Heart condition where disturbances in • Pacemaker impulse formation• Impulse conduction• Combination of the two

Results in rate and/or timing of contraction of heart muscle that is insufficient to maintain normal cardiac output (CO).

To understand how anti-arrhythmic drugs work, need to understand electrophysiology of normal contraction of heart.

Arrhythmias are common in most people and are usually not a problem but…

Arrhythmias esp VA’s are most common cause of sudden death

Majority of sudden death occurs in people with neither a previously known heart disease nor history of VA’s

Medications which decrease incidence of A’s do not decrease (and may increase) the risk of sudden death treatment may be worse then the disease!

Sinoatrial node Atrioventricular

node Bundle of His Bundle

Branches• Fascicles

Purkinje Network

Permits rapid organized depolarization of ventricular myocytes

Necessary for the efficient generation of pressure during systole

Atrial activation complete 0.09s after SAN firing

Delay at AVN Septum activated 0.16s Whole ventricle

activated by 0.23s

ECG (EKG) showing wave segments

Contraction of atria

Contraction of ventricles

Repolarization of ventricles

A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell

Caused by unequal distribution of ions inside vs. outside cell• Na+ higher outside than inside cell• Ca+ much higher “ “ “ “• K+ higher inside cell than outside

Maintenance by ion selective channels, active pumps and exchangers

Divided into five phases (0,1,2,3,4)• Phase 4 - resting phase (resting membrane potential)

Phase cardiac cells remain in until stimulated Associated with diastole portion of heart cycle

Addition of current into cardiac muscle (stimulation) causes • Phase 0 – opening of fast Na channels and rapid

depolarization Drives Na+ into cell (inward current), changing membrane

potential Transient outward current due to movement of Cl- and K+

• Phase 1 – initial rapid repolarization Closure of the fast Na+ channels Phase 0 and 1 together correspond to the R and S waves of

the ECG

Phase 2 - plateau phase• sustained by the balance between the inward movement of Ca+

and outward movement of K + • Has a long duration compared to other nerve and muscle tissue• Normally blocks any premature stimulator signals (other muscle

tissue can accept additional stimulation and increase contractility in a summation effect)

• Corresponds to ST segment of the ECG.

Phase 3 – repolarization • K+ channels remain open, • Allows K+ to build up outside the cell, causing the cell to

repolarize• K + channels finally close when membrane potential reaches

certain level• Corresponds to T wave on the ECG

PCs - Slow, continuous depolarization during rest Continuously moves potential towards threshold

for a new action potential (called a phase 4 depolarization)

SNS - Increased with concurrent inhibition vagal tone: 

NA binds to B1 Rec Increases cAMP Increases Ca and Na in Decreases K out Increases slope phase 0 Non-Nodal tissue: More rapid depolarisation More forceful contraction Pacemaker current (If)

enhanced  Increase slope phase 4 Pacemaker potential more

rapidly reaches threshold Rate increased

PSNS (Vagal N) Ach binds M2 rec Increases gK+ Decreases inward Ca & Na Non-Nodal tissue: Less rapid depolarisation Less forceful contraction Pacemaker current (If)

suppressed Decreases pacemaker rate Decrease slope of Phase 4 Hyperpolarizes in Phase 4 Longer time to reach

threshold voltage

Changes in automaticity of the PM Ectopic foci causing abnormal APs Reentry tachycardias Block of conduction pathways Abnormal conduction pathways (WPW) Electrolyte disturbances and DRUGS Hypoxic/Ischaemic tissue can undergo

spontaneous depolarisation and become an ectopic pacemaker

Branch 2 has a unidirectional block Impulses can travel retrograde (3 to

2) but not orthograde.  An AP will travel down the branch 1,

into the common distal path (br 3), then travel retrograde through the unidirectional block in branch 2.

When the AP exits the block, if it finds the tissue excitable, it will continue by traveling down (reenter) the branch 1.

If it finds the tissue unexcitable (ERP) the AP will die.

Tming is critical –AP exiting the block must find excitable tissue to propagate.

If it can re-excite the tissue, a circular pathway of high frequency impulses (tachyarrhythmia) will become the source of APs that spread throughout a region of the heart (ventricle) or the entire heart.

Anaesthetic technique (general>regional>local)

Anaesthetic agents Vasopressors Parasympatholytics Muscle relaxants Intubation and ventillation Surgical procedures. Electrolyte imbalance.

Wandering pacemaker.

AV Dissociation. Nodal rhythm. PVC’ s. Sinus

bradycardia. SVT. VT.

HR< 60 bpm; every QRS narrow, preceded by p wave

Can be normal in well-conditioned athletes HR can be<30 bpm in children, young adults

during sleep, with up to 2 sec pauses

HR > 100 bpm, regular Often difficult to distinguish p and t waves

Variations in the cycle lengths between p waves/ QRS complexes

Will often sound irregular on exam Normal p waves, PR interval, normal, narrow QRS

•All result in bradycardia

•Sinus bradycardia (rate of ~43 bpm) with a sinus pause

•Often result of tachy-brady syndrome: where a burst of atrial tachycardia (such as afib) is then followed by a long, symptomatic sinus pause/arrest, with no breakthrough junctional rhythm.

Refers to supra-ventricular tachycardia other than afib, aflutter and MAT

Usually due to reentry—AVNRT or AVRT

Irregular rhythm Absence of definite p waves Narrow QRS Can be accompanied by rapid ventricular response

P wave from another atrial focus Occurs earlier in cycle Different morphology of p wave

PR interval >200ms If accompanied by wide QRS, refer to cardiology,

high risk of progression to 2nd and 3rd deg block Otherwise, benign if asymptomatic

Progressive PR longation, with eventual non-conduction of a p wave

May be in 2:1 or 3:1

Usually asymptomatic, but with accompanying bradycardia can cause angina, syncope esp in elderly—will need pacing if sxs

Also can be caused by drugs that slow conduction (BB, CCB, dig)

2-10% long distance runners Correct if reversible cause, avoid meds that block

conduction

Normal PR intervals with sudden failure of a p wave to conduct

Usually below AV node and accompanied by BBB or fascicular block

Often causes pre/syncope; exercise worsens sxs Generally need pacing, possibly urgently if symptomatic

Complete AV disassociation, HR is a ventricular rate Will often cause dizziness, syncope, angina, heart

failure Can degenerate to Vtach and Vfib Will need pacing, urgent referral

Extremely common throughout the population, both with and without heart disease

Usually asymptomatic, except rarely dizziness or fatigue in patients that have frequent PVCs and significant LV dysfunction

Defined as 3 or more consecutive ventricular beats

Rate of >120 bpm, lasting less than 30 seconds May be discovered on Holter, or other exercise

testing

Defibrillation

Pharmacological agents

Non Pharmacological agents

“The ideal antiarrhythmic agent does not yet exist, and it is unlikely that it will in the foreseeable future. All the available agents have side effects, and therapy should be regarded as each patient’s dysrhythmia remain an individuals pharmacologic experiment, determined empirically by clinical judgment. Although in some patients one drug may suppress a ventricular tachycardia that is refractory to all other agents, other patients require several combination of drugs. (D.P. Zipes, new eng. J. Med. 304:475, 1981)”

Restore normal rhythm, rate and conduction or prevent more dangerous arrhythmias

1. Alter conduction velocity (SAN or AVN) Alter slope 0 depolarisation or refractoriness2. Alter excitability of cardiac cells by changing

duration of ERP (usually via changing APD) ERPinc – Interrupts tachy caused by reentry APDinc – Can precipitate torsades 3. Suppress abnormal automaticity

EmpiricArrhythmia Diagnosis

Interventions

Clinical Outcomes

Interventions

Clinical Outcomes

PathophysiologicArrhythmia Diagnosis

Known or suspected

mechanismsCritical components

Vulnerable parameters

Targeted subcellular units

BLACK BOX

PathophysiologicArrhythmia Diagnosis

Interventions

Clinical Outcomes

Known or suspected mechanisms

Critical components

Vulnerable parameters

Targeted subcellular units

AV node reentrant tachycardia

AV node reentry

Anatomical fast/slow pathwayAV node (slow conduction)AV nodal action potential

L-type Ca++ channel

Ca++ channel blocker-blocker

Sinus rhythm

Based on cellular properties of normal His-Purkinje cells

Classified on drug’s ability to block specific ionic currents (i.e. Na+, K+, Ca++) and beta-adrenergic receptors

Advantages:• Physiologically based• Highlights beneficial/deleterious effects of

specific drugs

EmpiricArrhythmia Diagnosis

Interventions

Clinical Outcomes

BLACK BOX

Goals•Identify the type of dysrhythmia•Be familiar with more common antiarrhythmics and their Vaughn-Williams Classification

Class I - Na+ - channel blockers (direct membrane action)

Class II - Sympatholytic agents Class III - Prolong repolarization Class IV- Ca++ - channel blockers Purinergic agonists Digitalis glycosides

IA - Quinidine/Procainamide/Disopyramide IB - Lidocaine/Mexiletine/Phenytoin IC - Flecainide/Propafenone/Ethmozine

1

0

2

3

4

ERP RRP

AffectsPhase 0

Block open ACTIVATED Na channels Slow phase 0 depolarisation - upstroke of AP Lengthen APD and ERP. (Atrial, His-Purkinje,

ventricular tissue) Prolong PR and QRS duration on ECG Anticholinergic S/E. Also blocks K Ch. Greater affinity for rapidly firing channels Toxicity: QTc increases by 30% or QT > 0.5 sec Disopyramide: Prevent rec VT. - Inotrope Quinidine: SVT and VT. Torsades Procainamide

Procainamide has been a long-used intravenous

infusion for a wide range of dysrhythmias:• Narrow complex tachycardia:

Atrial tachycardia, resistant re-entrant tachycardia

• Wide-complex tachycardia: Ventricular tachycardia

Downside: Side effects, negative inotrope, pro-

arrhythmic

Block INACTIVATED Na channels Slow phase 0 depolarisation- Slows

upstroke of AP Shorten APD and ERP in purkinge fibres

and increase VF threshold Ratio ERP/APD is increased Greater affinity for ischaemic tissue that

has more inactivated channels, little effect on normal cells – dissociates quickly (0.5sec)

ECG Changes decrease QT interval. Lignocaine: VT in heart with normal EF Phenytoin

Use: VT (acute)• Acts rapidly; no depression of contractility/AV

conduction Kinetics

• t1/2 : 5-10 min (1st phase); 80-110 min (2nd phase)

Drug interactions• Decreased metabolism w/ CHF/hepatic failure,

propranolol, cimetidine• Increased metabolism w/ isuprel,

phenobarbital, phenytoin

Use: VT (acute)• Acts rapidly; no depression of contractility/AV

conduction Kinetics

• t1/2 : 5-10 min (1st phase); 80-110 min (2nd phase)

Drug interactions• Decreased metabolism w/ CHF/hepatic failure,

propranolol, cimetidine• Increased metabolism w/ isuprel,

phenobarbital, phenytoin

Dose• 1 mg/kg, then 20-50 g/kg/min (level: 2-5

g/ml) Side effects

• CNS toxicity w/ levels > 5 g/ml

Dose• 1 mg/kg, then 20-50 g/kg/min (level: 2-5

g/ml) Side effects

• CNS toxicity w/ levels > 5 g/ml

Use: VT (post-op CHD) Kinetics: t1/2 = 8 - 12 hrs Drug interactions- rare Dose

• 3-5 mg/kg/dose (adult 200-300mg/dose) po q 8 hrs

Side effects• Nausea (40%)• CNS - dizziness/tremor (25%)

Uses• VT (post-op CHD), digoxin-induced

arrhythmias Drug interactions

• Coumadin- PT; Verapamil- effect (displaces from protein)

Dose• PO: 4 mg/kg q 6 hrs x 1 day, then 5-6

mg/kg/day ÷ q 12hr• IV: bolus 15 mg/kg over 1 hr; level 15-20

g/ml Side effects

• Hypotension, gingival hyperplasia, rash

Class IB antiarrhythmics are very effective and very safe.

Little or no effect on “normal” tissues First line for ischemic, automatic arrhythmia's

(Ventricular tachycardia) Not a lot of effect on normal conduction tissue –

not a good medicine for reentry and atrial tachycardias.

Block Na channels. Most potent Na channel block Dissociate very slowly (10-20 sec) Strongly depress conduction in

myocardium Slow phase 0 depolarisation - upstroke of

AP No effect on APD No effect on QRS ECG Changes prolong QT interval. Flecainide: Prophylaxis in paroxysmal AF Propafenone

Uses: PJRT, AET, CAT, SVT, VT, Afib Kinetics

• t1/2 = 13 hrs (shorter if between 1-15 mos old) Drug interactions

• Increases digoxin levels (slight)• Amiodarone: increases flecainide levels.

Dose• 70-225 mg/m2/day ÷ q 8-12 hr• Level: 0.2-1.0 g/ml

Side effects• Negative inotrope- use in normal hearts

only (NO POST-OPs)

• PROARRHYTHMIA - 5-12% (CAST)

IC’s have a lot of side effects that make them appropriate for use only by experienced providers.

Propranolol Atenolol Metoprolol Nadolol Esmolol d,l-Sotalol

Beta Blockers - Block B1 receptors in the heart

Decrease Sympathetic activity Non-Nodal Tissue: Increase APD and ERP SA and AVN: Decrease SR Decrease conduction velocity (Block re-

entry) Inhibit aberrant PM activity

Beta-blockers are good for re-entry circuits and automatic dysrhythmias.

Their effect of decreasing contractility

may be limiting.

Non-selective B-Blocker (B1 and B2) Indications: Convert or Slow rate in SVTs 2nd line after Adenosine/Digoxin/Diltiazem IV atenolol 5 mg over 5 minutes Repeat to maximum 15 mg. 50 mg PO BID if IV works Contraindiactions: Asthma CCF. Poor EF. High degree heart block. Ca channel blockers. Cocaine use.

Anti-Fibrillatory agents. Block K channels Prolong repolarisation Prolong APD and ERP Useful in Re-Entry tachycardias AMIODARONE (also Class IA, II BB) SOTALOL (also Class II BB)

Most tachyarrhythmias OK if impaired LV function Rate control and converts rhythm Cardiac arrest: 300 mg IV push (max 2.2g/24hrs) Stable VT: 150 mg IV repeat 10 min or infusion

360 mg IV over 6 hrs (1mg/min) Maintenance infusion: 540 mg over 18 hrs

(0.5mg/min) Side Effects: Hypotension. Negative Inotropy. Prolonged QT. Photosensitivity. Thyroid disorders. Pulmonary alveolitis. Neuropathy.

Calcium Channel Blockers Bind to L-type Ca channels Vascular SmM, Cardiac nodal & non-nodal

cells Decrease firing rate of aberrant PM sites Decrease conduction velocity Prolong repolarisation Especially active at the AVN VERAPAMIL DILTIAZEM

Narrow complex tachycardias Terminates PSVT/SVT Rate control in AFib/Aflutter NOT WPW or VT or high degree block NOT with BBlockers Negative Inotropy Vasodilation – Hypotension Dose: 5mg IV bolus. Rpt 15 min max 30

mg Diltiazem less adverse effects

Purine nucleoside Acts on A1 adenosine receptors Opens Ach sensitive K channels Inhibits Ca in current – Suppresses Ca

dependent AP (Nodal) Increases K out current – Hyperpolarisation Inhibits AVN > SAN Increases AVN refractory period ECG Changes slows AV Node conduction.

Uses• SVT- termination of reentry• Aflutter- AV block for diagnosis

Kinetics• t1/2 = < 10 secs• Metabolized by RBCs and vascular

endothelial cells Dose

• IV: 100-300 g/kg IV bolus

Interrupts re-entry and aberrant pathways through AVN – Diagnosis and Treament

Drug for narrow complex PSVT SVT reliant on AV node pathway NOT atrial flutter or fibrillation or VT Contraindications: VT – Hypotension and deterioration High degree AV block Poison or drug induced tachycardia Bronchospasm but short DOA

Cardiac glycoside Blocks Na/K ATPase pump in heart Less ECF Na for Na/Ca pump Increased IC Ca Inotropic: Increases force of contraction AVN increased refractoriness Decreases conduction through AVN and SAN Negative chronotrope: Slows HR

Reduces ventricular response to SVTs

ECG changes• Increases PR interval• Depresses ST

segment• Decreases QT

interval

Contraindications: WPW. SSS. Elderly or renal failure – reduce dose or TOXICITY 0.25 to 0.5 mg IV; then 0.25 mg IV every 4 to 6

hours to maximum of 1 mg 0.125 to 0.25 mg per day IV or orally

Dronedarone-SR33589 • Inhibits Ikr , Iks, B1 ,ICa (L-type), Ito • Lacks iodine moiety • No thyroid or pulmonary toxicity • Similar electrophysiology to amiodarone • Half-life = 24 h, dose BID • Food increases levels 2-3 x • Undergoes 1st pass metabolism, ~ 15% Available

Tedisamil • Class III antiarrhythmic • Blocks multiple K channels and slows SR • Blocks Ito , IK-ATP, IKr, IKs, Ikur • Prolongs APD atria > ventricles • Excreted by the kidney • T ½ 8-13 hours • Has significant anti-anginal, anti-ischemic properties

Wide range from Carotid massage to radiofrequency ablation.

Cardioversion success rate in AF

Size of RA. Duration of AF Sleep apnoea Anti arrhythmic

drugs. Obesity

Implantable cardioverter defibrillator (ICD) reduces the chances of dying from a second SCA. An ICD is surgically placed under the skin in the chest or abdomen. The device has wires with electrodes on the ends that connect to the heart's chambers. The ICD monitors the heartbeat.If the ICD detects a dangerous heart rhythm, it gives an electric shock to restore the heart's normal rhythm. The electrodes are inserted into the heart through a vein.

Success rate >90% in AVNRT AVRT Atrial tachycardia