Catecholaminergic polymorphic ventricular tachycardia medical therapy: Difference between revisions

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==Medical Therapy==
==Medical Therapy==
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Disease Name===


* '''1 Stage 1 - Name of stage'''
Pharmacologic medical therapies for [[CPVT]] include [[beta blockers]], [[flecainide]] and [[verapamil]].
** 1.1 '''Specific Organ system involved 1'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. '<nowiki/>'''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 1.2 '''Specific Organ system involved 2'''
*** 1.2.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 1.2.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
===Beta-blockers===
** 2.1 '''Specific Organ system involved 1 '''
*The first-line [[therapeutic]] option for patients with [[CPVT]] is exercise restriction combined with [[beta-blockers]] without [[beta-blockers|intrinsic sympathomimetic activity]].<ref name="nihon">{{cite journal|title=Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death|journal=Heart|date=January 2003|first=Naokata|last=Sumitomo|coauthors=Harada K, Nagashima M, Yasuda T, Nakamura Y, Aragaki Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S, Matsuoka S, Oono T, Hayakawa S, Miura M, Ushinohama H, Shibata T, Niimura I|volume=89|issue=1|pages=66–70|pmid=12482795 |format=|doi=10.1136/heart.89.1.66|pmc=1767500 }}</ref>
**: '''Note (1):'''
*Because of the [[adrenergic]] nature of [[arrhythmias]] in [[CPVT]], [[beta-blockers|non-selective beta-blockers]], titrated at the maximum tolerated dose in the absence of [[contraindications]] (example, [[asthma]]) are considered the most effective pharmacological therapy.
**: '''Note (2)''':  
*Indications:
**: '''Note (3):'''
**All patients with stress-induced [[ventricular arrhythmias]].
*** 2.1.1 '''Adult'''
**[[carrier|Silent carriers]] of a pathogenic [[mutation]], even when they do not exhibit [[arrhythmias]] during [[exercise stress testing]] since [[cardiac arrest]] may occur in them.<ref name="HayashiDenjoy2012">{{cite journal|last1=Hayashi|first1=Miyuki|last2=Denjoy|first2=Isabelle|last3=Hayashi|first3=Meiso|last4=Extramiana|first4=Fabrice|last5=Maltret|first5=Alice|last6=Roux-Buisson|first6=Nathalie|last7=Lupoglazoff|first7=Jean-Marc|last8=Klug|first8=Didier|last9=Maury|first9=Philippe|last10=Messali|first10=Anne|last11=Guicheney|first11=Pascale|last12=Leenhardt|first12=Antoine|title=The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands|journal=EP Europace|volume=14|issue=9|year=2012|pages=1344–1351|issn=1532-2092|doi=10.1093/europace/eus031}}</ref>
**** Parenteral regimen
*Drugs used:
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
**[[Nadolol]]<ref name="HayashiDenjoy2009">{{cite journal|last1=Hayashi|first1=Meiso|last2=Denjoy|first2=Isabelle|last3=Extramiana|first3=Fabrice|last4=Maltret|first4=Alice|last5=Buisson|first5=Nathalie Roux|last6=Lupoglazoff|first6=Jean-Marc|last7=Klug|first7=Didier|last8=Hayashi|first8=Miyuki|last9=Takatsuki|first9=Seiji|last10=Villain|first10=Elisabeth|last11=Kamblock|first11=Joël|last12=Messali|first12=Anne|last13=Guicheney|first13=Pascale|last14=Lunardi|first14=Joël|last15=Leenhardt|first15=Antoine|title=Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=119|issue=18|year=2009|pages=2426–2434|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.108.829267}}</ref><ref name="LerenSaberniak2016">{{cite journal|last1=Leren|first1=Ida S.|last2=Saberniak|first2=Jørg|last3=Majid|first3=Eman|last4=Haland|first4=Trine F.|last5=Edvardsen|first5=Thor|last6=Haugaa|first6=Kristina H.|title=Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia|journal=Heart Rhythm|volume=13|issue=2|year=2016|pages=433–440|issn=15475271|doi=10.1016/j.hrthm.2015.09.029}}</ref>
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***Long-acting, [[beta-blockers|non-selective beta-blocker]].
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
***Preferred for [[prophylactic treatment of CPVT]].
**** Oral regimen
***It is considered the most clinically effective choice.
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***Dosage: 1-2 mg/kg per day.
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
**[[Propranolol]]  
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***Long-acting, [[beta-blockers|non-selective beta-blocker]].
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***It is also considered an effective medication when [[Nadolol]] is unavailable.
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***Dosage: 3-5 mg/kg per day.
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*[[Holter monitor|Holter monitoring]] and [[exercise stress testing]] should be repeated periodically throughout [[beta blocker]] therapy, to ensure that the [[heart-rate]] is in control during exercise.
*** 2.1.2 '''Pediatric'''
*Non-[[compliance]] and abrupt interruption of [[beta blockade]] may cause a [[rebound effect]] of [[catecholamines]] on the heart, leading to [[arrhythmias|arrhythmic events]] while on therapy. Thus, it is important to educate and highlight to patients the need to be [[compliance|compliant]] with therapy.<ref name="LeenhardtLucet1995">{{cite journal|last1=Leenhardt|first1=Antoine|last2=Lucet|first2=Vincent|last3=Denjoy|first3=Isabelle|last4=Grau|first4=Francis|last5=Ngoc|first5=Dien Do|last6=Coumel|first6=Philippe|title=Catecholaminergic Polymorphic Ventricular Tachycardia in Children|journal=Circulation|volume=91|issue=5|year=1995|pages=1512–1519|issn=0009-7322|doi=10.1161/01.CIR.91.5.1512}}</ref><ref name="PrioriBlomström-Lundqvist2015">{{cite journal|last1=Priori|first1=Silvia G.|last2=Blomström-Lundqvist|first2=Carina|last3=Mazzanti|first3=Andrea|last4=Blom|first4=Nico|last5=Borggrefe|first5=Martin|last6=Camm|first6=John|last7=Elliott|first7=Perry Mark|last8=Fitzsimons|first8=Donna|last9=Hatala|first9=Robert|last10=Hindricks|first10=Gerhard|last11=Kirchhof|first11=Paulus|last12=Kjeldsen|first12=Keld|last13=Kuck|first13=Karl-Heinz|last14=Hernandez-Madrid|first14=Antonio|last15=Nikolaou|first15=Nikolaos|last16=Norekvål|first16=Tone M.|last17=Spaulding|first17=Christian|last18=Van Veldhuisen|first18=Dirk J.|title=2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death|journal=European Heart Journal|volume=36|issue=41|year=2015|pages=2793–2867|issn=0195-668X|doi=10.1093/eurheartj/ehv316}}</ref>
**** Parenteral regimen
*Even with appropriate use, [[beta blockers]] cannot completely suppress the [[arrhythmias]].
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
*Recurrent [[arrhythmias]] or persistence of complex [[arrhythmias]] at [[exercise stress test]] may occur in up to one-third of the [[CPVT]] patients, with the annual [[arrhythmias|arrhythmic]] event [[rate]] ranging between 11% per year and 3% per year.<ref name="HayashiDenjoy2009">{{cite journal|last1=Hayashi|first1=Meiso|last2=Denjoy|first2=Isabelle|last3=Extramiana|first3=Fabrice|last4=Maltret|first4=Alice|last5=Buisson|first5=Nathalie Roux|last6=Lupoglazoff|first6=Jean-Marc|last7=Klug|first7=Didier|last8=Hayashi|first8=Miyuki|last9=Takatsuki|first9=Seiji|last10=Villain|first10=Elisabeth|last11=Kamblock|first11=Joël|last12=Messali|first12=Anne|last13=Guicheney|first13=Pascale|last14=Lunardi|first14=Joël|last15=Leenhardt|first15=Antoine|title=Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=119|issue=18|year=2009|pages=2426–2434|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.108.829267}}</ref><ref name="CerroneColombi2005">{{cite journal|last1=Cerrone|first1=Marina|last2=Colombi|first2=Barbara|last3=Santoro|first3=Massimo|last4=di Barletta|first4=Marina Raffaele|last5=Scelsi|first5=Mario|last6=Villani|first6=Laura|last7=Napolitano|first7=Carlo|last8=Priori|first8=Silvia G|title=Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor|journal=Circulation Research|volume=96|issue=10|year=2005|issn=0009-7330|doi=10.1161/01.RES.0000169067.51055.72}}</ref><ref name="PrioriNapolitano2002">{{cite journal|last1=Priori|first1=Silvia G.|last2=Napolitano|first2=Carlo|last3=Memmi|first3=Mirella|last4=Colombi|first4=Barbara|last5=Drago|first5=Fabrizio|last6=Gasparini|first6=Maurizio|last7=DeSimone|first7=Luciano|last8=Coltorti|first8=Fernando|last9=Bloise|first9=Raffaella|last10=Keegan|first10=Roberto|last11=Cruz Filho|first11=Fernando E.S.|last12=Vignati|first12=Gabriele|last13=Benatar|first13=Abraham|last14=DeLogu|first14=Angelica|title=Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=106|issue=1|year=2002|pages=69–74|issn=0009-7322|doi=10.1161/01.CIR.0000020013.73106.D8}}</ref>
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
 
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '<nowiki/>'''''(Contraindications/specific instructions)''''''
===Verampil===
**** Oral regimen
*[[Calcium channel blocker]].
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
*[[Verapamil]] might be considered as adjunctive therapy for [[CPVT]] patients with ongoing [[ventricular arrhythmias]] despite therapy with [[beta blockers]].<ref name="SwanLaitinen2005">{{cite journal|last1=Swan|first1=Heikki|last2=Laitinen|first2=Paivi|last3=Kontula|first3=Kimmo|last4=Toivonen|first4=Lauri|title=Calcium Channel Antagonism Reduces Exercise-Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations|journal=Journal of Cardiovascular Electrophysiology|volume=16|issue=2|year=2005|pages=162–166|issn=1045-3873|doi=10.1046/j.1540-8167.2005.40516.x}}</ref><ref name="RossoKalman2007">{{cite journal|last1=Rosso|first1=Rafael|last2=Kalman|first2=Jonathan M.|last3=Rogowski|first3=Ori|last4=Diamant|first4=Shmuel|last5=Birger|first5=Amir|last6=Biner|first6=Simon|last7=Belhassen|first7=Bernard|last8=Viskin|first8=Sami|title=Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia|journal=Heart Rhythm|volume=4|issue=9|year=2007|pages=1149–1154|issn=15475271|doi=10.1016/j.hrthm.2007.05.017}}</ref>
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
*However, the long-term [[efficacy]] of [[verapamil]] is still controversial.
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
 
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
===Flecainide===
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
*[[Flecainide]] which is best known as a cardiac [[sodium channel]] blocker (a Class IC [[antiarrhythmic]]) is also found to inhibit the [[Ryanodine receptor 2|cardiac ryanodine receptor]] ([[Ryanodine receptor 2|RyR2]]. This dual-action makes it an effective medication for [[CPVT]].<ref name="WatanabeChopra2009">{{cite journal|last1=Watanabe|first1=Hiroshi|last2=Chopra|first2=Nagesh|last3=Laver|first3=Derek|last4=Hwang|first4=Hyun Seok|last5=Davies|first5=Sean S|last6=Roach|first6=Daniel E|last7=Duff|first7=Henry J|last8=Roden|first8=Dan M|last9=Wilde|first9=Arthur A M|last10=Knollmann|first10=Björn C|title=Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans|journal=Nature Medicine|volume=15|issue=4|year=2009|pages=380–383|issn=1078-8956|doi=10.1038/nm.1942}}</ref>
** 2.2  '<nowiki/>'''''Other Organ system involved 2''''''
*Indications:<ref name="WatanabeChopra2009">{{cite journal|last1=Watanabe|first1=Hiroshi|last2=Chopra|first2=Nagesh|last3=Laver|first3=Derek|last4=Hwang|first4=Hyun Seok|last5=Davies|first5=Sean S|last6=Roach|first6=Daniel E|last7=Duff|first7=Henry J|last8=Roden|first8=Dan M|last9=Wilde|first9=Arthur A M|last10=Knollmann|first10=Björn C|title=Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans|journal=Nature Medicine|volume=15|issue=4|year=2009|pages=380–383|issn=1078-8956|doi=10.1038/nm.1942}}</ref><ref name="van der WerfKannankeril2011">{{cite journal|last1=van der Werf|first1=Christian|last2=Kannankeril|first2=Prince J.|last3=Sacher|first3=Frederic|last4=Krahn|first4=Andrew D.|last5=Viskin|first5=Sami|last6=Leenhardt|first6=Antoine|last7=Shimizu|first7=Wataru|last8=Sumitomo|first8=Naokata|last9=Fish|first9=Frank A.|last10=Bhuiyan|first10=Zahurul A.|last11=Willems|first11=Albert R.|last12=van der Veen|first12=Maurits J.|last13=Watanabe|first13=Hiroshi|last14=Laborderie|first14=Julien|last15=Haïssaguerre|first15=Michel|last16=Knollmann|first16=Björn C.|last17=Wilde|first17=Arthur A.M.|title=Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Journal of the American College of Cardiology|volume=57|issue=22|year=2011|pages=2244–2254|issn=07351097|doi=10.1016/j.jacc.2011.01.026}}</ref>
**: '''Note (1):'''
**Patients with persistent [[arrhythmias]] despite [[beta blocker]] therapy.
**: '''Note (2)''':  
**Patients with an [[ICD]] who continue to have stress-induced [[ventricular arrhythmias]] despite [[beta-blocker]] therapy.
**: '''Note (3):'''
*Dosage: 100-300 mg/day (1.5-4.5 mg/kg/day).<ref name="PrioriBlomström-Lundqvist2015">{{cite journal|last1=Priori|first1=Silvia G.|last2=Blomström-Lundqvist|first2=Carina|last3=Mazzanti|first3=Andrea|last4=Blom|first4=Nico|last5=Borggrefe|first5=Martin|last6=Camm|first6=John|last7=Elliott|first7=Perry Mark|last8=Fitzsimons|first8=Donna|last9=Hatala|first9=Robert|last10=Hindricks|first10=Gerhard|last11=Kirchhof|first11=Paulus|last12=Kjeldsen|first12=Keld|last13=Kuck|first13=Karl-Heinz|last14=Hernandez-Madrid|first14=Antonio|last15=Nikolaou|first15=Nikolaos|last16=Norekvål|first16=Tone M.|last17=Spaulding|first17=Christian|last18=Van Veldhuisen|first18=Dirk J.|title=2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death|journal=European Heart Journal|volume=36|issue=41|year=2015|pages=2793–2867|issn=0195-668X|doi=10.1093/eurheartj/ehv316}}</ref>
*** 2.2.1 '''Adult'''
*[[Randomized clinical trials]] for the long-term [[efficacy]] of [[flecainide]] are still ongoing.<ref>{{cite web |url=https://clinicaltrials.gov/ct2/show/NCT01117454 |title=Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref>
**** Parenteral regimen
===Medical therapy===
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
Medications to treat CPVT include [[beta blockers]], [[flecainide]] and [[verapamil]].
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
 
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
====Beta-blockers====
**** Oral regimen
*The first-line [[therapeutic]] option for patients with [[CPVT]] is exercise restriction combined with [[beta-blockers]] without [[beta-blockers|intrinsic sympathomimetic activity]].<ref name="nihon">{{cite journal|title=Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death|journal=Heart|date=January 2003|first=Naokata|last=Sumitomo|coauthors=Harada K, Nagashima M, Yasuda T, Nakamura Y, Aragaki Y, Saito A, Kurosaki K, Jouo K, Koujiro M, Konishi S, Matsuoka S, Oono T, Hayakawa S, Miura M, Ushinohama H, Shibata T, Niimura I|volume=89|issue=1|pages=66–70|pmid=12482795 |format=|doi=10.1136/heart.89.1.66|pmc=1767500 }}</ref>
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
*Because of the [[adrenergic]] nature of [[arrhythmias]] in [[CPVT]], [[beta-blockers|non-selective beta-blockers]], titrated at the maximum tolerated dose in the absence of [[contraindications]] (example, [[asthma]]) are considered the most effective pharmacological therapy.
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
*Indications:
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
**All patients with stress-induced [[ventricular arrhythmias]].
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**[[carrier|Silent carriers]] of a pathogenic [[mutation]], even when they do not exhibit [[arrhythmias]] during [[exercise stress testing]] since [[cardiac arrest]] may occur in them.<ref name="HayashiDenjoy2012">{{cite journal|last1=Hayashi|first1=Miyuki|last2=Denjoy|first2=Isabelle|last3=Hayashi|first3=Meiso|last4=Extramiana|first4=Fabrice|last5=Maltret|first5=Alice|last6=Roux-Buisson|first6=Nathalie|last7=Lupoglazoff|first7=Jean-Marc|last8=Klug|first8=Didier|last9=Maury|first9=Philippe|last10=Messali|first10=Anne|last11=Guicheney|first11=Pascale|last12=Leenhardt|first12=Antoine|title=The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands|journal=EP Europace|volume=14|issue=9|year=2012|pages=1344–1351|issn=1532-2092|doi=10.1093/europace/eus031}}</ref>
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
*Drugs used:
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
**[[Nadolol]]<ref name="HayashiDenjoy2009">{{cite journal|last1=Hayashi|first1=Meiso|last2=Denjoy|first2=Isabelle|last3=Extramiana|first3=Fabrice|last4=Maltret|first4=Alice|last5=Buisson|first5=Nathalie Roux|last6=Lupoglazoff|first6=Jean-Marc|last7=Klug|first7=Didier|last8=Hayashi|first8=Miyuki|last9=Takatsuki|first9=Seiji|last10=Villain|first10=Elisabeth|last11=Kamblock|first11=Joël|last12=Messali|first12=Anne|last13=Guicheney|first13=Pascale|last14=Lunardi|first14=Joël|last15=Leenhardt|first15=Antoine|title=Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=119|issue=18|year=2009|pages=2426–2434|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.108.829267}}</ref><ref name="LerenSaberniak2016">{{cite journal|last1=Leren|first1=Ida S.|last2=Saberniak|first2=Jørg|last3=Majid|first3=Eman|last4=Haland|first4=Trine F.|last5=Edvardsen|first5=Thor|last6=Haugaa|first6=Kristina H.|title=Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia|journal=Heart Rhythm|volume=13|issue=2|year=2016|pages=433–440|issn=15475271|doi=10.1016/j.hrthm.2015.09.029}}</ref>
*** 2.2.2 '''Pediatric'''
***Long-acting, [[beta-blockers|non-selective beta-blocker]].
**** Parenteral regimen
***Preferred for [[prophylactic treatment of CPVT]].
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***It is considered the most clinically effective choice.
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***Dosage: 1-2 mg/kg per day.
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**[[Propranolol]]  
**** Oral regimen
***Long-acting, [[beta-blockers|non-selective beta-blocker]].
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***It is also considered an effective medication when [[Nadolol]] is unavailable.
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***Dosage: 3-5 mg/kg per day.
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
*[[Holter monitor|Holter monitoring]] and [[exercise stress testing]] should be repeated periodically throughout [[beta blocker]] therapy, to ensure that the [[heart-rate]] is in control during exercise.
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
*Non-[[compliance]] and abrupt interruption of [[beta blockade]] may cause a [[rebound effect]] of [[catecholamines]] on the heart, leading to [[arrhythmias|arrhythmic events]] while on therapy. Thus, it is important to educate and highlight to patients the need to be [[compliance|compliant]] with therapy.<ref name="LeenhardtLucet1995">{{cite journal|last1=Leenhardt|first1=Antoine|last2=Lucet|first2=Vincent|last3=Denjoy|first3=Isabelle|last4=Grau|first4=Francis|last5=Ngoc|first5=Dien Do|last6=Coumel|first6=Philippe|title=Catecholaminergic Polymorphic Ventricular Tachycardia in Children|journal=Circulation|volume=91|issue=5|year=1995|pages=1512–1519|issn=0009-7322|doi=10.1161/01.CIR.91.5.1512}}</ref><ref name="PrioriBlomström-Lundqvist2015">{{cite journal|last1=Priori|first1=Silvia G.|last2=Blomström-Lundqvist|first2=Carina|last3=Mazzanti|first3=Andrea|last4=Blom|first4=Nico|last5=Borggrefe|first5=Martin|last6=Camm|first6=John|last7=Elliott|first7=Perry Mark|last8=Fitzsimons|first8=Donna|last9=Hatala|first9=Robert|last10=Hindricks|first10=Gerhard|last11=Kirchhof|first11=Paulus|last12=Kjeldsen|first12=Keld|last13=Kuck|first13=Karl-Heinz|last14=Hernandez-Madrid|first14=Antonio|last15=Nikolaou|first15=Nikolaos|last16=Norekvål|first16=Tone M.|last17=Spaulding|first17=Christian|last18=Van Veldhuisen|first18=Dirk J.|title=2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death|journal=European Heart Journal|volume=36|issue=41|year=2015|pages=2793–2867|issn=0195-668X|doi=10.1093/eurheartj/ehv316}}</ref>
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
*Even with appropriate use, [[beta blockers]] cannot completely suppress the [[arrhythmias]].
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
*Recurrent [[arrhythmias]] or persistence of complex [[arrhythmias]] at [[exercise stress test]] may occur in up to one-third of the [[CPVT]] patients, with the annual [[arrhythmias|arrhythmic]] event [[rate]] ranging between 11% per year and 3% per year.<ref name="HayashiDenjoy2009">{{cite journal|last1=Hayashi|first1=Meiso|last2=Denjoy|first2=Isabelle|last3=Extramiana|first3=Fabrice|last4=Maltret|first4=Alice|last5=Buisson|first5=Nathalie Roux|last6=Lupoglazoff|first6=Jean-Marc|last7=Klug|first7=Didier|last8=Hayashi|first8=Miyuki|last9=Takatsuki|first9=Seiji|last10=Villain|first10=Elisabeth|last11=Kamblock|first11=Joël|last12=Messali|first12=Anne|last13=Guicheney|first13=Pascale|last14=Lunardi|first14=Joël|last15=Leenhardt|first15=Antoine|title=Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=119|issue=18|year=2009|pages=2426–2434|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.108.829267}}</ref><ref name="CerroneColombi2005">{{cite journal|last1=Cerrone|first1=Marina|last2=Colombi|first2=Barbara|last3=Santoro|first3=Massimo|last4=di Barletta|first4=Marina Raffaele|last5=Scelsi|first5=Mario|last6=Villani|first6=Laura|last7=Napolitano|first7=Carlo|last8=Priori|first8=Silvia G|title=Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor|journal=Circulation Research|volume=96|issue=10|year=2005|issn=0009-7330|doi=10.1161/01.RES.0000169067.51055.72}}</ref><ref name="PrioriNapolitano2002">{{cite journal|last1=Priori|first1=Silvia G.|last2=Napolitano|first2=Carlo|last3=Memmi|first3=Mirella|last4=Colombi|first4=Barbara|last5=Drago|first5=Fabrizio|last6=Gasparini|first6=Maurizio|last7=DeSimone|first7=Luciano|last8=Coltorti|first8=Fernando|last9=Bloise|first9=Raffaella|last10=Keegan|first10=Roberto|last11=Cruz Filho|first11=Fernando E.S.|last12=Vignati|first12=Gabriele|last13=Benatar|first13=Abraham|last14=DeLogu|first14=Angelica|title=Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Circulation|volume=106|issue=1|year=2002|pages=69–74|issn=0009-7322|doi=10.1161/01.CIR.0000020013.73106.D8}}</ref>
 
====Verampil====
*[[Calcium channel blocker]].
*[[Verapamil]] might be considered as adjunctive therapy for [[CPVT]] patients with ongoing [[ventricular arrhythmias]] despite therapy with [[beta blockers]].<ref name="SwanLaitinen2005">{{cite journal|last1=Swan|first1=Heikki|last2=Laitinen|first2=Paivi|last3=Kontula|first3=Kimmo|last4=Toivonen|first4=Lauri|title=Calcium Channel Antagonism Reduces Exercise-Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations|journal=Journal of Cardiovascular Electrophysiology|volume=16|issue=2|year=2005|pages=162–166|issn=1045-3873|doi=10.1046/j.1540-8167.2005.40516.x}}</ref><ref name="RossoKalman2007">{{cite journal|last1=Rosso|first1=Rafael|last2=Kalman|first2=Jonathan M.|last3=Rogowski|first3=Ori|last4=Diamant|first4=Shmuel|last5=Birger|first5=Amir|last6=Biner|first6=Simon|last7=Belhassen|first7=Bernard|last8=Viskin|first8=Sami|title=Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia|journal=Heart Rhythm|volume=4|issue=9|year=2007|pages=1149–1154|issn=15475271|doi=10.1016/j.hrthm.2007.05.017}}</ref>
*However, the long-term [[efficacy]] of [[verapamil]] is still controversial.
 
====Flecainide====
 
*[[Flecainide]] which is best known as a cardiac [[sodium channel]] blocker (a Class IC [[antiarrhythmic]]) is also found to inhibit the [[Ryanodine receptor 2|cardiac ryanodine receptor]] ([[Ryanodine receptor 2|RyR2]]. This dual-action makes it an effective medication for [[CPVT]].<ref name="WatanabeChopra2009">{{cite journal|last1=Watanabe|first1=Hiroshi|last2=Chopra|first2=Nagesh|last3=Laver|first3=Derek|last4=Hwang|first4=Hyun Seok|last5=Davies|first5=Sean S|last6=Roach|first6=Daniel E|last7=Duff|first7=Henry J|last8=Roden|first8=Dan M|last9=Wilde|first9=Arthur A M|last10=Knollmann|first10=Björn C|title=Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans|journal=Nature Medicine|volume=15|issue=4|year=2009|pages=380–383|issn=1078-8956|doi=10.1038/nm.1942}}</ref>
*Indications:<ref name="WatanabeChopra2009">{{cite journal|last1=Watanabe|first1=Hiroshi|last2=Chopra|first2=Nagesh|last3=Laver|first3=Derek|last4=Hwang|first4=Hyun Seok|last5=Davies|first5=Sean S|last6=Roach|first6=Daniel E|last7=Duff|first7=Henry J|last8=Roden|first8=Dan M|last9=Wilde|first9=Arthur A M|last10=Knollmann|first10=Björn C|title=Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans|journal=Nature Medicine|volume=15|issue=4|year=2009|pages=380–383|issn=1078-8956|doi=10.1038/nm.1942}}</ref><ref name="van der WerfKannankeril2011">{{cite journal|last1=van der Werf|first1=Christian|last2=Kannankeril|first2=Prince J.|last3=Sacher|first3=Frederic|last4=Krahn|first4=Andrew D.|last5=Viskin|first5=Sami|last6=Leenhardt|first6=Antoine|last7=Shimizu|first7=Wataru|last8=Sumitomo|first8=Naokata|last9=Fish|first9=Frank A.|last10=Bhuiyan|first10=Zahurul A.|last11=Willems|first11=Albert R.|last12=van der Veen|first12=Maurits J.|last13=Watanabe|first13=Hiroshi|last14=Laborderie|first14=Julien|last15=Haïssaguerre|first15=Michel|last16=Knollmann|first16=Björn C.|last17=Wilde|first17=Arthur A.M.|title=Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia|journal=Journal of the American College of Cardiology|volume=57|issue=22|year=2011|pages=2244–2254|issn=07351097|doi=10.1016/j.jacc.2011.01.026}}</ref>
**Patients with persistent [[arrhythmias]] despite [[beta blocker]] therapy.
**Patients with an [[ICD]] who continue to have stress-induced [[ventricular arrhythmias]] despite [[beta-blocker]] therapy.
*Dosage: 100-300 mg/day (1.5-4.5 mg/kg/day).<ref name="PrioriBlomström-Lundqvist2015">{{cite journal|last1=Priori|first1=Silvia G.|last2=Blomström-Lundqvist|first2=Carina|last3=Mazzanti|first3=Andrea|last4=Blom|first4=Nico|last5=Borggrefe|first5=Martin|last6=Camm|first6=John|last7=Elliott|first7=Perry Mark|last8=Fitzsimons|first8=Donna|last9=Hatala|first9=Robert|last10=Hindricks|first10=Gerhard|last11=Kirchhof|first11=Paulus|last12=Kjeldsen|first12=Keld|last13=Kuck|first13=Karl-Heinz|last14=Hernandez-Madrid|first14=Antonio|last15=Nikolaou|first15=Nikolaos|last16=Norekvål|first16=Tone M.|last17=Spaulding|first17=Christian|last18=Van Veldhuisen|first18=Dirk J.|title=2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death|journal=European Heart Journal|volume=36|issue=41|year=2015|pages=2793–2867|issn=0195-668X|doi=10.1093/eurheartj/ehv316}}</ref>
*[[Randomized clinical trials]] for the long-term [[efficacy]] of [[flecainide]] are still ongoing.<ref>{{cite web |url=https://clinicaltrials.gov/ct2/show/NCT01117454 |title=Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref>


==References==
==References==

Revision as of 14:31, 23 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR

The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Medical Therapy

Pharmacologic medical therapies for CPVT include beta blockers, flecainide and verapamil.

Beta-blockers

Verampil

Flecainide

Medical therapy

Medications to treat CPVT include beta blockers, flecainide and verapamil.

Beta-blockers

Verampil

Flecainide

References

  1. ↑ 1.0 1.1 Sumitomo, Naokata (January 2003). "Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death". Heart. 89 (1): 66–70. doi:10.1136/heart.89.1.66. PMC 1767500. PMID 12482795. Unknown parameter |coauthors= ignored (help)
  2. ↑ 2.0 2.1 Hayashi, Miyuki; Denjoy, Isabelle; Hayashi, Meiso; Extramiana, Fabrice; Maltret, Alice; Roux-Buisson, Nathalie; Lupoglazoff, Jean-Marc; Klug, Didier; Maury, Philippe; Messali, Anne; Guicheney, Pascale; Leenhardt, Antoine (2012). "The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands". EP Europace. 14 (9): 1344–1351. doi:10.1093/europace/eus031. ISSN 1532-2092.
  3. ↑ 3.0 3.1 3.2 3.3 Hayashi, Meiso; Denjoy, Isabelle; Extramiana, Fabrice; Maltret, Alice; Buisson, Nathalie Roux; Lupoglazoff, Jean-Marc; Klug, Didier; Hayashi, Miyuki; Takatsuki, Seiji; Villain, Elisabeth; Kamblock, Joël; Messali, Anne; Guicheney, Pascale; Lunardi, Joël; Leenhardt, Antoine (2009). "Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 119 (18): 2426–2434. doi:10.1161/CIRCULATIONAHA.108.829267. ISSN 0009-7322.
  4. ↑ 4.0 4.1 Leren, Ida S.; Saberniak, Jørg; Majid, Eman; Haland, Trine F.; Edvardsen, Thor; Haugaa, Kristina H. (2016). "Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia". Heart Rhythm. 13 (2): 433–440. doi:10.1016/j.hrthm.2015.09.029. ISSN 1547-5271.
  5. ↑ 5.0 5.1 Leenhardt, Antoine; Lucet, Vincent; Denjoy, Isabelle; Grau, Francis; Ngoc, Dien Do; Coumel, Philippe (1995). "Catecholaminergic Polymorphic Ventricular Tachycardia in Children". Circulation. 91 (5): 1512–1519. doi:10.1161/01.CIR.91.5.1512. ISSN 0009-7322.
  6. ↑ 6.0 6.1 6.2 6.3 Priori, Silvia G.; Blomström-Lundqvist, Carina; Mazzanti, Andrea; Blom, Nico; Borggrefe, Martin; Camm, John; Elliott, Perry Mark; Fitzsimons, Donna; Hatala, Robert; Hindricks, Gerhard; Kirchhof, Paulus; Kjeldsen, Keld; Kuck, Karl-Heinz; Hernandez-Madrid, Antonio; Nikolaou, Nikolaos; Norekvål, Tone M.; Spaulding, Christian; Van Veldhuisen, Dirk J. (2015). "2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death". European Heart Journal. 36 (41): 2793–2867. doi:10.1093/eurheartj/ehv316. ISSN 0195-668X.
  7. ↑ 7.0 7.1 Cerrone, Marina; Colombi, Barbara; Santoro, Massimo; di Barletta, Marina Raffaele; Scelsi, Mario; Villani, Laura; Napolitano, Carlo; Priori, Silvia G (2005). "Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor". Circulation Research. 96 (10). doi:10.1161/01.RES.0000169067.51055.72. ISSN 0009-7330.
  8. ↑ 8.0 8.1 Priori, Silvia G.; Napolitano, Carlo; Memmi, Mirella; Colombi, Barbara; Drago, Fabrizio; Gasparini, Maurizio; DeSimone, Luciano; Coltorti, Fernando; Bloise, Raffaella; Keegan, Roberto; Cruz Filho, Fernando E.S.; Vignati, Gabriele; Benatar, Abraham; DeLogu, Angelica (2002). "Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 106 (1): 69–74. doi:10.1161/01.CIR.0000020013.73106.D8. ISSN 0009-7322.
  9. ↑ 9.0 9.1 Swan, Heikki; Laitinen, Paivi; Kontula, Kimmo; Toivonen, Lauri (2005). "Calcium Channel Antagonism Reduces Exercise-Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations". Journal of Cardiovascular Electrophysiology. 16 (2): 162–166. doi:10.1046/j.1540-8167.2005.40516.x. ISSN 1045-3873.
  10. ↑ 10.0 10.1 Rosso, Rafael; Kalman, Jonathan M.; Rogowski, Ori; Diamant, Shmuel; Birger, Amir; Biner, Simon; Belhassen, Bernard; Viskin, Sami (2007). "Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia". Heart Rhythm. 4 (9): 1149–1154. doi:10.1016/j.hrthm.2007.05.017. ISSN 1547-5271.
  11. ↑ 11.0 11.1 11.2 11.3 Watanabe, Hiroshi; Chopra, Nagesh; Laver, Derek; Hwang, Hyun Seok; Davies, Sean S; Roach, Daniel E; Duff, Henry J; Roden, Dan M; Wilde, Arthur A M; Knollmann, Björn C (2009). "Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans". Nature Medicine. 15 (4): 380–383. doi:10.1038/nm.1942. ISSN 1078-8956.
  12. ↑ 12.0 12.1 van der Werf, Christian; Kannankeril, Prince J.; Sacher, Frederic; Krahn, Andrew D.; Viskin, Sami; Leenhardt, Antoine; Shimizu, Wataru; Sumitomo, Naokata; Fish, Frank A.; Bhuiyan, Zahurul A.; Willems, Albert R.; van der Veen, Maurits J.; Watanabe, Hiroshi; Laborderie, Julien; Haïssaguerre, Michel; Knollmann, Björn C.; Wilde, Arthur A.M. (2011). "Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia". Journal of the American College of Cardiology. 57 (22): 2244–2254. doi:10.1016/j.jacc.2011.01.026. ISSN 0735-1097.
  13. ↑ "Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia - Full Text View - ClinicalTrials.gov".
  14. ↑ "Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia - Full Text View - ClinicalTrials.gov".

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