a novel target for anti-arrhythmic therapy
    Billman, GE
  • Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas
    Englert, HC; Gerlach, U; Goegelein, H