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Electrical conversion of cardiac arrhythmias
J. chron. Dis.
1965, Vol. 18, pp. 899-904. Pergamon Press Ltd. Printed in Great Britain
ELECTRICAL
CONVERSION OF CARDIAC ARRHYTHMIAS*
BERNARD LOWN, M.D. Assistant Professor of Medicine, Department of Nutrition, Harvard Public Health, Boston, Massachusetts, U.S.A.
University
School of
OVER the past 50 years the treatment of chronic arrhythmias has remained essentially
pharmacologic. Initiated at the turn of the century by the pioneering work of Wenckebach and Frey, it has rested on the use of three drugs, namely, procaine amide, quinidine, and the digitalis glycosides. This therapeutic approach is now undergoing profound alteration. Before dealing with the new, it would be worth while to get a perspective on what the problems with drugs have been in the past and how these problems are being circumvented with new methods. The heart accomplishes three types of work, namely, rate, pressure, and volume work. The least well tolerated is a disturbance in rate. Dr. Schwedel dealt with one aspect of this, the consequences of slow rates, but rapid rates are often more taxing on the myocardium, especially if they are initiated in the ventricle. Serious compromise of cardiac output and of coronary flow may occur, often jeopardizing survival. Antiarrhythmic drugs have a number of limitations. In the first place, there is no way for the physician to know ill priori the specific drug requirements necessary to terminate a rhythm disorder. In effect, a biologic titration is necessary, and this may take minutes, hours, days, or even weeks. In the second place, toxicity often accompanies the use of antiarrhythmic drugs. The agents in current use compromise peripheral resistance and reduce cardiac contractility. Such deleterious changes occur at the very time when the heart is already maximally taxed in its reserve function. There is a third drawback to the use of drugs which relates to their mode of action. If one assumes that the majority of human ectopic arrythmias are sustained by a circus movement, i.e., the existence of a re-entry pathway, then these drugs presumably act by lengthening the refractory period of conduction; this would tend to extinguish the circulating wave of depolarization. However, at the same time, antiarrhythmic drugs slow conduction; this would tend to sustain the disorder. Whether or not an arrhythmia is terminated depends upon which of these two effects is dominant. At the same time, the antiarrhythmic drugs depress rhythmicity of the sinus node and thereby further inhibit the establishment of a normal rhythm. The final limitation of antiarrhythmic drugs is that they are not always effective. When atria1 fibrillation is the arrhythmia under treatment, the physician still has recourse to the digitalis drugs to slow the ventricular rate. However, in the case of ventricular tachycardia, no such recourse exists, and the patient then succumbs to *The work reported here was supported by Grant I-E-07776-02, National Institutes of Health. 899
900
BERNARDLOWN
the arrhythmia. These have been the major problems in the use of antiarrhythmic drugs. Electrical discharge has been suggested as an alternative method [l]. It rests on three suppositions : (1) The factors which initiate ventricular or atria1 arrhythmias are generally transient. Once initiated, the mechanism is self-sustaining. This is due to the fact that the majority of human ectopic tachycardias are maintained by a continuing passage of recirculating wave fronts of excitation over fixed or variable pathways. (2) Once an ectopic pathway is momentarily extinguished, the sinus node resumes as the dominant pacemaker of the heart. (3) Depolarization of the entire heart can be achieved by electrical means across the intact chest. If such an electrical method were shown to be safe, it would constitute a physiologic approach to the treatment of cardiac arrhythmias. Why has electricity not been used for reversion of the ectopic arrhythmias ? This is especially surprising since alternating current (a.c.) has now been employed in the experimental laboratory for 30 yr and clinically for about 10 yr. The failure of a.c. countershock to gain wide acceptance for treatment of disorders other than ventricular fibrillation has been due to the fear of inducing either ventricular standstill or ventricular fibrillation. In 1960, we were the first to employ alternating current for terminating a drug-refractory episode of ventricular tachycardia [2]. Sinus rhythm was restored. This dramatic result led us to employ this method again. However, in the next episode, the a.c. shock induced ventricular fibrillation. This untoward experience led to intensive laboratory investigation of the effects of a.c. discharge on the cardiovascular apparatus. Dogs in normal sinus rhythm were shocked across the intact chest with a.c. at levels which defibrillate the heart. There occurred a high incidence of diverse ectopic arrhythmias, including (a) atria1 fibrillation, which was the most common disorder (Fig. l), (b) ventricular tachycardia, which was directly related to the voltage setting, and (c) ventricular fibrillation, which was inversely related to the voltage setting. There was no voltage setting within the range of 150 to 750 at which a.c. discharge was entirely free of occurrence of ventricular fibrillation. What was even more disquieting was that after multiple a.c. shock, there was evidence of myocardial damage. Within 24 hr after such repeated shocks across the intact chest, a high percentage of animals showed significant electrocardiographic changes. These were characteristic of myocardial infarction and included S-T segment elevation, T-wave inversions, and development of abnormal Q waves. There was an accompanying rise in serum glutamic oxalacetic transaminase. A number of these animals died. This experience indicated that a.c. should not be employed clinically for the elective treatment of ectopic arrhythmias. Would discharge from a capacitor-so-called direct current (d.c.)--be effective in defibrillating or depolarizing the heart and afford less hazard than a.c.? A capacitor gives rise to a sharply peaked and exponentially decaying discharge, with a surge of voltage delivered over a very brief time. When given transthoracically, a capacitor discharge effectively depolarizes the heart but causes more damage even than does a.c. If a dog is given 20 successive shocks transthoracically, death may result from
EtiG. 1. Effect of alternating current countershock on an animal without organic heart disease is demonstrated. Ventricular tachycardia occurs, followed by a brief bout of atria1 fibrillation with recurrence of the tachycardia associated with the emergence of a curre’nt of injury. Voltage used is that required for defibrillating 65 per cent of episodes of ventricular fibrillation transthoracically.
FIG. 2. Episode of ventricular tachycardia occurring in throes of acute myocardial infarction. Arrhythmia was aot responsive to the usual drugs. A single synchronized discharge with cardioverter results in normal sinus rhythm.
FIG. 3. Atria1 fibrillation in patient with mitral stenosis which could not be reverted with quinidine is restored to normal sinus rhythm with single discharge. A ‘nodal escape beat and an atria1 premature beat precede the onset of sinus rhythm. (TO
facep. !2oo)
FIG. 4. Reversion of atria1 fibrillation is often accompanied by significant slowing in the ventricular response. The faster the initial rate, the more striking is the reduction in heart rate on restoration of sinus rhythm.
FIG. 5. An episode of atria1 flutter resistant version. This is a continuous tracing of baseline between the flutter and normal artifact, since pressure monitoring during beat after cardioversion.
to drugs readily controlled by cardiothe entire procedure. The isoelectric sinus rhythm represents an electrical reversion shows loss of but a single
Electrical
Conversion
of Cardiac
Arrhythmias
901
hyperkalemia. The capacitor induces severe muscle damage, with release of tissue potassium. Thus, it seemed as though we had reached a dead end. As Huxley once said: “The tragedy of all scientific inquiry is that a beautiful hypothesis can be slain by an ugly fact.” The ugly fact in this investigation appeared to be the inescapable danger of electrical discharge to the heart. Before quitting this area of endeavor, one additional approach was tested. The capacitor was modified by inductors in the discharge circuit to yield a monophasic wave form simulating the type of impulse generated by the excitable tissues of the heart. After testing various combinations of capacitors and inductors, it was found that an underdamped monophasic discharge of about 2.5 msec held out the most promise. In extensive animal studies, it was found that this so-called direct current (dc.) discharge was more effective than a.c. in defibrillating the heart. Furthermore, it never resulted in standstill and caused little tissue damage. Ventricular tachycardia was infrequent, and atria1 fibrillation was never observed. What was remarkable was that animals survived 200 to 300 consecutive transthoracic high-energy shocks. The one limitation was the sporadic occurrence of ventricular fibrillation. This was observed after 2 per cent of discharges. In effect, then, we had here a safer method for depolarizing the heart, but one as yet unsuitable for elective use in treating arrhythmias. The occurrence of ventricular fibrillation after 1 in 50 shocks was prohibitive, especially since this was a result obtained in healthy dogs and its intended clinical application was for patients with heart disease, frequently serious heart disease at that. The important question, therefore, was to determine the basis for the random occurrence of ventricular fibrillation after this type of d.c. shock. Physiologists for many years have been aware of the presence of a vulnerable period in the cardiac cycle during which the heart is susceptible to ventricular fibrillation [3, 41. In recent years, the existence of such a vulnerable period in the intact animal has been questioned [5]. Nevertheless, we systematically examined the cardiac cycle at intervals of 20 msec to determine if cardiac vulnerability could be demonstrated in the intact organism. If such a period did exist, was it the factor accounting for the sporadically occurring episodes of ventricular fibrillation following d.c. discharge? These studies clearly demonstrated the existence of a ventricular vulnerable period, located consistently during inscription of the apex of the T wave of the surface electrocardiogram. If a shock was delivered outside of the T wave, ventricular fibrillation never resulted. In the normal animals this brief interval generally ranged in duration from 20 to 30 msec. Such a vulnerable period has now been demonstrated in a number of diverse animals, including subhuman primates 161. We have also demonstrated in the intact animal the presence of a vulnerable period for the production of atria1 fibrillation. It followed from these experiments that if electrical discharge was triggered outside of these vulnerable periods, serious arrhythmias could be avoided. This hypothesis was confirmed in thousands of shocks administered to hundreds of animals: no serious arrhythmias occurred when the shock was discharged outside the vulnerable periods. These investigations led to the development of the method of cardioversion, which consists of depolarization of the heart by means of a monophasic underdamped electrical discharge delivered within a preselected and safe part of the cardiac cycle.
902
BERNARD LOWN
The instrument* has four components: a direct current defibrillator unit with the capacitor wave form just described as a source of energy; a synchronizer, which programs the discharge to fall within a safe part of the cardiac cycle; a cardiac monitor, which provides an R-wave reference for the synchronizer: and an oscilloscope to observe continuous display of cardiac activity. The experience with cardioversion has now been extensive. At the Peter Bent Brigham Hospital, where this method was introduced, 4 or more patients are ‘reverted’ every week. However, when the method was first introduced, no patients were available for treatment. After months of waiting, at three o’clock one morning, I was advised by the house staff that at last a suitable candidate had been found. The patient turned out to be an elderly woman in a moribund state from drugrefractory ventricular tachycardia precipitated during an acute myocardial infarction. She had pulmonary edema extending to the very apices of her lungs, and blood pressure could not be maintained even with large doses of levarterenol intravenously administered. It seemed unlikely that she would survive the next few minutes. She was given a single synchronized discharge of 1QOwsec and promptly reverted to sinus rhythm. When she awoke several minutes later, she was feeling so well that our major problem was to assure her that she was not facing St. Peter and that the Peter Bent Brigham recovery room was not the hereafter. To date, we have treated over 300 episodes of diverse arrhythmias, and have reverted over 90 per cent of these disorders to sinus rhythm. There have been no fatalities or serious complications due to the procedure itself. The first group that we treated were patients with ventricular tachycardia. Of 34 episodes of ventricular tachycardia, normal rhythm was restored in 33. The results have been nearly instantaneous and, generally, a single discharge sufficed (Fig. 2). In many of the patients treated, as was true in the first patient, the arrhythmia was the result of acute myocardial infarction. In this group of critically ill patients the prompt restoration of cardiac compensation and the absence of any untoward effects were striking. The most common disorder treated was chronic atria1 fibrillation. We have now had experience with over 200 episodes. Our reversion rate has been 90 per cent, which is a little less than the 95 per cent success rate for other rhythm disorders. In this group of patients with atria1 fibrillation, 80 per cent had rheumatic heart disease, and of these, about one-third had mitral stenosis and 15 per cent had pure mitral incompetence. The mean duration of documented arrhythmia for the entire group was 3 years. Such patients are generally difficult, if not impossible, to revert with drugs. Indeed, early in our experience, we treated all patients with large doses of quinidine, and only the drug failures were then subjected to cardioversion. The 90 per cent reversion rate is, therefore, especially remarkable. A typical reversion of atria1 fibrillation is illustrated in Fig. 3. The discharge is given during inscription of the QRS. There is a brief electrical artifact lasting 2 sec. This artifact is due to the massive electrical field imposed across the chest. If a pressure tracing is recorded during cardioversion, it is clear that there is no such asystole. The heart responds as though a ventricular ectopic beat has occurred, and the only interruption in its activity is but a brief compensatory pause. *The instrument employed in these studies Company, Buffalo, New York.
was the ‘Lown Cardioverter’,
American
Optical
Electrical
Conversion
of Cardiac
Arrhythmias
903
Cardioversion has taught us much about arrhythmias generally and atria1 fibrillation specifically. Time permits the detailing of only a few highlights : First, in the majority of patients with chronic atria1 fibrillation, immediately upon reversion to normal sinus rhythm there is a significant slowing in ventricular rate. On the average the degree of slowing has equaled 30 beats/min (Fig. 4). The better rate control with sinus rhythm may be its major hemodynamic advantage. Second, we find that a full or prolonged P-R interval is an almost invariable attribute of patients who have had chronic atria1 fibrillation. Initially, we ascribed this to overdigitalization. However, discontinuing digitalis did not abbreviate atrioventricular conduction in the majority of these patients. We have since noted that patients with mitral valvular disease who show a progressive lengthening of the P-R interval may develop atria1 fibrillation. We have also observed that atria1 fibrillation generally recurs if an advanced degree of A-V block is present after cardioversion. Third, on occasion we find the ‘sick sinus syndrome’. This is a whimsical and arbitrary designation of an entity found in about 5 to 10 per cent of patients with atria1 fibrillation immediately after reversion. They exhibit an array of abnormal atria1 mechanisms, including sino-atria1 standstill, sino-atria1 block, multiple atria1 extrasystoles, and paroxysms of atria1 tachycardia alternating with slow nodal rhythm. Frequently, the sinus rhythm is only transient, and atria1 fibrillation promptly recurs. Fourth is the fact that nearly all patients feel better immediately on reversion. Even those who have never experienced palpitation have commented on the calm in their chest when sinus rhythm is restored. Fifth is the observation that in about 10 per cent of patients there is an immediate lessening of S-T segment depression noted in the precordial leads on re-establishment of a sinus mechanism. Should all patients with chronic atria1 fibrillation be ‘reverted’? The answer is a categoric “no.” It is my opinion that reversion should be limited to patients who will maintain a sinus mechanism and those who have intractable heart failure because of the arrhythmia. The patient with a giant left atrium will generally not be able to sustain a sinus rhythm. The patient with long-standing atria1 fibrillation and uncorrected valvular disease is also a poor candidate. When reversion had been carried out with quinidine, and despite adequate maintenance doses of the drug, fibrillation has recurred, then cardioversion is usually contraindicated. The patient who is unduly sensitive to quinidine and has significant cardiomegaly ought not to be reverted, because no other effective antiarrhythmic maintenance therapy is presently available. A number of patients having some of the contraindications that have been cited have, however, been reverted. These patients had intractable heart failure, and even a brief spell of normal rhythm was deemed to have a salutory effect. We have also treated a number of episodes of chronic atria1 flutter. While this arrhythmia is often difficult to terminate with drugs, it has been the easiest disorder to control with cardioversion. All 31 episodes were instantly restored to sinus rhythm. One such reversion is illustrated in Fig. 5. The patient whose electrocardiogram is shown had previously been given 6 g of quinidine daily, which produced severe toxicity but did not restore sinus rhythm. Termination of atria1 flutter has required less energy than for any other arrhythmia. This may be related
904
BERNARDLOWN
to the observation that in atria1 fibrillation, the larger the F waves, the easier it is to restore sinus rhythm. It is our view that cardioversion is the treatment of choice for patients with chronic atria1 flutter. Cardioversion also lends itself to the treatment of drug-refractory supraventricular tachycardias. We have treated 10 such patients and have restored sinus rhythm in 7. Our experience suggests that cardioversion is less likely to be effective in those arrhythmias having slow atria1 rates, or when the disorder has been provoked by excessive doses of digitalis drugs. What about complications? In the 300 episodes of arrhythmia treated by means of cardioversion there have been no episodes of ventricular fibrillation and no episodes of ventricular standstill. There were 3 transient paroxysms of ventricular tachycardia, 1 of which required cardioversion. Among patients with chronic atria1 fibrillation, 3 postreversion embolic episodes occurred. No other serious complications were encountered. This is especially remarkable since many of the patients were chronically and critically ill with far-advanced heart disease. There are now close to 2,000 medical centers in the United States that practice cardioversion. Patient-experience with this form of treatment no doubt runs into tens of thousands. This is a remarkable record of acceptance, since this method was introduced to medicine only three years ago. Cardioversion represents a new therapeutic principle. It is physiologic in conception and simple in application. It is the most effective method yet devised for terminating arrhythmias. It is devoid of the hazards associated with the use of large doses of antiarrhythmic drugs. Since reliance on maintenance therapy is necessary to prevent recurrence of arrhythmia, it will no doubt stimulate and intensify investigation for more effective and safer drugs.
1. 2. 3. 4. 5. 6.
REFERENCES LOWN, B. et al.: Use of synchronized direct current countershock in treatment of cardiac arrhythmas. Presented before the 54th Annual Meeting, American Society for Clinical Investigation, 30 April 1962. in ALEXANDER,S., KL.EIGER, R. and LOWN, B. : Use of external electric countershock treatment of ventricular tachycardia, J. Amer. med. Ass. 177, 916, 1961. KING, B. G.: Effects of electric shock on heart action with special reference to varying susceptibility in different parts of cardiac cycle. Columbia University Doctoral Thesis, New York City. Aberdeen Press, May 1934. WIGGERS, C. J. and WE.GRIA,R.: Ventricular fibrillation due to single localized induction and condenser shocks applied during vulnerable phase of ventricular systole, Amer. .I. Physiol. 128, 500, 1939. MAASKE, C. A. and BROMBJXRGER-BARNEA, B.: Excitability of the normally beating hearts, Amer. J. Physiol. 195,575, 1958. LOWN, B., BEY, S. K., PIXJ.XOTH, M. and Ann,, T.: Comparative studies of ventricular vulnerability to fibrillation, J. ciin. Invest. 42,953, 1963.
1965, Vol. 18, pp. 899-904. Pergamon Press Ltd. Printed in Great Britain
ELECTRICAL
CONVERSION OF CARDIAC ARRHYTHMIAS*
BERNARD LOWN, M.D. Assistant Professor of Medicine, Department of Nutrition, Harvard Public Health, Boston, Massachusetts, U.S.A.
University
School of
OVER the past 50 years the treatment of chronic arrhythmias has remained essentially
pharmacologic. Initiated at the turn of the century by the pioneering work of Wenckebach and Frey, it has rested on the use of three drugs, namely, procaine amide, quinidine, and the digitalis glycosides. This therapeutic approach is now undergoing profound alteration. Before dealing with the new, it would be worth while to get a perspective on what the problems with drugs have been in the past and how these problems are being circumvented with new methods. The heart accomplishes three types of work, namely, rate, pressure, and volume work. The least well tolerated is a disturbance in rate. Dr. Schwedel dealt with one aspect of this, the consequences of slow rates, but rapid rates are often more taxing on the myocardium, especially if they are initiated in the ventricle. Serious compromise of cardiac output and of coronary flow may occur, often jeopardizing survival. Antiarrhythmic drugs have a number of limitations. In the first place, there is no way for the physician to know ill priori the specific drug requirements necessary to terminate a rhythm disorder. In effect, a biologic titration is necessary, and this may take minutes, hours, days, or even weeks. In the second place, toxicity often accompanies the use of antiarrhythmic drugs. The agents in current use compromise peripheral resistance and reduce cardiac contractility. Such deleterious changes occur at the very time when the heart is already maximally taxed in its reserve function. There is a third drawback to the use of drugs which relates to their mode of action. If one assumes that the majority of human ectopic arrythmias are sustained by a circus movement, i.e., the existence of a re-entry pathway, then these drugs presumably act by lengthening the refractory period of conduction; this would tend to extinguish the circulating wave of depolarization. However, at the same time, antiarrhythmic drugs slow conduction; this would tend to sustain the disorder. Whether or not an arrhythmia is terminated depends upon which of these two effects is dominant. At the same time, the antiarrhythmic drugs depress rhythmicity of the sinus node and thereby further inhibit the establishment of a normal rhythm. The final limitation of antiarrhythmic drugs is that they are not always effective. When atria1 fibrillation is the arrhythmia under treatment, the physician still has recourse to the digitalis drugs to slow the ventricular rate. However, in the case of ventricular tachycardia, no such recourse exists, and the patient then succumbs to *The work reported here was supported by Grant I-E-07776-02, National Institutes of Health. 899
900
BERNARDLOWN
the arrhythmia. These have been the major problems in the use of antiarrhythmic drugs. Electrical discharge has been suggested as an alternative method [l]. It rests on three suppositions : (1) The factors which initiate ventricular or atria1 arrhythmias are generally transient. Once initiated, the mechanism is self-sustaining. This is due to the fact that the majority of human ectopic tachycardias are maintained by a continuing passage of recirculating wave fronts of excitation over fixed or variable pathways. (2) Once an ectopic pathway is momentarily extinguished, the sinus node resumes as the dominant pacemaker of the heart. (3) Depolarization of the entire heart can be achieved by electrical means across the intact chest. If such an electrical method were shown to be safe, it would constitute a physiologic approach to the treatment of cardiac arrhythmias. Why has electricity not been used for reversion of the ectopic arrhythmias ? This is especially surprising since alternating current (a.c.) has now been employed in the experimental laboratory for 30 yr and clinically for about 10 yr. The failure of a.c. countershock to gain wide acceptance for treatment of disorders other than ventricular fibrillation has been due to the fear of inducing either ventricular standstill or ventricular fibrillation. In 1960, we were the first to employ alternating current for terminating a drug-refractory episode of ventricular tachycardia [2]. Sinus rhythm was restored. This dramatic result led us to employ this method again. However, in the next episode, the a.c. shock induced ventricular fibrillation. This untoward experience led to intensive laboratory investigation of the effects of a.c. discharge on the cardiovascular apparatus. Dogs in normal sinus rhythm were shocked across the intact chest with a.c. at levels which defibrillate the heart. There occurred a high incidence of diverse ectopic arrhythmias, including (a) atria1 fibrillation, which was the most common disorder (Fig. l), (b) ventricular tachycardia, which was directly related to the voltage setting, and (c) ventricular fibrillation, which was inversely related to the voltage setting. There was no voltage setting within the range of 150 to 750 at which a.c. discharge was entirely free of occurrence of ventricular fibrillation. What was even more disquieting was that after multiple a.c. shock, there was evidence of myocardial damage. Within 24 hr after such repeated shocks across the intact chest, a high percentage of animals showed significant electrocardiographic changes. These were characteristic of myocardial infarction and included S-T segment elevation, T-wave inversions, and development of abnormal Q waves. There was an accompanying rise in serum glutamic oxalacetic transaminase. A number of these animals died. This experience indicated that a.c. should not be employed clinically for the elective treatment of ectopic arrhythmias. Would discharge from a capacitor-so-called direct current (d.c.)--be effective in defibrillating or depolarizing the heart and afford less hazard than a.c.? A capacitor gives rise to a sharply peaked and exponentially decaying discharge, with a surge of voltage delivered over a very brief time. When given transthoracically, a capacitor discharge effectively depolarizes the heart but causes more damage even than does a.c. If a dog is given 20 successive shocks transthoracically, death may result from
EtiG. 1. Effect of alternating current countershock on an animal without organic heart disease is demonstrated. Ventricular tachycardia occurs, followed by a brief bout of atria1 fibrillation with recurrence of the tachycardia associated with the emergence of a curre’nt of injury. Voltage used is that required for defibrillating 65 per cent of episodes of ventricular fibrillation transthoracically.
FIG. 2. Episode of ventricular tachycardia occurring in throes of acute myocardial infarction. Arrhythmia was aot responsive to the usual drugs. A single synchronized discharge with cardioverter results in normal sinus rhythm.
FIG. 3. Atria1 fibrillation in patient with mitral stenosis which could not be reverted with quinidine is restored to normal sinus rhythm with single discharge. A ‘nodal escape beat and an atria1 premature beat precede the onset of sinus rhythm. (TO
facep. !2oo)
FIG. 4. Reversion of atria1 fibrillation is often accompanied by significant slowing in the ventricular response. The faster the initial rate, the more striking is the reduction in heart rate on restoration of sinus rhythm.
FIG. 5. An episode of atria1 flutter resistant version. This is a continuous tracing of baseline between the flutter and normal artifact, since pressure monitoring during beat after cardioversion.
to drugs readily controlled by cardiothe entire procedure. The isoelectric sinus rhythm represents an electrical reversion shows loss of but a single
Electrical
Conversion
of Cardiac
Arrhythmias
901
hyperkalemia. The capacitor induces severe muscle damage, with release of tissue potassium. Thus, it seemed as though we had reached a dead end. As Huxley once said: “The tragedy of all scientific inquiry is that a beautiful hypothesis can be slain by an ugly fact.” The ugly fact in this investigation appeared to be the inescapable danger of electrical discharge to the heart. Before quitting this area of endeavor, one additional approach was tested. The capacitor was modified by inductors in the discharge circuit to yield a monophasic wave form simulating the type of impulse generated by the excitable tissues of the heart. After testing various combinations of capacitors and inductors, it was found that an underdamped monophasic discharge of about 2.5 msec held out the most promise. In extensive animal studies, it was found that this so-called direct current (dc.) discharge was more effective than a.c. in defibrillating the heart. Furthermore, it never resulted in standstill and caused little tissue damage. Ventricular tachycardia was infrequent, and atria1 fibrillation was never observed. What was remarkable was that animals survived 200 to 300 consecutive transthoracic high-energy shocks. The one limitation was the sporadic occurrence of ventricular fibrillation. This was observed after 2 per cent of discharges. In effect, then, we had here a safer method for depolarizing the heart, but one as yet unsuitable for elective use in treating arrhythmias. The occurrence of ventricular fibrillation after 1 in 50 shocks was prohibitive, especially since this was a result obtained in healthy dogs and its intended clinical application was for patients with heart disease, frequently serious heart disease at that. The important question, therefore, was to determine the basis for the random occurrence of ventricular fibrillation after this type of d.c. shock. Physiologists for many years have been aware of the presence of a vulnerable period in the cardiac cycle during which the heart is susceptible to ventricular fibrillation [3, 41. In recent years, the existence of such a vulnerable period in the intact animal has been questioned [5]. Nevertheless, we systematically examined the cardiac cycle at intervals of 20 msec to determine if cardiac vulnerability could be demonstrated in the intact organism. If such a period did exist, was it the factor accounting for the sporadically occurring episodes of ventricular fibrillation following d.c. discharge? These studies clearly demonstrated the existence of a ventricular vulnerable period, located consistently during inscription of the apex of the T wave of the surface electrocardiogram. If a shock was delivered outside of the T wave, ventricular fibrillation never resulted. In the normal animals this brief interval generally ranged in duration from 20 to 30 msec. Such a vulnerable period has now been demonstrated in a number of diverse animals, including subhuman primates 161. We have also demonstrated in the intact animal the presence of a vulnerable period for the production of atria1 fibrillation. It followed from these experiments that if electrical discharge was triggered outside of these vulnerable periods, serious arrhythmias could be avoided. This hypothesis was confirmed in thousands of shocks administered to hundreds of animals: no serious arrhythmias occurred when the shock was discharged outside the vulnerable periods. These investigations led to the development of the method of cardioversion, which consists of depolarization of the heart by means of a monophasic underdamped electrical discharge delivered within a preselected and safe part of the cardiac cycle.
902
BERNARD LOWN
The instrument* has four components: a direct current defibrillator unit with the capacitor wave form just described as a source of energy; a synchronizer, which programs the discharge to fall within a safe part of the cardiac cycle; a cardiac monitor, which provides an R-wave reference for the synchronizer: and an oscilloscope to observe continuous display of cardiac activity. The experience with cardioversion has now been extensive. At the Peter Bent Brigham Hospital, where this method was introduced, 4 or more patients are ‘reverted’ every week. However, when the method was first introduced, no patients were available for treatment. After months of waiting, at three o’clock one morning, I was advised by the house staff that at last a suitable candidate had been found. The patient turned out to be an elderly woman in a moribund state from drugrefractory ventricular tachycardia precipitated during an acute myocardial infarction. She had pulmonary edema extending to the very apices of her lungs, and blood pressure could not be maintained even with large doses of levarterenol intravenously administered. It seemed unlikely that she would survive the next few minutes. She was given a single synchronized discharge of 1QOwsec and promptly reverted to sinus rhythm. When she awoke several minutes later, she was feeling so well that our major problem was to assure her that she was not facing St. Peter and that the Peter Bent Brigham recovery room was not the hereafter. To date, we have treated over 300 episodes of diverse arrhythmias, and have reverted over 90 per cent of these disorders to sinus rhythm. There have been no fatalities or serious complications due to the procedure itself. The first group that we treated were patients with ventricular tachycardia. Of 34 episodes of ventricular tachycardia, normal rhythm was restored in 33. The results have been nearly instantaneous and, generally, a single discharge sufficed (Fig. 2). In many of the patients treated, as was true in the first patient, the arrhythmia was the result of acute myocardial infarction. In this group of critically ill patients the prompt restoration of cardiac compensation and the absence of any untoward effects were striking. The most common disorder treated was chronic atria1 fibrillation. We have now had experience with over 200 episodes. Our reversion rate has been 90 per cent, which is a little less than the 95 per cent success rate for other rhythm disorders. In this group of patients with atria1 fibrillation, 80 per cent had rheumatic heart disease, and of these, about one-third had mitral stenosis and 15 per cent had pure mitral incompetence. The mean duration of documented arrhythmia for the entire group was 3 years. Such patients are generally difficult, if not impossible, to revert with drugs. Indeed, early in our experience, we treated all patients with large doses of quinidine, and only the drug failures were then subjected to cardioversion. The 90 per cent reversion rate is, therefore, especially remarkable. A typical reversion of atria1 fibrillation is illustrated in Fig. 3. The discharge is given during inscription of the QRS. There is a brief electrical artifact lasting 2 sec. This artifact is due to the massive electrical field imposed across the chest. If a pressure tracing is recorded during cardioversion, it is clear that there is no such asystole. The heart responds as though a ventricular ectopic beat has occurred, and the only interruption in its activity is but a brief compensatory pause. *The instrument employed in these studies Company, Buffalo, New York.
was the ‘Lown Cardioverter’,
American
Optical
Electrical
Conversion
of Cardiac
Arrhythmias
903
Cardioversion has taught us much about arrhythmias generally and atria1 fibrillation specifically. Time permits the detailing of only a few highlights : First, in the majority of patients with chronic atria1 fibrillation, immediately upon reversion to normal sinus rhythm there is a significant slowing in ventricular rate. On the average the degree of slowing has equaled 30 beats/min (Fig. 4). The better rate control with sinus rhythm may be its major hemodynamic advantage. Second, we find that a full or prolonged P-R interval is an almost invariable attribute of patients who have had chronic atria1 fibrillation. Initially, we ascribed this to overdigitalization. However, discontinuing digitalis did not abbreviate atrioventricular conduction in the majority of these patients. We have since noted that patients with mitral valvular disease who show a progressive lengthening of the P-R interval may develop atria1 fibrillation. We have also observed that atria1 fibrillation generally recurs if an advanced degree of A-V block is present after cardioversion. Third, on occasion we find the ‘sick sinus syndrome’. This is a whimsical and arbitrary designation of an entity found in about 5 to 10 per cent of patients with atria1 fibrillation immediately after reversion. They exhibit an array of abnormal atria1 mechanisms, including sino-atria1 standstill, sino-atria1 block, multiple atria1 extrasystoles, and paroxysms of atria1 tachycardia alternating with slow nodal rhythm. Frequently, the sinus rhythm is only transient, and atria1 fibrillation promptly recurs. Fourth is the fact that nearly all patients feel better immediately on reversion. Even those who have never experienced palpitation have commented on the calm in their chest when sinus rhythm is restored. Fifth is the observation that in about 10 per cent of patients there is an immediate lessening of S-T segment depression noted in the precordial leads on re-establishment of a sinus mechanism. Should all patients with chronic atria1 fibrillation be ‘reverted’? The answer is a categoric “no.” It is my opinion that reversion should be limited to patients who will maintain a sinus mechanism and those who have intractable heart failure because of the arrhythmia. The patient with a giant left atrium will generally not be able to sustain a sinus rhythm. The patient with long-standing atria1 fibrillation and uncorrected valvular disease is also a poor candidate. When reversion had been carried out with quinidine, and despite adequate maintenance doses of the drug, fibrillation has recurred, then cardioversion is usually contraindicated. The patient who is unduly sensitive to quinidine and has significant cardiomegaly ought not to be reverted, because no other effective antiarrhythmic maintenance therapy is presently available. A number of patients having some of the contraindications that have been cited have, however, been reverted. These patients had intractable heart failure, and even a brief spell of normal rhythm was deemed to have a salutory effect. We have also treated a number of episodes of chronic atria1 flutter. While this arrhythmia is often difficult to terminate with drugs, it has been the easiest disorder to control with cardioversion. All 31 episodes were instantly restored to sinus rhythm. One such reversion is illustrated in Fig. 5. The patient whose electrocardiogram is shown had previously been given 6 g of quinidine daily, which produced severe toxicity but did not restore sinus rhythm. Termination of atria1 flutter has required less energy than for any other arrhythmia. This may be related
904
BERNARDLOWN
to the observation that in atria1 fibrillation, the larger the F waves, the easier it is to restore sinus rhythm. It is our view that cardioversion is the treatment of choice for patients with chronic atria1 flutter. Cardioversion also lends itself to the treatment of drug-refractory supraventricular tachycardias. We have treated 10 such patients and have restored sinus rhythm in 7. Our experience suggests that cardioversion is less likely to be effective in those arrhythmias having slow atria1 rates, or when the disorder has been provoked by excessive doses of digitalis drugs. What about complications? In the 300 episodes of arrhythmia treated by means of cardioversion there have been no episodes of ventricular fibrillation and no episodes of ventricular standstill. There were 3 transient paroxysms of ventricular tachycardia, 1 of which required cardioversion. Among patients with chronic atria1 fibrillation, 3 postreversion embolic episodes occurred. No other serious complications were encountered. This is especially remarkable since many of the patients were chronically and critically ill with far-advanced heart disease. There are now close to 2,000 medical centers in the United States that practice cardioversion. Patient-experience with this form of treatment no doubt runs into tens of thousands. This is a remarkable record of acceptance, since this method was introduced to medicine only three years ago. Cardioversion represents a new therapeutic principle. It is physiologic in conception and simple in application. It is the most effective method yet devised for terminating arrhythmias. It is devoid of the hazards associated with the use of large doses of antiarrhythmic drugs. Since reliance on maintenance therapy is necessary to prevent recurrence of arrhythmia, it will no doubt stimulate and intensify investigation for more effective and safer drugs.
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REFERENCES LOWN, B. et al.: Use of synchronized direct current countershock in treatment of cardiac arrhythmas. Presented before the 54th Annual Meeting, American Society for Clinical Investigation, 30 April 1962. in ALEXANDER,S., KL.EIGER, R. and LOWN, B. : Use of external electric countershock treatment of ventricular tachycardia, J. Amer. med. Ass. 177, 916, 1961. KING, B. G.: Effects of electric shock on heart action with special reference to varying susceptibility in different parts of cardiac cycle. Columbia University Doctoral Thesis, New York City. Aberdeen Press, May 1934. WIGGERS, C. J. and WE.GRIA,R.: Ventricular fibrillation due to single localized induction and condenser shocks applied during vulnerable phase of ventricular systole, Amer. .I. Physiol. 128, 500, 1939. MAASKE, C. A. and BROMBJXRGER-BARNEA, B.: Excitability of the normally beating hearts, Amer. J. Physiol. 195,575, 1958. LOWN, B., BEY, S. K., PIXJ.XOTH, M. and Ann,, T.: Comparative studies of ventricular vulnerability to fibrillation, J. ciin. Invest. 42,953, 1963.