Electrocardiogram: Marker of cellular mechanisms of arrhythmias

TECHNOLOGY Electrocardiogram: Cellular Mechanisms Arrhythmias

Marker of

SERIES tern. It has been also recorded in the muscular components of the mitral and tricuspid valves and some areas of the atria. The underlying cellular mechanism is a gradual loss of the resting potential. When the resting potential reaches the threshold potential a propagated response is initiated (Figure 1). In addition to the dominant pacemakers there are “latent” pacemakers that may also convert to dominant pacemakers. The most common initiating events responsible for conversion of a non-automatic to an automatic cell include anoxia, stretch, edema, adrenergic activity, ischemia of MI and digitalis (Figure 2). Although the basic mechanisms of normal or abnormal automaticity are cellular in nature, there are occasional electrocardiographic clues which point to automaticity as the initiating mechanism. The clues and the arrhythmias are listed in Table 1. It should be remembered, however, that evidence for electrocardiographic expression of cellular mechanisms is indirect and purely deductive.

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Charles Fisch, MD, Indiana University School of Medicine, Krannert Institute of Cardiology, Indianapolis, Indiana

lectrocardiography serves as the gold standard for diagnosis of arrhythmias. Although arrhythmias ml have been studied by a variety of methods for centuries, none exhibited the sensitivity and specificity inherent in the electrocardiogram (ECG). More than 95 years since William Einthoven (1) introduced the ECG and 75 years since Sir Thomas Lewis (2) summarized the early knowledge of electrocardiography, the ECG remains the only practical method of recording cardiac rhythms. When recorded during an arrhythmia its sensitivity is obviously 100% specificity for arrhythmias is equally quite high. In contrast, the sensitivity of the first ECG for the diagnosis of acute myocardial infarction (MI) showed the ECG to be normal in 10 to 15% and atypical in another 40% of the patients. Free of theoretical assumptions important in the analysis of the electrocardiographic waveforms relative to the diagnosis of myocardial structural abnormalities, arrhythmias recorded from the surface of the body can be said, with some exceptions, to directly reflect the intracardiac events responsible for the ECG manifestations of cardiac arrhythmias (3). It is important to recall that the ECG reflects the voltage generated by the atria1 and ventricular myocardium while arrhythmias are frequently the result of abnormalities of impulse formation or conduction, or both, of the specialized conduction tissue. Because the activity of the specialized tissue is not recorded on the ECG, its function must be extrapolated from the temporal relations of the waveforms generated by the myocardium. Such deductive analysis has led to the recognition of many electrophysiologic concepts: the aberrations that later became known as the Ashman phenomenon; electrical altemans; acceleration-dependent aberration; ventricular fusion; reciprocation; parasystole; exit block, supernormality and concealed conduction were all clearly described and understood by the year 1922. More difficult to achieve is electrocardiographic recognition of the cellular basis of an arrhythmia. Occasionally, however, there are clues that allow for such an extrapolation. Currently recognized basic mechanisms include automaticity, reentry and “triggered” automaticity.

Reentry (Reciprocation, Echo) The concept of reentry and its responsible mechanism put forth by Mines in 1913 (4) has stood the test of subsequent investigation. Working with the frog, Mines wrote, “A slight difference in the rate of recovery of two divisions of the AV connection might determine that an extrasystole of the ventricle, provoked by a stimulus applied to the ventricle shortly after activity of the AV connection, should spread up to the auricle by that part of the AV connection having the quicker recovery process and not by the other part. In such a case, when the auricle became excited by this impulse, the other portion of the AV connection would be ready to take up the transmission again back to the ventricle. Provided the transmission in each direction was slow, the chamber at either end would be ready to respond (its refractory phase being short) and thus the condition once established would tend to continue, unless upset by the interpolation of a premature systole. The experiments I have been able to make have given results in accord with this conclusion (4).” In essence, conditions necessary for reentry include the presence of dual pathways, slowing or asynchrony of conduction, unidirectional block and recovery of excitability in order for the tissue to be reexcited. The electrocardiographic clues for reentry are more helpful than for either automaticity or “triggered” automaticity. The clues and the respective arrhythmias are listed in Table 2 and illustrated in Figures 3 and 4.

“Triggered” Automaticity As a marker of triggered arrhythmias, ECG findings are the least specific. “Triggered” automaticity due to diastolic after-

Automaticity Automaticity is a property largely of the sinoatrial node, parts of the atrioventricle (AV) node and His-Purkinje sysACC 0 1997 by the American College of Cardiology Pubhshed by Elsevier Suence Inc

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CLUES AND ARRHYTHMIASASSOCIATEDWlTH AUTOHATKITY

and that of a pacemaker cell (lower tracing). The slow spontaneous diastolic depolarization is the characteristic feature of a pacemaker cell. The gradual loss of trammembrane potential to the level of the threshold potential gives rise to a pacemaker action potential which in turn acts as a stimulus to the myocardial cell (upper tracing).

Clues to Automaticity

Automatic

Rhythms

Long coupling intervals Variable coupling Gradual emergence Gradual acceleration First complex of a sequence is a firston

Slow dominant pacemaker Escape Parasystole Parasystoltc tachycardta Some forms of atria1 tachycardia Nonparoxysmal junctional tachycardia Fascicular ventricular tachycardia Accelerated idioventncular rhythm

depolarization at the cellular level (Figure 5) has been suggested as the mechanism of some arrhythmias in humans. Either a tachycardia or an isolated premature impulse may be the triggering mechanism. Arrhythmias in humans that follow the rules set out for “triggered” automaticity at the cellular level include accelerated junctional escape (Figure 6) and occasional ventricular arrhythmia (Figure 7), including torsade de pointes. Of the drugs commonly used today, digitalis plays an important role in the genesis of “triggered” arrhythmias.

Digitalis-induced enhanced automatidty. Twenty-two minutes after superfusion of a Pulkinje fiber with acetylstrophanthidin, phase 4 develops spontaneous pacemaker activity. The clinical ECG counterpart is manifest by conversion of atrial fibrillation (upper tracing) to automatic nonparoxysmal junctional tachycardia (middle tracing) and most likely an automatic ventricular tachvrardia (lower tracing).

Comment Although ECG recognition of the cellular mechanism of arrhythmias is indirect and, thus subject to error, there are occasional clues that permit recognition of one or another of the mechanisms: automaticity, reentry and “triggered” automaticity.

CLUES AND ARRHYTHMIASASSOCIATEDWITH REENTRY Clues to Reentry

Reentrant

Fixed coupling Presence of dual pathways Onset of tachycardia preceded by a prolonged P-R interval Abrupt onset and termination

Atrial, AV nodal, ventricular reentry Sinus node reentry AV junctional reentrant tachycardia AV reentrant tachycardia “Permanent” junctional reentrant tachycardia Ventricular tachycardia

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Ventricular couplet with Wenckebach retrograde (V-A) conduction and ventricular reentry (reciprocation). The first of the two R-P intervals is short, not allowing sufficient time for recovery of the ventricles and, thus, failure of reciprocation. The longer R-P interval allows for ventricular recovery and ventricular reentry.

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tachycardra mmated by an atrial premature impulse (APC) with a prolonged P-R interval is also terminated by an APC. The abrupt onset and termination induced by an APC coupled with delayed A-V conduction of the first APC are characteristic of reentry.

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ACETVLSTROPWNTHIDIN , 2 x 10-7 I

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paced at progressive shorter cyde length. A single diastolic afterdepolarization (ADA) is recorded in panels B and C. In panels D and E the ADA reached the threshold potential giving rise to a single action potential. In panel F at a cyde length of 300 ms and 38 minutes of perfusion the ADA gives rise to four consecutive fully developed action potentials. (Figure courtesy of John C. Bailey, MD)

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BCL 950 f!SEC

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upper tracing the sinus rhythm with a P-P of 680 ms is interrupted by a PVC with a couolinu interval of 340 ms. The latter is followed by ab accelerated junctidnalWescape and nonparoxysmal junctional ’ tachycardia In the lower tracing the sinus rhythm with a P-P of 780 is interrupted by a PVC with a coupling interval of 480 ms. The latter is followed by a single accelerated escape impulse.

480

780

960 (900)

( “Triggered” ventricular tachycardia induced by supraventricular tachycardia (VT), the latter treated with large doses of digitalis and terminated with carotid sinus pressure. The first number in each panel denotes the RR cyde of the supraventricular tachycardia and the second number denotes the coupling interval of the ventricular ectopic impulse and the last complex of the supraventriarlar tachycardia. The ventricular arrhythmias in panels 8 and C reoresent VT with 3:2 exit block

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6 Pick A, Langendorf R. lnterpretatton phia: Lea & Febiger, 1979:586.

BIBLIOGRAPHY 1. Einthoven 1901;6:625-33.

W’. Un nouveau

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2 Lews T. The Mechanism and Graphic London: Shaw and Sons, 1920: preface.

Arch Need Sci Exactes Nat Registratmn

7 Fisch C, Knoebel SB. AcceleratedJunctronal tation of “triggered” automanctty? In: Zipes Electrophysrology and Arrhythmias. Orlando:

of the Heart Beat.

College of Cardiology Tenth Bethesda Conference. Electrocardtography. Am J Cardiol 1978,41.111-91. 4. &Imes GR. On dynamrc equihbnum m the heart. J Physiol

Optimal

8. Surawicz B. Electrophysiologic Baltimore: Wlliams and Wrlkins.

Philadel-

escape: A chmcal mamfesDP, Jalife J, eds. Cardrac Grune & Stratton, 1984:

Phrladelphra:

Lea &

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Basis of ECG and Cardiac 1995

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1913:43:

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of Arrhythmias.

Arrhythmtas.

467-73.

3. Amencan

5. Frsch C. Electrocardiography Febiger, 1989

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Address correspondence and reprint L’niversity School of Medicine, Krannert Street, Indiunapolis, IN 46202.

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requests to Charles Fisch, MD, Indiana Institute t~j Cardiology, 1 I I1 West 10th