Cardiac Conduction, Rhythm, and Related Disorders PDF

Cardiac Conduction, Rhythm, and Related Disorders Cardiovascular Perfusion Program Cindy D. Powell, MD, MPH The Queen, Tina Turner https://www.pinterest.com/pin/404338872810337142/ Outline and Objectives of Part 1: Mechanisms of Cardiac Arrhythmias Section 1: Normal impulse formation • • • • Ion...

Cardiac Conduction, Rhythm, and Related Disorders Cardiovascular Perfusion Program Cindy D. Powell, MD, MPH The Queen, Tina Turner https://www.pinterest.com/pin/404338872810337142/ Outline and Objectives of Part 1: Mechanisms of Cardiac Arrhythmias Section 1: Normal impulse formation • • • • Ionic basis of automaticity Native and latent pacemakers Overdrive suppression Electrotonic interactions Section 2: Altered impulse formation • • • • • Alterations in sinus node automaticity Escape rhythms Enhanced automaticity of latent pacemakers Abnormal automaticity Triggered activity Section 3: Altered impulse conduction • Conduction block • Unidirectional block and reentry • Wolff-Parkinson-White Syndrome Section 4: Physiologic basis of antiarrhythmic therapy (d–e) Segmentation of entire human CCS. Volume rendering viewed from anterior and sliced coronally to show the location of the CCS components. Volume rendering removed in (e). AVCA, atrioventricular conduction axis; CT, crista terminalis; LPN, left Purkinje network; RPN, right Purkinje network; SAN; sinoatrial node. Areej, A. + Atkinson, A.J. A 21st century view of the anatomy of the cardiac conduction system. Translational Research in Anatomy, Volume 28, September 2022, 100204. Source - Adapted from Stephenson et al., Sci Rep 2017 7:7188. 10.1038/s41598-017-07694-8. • Bradyarrhythmias • Tachyarrhythmias Introduction • Arrhythmias are among the most common clinical problems encountered and range from common benign palpitations to severe symptoms of low cardiac output and death. • Heart rhythm disorders result from alterations of impulse formation, conduction, or both. • Tachycardias are divided into groups based on their origin: Recall during this discussion that cardiac tissue is composed of cells that are electrically coupled and operate as a syncytium. As a result, the leading edge of a depolarization may be located several centimeters ahead of its trailing edge, and this property plays an important role in the genesis of certain arrhythmias. • Supraventricular when they involve the atrium or atrioventricular (AV) node • Ventricular when they originate from the His–Purkinje system or ventricles. • Bradycardias result from decreased automaticity or conduction block. Section 1: Normal Impulse Formation • Impulse formation in the heart arises from the intrinsic automaticity of specialized cardiac cells. • Automaticity = ability to spontaneously depolarize to a threshold voltage to generate an action potential • Specialized cells of the conducting system, pacemaker cells, do possess natural automaticity. • The specialized conducting system includes: • The sinoatrial (SA) node • The AV nodal region • The ventricular conducting system • The bundle of His • The bundle branches • The Purkinje fibers • Normally, atrial and ventricular myocytes do not exhibit this property, but in pathologic situations, myocardial cells outside the conducting system may also acquire automaticity. Anatomy of the Conduction System of the Heart • Sinoatrial (SA) node – the pacemaker of the heart. Intrinsic rate of 60-100 bpm. • Atrioventricular (AV) node • Delays the electrical impulse to allow the action potential to spread across both atria for coordinated atrial contraction that precedes ventricular contraction. • Intrinsic rate is 45-50 bpm. • In a healthy heart, the atrial muscle is separated from the ventricular muscle except at the AV node. • Bundle of His. Because of its proximity to the AV and the MV rings, the B of His is predisposed to inflammation and deposits of calcified debris that can interfere with impulse conduction. • Purkinje fibers. Intrinsic rate of 15-40 bpm. • Fig. 10.7 • Action potentials differ in different cardiac regions and cells. Cells of the sinoatrial node, atrial muscle, and ventricular muscle have action potentials with distinctive phases and shapes. • Rapid propagation through electrically coupled cells is facilitated by gap junctions and is capable of bidirectional movement The Pathways and Effects of Electrical Impulses -Membrane potential: the electrical potential (difference) across the cell membrane. -The Na+/K+ ATPase pump functions to maintain resting membrane potential by pumping 3 Na+ out across the cell membrane and returning 2 K+ to the inside of the membrane. -During depolarization of nonpacemaker myocytes, the membrane potential becomes less negatively charged as Na+ ions rapidly rush into the cell. -During repolarization, K+ ions leave the cell to reestablish the resting membrane potential. Action potential of a nonpacemaker myocyte. • The fast response occurs in the normal myocardial cells of the atria, the ventricles, and the Purkinje fibers. These cells do not normally initiate APs. • Their APs are characterized by the opening of fast voltage-dependent Na+ channels. • They have a constant resting potential, rapid depolarization, and a longer period of sustained depolarization before repolarization. • Impulse conduction is rapid (0.5 to 5.0 m/second), thereby providing a high safety factor for conduction and a coordinated contraction. • The slow response occurs in the SA and the AV nodes. • The hallmark of these pacemaker cells is a spontaneous phase 4 depolarization. • They allow a slow inward leak of current (the pacemaker current, I f) to occur through the slow channels during phase 4 until the cell spontaneously depolarizes. • Under normal conditions, the primary role of this slow response, which includes a slow calcium current, in other nonpacemaker atrial and ventricular muscle cells is to provide for the entrance of calcium for the excitation and resultant muscle contraction. Fast and Slow Cardiac Ion Channels APs in Nonpacemaker Cells • Phase 0 is rapid depolarization caused by opening of fast Na+ channels and influx of Na+. • Phase 1 is transient early repolarization. During this phase, Na+ channels inactivate and transient outward K + channels open briefly and begin to repolarize the membrane. These channels are open only for a brief period. • Phase 2 is called the plateau phase, because the membrane potential remains fairly stable at a mostly depolarized state. In this phase, Ca 2+ influx via the slow, long-lasting (L)–type Ca 2+ channels and K+ efflux via repolarizing K+ channels balance each other. Fast Na + channels remain inactivated. Ca2+ entering the contractile cardiac muscle cells during this phase triggers Ca2+ release from the sarcoplasmic reticulum (Ca2+-induced Ca2+ release), a vital step in excitation–contraction coupling. • Phase 3 is membrane repolarization. During this phase, Ca2+ channels close but slow K+ channels remain open, and the K+ leaving the cells returns membrane potential toward baseline. In this phase, fast Na+ channel gates progressively reset to their resting position. The Na+/K+ pump and Ca2+ transporters reestablish the ion gradients, and the cell membrane returns to resting membrane potential (phase 4). • Phase 4 is the resting membrane potential (−90 mV). In this phase, K+ leak channels are open and K+ is leaking out of the cell; other channels are closed. Ion Channels and the Action Potential 1. The sodium–potassium ATPase pump maintains concentration gradients for these ions. 2. Also, after contraction, active calcium transporters aid removal of calcium to the external environment and into the sarcoplasmic reticulum. In addition, a sodium–calcium exchanger helps maintain the low intracellular calcium concentration. 3. When re-excited by an AP, sodium entry through the fast sodium channel is responsible for the rapid upstroke (phase 0) of the action potential (AP) in nonpacemaker cells. 4. Calcium again enters the cell through calcium channels during (phase 2) of the Purkinje fiber and muscle cell AP. In the pacemaker cells, however, calcium is the main ion responsible for spontaneous depolarization of these cells (phase 4). 5. K+ exits through a number of different K+ channels to repolarize the cell (phase 3). Also, open K+ channels contribute to the resting potential (phase 4) of nonpacemaker cells. Cardiac Ion Channels (From TKACS) • FIGURE 10.5 • Cardiac cell membrane proteins. These proteins are responsible for action potential propagation and contractile activity. The sarcolemma contains voltage-gated sodium (Na+), calcium (Ca2+), and potassium (K+) channels that shape the action potentials. Gap junction ion channels allow electrical impulses to be propagated between adjacent cells. The Na+/K+ pump maintains ion gradients and the resting membrane potential, and the Ca2+ pump and Na+–Ca2+ exchanger contribute to low intracellular Ca 2+ concentration at rest. The SR membrane contains a Ca2+ release channel, also known as the ryanodine receptor, and the sarco-endoplasmic reticulum calcium ATPase (SERCA). SERCA sequesters Ca2+ in the SR, causing diastolic relaxation that allows ventricular filling after each contraction. Resting Potential • The resting potential of a cardiac muscle cell is determined the Na+/K+ ATPase pump and by the balance between the concentration gradient and electrostatic forces for potassium, because with the exception of a very small amount of sodium movement, K+ channels are the main ones open at rest. • The K+ leaks from the inside of the cell to the outside down its concentration gradient via K+ leak channels (inward rectifier channels) and generate a negative charge in the inside of the membrane vs the outside. • The concentration gradient favors outward movement of K+, however, the electrical force attracts the positively charged K+ ions inward. • The resting potential is approximated by the Nernst equation for potassium. Ionic Basis of Automaticity in Pacemaker Cells • Cells with natural automaticity do not have a static resting voltage. • These cells inherently display gradual depolarization during phase 4 of the action potential. • If this spontaneous diastolic depolarization reaches the threshold condition (-40 mV), an action potential upstroke is generated. • The ionic current largely responsible for phase 4 spontaneous depolarization is known as the pacemaker current (If). AP of a Pacemaker Cell (SA or AV Node) • Pacemaker cells undergo spontaneous depolarization during phase 4 of their APs, in which there is a progressive depolarization caused by 3 different ion channels: • Na+ enters first through hyperpolarization-activated cyclic nucleotide-gated channels (the If, or “funny” sodium current), which begin to open when the membrane voltage becomes more negative than approximately −50 mV. • Then a small Ca2+ current begins carried by transient Ttype Ca2+ channels (Ca2+(T)), which is then • followed by the opening of L-type Ca2+ channels third. • This continues until the threshold is reached for opening more voltage-gated L-type Ca 2+ channels (Ca2+(L)). The upstroke (phase 0) mediated by Ca2+ entry through L channels does not have the rapid rate of voltage change associated with nonpacemaker cells. • Additional contributing currents to phase 4 depolarization are: • A progressively declining outward potassium current • An additional inward sodium current mediated by activation of the electrogenic sodium–calcium exchanger by calcium release from the sarcoplasmic reticulum Phase 3 repolarization results from K+ efflux through voltage-gated K+ channels, similar to nonpacemaker cells. AP of Pacemaker Cells (More Detail) • The primary current through the HCN channels occurs because of Na+ influx. The funny channels are so called because unlike the fast Na+ channels of nonpacemaker cells, which open in response to depolarization, the HCN channels open when the membrane is most (hyper)polarized at the end of repolarization. • As a result of these channels, as soon as the pacemaker cells are repolarized at the end of an action potential, they begin to depolarize again. Thus, in these cells, the most negative membrane potential occurs as phase 3 transitions to phase 4. This point is termed the MDP, the maximum negative diastolic potential, as these cells do not have a stable resting membrane potential. The MDP is ~ -60 mV for the sinus node pacemaker cells. • Na+ influx via the HCN channels is responsible for most of the phase 4 depolarization, but transient (T-type) Ca2+ channels also open and contribute to the later part of the pacemaker potential. T-type Ca2+ channels are different from the slow L-type Ca2+ channels responsible for phase 0. The slope (rate) of this spontaneous depolarization is a very important determinant of heart rate. • The combination of decreased K+ permeability at the end of phase 0, Na+ entry through funny channels, and Ca2+ entry through Ttype Ca2+ channels constitutes the upward slope of membrane potential that controls pacemaker cell action potential frequency. Summary of the Actions of L-type Calcium Channels These Ca2+ channels are the targets of calcium channel blockers: • Nifedipine and amlodipine: work primarily on vascular smooth muscle to cause vasodilatation. • Diltiazem and verapamil: cardioselective. Work primarily on the SA and AV nodes to slow heart rate. They also decrease contractility, however. Play a role in cardiac and vascular function Arterioles – vascular tone Heart • Contractile cells • Plateau of the fast-response action potential (vital step in excitation-contraction coupling: Ca 2+ mediated Ca2+ release) • Pacemaker cells • Upstroke of slow-response action potentials • In SA node - Heart rate acceleration • In AV node – increased conduction speeds Calcium channel blockers impact the above Cells: The degree of refractoriness primarily reflects the percentage of fast Na+ channels that have recovered from their inactive state and are capable of reopening. Refractory periods are physiologically necessary to allow sufficient time for the ventricles to empty and refill before the next contraction. Refractory Periods in the Cardiac AP and the EKG • Absolute refractory period – An action • • potential (AP) cannot be initiated by any stimulus. Includes phases 0, 1,2, and part of 3. Relative refractory period – An AP can be initiated, but it requires a “larger than normal” stimulus. Repolarization returns the membrane potential to below threshold. Begins when in phase 3 when the threshold potential is reached, and ends nearly at the end of phase 3. Supernormal excitatory period- Extends from end of phase 3 to beginning of phase 4. A small stimulus and trigger an AP. This area is a vulnerable zone in which dysrhythmias can develop. The Mechanisms Behind the Refractory Periods • Refractory periods are caused by unique two-part gating of fast Na+ channels. The fast Na+ channel has two gates that close the ion channel pore: the activation gate, which is normally closed during resting membrane potential; and the inactivation gate, which is normally open at rest. • At resting membrane potential, the activation gate keeps the channel closed, so Na+ cannot enter the cell. A depolarizing stimulus that reaches the channel’s voltage threshold opens the activation gate, enabling Na+ to enter the cell (because both activation and inactivation gates are open); this creates the upstroke of the action potential. • Once the membrane potential becomes positive (at the peak of the action potential), the inactivation gate closes the channel, preventing further Na+ entry (despite the activation gate being still open). In this state, the Na+ channels are blocked by the inactivation gate, so further depolarization is not possible; this causes the absolute refractory period. Voltage Gating of Fast Sodium Channels: Four covalently linked transmembrane domains (I, II, III, and IV) form the sodium channel, which is guarded by activation and inactivation gates Now back to the differences in the AP of pacemaker vs. nonpacemaker cells…. • In contrast to the phase 0 upstroke of cells in the Purkinje system, the AP of cells in the sinus and AV nodes is much slower. • The reason for the difference is that the membrane potential determines the proportion of fast sodium channels that are in a resting state capable of depolarization, compared with an inactivated state. • The number of available (or resting-state) fast sodium channels decreases as the resting (diastolic) membrane potential becomes less negative. Because sinus and AV nodal cells have less negative maximum diastolic membrane voltages (−50 to −60 mV) than do Purkinje cells (−90 mV), the large majority of fast sodium channels is inactivated in these pacemaker cells. • Thus, the action potential upstroke of PM cells relies to a great extent on a smaller calcium current (through the relatively slower opening of L-type Ca++ channels) and has a less rapid rate of rise than do cells of the Purkinje system or ventricular myocardium. Native and Latent Pacemakers • The distinct populations of automatic cells in the specialized conduction pathway have different intrinsic rates of firing. • These rates are determined by 3 variables that influence how fast the membrane potential reaches the threshold condition: • • • • (1) the rate (ie, the slope) of phase 4 spontaneous depolarization, (2) the maximum negative diastolic potential, and (3) the threshold potential. A more negative maximum diastolic potential, or a less negative threshold potential, slows the rate of impulse initiation because it takes longer to reach the threshold value. • Conversely, the greater the If, the steeper the slope of phase 4, and the faster the cell depolarizes. The size of If depends on the number and opening kinetics of the individual pacemaker channels through which this current flows. • The native pacemaker: The pacemaker cells with the fastest rate of depolarization (normally the SA node, 60-100 bpm) set the heart rate. The SA node’s repeated discharges prevent spontaneous firing of other potential pacemaker sites. • Latent (or ectopic) pacemakers: other cells within the specialized conduction system that harbor the potential to act as pacemakers if necessary. These include the AV node and the bundle of His (50-60 bpm), and cells of the Purkinje system (~30-40 bpm). These latent sites may initiate impulses and take over the pacemaker function if the SA node slows or fails to fire or if conduction abnormalities block the normal wave of depolarization from reaching them. Native and Latent Pacemakers Figure 11-3. Determinants of cell firing rates. A.Alterations in the pacemaker current (If) and in the magnitude of the maximum diastolic potential (MDP) alter the cell firing rate. (a) The normal action potential (AP) of a pacemaker cell. (b) Reduced If renders the slope of phase 4 less steep; thus, the time required to reach threshold potential (TP) is increased. (c) The MDP is more negative; therefore, the time required to reach TP is increased. B. Alterations in TP change the firing rate of the cell. Compared with the normal TP (a), the TP in (b) is less negative; thus, the duration of time to achieve threshold is increased, and the firing rate decreases. Overdrive Suppression • Overdrive suppression: pacemaker cells with the fastest intrinsic rhythm pre-empt all other automatic cells from spontaneously firing (directly suppressing their automaticity). • Ion distribution across the cardiac cell membrane is maintained by the continuously active Na+K+-ATPase which removes 3 Na+ ions from the cell in exchange for 2 K+ ions. • This creates a hyperpolarizing current, making the inside of the cell more negative. • As the cell potential becomes increasingly negative, additional time is required for spontaneous phase 4 depolarization to reach the threshold, so the rate of spontaneous firing is decreased. • Pacemaker cells firing at their own intrinsic rate have an If current sufficiently large to overcome this hyperpolarizing current. • The hyperpolarizing current increases when a cell is caused to fire more frequently than its intrinsic pacemaker rate because depolarization increases the quantity of Na+ ions that enter the cell per unit time. • As a result of the increased intracellular Na+ content, Na+K+-ATPase becomes more active, providing a larger hyperpolarizing current, opposing the depolarizing current If, and further decreasing the rate of spontaneous depolarization. • In this way, overdrive suppression decreases a cell’s automaticity when that cell is driven to depolarize faster than its intrinsic discharge rate. Electrotonic Interactions • A. Pacemaker cells that are not coupled to myocardial cells (as in the SA node) have a maximum diastolic potential (MDP) of approximately −60 mV, whereas myocardial cells have a resting potential (RP) of approximately −90 mV. • B. When pacemaker cells and myocytes are neighbors (as in the AV node), they may be connected electrically by gap junctions at their intercalated discs, allowing electrotonic interactions. • In this situation, electric current flows between the pacemaker cell and the myocardial cell, tending to hyperpolarize the former and depolarize the latter, driving their membrane potentials closer to one another. • The hyperpolarizing current renders the MDP more negative, causing it to take longer for spontaneous depolarization to reach the threshold value, thereby suppressing automaticity. • If a disease state impairs coupling between cells (such as ischemia affecting the AV nodal area), the influence of surrounding myocytes on the pacemaker cell is reduced, allowing I f to depolarize to threshold more readily, which can enhance automaticity. Changes to Cardiac Pacing • The rate of pacemaker cell discharge varies with the resting membrane potential and the slope of phase 4 depolarization. • Catecholamines (i.e., epinephrine and norepinephrine) increase heart rate by increasing the slope or rate of phase 4 depolarization. • Acetylcholine, a parasympathetic mediator, slows the heart rate by decreasing the slope of phase 4. • The fast response of atrial and ventricular muscle can be converted to a slow pacemaker response under certain conditions. For example, such conversions may occur spontaneously in people with severe coronary artery disease and in areas of the heart where blood supply has been markedly compromised. Impulses generated by these cells can lead to ectopic beats and serious arrhythmias. The Action Potential and the EKG The action potentials in cardiac muscle are typically divided into 5 phases: • Phase 0—At the depolarization threshold, the fast Na+ channels in the cell membrane are stimulated to open, resulting in the rapid influx of Na+. -90 to +20 mV. Corresponds to QRS on EKG. • Phase 1—Rapid repolarization period. Abrupt inactivation of the fast Na+ channels. The slight downward slope is thought to be caused by the influx of a small amount of negatively charged chloride ions and the efflux of potassium. • Phase 2— Slow. K+ permeability is low, allowing the membrane to remain depolarized throughout the phase 2 plateau. A simultaneous influx of Ca++ into the cell through the slow Ca++ channels produces the contractile process and contributes to the phase 2 plateau. Corresponds to ST segment. • Phase 3—Final, rapid repolarization period. The slow Ca++ channels close and the influx of Ca++ and Na+ ceases. There is a sharp rise in K+ permeability moving K+ out, allowing reestablishment of the resting membrane potential (−90 mV). The T wave on the EKG. • Phase 4—Diastolic depolarization. The activity of the Na+/K+ATPase pump contributes to maintaining the resting membrane potential by transporting Na+ out of the cell and moving K+ back in. Phase 4 corresponds to diastole. Electrocardiogram The Q-T interval is affected by a large number of drugs, and these can predispose to dysrhythmias. P wave: atrial depolarization, QRS complex: ventricular depolarization; T wave: ventricular repolarization Section 2: Altered Impulse Formation • Cages and knots in the normal sinus node on scanning electron micrograph. • D. Mandrioli, F. Ceci, T. Balbi, C. Ghimenton, G. Pierini, "SEM, TEM, and IHC Analysis of the Sinus Node and Its Implications for the Cardiac Conduction System", Anatomy Research International, vol. 2013, Article ID 961459, 6 pages, 2013. https://doi.org/10.1155/2013/961459 Dysrhythmias • Others causes of dysrhythmias: • Myocarditis, such as viral myocarditis • Other infectious or inflammatory conditions (such as Covid 19, sarcoidosis, etc.) • Hypertrophy of myocardial cells • Etc. • Cardiac arrhythmias represent disorders of cardiac rhythm related to alterations in one or more of 4 characteristics of specialized cells in the conduction system of the heart: • • • • Automaticity, Excitability, Conductivity, or Refractoriness Altered Impulse Formation • Arrhythmias may arise from altered impulse formation at the SA node or from other sites, including the specialized conduction pathways or regions of cardiac muscle. • The main abnormalities of impulse initiation that lead to arrhythmias are: • (1) altered automaticity (of the sinus node or latent pacemakers within the specialized conduction pathway), • (2) abnormal automaticity in atrial or ventricular myocytes, and • (3) triggered activity. The Influencers of Impulse Formation • The rate of impulse initiation by the sinus node, as well as by the latent pacemakers of the specialized conducting system, is regulated primarily by neurohumoral factors and the autonomic nervous system. • Sympathetic stimulation, acting through β1adrenergic receptors, or treatment with anticholinergic drugs, increases the probability that the pacemaker channels will be open, through which If can flow. The increase in If leads to a steeper slope of phase 4 depolarization, causing the SA node to reach threshold and fire earlier than normal and the heart rate to increase. • Parasympathetic cholinergic stimulation (or treatment with a β-blocker, which antagonizes sympathetic stimulation) decreases the probability of a channel being open and therefore inhibits depolarization. The Sympathetic Nervous System’s Effect The SNS increases heart rate by: • Norepinephrine binds to β1-receptors on sinoatrial node cells, leading to phosphorylation of hyperpolarization -activated cyclic nucleotide-gated sodium channels and L-type Ca2+ channels. • These changes increase the slope of diastolic depolarization and lower the threshold for action potential generation to a more negative voltage, allowing the cell to reach threshold faster. • β-receptor blocking drugs (“βblockers”) antagonize the βadrenergic sympathetic effect; therefore, they decrease the rate of phase 4 depolarization of the SA node and slow the heart rate. The Parasympathetic Effects • Parasympathetic activity decreases heart rate by three mechanisms: • (a) It decreases the slope of phase 4 depolarization, • (b) It increases K+ permeability by increasing the probability of acetylcholine-sensitive K+ channels being open at rest, making the maximum diastolic potential more negative. Positively charged K+ ions exit through these “inward rectifier” channels, which differ from the K+ channels that are active in phase 3 repolarization, producing an outward current that drives the diastolic potential more negative. • (c) It inhibits Ca2+ L-type channels,resulting in reduced I f, thus raising the threshold. • The overall effect of reduced If, a more negative maximum diastolic potential, and a less negative threshold level is a slowing of the intrinsic firing rate and therefore a reduced heart rate. • Atropine, an anticholinergic (antimuscarinic) drug blocks parasympathetic activity, and the rate of phase 4 depolarization increases and the heart rate accelerates. Escape Beats • An impulse initiated by a latent pacemaker because the SA node rate has slowed is called an escape beat. • Persistent impairment of the SA node will allow a continued series of escape beats, termed an escape rhythm. • Escape rhythms are protective in that they prevent the heart rate from becoming pathologically slow. • Suppression of sinus node activity may occur because of increased parasympathetic tone. • Different regions of the heart have varied sensitivities to parasympathetic (vagal) stimulation. The SA node and the AV node are most sensitive to such an influence, followed by atrial tissue. The ventricular conducting system is the least sensitive. • Moderate parasympathetic stimulation slows the sinus rate and can allow the pacemaker to shift to the AV node. • However, very strong parasympathetic stimulation suppresses excitability at both the SA node and AV node and may therefore result in the emergence of a ventricular escape pacemaker. Enhanced Automaticity of Latent Pacemakers: Ectopic Beats • An escape beat is late and terminates a pause caused by a slowed sinus rhythm. • An ectopic beat is premature and occurs when a latent pacemaker assumes control of impulse formation by developing an intrinsic rate of depolarization faster than that of the sinus node. • Ectopic beats may arise in several circumstances. Examples: • High catecholamine concentrations can enhance the automaticity of latent pacemakers • Hypoxemia • Ischemia • Electrolyte disturbances • Certain drug toxicities (like digitalis) Abnormal Automaticity • Cardiac tissue injury may lead to pathologic changes in impulse formation. • Altered myocardial cells outside the conduction system that do not usually possess automaticity may acquire automaticity and spontaneously depolarize. • The EKG signals may appear similar to impulses originating from latent pacemakers. • These ectopic beats can transiently take over the pacemaker function and become the source of an abnormal ectopic rhythm. • The mechanism behind this transformation is still being investigated, but when nonpacemaker myocardial cells become injured, their cellular membranes become “leaky” and unable to maintain the concentration gradients of ions, and the resting potential becomes less negative (ie, the cell partially depolarizes). • When a cell’s membrane potential is reduced to a value less negative than −60 mV, gradual phase 4 depolarization can be demonstrated even among nonpacemaker cells. • This spontaneous depolarization probably results from a very slowly inactivating calcium current, a decrease in the outward potassium current that normally acts to repolarize the cell, and less effect of the inward rectifier K+ current that normally holds cells at a more negative potential range. Triggered Activity • Under certain conditions, an action potential can “trigger” abnormal depolarizations that result in extra heart beats or tachyarrhythmias. • This process may occur when the first action potential leads to oscillations of the membrane voltage known as afterdepolarizations. • Unlike the spontaneous activity seen when enhanced automaticity occurs, this type of automaticity is stimulated by a preceding action potential. • There are 2 types of afterdepolarizations depending on their timing after the inciting action potential: • Early afterdepolarizations occur during the repolarization phase of the inciting beat • Delayed afterdepolarizations occur shortly after repolarization has been completed Triggered Activity: EADs • Early afterdepolarizations (EADS)are changes of the membrane potential in the positive direction that interrupt normal repolarization. • They can occur either: • During the plateau of the action potential (phase 2, associated with an inward Ca++ current) or • During rapid repolarization (phase 3, associated with the partial recovery of the inactivated Na+ channels which can then fire again). • EADs are more likely to develop in conditions that prolong the action potential duration as evidenced by a prolonged QT interval on EKG. • An EAD-triggered action potential can be selfperpetuating and lead to a series of depolarizations • Tachyarrhythmia • Polymorphic ventricular tachycardia (Torsades de pointes) Triggered Activity: DADs • Delayed after depolarizations (DADs) may occur shortly after repolarization is complete. • They most commonly develop in states of high intracellular calcium (such as digitalis intoxication) or during marked catecholamine stimulation. • The intracellular Ca2+ accumulation may cause the activation of chloride currents, or of the Na+ -Ca2+ exchanger, that results in brief inward currents that generate the DAD. • DADs can generate self-perpetuating action potentials that can lead to tachyarrhythmias, including atrial and ventricular tachycardias. Section 3: Altered Impulse Conduction DENNIS KUNKEL MICROSCOPY / SCIENCE PHOTO LIBRARY • Heart muscle with purkinje fibres on the surface of the heart muscle fibres, coloured scanning electron micrograph (SEM). Purkinje fibres are modified cardiac muscle fibres which originate from the atrioventricular node and spread into the two ventricles. They transmit the electrical impulse from the atrioventricular node to the ventricles enabling their almost simultaneous contraction. The spread of excitation through the ventricles from the atrioventricular node is extremely rapid, moving at one to four meters per second. Magnification: x700 when shortest axis printed at 25 millimetres. • https://www.sciencephoto.com/media/796 722/view Conduction Blocks • Alterations in impulse conduction also lead to arrhythmias. • Conduction blocks within the conducting system of the AV node or the His–Purkinje system prevents normal propagation of the cardiac impulse. AV block is common and a major reason for implantation of a permanent pacemaker. • Conduction blocks generally slow the heart rate (bradyarrhythmias); however, under certain circumstances (a unidirectional block) the process of reentry can ensue and produce abnormal fast rhythms (tachyarrhythmias). • A propagating impulse is blocked when it encounters a region of the heart that is electrically unexcitable. These blocks could be: • Transient (functional, due to refractory period of the cardiac cycle) or permanent. • Unidirectional or bidirectional • Various conditions may cause conduction block: • • • • Ischemia Fibrosis Inflammation Certain drugs Conduction Blocks • Functional block • Occurs because a propagating impulse encounters cardiac cells that are still refractory from a previous depolarization. • When the tissue is no longer refractory, the impulse may be conducted appropriately. • Antiarrhythmic drugs produce functional conduction blocks. • Fixed conduction blocks, on the other hand, that are caused by a barrier (myocytes replaced by fibrosis or scarring). Unidirectional Block and Re-entry • Reentry is a common mechanism by which altered impulse conduction leads to tachyarrhythmias. • During such a rhythm, an electric impulse circulates repeatedly around a reentry path, recurrently depolarizing a region of cardiac tissue. • During normal cardiac conduction, each electric impulse that originates in the SA node travels in an orderly, sequential fashion through the rest of the heart, ultimately depolarizing all the myocardial fibers, and the impulse stops when all of the heart muscle has been excited. The two critical conditions for reentry are: (1) unidirectional block and (2) slowed conduction through the reentry path. • Conduction blocks that prevent rapid depolarization of parts of the myocardium can create an environment conducive to continued impulse propagation and reentry. Unidirectional Block and Re• Figure 11-9. Mechanism ofentry reentry. • A. Normal conduction. When an action potential (AP) reaches a branch in the conduction pathway (point x), the impulse travels down both fibers (α and β) to excite distal conduction tissue. The α and β pathways have similar conduction velocities and refractory periods such that portions of the wave fronts that pass through them may collide in the distal conduction tissue and extinguish each other. • B. Unidirectional block. Forward passage of the impulse is blocked in the β pathway but proceeds normally down the α pathway. When the impulse reaches point y, if retrograde conduction of the β pathway is intact, the AP can enter β from below and conduct in a retrograde fashion. • C. When point x is reached again, if the α pathway has not had sufficient time to repolarize, then the impulse stops. • D. However, if conduction through the retrograde pathway is sufficiently slow (jagged line), it reaches point x after the α pathway has recovered. In that circumstance, the impulse is able to excite the α pathway again, and a Monomophic Vs. Polymorphic Reentrant Tachycardias • Reentry around distinct, fixed anatomic pathways usually appears as a monomorphic tachycardia on the electrocardiogram (ECG). • For example, in the case of ventricular tachycardia, each QRS has the same appearance as the preceding and subsequent QRS complexes. • This is because the reentry path is the same from beat to beat, producing a stable, regular tachycardia. • This is the most common mechanism of VT associated with areas of ventricular scar, as may result from a prior MI. • Other types of reentry do not require a stable, fixed path. For example, one form can occur in electrically heterogeneous myocardium, in which waves of spiral reentrant excitation travel through the tissue, continually changing direction (polymorphic). • These so-called spiral waves can be initiated when a wave front of depolarization encounters a broad region of functional block, which could be refractory from a preceding wave front, be poorly excitable tissue due to myocardial ischemia, or be under the influence of certain antiarrhythmic medications. • Forward propagation of the wave front is asymmetrically blocked by this region, as the remainder of the front proceeds around the block. As the region repolarizes and becomes excitable again, parts of the wave front then spread retrogradely through it and continue in a spiral path following in the wake of the depolarization that had just passed. • In the ventricles, the resulting tachycardia has a continually changing QRS appearance, producing polymorphic ventricular tachycardia. • If such activation is rapid and very disorganized, no distinct QRS complexes will be discernable, and the rhythm is ventricular fibrillation. Accessory Pathways and Preexcitation (Wolff-Parkinson-White Syndrome) • ~1 in 1500 people has the WPW syndrome and is born with an additional connection between an atrium and ventricle. • Termed an accessory pathway (or bypass tract), this connection allows conduction between the atria and ventricles to bypass the AV node. • The most common type of accessory pathway consists of microscopic fibers (known as a bundle of Kent) that span the AV groove somewhere along the mitral or tricuspid annuli. • The preexcitation of the ventricles via this accessory path results in an earlier portion of the QRS called the Delta wave. WPW (Continued) • During sinus rhythm, simultaneous conduction through the accessory pathway and AV node results in this interesting ECG appearance but causes no symptoms. • The presence of the abnormal pathway, however, creates an ideal condition for reentry because the refractory period of the pathway is usually different from that of the AV node. • If a premature beat then occurs, it may encounter block in the accessory pathway but conduct through the AV node, or vice versa. • If the propagating impulse then finds that the initially blocked pathway has recovered (unidirectional block), it can conduct in a retrograde direction up to the atrium and then down the other pathway back to the ventricles. • Thus, a large anatomic loop is established, with the accessory pathway serving as one limb and the normal conduction pathway through the AV node as the other. Mechanisms of Arrhythmia Development Section 4: The Physiologic Basis of Antiarrythmic Therapy Sánchez-Quintana D, Anderson RH, Tretter JT, et al Anatomy of the conduction tissues 100 years on: what have we learned? Heart 2022;108:1430-1437. Bradyarrhythmias Pharmacologic Therapy modifies the autonomic input to the heart in one of two ways: 1. Anticholinergic drugs (such as atropine) • Competitively bind to muscarinic receptors and thereby reduce the vagal effect that would normally slow the heart rate and conduction through the AV node. • Results in an increased heart rate and enhanced AV nodal conduction 2. β1-Receptor agonists (isoproterenol) • Mimics the effect of endogenous catecholamines. • This drug increase heart rate and speed of the AV nodal conduction. • Atropine and isoproterenol are both administered intravenously only. Electronic Pacemakers • Electronic pacemakers apply repeated electric stimulation to the heart to initiate depolarizations at a desired rate, thereby assuming control of the rhythm. • They can be installed on a temporary or a permanent basis. • Temporary units are used to stabilize patients who are: • Awaiting implantation of a permanent pacemaker • Having transient bradyarrhythmias (reversible drug toxicities, for example). • There are two types of temporary pacemakers. • External transthoracic (emergency use) • Transvenous Placing a Transvenous Pacemaker https://www.youtube.com/watch?app=desktop&v=00-T8PcbStE and https://thoracickey.com/pacemakers/ Electronic Permanent Pacemakers https://www.researchgate.net/figure/Chest-X-ray-PA-view-postpermanent-pacemaker-implantation_fig4_323359253 • Various configurations can sense and capture the electric activity of the atria and/or ventricles. • Wires (leads) with pacing electrodes are passed through an axillary or subclavian vein into the right ventricle or right atrium, or through the coronary sinus into a cardiac vein (to stimulate the left ventricle). • The pulse generator is connected to the leads and then implanted under the skin, typically in the infraclavicular region. • Pacemakers can incorporate complex functions to track the patient’s normal heart rate and can stimulate beats automatically in response to activity. • Cardiac resynchronization therapy can also be accomplished with stimulation of both chambers simultaneously. Tachyarrhythmias • Pharmacologic therapy is directed against the underlying mechanism: abnormal automaticity, reentrant circuits, and triggered activity. • Note: It is important to recognize that although these drugs suppress arrhythmias, they also have the potential to aggravate or provoke certain rhythm disturbances. Desired drug effects to eliminate rhythms caused by increased automaticity: • 1. Reduce the slope of phase 4 spontaneous depolarization. • 2. Make the diastolic potential more negative (hyperpolarize). • 3. Make the threshold potential less negative. Desired antiarrhythmic effects to interrupt reentrant circuits: 1. Inhibit conduction in the reentry circuit to the point that conduction fails, thus stopping the reentry impulse. 2. Increase the refractory period within the reentrant circuit so that a propagating impulse finds tissue within the loop unexcitable and thus stops. 3. Suppress premature beats that can initiate reentry. Desired drug Effects to eliminate triggered activity: 1. Shorten the action potential duration (to prevent early afterdepolarizations). 2. Correct conditions of calcium overload (to prevent delayed afterdepolarizations ). Antiarrhythmic Drugs • Class I drugs act by blocking the fast sodium channels. These drugs affect impulse conduction, excitability, and automaticity to various degrees and have been divided into three groups (IA, IB, and IC) based on the kinetics of their sodium channel effects. • Class IA are used in supraventricular and ventricular tachycardias. • Class IB are used to treat ventricular arrhythmias. • Class IC are effective for atrial and ventricular premature beats, ventricular tachycardias, atrial and ventricular fibrillation, and flutter. • Class II drugs are β-adrenergic–blocking drugs that act by blunting the effect of sympathetic nervous system stimulation on the heart, thereby inhibiting calcium channel opening. These drugs decrease automaticity by depressing phase 4 of the action potential. They also decrease heart rate and cardiac contractility. These medications are effective for treatment of supraventricular arrhythmias and tachyarrhythmias by counteracting action on arrhythmogenesis of catecholamines. • Class III drugs act by inhibiting the potassium current and repolarization, thereby extending the action potential and refractoriness. They have little inhibiting effect on depolarizing currents. These agents are used in the treatment of serious ventricular arrhythmias. • Class IV drugs act by blocking the slow calcium channels, thereby depressing phase 4 and lengthening phases 1 and 2 of the action potential. By blocking the release of intracellular calcium ions, these agents reduce the force of myocardial contractility, thereby decreasing myocardial oxygen demand. These drugs are used to slow the SA node pacemaker and inhibit conduction in the AV node, slowing the ventricular response in atrial tachycardias, and to terminate reentrant paroxysmal supraventricular tachycardias when the AV node has a reentrant pathway. Vagotonic Maneuvers for Tachyarrythmias • The AV node is sensitive to vagal modulation, and this characteristic can be utilized to interrupt tachyarrhythmias. • These maneuvers usually slow conduction through the AV node and can terminate some reentrant tachyarrhythmias as well by increasing vagal tone. • 3 maneuvers: • Carotid sinus massage: rubbing firmly for a few seconds over the carotid sinus (located at the bifurcation of the internal and external carotid arteries on either side of the neck) stimulates the baroreceptor reflex which elicits the desired increase in vagal tone and withdrawal of sympathetic tone. • Valsalva maneuver: asking the patient to inhale and then to forcefully exhale against a closed glottis for ~10 seconds. • Modified Valsalva maneuver: the Valsalva maneuver is undertaken in the semirecumbent position, immediately followed by shifting the patient to a supine position and lifting both of the patient’s legs (“passive leg raising”) for 45 seconds. Electric Cardioversion and Defibrillation for Tachyarrythmias • These techniques involve the application of an electric shock to terminate a tachycardia. • A shock with sufficient energy depolarizes the bulk of excitable myocardial tissue: • This interrupts reentrant circuits. • It establishes electric homogeneity, a new electrical baseline. • It also allows the sinus node to regain pacemaker control. • Tachyarrhythmias caused by reentry can usually be terminated by this procedure, whereas arrhythmias due to abnormal automaticity may simply persist. https://en.wikipedia.org/ wiki/Defibrillation#/medi a/File:Defibrillation_Elect rode_Position.jpg • External cardioversion is used to terminate supraventricular tachycardias or organized ventricular tachycardias. • The patient is sedated and two large electrode paddles (or adhesive electrodes) are placed against the chest on either side of the heart. • The electric discharge is synchronized to occur at the time of a QRS complex. • External defibrillation is performed to terminate ventricular fibrillation. • During fibrillation, there is no organized QRS complex on which to synchronize the electric discharge. • The shock is delivered using the “asynchronous” mode of the defibrillator device. Tachyarrhythmias Implantable Cardioverter–Defibrillators • ICDs automatically terminate dangerous ventricular arrhythmias using internal cardioversion/defibrillation or artificial pacing. • Implanted in patients at high risk of sudden cardiac death from ventricular arrhythmias. • Anti-tachycardia pacing (ATP) is a rapid burst of electric impulses (monomorphic) which can artificially pace the heart at a rate faster than the tachycardia (often by depolarizing a portion of a reentrant circuit, thereby rendering it refractory to further stimulation). • The ATP technique is painless, but not effective for terminating ventricular fibrillation. Catheter Ablation • Arrhythmias that originate from a distinct anatomical reentry circuit or an automatic focus can be treated with catheter ablation. This is a permanent therapeutic solution that spares patients from prolonged antiarrhythmic drug therapy. • Electrophysiologic mapping techniques can be used to localize the region of myocardium or conduction tissue responsible for the disturbance. Example: atrial flutter. • It is possible to ablate the site via a catheter that applies radio frequency current to heat and destroy the tissue. Part 2: Outline and Objectives of Clinical Aspects of Cardiac Arrhythmias • Bradyarrythmias • The sinoatrial node • Sinus bradycardia and sick sinus syndrome • Atrioventricular blocks • 1st, 2nd, and 3rd degree blocks • Tachyarrythmias • Supraventricular arrhythmias • • • • • • • Sinus tach, atrial premature beats Atrial flutter Atrial fibrillation Paroxysmal supraventricular tachycardia AV nodal reentry Ventricular preexcitation Focal and multifocal atrial tachycardias • • • • Ventricular premature beats Ventricular tachycardia Torsades de pointes Ventricular fibrillation • Ventricular arrythmias DENNIS KUNKEL MICROSCOPY / SCIENCE PHOTO LIBRARY Heart muscle with capillaries and green purkinje fibres passing amongst the heart muscle fibres, coloured scanning electron micrograp, https://www.sciencephoto.com/media/797609/view Steps to Confronting an Arrythmia There are five basic questions to consider when confronted with a patient with an abnormal heart rhythm: 1. Identification: What is the arrhythmia? 2. Pathogenesis: What is the underlying mechanism? 3. Precipitating factors: What conditions provoke it? 4. Clinical presentation: What symptoms and signs accompany the arrhythmia? 5. Treatment: What to do about it? • The sinus node has automaticity and normally fires at 60–100 beats/minute, and it reaches the threshold for excitation before other parts of the conduction system have recovered sufficiently to be depolarized. • If the SA node fires more slowly or SA node conduction is blocked, another site that is capable of automaticity takes over as pacemaker. • The SA node may be functioning properly, but because of additional precipitating factors, other cardiac cells can become ectopic pacemakers and assume accelerated properties of automaticity and begin to initiate impulses. • These additional factors might include injury, hypoxia, electrolyte disturbances, enlargement or hypertrophy of the atria or ventricles, and exposure to certain chemicals or drugs. Normal Sinus Rhythm • NSR follows a normal conduction pattern • Regular rhythm (R – R distance is regular) • There is a P wave before each QRS complex, and it has a normal shape and duration • The P-R interval normal indicating that the impulse originated in the SA node rather than in another area of the conduction system that has a slower inherent rate. • The QRS complex normal shape and duration Part 2, Section 1: Bradyarrythmias • Caption: (B) Specialized pacemaker cells of the cardiac conduction system are “walled up” in the dense fibrous tissue (thin black arrows); the sinoatrial nodal artery is shown with a star; Masson's trichrome stain, ×100. (C) Purkinje-like cells at the margins of the SAN (shown with a black arrow); haematoxylin and eosin, ×200. • Mitrofanova, L.B., Gorshkov, A.N., Konovalov, P.V. and Krylova, J.S. (2018), Telocytes in the human sinoatrial node. J. Cell. Mol. Med., 22: 521532. https://doi.org/10.1111/jcmm.13340 Sinus Bradycardia • This rhythm may be normal during rest or sleep and in trained athletes, who maintain a large stroke volume. • Vagal stimulation can decrease the firing rate of the SA node and conduction through the AV node. • Pathologic sinus bradycardia can result from either intrinsic SA node disease or extrinsic factors. Examples: Intrinsic factors: • Sinus node fires < 60 beats/minute • Normal conduction pattern • Regular rhythm (R – R distance is regular) • P wave before each QRS complex and has a normal shape and duration • P-R interval normal • QRS complex normal shape and duration 1. Aging 2. Ischemic heart disease 3. Cardiomyopathy Extrinsic factors: 1. Medications (β-blockers and certain calcium channel blockers) 2. Metabolic causes (hypothyroidism) • Sinus arrest refers to failure of the SA node to discharge and may result in prolonged periods of asystole and often predisposes to other arrhythmias. Sinus Nodal Rhythms A. Sinus rhythm B. Bradycardia C. Sinus tachycardia D. Respiratory arrhythmia • Sick sinus syndrome (SSS) is a term that describes a number of forms of cardiac impulse formation and intra-atrial and AV conduction abnormalities. • The syndrome is most frequently the result of total or subtotal destruction of the SA node, areas of nodal–atrial discontinuity, inflammatory or degenerative changes of the nerves and ganglia surrounding the node, or pathologic changes in the atrial wall (such as fibrosis). • Occlusion of the sinus node artery may be a significant contributing factor. • Can be seen in people with coronary artery disease, fibrosis infective processes, certain drugs, and collagen vascular diseases. In children, the syndrome is most commonly associated with congenital heart defects, particularly after corrective cardiac surgery. • Treatment frequently involves the implantation of a permanent pacemaker combined with drug therapy. Sick Sinus Syndrome https://litfl.com/sinus-node-dysfunction-sick-sinus-syndrome/ A Subset of SSS: The Bradycardia-Tachycardia Syndrome • SSS is common in elderly patients, who are also susceptible to supraventricular tachycardias (SVTs), most commonly atrial fibrillation (AF). • During the tachyarrhythmia, overdrive suppression of the SA node occurs, and when the tachycardia terminates, a period of profound sinus bradycardia may ensue. • This combination of slow and fast • Treatment generally requires the dysrhythmias is known as the bradycardia combination of antiarrhythmic drug therapy -tachycardia syndrome and is thought to to suppress the tachyarrhythmias plus a result from atrial fibrosis that impairs permanent pacemaker to prevent function of the SA node and predisposes bradycardia. to AF and atrial flutter. Escape Rhythms: Junctional Escapes • When SA node activity becomes impaired, or if there is conduction block, escape rhythms can emerge from the more distal latent pacemakers. • Junctional escape beats arise from the AV node or proximal bundle of His and have normal and narrow QRS complexes. https://www.leveluprn.com/blogs/ekg-interpretation/7-junctional-rhythms • Rates are 40 to 60 bpm. • The QRS complexes are not preceded by normal P waves. The P wave will be either absent, inverted, in the wrong place, or with a very short PR interval. • Retrograde P waves may be observed as an impulse propagates from the more distal pacemaker backward to the atrium. • Retrograde P waves typically follow the QRS complex (but may also fall just prior to it) and are abnormally inverted (negative deflection on the electrocardiogram [ECG]) in limb leads II, III, and aVF, indicating activation of the atria starting from the AV node and proceeding superiorly. Ventricular Escape Rhythms • Ventricular escape rhythms maintain a heartbeat and cardiac output when the sinus node or normal AV conduction fails. • The heart rate is usually 30 - 40 bpm and the QRS complexes are wide. • There may be LBBB or RBBB patterns depending on the site of origin of the ventricular escape rhythm. An escape rhythm originating from the left bundle branch will cause a right bundle branch block QRS pattern, and one originating from the RBB will yield a LBBB pattern. • Escape rhythms that originate more distally, in the ventricular myocardium itself, are characterized by even wider QRS complexes. Atrioventricular Conduction System Blocks: 1st Degree • The AV conduction system includes the AV node, the bundle of His, and the left and right bundle branches. Impaired conduction between the atria and ventricles can result in 3 types or degrees of AV conduction block. • First-degree AV block: prolongation of the normal delay between atrial and ventricular depolarization. The PR interval is lengthened (>0.2 seconds, which is >5 small boxes on the ECG), but the 1:1 relationship between P waves and QRS complexes is preserved. • The impairment is usually within the AV node itself and can be caused by a transient reversible influence or a structural defect. • Reversible causes include heightened vagal tone, transient AV nodal ischemia, and drugs that depress conduction through the AV node, including β-blockers, certain calcium channel antagonists, digitalis, and other antiarrhythmic medications. • Structural causes include myocardial infarction and chronic degenerative diseases of the conduction system, which may occur with aging. • First-degree AV block is typically a benign condition that does not require treatment. However, it can indicate disease in the AV node associated with susceptibility to higher degrees of AV block if drugs are administered that further impair AV conduction or if the conduction disease progresses. 2nd Degree AV Block: Mobitz Type 1 (Wenckebach) • There are 2 forms of 2nd degree AV block, and • both are characterized by intermittent failure of AV conduction, resulting in some P waves that are not followed by a QRS complex. • Mobitz type I block (Wenckebach): the degree • of AV delay gradually increases with each beat until an impulse is completely blocked, such that there is no QRS after the P wave for a single beat. • • The ECG shows a progressive increase in the PR interval from one beat to the next until a single QRS complex is absent, after which the PR interval shortens to its initial length, and the cycle starts anew. It is usually benign and may be seen in children, trained athletes, and people with high vagal tone, particularly during sleep. It may also occur during an acute MI (increased vagal tone or ischemia of the AV node) and is usually temporary. Treatment is typically not necessary, but in symptomatic cases, administration o intravenous atropine or isoproterenol usually improves AV conduction transiently. 2nd Degree AV Block: Mobitz Type 2 and High Grade Type 2 • Type II second-degree AV block is a more dangerous condition. • It is characterized by the sudden intermittent loss of AV conduction, without preceding gradual lengthening of the PR interval and with no QRS following the blocked atrial signal. • Type II block is usually caused by conduction block distal to the AV node (in the bundle of His or more distally in the Purkinje system). • The QRS pattern often is widened in a pattern of right or left bundle branch block. • This type of block may arise from extensive myocardial infarction involving the septum or from chronic degeneration of the His–Purkinje system. • It usually indicates severe disease and may progress to complete heart block without warning. • In hig