Pharmacological therapy of cardiac arrhythmias

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Pharmacological Therapy of Cardiac

ArrhythmiasBy: Mahmoud ShahProfessor of Cardiology

Zagazig University

Vaughan Williams Classification

Class I: * block fast Na channels

* can block K channels

IA: * V max (phase 0 AP)

* prolong AP duration

* include: quinidine, procainamide,

disopyramide

* intermediate onset and offset in blocking Na

channels (< 5 seconds)

IB * Doesn’t decrease V max

* Shorten AP duration

* Mexiletine, Phenytoin, Lidocaine

* Rapid onset and ofset (<500 msec)

Ic * Decrease V max

* Slow conduction

* Prolong refractoriness minimally

* Flecanide, propafenone , moricizine, ajmaline

* Slow onset and ofset (10-20 sec)

Class II *Block B receptors *propranolol, timolol, metoprolol

Class III *block k channels

*prolong repolarization

*Sotalol, Amoidarone,

bretylium, drondarone,

dofetilide, ibutilide, azimilide

Class IV *block slow ca Channel

* Verapamil ,Diltiazim

Unclassified drugs1 – Adenosine activates K channels (IK ach.,IK Ade) 2 – Ivabradine If current blocker3 – digoxin

Recommendations for acute management of hemodynamically stable and regular tachycardia

ECG Recommendation Class Level of evidence

Narrow QRS-complex tachycardia (SVT)

Vagal manoeuvresAdenosine

Verapamil, diltiazemBeta-blockersAmiodarone

Digoxin

III

lIblIblIb

BAACCC

Wide QRS-complex tachycardia SVT and BBB Pre-excited VT/AF +

See aboveFlecainide Ibutilide

Procainamide DC cardioversion

IIII

BBBC

Wide QRS-complex tachycardia of

unknown origin

Procainamide Sotalol

AmiodaroneUdocaine

Adenosine Beta-blockers

VerapamilDC cardioversion

III

IIbIIbIIIIIII

BBBBCCBB

Wide QRS-complex tachycardia of unknown origin in patients with

poor LV function

Amiodarone Lidorainp

DC cardioversion

II

BB

Specific Specific arrhythmiasarrhythmias

* Persistent high HR unrelated to level of physical , emotional, pathological or pharmacological stress

* 90% Female

* Asymptomatic to totally incapacitated Treatment

* Symptomatic driven * Catheter ablation – 66% of SAN modification

* Postural Orthostatic tachycardia syndrome (POTs) excluded before ablation.

1- Inappropriate Sinus Tachycardia )IST(

Recommendation for treatment of IST

Treatment Recommendation Class Level of evidence

Medical Beta-blockers I C

Verapamil, diltiazem II a C

Interventional Catheter ablation –

sinus node

modification/elimination

II b C

* Typical form slow – fast 85-90% RP<PR

* Atypical form fast – slow 10-15% RP>PR

* Standard treatment B blocker Ca blocker Adenosine

* Alternative ttt Ablation Tolerance of symptoms Tachycardia frequency

Patient inclination relative to chronic drug therapy vs ablation

The patient must accept risk (<1% Av block) P. pacemaker

2. Atrioventricular nodal reciprocating tachycardia )AVNRT(

A: during AVNRT and B: after cardioversion Note the pseudo r’ in V1 and pseudo S in II, III and a VF which are pathognomonic of typical AVNRT

ECG pattern of typical AVNRT

Recommendations for long-term treatment of patients with recurrent AVNRT

Clinical presentation

Intervention Class Level of

evidence

Poorly tolerated AVNRT with

haemodynamic intolerance

Catheter ablation I BB

Verapamil, diltiazem, beta-

blockers, sotalol, amiodarone

IIa CC

Flecainide, propafenone

IIa CC

I Recurrent symptomatic

AVNRT

Catheter ablation I BB

Verapamil I BB

Diltiazem, beta-blockers

I CC

Digoxin IIb CC

Recurrent AVNRT unresponsive to beta-blockade or calcium-channel

blocker and patient not desiring RF

ablation

Flecainide, propafenone,

sotalol

IIa BB

Amiodarone IIb CC

AVNRT with infrequent or

single episode in patients who

desire complete control of

arrhythmia

Catheter ablation I B

Documented PSVT with only dual AV-nodal pathways or

single echo beats demonstrated

during electrophysiological study and no other identified

cause of arrhythmia

Verapamil,diltiazem, beta-blockers,

flecainide*, propafenone

I C

Catheter ablation ++

I B

Infrequent, well-tolerated AVNRT

No therapy I C

Vagal manoeuvres

I B

«Pill-in-the-pocket»

I B

Verapamil,diltiazem, beta-blockers

I B

Catheter ablation I B

* Automatic ectopic tachycardia

* Junctional ectopic tachycardia

* Originate from AVN or His bundle

* ECG: - HR: 110-250 bpm

- Narrow QRS or BBB pattern with AV

dissociation

* Rare arrhythmia

* In young adult

* may produce CHF

* Drug therapy ----- Variable success

* Ablative therapy 5-10%risk A-V block

3- Focal and nonparoxymal junctional tachycardia

A - focal junctional tachycardia

Surface ECG recording from leads V1, II, and V5 in apatient with focal junctional tachycardia. The upper panel showssinus rhythm. The lower panel shows tachycardia onset with thecharacteristic finding of isorhythmic AV dissociation (arrows).The large arrow signifies continuous recording. AV indicatesatrioventricular.

* Benign arrhythmia * HR 70-120 bpm * due to abnormal automaticity or triggered activity * due to digitalis toxicity , post cardiac surgery , hypokalemia , myocardial ischemia

* Treatment directed toward the underlying condition

B – Nonparoxysmal junctional tachycardia (NJT)

Recommendation for treatment of focal and nonparoxymal junctional tachycardia

Clinical presentation

Recommendation Class Level of evidence

Focal junctional tachycardia

Beta-blockers IIa C

Flecainide IIa C

Propafenone IIa C

Sotalol IIa C

Amiodarone IIa C

Catheter ablation IIa C

Nonparoxysmal junctional

tachycardia

Reverse digitalis toxicity

I C

Correct hypokalemia

I C

Treat myocardial ischaemia

I C

Beta-blockers, calcium-channel

blockers

IIa C

* Extranodal AP

* Only retrograde conduction

concealed AP

* Antegrade conduction manifest AP

* WPW Syndrome Preexcitation

+ Tachycardia

4. A-V Reciprocating re-entry tachycardia )AVRT(

* orthodromic AVRT

* antidromic AVRT

* pre-excited tachycardia in AT or A.Fl with

bystander AP

* Pre-excited AF

* PJRT ( permanent form of JRT)

- Slowly conducting concealed

posteroseptal AP

- Incessant , long RP tachycardia with

negative pin II ,III ,avf

- rare syndrome

Forms

Orthodromic atrioventricular reentrant tachycardia. This patient has Wolff-Parkinson-White syndrome

Wolff-Parkinson-White pattern. Note the short PR interval and slurred upstroke (delta wave) to the QRS complexes

* AVN blocking agents not effective

* Adenosine may produce AF with rapid ventricular rate

* Anti-arrhythmic drugs preventing rapid conduction through AP

- Flecanide - Procainamide - Ibutilide - Amiodarone

Acute treatment of pre-excited tachycardias

effective even may not convert the atrial rhythm.

* Catheter ablation the preferred with 95% success option

* Antiarrhythmic drugs Another therapeutic option for - Infrequent episodes - Well-tolerated episodes

* Some patients with infrequent episodes Single dose (pill-in pocket approach)

* Only at the onset of tachycardia episode - Patient without pre-excitation - Uncommon and hemodynamically tolerated tachycardia.

Long-term therapy of pre-excited tachycardias

Recommendations for long-term therapy of AP-mediated

arrhythmias

* Atrial rate: 100-250 bpm (rarely 300)

* progressive increase in atrial rate with tachycardia onset (warm-up) and/or

* progressive decrease before termination of tachycadia suggests automatic mechanism

* 10 % have multiple foci

* Focal AT may be incessant tachycardia inducing CM

5 Focal atrial tachycardia )FAT(

Focal atrial tachycardia showing a long RP interval relationship. The P wave in AT usually occurs in the latter part of thetachycardia cycle (arrows) but can appear earlier, depending on the rate and status of AV-nodal conduction. AT indicates atrialtachycardia; AV, atrioventricular

* Rate control - B- blocker - Ca blocker - Digoxin * Or suppression of arrhythmias focus Class Ia - Flcamide - Propafenone * IV adenosine, B blocker or Ca blocker acute termination (unusual) or rate control

* Adenosine terminate FAT in significant number of patients.* chronic control: AV blocking agents* ablation: 80- 90% for RA focus and 70-80% in LA focus

Treatment

Recommendations for treatment of focal atrial tachycardia

* correction of underlying abnormalities:

- pulmonary disease

- metabolic

- electrolyte disorders

* CCB

* No role for DCC, AADs or ablation

6( multifocal atrial tachycardia

• Multifocal atrial tachycardia. Note the different P-wave morphologies and irregularly irregular ventricular response

* isthmus-dependent: more frequent

*Non-isthmus-dependent:less frequent

7( atrial flutter

• Atrial flutter. The patient's heart rate is approximately 135 bpm with 2:1 conduction. Note the sawtooth pattern formed by the flutter waves.

Hemodynamically destabilizing (HF, shock, ongoing ischemia): DCC

Hemodynamically stable: rate control by AVN blocking drugs

class Ic: may cause paradoxical increase in ventricular rate.

AVN blocking drugs and amiodarone are NOT effective for cardioversion

IV ibutilide is the most effective agent for acute drug termination of A Fl (38-76%)

Class III (especially dofetilide): effective chronic therapy (73%)

Chronic therapy: NOT required after sinus rhythm is restored if AFl occurs as part of acute disease process

TTT

Recommendations for acute management of atrial flutter

Recommendations for long-term management of atrial flutter

Management of atrial flutter depending on hemodynamic stability

Recommendations for treatment strategies for SVT

during pregnancy

Recommendations for treatment of SVTs in adults with congenital heart

disease

Response of narrow complex tachycardias to

adenosine

Acute management of patients with hemodynamically stable and regular

tachycardia

Objectives of management: * Rate control * Rhythm control * Prevention of thromboembolism Patterns of AF: Newly discovered AF Recurrent paroxysmal AF

Recurrent paroxysmal AF

Permanent AF

8. Atrial Fibrillation )AF(

• Atrial fibrillation. The patient's ventricular rate varies from 130-168 bpm. Rhythm is irregularly irregular. P waves are not discernible

Pharmacological management of patients with newly discovered AF

Pharmacological management of patients with recurrent paroxysmal AF

Pharmacological management of patients with recurrent persistent or permanent

AF

Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation

Recommendations for Pharmacological Cardioversion of Atrial Fibrillation of Less Than or Equal to 7 Days’ Duration

Recommendations for Pharmacological Cardioversion of Atrial Fibrillation of More Than 7

Days’ Duration

Recommended Doses of Drugs Proven Effective for Pharmacological Cardioversion of Atrial

Fibrillation

Pharmacological Treatment Before Cardioversion in Patients With Persistent Atrial Fibrillation: Effects of

VariousAntiarrhythmic Drugs on Acute and Subacute

Outcome of Transthoracic Direct Current Shock

Typical Doses of Drugs Used to Maintain Sinus Rhythm in Patients With

Atrial Fibrillation

Intravenous Pharmacological Agents for Heart Rate Control in Patients

With Atrial Fibrillation

Orally Administered Pharmacological Agents for Heart Rate Control in Patients

With Atrial Fibrillation

Recommendations for management of AF:

I. Pharhacological rate control during AF:

Class I:

1. Rate control for patients with persistent or permanent AF

(LOE: B)

2. With no pre-excitation: IV BB or CCB to slow acute settings

without hypotension or HF (LOE: B)

3. IV digoxin or amiodarone in AF with HF (LOE: B)

4. digoxin effective to control HR at rest (LOE: C)

1. digoxin + BB or CCB for control of HR at

rest and during exercise (LOE: B)

2. Ablation of AVN or AP to control HR

when drugs are insufficient or with side

effects (LOE: B)

3. IV amiodarone when other measures are

unsuccessful or contraindicated (LOE: C)

4. IV procainamide or ibutilide when DCC is

not necessary in Af+AP (LOE: C)

Class IIa:

1.oral amiodarone when HR can’t be controlled using BB, CCB or digoxin alone or in combination (LOE: C)

2. IV procainamide, disopyramide, ibutilide, or amiodarone forhemodynamically stable patients with AF + AP (LOE: B)

3. When HR can’t be controlled by drugs or tachycardia-mediated myopathy is suspected : Ablation of AVN (LOE: C)

Class IIb:

1. digitalis is not used as the sole agent to control HR in patients with paroxysmal AF (LOE: B)

2. Ablation of AVN: is not attempted without prior trial of medication to control rate (LOE: C)

3. HF+AF: IV CCB exacerbate AF so NOT recommended (LOE: C)

4. IV digitalis or CCB in AF+AP increase ventricular rate so not recommended (LOE: C)

Class III:

Pharmacological Cardioversion of AF:

Class I: Flecainide, dofetilide, propafenone or Ibutilide (LOE: A)

Class IIa : 1. IV amiodarone (LOE: A)2. single oral dose of propafenone or flecainide

(pill in the pocket) may terminete persistent AF (LOE: C)

3. amiodarone in paroxysmal or persistent AF when rapid restoration of sinus rhythm is not necessary (LOE: C)

Class IIb: Quinidine or procainamide considered for

AF cardioversion but not well established (LOE: C)

CLASS III:

1. Digoxin and sotalol are not recommended for pharmacologic carioversion of AF (LOE: A)

2. quinidine , procainamide, dofetilide not started out of hospital for cardioversion of AF (LOE: B)

Maintenance of sinus rhythm:

Class I: before starting AADs treat precipitating or reversible

causes of AF

Class II:1. lone AF without structural heart disease

propafenone or flecainide in outpatients with paroxysmal AF who are in SR (LOE: B)

2. Sotalol in patients with SR with little or no heart disease prone to paroxysmal AF (LOE: C)

3. Amiodarone (LOE: C)

Class III Class III 1. Antiarrhythmic therapy not 1. Antiarrhythmic therapy not

recommended in patient with AF recommended in patient with AF who have risk factors for who have risk factors for proarrhythmia (LOE:A)proarrhythmia (LOE:A)

2. Pharmacological therapy not 2. Pharmacological therapy not recommended in patients with recommended in patients with advanced SAN disease or AVN advanced SAN disease or AVN dysfunction unless have dysfunction unless have functioning pacemaker (LOE:C)functioning pacemaker (LOE:C)

Class I

1- Oral B blocker prevent postoperative AF for patients undergoing cardiac surgery (LOE:A)

2- AVN blocking agents for rate control in patients who develop postoperative AF (LOE:B)

Postoperative AF

Class II a 1- Preoperative amoidarone decrease incidence postoperative AF (LOE:A)

2- Ibutilide or DC conversion of postoperative AF (LOE:B)

3- Antiarrhythmic medications maintain SR in recurrent or refractory AF (LOE:B)

Class II b prophylactic satalol for patient at risk of developing AF after cardiac surgery (LOE:B)

Class I

1- DC cardioversion haemodynamic compromise (LOE:C)

2- IV amiodarone slow ventricular rate response to AF (LOE:C)

3- IV blocker or Ca blocker slow ventricular rate response to AF who do not have LV dysfunction, bronchospasm or A-V block (LOE:C)

Post AMI AF

Class II a

1- IV digitalis in AMI + LV dysfunction (LOE:C) Class III

2- Class Ic antiarrhythmic drugs are not recommended in AMI + AF (LOE:C)

Class I 1- catheter ablation (LOE:B)

2- Immediate DC shock in haemodynamic instability (LOE:B)

3- IV procainamide or Ibutilide restore AF to SRC if haemodynamically stable + wide QRS (LOE:C)

Class IIa

IV Flecanide or direct DC very rapid Vent. Rate (LOE:B)

Management of AF + WPW syndrome

Class IIb

1- IV quinidine, procainamide, disopyramide or amiodarone , ibutilide if haemodynamically stable (LOE:B)

Class III

1- IV digitalis or Ca blocker ___ not recommended (LOE:B)

Hyperthyroidism and AF

Class I

1- B blocker (LOE:B)

2- Ca blocker (when B blockers can not be used) (LOE:B)

Class I

1- Digoxin, B blocker, Ca blocker (LOE:C) 2- DC shock if Haemodynamically unstable (LOE:C)

Class IIb 1- Quinidine or procainamide if pharmacological cardioversion in haemodynamically stable (LOE:C)

Management of AF during prgnancy:

Management of AF + HCM

Class IIa

1- Disopyramide + B blocker or Ca blocker or amiodarone ___ prevent recurrence of AF (LOE:C)

Management of AF + pulmonary disease

Class I 1- Diltiazime or Verapamil (LOE:C) if stable 2- DC shock (LOE:C) if unstable

Class II 1- Theophylline and B agonist not

recommended in pulmonary disease +AF (LOE:C)

2- B blocker , Satolol , Propafenone, Adenosine not recommended (LOE:C)

Management of Ventricular

arrhythmias

Class I

DC shock (LOE:C)

Class IIa • 1- IV procainamide or ajmaline (LOE:B)

• 2- IV amiodarone (LOE:C)

Class IIb• 1- IV Lidocaine if Stable with AMI or acute Ischemia (LOE:C)

• Class III• 1- Ca blocker Not used to terminate wide QRS – complete VT of unknown origin (LOE:C)

1- Sustained monomorphic VT

monomorphic VT

Class IIa

1- IV amiodarone , B blocker and procainamide , Sotalol or ajmaline in CHD or idiopathic VT (LOE:C)

2. Repetitive monomorphic VT

3. Polymorphic VT

ClassI 1- DC Shock if Haemodynamically compromised

(LOE:B) 2- IV B blocker if especially in ischemia (LOE:B)

3- IV amoidarone if in absence of abnormal repolarization related to congenital or acquired QT syndrome

(LOE:C)

ClassIIb 1- IV Lidocaine especially in AMI or Ischemia (LOE:C)

Class I

1- Withdrawal of offending drugs and correction of electrolyte abnormalities (LOE:A)

2- Acute and long-term pacing if TdP due to heart block and symptomatic bradycardia (LOE:A)

4. Torsades de pointes

Class II a 1- IV magnesium __ Long QT + TDP ( Mg

not effective in normal QT) (LOE:B) 2- Acute and long term pacing __

Recurrent pause-dependent TDP (LOE:B)

3- B blocker + Pacing__TDP + sinus bradycardia (LOE:C)

4- IV Isopproterenol __ Temporary in recurrent pause-dependent TDP + no congenital LQTs (LOE:B)

Class IIb 1- 1<repletion to 405-5 MM/L (LOE:B) 2- IV Lidocaine or oral mexiletine __ in

LQT3 + TDP (LOE:C)

5. Incessant VT

Class I

1- Revascularization +B blocker followed by IV procainamide or IV Amoidarone ____ Recurrent or incessent polymorphic due to myocardial ischemia (LOE:C)

Class IIA

1- Amoidarone or Procainamide followed by VT ablation (LOE:B)

Class IIb

1- IV amoidarone and IV B blockers separately or combined ___ VT storm (LOE:C)

2- Overdrive pacing or general anesthesia (LOE:C)

3- Spinal cord modulation (LOE:C)

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