Arrhythmias - Medical Therapy

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Arrhythmias - Medical Therapy

• David Luria, Sheba Medical Center

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Antiarrhythmic medications

• 1st class (Na channel blockers)
• 1A
• Quinidine
• Procainamide
• Disopyramide (Rithmical)
• Giluritmal
• 1B
• Lidocaine
• Mexiletine (mexillene)
• 1C
• Propapfenone (rythmex)
• Flecainide (tambocor)

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Antiarrhythmic medications (2)

• 2nd class
• Beta blockers
• 3rd class (K channel blockers)
• Amiodarone (Procor)
• Sotalol
• Dofetilide
• 4th class (Ca channels blockers)
• Verapamil

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SVT - Medical therapy

• Termination
• adenosin, verapamil, beta blockers IV
• pill in the pocket (1c drugs)
• Prevention
• any antiarrhythmic drug
• first choice are beta blockers
• Ca channels blockers

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VT - medical therapy

• Ischemic VT
• No AAD prevents SCD
• CAST study
• Termination (IV)
• Lidocaine
• Amiodarone
• Procainamide
• Prevention
• Amiodarone
• Mexilletine
• Sotalol
• 1A drugs

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VT - medical therapy (2)

• Non-ischemic cardiomyopathy
• (ARVD, DCM, HCM)
• Sotalol
• Amiodarone
• Disopyramide (HOCM)
• Idiopathic VT
• RVOT VT (beta-blockers, AAD)
• Fascicular VT (Verapamil, AAD)

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AF - medical therapy
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Rate Control

• Beta Blockers
• Verapamil
• Digoxin

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Antiarrhythmic therapy (guidelines)
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Proarrhythmia

• Torsade de pointes
• Sustained VT
• 11 flutter

• start of the therapy
• drug interactions (diuretics, antidepressants)
• - concomitant medical conditions

Nattel S, Am Heart J 1995
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Total mortality with Quinidine
Circulation 1990
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Recent Quinidine rehabilitation?

• PAFAC SOPAT European trials
• Combine therapy of Quinidine (480/d) and
  Verapamil (240/day) vs Sotalol (320/day)
• Persistent/paroxysmal AF
• Same efficacy (about 50 1 y)
• Same rate of combine death/syncope/TdP/NSVT
  (about 5 during 2y)
• TdP only in SOTALOL group

EHJ, 2004
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Side effects

• CHF exacerbation
• Pulmonary toxicity
• GE symptoms
• Thyroid dysfunction
• Hepatic dysfunction
• Blood dyscrasias
• Sleep disturbances

20-30 of pts stop antiarrhythmics due to side
effects
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Antiarrhythmic therapy (guidelines)

• 1C drug up to QRS widening 150
• 1A and Sotalol up to QTc 520 msec
• Before DC (to enhance conversion and prevent
  IRAF) 1C and III

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Start antiarrhythmic therapy

• In hospital
• - IA drugs (QT monitoring)
• - 1C drug in pts with heart disease (QRS/VT
  monitoring)
• - Sotalol in pts with heart disease (QT
  monitoring)

• Outpatient
• - Lone AF (1C, III)
• - Amiodarone

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Antithrombotic therapy
Antithrombotic therapy to prevent thromboembolism
is recommended for all patients with AF, except
those with lone AF or contraindications. (Level
of Evidence A)
For patients without mechanical heart valves at
high risk of stroketo achieve the target
intensity international normalized ratio (INR) of
2.0 to 3.0, unless contraindicated.
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Risk factors for Stroke

• High (one enough for COUMADIN)
• Previous embolic event
• Rheumatic MS
• Mechanical prosthetic valves

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Risk factors for Stroke

• Moderate validated (two
  required COUMADIN, one - ASPIRIN)
• Age gt75
• HTN
• Heart failure
• Low EF (lt35)
• Diabetes

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Risk factors for Stroke

• Moderate, less well validated
  (one or more could be managed with COUMADIN or
  ASPIRIN)
• Age 65-75
• Female gender
• Coronary artery Disease

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Interruption of anticoagulation
In patients with AF who do not have mechanical
prosthetic heart valves, it is reasonable to
interrupt anticoagulation for up to 1 wk without
substituting heparin for surgical or diagnostic
procedures that carry a risk of bleeding.
(Level of Evidence C)
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Cardioversion -Anticoagulation therapy

• Before cardioversion of AF (ALL TYPES)
• COUMADIN if AF 48 h
• (1 mo before and 3 after)

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TEE-guided cardioversion

• As good as Coumadin to prevent embolism
• Dense spontaneous ECHO contrast is a risk
  factor for embolism contraindication to
  cardioversion
• Absence of thrombus/smoke is not guarantee for
  post cardioversion thrombus formation need
  anticoagulation post CV

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Cardioversion role of drugs

• Flecainide, Amiodarone and Ibutilide decrease
  atrial DFT
• Any antiarrhythmics can prevent immediate
  recurrence
• Risk of SSS aggravation by drugs

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Stop anticoagulation after DC?

• NO
• Risk for embolism is the same during successful
  rhythm control in PAF pts
• Asymptomatic AF is potential explanation
  
  (in PAFAC 70, in SOPAT 50 by daily ECG
  transmission)
• Drugs can mitigate symptoms
• Particular cases could be of exception

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Pill in the pocket strategy

• Oral 1C drugs in ER effective (up to 85) and
  safe in termination of PAF.
• J Am
  Coll Cardiol 2001
• Outpatient self use of single loading dose 165
  pts, 569 AF episodes, 95 terminated
  successfully without need in ER

NEJM 2005
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Pill in the pocket strategy

• Potential side effects
• Hypotension
• QRS widening
• Proarrhythmia
• - VT
• - atrial flutter with 11 conduction,
• - bradicardia /pauses (during conversion)

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Antiarrhythmic therapyAFFIRM substudy (JACC,
2003)

• Stop drug due to adverse events (one year)
• Amio-12.3 Sotalol- 11.1 Class I
  28.1
• After 5 years only half pts are in sinus

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Angiotensin system blockadefor AF therapy

• ACE inhibitors (SOLVD)
• Circ 2003

• Angiotensin receptor blockers
• Circ 2002

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Beta blocker vs. A II blocker
LIFE study, JACC 2005
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Mechanism of ACE blocker effect

• Improve of hemodynamic parameters and atrial
  stretch
• Attenuation of hypokalemia
• (diuretics therapy)
• Reduce atrial arrhythmogenic remodeling
• - fibrosis
• - conduction abnormalities

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Drugs on the way Ibutilide

• Class III drug, IV for cardioversion
• 4 of TdP (women 5.6 vs men 3)
• Contraindicated to low EF due to proarrhythmia
• Adverse effect - hypotension

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Dofetilide

• Class III drug selective IKr blocker
• SAFIRE-D 87 conversion to SR within 30 h 58
  in SR after 1 year
• DIAMOND
• - patients with decreased LV function
• - 79 maintain SR
• - 0.8 had TdP within first 3 days

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Drugs under investigation

• Azimilide group III Na and K channel blocker,
  good for CHF pts, low toxicity
• Dronedarone noniodinated amiodarone
• Atrioselective agents I kur blockers
  only atrial antiarrhythmic effect
  (no pro- arrhythmia)

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Torsade de pointes emergency therapy

• Magnesium IV 2.0 g (x 2), up to 10 g during 24
  hours (3-10mg/min IV)
• (CAUTION RF, knee reflex, lethargy)
• Potassium supplementation (up to 4.5 mmol/l)
• Pacing (100-140/min) or Isoproterenol (not for
  congenital LQTS)
• NOTE danger from antiarrhythmic drugs (lidocaine
  help in 50)

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Brugada Syndromecellular basis
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Medical therapy

• Ito blockers Quinidine and Tedisamil
• Normalization ECG (both)
• Electrical storm (both)
• Efficacy was shone in experimental work to
  normalize epicardial dome, ECG and prevent faze
  II re-entry (only Quinidin)
• Long term efficacy (only Quinidin)
• 
  

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• 25pts with Brugada ECG and inducible VF (7 after
  CA, 8- syncope)
• Quinidin 1200-1500 mg
• Non-inducibility 88
• F/u for 6 mo to 22 years
• No arrhythmic events

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CIRCULATION 1981
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Isoproterenol therapy
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Pregnancy
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Medical therapy

• No entirely safe drugs
• use as less as possible !
• Acute setting
• Adenosine for SVT (Verapamil IV - second choice,
  care with hypotension)
• Lidocaine for VT (organic)
• Metopralol for idiopathic VT (adenosine)
• DC for PAF/flutter or any unstable arrhythmia

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Medical therapy (cont)

• Preventive therapy
• 1st choice Cardio-selective beta blockers
• 2nd choice Sotalol
• 3rd choice Quinidine, Flecainide
• Anticoagulation
  (AF, standard indications)
• All type carry risk of retro-placental bleeding
• Coumadin is contraindicated first 8-10 weeks and
  before delivery substitution by Heparin /
  Enoxaparin