Cardiac arrhythmia

• Abnormal cardiac rhythm usually involving a change in rate or regularity.

• Synonym: dysrhythmia

EtiologyPhysiological:

-sympathetic or parasympathetic control changes eg. Stress , anxiety, exercise , smoking.Hypothyroidism, HyperthyroidismHypoadrenalismHyperkalemiahypokalemia and other electrolyte changes.

Pathological:Valvular heart disease.Ischemic heart disease.----------MI causing death of

pacemaker cells or conducting tissue.Hypertensive heart diseases.Congenital heart disease.Cardiomyopathies.Carditis.RV dysplasia.Drug related.Pericarditis. Pulmonary diseases.Others.

CLINICAL EVALUATIONI. PHYSICAL FINDINGS

Palpitation.Dizziness.Chest Pain.Abnormal pulse rate , rhythm or amplitudeDyspnea.Anxiety and confusion (from reduced brain perfusion)Fainting (syncope)Skin pallor or cyanosisReduced blood pressureWeaknessConvulsionsDecreased urinary outputSudden cardiac death.

II. DIAGNOSTIC TEST RESULTS ECG

electrophysiological (EP) testingHis bundle study

III. LAB FINDINGS:hyperkalemia (>5mEq/L)Hypocalcemia (<4.5mEq/L)hypomagnesemia(<2.5mEq/L)

Mechanism of Arrhythmogensis1. Disorder of impulse formation.

a) Automaticity.b) Triggered Activity.

1) Early after depolarization.2) Delayed after depolarization.

2. Disorder of impulse conduction.a) Block – Reentry.b) Reflection.

3. Combined disorder.

Nomenclature for describing arrhythmias

• Ratetachycardiabradycardia

• Origin:sinusatrialnodalsupraventricularre-entrantventricular

• Pattern:ectopicPremature contractionparoxysmalflutterfibrillationblocktorsadeselectromechanical dissociation

Duration:i) paroxysmal- self terminating

episodes upto 7 daysii) persistent -non self terminating more than 7

daysiii) permanent - not responding to

cardioversion attemptsiv) recurrent: returning after once stopped.

Electrophysiological treatment

1) Cardioversion2) Implantable Cardiac Defibrillator (ICD)3) Pace maker4) Lead extraction

Pharmacology of anti- arrhythmic drugs

Quinidine (Class IA prototype)

• Other examples: Procainamide, DisopyrimideGeneral properties:a. D-isomer of quinine

b. As with most of the Class I agents- moderate block of sodium channels- decreases automaticity of pacemaker cells- increases effective refractory period/AP duration

Actions of quinidine• Cardiac effects

a. ↓ automaticity, conduction velocity and excitability ofcardiac cells.

b. Preferentially blocks open Na channelsc. Recovery from block slow in depolarized tissue;

lengthens refractory period (RP)d. All effects are potentiated in depolarized tissuese. Increases action potential duration (APD) and

prolongs AP repolarization via block of K channels; decreases reentryf. Indirect action: anticholinergic effect (accelerates

heart), which can speed A-V conduction.

– Cardiac tissue:• Reduce automaticity• Reduce excitability• Reduce conductivity• Prolong refractory period• Reflex tachycardia

– Other action:• Anti-malarial• Anti-pyretic• Decrease B.P (vasodilation)

Pharmacokinetics:– Orally active; i.v. in emergency; i.m. painful– 80% bound to plasma proteins– Half-life: 4-6 hrs– Metabolized by liver (75%)– Excretion: unchanged fraction by kidney

Extracardiaca. Blocks alpha-adrenoreceptors to yield vasodilatation.b. Other strong antimuscarinic actionsToxicity- "Quinidine syncope"(fainting)- due to disorganized ventriculartachycardia- associated with greatly lengthened Q-T interval; can lead to

Torsades de Pointes (VT, precursor to ventricular fibrillation)- negative inotropic action (decreases contractility)- GI - diarrhea, nausea, vomiting- CNS effects - headaches, dizziness, tinnitus (quinidine“Cinchonism”)

• Adverse effects:– Heart block– Sinus arrest– Myocardial depression– Q-T prolongation– Ventricular fibrillation– Nausea – Vomiting– Diarrhoea – Rash – Oedema

Indications :1) Premature atrial contractions2) Paroxysmal atrial fibrillation and flutter3) Intra-atrial and A-V nodal reentrant dysrhythmias4) Wolff-Parkinson-White tachycardias (SVT, A-V bypass)5) Premature ventricular contractions (PVCs)6) Useful in treating chronic dysrhythmias requiring outpatient

treatment• Also as anti-malarial• Anti-pyretic• During digitalis therapy

• Contraindications:– Quinidine intolerance– Digitalis intoxication– Heart failure– Hypotension– hypokalemia

Procainamide (Class 1A) also DisopyrimideCardiac effectsa) Similar to quinidine, less muscarinic & alpha-

adrenergic blockadeb) Also has negative inotropic action .Extracardiac effectsa) Ganglionic blocking reduces peripheral vascular

resistanceToxicity

a) Cardiac: Similar to quinidine; cardiac depressionb) Noncardiac: Syndrome resembling lupus erythematosus

Pharmacokinetics/therapeuticsa. Administered orally, i-vb. Major metabolite in liver is N-acetylprocainamide (NAPA), a weak Na channel blocker with class III activity. Bimodal distribution in population of rapid acetylators, who can accumulate high levels of NAPA.c. T1/2 = 3-4 hours; necessitates frequent dosing; kidney chief elimination path. NAPA has longer T1/2 and can accumulated. Usually used short-term. Commonly used in CCUs for ventricular dysrhythmias associated with acute myocardial infarctions (MI)

Lidocaine (Class IB prototype)

Other examples: Mexiletine, Phenytoin, TocainideGeneral

a). Commonly used antidysrhythmic agent in emergency care (decreasing use)b) Given i-v; widely used in ICU-critical care units c)Low toxicity (especially cardiac, good therapeutic index)d) A local anesthetic, works on nerve at higher doses

• Mechanism of anti-arrhythmic effect of lignocaine:– It has membrane stabilizing effect by blocking

both activated and inactivated sodium channels; which in turn supresses SA node and also ectopic beats.

– Shortens refractory period and action potential; make uniform rhythm

Cardiac effectsa. Generally decreases APD, hastens AP repolarization, decreases

automaticity and increases refractory period in depolarized cells.

b. Exclusively acts on Na channels in depolarized tissue by blocking open and inactivated (mainly) Na channels

c. Potent suppresser of abnormal activityd. Most Na channels of normal cells rapidly unblock from

lidocaine during diastole; few electrophysiological effects in normal tissue

Toxicity: - least cardiotoxic, high dose can lead to hypotension• - tremors, nausea, slurred speech, convulsions– Bradycardia, Hypotension, Dizziness, Blurred vision,

Sleepiness, Confusion

• Pharmacokineticsa. i-v, since extensive first pass hepatic metabolismb. T1/2 = 0.5-4 hours Indications a) Effective in suppressing dysrhythmia associated with

depolarised.( Tissue ischemia; digitalis toxicity); ineffective against dysrhythmias in normal tissue (atrial flutter).

b) Suppresses ventricular tachycardia; prevents fibrillation after acute MI; rarely used in supraventricular dysrhythmias

Contraindications of lidocaine• Heart block, second or third degree (without pacemaker)• Severe sinoatrial block (without pacemaker)• Serious adverse drug reaction to lidocaine or amide local

anaesthetics• Concurrent treatment with quinidine, flecainide, disopyramide,

procainamide (Class I antiarrhythmic agents)• Prior use of Amiodarone hydrochloride• Hypotension not due to Arrhythmia• Bradycardia• Accelerated idioventricular rhythm• Pacemaker• Porphyria, especially acute porphyria (AIP)

Phenytoin

1. Non-sedative anticonvulsant used in treating epilepsy('Dilantin')2. Limited efficacy as antidysrhythmic (second lineantiarrythmic)3. Suppresses ectopic activation by blocking Na and Cachannels4. Especially effective against digitalis-induceddysrhythmias5. T1/2 = 24 hr – metabolized in liver6. Gingival hyperplasia (40%)

Flecainide (Class IC prototype)

Other examples: Lorcainide, Propafenone, Indecainide, Moricizine

Depress rate of rise of AP without change in refractoriness or APD1. Decreases automaticity, conduction in depolarized cells.2. Marked block of open Na channels (decreases Ph. 0); no change

repolarization.3. Used primarily for ventricular dysrhythmias but effective for atrial too4. No antimuscarinic action5. Suppresses premature ventricular contractions (PVCs)6. Associated with significant mortality; thus, use limited to last resort

applications like treating ventricular tachycardias7. Significant negative inotropic effect

Propranolol (Class II, beta-adrenoreceptor blockers)

• Other agents: Metoprolol, Esmolol (short acting), Sotalol (also Class III), Acebutolol

• Propranolol as anti-arrhythmic drug:– It blocks β-receptors in heart, thereby exerts

• Negative inotropic effect• Negative chronotropic effect• Depress atrioventricular conduction• Depresses automaticity

– It has:• Anti-arrhythmic effect• Anti-hypertensive effect• Anti-anginal-effect in CVS.

a. Slow A-V conductionb. Prolong A-V refractory period

Cardiac effects (of propranolol), a non-selective beta blocker

a. Main mechanism of action is blockade of beta receptors; ↓ Ph 4 slope which decreases automaticity under certain conditions

b. Some direct local anesthetic effect by block of Na channels (membrane stabilization) at higher doses

c. Increases refractory period in depolarized tissuesd. Increases A-V nodal refractory periodNon-cardiac: Hypotension

• Therapeuticsa. Blocks abnormal pacemakers in cells receiving

excess catecholamines (e.g. pheochromocytoma) or up-regulated beta-receptors (ie. hyperthyroidism)

b. Blocks A-V nodal reentrant tachycardias; inhibits ectopic foci

c. Beta-blockers are used to treat supraventricular tachydysrhythmias

d. Propranolol contraindicated in ventricular failure; can lead to A-V block.

Amiodarone (Class III)

• others: Ibutilide, Bretylium, Sotalol, Dofetilide• Dronedarone • Generala. New DOC for ventricular dysrhythmias (Lidocaine, old DOC)b. prolongs refractory period by blocking potassium channelsc. also member of Classes IA,II,III,IV since blocks Na, K, Ca

channels and alpha and beta adrenergic receptorsd. serious side effects (cardiac depression, pulmonary fibrosis,

thyroid)e. effective against atrial, A-V and ventricular dysrhythmiasf. widely used, very long acting (>25 d)

Effects of amiodaroneCardiac effectsa. Block Na channels (1A), but low affinity for open

channels; mainly blocks inactivated Na channelsb. Block is most pronounced in tissues with long action

potentialsc. Weak Ca channel blocker also (Class IV activity)d. A powerful inhibitor of abnormal automaticity, decreases

conduction, increases refractory period and APD.e. Has antianginal effects (blocks alpha/beta receptors and

Ca channels)Extracardiac effects:

Vasodilation via block of Ca channels and alpha receptors

• B. Non-cardiac:• i. Deposits into almost every organ• ii. Reduces clearance of drugs like procainamide, flecainide, digitalis,• quinidine and diltiazem.• iii. Thyroid dysfunction (hypo or hyperthyroidism)• iv. Pulmonary fibrosis is most serious adverse effect• v. Paresthesias (tingling, pricking, or numbness)• vi. Photosensitivity• vii. Corneal microdeposits and blurred vision• viii. Ataxia, dizziness, tremor• ix. Anorexia, nausea

Adverse effects of amiodarone

• A. Cardiac• i. Sinus bradycardia, increase QT interval

↑risk TdP• ii. Negative inotropic action due to block of Ca

channels and beta• receptors; but can improve heart failure via

vasodilation.• iii. A-V block, paradoxical VTs.

Verapamil (Class IV, Ca++ channel blockers)

• Other example: Diltiazem - CCBs increasing use and importance

a. Blocks active and inactivated Ca channels, prevents Ca entryb. More effective on depolarized tissue, tissue firing frequently

or areas where activity dependent on Ca channels (SA node; A-V node)

c. Increases A-V conduction time and refractory period; directly slows SA and A-V node automaticity

d. suppresses oscillatory depolarizing after depolarizations due to digitalis

e. Dihydropyridine CCBs are generally poor antiarrythmics

Ca++ Channel Blockers - Actions

Extracardiaca. Peripheral vasodilatation via effect on smooth muscleb. Used as antianginal / antihypertensivec. Hypotension may increase HR reflexivelyToxicitya. Cardiac- Too negative inotropic for damaged heart, depresses

contractility- Can produce complete A-V blockb. Extracardiac- Hypotension- Constipation

Other antiarrythmics A. Adenosine: i.v. (15 secs), activates P1 purinergicreceptors (A1) coupled to K channels, ↓CV, ↑refractoryperiod. SVT. Flushing, hypotension, burning sensationB. Potassium ions (K+): Depress ectopic pacemakers- can depress CV → reentrant dysrhythmiaC. Digoxin: used to treat atrial flutter and fibrillation- AV node ↓conduction (vagal stimulation)- myocardium ↓refractory period- Purkinje fibers ↑refractory period, ↓conductionD. Magnesium: used to treat Torsades de PointesE. Autonomic agents: used to treat A-V block- β-agonists , anticholinergics (ie. atropine)Anticoagulant therapy:- prevent formation of systemic emboli & stroke

Life style changes

• Eat heart-healthy foods.• Increase your physical activity.• Quit smoking.• Cut back on caffeine and alcohol.• Find ways to reduce the amount of stress in

your life.• Avoid stimulant medications, such as

medications found in over-the-counter treatments for colds and nasal congestion.

Arrythmia detected

yesIs it life threatening? emergency resuscitation no is it affecting cardiac output Or threatening to do so yes monitor , check electrolytes andOr unpleasant for the patient ? possible causes.

yes yes is the rate slow? Consider electrolyte pacing no correct elctrolyte abnormalities

choose a drug according to origin Of arrhythmia

Algorithm for treatment of arrhythmia

Condition Drug

Sinus tachycardia Class II, IV

Atrial fibrillation/flutter

Class IA, IC, II, III, IV digitalis adenosine

Paroxysmal supraventricular tachycardia

Class IA, IC, II, III, IV adenosine

AV block Atropine

Ventricular tachycardia Class I, II, III

Premature ventricular complexes Class II, IV Mg++ salts

Digitalis toxicityClass IB Mg++ salts; KCl

Diagnosis Treatment Avoid

Atrial Fibrillationin Patient withWPW Syndrome

DirectCardioversion+Lidocaine or Procainamide Or Ibutilide

DigoxinAmiodaroneVerapamil

WPW andPseudo-InferiorMI

BetablockerCCBQuinidineFlecainide

Pace-makerDigoxinVerapamil

Atrial Flutterwith 2:1 AvConduction

Digoxin 0.25Esmolol 0.5 Mg/KgAmiodarone 150mg

Quinidine

Ventricular tachycardia Magnesium-SulphateProcainamide Amiodarone LidocaineIf failed:Cardioversion

Verapamil Adenosine

Atrial flutter Digoxin 0.25Esmolol 0.5 Mg/KgAmiodarone 150mg

Quinidine

Drug choice in treating chronic or persistent atrial fibrillation

Associated factors First choice Second choice Avoid

Acute systemic illness Nothing or II IV, II I

Paroxysmal exercise induced vagal origin elderly

IIDisopyramideSotalol/Amiodarone

Sotalol, ICSotalo, IC

Digoxin

Sustained AF ventricular rate control cardioversion

IIIC

Digoxin, IVIA, III II, IV, Digoxin

Respiratory disorders II, sotalol

IHD Sotalol Amiodarone I

Heart failure Amiodarone Digoxin I

Hypertension Sotalol Amiodarone

Drug classes in chronic tachyarrythmias

SA node Atria AV node Accessory pathway

Ventricles

Commonly used

II IIIV

IV for urgent cardioversionII

IC IIIII

Also used DigoxinIIIICIA

DigoxinIC

IIIA

I

Common therapeutic problems in the management of arryhthmias

Problem Management

Narrow therapeutic range of digoxin Encourage compliance and perform TDM

Beta blockers contraindicated in bronchial and peripheral vascular diseases

Consider verapamil or diltiazem

Verapamil induced constipation Give regular laxatives

Pro-arrythmic actions of antiarrhytmics Minimise requirements of drugs , else switch to pacemaker or elctrical therapy

Amiodarone sun burn Stay indoors , use sunblock