Cardiac electrophysiology and ECG1

Question 1

What are the main characteristics of cardiac electrical activation?

Answer 1

1. Automaticity: cardiac muscle tissue contracts without neural stimulation
2. Absence of tetany: after contracting, the heart must relax to fill up again. Sustained contraction of the heart without relaxation would be fatal, and this is prevented by a temporary inactivation of certain ion channels
3. Substantial atrial to ventricular delay: this allows the atria to completely empty their contents into the ventricles; simultaneous contraction would cause inefficient filling and backflow.
4. Coordinated contraction of ventricular cells: the ventricles must maximize systolic pressure to force blood through the circulation, so all the ventricular cells must work together
5. Rapid depolarization propagation: cells of the ventricles contract nearly simultaneously
6. Long action potential. This prevents premature relaxation, maintaining initial contraction until the entire myocardium has had time to depolarize and contract

Question 2

What does the cardiac conduction system enable?

Answer 2

A fast and co-ordinated contraction of the heart.

Question 3

What pathway does the normal electrical conduction through the heart muscle take?

Answer 3

A predicted pathway. It travels from the Sinoatrial node (SA node) to the Atrioventricular node (AV node) to the Bundle of His and then onto the left and right bundle branches (usually in a left to right pattern), ultimately ending up in the Purkinje fibers. that reach the ventricular wall. The cardiac pacemaker cells in the sinoatrial node are characterised by spontaneous depolarisation during the resting phase 4 mediated by Na+ and K+ entry into the cells via the If current through the hyperpolarisation-activated cyclic nucleotide gated (HCN) channels.

Question 4

What is the cardiac conduction system composed of?

Answer 4

It is composed of specialized cardiac structures that are responsible for impulse formation and propagation.

Question 5

The cardiac electrical activation is the result of what?

Answer 5

Voltage shifts across the cell membrane coordinated by multiple transmembrane proteins (ion channels), each regulating inward or outward electrical currents that determine the duration and electrophysiological properties of the cardiac action potential (AP).

The AP reflects the processes of depolarisation (linked to myocardial excitation) and repolarisation (linked to subsequent relaxation), which are reflected on the surface ECG, and is divided into phases.

Question 6

What does the cardiac action potential (AP) reflect?

Answer 6

The processes of depolarisation (linked to myocardial excitation) and repolarisation (linked to subsequent relaxation), which are reflected on the surface ECG, and is divided into phases.

Question 7

What is fundamental to maintain the cells’ negative resting potential at approximately -90mV?

Answer 7

The Na+/K+-ATPase pump

Question 8

What is involved in the excitation-contraction coupling and relaxation of cardiac cells?

Answer 8

The sodium/calcium (Na+/Ca++) exchanger

Question 9

What channels regulate the cardiac AP phases?

Answer 9

The voltage-gated (Na+), potassium (K+) and L-Type calcium (Ca++)

Question 10

Define phase 0 and 1 of the cardiac conduction system.

Answer 10

The ventricular myocytes show a rapid upstroke of the AP (phase 0) determined by a large positive inward current through voltage-gated Na+ channels (INa), triggered by a threshold voltage of about -75 mV (e.g. caused by an adjacent cell depolarisation AP), and is followed by a transient repolarisation (phase 1) reflecting the Na+ channel inactivation, together with the activation of the voltage-gated transient outward K+ currents (Ito).

This transient repolarisation “notch” influences the height and duration of the plateau phase (phase 2), which is modulated by the balance between inward Ca++ (ICa), predominant, and Na +currents, and outward K+ currents.

Question 11

Define phase 2 of the cardiac conduction system.

Answer 11

This transient repolarisation “notch” influences the height and duration of the plateau phase (phase 2), which is modulated by the balance between inward Ca++ (ICa), predominant, and Na +currents, and outward K+ currents.

Question 12

Define phase 3 of the cardiac conduction system.

Answer 12

When the L-type Ca++ channels undergo voltage-dependent inactivation, the K+ currents prevail (IKr, IKs) and a second repolarisation phase (phase 3) occurs.

Question 13

During phases 0-3 and early phase 4, no new AP can be initiated as the fast Na+ channels are still inactive (absolute refractory period, ARP).

True or false

Answer 13

True

Question 14

After the absolute refractory period (ARP) only…

Answer 14

Impulses that exceed the threshold can cause re-excitation (relative refractory period, RRR), until the cell is completely repolarised and ready for a new excitation.

Question 15

What does the the absolute refractory period (ARP) prevent?

Answer 15

Multiple, compounded action potentials from occurring (i.e., it limits the frequency of depolarisation and therefore the heart rate), allowing adequate cardiac filling and reducing the risk of arrythmia occurring.

Question 16

What does the surface ECG reflect?

Answer 16

The phases of the cardiac AP in the different regions of the heart.

The P wave represents the atrial depolarisation; the PR interval reflects the conduction velocity through the A-V node; the QRS complex reflects the ventricular depolarisation, while the QT interval represents the duration of the ventricular AP. The J point, the end of the QRS complex, occurs during phase 1 of the AP i.e. the notch at the beginning of the AP plateau.

Question 17

What is an ECG?

Answer 17

a graph of voltage versus time of the electrical activity of the heart, obtained using electrodes placed on the skin that can detect the sum of all cardiac cells depolarizations and repolarizations.

Question 18

What does an ECG convey?

Answer 18

The ECG conveys a large amount of information about the structure of the heart and the function of its electrical conduction system.

Question 19

Among other things, an ECG can be used to measure what?

Answer 19

The rate and rhythm of heartbeats, the size and position of the heart chambers, the presence of any damage to the heart’s muscle cells or conduction system, the effects of heart drugs, and the function of implanted pacemakers

Question 20

When can ECGs be recorded?

Answer 20

At rest, during exercise, for one day or several days.

Question 21

Why and how is an EP study performed?

Answer 21

To study more in detail the conduction system of the heart.

It’s performed via a right-sided cardiac catheterization: a wire with an electrode at its tip is inserted into the right heart chambers from a peripheral vein, and placed in various positions in close proximity to the conduction system

Question 22

What does the intracardiac Electrograms (EGM) record?

Answer 22

The electrical activity at a localized area between two electrodes on a catheter

Question 23

What are the benefits and disadvantages of an ECG?

Answer 23

Benefits:
Accurate measurement of cardiac conduction

Can locate area of disease

Can help diagnose arrhythmias that cant be identified noninvasively

Can be used to estimate risk of future cardiac arrest in certain diseased

Disadvantages:

Invasive

Risk of complications

Question 24

What is presented on a normal ECG?

Answer 24

Sinus rhythm
Heart rate between 60 - 100 beats per minute

P wave positive in lead II, negative in aVR , ≤ 0.11 s
PR interval between 0.12 and 0.20 s

QRS complex ≤ 0.12 s, amplitude greater than 0.5 mV in at least one standard lead, and greater than 1.0 mV in at least one precordial lead.

Proceeding from V1 to V6, the R waves get taller while the S waves get smaller

ST segment isoelectric, can be slightly elevated (up to 2.0 mm in some precordial leads BUT never normally depressed greater than 0.5 mm

T wave same direction as the QRS complex
QT interval ≤ 0.40 s in males, 0.44 s in females

Question 25

What are conduction disorders?

Answer 25

Abnormalities in the electrical system affecting the heart rate/rhythm:
the cardiac electrical signal either does not generate properly, or it does not travel properly through the heart, or both.

They can occur in both structurally normal hearts and abnormal hearts (i.e. partial or total absence of structures, gradual replacement by fatty and/or fibrous infiltration and calcification)

Question 26

What are acquired causes of conduction disorders?

Answer 26

electrolyte problems
hypothermia
drugs
ischemic heart disease
degenerative heart disease
infiltrative heart disease
infections

Question 27

What are congenital causes of conduction disorders?

Answer 27

damages during foetal development(i.e. infections, toxic agents)

autoimmune disease (myocarditis, vasculitis)

inheritable genetic defects

Question 28

What are sites in which conduction disorders occur?

Answer 28

Sino-atrial node results in Sick sinus syndrome

Atrio-ventricular node results in A-V block

Bundle branches results in Left or right bundle branch block

Ion channel disease, all sites can have issues

Question 29

What are ECG manifestations of Sino-atrial node?

Answer 29

irregular P waves cycle that can determine sinus bradycardia, sino-atrial block, brady-tachy alternans, sinus arrest

Question 30

What are ECG manifestations of Atrio-ventricular node?

Answer 30

A-V block which can be characterised by increased PR interval or no correspondence between P and QRS

Question 31

What are ECG manifestations of Bundle branches?

Answer 31

Left or right bundle branch block. This is characterised by broad QRS and axis deviation.

Question 32

Hyperkalaemia is an important acquired cause of conduction disease.

How is it defined?

Answer 32

Increased extracellular potassium reduces myocardial excitability, with depression of pacemaker and conducting activity. From mild repolarization abnormalities (peaked T waves), to progressive paralysis of the atria, conduction abnormalities and bradycardia, cardiac arrest

Question 33

Ischemia is an important acquired cause of conduction disease.

How is it defined?

Answer 33

Conduction defects at any level of the conduction system:
RCA : Sinus bradycardia, A-V blocks (often reversible)
LCA : A-V blocks with wide QRS, cardiac arrest

Question 34

Congenital/inheritable cardiac conditions can cause conduction defects in the heart. They are defined in what two categories?

Answer 34

1. Cardiomyopathies

Hypertrophic cardiomyopathy, non-ischemic dilated cardiomyopathy, arrhythmogenic cardiomyopathy

Scarring within the myocardium can damage conduction tissue

Conduction abnormalities can be seen on the ECG before any structural changes are visible on cardiac imaging

2. Primary arrhythmia syndromes : Brugada Syndrome

Autosomal dominant condition linked to loss-of-function SCN5A gene mutations

Significant cause of autopsy negative sudden death

Diagnostic ECG pattern (Type 1 Brugada pattern) – spontaneous or concealed (unmasked after drug provocation with Class 1 antiarrhythmic agents given intravenously)

Requires ECG placement in “high precordial position”
to better explore the right ventricular outflow tract

Question 35

What is Ajmaline?

Answer 35

antiarrhythmic agent

Question 36

What is Premature Cardiac Conduction Disease (PCCD)?

Answer 36

Primary arrhythmia syndrome

Conduction disease is common with advancing age and in the presence of cardiac structural abnormalities – when present in isolation an ion channel disorder should be suspected (Na++ channel disorders)

Sinus node disease – absence of P waves

Atrioventricular node disease - varying degrees of A-V block

Intraventricular conduction delay (BBB, axis deviation)

Question 37

What is Long QT Sydrome (LQTS)?

Answer 37

Primary arrhythmia syndrome

Due to loss of function mutation in K+ channel (LQTS1-2)

Affects flow of K+ out of the cell (delay in action potential returning to baseline)

Rarer forms include gain of function mutation in Na++ channels and loss of function in Ca++ channels

Resting ECG may show normal QT interval

Exercise ECG often shows paradoxical prolongation
Increased risk of ventricular arrhythmias

Question 38

What can the three Long QT Sydrome (LQTS) types be treated with?

Answer 38

LQTS1 and 2- beta blockers

LQTS3- Flecainide and Mexilitine

Question 39

What is Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?

Answer 39

Primary arrhythmia syndrome

Most commonly results from mutations in two genes, RYR2 and CASQ2, causing disruption in the handling of calcium within myocytes.

Affected individuals develop life threatening arrhythmia in response to adrenaline - activity or stress

Can result in recurrent collapse during exercise

Surface ECG is normal

Exercise ECG or epinephrine provoked ECG are the testing modalities of choice. The former is more specific for CPVT than epinephrine

Bidirectional ventricular extra systole DURING exercise is a diagnostic feature

Question 40

The cardiac conduction system is composed of structures that are responsible for impulse formation and propagation

True or false

Answer 40

False

The cardiac conduction system is composed of specialized cardiac structures that are responsible for impulse formation and propagation

Question 41

The cardiac electrical activation is the result of voltage shifts across the cell membrane coordinated by multiple transmembrane proteins (ion channels)

True or false

Answer 41

True

Question 42

Acquired/congenital cardiac conditions cannot affect the cardiac electrical activation at different sites of the conduction system and cause symptoms and/or increase susceptibility to life-threatening arrhythmias

True or false

Answer 42

False

Acquired/congenital cardiac conditions can affect the cardiac electrical activation at different sites of the conduction system and cause symptoms and/or increase susceptibility to life-threatening arrhythmias

Question 43

The electrocardiogram (ECG) recording reflects the cardiac electrical activity and is fundamental to diagnose electrical or suspect structural disorders affecting the cardiac activation and conduction

True or false

Answer 43

True

Question 44

What is the first part of the cardiac cycle is called?

Answer 44

Atrial depolarization

Question 45

At what rate does the paper move through an ECG machine?

Answer 45

25 mm/s.

Question 46

What distance across ECG paper represents 1.0 seconds?

Answer 46

5 large squares

Question 47

What is the normal duration of a QRS complex?

Answer 47

0.12s (3 small squares)

Question 48

If there were 3 large squares in an R-R interval what would the heart rate be?

Why?

Answer 48

100bpm

To calculate heart rate from an ECG you can count the number of large squares in an R-R interval then divide 300 by this number. Therefore 300/3 = 100 bpm.