B P7 C62 Mechanisms of Cardiac Arrhythmias

Question 1

Cardiac cells normally have a negative intracellular resting potential, which for most of the heart (working atrial and ventricular muscle, specialized His-Purkinje conducting system) is about __________

Answer 1

−80 to −90 mV

Question 2

RMP of sinoatrial (SA) and central AV (AV) node regions

Answer 2

−50 and −65 mV

Question 3

The cardiac AP is by convention divided into four phases, the_____.

Answer 3

Phase 0: AP-upstroke, which depolarizes the cell from its negative resting potential to a potential positive to 0 mV;

Phase 1: the initial rapid repolarization phase;

Phase 2: the so-called plateau, in which the AP voltage changes relatively slowly;

Phase 3: the final rapid repolarization phase, which brings the cell back to its resting potential

Phase 4: Resting potential

Question 4

Phase 0 happens when there is a rapid increase in membrane permeability to _______ , and K + permeability falls, making Na + the dominant conductance

Answer 4

Na+

At the peak of phase 0 (the “overshoot”), the cell moves close to the Na + equilibrium potential, which is quite positive because in contrast to K+ , Na + is more concentrated outside the cell than inside and the Na + chemical force makes it move into the cell, making the interior more positive.

Question 5

Phase ____ is carried by a transient, rapid exit of K +from the cell.

Answer 5

Phase 1

Question 6

____________ is the portion of the AP during which Ca 2+ enters the cell and causes a large secondary release of Ca 2+ from the sarcoplasmic reticulum (SR), the main cellular Ca2+ -storage organelle. The SR Ca2+ -release rapidly increases free intracellular [Ca2+ ], which causes cellular contraction and mediates electromechanical coupling.

Answer 6

Phase 2

During phase 2, the transmembrane potential is governed by balanced permeabilities to Ca 2+and K+,

Question 7

Phase ______, a rapid increase in K + permeability offsets the decreasing Ca 2+ conductance and repolarizes the cell.

Answer 7

Phase 3

Finally, phase 3 (carried by a rapid egress of K+ ) brings the cell back to its negative resting potential. Because the cell cannot be activated by normal means at voltages positive to −60 mV, from when the cell reaches −60 mV during phase 0 until the time that it repolarizes to −60 mV during phase 3 the cell cannot be fired and is “refractory” to activation.Thus, the timing of phase 3 sets the refractory period (RP)

Question 8

Finally, phase 3 (carried by a rapid egress of K+) brings the cell back to its negative resting poten- tial.

Because the cell cannot be activated by normal means at voltages positive to −60 mV, from when the cell reaches −60 mV during phase 0 until the time that it repolarizes to −60 mV during phase 3 the cell cannot be fired and is “refractory” to activation. Thus,the timing of phase 3 sets the _____ period

Answer 8

Refractory period (RP)

Question 9

The _____ ions are the major charge carriers, and their movement across the cell membrane through channel pores creates a flow of current that generates excitation and signals in cardiac myocytes

Answer 9

Sodium, potassium, calcium, and chloride (Na+, K+, Ca2+, and Cl−)

Question 10

Functions of the Cardiac Electrical System

Answer 10

To initiate rhythmic contraction at a rate appropriate to the needs of the body

To ensure appropriate timing of contraction for each cardiac chamber

To prevent heart rates that are excessively slow or rapid for the body’s needs

Question 11

Equilibrium is created when the chemical force tending to push K+ out of the cell is balanced by an equal and opposite electrical force created by the net intracellular negative charge tending to pull the K+ back into the cell. The voltage at which these forces balance is called the _____

Answer 11

Equilibrium potential

Question 12

In the case of K+, the equilibrium potential is given by the Nernst equation _____, where R is the universal gas constant, T = absolute temperature, F = Faraday’s constant, and [K+o], [K+i] = extracellular and intracellular K+ concentration, respectively.

This value, designated “EK” for K+ equilibrium potential, is about −__ mV

Answer 12

(E = RT/F·ln([K+o]/[K+i])

-95 mV

Question 13

The _____ ratio is commonly used to define a channel’s ionic selectivity, defined as the ratio of the permeability of one ion type to that of the main permeant ion type.

Answer 13

Permeability ratio

Question 14

Spindle-shaped structure composed of a fibrous tissue matrix containing closely packed cells. In man, it is 10 to 20 mm long and 2 to 3 mm wide, narrowing caudally toward the inferior vena cava (IVC).

Answer 14

SA node

The SA node is superficial, lying less than 1 mm from the epicardial surface, laterally in the RA sulcus terminalis at the junction of the superior vena cava (SVC) and right atrium

Question 15

Resting potential (mV)

Answer 15

SA node: -50 to -60
AV nodal cell: -60 to -70

Atrial myocyte: -80 to -90
His Purkinje cell: -90 to -95
Ventricular myocyte: -80 to -90

Question 16

_____ are the proteins that form the intercellular channels of gap junctions.

Answer 16

Connexins

Question 17

_____, a 43-kDa polypeptide, is the most abundant cardiac connexin in heart cells, with connexins 40 and 45 being found in smaller amounts

Answer 17

Connexin 43

Question 18

Ventricular muscle expresses connexins _____, whereas atrial muscle and the specialized conduction system express connexins _____.

Answer 18

Ventricular muscle: 43 and 45

Atrial muscle/specialized conduction system: 40, 43, 45

Question 19

Alterations in the distribution and function of cardiac gap junctions are associated with increased susceptibility to arrhythmias.

Conduction slowing and arrhythmogenesis have been associated with redistribution of connexin 43 (Cx43) gap junctions from the end of cardiomyocytes to the _____ borders and with decreased phosphorylation of Cx43 in a dog model of nonischemic dilated cardiomyopathy

Answer 19

Lateral borders

Question 20

Artery supplying the SA node in 55-60% of cases

Answer 20

RCA

The artery supplying the SAN branches from the right (55% to 60% of the time) or the left (40% to 45%) circumflex coronary artery and approaches the node around the junction of the SVC and right atrium

Question 21

The artery supplying the SAN branches from the _____ and approaches the node around the junction of the SVC and right atrium

Answer 21

RCA (55% to 60%)

or

LCx (40% to 45%)

Question 22

The proximity to the _____ nerve is an important consideration when catheter ablation or modification of the sinoatrial node (SAN) is contemplated.

Answer 22

Right phrenic nerve

Question 23

Sinoatrial node (SAN) artery variations in the arterial supply of the sinus node.

The SAN blood supply originates from a single coronary artery in __% of cases and from both coronary arteries in __%

Answer 23

Single CA: 96%
Both CA: 4%

R anterior atrial artery: 64%
L anterior atrial artery: 22%
L lateral atrial artery: 8%
R lateral atrial artery: 2%

Question 24

If the origin is from the _____coronary artery, the nodal artery crosses the roof or the anterior wall of the left atrium.

Answer 24

Left coronary artery

Question 25

Anatomic landmarks of the triangle of Koch

Answer 25

Superior: Tendon of Todaro Inferior: Attachment of the septal leaflet of the TV Base: mouth of the coronary sinus

Question 26

The normal AV junctional area is composed of multiple distinct structures, including transitional tissue, inferior nodal extension (INE), compact portion, penetrating bundle, His bundle, atrial and ventricular muscle, central fibrous body, tendon of Todaro, and valves At the level of the AV junction, the tract of nodal tissue is divided into two major components, the ______ and the ____________

Answer 26

INE Penetrating bundle

Question 27

The ________ is continuous with the penetrating bundle, which penetrates the fibrous tissue separating the atria and ventricles and emerges in the ventricles as the bundle of His. Both structures are covered by connective tissue and are therefore enclosed.

Answer 27

INE

Question 28

The ____________ is a superficial structure lying just beneath the right atrial endocardium, anterior to the ostium of the coronary sinus, and directly above the insertion of the septal leaflet of the tricuspid valve. It is at the apex of a triangle formed by the tricuspid annulus and the tendon of Todaro, which originates in the central fibrous body and passes posteriorly through the atrial septum to continue with the Eustachian valve.

Answer 28

Compact portion of the AV node

Question 29

In 85% to 90% of human hearts, the arterial supply to the AV node is derived from a branch of the _______________ that originates at the posterior intersection of the AV and interventricular grooves (crux). A branch of the circumflex coronary artery provides the arterial supply to the AV node in the remaining hearts

Answer 29

RCA

Question 30

This structure is the continuation of the penetrating bundle on the ventricular side of the AV junction before it divides to form the left and right bundles

Answer 30

Bundle of His Branches from the **anterior and posterior descending coronary arteries supply the upper muscular interventricular septum** with blood, which makes the conduction system at this site more impervious to ischemic damage unless the ischemia is extensive.

Question 31

Branches from the _____coronary arteries supply the upper muscular interventricular septum with blood, which makes the conduction system at this site more impervious to ischemic damage unless the ischemia is extensive.

Answer 31

Anterior and posterior descending coronary arteries

Question 32

The bundle branches begin at the superior margin of the muscular interventricular septum, immediately beneath the membranous septum, with cells of the ______ bundle branch cascading downward as a continuous sheet onto the septum beneath the noncoronary aortic cusp

Answer 32

Left bundle branch (LBB)

Question 33

The _______________ continues intamyocardially as an unbranched extension of the AV bundle down the right side of the interventricular septum to the apex of the right ventricle

Answer 33

Right bundle branch

Question 34

The __________________ connect with the ends of the bundle branches to form interweaving networks on the endocardial surface of both ventricles and transmit the cardiac impulse almost simultaneously to the right and left ventricular endocardium.

Answer 34

Purkinje fibers APs propagate within the thin Purkinje fiber bundles from the **base to the apex** before activating surrounding myocytes. Purkinje myocytes have less well-developed transverse tubules which reduces membrane capacitance and thus accelerates AP propagation.

Question 35

In humans, Purkinje fibers penetrate only the _____of the endocardium, whereas in pigs, they almost reach to the epicardium

Answer 35

Inner third

Question 36

Although conduction of cardiac impulses is their principal function, large free-running Purkinje fibers composed of **many Purkinje cells**, often called _____, are capable of contraction

Answer 36

False tendons

Question 37

APs propagate within the thin Purkinje fiber bundles from the _____ before activating surrounding myocytes.

Answer 37

Base to apex

Question 38

Purkinje fiber coupling relies on connexins _____.

Answer 38

Connexins 40 and 45

Question 39

In general, autonomic neural input to the heart exhibits some degree of “sidedness,” with the right sympathetic and vagal nerves affecting the __________ and the left sympathetic and vagal nerves affecting the __________ more than the SA node.

Answer 39

Right - SA node Left - AV node Stimulation of the **right stellate ganglion produces sinus tachycardia** with less effect on AV nodal conduction, whereas stimulation of the **left stellate ganglion generally shifts the sinus pacemaker to an ectopic site and consistently shortens AV nodal conduction time and refractoriness**. Left stellate stimulation produces variable and usually smaller degrees of SAN acceleration. Stimulation of the **right cervical vagus nerve primarily slows the SA nodal discharge rate**, whereas stimulation of the **left vagus primarily prolongs AV nodal conduction time and refractoriness**. Neither sympathetic nor vagal stimulation affects normal conduction in the His bundle.

Question 40

Most efferent sympathetic impulses reach the canine ventricles over the ansae subclavia, branches from the stellate ganglia. Sympathetic nerves then synapse primarily in the caudal cervical ganglia and form individual cardiac nerves that innervate relatively localized parts of the ventricles. The major route to the heart is the _____ nerve on the right side and the _____ nerve on the left.

Answer 40

Right: recurrent cardiac nerve Left: ventrolateral cardiac nerve

Question 41

The principal effects of **vagus nerve activation** are due to opening of _____ channels. In addition, vagal discharge **modulates cardiac sympathetic activity at prejunctional and postjunctional sites** by regulating the amount of norepinephrine released and by inhibiting cAMP-induced phosphorylation of cardiac proteins, including ion channels and calcium pumps

Answer 41

IK, ACh channels

Question 42

**Tonic vagal stimulation** thus produces a **greater absolute reduction** in the SAN rate in the presence of tonic background sympathetic stimulation, a sympathetic-parasympathetic interaction termed _____ antagonism.

Answer 42

Accentuated antagonism

Question 43

_____ vagal bursting, as may occur each time that a **systolic pressure wave arrives** at the baroreceptor regions in the aortic and carotid sinuses, induces **phasic changes in sinus cycle length** and can **entrain the sinus node to discharge faster or slower at periods** identical to those of the vagal burst

Answer 43

Periodic vagal bursting

Question 44

Because the **peak vagal effects** on sinus rate and AV nodal conduction **occur at different times in the cardiac cycle**, a brief vagal burst can _____.

Answer 44

**Slow the sinus rate** without affecting AV nodal conduction OR **Prolong AV nodal conduction time** and not slow the sinus rate

Question 45

Nonuniform distribution of sympathetic nerves—and thus norepinephrine levels—may produce nonuniform electrophysiologic effects during sympathetic activation because the **ventricular content of norepinephrine** is greater at the _____ of the heart

Answer 45

Base than at the apex

Question 46

**Afferent vagal activity is higher** in the _____ ventricular myocardium, which may account for the **vagomimetic effects of inferior MI**.

Answer 46

Posterior ventricular

Question 47

**Sympathetic hypoinnervation** has been shown to **increase the sensitivity of adrenergic receptors to activation** by circulating catecholamines ("_____")

Answer 47

Denervation supersensitivity

Question 48

Enumerate the disorders of impulse formation

Answer 48

**I. Automaticity** Normal: Sinus tachycardia or bradycardia inappropriate for the clinical situation; possibly ventricular parasystole Abnormal: Accelerated ventricular rhythms after myocardial infarction **II. Triggered activity:** EADs: Acquired LQTS and associated ventricular arrhythmias DADs: CPVT; atrial ectopic beats

Question 49

Enumerate the disorders of impulse conduction

Answer 49

* Block and reentry * Bidirectional or unidirectional without reentry: SA, AV, bundle branch block * Unidirectional block with reentry: Reciprocating tachycardia in WPWS, AVNRT, VT caused by bundle branch reentry

Question 50

Enumerate the combined disorders

Answer 50

Interactions between automatic foci: Modulated parasystole Interactions b/n automaticity and conduction: Similar to experimenta

Question 51

Disorders of ____________ are characterized by an inappropriate discharge rate of the normal pacemaker, the SA node (e.g., sinus rates too fast or too slow for physiologic needs of patient), or discharge of an ectopic pacemaker that then controls the atrial or ventricular rhythm, either as an escape rhythm or accelerated automaticity.

Answer 51

Disorders of impulse formation

Question 52

Identify the mechanism A patient with persistent sinus tachycardia at rest or sinus bradycardia during exertion exhibits inappropriate SAN rates, but the underlying ionic mechanisms responsible can still be basically normal, with changes in the kinetics or magnitude of relevant currents underlying the abnormal rate.

Answer 52

Normal automaticity

Question 53

The discharge rate of a latent pacemaker can accelerate inappropriately and usurp control of cardiac rhythm from the SA node, as may occur with a premature ventricular complex (PVC) or a burst of ventricular tachycardia (VT)

Answer 53

Normal automaticity Such disorders of impulse formation can be caused by alteration in a normal pacemaker mechanism (e.g., phase 4 diastolic depolarization that is physiologically normal for SA node or for ectopic site such as a Purkinje fiber, but occurs inappropriately fast or slow) or by a physiologically abnormal pacemaker mechanism.

Question 54

Identify mechanism Slow atrial, junctional, or ventricular escape rhythms; certain types of atrial tachycardias (ATs) (e.g., those produced by digitalis or perhaps those coming from PVs); accelerated junctional (nonparoxysmal junctional tachycardia) and idioventricular rhythms

Answer 54

Abnormal automaticity Abnormal automaticity can arise from cells that have reduced maximum diastolic potentials, often at membrane potentials positive to −50 mV, in the activation range of both I Kand ICaL. Automaticity at membrane potentials more negative than −70 mV may be caused by If Partial depolarization and failure to reach normal maximal diastolic potential can induce automatic discharges in most if not all cardiac fibers.

Question 55

Initiated by **afterdepolarizations**, which are depolarizing oscillations in membrane voltage induced by one or more preceding APs.

Answer 55

Triggered activity Thus, triggered activity is related to the consequences of a preceding impulse or series of impulses, without which electrical quiescence occurs

Question 56

Afterdepolarizations arising before full repolarization of the fiber

Answer 56

Early afterdepolarizations

Question 57

Afterdepolarizations occuring after completion of repolarization (phase 4)

Answer 57

Delayed afterdepolarizations

Question 58

Identify the mechanism Arrhythmias precipitated by digitalis, spontaneous atrial ectopic beats, CPVT

Answer 58

Delayed afterdepolarization

Question 59

_________ depolarizations result from the **activation of a calcium sensitive inward current** elicited by spontaneous increases in intracellular free calcium concentration due to aberrant diastolic Ca 2+ release

Answer 59

Delayed afterdepolarizations

Question 60

____ afterdepolarizations almost certainly play a central role in the tachyarrhythmias seen in the acquired and congenital forms of LQTS

Answer 60

Early afterdepolarizations

Question 61

Mutations in the human RYR2 gene and in CASQ2, which encodes calsequestrin

Answer 61

CPVT - DADs RYR2 and CASQ2 mutations that underlie CPVT increase the sensitivity of the RyR2 channel to luminal Ca 2+activation. Thus, increased catecholamine release due to adrenergic stimulation (e.g., from emotional or physical stress), which increases SR Ca2+ stores and phosphorylates RyR2 (increasing its Ca 2+ sensitivity further), enhances the propensity for spontaneous, diastolic SR Ca 2+ release and DAD-triggered arrhythmias (accounting for the “C” in CPVT)

Question 62

The sentinel finding in clinically identifiable EAD associated syndromes is thus prolongation of the __________________, the macroscopic manifestation of cellular APD prolongation.

Answer 62

Electrocardiographic QT interval

Question 63

Identify the mechanism Acquired and congenital LQTS

Answer 63

Early afterdepolarization

Question 64

When the AP is excessively prolonged, the membrane potential remains at levels that allow recovery of enough steady-state Ca 2+ (particularly during ___________) or Na + (during phase 3) current to depolarize the cell, producing an EAD.

Answer 64

Phase 2 It appears that, because of their longer APD and unique Ca 2+ handling properties, Purkinje cells are particularly sensitive to EAD-inducing interventions. Purkinje cell EADs raise to threshold adjacent ventricular muscle cells that have already repolarized, producing an unstimulated extrasystole. This activation can initiate tachyarrhythmias either by the induction of unstable transmural reentry or via repetitive rapid EADs inducing repetitive ventricular beats in rapid succession.

Question 65

_____ patients are particularly prone to adrenergic provocation of ventricular arrhythmias and tend to respond well to beta-adrenoceptor blockers.

Answer 65

LQT1

Question 66

Acquired LQTS and torsades de pointes from _____, likely mediated by EADs

Answer 66

Class III antiarrhythmic drugs like quinidine, sotalol, or dofetilide and Non-cardiac agents like cisapride, erythromycin, moxifloxacin, and psychoactive drugs

Question 67

_______________ occur when the propagating impulse is blocked and is followed by asystole or a slower escape rhythm

Answer 67

Bradyarrhythmias

Question 68

_________________ occur when the delay and block produce reentrant excitation

Answer 68

Tachyarrhythmias

Question 69

Various factors involving both **active and passive membrane properties** determine the **CV and successful propagation of an impulse**.These factors include the _____.

Answer 69

(1) **Stimulating efficacy of the propagating impulse**, which is related to the amplitude and rate of rise of phase 0 (an indicator of the size of the activating phase 0 inward current) (2) **Excitability of the tissue** into which the impulse is conducted (3) **Geometry of the tissue**

Question 70

Identify the mechanism Sinoatrial block, AV block, bundle branch block

Answer 70

Bidirectional or unidirectional without reentry

Question 71

Identify the mechanism AVNRT VT caused by Bundle branch block reentry Reciprocating tachycardia in WPW

Answer 71

Unidirectional block with reentry

Question 72

_______ depolarization has been suggested as a **cause of conduction block at slow rates**, so-called **bradycardia- or deceleration-dependent block**; also called as __________ block

Answer 72

Diastolic depolarization Phase 4 block

Question 73

**Impulses are blocked at rapid rates or short cycle lengths** as a result of incomplete recovery of refractoriness (postrepolarization refractoriness) caused by incomplete time- or voltage-dependent recovery of excitability.

Answer 73

Tachycardia-dependent block For eg, such incomplete recovery is the usual mechanism responsible for a nonconducted premature P wave or one that conducts with a functional bundle branch block.

Question 74

This refers to the phenomenon whereby an **impulse with a low safety factor loses activation effectiveness** as it spreads anterogradely.

Answer 74

Decremental conduction This property is most typically seen in the AV node, in relation to the relatively small amplitude of phase 0 Ca2+ current in slow channel tissue, especially at fast rates and in the presence of disease. It is also a feature of diseased tissue with conduction impairment due to cell death, fibrosis, and/or reduced phase 0 activating current.

Question 75

During this absolute RP, the cardiac impulse has “no place to go.” Activation is then reinitiated by the next sinus impulse. If, however, a group of fibers not activated during the initial wave of depolarization recovers excitability in time to be reactivated before the impulse dies out, the fibers may serve as a link to reexcite areas that were just discharged and have now recovered from the initial depolarization.

Answer 75

Reentry

Question 76

_____________ is the capture or continuous resetting of the tachycardia by the pacing-induced activation.

Answer 76

Entrainment Entraining a tachycardia (i.e., **increasing the rate of the tachycardia** through **capture of the reentry circuit by pacing**), with **resumption of the intrinsic rate of the tachycardia when pacing is stopped**, is a clinically accessible way to establish the presence of reentry

Question 77

In _____ reentry, there is a discrete **anatomical barrier** separating alternate conduction pathways, and allowing reentry to be initiated and maintained.

Answer 77

Anatomic reentry Figure 62.18A Premature beat arriving during the RP of the fast pathway (here designated Pathway 1) but after the shorter-RP pathway (Pathway 2) has recovered excitability. The impulse then travels antegradely down Pathway 2 to the His bundle entrance, conducting via the His bundle to the ventricles (Fig. 62.18B). If the distal end of Pathway 1 has now had time to recover, the impulse will propagate retrogradely up Pathway 1 (Fig 62.18C). If the circuit time (the time to leave each point in the circuit and get back to the initial point of reference) is longer than the RP of Pathway 2, it will now be reexcited in the antegrade direction and the process can continue indefinitely (Fig 62.18D) if the conditions are right.

Question 78

Fast pathway _______ RP Slow pathway ______ RP

Answer 78

Long RP Short RP

Question 79

______ reentry **lacks confining anatomic boundaries** and can occur in contiguous fibers that exhibit functionally different electrophysiologic properties caused by local differences in transmembrane AP, APD, or other determinants of excitability

Answer 79

Functional reentry Dispersion of excitability, refractoriness, or both, as well as anisotropic distributions of intercellular resistance, permit initiation and maintenance of reentry.

Question 80

______________ is the most likely cause of the usual form of **atrial flutter**, with the reentrant circuit being confined to the right atrium in typical atrial flutter, where it **usually travels counterclockwise** in a caudocranial direction in the interatrial septum and in a craniocaudal direction in the right atrial free wall

Answer 80

Reentry An area of slow conduction is present in the posterolateral to posteromedial inferior area of the right atrium, along with a central area of block that can include an anatomic (IVC) and functional component. This area of slow conduction is rather constant and represents the site of successful ablation of typical atrial flutter.

Question 81

AF is characterized by **rapid irregular atrial activity** The classical theory is that of multiple disorganized reentrant waves, encapsulated by Moe’s “_____ hypothesis"

Answer 81

Multiple-wavelet hypothesis

Question 82

In atrial fibrillation, there is extensive evidence that the __________ are particularly prone to host both focal and reentrant sources

Answer 82

Pulmonary veins **PV ablation** is the **single most effective** procedure for AF management

Question 83

________________ results from fibers that **bypass the AV node** and allow for more rapid communication between atria and ventricles than is normally permitted by the AV node. These connections can produce the substrate for anatomical reentry involving the atria, AV node, ventricles, and bypass tract, generally referred to as __________

Answer 83

Preexcitation “Atrioventricular reciprocating tachycardia” (AVRT).

Question 84

Example of pre-excitation

Answer 84

WPW syndrome The **usual (orthodromic)** activation wave during such a reciprocating tachycardia in a patient with an accessory pathway occurs **anterogradely over the normal AV node–His-Purkinje system and retrogradely over the accessory pathway**, which results in a normal-duration QRS complex. Occasionally, the activation wave travels in a **reverse (antidromic)** direction to the **ventricles over the accessory pathway and to the atria retrogradely up the AV node**.

Question 85

After the ventricles have been excited, the impulse is able to enter the accessory pathway retrogradely and return to the atrium.A continuous conduction loop of this type establishes the circuit for the tachycardia. The usual (_____) activation wave during such a reciprocating tachycardia in a patient with an accessory pathway occurs anterogradely over the normal AV node–His-Purkinje system and retrogradely over the accessory pathway, which results in a normal-duration QRS complex

Answer 85

Orthodromic

Question 86

In some patients, the accessory pathway may be capable of only retrograde conduction (“_____”),but the circuit and mechanism of AVRT remain the same

Answer 86

Concealed

Question 87

Reentry in ventricular muscle, with or without contributions from specialized tissue, is responsible for many or most VTs in patients with ischemic heart disease. ___________________, macroreentry using the specialized conduction system, can cause sustained VT, particularly in patients with dilated cardiomyopathy.

Answer 87

Bundle branch reentry

Question 88

During acute ischemia, various factors, including elevated_____ and reduced _____, combine to create depressed APs in ischemic cells that impede conduction and can lead to reentry

Answer 88

Elevated [K+]o Reduced pH

Question 89

_____________ congenital sudden death syndrome which include typical ST-segment elevation (unrelated to ischemia, electrolyte abnormalities, or structural heart disease) in the right precordial (V 1 to V3 ) leads of the ECG, often but not always accompanied by an apparent right bundle branch block Single most common genetic abnormality?

Answer 89

Brugada Syndrome **loss-of-function mutations in SCN5A** which encodes the poreforming cardiac sodium channel alpha subunit Nav1.5

Question 90

In Brugada syndrome, ____ in localized myocardial regions is often a central factor, although conduction abnormalities have also been observed, and the relative role of repolarization versus depolarization abnormalities remains controversial.

Answer 90

Early repolarization

Question 91

The single most common genetic abnormality in Brugada syndrome are _____.

Answer 91

Loss-of-function mutations in SCN5A

Question 92

________________ inherited arrhythmogenic syndrome characterized by stress-induced, adrenergically mediated polymorphic VT occurring in structurally normal hearts Genetic mechanism?

Answer 92

CPVT The common mechanism underlying RyR2associated CPVT is spontaneous diastolic Ca 2+ leak from the SR via RyR2, leading to intracellular Ca 2+waves and triggered activity Beta-adrenergic tone resulting from stimulation by c echolamines has a central role in modulating RyR2 function, both by increasing RyR2-sensitivity to Ca 2+ by enhancing PKA and CaMKIImediated phosphorylation, and by increasing SR Ca2+ -loading through increased I Ca,L and SERCA activity, effects that largely account for the “C” in CPVT. Thus, beta-adrenergic receptor blockade is the mainstay of CPVT therapy.

Question 93

The common mechanism underlying RyR2- associated CPVT is _____ from the SR via RyR2, leading to intracellular Ca2+ waves and triggered activity.

Answer 93

Spontaneous diastolic Ca2+ leak

Question 94

While RyR2 mutations are responsible for about 95% of cases, CPVT can also occur because of mutations in genes encoding _____, all proteins that interact with RyR2 and regulate its function.

Answer 94

Calsequestrin Calmodulin Triadin

Question 95

_________________ is an inherited myopathy characterized by sustained monomorphic VT and sudden death Mutations?

Answer 95

ARVC The majority are mutations in genes encoding proteins of the cardiac desmosome, a component of the intercalated disc essential for mechanical coupling between cardiomyocytes.

Question 96

Approximately 20% to 45% of the pathogenic mutations linked to ARVC are in the gene encoding _____, which interacts with other cytoskeletal proteins to stabilize the desmosome.

Answer 96

Plakophilin 2 (PKP2)

Question 97

Loss of _____ expression in ARVC reduces the voltage-gated sodium current and connexin 43 expression at the intercalated disc and thus results in slowed AP propagation

Answer 97

Loss of PKP2 expression

Question 98

While the reentry underlying VF was classically thought to be randomly maintained by _____, more recent investigations have suggested underlying spatiotemporal organization and pointed to the role of _____ reentry in maintaining VF.

Answer 98

Wandering wavelets of activation Spiral-wave reentry

Question 99

The hallmark of cardiac fibrillation is ongoing ________________

Answer 99

Wave break (or wave splitting) Wave break is caused by conduction block occurring at a specific site along the wavefront while the remaining portions of the front continue to propagate. This localized block, wave break, causes splitting of a primary spiral wavefront into two daughter wavelets. The daughter wavefronts can collide and annihilate each other, or can form independent reentry-supporting spiral-wave generators.

Question 100

Give the mechanisms: AFlutter AFibrillation LQTS VT post MI WPW Syndrome AVNRT CPVT Ventricular Fibrillation AV Block SA Block

Answer 100

AFl - Reentry AF - Reentry +++ LQTS - Early afterdepolarization VT post MI - BBB reentry; unidirectional block with reentry WPW - unidirectional block with reentry AVNRT - unidirectional block with reentry CPVT - Delayed afterdepolarization VF - reentry AV/SA block - bidirectional or unidirectional without reentry