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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

VerapamilDigoxin

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Antiarrhythmic therapy (guidelines)

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Total mortality with Quinidine

RCT

Boissel

Byrne-Quinn

Hartel

Hillestad

Lloyd

Sodermark

ALL STUDIES N = 808

0 1 2 3 4 5 6 7 8 9 10 11 12

Quinidine Better Quinidine Worse

212

92

175

100

53

176

n

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 sto

antiarrhythmicsdue 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 >75 HTN Heart failure Low EF (

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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 interruptanticoagulation 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 tocardioversion

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 duringsuccessful rhythm control in PAF pts

Asymptomatic AF is potential explanation(in PAFAC

70%, in SOPAT 50% by daily ECGtransmission)

Drugs can mitigate symptoms

Particular cases could be of exception

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Pill in the pocket strategy

Potential side effects:

Hypotension

QRS widening Proarrhythmia:

- VT

- atrial flutter with 1:1 conduction,- bradicardia /pauses (during conversion)

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Antiarrhythmic therapy

AFFIRM 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 blockade

for AF therapy

ACE inhibitors (SOLVD)

Circ 2003

Angiotensin receptor

blockers

Circ 2002

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Beta blocker vs. A II blocker

LIFE study,JACC2005

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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: Ikurblockers

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%)

Brugada Syndrome

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Brugada Syndrome

cellular basis

Na

I TO (K)

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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 ECGand inducible VF (7 afterCA, 8- syncope)

Quinidin 1200-1500 mg

Non-inducibility 88%

F/u for 6 mo to 22 years

No arrhythmic events

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CIRCULATION1981

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Isoproterenol therapy

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CIRCULATION1988

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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 / Enoxapari