Electrophysiology Lecture 2 -- Mechanisms of arrhythmia

Question 1

Define bradycardia

Answer 1

HR <60 bpm

Question 2

Define tachycardia

Answer 2

HR >100 bpm

Question 3

2 examples of physiologic arrhythmias

Answer 3

Sinus bradycardia in a trained athlete Sinus tachycardia during exercise

Question 4

Two types of pathologic arrhythmias

Answer 4

Ectopic complexes (ectopic beats) Ectopic tachycardias

Question 5

Definition of ectopic complex

Answer 5

A beat that arises from a site other than the sinus node (may be atrial, AV nodal/junctional, or ventricular)

Question 6

2 types of premature ectopic complexes

Answer 6

Premature atrial ectopic complexes/beats (PACs, APCs, APBs) Premature ventricular ectopic complexes/beats (PVCs, VPCs, VPBs)

Question 7

Location of ectopic tachycardias

Answer 7

Arise from a site other than the sinus node (in atrium or ventricles)

Question 8

4 types of ectopic tachycardias

Answer 8

Paroxysmal Nonparoxysmal Sustained Nonsustained

Question 9

Define a paroxysmal ectopic tachycardia

Answer 9

Start and stop abruptly, usually by initiating or terminating factor

Question 10

Define a nonparoxysmal ectopic tachycardia

Answer 10

Present constantly, tend to appear or disappear by gradual changes in rate

Question 11

Define a sustained ectopic tachycardia

Answer 11

Continuing for prolonged period or until stopped by an intervention

Question 12

Define a nonsustained ectopic tachycardia

Answer 12

Terminating spontaneously

Question 13

Most common types of ectopic tachycardia

Answer 13

Ventricular tachycardia (VT) Paroxysmal atrial tachycardia (PAT)

Question 14

2 types of automaticity in pathologic arrhythmias + subgroups

Answer 14

Enhances Abnormal forms – Early Afterdepolarizations – Delayed afterdepolarizations

Question 15

3 ways automaticity can be enhanced

Answer 15

Less negative diastolic potential (closer to threshold) Steeper slope of phase 4 More negative threshold (closer to max diastolic potential)

Question 16

2 ways of suppressing enhanced automaticity

Answer 16

Make threshold potential more positive Antagonize components that enhance automaticity

Question 17

Example of how to make the threshold potential more positive

Answer 17

Suppress: - current needed to fire cell during phase 0 - Ca++ current in SA/VA nodes - Na+ current in HP system

Question 18

Example of how to antagonize compound that enhance automaticity

Answer 18

Beta blockers in situations where beta-adrenergic stimulation contributes to enhanced automaticity

Question 19

AP curve of early afterdepolarizations

Answer 19

Question 20

AP curve of delayed afterdepolarizations

Answer 20

Question 21

How does an early afterdepolarizatoin occur?

Answer 21

When the action potential has been parkedly prolonged, causing Ca++ current to depolarize cell.

Question 22

Around what phase does an early afterdepolarization occur?

Answer 22

On the plateau phase (2) of the action potential (before full repolarization)

Question 23

Potential consequence of early afterdepolarization

Answer 23

Ventricular tachycardia, often with characteristic ECG appearance (“Torsades de Pointes”)

Question 24

Define Torsades de Pointes

Answer 24

ECG appearance characteristic of EAD-induced VT, which is a rapid VT with alternation of the points of the QRS

Question 25

3 common factors that cause EAD-induced arrhythmias

Answer 25

Factors that increase APD: * Certain antiarrhythmic drugs that block K+ channels involved in repolarization * Slow heart rate * Hypokalemia (low EC K+)

Question 26

What largely determines the QT interval on a ECG

Answer 26

Ventricular APD

Question 27

Common ECG association to EAD-Induced afterdepolarizations

Answer 27

Marked QT prolongation ("long QT syndrome")

Question 28

3 ways to treat EAD-induced arrhythmias

Answer 28

* Eliminate reversible factors (i.e. drug therapy) that may be causative or contributory * Treat hypokalemia if present * Increase HR (i.e. electrical pacemaker or isoproterenol)

Question 29

Cause of delayed afterdepolarizations (DAD)

Answer 29

Cellular calcium overload in fast channel tissues --\> diastolic spillover of Ca++ from SR release channels (ryanodine receptors)

Question 30

What causes ryanodine (RyR2) receptors to open?

Answer 30

High intra-SR Ca++ concentrations

Question 31

What are two pathological situations where RyR2 is hypersensitive to intra-SR Ca++?

Answer 31

CHF Come RyR2 mutations

Question 32

Define a premature beat

Answer 32

Premature activation of an action potential if an afterdepolarization reaches threshold

Question 33

When can DAD's cause a tachycardia?

Answer 33

A series of afterdepolarizations which reach a threshold

Question 34

4 factors enhancing DAD's and how they contribute to the problem

Answer 34

* Increase HR, premature complexes (increase intracellular Ca++) * Hypercalcemia (increase intracellular Ca++) * Catecholamines (increase intracellular Ca++, increase RyR2 sensitivity to Ca++) * Mutations of RyR2 --\> hypersentivity to Ca++

Question 35

2 ways to treat DAD-induced arrhythmias

Answer 35

* Eliminate reversible contributory or causative factors * Various drugs can reduce DAD's

Question 36

Purpose of Ca++ antagonists for DAD-induced arrhythmia

Answer 36

Reduce calcium entry during each action potential (may be problematic with negative inotropy)

Question 37

What is the importance of re-entrant cardiac arrhythmias

Answer 37

Cause of many important cardiac arrhythmias, including many that are implicated in sudden cardiac death

Question 38

2 examples of drugs that can reduce DAD's

Answer 38

Ca++ antagonists (i.e. verapamil) Na+ channel blockers (i.e. lidocaine, quinidine)

Question 39

Purpose of Na+ channel blockers for DAD-induced arrhythmias

Answer 39

Make threshold potential more positive, so harder for DAD to reach threshold

Question 40

Diagram of normal activation of cardiac rhythm

Answer 40

Question 41

Diagram of re-entrant cardiac arrhythmia

Answer 41

Question 42

Where can re-entrant arrhythmias occur?

Answer 42

Anywhere in the heart provided there are two pathways connected proximally (X) and distally (Y) Also, anywhere with fibers interconnected at more than one point

Question 43

Where is a common anatomic arrangement for reentrant arrhythmias?

Answer 43

AV node (there can be 2 distinct alternative conduction pathways)

Question 44

Necessary impulse condition for a reentrant arrhythmia to occur

Answer 44

Impulse must first arrive from X at a time when one pathway (B) is still refractory, but the other (A) has recovered excitability

Question 45

Why is a premature beat much more likely than a sinus beat to encounter refractoriness in a pathway conducive to reetrant arrhythmia?

Answer 45

Refractory period is usually over wel before the next expected sinus beat

Question 46

Why is timing crucial for a reentrant arrhythmia to occur?

Answer 46

If the premature beat arrives too early, both A and B will be refractory

Question 47

Impulse pathway if the distal end of pathway B has recovered excitability

Answer 47

Can travel retrogradely over pathway B --\> arrive at proximal end of pathway A

Question 48

Impulse pathway is the proximal end of pathway A has recovered excitability after retrogradely flowing through B

Answer 48

Propagation antegradely down pathway A

Question 49

How can one premature impulse initiate a self-sustaining tachycardia?

Answer 49

If reetrance can be sustained; distal end of B and proximal end of A always regain excitability when the reentrant impulse reaches them

Question 50

3 conditions necessary for reentrance

Answer 50

* Premature beats * Differences in refractoriness between alternate pathways * Conduction which is slow enough so that the reentrant impulse never encounters refractory tissue (would be blocked)

Question 51

Equation for the time to complete one circuit of the reetrant pathway

Answer 51

T = L/V where: * T = time * L = total length of reetrant pathway * V = conduction velocity

Question 52

Time condition for successful sustained reentry

Answer 52

T \> RP (L/V \> RP) Circuit time has to be longer than the longest refractory period

Question 53

Consequence of the circuit time not being longer than the longest refractory period

Answer 53

The impulse would leave the area of greatest refractoriness and return to it before excitability is restored

Question 54

How can reentrant arrhythmias be terminated or prevented?

Answer 54

Increasing the refractory period so that it exceeds conduction time (short refractoriness increases re-entrant likelihood)

Question 55

Effect of conduction on reentrant arrhythmia likelihood

Answer 55

Fast conduction (V large) makes reentry less likely Slow conduction facilitates reentry (EXCEPT when sufficient to completely block conduction in reentry circuit)