Essential Cardiac Electrophysiology Self Assessment - Part 1 pps

Foreword, vii Preface, ix Acknowledgements, xi List of Abbreviations, xiii 1 Ions, channels, and currents, 1 1.1 Potassium channels and currents, 6 1.2 Sodium channels and currents, 12 1

Associate Professor of Clinical Medicine

Texas Tech University Health Sciences Center

El Paso, TX

Adjunct Associate Professor of Electrical Engineering and Computer Science

University of Texas at El Paso

In loving memory of my brother Husainali

Associate Professor of Clinical Medicine

Texas Tech University Health Sciences Center

El Paso, TX

Adjunct Associate Professor of Electrical Engineering and Computer Science

University of Texas at El Paso

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First published 2007

1 2007

Library of Congress Cataloging-in-Publication Data

Abedin, Zainul, MD.

Essential cardiac electrophysiology : self assessment/by

Zainul Abedin and Robert Conner.

p ; cm.

Includes bibliographical references and index.

ISBN-13: 978-1-4051-5108-5 (pbk : alk paper)

ISBN-10: 1-4051-5108-0 (pbk : alk paper)

1 Heart–Electric properties–Handbooks, manuals, etc.

2 Arrhythmia–Pathophysiology–Handbooks, manuals, etc.

3 Electrophysiology–Handbooks, manuals, etc 4 Heart conduction system–Handbooks, manuals, etc I Conner, Robert P II Title.

ISBN-10: 1-4051-51080

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Foreword, vii

Preface, ix

Acknowledgements, xi

List of Abbreviations, xiii

1 Ions, channels, and currents, 1

1.1 Potassium channels and currents, 6

1.2 Sodium channels and currents, 12

1.3 Calcium channels and currents, 16

2 Electrophysiologic effects of cardiac autonomic activity, 21

5.4 Automatic junctional tachycardia, 93

5.5 AV node reentry tachycardias, 94

5.6 AV reentrant tachycardia, 103

6 Differential diagnosis of wide complex tachycardia, 127

v

vi Contents

7 Ventricular tachycardia and ventricular fibrillation, 132

7.1 Ventricular tachycardia in the presence of coronary artery disease, 1457.2 Arrhythmogenic right ventricular dysplasia/cardiomyopathy

7.6 Ventricular tachycardia in structurally normal heart, 183

7.7 Bundle branch reentry ventricular tachycardia, 190

7.8 Catecholaminergic polymorphic ventricular tachycardia, 194

7.9 Miscellaneous forms of ventricular arrhythmias, 197

8 Sudden cardiac death and risk stratification, 202

9 Cardiac arrhythmias in patients with neuro-muscular disorders, 214

10 Syncope, 218

11 Pharmacologic therapy of arrhythmias, 229

11.1 Pharmacologic principles as applied to antiarrhythmic drugs, 23011.2 Antiarrhythmic drugs, 234

11.3 Beta blockers, 239

11.4 Class III antiarrhythmic drugs, 240

11.5 Calcium channel blockers, 246

xiv List of Abbreviations

IKur Ultra rapid potassium current

INa Sodium current

IP3 Innositol triphosphate

IST Inappropriate sinus tachycardia

Ito Transient outward current

IVC Inferior vena cava

K Potassium

KvLQT1 Voltage dependent potassium

controlling protein

LA Left atrium

LAFB Left anterior fascicular block

LIPV Left inferior pulmonary vein

LOC Loss of consciousness

LQTS Long QT syndrome

LSPV Left superior pulmonary vein

LV Left ventricle

LVH Left ventricular hypertrophy

LVOT Left ventricular outflow tract

M Muscarinic

MHC Myosin heavy chain

MDP Maximum diastolic potential

PAC Premature atrial contractions

PCA Pulseless cardiac electrical activity

PES Programmed electrical

RV Right ventricle RVOT Right ventricular outflow tract SACT Sino atrial conduction time SAEKG Signal average ECG SAN Sino atrial node SCD Sudden cardiac death SCRC Sarcoplasmic Ca release

channel SND Sinus node dysfunction SNRT Sinus node recovery time

SR Sarcoplasmic reticulum SUR Sulfonylurea receptor SVC Superior vena cava SVT Supraventricular tachycardia

TA Tricuspid annulus TCL Tachycardia cycle length TDP Torsade de pointes TEE Trans-esophageal

echocardiography TIA Transient ischemic attack TWA T wave alternans ULV Upper limit of vulnerability

VA Ventriculo atrial

VF Ventricular fibrillation

VT Ventricular tachycardia WCT Wide complex tachycardia WPW Wolf Parkinson white

syndrome

2 Essential Cardiac Electrophysiology

4 How does congestive heart failure affect depolarizing/repolarizing currents?

A Outward repolarizing currents are reduced

B Inward depolarizing currents are reduced

C Outward repolarizing currents are increased

D APD is decreased

5 Which one of the following is least likely to occur with prolongation of the

plateau phase of the AP?

A Increase in strength of contraction

B Increase in conduction velocity

C Increase in the duration of contraction

D Increase in refractoriness

6 Which one of the following is likely to increase the activity of IKr?

A Increased extracellular potassium

B Exposure to Sotalol

C Decreased extracellular potassium

D Increase in chloride current

7 Which one of the following agents is likely to block IKs?

A Aminophylline

B Indapamide

C Activation of protein Kinase C

D Erythromycin

8 When does the reverse use dependent block occur?

A It occurs with repeated activation of the channel

B It occurs when the sodium channel is blocked

C It occurs at a slow heart rate but not at a fast heart rate

D It occurs in the presence of catecholamines

9 Which one of the following is the least likely attribute of Ito?

A It is present in ventricular epicardium but not in endocardium

B It is responsible for the spike and dome characteristic

C It is a chloride current

D It is also present in the human atrium

10 Which one of the following is associated with Brugada syndrome?

A Defect in the SCN5A gene

B Loss of IKr

C ST segment depression in precordial leads

D Deafness

Ions, Channels, and Currents 3

1 2 S O D I U M C H A N N E L S A N D C U R R E N T S

1 Which one of the following currents is likely to occur when the Na moves across

the cell membrane and into the cell?

A Inward current

B Outward current

C Repolarizing current

D No change in current

2 A patient receiving a Na channel blocker develops AF with rapid ventricular

response What changes on ECG can be anticipated to occur?

A Narrowing of the QRS complex during tachycardia

B Widening of the QRS complex during tachycardia

C Prolongation of the QT interval

D Shortening of the QT interval

3 What is likely to happen when a Na channel is blocked?

A Increase in intracellular Ca and increased contractility

B Increase in EAD and DAD

C Decrease in contractility

D Increase in extracellular Na

4 Which one of the following is not associated with Brugada syndrome?

A Mutation in SCN5A resulting in loss of function

B Increase in Itocurrent

C Inhibition of ICaduring the plateau phase

D Mutation in SCN5A, resulting in gain of function

5 What type of channel block, by lidocaine, results in effective suppression of

arrhythmias during myocardial ischemia?

A Inactivated state block

B Resting state block

C Open state block

D Closed state block

6 Which one of the following agents is likely to be effective in treating

4 Essential Cardiac Electrophysiology

7 Which one of the following metabolic abnormalities is likely to decrease

lidocaine dissociation from the channel sites?

D Depolarization of the SA and AV nodes

2 Which of the following statements is incorrect?

A β-Adrenergic agonists increase ICaLchannel activity

B β Blockers act as Ca channel blockers

C Parasympathetic stimulation decreases ICaLactivity

D T-type Ca channel density is increased by growth hormone, endothelin, and

Ions, Channels, and Currents 5

4 Which of the following statements for the sarcoplasmic Ca release channel

(SCRC) is incorrect?

A Caffeine releases Ca from SCRC

B Doxorubicin depletes sarcoplasmic reticulum Ca

C It is blocked by verapamil

D Ischemia decreases Ca release from the sarcoplasmic reticulum

5 Which of the following agents does not block Ca channel?

A Terfenadine

B Magnesium

C Diltiazem

D Sotalol

6 Which of the following statements is incorrect?

A ICaLparticipates in the occurrence of DAD

B Phase-3 EAD shares the mechanisms of DAD

C EAD is associated with bradycardia and prolongation of APD

D DAD is associated with increased heart rate and Ca overload

Ions, Channels, and Currents 7

Fig 1.1 Outward currents.

• K channels carry a positive charge, which acts as a voltage sensor

• Potassium channels are closed at resting potential and open afterdepolarization

• Two types of voltage-gated channels play a major role in repolarization

i Transient outward current (Ito), which is characterized by rapid activation

and inactivation

ii Delayed rectifier IK, which has several components (Fig 1.1):

• IKris a rapidly activating current with inward rectification

• IKsis a slowly activating current

• IKpis a time independent background plateau current

• IKuris an ultra rapid current

Transient outward potassium current(Ito)5

• There are two types of Itocurrents: Ito1and Ito2

• Itois present in ventricular epicardium but not in endocardium It is responsiblefor spike and dome morphology of AP in epicardium

• In human atrium it recovers rapidly from inactivation, thus allowing rapidrepolarization at a fast heart rate

• Flecainide, Quinidine, and Ambasilide inhibit Ito Flecainide binds to inactivated

Ito1 It also demonstrates fast unbinding Quinidine binds to open channel; itsslow recovery from block causes a rate dependent effect

• Inhibition of Itoprolongs repolarization in diseased human ventricle

• Ito2is calcium activated

8 Essential Cardiac Electrophysiology

Rapidly activating delayed rectifierIKr

• It is blocked by methane sulfonamide, class III agents (D-Sotalol)

• Inward rectification of IKrresults in a small outward current

• It plays an important role in atrial pacemaker cells It rapidly recovers frominactivation and it peaks at−40 mV

• KCNH2 (HERG, Human Ether Related-a-go-go gene protein) encodes IKr

• The effect of IKsbut not of IKris enhanced byβ-adrenergic stimulation Thus,

the effects of pure IKrblockers will be antagonized by sympathetic stimulation

• Selective IKr blockers (D-Sotalol) lose efficiency at high rates and duringsympathetic stimulation

• IKrand IKsare present in the human atrium and ventricle

Slowly activating delayed rectifierIKs

• IKsis controlled by the gene KvLQT1 (voltage-dependent potassium controllingprotein) and MinK (minimal potassium current controlling protein) MinK com-

bined with protein of KvLQT1 induces IKs Expression of both these proteins is

necessary for normal function of IKs1

• MinK, a protein, acts as a function altering β subunit of KvLQT1 MinK modifies

KvLQT1 gating and pharmacology

• Mutation in MinK and KvLQT1 causes congenital long QT syndrome(LQTS)

• MinK suppression leads to inner ear abnormalities and deafness, seen in theJarvell Lange-Nielson syndrome

• Reduced activity of IKsin M cells prolongs APD

• Bradycardia and class III drugs, which reduce IKsin M cells, prolong APD andpredispose to arrhythmias

• Slow deactivation of IKs is important for rate dependent shortening of

AP As the heart rate increases, IKs has less time to deactivate duringshortened diastole, it accumulates in an open state, and contributes to fasterrepolarization

• Increase in intracellular magnesium decreases and increase in intracellular

calcium increases IKs

Ions, Channels, and Currents 9

• Indapamide (Diuretic), Thiopental, Propafol (Anesthetics) Benzodiazepine, and

• It is responsible for atrial repolarization It is a potassium selective outwardly

rectifying current Short APD of the atria is due to IKur

• IKuris also found in intercalated disks

• IKuris absent from the human ventricular myocardium

• It is enhanced by β-adrenergic agonists and is inhibited by α-adrenergic agonists.

• Drugs inhibiting IKs (Amiodarone, Ambasilide) or IKur (Ambasilide) will betherapeutically superior

• The presence of IKurin the human atrium makes atrial repolarization relativelyinsensitive to agents that fail to inhibit this current (D-Sotalol and Flecainide)

Quinidine and Ambasilide block IKurin a rate independent fashion

• IKurdecreases with increasing heart rate

Inwardly rectifying currents

• Intracellular magnesium, calcium, and polyamines block IK1 Increase in

intra-cellular pH inactivates IK1 Increase in extracellular potassium depolarizes theresting membrane

• Inwardly rectifying potassium channels (K1) produce less outward currents thaninward currents They stabilize the resting membrane potential by high rest-ing potassium conductance, but during depolarization produce little outwardcurrent

ATP sensitive potassium channel (Katp) 6,7

• Katpchannel opens when the intracellular ATP level falls and closes when theATP levels rise ATP produced by the glycolytic pathway is preferentially sensed

by the Katpchannel

• IKatp is a weak inward rectifier but produces a large outward current duringdepolarization and its activation decreases APD

10 Essential Cardiac Electrophysiology

• It is responsible for ischemia preconditioning where brief episodes of ischemiaprotect the myocardium from prolonged episodes of ischemia

• During ischemia, intracellular magnesium and sodium levels increase, IKatp

current decreases, and extracellular potassium increases

• Protons, lactates, oxygen free radicals, adenosine, and muscarinic receptorstimulation desensitize the Katpchannel to the effects of the ATP level

• Sodium and potassium pump and other ATPases degrade ATP

• Cromakalim, Bimakalim, Aprikalim, Nicorandil, Adenosine, and protein kinase

C open the Katp channel and mimic preconditioning Sulfonylureas such asGlipizide and Tolbutamide block Katpand abolish preconditioning

• During ischemia there is loss of intracellular potassium and increase in cellular potassium resulting in membrane depolarization, slow conduction,and altered refractoriness resulting in reentrant arrhythmias Katpcounteractsthese effects by shortening APD, decreasing workload, promoting inexcitability,and increasing potassium conductance during ischemia and hypoxia Increasedpotassium conductance is a result of an increased level of intracellular sodiumthat occurs during ischemia

extra-• IKatpdecreases APD and calcium influx It preserves high-energy phosphates

• Diazoxide does not activate IKatp in sarcolemma but mimics preconditioning.This suggests that there may be other pathways involved in preconditioning

• IKatpcauses coronary vasodilatation

IKach (Acetylcholine-dependent K current)

• Stimulation of muscarinic receptors activates this current It is mediated by

acetylcholine IKachis inwardly rectifying potassium current

• Parasympathetic stimulation slows heart rate by activating muscarinic

recept-ors, which reduces If (hyperpolarizing cation current; f stands for funny) inpacemaker cells

• The effect of potassium channel blockers on atrial repolarization depends on

their ability to counteract cholinergic activation of IKach, either by direct blocking

of the channel (Quinidine) or by muscarinic receptor antagonism (Ambasilide,Disopyramide)

• These currents contribute to repolarization and resting membrane potential

• These currents are inhibited by decreasing intracellular pH

• Arachidonic acid and polyunsaturated fatty acids modulate these channels

Characteristics of potassium channel block 5,8,9

• Voltage gated potassium channels are activated during upstroke of AP

• Rapidly activating and inactivating voltage sensitive transient outward currentproduces phase 1 of repolarization