InternalMed_Harrison

InternalMed_Harrison. The normal cardiac impulse is generated by pacemaker cells in the sinoatrial node situated at the junction of the right atrium and the superior vena cava (see Fig. 268-1). This impulse is transmitted slowly through nodal tissue to the anatomically complex atria, where it is conducted more rapidly to the atrioventricular node (AVN), inscribing the P wave of the ECG (see Fig. 268-2). There is a perceptible delay in conduction through the anatomically and functionally heterogeneous AVN. The time needed for activation of the atria and the AVN delay is represented as the PR interval of the ECG. The AVN is the only electrical connection between the atria and the ventricles in the normal heart. The electrical impulse emerges from the AVN and is transmitted to the His-Purkinje system, specifically the common bundle of His, then the left and right bundle branches, and then to the Purkinje network, facilitating activation of ventricular muscle. In normal circumstances, the ventricles are


InternalMed_Harrison

InternalMed_Harrison. the common bundle of His, then the left and right bundle branches, and then to the Purkinje network, facilitating activation of ventricular muscle. In normal circumstances, the ventricles are activated rapidly in a well-defined fashion that is determined by the course of the Purkinje network, and this inscribes the QRS complex (see Fig. 268-2). Recovery of electrical excitability occurs more slowly and is governed by the time of activation and duration of regional action potentials. The relative brevity of epicardial action potentials in the ventricle results in repolarization that occurs first on the epicardial surface and then proceeds to the endocardium, which inscribes a T wave normally of the same polarity as the QRS complex. The duration of ventricular activation and recovery is determined by the action potential duration and is represented on the body surface ECG by the QT interval (see Fig. 268-2).


InternalMed_Harrison

InternalMed_Harrison. Cardiac myocytes exhibit a characteristically long action potential (200–400 ms) compared with neurons and skeletal muscle cells (1–5 ms). The action potential profile is sculpted by the orchestrated activity of multiple distinctive timeand voltage-dependent ionic currents (Fig. 273e-1A). The currents are carried by transmembrane CHAPTER 273e Principles of Electrophysiology


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InternalMed_Harrison. PART 10 Disorders of the Cardiovascular System 273e-2 proteins that passively conduct ions down their electrochemical gradients through selective pores (ion channels), actively transport ions against their electrochemical gradient (pumps, transporters), or electrogenically exchange ionic species (exchangers). Action potentials in the heart are regionally distinct. The regional variability in cardiac action potentials is a result of differences in the number and types of ion channel proteins expressed by different cell types in the heart. Further, unique sets of ionic currents are active in pacemaking and muscle cells, and the relative contributions of these currents may vary in the same cell type in different regions of the heart (Fig. 273e-1A). Ion channels are complex, multisubunit transmembrane glycoproteins that open and close in response to a number of biologic stimuli, including a change in membrane voltage, ligand binding (directly to the channel or to a G protein–coupled


InternalMed_Harrison

InternalMed_Harrison. transmembrane glycoproteins that open and close in response to a number of biologic stimuli, including a change in membrane voltage, ligand binding (directly to the channel or to a G protein–coupled receptor), and mechanical deformation (Fig. 273e-2). Other ion motive exchangers and transporters contribute importantly to cellular excitability in the heart. Ion pumps establish and maintain the ionic gradients across the cell membrane that serve as the driving force for current flow through ion channels. Transporters or exchangers that do not move ions in an electrically neutral manner (e.g., the sodium-calcium exchanger transports three Na+ for one Ca2+) are termed electrogenic and contribute directly to the action potential profile. The most abundant superfamily of ion channels expressed in the heart is voltage gated. Several structural themes are common to all voltage-dependent ion channels. First, the architecture is modular, consisting either of four homologous subunits (e.g., K


InternalMed_Harrison

InternalMed_Harrison. in the heart is voltage gated. Several structural themes are common to all voltage-dependent ion channels. First, the architecture is modular, consisting either of four homologous subunits (e.g., K channels) or of four internally homologous domains (e.g., Na and Ca channels). Second, the proteins fold around a central pore lined by amino acids that exhibit exquisite conservation within a given channel family of like selectivity (e.g., all Na channels have very similar P segments). Third, the general strategy for activation gating (opening and closing in response to changes in membrane voltage) is highly conserved: the fourth trans-membrane segment (S4), studded with positively charged residues, lies within the membrane field and moves in response to depolarization, opening the channel. Fourth, most ion channel complexes include not only the pore-forming proteins (α subunits) but also auxiliary subunits (e.g., β subunits) that modify channel function (Fig. 273e-2). Na and Ca channels


InternalMed_Harrison

InternalMed_Harrison. most ion channel complexes include not only the pore-forming proteins (α subunits) but also auxiliary subunits (e.g., β subunits) that modify channel function (Fig. 273e-2). Na and Ca channels are the primary carriers of depolarizing current in both the atria and the ventricles; inactivation of these currents and activation of repolarizing K currents hyperpolarize the heart cells, reestablishing the negative resting membrane potential (Fig. 273e-1B). The plateau phase is a time when little current is flowing, and relatively minor changes in depolarizing or repolarizing currents can have profound effects on the shape and duration of the action profile. Mutations in subunits of these channel proteins produce arrhythmogenic alterations in the action potentials that cause long and short QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, familial atrial fibrillation, and some forms of conduction system disease.


InternalMed_Harrison

InternalMed_Harrison. Cardiac arrhythmias result from abnormalities of electrical impulse generation, conduction, or both. Bradyarrhythmias typically arise from disturbances in impulse formation at the level of the sinoatrial node or from disturbances in impulse propagation at any level, including exit block from the sinus node, conduction block in the AVN, and impaired conduction in the His-Purkinje system. Tachyarrhythmias can be classified according to mechanism, including enhanced automaticity (spontaneous depolarization of atrial, junctional, or ventricular pacemakers), triggered arrhythmias (initiated by afterdepolarizations occurring during or immediately after cardiac repolarization, during phase 3 or 4 of the action potential), or reentry (circus propagation of a depolarizing wavefront). A variety of mapping and pacing maneuvers typically performed during invasive electrophysiologic testing can often determine the underlying mechanism of a tachyarrhythmia (Table 273e-1).


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InternalMed_Harrison. Alterations in Impulse Initiation: Automaticity Spontaneous (phase 4) diastolic depolarization underlies the property of automaticity characteristic of pacemaking cells in the sinoatrial (SA) and atrioventricular


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InternalMed_Harrison. FIGURE 273e-2 Topology and subunit composition of the voltage-dependent ion channels. Potassium channels are formed by the tetramerization of α or pore-forming subunits and one or more β subunits; only single β subunits are shown for clarity. Sodium and calcium channels are composed of α subunits with four homologous domains and one or more ancillary subunits. In all channel types, the loop of protein between the fifth and sixth membrane-spanning repeat in each subunit or domain forms the ion-selective pore. In the case of the sodium channel, the channel is a target for phosphorylation, the linker between the third and fourth homologous domain is critical to inactivation, and the sixth membrane-spanning repeat in the fourth domain is important in local anesthetic antiarrhythmic drug binding. The Ca channel is a muiltisubunit protein complex with the α1 subunit containing the pore and major drug binding domain.


InternalMed_Harrison

InternalMed_Harrison. Normal or enhanced automaticity of subsidiary latent pacemakers 273e-3 produces escape rhythms in the setting of failure of more dominant pacemakers. Suppression of a pacemaker cell by a faster rhythm leads to an increased intracellular Na+ load ([Na+]i), and extrusion of Na+ from the cell by Na, K-ATPase produces an increased background repolarizing current that slows phase 4 diastolic depolarization. At slower rates, [Na+]i is decreased, as is the activity of the Na, K-ATPase, warm-up of the tachycardia rate. Overdrive suppression and warm-up are characteristic of, but may not be observed in, all automatic tachy cardias. Abnormal conduction into tissue with enhanced automaticity (entrance block) may blunt or eliminate the phenomena of overdrive CHAPTER 273e Principles of Electrophysiology suppression and warm-up of automatic tissue.


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InternalMed_Harrison. CHAPTER 273e Principles of Electrophysiology suppression and warm-up of automatic tissue. Abnormal automaticity may produce atrial tachycardia, acceler ated idioventricular rhythms, and ventricular tachycardia, particularly associated with ischemia and reperfusion. It has also been suggested that injury currents at the borders of ischemic myocardium may depolarize adjacent nonischemic tissue, predisposing to automatic ventricular tachycardia. Abbreviations: AP, action potential; AV, atrioventricular; DADs, delayed afterdepolarizations; EADs, early afterdepolarizations; HF, heart failure; LVH, left ventricular hypertrophy; VF, ventricular fibrillation; VT, ventricular tachyarrhythmia.


InternalMed_Harrison

InternalMed_Harrison. (AV) nodes, His-Purkinje system, coronary sinus, and pulmonary veins. Phase 4 depolarization results from the concerted action of a number of ionic currents, including K+ currents, Ca2+ currents, electrogenic Na, K-ATPase, the Na-Ca exchanger, and the so-called funny, or pacemaker, current (If); however, the relative importance of these currents remains controversial.


InternalMed_Harrison

InternalMed_Harrison. The rate of phase 4 depolarization and, therefore, the firing rates of pacemaker cells are dynamically regulated. Prominent among the factors that modulate phase 4 is autonomic nervous system tone. The negative chronotropic effect of activation of the parasympathetic nervous system is a result of the release of acetylcholine that binds to muscarinic receptors, releasing G protein βγ subunits that activate a potassium current (IKACh) in nodal and atrial cells. The resulting increase in K+ conductance opposes membrane depolarization, slowing the rate Afterdepolarizations and Triggered Automaticity Triggered automaticity or activity refers to impulse initiation that is dependent on afterdepolarizations (Fig. 273e-3). Afterdepolarizations are membrane voltage oscillations that occur during (early afterdepolarizations, EADs) or after (delayed afterdepolarizations, DADs) an action potential.


InternalMed_Harrison

InternalMed_Harrison. The cellular feature common to the induction of DADs is the presence of an increased Ca2+ load in the cytosol and sarcoplasmic reticulum. Digitalis glycoside toxicity, catecholamines, and ischemia all can enhance Ca2+ loading sufficiently to produce DADs. Accumulation of lysophospholipids in ischemic myocardium with consequent Na+ and Ca2+ overload has been suggested as a mechanism for DADs and triggered automaticity. Cells from damaged areas or cells that survive a myocardial infarction may display spontaneous release of calcium from the sarcoplasmic reticulum, and this may generate “waves” of intracellular calcium elevation and arrhythmias.


InternalMed_Harrison

InternalMed_Harrison. EADs occur during the action potential and interrupt the orderly repolarization of the myocyte. Traditionally, EADs have been thought to arise from action potential prolongation and reactivation of depolarizing currents, but more recent experimental evidence suggests a previously unappreciated interrelationship between intracellular calcium loading and EADs. Cytosolic calcium may increase when action potentials are prolonged. This, in turn, appears to enhance L-type Ca current, further prolonging action potential duration as well as providing the inward current driving EADs. Intracellular calcium loading by action potential prolongation may also enhance the likelihood of DADs. The interrelationship among intracellular [Ca2+], EADs, and DADs may be one explanation for the susceptibility of hearts that are of rise of phase 4 of the action potential. Conversely, augmentation of 0 mV sympathetic nervous system tone increases myocardial catecholamine concentrations, which activate both


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InternalMed_Harrison. of hearts that are of rise of phase 4 of the action potential. Conversely, augmentation of 0 mV sympathetic nervous system tone increases myocardial catecholamine concentrations, which activate both α-and β-adrenergic receptors. The effect of β1-adrenergic stimulation predominates in pacemaking cells, augmenting both L-type Ca current (I ) and I , thus increasing the slope of phase 4. Enhanced sympathetic nervous system activity can dramatically increase the rate of firing of SA nodal cells, producing sinus tachycardia with rates >200 beats/min. By contrast, the increased rate of firing of Purkinje cells is more limited, rarely producing ven tricular tachyarrhythmias >120 beats/min.


InternalMed_Harrison

InternalMed_Harrison. Normal automaticity may be affected by a number of other factors 0.5 s associated with heart disease. Hypokalemia and ischemia may reduce the activity of Na, K-ATPase, thereby reducing the background repolar-FIGURE 273e-3 Schematic action potentials with early after-izing current and enhancing phase 4 diastolic depolarization. The end depolarizations (EADs) and delayed afterdepolarizations (DADs). result would be an increase in the spontaneous firing rate of pacemaking Afterdepolarizations are spontaneous depolarizations in cardiac cells. Modest increases in extracellular potassium may render the maxi-myocytes. EADs occur before the end of the action potential (phases mum diastolic potential more positive, thereby also increasing the firing 2 and 3), interrupting repolarization. DADs occur during phase 4 of rate of pacemaking cells. A more significant increase in [K+]o, however, the action potential after completion of repolarization. The cellular renders the heart inexcitable by


InternalMed_Harrison

InternalMed_Harrison. occur during phase 4 of rate of pacemaking cells. A more significant increase in [K+]o, however, the action potential after completion of repolarization. The cellular renders the heart inexcitable by depolarizing the membrane potential. mechanisms of EADs and DADs differ (see text).


InternalMed_Harrison

InternalMed_Harrison. PART 10 Disorders of the Cardiovascular System 273e-4 calcium loaded (e.g., in ischemia or congestive heart failure) to develop arrhythmias, particularly on exposure to action potential–prolonging drugs. EAD-triggered arrhythmias exhibit rate dependence. In general, the amplitude of an EAD is augmented at slow rates when action potentials are longer. Indeed, a fundamental condition that underlies the development of EADs is action potential and QT prolongation. Hypokalemia, hypomagnesemia, bradycardia, and, most commonly, drugs can predispose to the generation of EADs, invariably in the context of prolonging the action potential. Antiarrhythmics with class IA and III action (see below) produce action potential and QT prolongation intended to be therapeutic but frequently causing arrhythmias. Noncardiac drugs such as phenothiazines, nonsedating antihistamines, and some antibiotics can also prolong the action potential duration and predispose to EAD-mediated triggered arrhythmias.


InternalMed_Harrison

InternalMed_Harrison. Noncardiac drugs such as phenothiazines, nonsedating antihistamines, and some antibiotics can also prolong the action potential duration and predispose to EAD-mediated triggered arrhythmias. Decreased [K+]o paradoxically may decrease membrane potassium currents (particularly the delayed rectifier current, IKr) in the ventricular myocyte, explaining why hypokalemia causes action potential prolongation and EADs. In fact, potassium infusions in patients with the congenital long QT syndrome (LQTS) and in those with drug-induced acquired QT prolongation shorten the QT interval. EAD-mediated triggered activity probably underlies initiation of the characteristic polymorphic ventricular tachycardia, torsades des pointes, seen in patients with congenital and acquired forms of LQTS. Structural heart disease, such as cardiac hypertrophy and heart failure, may also delay ventricular repolarization (so-called electrical remodeling) and predispose to arrhythmias related to abnormalities of


InternalMed_Harrison

InternalMed_Harrison. heart disease, such as cardiac hypertrophy and heart failure, may also delay ventricular repolarization (so-called electrical remodeling) and predispose to arrhythmias related to abnormalities of repolarization. The abnormalities of repolarization in hypertrophy and heart failure are often magnified by concomitant drug therapy or electrolyte disturbances.


InternalMed_Harrison

InternalMed_Harrison. Abnormal Impulse Conduction: Reentry The most common arrhythmia mechanism is reentry resulting from abnormal electrical impulse conduction and is defined as the circulation of an activation wave around an inexcitable obstacle. The requirements for reentry are two electrophysiologically dissimilar pathways for impulse propagation around an inexcitable region (Fig. 273e-4). Reentry can occur around a fixed anatomic structure (e.g., myocardial scar), with a stable pattern of cardiac depolarization moving in series over the anterograde and retrograde limbs of the circuit. This form of reentry, referred to as anatomic reentry or excitable gap reentry (see below), is initiated when a depolarizing wavefront encounters an area of unidirectional conduction block in the retrograde limb of the circuit. Conduction across the anterograde limb occurs with a delay that, if of sufficient duration, allows for recovery of conduction in the retrograde limb with reentry of the depolarization wave into


InternalMed_Harrison

InternalMed_Harrison. Conduction across the anterograde limb occurs with a delay that, if of sufficient duration, allows for recovery of conduction in the retrograde limb with reentry of the depolarization wave into the retrograde limb of


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InternalMed_Harrison. FIGURE 272-4 Schematic diagram of reentry. A. The circuit contains two limbs, one with slow conduction. B. A premature impulse blocks in the fast pathway and conducts over the slow pathway, allowing the fast pathway to recover so that the activation wave can reenter the fast pathway from the retrograde direction. C. During sustained reentry utilizing such a circuit, a gap (excitable gap) exists between the activating head of the wave and the recovering tail. D. One mechanism of termination of reentry occurs when the conduction and recovery characteristics of the circuit change and the activating head of the wave collides with the tail, extinguishing the tachycardia.


InternalMed_Harrison

InternalMed_Harrison. the circuit. Sustained reentry requires that the functional dimension of depolarized tissue or the tachycardia wavelength (λ = conduction velocity × refractory period) fits within the total anatomic length of the circuit, referred to as the path length. When the path length of the circuit exceeds the λ of the tachycardia, the region between the head of the activation wave and the refractory tail is referred to as the excitable gap. Anatomically determined, excitable gap reentry can explain several clinically important tachycardias, such as AV reentry, atrial flutter, bundle branch reentry ventricular tachycardia, and ventricular tachycardia in scarred myocardium.


InternalMed_Harrison

InternalMed_Harrison. Reentrant arrhythmias may exist in the heart in the absence of an excitable gap and with a tachycardia wavelength nearly the same size as the path length. In this case, the wavefront propagates through partially refractory tissue without a fixed anatomic obstacle and no fully excitable gap; this is referred to as leading circle reentry, a form of functional reentry (reentry that depends on functional properties of the tissue). Unlike excitable gap reentry, there is no fixed anatomic circuit in leading circle reentry, and it may, therefore, not be possible to disrupt the tachycardia with pacing or destruction of a part of the circuit. Furthermore, the circuit in leading circle reentry tends to be less stable than that in excitable gap reentrant arrhythmias, with large variations in cycle length and a predilection to termination. There is strong evidence to suggest that less organized arrhythmias, such as atrial and ventricular fibrillation, are associated with more complex activation


InternalMed_Harrison

InternalMed_Harrison. length and a predilection to termination. There is strong evidence to suggest that less organized arrhythmias, such as atrial and ventricular fibrillation, are associated with more complex activation of the heart and are due to functional reentry.


InternalMed_Harrison

InternalMed_Harrison. Catheter-based and pharmacologic therapies for reentrant arrhythmias are designed to disrupt the anatomic circuit or alter the relationship between the wavelength and path length of the arrhythmia circuit, eliminating pathologic conduction. For example, antiarrhythmic drugs that prolong the action potential (Class III) are effective if they sufficiently prolong the λ such that it can no longer fit within the anatomic circuit. Catheter ablation is often undertaken with the goal of identifying and destroying a critical limb of the reentrant circuit (i.e., ablation of the cavotricuspid isthmus in the treatment of typical, right atrial flutter). Due to the less defined pathways of myocardial activation seen in functional reentry, ablation of these rhythms tends to target initiating triggers (e.g., pulmonary vein potentials in catheter ablation of atrial fibrillation) rather than the anatomic circuit.


InternalMed_Harrison

InternalMed_Harrison. Structural heart disease is associated with changes in conduction and refractoriness that increase the risk of reentrant arrhythmias. Chronically ischemic myocardium exhibits a downregulation of the gap junction channel protein (connexin 43) that carries intercellular ionic current. The border zones of infarcted and failing ventricular myocardium exhibit not only functional alterations of ionic currents but also remodeling of tissue and altered distribution of gap junctions. The changes in gap junction channel expression and distribution, in combination with macroscopic tissue alterations, support a role for slowed conduction in reentrant arrhythmias that complicate chronic coronary artery disease (CAD). Aged human atrial myocardium exhibits altered conduction, manifest as highly fractionated atrial electrograms, producing an ideal substrate for the reentry that may underlie the very common development of atrial fibrillation in the elderly. APPROACH TO THE PATIENT:


InternalMed_Harrison

InternalMed_Harrison. APPROACH TO THE PATIENT: The evaluation of patients with suspected cardiac arrhythmias is highly individualized; however, two key features—the history and ECG—are pivotal in directing the diagnostic workup and therapy. Patients with cardiac arrhythmias exhibit a wide spectrum of clinical presentations that range from asymptomatic ECG abnormalities to survival from cardiac arrest. In general, the more severe the presenting symptoms are, the more aggressive the evaluation and treatment are. Loss of consciousness that is believed to be of cardiac origin typically mandates an exhaustive search for the etiology and often requires invasive, device-based therapy. The presence of structural heart disease and prior myocardial infarction dictates a change in the approach to the management of syncope or ventricular arrhythmias. The presence of a family history of serious ventricular arrhythmias or premature sudden death will influence the evaluation of presumed heritable arrhythmias.


InternalMed_Harrison

InternalMed_Harrison. The physical examination is focused on determining whether there is cardiopulmonary disease that is associated with specific cardiac arrhythmias. The absence of significant cardiopulmonary disease often, but not always, suggests benignity of the rhythm disturbance. In contrast, palpitations, syncope, or near syncope in the setting of significant heart or lung disease have more ominous implications. In addition, the physical examination may reveal the presence of a persistent arrhythmia such as atrial fibrillation.


InternalMed_Harrison

InternalMed_Harrison. The judicious use of noninvasive diagnostic tests is an important element in the evaluation of patients with arrhythmias, and there is no test more important than the ECG, particularly if recorded at the time of symptoms. Uncommon but diagnostically important signatures of electrophysiologic disturbances may be unearthed on the resting ECG, such as delta waves in Wolff-Parkinson-White (WPW) syndrome, prolongation or shortening of the QT interval, right precordial ST-segment abnormalities in Brugada syndrome, and epsilon waves in arrhythmogenic right ventricular dysplasia. Variants of body surface ECG recording can provide important information about arrhythmia substrates and triggers. Holter monitoring and event recording, either continuous or intermittent, record the body surface ECG over longer periods, enhancing the possibility of observing the cardiac rhythm during symptoms. Holter monitoring is particularly useful in assessing daily symptoms thought to be attributable to


InternalMed_Harrison

InternalMed_Harrison. ECG over longer periods, enhancing the possibility of observing the cardiac rhythm during symptoms. Holter monitoring is particularly useful in assessing daily symptoms thought to be attributable to arrhythmia or for quantifying a particular arrhythmia phenomenon (e.g., premature ventricular complex burden). Ambulatory event monitors are indicated when symptoms thought to be due to arrhythmia occur less frequently (i.e., several episodes per month), and, because the monitors are typically patient-activated, they are optimal for correlating symptoms with rhythm disturbances. Implantable long-term monitors permit prolonged telemetric monitoring both for diagnosis and to assess the efficacy of therapy. Implantable monitors are typically used for the evaluation of malignant symptoms that occur quite infrequently and that cannot be provoked at diagnostic electro-physiology study.


InternalMed_Harrison

InternalMed_Harrison. Exercise electrocardiography is important in determining the presence of myocardial demand ischemia; more recently, analysis of the morphology of the QT interval with exercise has been used to assess the risk of serious ventricular arrhythmias. The exercise ECG may be particularly useful in patients with symptoms that occur during activity. Cardiac imaging plays an important role in the detection and characterization of myocardial structural abnormalities that may render the heart more susceptible to arrhythmia. Ventricular tachyarrhythmias, for instance, occur more frequently in patients with ventricular systolic dysfunction and chamber dilation, in hypertrophic cardiomyopathy, and in the setting of infiltrative diseases such as sarcoidosis. Supraventricular arrhythmias may be associated with particular congenital conditions, including AV reentry in the setting of Ebstein’s anomaly. Echocardiography is a frequently employed imaging technique to screen for disorders of cardiac


InternalMed_Harrison

InternalMed_Harrison. with particular congenital conditions, including AV reentry in the setting of Ebstein’s anomaly. Echocardiography is a frequently employed imaging technique to screen for disorders of cardiac structure and function. Increasingly, magnetic resonance imaging of the myocardium is being used to screen for scar burden, fibrofatty infiltration of the myocardium as seen in arrhythmogenic right ventricular cardiomyopathy, and other structural changes that affect arrhythmia susceptibility.


InternalMed_Harrison

InternalMed_Harrison. Head-up tilt (HUT) testing is useful in the evaluation of patients with syncope in whom there is a suspicion that exaggerated vagal tone or vasodepression may play a causal role. The physiologic response to HUT is incompletely understood; however, redistribution of blood volume and increased ventricular contractility occur consistently. Exaggerated activation of a central reflex in response to HUT produces a stereotypic response of an initial increase in heart rate, then a drop in blood pressure followed by a reduction in heart rate characteristic of neurally mediated hypotension. Other responses to HUT may be observed in patients with orthostatic hypotension and autonomic insufficiency. HUT is used most often in patients with recurrent syncope, although it may be useful in patients with single syncopal episodes with associated injury, particularly in the absence of structural heart disease. In patients with structural heart disease, HUT may be indicated in those with syncope, in whom


InternalMed_Harrison

InternalMed_Harrison. syncopal episodes with associated injury, particularly in the absence of structural heart disease. In patients with structural heart disease, HUT may be indicated in those with syncope, in whom other causes (e.g., asystole, ventricular tachyarrhythmias) have been excluded. HUT has been suggested as a useful tool in the diagnosis of and therapy for recurrent idiopathic vertigo, chronic fatigue syndrome, recurrent transient ischemic attacks, and repeated falls of unknown etiology in the elderly. Importantly, HUT is relatively contraindicated in the presence of severe CAD with proximal coronary stenoses, known severe cerebrovascular disease, severe mitral stenosis, and obstruction to left ventricular outflow (e.g., aortic stenosis).


InternalMed_Harrison

InternalMed_Harrison. Electrophysiologic testing is central to the understanding and treatment of many cardiac arrhythmias. Indeed, most frequently, electrophysiologic testing is interventional, providing both diagnosis and therapy. The indications for electrophysiologic testing fall into several categories: to define the mechanism of an arrhythmia; to deliver catheter-based ablative treatment; and to determine the etiology of symptoms that may be caused by an arrhythmia (e.g., syncope, palpitations). The components of the electrophysiologic test are baseline measurements of conduction under resting and stressed (rate or pharmacologic) conditions and maneuvers, both pacing and pharmacologic, to induce arrhythmias. A number of sophisticated electrical mapping and catheter-guidance techniques have been developed to facilitate catheter-based therapeutics in the electrophysiology laboratory.


InternalMed_Harrison

InternalMed_Harrison. The interaction of antiarrhythmic drugs with cardiac tissues and the resulting electrophysiologic changes are complex. An incomplete understanding of the effects of these drugs has produced serious missteps that have had adverse effects on patient outcomes and the development of newer pharmacologic agents. Currently, antiarrhythmic drugs have been relegated to an ancillary role in the treatment of most cardiac arrhythmias.


InternalMed_Harrison

InternalMed_Harrison. There are several explanations for the complexity of antiarrhythmic drug action: the structural similarity of target ion channels; regional differences in the levels of expression of channels and transporters, which change with disease; time and voltage dependence of drug action; and the effect of these drugs on targets other than ion channels. Because of the limitations of any scheme to classify antiarrhythmic agents, a shorthand that is useful in describing the major mechanisms of action is of some utility. Such a classification scheme was proposed in 1970 by Vaughan-Williams and later modified by Singh and Harrison. The classes of antiarrhythmic action are class I, local anesthetic effect due to blockade of Na+ current; class II, interference with the action of catecholamines at the β-adrenergic receptor; class III, delay of repolarization due to inhibition of K+ current or activation of depolarizing current; and class IV, interference with calcium conductance (Table 273e-2). Class


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InternalMed_Harrison. receptor; class III, delay of repolarization due to inhibition of K+ current or activation of depolarizing current; and class IV, interference with calcium conductance (Table 273e-2). Class I antiarrhythmics have been further subdivided based on the kinetics and potency of Na+ channel binding; class Ia agents (quinidine, procainamide) are those with moderate potency and intermediate kinetics; class Ib agents (lidocaine, mexiletine) are those with low potency and rapid kinetics; and class Ic drugs (flecainide, propafenone) are those with high potency and the slowest kinetics. The limitations of the Vaughan-Williams classification scheme include multiple actions of most drugs, overwhelming consideration of antagonism as a mechanism of action, and the fact that several agents have none of the four classes of action in the scheme.


InternalMed_Harrison

InternalMed_Harrison. The use of catheter ablation is based on the principle that there is a critical anatomic region of impulse generation or propagation that CHAPTER 273e Principles of Electrophysiology is required for the initiation and maintenance of cardiac arrhythmias. Destruction of such a critical region results in the elimination of the arrhythmia. The use of radiofrequency (RF) energy in clinical medicine is nearly a century old. The first catheter ablation using a DC energy source was performed in the early 1980s by Scheinman and colleagues. By the early 1990s, RF had been adapted for use in catheter-based ablation in the heart (Fig. 273e-5).


InternalMed_Harrison

InternalMed_Harrison. The RF band (300–30,000 kHz) is used to generate energy for several biomedical applications, including coagulation and cauterization of tissues. Energy of this frequency will not stimulate skeletal muscle or the heart and heats tissue by a resistive mechanism, with the intensity of heating and tissue destruction being proportional to the delivered power. Alternative, less frequently used energy sources for catheter ablation of cardiac arrhythmias include microwaves (915 MHz or 2450 MHz), lasers, ultrasound, and freezing (cryoablation). Of these alternative ablation techniques, cryoablation is being used clinically with the most frequency, especially ablation in the region of the AVN. At temperatures just below 32°C, membrane ion transport is disrupted, producing depolarization of cells, decreased action potential amplitude and duration, and slowed conduction velocity (resulting in local conduction block)—all of which are reversible if the tissue is rewarmed in a timely fashion.


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InternalMed_Harrison. FIGURE 273e-5 Catheter ablation of cardiac arrhythmias. A. A schematic of the catheter system and generator in a patient undergoing radiofrequency catheter ablation (RFCA); the circuit involves the catheter in the heart and a dispersive patch placed on the body surface (usually the back). The inset shows a diagram of the heart with a catheter located at the AV valve ring for ablation of an accessory pathway.


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InternalMed_Harrison. B. A right anterior oblique fluoroscopic image of the catheter position for ablation of a left-sided accessory pathway. A catheter is placed in the atrial side of the mitral valve ring (abl) via a transseptal puncture. Other catheters are placed in the coronary sinus (CS), in the right atrium (RA), and in the right ventricular (RV) apex to record local electrical activation. C. Body surface electrocardiogram recordings (I, II, V1) and endocardial electrograms (HRA, high right atrium; HISp, proximal His bundle electrogram; CS 7, 8, recordings from poles 7 and 8 of a decapolar catheter placed in the coronary sinus) during RFCA of a left-sided accessory pathway in a patient with Wolff-Parkinson-White syndrome. The QRS narrows at the fourth complex; the arrow shows the His bundle electrogram, which becomes apparent with elimination of ventricular preexcitation over the accessory pathway.


InternalMed_Harrison

InternalMed_Harrison. Tissue cooling can be used for mapping and ablation. Cryomapping can be used to confirm the location of a desired ablation target, such as an accessory pathway in WPW syndrome, or can be used to determine the safety of ablation around the AVN by monitoring AV conduction during cooling. Another advantage of cryoablation is that once the catheter tip cools below freezing, it adheres to the tissue, increasing catheter stability independent of the rhythm or pacing. Bradyarrhythmias due either to primary sinus node dysfunction or to atrioventricular conduction defects are readily treated through implantation of a permanent pacemaker. Clinical indications for pacemaker implantation often depend on the presence either of symptomatic bradycardia or of an unreliable endogenous escape rhythm and are more fully reviewed in Chaps. 274 and 275.


InternalMed_Harrison

InternalMed_Harrison. Ventricular tachyarrhythmias, particularly those occurring in the 273e-7 context of progressive structural heart diseases such as ischemic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy, may recur despite therapy with antiarrhythmic drugs or catheter ablation. In appropriate candidates, implantation of an internal cardioverter-defibrillator (ICD) may reduce mortality rates from sudden cardiac death. In a subset of patients with congestive heart failure (CHF) and ventricular mechanical dyssynchrony, ICD or pacemaker platforms can be used to provide cardiac resynchronization therapy, typically through implantation of a left ventricular pacing lead. In patients with dyssynchronous CHF, such therapy has been shown to improve both morbidity and mortality rates. CHAPTER 273e Principles of Electrophysiology


InternalMed_Harrison

InternalMed_Harrison. The Bradyarrhythmias: Disorders of the Sinoatrial node David D. Spragg, Gordon F. Tomaselli Electrical activation of the heart normally originates in the sinoatrial (SA) node, the predominant pacemaker. Other subsidiary 274 120 negative resting membrane potential compared with atrial or ventricular myocytes. Electrical diastole in nodal cells is characterized by slow diastolic depolarization (phase 4), which generates an action potential as the membrane voltage reaches threshold. The action potential upstrokes (phase 0) are slow compared with atrial or ventricular myocytes, being mediated by calcium rather than sodium current. Cells with properties of SA and AV nodal tissue are electrically connected to the remainder of the myocardium by cells with an electrophysiologic phenotype between that of nodal cells and that of atrial or ventricular myocytes. Cells in the SA node exhibit the most rapid phase 4 depolarization and thus are the dominant pacemakers in a normal heart.


InternalMed_Harrison

InternalMed_Harrison. Bradycardia results from a failure of either impulse initiation or impulse conduction. Failure of impulse initiation may be caused by depressed automaticity resulting from a slowing or failure of phase 4 diastolic depolarization (Fig. 274-2), which may result from disease or exposure to drugs. Prominently, the autonomic nervous system modulates the rate of phase 4 diastolic depolarization and thus the firing rate of both primary (SA node) and subsidiary pacemakers. Failure of conduction of an impulse from nodal tissue to atrial or ventricular myocardium may produce bradycardia as a result of exit block. Conditions that alter the activation and connectivity of cells (e.g., fibrosis) in the heart may result in failure of impulse conduction.


InternalMed_Harrison

InternalMed_Harrison. SA node dysfunction and AV conduction block are the most common causes of pathologic bradycardia. SA node dysfunction may be difficult to distinguish from physiologic sinus bradycardia, particularly in the young. SA node dysfunction increases in frequency between the fifth and sixth decades of life and should be considered in patients with fatigue, exercise intolerance, or syncope and sinus bradycardia. Permanent pacemaking is the only reliable therapy for symptomatic bradycardia in the absence of extrinsic and reversible etiologies such as increased vagal tone, hypoxia, hypothermia, and drugs (Table 274-1). Approximately 50% of the 150,000 permanent pacemakers implanted in the United States and 20–30% of the 150,000 of those in Europe were implanted for SA node disease.


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InternalMed_Harrison. The SA node is composed of a cluster of small fusiform cells in the sulcus terminalis on the epicardial surface of the heart at the right atrial– superior vena caval junction, where they envelop the SA nodal artery. The SA node is structurally heterogeneous, but the central prototypic nodal cells have fewer distinct myofibrils than does the surrounding atrial myocardium, no intercalated disks visible on light microscopy, a poorly developed sarcoplasmic reticulum, and no T-tubules. Cells in the peripheral regions of the SA node are transitional in both structure and function. The SA nodal artery arises from the right coronary artery in 55–60% and the left circumflex artery in 40–45% of persons. The SA node is richly innervated by sympathetic and parasympathetic nerves and ganglia.


InternalMed_Harrison

InternalMed_Harrison. pacemakers in the atrioventricular (AV) node, specialized conducting system, and muscle may initiate elec- trical activation if the SA node is dysfunctional or sup- pressed. Typically, subsidiary pacemakers discharge at a slower rate and, in the absence of an appropriate increase in stroke volume, may result in tissue hypoperfusion. Spontaneous activation and contraction of the heart are a consequence of the specialized pacemaking tissue


InternalMed_Harrison

InternalMed_Harrison. Spontaneous activation and contraction of the heart are a consequence of the specialized pacemaking tissue Voltage, mV in these anatomic locales. As described in Chap. 273e, –100 action potentials in the heart are regionally heterogeneous. The action potentials in cells isolated from nodal FIGURE 274-1 Action potential profiles recorded in cells isolated from sinoatrial tissue are distinct from those recorded from atrial and or atrioventricular nodal tissue compared with those of cells from atrial or ventricuventricular myocytes (Fig. 274-1). The complement lar myocardium. Nodal cell action potentials exhibit more depolarized resting memof ionic currents present in nodal cells results in a less brane potentials, slower phase 0 upstrokes, and phase 4 diastolic depolarization.


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InternalMed_Harrison. FIGURE 274-2 Schematics of nodal action potentials and the currents that contribute to phase 4 depolarization. Relative increases in depolarizing L(I ) and T(I ) type calcium and pacemaker cur rents (If) along with a reduction in repolarizing inward rectifier (IK1) and delayed rectifier (IK) potassium currents result in depolarization. Activation of ACh-gated (IKACh) potassium current and beta blockade slow the rate of phase 4 and decrease the pacing rate. (Modified from J Jalife et al: Basic Cardiac Electrophysiology for the Clinician, Blackwell Publishing, 1999.)


InternalMed_Harrison

InternalMed_Harrison. Irregular and slow propagation of impulses from the SA node can be explained by the electrophysiology of nodal cells and the structure of the SA node itself. The action potentials of SA nodal cells are characterized by a relatively depolarized membrane potential (Fig. 274-1) of −40 to −60 mV, slow phase 0 upstroke, and relatively rapid phase 4 diastolic depolarization compared with the action potentials recorded in cardiac muscle cells. The relative absence of inward rectifier


InternalMed_Harrison

InternalMed_Harrison. Vasovagal (cardioinhibitory) stimulation Inflammatory Drugs Pericarditis Beta blockers Myocarditis (including viral) Calcium channel blockers Rheumatic heart disease Digoxin Collagen vascular diseases Ivabradine Lyme disease Antiarrhythmics (class I and III) Senile amyloidosis Adenosine Congenital heart disease Clonidine (other sympatholytics) TGA/Mustard and Fontan repairs Lithium carbonate Iatrogenic Cimetidine Radiation therapy Amitriptyline Postsurgical Phenothiazines Chest trauma Narcotics (methadone) Familial Pentamidine SSS2, AD, OMIM #163800 (15q24-25) Hypothyroidism SSS1, AR OMIM #608567 (3p21) Sleep apnea SSS3, AD, OMIM #614090 (14q11.2) Hypoxia SA node disease with myopia, OMIM #182190 Endotracheal suctioning (vagal maneuvers) Kearns-Sayre syndrome, OMIM #530000 Increased intracranial pressure Type 1, OMIM #160900 (19q13.2-13.3) Type 2, OMIM #602668 (3q13.3-q24) Friedreich’s ataxia, OMIM #229300 (9q13, 9p23-p11)


InternalMed_Harrison

InternalMed_Harrison. Increased intracranial pressure Type 1, OMIM #160900 (19q13.2-13.3) Type 2, OMIM #602668 (3q13.3-q24) Friedreich’s ataxia, OMIM #229300 (9q13, 9p23-p11) Abbreviations: AD, autosomal dominant; AR, autosomal recessive; MI, myocardial infarction; OMIM, Online Mendelian Inheritance in Man (database); TGA, transposition of the great arteries.


InternalMed_Harrison

InternalMed_Harrison. potassium current (IK1) accounts for the depolarized membrane poten-1467 tial; the slow upstroke of phase 0 results from the absence of available fast sodium current (INa) and is mediated by L-type calcium current ); and phase 4 depolarization is a result of the aggregate activity (ICa-L of a number of ionic currents. Prominently, both Land T-type (ICa-T) calcium currents, the pacemaker current (so-called funny current, or If) formed by hyperpolarization-activated cyclic nucleotide-gated channels, and the electrogenic sodium-calcium exchanger provide depolarizing current that is antagonized by delayed rectifier (IKr) and acetylcholine-gated (IKACh) potassium currents. ICa-L , and If are modulated by , ICa-T β-adrenergic stimulation and IKACh by vagal stimulation, explaining the exquisite sensitivity of diastolic depolarization to autonomic nervous system activity. The slow conduction within the SA node is explained by the absence of INa and poor electrical coupling of cells in the


InternalMed_Harrison

InternalMed_Harrison. sensitivity of diastolic depolarization to autonomic nervous system activity. The slow conduction within the SA node is explained by the absence of INa and poor electrical coupling of cells in the node, resulting from sizable amounts of interstitial tissue and a low abundance of gap junctions. The poor coupling allows for graded electrophysiologic properties within the node, with the peripheral transitional cells being silenced by electrotonic coupling to atrial myocardium.


InternalMed_Harrison

InternalMed_Harrison. SA nodal dysfunction has been classified as intrinsic or extrinsic. The distinction is important because extrinsic dysfunction is often reversible and generally should be corrected before pacemaker therapy is considered (Table 274-1). The most common causes of extrinsic SA node dysfunction are drugs and autonomic nervous system influences that suppress automaticity and/or compromise conduction. Other extrinsic causes include hypothyroidism, sleep apnea, and conditions likely to occur in critically ill patients such as hypothermia, hypoxia, increased intracranial pressure (Cushing’s response), and endotracheal suctioning via activation of the vagus nerve.


InternalMed_Harrison

InternalMed_Harrison. Intrinsic sinus node dysfunction is degenerative and often is characterized pathologically by fibrous replacement of the SA node or its connections to the atrium. Acute and chronic coronary artery disease (CAD) may be associated with SA node dysfunction, although in the setting of acute myocardial infarction (MI; typically inferior), the abnormalities are transient. Inflammatory processes may alter SA node function, ultimately producing replacement fibrosis. Pericarditis, myocarditis, and rheumatic heart disease have been associated with SA nodal disease with sinus bradycardia, sinus arrest, and exit block. Carditis associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and mixed connective tissue disorders (MCTDs) may also affect SA node structure and function. Senile amyloidosis is an infiltrative disorder in patients typically in the ninth decade of life; deposition of amyloid protein in the atrial myocardium can impair SA node function. Some SA node disease


InternalMed_Harrison

InternalMed_Harrison. amyloidosis is an infiltrative disorder in patients typically in the ninth decade of life; deposition of amyloid protein in the atrial myocardium can impair SA node function. Some SA node disease is iatrogenic and results from direct injury to the SA node during cardiothoracic surgery.


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InternalMed_Harrison. Rare heritable forms of sinus node disease have been described, and several have been characterized genetically. Autosomal dominant sinus node dysfunction in conjunction with supraventricular tachycardia (i.e., tachycardia-bradycardia variant of sick-sinus syndrome [SSS2]) has been linked to mutations in the pacemaker current (If) subunit gene HCN4 on chromosome 15. An autosomal recessive form of SSS1 with the prominent feature of atrial inexcitability and absence of P waves on the electrocardiogram (ECG) is caused by mutations in the cardiac sodium channel gene, SCN5A, on chromosome 3. Variants in myosin heavy chain 6 (MYH6) increase the susceptibility to SSS (SSS3). SA node dysfunction associated with myopia has been described but not genetically characterized. There are several neuromuscular diseases, including Kearns-Sayre syndrome (ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy) and myotonic dystrophy, that have a predilection for the conducting system


InternalMed_Harrison

InternalMed_Harrison. diseases, including Kearns-Sayre syndrome (ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy) and myotonic dystrophy, that have a predilection for the conducting system and SA node.


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InternalMed_Harrison. SSS in both the young and the elderly is associated with an increase in fibrous tissue in the SA node. The onset of SSS may be hastened by coexisting disease, such as CAD, diabetes mellitus, hypertension, and valvular diseases and cardiomyopathies. SA node dysfunction may be completely asymptomatic and manifest as an ECG anomaly such as sinus bradycardia; sinus arrest and


InternalMed_Harrison

InternalMed_Harrison. The Bradyarrhythmias: Disorders of the Sinoatrial Node 1468 exit block; or alternating supraventricular tachycardia, usually atrial fibrillation, and bradycardia. Symptoms associated with SA node dysfunction, in particular tachycardia-bradycardia syndrome, may be related to both slow and fast heart rates. For example, tachycardia may be associated with palpitations, angina pectoris, and heart failure, and bradycardia may be associated with hypotension, syncope, presyncope, fatigue, and weakness. In the setting of SSS, overdrive suppression of the SA node may result in prolonged pauses and syncope upon termination of the tachycardia. In many cases, symptoms associated with SA node dysfunction result from concomitant cardiovascular disease. A significant minority of patients with SSS develop signs and symptoms of heart failure that may be related to slow or fast heart rates.


InternalMed_Harrison

InternalMed_Harrison. One-third to one-half of patients with SA node dysfunction develop supraventricular tachycardia, usually atrial fibrillation or atrial flutter. The incidence of persistent atrial fibrillation in patients with SA node dysfunction increases with advanced age, hypertension, diabetes mellitus, left ventricular dilation, valvular heart disease, and ventricular pacing. Remarkably, some symptomatic patients may experience an improvement in symptoms with the development of atrial fibrillation, presumably from an increase in their average heart rate. Patients with the tachycardia-bradycardia variant of SSS, similar to patients with atrial fibrillation, are at risk for thromboembolism, and those at greatest risk, including patients ≥65 years and patients with a prior history of stroke, valvular heart disease, left ventricular dysfunction, or atrial enlargement, should be treated with anticoagulants. Up to one-quarter of patients with SA node disease will have concurrent AV conduction disease,


InternalMed_Harrison

InternalMed_Harrison. disease, left ventricular dysfunction, or atrial enlargement, should be treated with anticoagulants. Up to one-quarter of patients with SA node disease will have concurrent AV conduction disease, although only a minority will require specific therapy for high-grade AV block.


InternalMed_Harrison

InternalMed_Harrison. The natural history of SA node dysfunction is one of varying intensity of symptoms even in patients who present with syncope. Symptoms related to SA node dysfunction may be significant, but overall mortality usually is not compromised in the absence of other significant comorbid conditions. These features of the natural history need to be taken into account in considering therapy for these patients.


InternalMed_Harrison

InternalMed_Harrison. The electrocardiographic manifestations of SA node dysfunction include sinus bradycardia, sinus pauses, sinus arrest, sinus exit block, tachycardia (in SSS), and chronotropic incompetence. It is often difficult to distinguish pathologic from physiologic sinus bradycardia. By definition, sinus bradycardia is a rhythm driven by the SA node with a rate of <60 beats/min; sinus bradycardia is very common and typically benign. Resting heart rates <60 beats/min are very common in young healthy individuals and physically conditioned subjects. A sinus rate of <40 beats/min in the awake state in the absence of physical conditioning generally is considered abnormal. Sinus pauses and sinus arrest result from failure of the SA node to discharge, producing a pause without P waves visible on the ECG (Fig. 274-3). Sinus pauses of up to 3 s are common in awake athletes, and pauses of this duration or longer may be observed in asymptomatic elderly subjects. Intermittent failure of conduction from the


InternalMed_Harrison

InternalMed_Harrison. 274-3). Sinus pauses of up to 3 s are common in awake athletes, and pauses of this duration or longer may be observed in asymptomatic elderly subjects. Intermittent failure of conduction from the SA node produces sinus exit block. The severity of sinus exit block may vary in a manner similar to that of AV block (Chap. 275). Prolongation of conduction from the sinus node will not be apparent on the ECG; second-degree SA block will produce intermittent conduction from the SA node and a regularly irregular atrial rhythm.


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InternalMed_Harrison. FIGURE 274-3 Sinus slowing and pauses on the electrocardiogram (ECG). The ECG is recorded during sleep in a young patient without heart disease. The heart rate before the pause is slow, and the PR interval is prolonged, consistent with an increase in vagal tone. The P waves have a morphology consistent with sinus rhythm. The recording is from a two-lead telemetry system in which the tracing labeled II mimics frontal lead II and V represents Modified Central Lead 1, which mimics lead V1 of the standard 12-lead ECG.


InternalMed_Harrison

InternalMed_Harrison. Type I second-degree SA block results from progressive prolongation of SA node conduction with intermittent failure of the impulses originating in the sinus node to conduct to the surrounding atrial tissue. Second-degree SA block appears on the ECG as an intermittent absence of P waves (Fig. 274-4). In type II second-degree SA block, there is no change in SA node conduction before the pause. Complete or third-degree SA block results in no P waves on the ECG. Tachycardia-bradycardia syndrome is manifest as alternating sinus bradycardia and atrial tachyarrhythmias. Although atrial tachycardia, atrial flutter, and atrial fibrillation may be observed, the latter is the most common tachycardia. Chronotropic incompetence is the inability to increase the heart rate in response to exercise or other stress appropriately and is defined in greater detail below.


InternalMed_Harrison

InternalMed_Harrison. SA node dysfunction is most commonly a clinical or electrocardiographic diagnosis. Sinus bradycardia or pauses on the resting ECG are rarely sufficient to diagnose SA node disease, and longer-term recording and symptom correlation generally are required. Symptoms in the absence of sinus bradyarrhythmias may be sufficient to exclude a diagnosis of SA node dysfunction. Electrocardiographic recording plays a central role in the diagnosis and management of SA node dysfunction. Despite the limitations of the resting ECG, longer-term recording employing Holter or event monitors may permit correlation of symptoms with the cardiac rhythm. Many contemporary event monitors may be automatically triggered to record the ECG when certain programmed heart rate criteria are met. Implantable ECG monitors permit long-term recording (12–18 months) in particularly challenging patients.


InternalMed_Harrison

InternalMed_Harrison. Failure to increase the heart rate with exercise is referred to as chronotropic incompetence. This is alternatively defined as failure to reach 85% of predicted maximal heart rate at peak exercise or failure to achieve a heart rate >100 beats/min with exercise or a maximal heart rate with exercise less than two standard deviations below that of an age-matched control population. Exercise testing may be useful in dis-criminating chronotropic incompetence from resting bradycardia and may aid in the identification of the mechanism of exercise intolerance.


InternalMed_Harrison

InternalMed_Harrison. FIGURE 274-4 Mobitz type I SA nodal exit block. A theoretical SA node electrogram (SAN EG) is shown. Note that there is grouped beating producing a regularly irregular heart rhythm. The SA node EG rate is constant with progressive delay in exit from the node and activation of the atria, inscribing the P wave. This produces subtly decreasing P-P intervals before the pause, and the pause is less than twice the cycle length of the last sinus interval. Autonomic nervous system testing is useful in diagnosing carotid sinus hypersensitivity; pauses >3 s are consistent with the diagnosis but may be present in asymptomatic elderly subjects. Determining the intrinsic heart rate (IHR) may distinguish SA node dysfunction from slow heart rates that result from high vagal tone. The normal IHR after administration of 0.2 mg/kg propranolol and 0.04 mg/kg atropine is 117.2 − (0.53 × age) in beats/min; a low IHR is indicative of SA disease.


InternalMed_Harrison

InternalMed_Harrison. Electrophysiologic testing may play a role in the assessment of patients with presumed SA node dysfunction and in the evaluation of syncope, particularly in the setting of structural heart disease. In this circumstance, electrophysiologic testing is used to rule out more malignant etiologies of syncope, such as ventricular tachyarrhythmias and AV conduction block. There are several ways to assess SA node function invasively. They include the sinus node recovery time (SNRT), defined as the longest pause after cessation of overdrive pacing of the right atrium near the SA node (normal: <1500 ms or, corrected for sinus cycle length, <550 ms), and the sinoatrial conduction time (SACT), defined as one-half the difference between the intrinsic sinus cycle length and a noncompensatory pause after a premature atrial stimulus (normal <125 ms). The combination of an abnormal SNRT, an abnormal SACT, and a low IHR is a sensitive and specific indicator of intrinsic SA node disease.


InternalMed_Harrison

InternalMed_Harrison. Since SA node dysfunction is not associated with increased mortality rates, the aim of therapy is alleviation of symptoms. Exclusion of extrinsic causes of SA node dysfunction and correlation of the cardiac rhythm with symptoms is an essential part of patient management. Pacemaker implantation is the primary therapeutic intervention in patients with symptomatic SA node dysfunction. Pharmacologic considerations are important in the evaluation and management of patients with SA nodal disease. A number of drugs modulate SA node function and are extrinsic causes of dysfunction (Table 274-1). Beta blockers and calcium channel blockers increase SNRT in patients with SA node dysfunction, and antiarrhythmic drugs with class I and III action may promote SA node exit block. In general, such agents should be discontinued before decisions regarding the need for permanent pacing in patients with SA node disease are made. Chronic pharmacologic therapy for sinus bradyarrhythmias is limited. Some


InternalMed_Harrison

InternalMed_Harrison. should be discontinued before decisions regarding the need for permanent pacing in patients with SA node disease are made. Chronic pharmacologic therapy for sinus bradyarrhythmias is limited. Some pharmacologic agents may improve SA node function; digitalis, for example, has been shown to shorten SNRT in patients with SA node dysfunction. Isoproterenol or atropine administered IV may increase the sinus rate acutely. Theophylline has been used both acutely and chronically to increase heart rate but has liabilities when used in patients with tachycardiabradycardia syndrome, increasing the frequency of supraventricular tachyarrhythmias, and in patients with structural heart disease, increasing the risk of potentially serious ventricular arrhythmias. Currently, there is only a single randomized study of therapy for SA node dysfunction. In patients with resting heart rates <50 and >30 beats/min on a Holter monitor, patients who received dual-chamber pacemakers experienced significantly


InternalMed_Harrison

InternalMed_Harrison. study of therapy for SA node dysfunction. In patients with resting heart rates <50 and >30 beats/min on a Holter monitor, patients who received dual-chamber pacemakers experienced significantly fewer syncopal episodes and had symptomatic improvement compared with patients randomized to theophylline or no treatment.


InternalMed_Harrison

InternalMed_Harrison. In certain circumstances, sinus bradycardia requires no specific treatment or only temporary rate support. Sinus bradycardia is common in patients with acute inferior or posterior MI and can be exacerbated by vagal activation induced by pain or the use of drugs such as morphine. Ischemia of the SA nodal artery probably occurs in acute coronary syndromes more typically with involvement with the right coronary artery, and even with infarction, the effect on SA node function most often is transient.


InternalMed_Harrison

InternalMed_Harrison. Sinus bradycardia is a prominent feature of carotid sinus hypersensitivity and neurally mediated hypotension associated with vasovagal syncope that responds to pacemaker therapy. Carotid hypersensitivity with recurrent syncope or presyncope associated 1469 with a predominant cardioinhibitory component responds to pacemaker implantation. Several randomized trials have investigated the efficacy of permanent pacing in patients with drug-refractory vasovagal syncope, with mixed results. Although initial trials suggested that patients undergoing pacemaker implantation have fewer recurrences and a longer time to recurrence of symptoms, at least one follow-up study did not confirm these results.


InternalMed_Harrison

InternalMed_Harrison. Nomenclature and Complications The main therapeutic intervention in SA node dysfunction is permanent pacing. Since the first implementation of permanent pacing in the 1950s, many advances in technology have resulted in miniaturization, increased longevity of pulse generators, improvement in leads, and increased functionality. To better understand pacemaker therapy for bradycardias, it is important to be familiar with the fundamentals of pacemaking. Pacemaker modes and function are named using a five-letter code.


InternalMed_Harrison

InternalMed_Harrison. The first letter indicates the chamber(s) that is paced (O, none; A, atrium; V, ventricle; D, dual; S, single), the second is the chamber(s) in which sensing occurs (O, none; A, atrium; V, ventricle; D, dual; S, single), the third is the response to a sensed event (O, none; I, inhibition; T, triggered; D, inhibition + triggered), the fourth refers to the programmability or rate response (R, rate responsive), and the fifth refers to the existence of antitachycardia functions if present (O, none; P, antitachycardia pacing; S, shock; D, pace + shock). Almost all modern pacemakers are multiprogrammable and have the capability for rate responsiveness using one of several rate sensors: activity or motion, minute ventilation, or QT interval. The most commonly programmed modes of implanted singleand dual-chamber pacemakers are VVIR and DDDR, respectively, although multiple modes can be programmed in modern pacemakers.


InternalMed_Harrison

InternalMed_Harrison. Although pacemakers are highly reliable, they are subject to a number of complications related to implantation and electronic function. In adults, permanent pacemakers are most commonly implanted with access to the heart by way of the subclavian–superior vena cava venous system. Rare, but possible, acute complications of transvenous pacemaker implantation include infection, hematoma, pneumothorax, cardiac perforation, diaphragmatic/phrenic nerve stimulation, and lead dislodgment. Limitations of chronic pacemaker therapy include infection, erosion, lead failure, and abnormalities resulting from inappropriate programming or interaction with the patient’s native electrical cardiac function. Rotation of the pacemaker pulse generator in its subcutaneous pocket, either intentionally or inadvertently, often referred to as “twiddler’s syndrome,” can wrap the leads around the generator and produce dislodgment with failure to sense or pace the heart. The small size and light weight of


InternalMed_Harrison

InternalMed_Harrison. inadvertently, often referred to as “twiddler’s syndrome,” can wrap the leads around the generator and produce dislodgment with failure to sense or pace the heart. The small size and light weight of contemporary pacemakers make this a rare complication.


InternalMed_Harrison

InternalMed_Harrison. Complications stemming from chronic cardiac pacing also result from disturbances in atrioventricular synchrony and/or left ventricular mechanical synchrony. Pacing modes that interrupt or fail to restore atrioventricular synchrony may lead to a constellation of signs and symptoms, collectively referred to as pacemaker syndrome, that include neck pulsation, fatigue, palpitations, cough, confusion, exertional dyspnea, dizziness, syncope, elevation in jugular venous pressure, canon A waves, and stigmata of congestive heart failure, including edema, rales, and a third heart sound. Right ventricular apical pacing can induce dyssynchronous activation of the left ventricle, leading to compromised left ventricular systolic function, mitral valve regurgitation, and the previously mentioned stigmata of congestive heart failure. Maintenance of AV synchrony can minimize the sequelae of pacemaker syndrome. Selection of pacing modes that minimize unnecessary ventricular pacing or implantation of a


InternalMed_Harrison

InternalMed_Harrison. of congestive heart failure. Maintenance of AV synchrony can minimize the sequelae of pacemaker syndrome. Selection of pacing modes that minimize unnecessary ventricular pacing or implantation of a device capable of right and left ventricular pacing (biventricular pacing) can help minimize the deleterious consequences of pacing-induced mechanical dyssynchrony at the ventricular level.


InternalMed_Harrison

InternalMed_Harrison. The Bradyarrhythmias: Disorders of the Sinoatrial Node 1470 Pacemaker Therapy in SA Node Dysfunction Pacing in SA nodal disease is indicated to alleviate symptoms of bradycardia. Consensus guidelines published by the American Heart Association (AHA)/American College of Cardiology/Heart Rhythm Society (ACC/HRS) outline the indications for the use of pacemakers and categorize them by class based on levels of evidence. Class I conditions are those for which there is evidence or consensus of opinion that therapy is useful and effective. In class II conditions, there is conflicting evidence or a divergence of opinion about the efficacy of a procedure or treatment; in class IIa conditions, the weight of evidence or opinion favors treatment; and in class IIb conditions, efficacy is less well established by the evidence or opinion of experts. In class III conditions, the evidence or weight of opinion indicates that the therapy is not efficacious or useful and may be harmful. Class I


InternalMed_Harrison

InternalMed_Harrison. well established by the evidence or opinion of experts. In class III conditions, the evidence or weight of opinion indicates that the therapy is not efficacious or useful and may be harmful. Class I indications for pacing in SA node dysfunction include documented symptomatic bradycardia, sinus node dysfunction– associated long-term drug therapy for which there is no alternative, and symptomatic chronotropic incompetence. Class IIa indications include those outlined previously in which sinus node dysfunction is suspected but not documented and for syncope of unexplained origin in the presence of major abnormalities of SA node dysfunction. Mildly symptomatic individuals with heart rates consistently <40 beats/min constitute a class IIb indication for pacing. Pacing is not indicated in patients with SA node dysfunction who do not have symptoms and in those in whom bradycardia is associated with the use of nonessential drugs (Table 274-2). There is some controversy about the mode of


InternalMed_Harrison

InternalMed_Harrison. patients with SA node dysfunction who do not have symptoms and in those in whom bradycardia is associated with the use of nonessential drugs (Table 274-2). There is some controversy about the mode of pacing that should be employed in SA node disease. A number of randomized, single-blind trials of pacing mode have been performed. There are no trials that demonstrate an improvement in mortality rate with AV synchronous pacing compared with single-chamber pacing in SA node disease. In some of these studies, the incidence of atrial fibrillation and thromboembolic events was reduced with AV synchronous pacing. In trials of patients with dual-chamber pacemakers designed to compare single-chamber with dual-chamber pacing by crossover design, the need for AV synchronous pacing due to pacemaker syndrome was common. Pacing modes that preserve AV synchrony appear to be associated with a reduction in the incidence of atrial fibrillation and improved quality of life. Because of the low but finite


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InternalMed_Harrison. was common. Pacing modes that preserve AV synchrony appear to be associated with a reduction in the incidence of atrial fibrillation and improved quality of life. Because of the low but finite 1.


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InternalMed_Harrison. SA node dysfunction with symptomatic bradycardia or sinus pause 2. Symptomatic SA node dysfunction as a result of essential long-term drug therapy with no acceptable alternatives 3. 4. Atrial fibrillation with bradycardia and pauses >5 s 1. SA node dysfunction with heart rates <40 beats/min without a clear and consistent relationship between bradycardia and symptoms 2. SA node dysfunction with heart rates <40 beats/min on an essential longterm drug therapy with no acceptable alternatives, without a clear and consistent relationship between bradycardia and symptoms 3. Syncope of unknown origin when major abnormalities of SA node dysfunction are discovered or provoked by electrophysiologic testing 1. Mildly symptomatic patients with waking chronic heart rates <40 beats/min 1. SA node dysfunction in asymptomatic patients, even those with heart rates <40 beats/min 2. SA node dysfunction in which symptoms suggestive of bradycardia are not associated with a slow heart rate 3.


InternalMed_Harrison

InternalMed_Harrison. SA node dysfunction in which symptoms suggestive of bradycardia are not associated with a slow heart rate 3. SA node dysfunction with symptomatic bradycardia due to nonessential drug therapy Source: Modified from AE Epstein et al: J Am Coll Cardiol 51:e1, 2008 and CM Tracy et al: J Am Coll Cardiol 61:e6, 2013. incidence of AV conduction disease, patients with SA node dysfunction usually undergo dual-chamber pacemaker implantation.


InternalMed_Harrison

InternalMed_Harrison. Pacemaker Therapy in Carotid Sinus Hypersensitivity and Vasovagal Syncope Carotid sinus hypersensitivity, if accompanied by a significant cardioinhibitory component, responds well to pacing. In this circumstance, pacing is required only intermittently and single-chamber ventricular pacing is often sufficient. The mechanism of vasovagal syncope is incompletely understood but appears to involve activation of cardiac mechanoreceptors with consequent activation of neural centers that mediate vagal activation and withdrawal of sympathetic nervous system tone. Several randomized clinical trials have been performed in patients with drug-refractory vasovagal syncope, with some studies suggesting reduction in the frequency and the time to recurrent syncope in patients who were paced compared with those who were not. A recent follow-up study to one of those initial trials, however, found less convincing results, casting some doubt on the utility of pacing for vagally mediated syncope.


InternalMed_Harrison

InternalMed_Harrison. The Bradyarrhythmias: Disorders of the Atrioventricular node David D. Spragg, Gordon F. Tomaselli Impulses generated in the sinoatrial (SA) node or in ectopic atrial loci are conducted to the ventricles through the electrically and anatomically complex atrioventricular (AV) node. As described in Chap. 274, the electrophysiologic properties of nodal tissue are distinct from atrial and ventricular myocardium. Cells located in the AV node sit at a relatively higher resting membrane potential than surrounding atrial and ventricular myocytes, exhibit spontaneous depolarization during phase 4 of the action potential, and have slower phase 0 depolarization (mediated by calcium influx in nodal tissue) than that seen in ventricular tissue (mediated by sodium influx).


InternalMed_Harrison

InternalMed_Harrison. Bradycardia may occur when conduction across the AV node is compromised, resulting in ineffective ventricular rates, with the possibility of attendant symptoms, including fatigue, syncope, and (if subsidiary pacemaker activity is insufficient) even death. It is important to recognize that in the setting of disturbed AV conduction, SA activation and atrial systole may occur at normal or even accelerated rates, while ventricular activation is either slowed or nonexistent. Transient AV conduction block is common in the young and is most likely the result of high vagal tone found in up to 10% of young adults. Acquired and persistent failure of AV conduction is decidedly rare in healthy adult populations, with an estimated incidence of 200 per million population per year. In the setting of myocardial ischemia, aging and fibrosis, or cardiac infiltrative diseases, however, persistent AV block is much more common.


InternalMed_Harrison

InternalMed_Harrison. As with symptomatic bradycardia arising from SA node dysfunction, permanent pacing is the only reliable therapy for symptoms arising from AV conduction block. Approximately 50% of the 150,000 permanent pacemakers implanted in the United States and 70–80% of those in Europe are implanted for disorders of AV conduction.


InternalMed_Harrison

InternalMed_Harrison. The AV conduction axis is structurally complex, involving the atria and ventricles as well as the AV node. Unlike the SA node, the AV node is a subendocardial structure originating in the transitional zone, which is composed of aggregates of cells in the posterior-inferior right atrium. Superior, medial, and posterior transitional atrionodal bundles converge on the compact AV node. The compact AV node (~1 × 3 × 5 mm) is situated at the apex of the triangle of Koch, which is defined by the coronary sinus ostium posteriorly, the septal tricuspid valve annulus anteriorly, and the tendon of Todaro superiorly. The compact AV node continues as the penetrating AV bundle where it immediately traverses the central fibrous body and is in close proximity to the aortic, mitral, and tricuspid valve annuli; thus, it is subject to injury in the setting of valvular heart disease or its surgical treatment. The penetrating AV bundle continues through the annulus fibrosis and emerges along the


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InternalMed_Harrison. valve annuli; thus, it is subject to injury in the setting of valvular heart disease or its surgical treatment. The penetrating AV bundle continues through the annulus fibrosis and emerges along the ventricular septum adjacent to the membranous septum as the bundle of His. The right bundle branch (RBB) emerges from the distal AV bundle in a band that traverses the right ventricle (moderator band). In contrast, the left bundle branch (LBB) is a broad subendocardial sheet of tissue on the septal left ventricle. The Purkinje fiber network emerges from the RBB and LBB and extensively ramifies on the endocardial surfaces of the right and left ventricles, respectively.


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InternalMed_Harrison. The blood supply to the penetrating AV bundle is from the AV nodal artery and first septal perforator of the left anterior descending coronary artery. The bundle branches also have a dual blood supply from the septal perforators of the left anterior descending coronary artery and branches of the posterior descending coronary artery. The AV node is highly innervated with postganglionic sympathetic and parasympathetic nerves. The bundle of His and distal conducting system are minimally influenced by autonomic tone.


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InternalMed_Harrison. The cells that constitute the AV node complex are heterogeneous with a range of action potential profiles. In the transitional zones, the cells have an electrical phenotype between those of atrial myocytes and cells of the compact node (see Fig. 274-1). Atrionodal transitional connections may exhibit decremental conduction, defined as slowing of conduction with increasingly rapid rates of stimulation. Fast and slow AV nodal pathways have been described, but it is controversial whether these two types of pathway are anatomically distinct or represent functional heterogeneities in different regions of the AV nodal complex. Myocytes that constitute the compact node are depolarized (resting membrane potential ~–60 mV) and exhibit action potentials with low amplitudes, slow upstrokes of phase 0 (<10 V/s), and phase 4 diastolic depolarization; high-input resistance; and relative insensitivity to external [K+]. The action potential phenotype is explained by the complement of ionic currents


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InternalMed_Harrison. 0 (<10 V/s), and phase 4 diastolic depolarization; high-input resistance; and relative insensitivity to external [K+]. The action potential phenotype is explained by the complement of ionic currents expressed. AV nodal cells lack a robust inward rectifier potassium current (IK1) and fast sodium current (INa); L-type calcium current (ICa-L) is responsible for phase 0; and phase 4 depolarization reflects the composite activity of the depolarizing currents—funny current (I ), I , T-type calcium current (I ), and sodium calcium exchanger current (INCX)—and the repolarizing currents—delayed rectifier (I ) and acetylcholine-gated (I ) potassium currents. Electrical coupling between cells in the AV node is tenuous due to the relatively sparse expression of gap junction channels (predominantly connexin-40) and increased extracellular volume.


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InternalMed_Harrison. The His bundle and the bundle branches are insulated from ventricular myocardium. The most rapid conduction in the heart is observed in these tissues. The action potentials exhibit very rapid upstrokes (phase 0), prolonged plateaus (phase 2), and modest automaticity (phase 4 depolarization). Gap junctions, composed largely of connexin-40, are abundant, but bundles are poorly connected transversely to ventricular myocardium.


InternalMed_Harrison

InternalMed_Harrison. Conduction block from the atrium to the ventricle can occur for a variety of reasons in a number of clinical situations, and AV conduction block may be classified in a number of ways. The etiologies may be functional or structural, in part analogous to extrinsic and intrinsic causes of SA nodal dysfunction. The block may be classified by its severity from first to third degree or complete AV block or by the location of block within the AV conduction system. Table 275-1 summarizes the etiologies of AV conduction block. Those that are functional (autonomic, metabolic/endocrine, and drug-related) tend to be reversible. Most other etiologies produce structural changes, typically fibrosis, in segments of the AV conduction axis that are generally permanent. Heightened vagal tone during sleep or in well-conditioned individuals can be associated with all grades of AV block. Carotid sinus hypersensitivity, vasovagal syncope, and cough and micturition syncope may be associated with SA node


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InternalMed_Harrison. or in well-conditioned individuals can be associated with all grades of AV block. Carotid sinus hypersensitivity, vasovagal syncope, and cough and micturition syncope may be associated with SA node slowing and AV conduction block. Transient metabolic and endocrinologic disturbances as well as a number of pharmacologic agents also may produce reversible AV conduction block.


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InternalMed_Harrison. Congenital heart disease Facioscapulohumeral MD, OMIM #158900 (4q35) Maternal SLE Emery-Dreifuss MD, OMIM Kearns-Sayre syndrome, OMIM #310300 (Xq28) #530000 Progressive familial heart block, Myotonic dystrophy type IA OMIM #113900 (3p21) Type 1, OMIM #160900 Progressive familial heart block, (19q13.2-13.3) type IB, OMIM #604559 (19q13.32) Type 2, OMIM #602668 Progressive familial heart block, (3q13.3-q24) type II, OMIM %140400 Abbreviations: MCTD, mixed connective tissue disease; MI, myocardial infarction; OMIM, Online Mendelian Inheritance in Man (database; designations: #, phenotypic description, molecular basis known; %, phenotypic description); SLE, systemic lupus erythematosus.


InternalMed_Harrison

InternalMed_Harrison. Several infectious diseases have a predilection for the conducting system. Lyme disease may involve the heart in up to 50% of cases; 10% of patients with Lyme carditis develop AV conduction block, which is generally reversible but may require temporary pacing support. Chagas’ disease, which is common in Latin America, and syphilis may produce more persistent AV conduction disturbances. Some autoimmune and infiltrative diseases may produce AV conduction block, including systemic lupus erythematosus (SLE), rheumatoid arthritis, mixed connective tissue disease, scleroderma, amyloidosis (primary and secondary), sarcoidosis, and hemochromatosis; rare malignancies also may impair AV conduction.


InternalMed_Harrison

InternalMed_Harrison. Idiopathic progressive fibrosis of the conduction system is one of the more common and degenerative causes of AV conduction block. Aging is associated with degenerative changes in the summit of the ventricular septum, central fibrous body, and aortic and mitral annuli and has been described as “sclerosis of the left cardiac skeleton.” The process typically begins in the fourth decade of life and may be accelerated by atherosclerosis, hypertension, and diabetes mellitus. Accelerated forms The Bradyarrhythmias: Disorders of the Atrioventricular Node


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InternalMed_Harrison. The Bradyarrhythmias: Disorders of the Atrioventricular Node FIGURE 275-1 First-degree AV block with slowing of conduction in the AV node as indicated by the prolonged atrial-to-His bundle electro-gram (AH) interval, in this case 157 ms. The His bundle-to-earliest ventricular activation on the surface ECG (HV) interval is normal. The normal HV interval suggests normal conduction below the AV node to the ventricle. I and V1 are surface ECG leads, and HIS is the recording of the endocavitary electrogram at the His bundle position. A, H, and V are labels for the atrial, His bundle, and right ventricular electrograms, respec tively. of progressive familial heart block have been identified in families with mutations in the cardiac sodium channel gene (SCN5A) and other loci that have been mapped to chromosomes 1 and 19.


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InternalMed_Harrison. AV conduction block has been associated with heritable neuromuscular diseases, including the nucleotide repeat disease myotonic dystrophy, the mitochondrial myopathy Kearns-Sayre syndrome (Chap. 462e), and several of the monogenic muscular dystrophies. Congenital AV block may be observed in complex congenital cardiac anomalies (Chap. 282), such as transposition of the great arteries, ostium primum atrial septal defects (ASDs), ventricular septal defects (VSDs), endocardial cushion defects, and some single-ventricle defects. Congenital AV block in the setting of a structurally normal heart has been seen in children born to mothers with SLE. Iatrogenic AV block may occur during mitral or aortic valve surgery, rarely in the setting of thoracic radiation, and as a consequence of catheter ablation. AV block is a decidedly rare complication of the surgical repair of VSDs or ASDs but may complicate repairs of transposition of the great arteries.


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InternalMed_Harrison. Coronary artery disease may produce transient or persistent AV block. In the setting of coronary spasm, ischemia, particularly in the right coronary artery distribution, may produce transient AV block. In acute myocardial infarction (MI), AV block transiently develops in 10–25% of patients; most commonly, this is first-or second-degree AV block, but complete heart block (CHB) may also occur. Second-degree and higher-grade AV block tends to occur more often in inferior than in anterior acute MI; however, the level of block in inferior MI tends to be in the AV node with more stable, narrow escape rhythms. In contrast, acute anterior MI is associated with block in the distal AV nodal complex, His bundle, or bundle branches and results in wide complex, unstable escape rhythms and a worse prognosis with high mortality rates.


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InternalMed_Harrison. AV conduction block typically is diagnosed electrocardiographically, which characterizes the severity of the conduction disturbance and allows one to draw inferences about the location of the block. AV conduction block manifests as slow conduction in its mildest forms and failure to conduct, either intermittent or persistently, in more severe varieties. First-degree AV block (PR interval >200 ms) is a slowing of conduction through the AV junction (Fig. 275-1). The site of delay is typically in the AV node but may be in the atria, bundle of His, or His-Purkinje system. A wide QRS is suggestive of delay in the distal conduction system, whereas a narrow QRS suggests delay in the AV node proper or, less commonly, in the bundle of His. In second-degree AV block there is an intermittent failure of electrical impulse conduction from atrium to ventricle. Second-degree AV block is subclassified as Mobitz type I (Wenckebach) or Mobitz type II. The periodic failure of conduction in Mobitz type I


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InternalMed_Harrison. of electrical impulse conduction from atrium to ventricle. Second-degree AV block is subclassified as Mobitz type I (Wenckebach) or Mobitz type II. The periodic failure of conduction in Mobitz type I block is characterized by a progressively lengthening PR interval, shortening of the RR interval, and a pause that is less than two times the immediately preceding RR interval on the electrocardiogram (ECG). The ECG complex after the pause exhibits a shorter PR interval than that immediately preceding the pause (Fig. 275-2). This ECG pattern most often arises because of decremental conduction of electrical impulses in the AV node.


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InternalMed_Harrison. 0.40 FIGURE 275-2 Mobitz type I second-degree AV block. The PR interval prolongs before the pause, as shown in the ladder diagram. The ECG pattern results from slowing of conduction in the AV node. FIGURE 275-3 Paroxysmal AV block. Multiple nonconducted P waves after a period of sinus bradycardia with a normal PR interval. This implies significant conduction system disease, requiring permanent pacemaker implantation.


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InternalMed_Harrison. It is important to distinguish type I from type II second-degree AV nodal block because the latter has more serious prognostic implications. Type II second-degree AV block is characterized by intermittent failure of conduction of the P wave without changes in the preceding PR or RR intervals. When AV block is 2:1, it may be difficult to distinguish type I from type II block. Type II second-degree AV block typically occurs in the distal or infra-His conduction system, is often associated with intraventricular conduction delays (e.g., bundle branch block), and is more likely to proceed to higher grades of AV block than is type I second-degree AV block. Second-degree AV block (particularly type II) may be associated with a series of nonconducted P waves, referred to as paroxysmal AV block(Fig. 275-3), and implies significant conduction system disease and is an indication for permanent pacing. Complete failure of conduction from atrium to ventricle is referred to as complete or


InternalMed_Harrison

InternalMed_Harrison. block(Fig. 275-3), and implies significant conduction system disease and is an indication for permanent pacing. Complete failure of conduction from atrium to ventricle is referred to as complete or third-degree AV block. AV block that is intermediate between second degree and third degree is referred to as high-grade AV block and, as with CHB, implies advanced AV conduction system disease. In both cases, the block is most often distal to the AV node, and the duration of the QRS complex can be helpful in determining the level of the block. In the absence of a preexisting bundle branch block, a wide QRS escape rhythm (Fig. 275-4B) implies a block in the distal His or bundle branches; in contrast, a narrow QRS rhythm implies a block in the AV node or proximal His and an escape rhythm originating in the AV junction (Fig. 275-4A). Narrow QRS escape rhythms are typically faster and more stable than wide QRS escape rhythms and originate more proximally in the AV conduction system.


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InternalMed_Harrison. Diagnostic testing in the evaluation of AV block is aimed at determining the level of conduction block, particularly in asymptomatic patients, since the prognosis and therapy depend on whether the block is in or below the AV node. Vagal maneuvers, carotid sinus massage, exercise, and administration of drugs such as atropine and isoproterenol may be diagnostically informative. Owing to the differences in the innervation of the AV node and infranodal conduction system, vagal stimulation and carotid sinus massage slow conduction in the AV node but have less of an effect on infranodal tissue and may even improve conduction due to a reduced rate of activation of distal tissues. Conversely, atropine, isoproterenol, and exercise improve conduction through the AV node and impair infranodal conduction. In patients with congenital CHB and a narrow QRS complex, exercise typically increases heart rate; by contrast, those with acquired CHB, particularly with wide QRS, do not respond to exercise


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InternalMed_Harrison. In patients with congenital CHB and a narrow QRS complex, exercise typically increases heart rate; by contrast, those with acquired CHB, particularly with wide QRS, do not respond to exercise with an increase in heart rate.


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InternalMed_Harrison. Additional diagnostic evaluation, including electrophysiologic testing, may be indicated in patients with syncope and suspected high-grade AV block. This is particularly relevant if noninvasive testing does not reveal the cause of syncope or if the patient has structural heart disease with ventricular tachyarrhythmias as a cause of symptoms. Electrophysiologic testing provides more precise information regarding the location of AV conduction block and permits studies of AV conduction under conditions of pharmacologic stress and exercise. Recording of the His bundle electrogram by a catheter positioned at the superior margin of the tricuspid valve annulus provides information about conduction at all levels of the AV conduction axis. A properly recorded His bundle electrogram reveals local atrial activity, the His electrogram, and local ventricular activation; when it is monitored simultaneously with recorded body surface electrocardiographic traces, intraatrial, AV nodal, and infranodal


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InternalMed_Harrison. activity, the His electrogram, and local ventricular activation; when it is monitored simultaneously with recorded body surface electrocardiographic traces, intraatrial, AV nodal, and infranodal conduction times can be assessed (Fig. 275-1). The time from the most rapid deflection of the


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InternalMed_Harrison. CHAPTER 275 The Bradyarrhythmias: Disorders of the Atrioventricular Node FIGURE 275-4 High-grade AV block.A. Multiple nonconducted P waves with a regular narrow complex QRS escape rhythm probably emanating from the AV junction. B. A wide complex QRS escape and a single premature ventricular contraction. In both cases, there is no consistent temporal relationship between the P waves and QRS complexes.


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InternalMed_Harrison. FIGURE 275-5 High-grade AV block below the His. The AH interval is normal and is not changing before the block. Atrial and His bundle electrograms are recorded consistent with block below the distal AV junction. I, II, III, and V1 are surface ECG leads. HISp, HISd, and RVA are the proximal HIS, distal HIS, and right ventricular apical electrical recordings, respectively. A, H, and V represent the atrial, His, and ventricular electro-grams on the His bundle recording, respectively. (Tracing courtesy of Dr. Joseph Marine; with permission.) atrial electrogram in the His bundle recording to the His electrogram (AH interval) represents conduction through the AV node and is normally <130 ms. The time from the His electrogram to the earliest onset of the QRS on the surface ECG (HV interval) represents the conduction time through the His-Purkinje system and is normally ≤55 ms.


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InternalMed_Harrison. Rate stress produced by pacing can unveil abnormal AV conduction. Mobitz I second-degree AV block at short atrial paced cycle lengths is a normal response. However, when it occurs at atrial cycle lengths >500 ms (<120 beats/min) in the absence of high vagal tone, it is abnormal. Typically, type I second-degree AV block is associated with prolongation of the AH interval, representing conduction slowing and block in the AV node. AH prolongation occasionally is due to the effect of drugs (beta blockers, calcium channel blockers, digitalis) or increased vagal tone. Atropine can be used to reverse high vagal tone; however, if AH prolongation and AV block at long pacing cycle lengths persists, intrinsic AV node disease is likely. Type II second-degree block is typically infranodal, often in the His-Purkinje system. Block below the node with prolongation of the HV interval or a His bundle electrogram with no ventricular activation (Fig. 275-5) is abnormal unless it is elicited at fast pacing


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InternalMed_Harrison. His-Purkinje system. Block below the node with prolongation of the HV interval or a His bundle electrogram with no ventricular activation (Fig. 275-5) is abnormal unless it is elicited at fast pacing rates or short coupling intervals with extra stimulation. It is often difficult to determine the type of second-degree AV block when 2:1 conduction is present; however, the finding of a His bundle electrogram after every atrial electrogram indicates that block is occurring in the distal conduction system.


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InternalMed_Harrison. Intracardiac recording at electrophysiologic study that reveals prolongation of conduction through the His-Purkinje system (i.e., long HV interval) is associated with an increased risk of progression to higher grades of block and is generally an indication for pacing. In the setting of bundle branch block, the HV interval may reveal the condition of the unblocked bundle and the prognosis for developing more advanced AV conduction block. Prolongation of the HV interval in patients with asymptomatic bundle branch block is associated with an increased risk of developing higher-grade AV block. The risk increases with greater prolongation of the HV interval such that in patients with an HV interval >100 ms, the annual incidence of complete AV block approaches 10%, indicating a need for pacing. In patients with acquired CHB, even if intermittent, there is little role for electrophysiologic testing, and pacemaker implantation is almost always indicated.


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InternalMed_Harrison. TREATMEnT ManageMent of aV conduction Block