Cardiac Arrhythmia and Cardiac Death RAYMOND D. PRIJITT
SINCE the time of Mackenzie, recognition has been accorded the observation that the patient whose only affliction is a disturbance in cardiac rhythm may live for many years in freedom from significant consequences of cardiac disease. While revision of this well-established concept does not appear appropriate, emphasis justifiably may be given the fact that cardiac arrhythmias may cause the death of certain patients who would have survived the other consequences of heart disease.
VENTRICULAR ARREST AND VENTRICULAR TACHYCARDIA OR FIBRILLATION
The somber context of this latter theme is identified in the record of Case I which is typical of a group whose representatives are common in the experience of many physicians. CASE I. A man, 51 years of age, came in for examination on April 2, 1957. For 3 months he -had been experiencing symptoms which were judged to be suggestive but not typical of angina pectoris. On March 26, he had lost consciousness for a few moments immediately after awakening. On March 30, he experienced a second and similar attack. These two episodes led him to seek medical consultation. Neurologic examination including electroencephalographic study gave negative results. Because of the atypical nature of the patient's anginal symptoms, an exercise test was performed on April 4. The results of this test, as shown in Figure 85, were positive, and the diagnosis of coronary insufficiency was made. On the morning of April 6, while dressing, the patient said to his wife, "I feel weak." Immediately thereafter he fell to the floor. A physician who arrived a few moments later pronounced the patient dead. At necropsy the only relevant finding was coronary sclerosis varying in different arteries from mild to moderate degree. There was no evidence of acute myocardial infarction nor of old or recent coronary occlusion.
This man died as a consequence of what has been called "failure of the cardiac mechanism." More specifically, his death resulted from a failure of the heart to maintain circulation of the blood because of complete ventricular arrest or ventricular fibrillation. In this patient, as in the overwhelming majority who die in similar fashion, the terminal event was not documented, for to do so would require direct inspection of the 881
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heart at the time of the event or the recording of an electrocardiogram at that moment. Belief that one of these two disturbances in rhythm occurs is derived from observations on other patients, some of whom are subject to repetitions of syncopal attacks of cardiac origin. In Figure 86 are reproduced electrocardiograms from a woman who was subject to Stokes-Adams seizures. Such seizures may result either from prolonged periods of ventricular asystole or from ventricular tachycardia. This patient presented the trying circumstance of having synco-
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istence highlights a therapeutic dilemma to which consideration will be given in a later paragraph. But first certain facts bearing on the incidence of death as a result of ventricular arrest or fibrillation among patients with one type of heart disease, namely, coronary sclerosis with myocardial infarction, are deserving of consideration. Achor and associates have summarized the results of an analysis of the cause of death in 250 cases of healed myocardial infarction. In 93 cases, death resulted from noncardiac causes. Among the 157 patients dying from causes primarily cardiac in nature, 44 (28.0 per cent) died of congestive heart failure without acute myocardial infarction, 49 (31.2 per cent) died during an episode of recurrent acute myocardial infarction, and 64 (40.8 per cent), the largest single group, died suddenly without congestive failure or acute myocardial infarction. By implication four in every 10 patients among this group of 157 died of "mechanism failure." Many of these patients, like the one whose story and findings constituted the introductory record in this account, had a reasonably intact ventricular myocardial mass and sufficient coronary flow to permit them to live comfortable and productive lives. Prevention of these deaths is a therapeutic problem of challenging proportions to which physicians cannot supply an adequate answer. It behooves us, however, to reflect on the sources of frustration, hoping that from such consideration may come a clearer perception of the problem which should be resolved. Broadly speaking there are two 'approaches to the treatment of ventricular standstill and of ventricular tachycardia or fibrillation, namely, the pharmacologic and the mechanical. These will now be considered. Pharlllacologic Treatlllent
The pharmacologic treatment of ventricular arrest consists in the administration of drugs designed to stimulate the production of repetitive and effective ventricular beats often by improving the conductivity of the junctional tissues between the atria and ventricles. Chief among these drugs currently in use are the sympathomimetic group including epinephrine, isoproterenol hydrochloride (Isuprel) and ephedrine, and certain other agents of which molar sodium lactate is the favorite of the hour. Each of these agents has the potentiality of increasing myocardial irritability, and on this quality depends at least in part its effectiveness in relieving ventricular arrest. Therefore, while decreasing the degree of atrioventricular block, the agent may invoke ventricular extrasystoles and may predispose to development of ventricular tachycardia and ventricular fibrillation. The pharmacologic treatment of ventricular tachycardia and ventricular fibrillation, on the other hand, consists in the administration of drugs, principally quinidine and procainamide hydrochloride (Pro-
Cardiac Arrhythmia and Cardiac Death
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nestyl), designed to decrease .myocardial irritability and interrupt the rapid sequence of ventricular beats. Yet these drugs not only may decrease myocardial irritability but also may further depress myocardial function. Consequently, unless the rhythmic disorder is righted rather promptly, particularly in the heart afflicted by organic disease, this depression of myocardial function may present an increasing hazard which necessitates cessation of administration of the drug. Thus the dilemma is posed in the treatment of potentially lethal cardiac arrhythmias by pharmacologic means. The heart which has gone into ventricular standstill may be roused by drugs which improve atrioventricular conduction, but these same drugs may increase the irritability of a myocardium already predisposed to ventricular fibrillation by the ischemic effects of ventricular arrest. The heart afflicted by ventricular tachycardia may be quieted by drugs which reduce its irritability, but these same drugs, unless they promote reversion to a physiologically more effective rhythm, may depres~ further the failing myocardial function. The kinship of those circumstances which induce ventricular standstill and ventricular tachycardia is illustrated precisely in the record of the patient already discussed whose electrocardiograms are reproduced in Figure 86. Here is represented also the dilemma of therapy by pharmacologic means in a patient who presents in sequence both varieties of potentially lethal cardiac arrhythmias. Mechanical Measures
Because of the limited effectiveness and the hazards inherent in treatment of ventricular arrest and ventricular fibrillation by drugs, mechanical measures of therapy have received increasing amounts of attention. Bellet, in his excellent summary of treatment for Stokes-Adams syndrome, proposed a possible treatment for cardiac arrest which, if effective, would possess attributes in which certain other methods are deficient. He stated that by direct vigorous thumping on the precordium of the patient, ventricular contractions have been restored after cardiac standstill and patients kept alive for as long as 12 hours. What evermay be the deficiencies of this method, the feasibility of its application by those most likely to be on hand at the onset of an episode of ventricular arrest distinguishes it from the more effective and specific approaches represented by the ventricular pacemaker developed by Zoll and his associates and the traditional efforts to stimulate the myocardium by pricking it with a needle through which epinephrine mayor may not be delivered. The mechanical pacemaker represents a significant addition to the therapeutic resources of a cardiac treatment unit in a center for patients recovering from the acute phase of a cardiac illness either after surgical correction of a cardiac lesion or in the immediate postmyocardial infarction period. The very chronicity of coronary heart disease and the
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unpredictability of crises which may develop minimize the effectiveness of the external pacemaker as an instrument in the hands of the majority of physicians. A similar comment may be entered in respect to defibrillators whether applied externally to the thorax or directly to the surface of the ventricles after thoracotomy. In summary of this discussion of therapy in ventricular arrest and ventricular tachycardia or fibrillation, the following points may be set down: 1. Establish, if time and circumstances permit, the exact nature of the rhythmic disturbances. One catastrophic arrhythmia may mimic the other in its clinical expressions, yet therapeutic measures are antithetical. 2. If simple mechanical measures of treatment fail and technically complex mechanical measures are not available or applicable, initiate pharmacologic therapy appropriate to the specific arrhythmia. 3. Monitor developments with care observing for evidences of increased myocardial irritability when sympathomimetic drugs or molar sodium lactate is used and for evidences of depressed or failing myocardial function as expressed in falling blood pressure or widening QRS interval when the myocardial depressants, quinidine or Pronestyl, are administered. 4. Recognize that at the level of effective therapy for the chronically afflicted patient or the patient subject to unpredictable catastrophic arrhythmias, our present methods of treatment are inadequate. From this realization may stem the investigative efforts which ultimately will provide the effective measures that are needed today. And now, for relief and diversion, I would recall the experiences of one of our patients who died in 1952 at the age of 72. CASE 11. This man first presented himself to our cardiologic consultants in 1917 when he was 37 years of age. He was found initially to have atrial flutter with complete atrioventricular dissociation and a ventricular rate of 46 beats per minute. Digitalis was administered, whereupon his atria converted to a sinus rhythm at a rate of 79, but the atrioventricular block persisted, the ventricles beating 42 times per minute (Fig. 87). The decision was reached to abandon further therapeutic efforts. In later years, the patient insisted that he was told at our Clinic he had a fatal illness and should go home and prepare to die. Of this advice, I can find no notation in the consultant's comments of 1917 nor any time thereafter. For 30 years, this man found pleasure in reminding his counselors how erroneous had been their alleged prognostications in his behalf. He returned for care in 1947 at which time he was in mild congestive heart failure. He was digitalized and maintained on treatment with this drug. In 1949 at age 69 years, his condition (Fig. 87) was such that he could still work 13 or 14 hours uninterruptedly. We were informed by his wife that he died in 1952, although in what manner she did not say.
The record of this man's experiences supports the conclusion that complete heart block sometimes may exist benignly and asymptomati-
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cally for many years. That ventricular tachycardia also may occur in the absence of other evidences of cardiac disease is illustrated in the clinical account which follows. CASE Ill. A youth, 18 years of age, came to the Clinic in 1952 because of episodic ventricular tachycardia. During the preceding year he had experienced attacks lasting as long as 10 days and attended frequently by pain of coronary insufficiency and on one occasion by physical findings of congestive heart failure. Examination at the time of admission to the Clinic disclosed no evidence of
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Fig. 89 (Case III continued). Additional electrocardiograms. The record of 10-22-52 is characterized by the presence of inverted T waves in leads 11, Ill, aVF, V 5 and V 6, changes believed to be secondary to ischemic effects induced by the episode of ventricular tachycardia. In the records of 11-15-52, T deflections in these same leads have reverted to an upright position.
heart disease other than these episodes (Figs. 88 and 89). Quinidine administered by the patient's family physician had proved inadequate in controlling the arrhythmia, and procainamide hydrochloride (Pronestyl) given intravenously under supervision at the Clinic would interrupt an attack but giv.en orally did not prevent recurrences. Since the lad came from a distant country and his father feared lest his care there \vould be inadequate to the necessities of his illness and because emotional elements definitely played a large role in the precipitation of the patient's attacks, bilateral cervicothoracic sympathectomy ultimately was advised and performed. The patient's margin of freedom from attacks was increased. At last report supplied by his father, the patient had experienced only one or two mild episodes, and these had occurred when he
890
Raymond D. Pruitt
broke with his father's interdictions and raced on his bicycle against the school bus down the roads of his native Afghanistan.
The experiences with Cases 11 and III support the time-honored dictum that cardiac arrhythmias, when unattended by serious organic heart disease, commonly carry a benign prognosis, and that this may be so for patients subject to complete heart block and to ventricular tachycardia as well as to those with milder types of disturbed cardiac rhythm. ATRIAL FIBRILLATION WITHOUT OTHER CARDIAC DISEASE
The final portion of this discussion will be devoted to a consideration of atrial fibrillation and principally to that category without other evidences of organic heart disease. Admittedly in many patients, particularly those at advanced age, atrial fibrillation develops and is tolerated without evident impairment of cardiac function until the end of their long lives. When the patient's health is compromised as the result primarily of the atrial fibrillation and not of some coexisting valvular or myocardial lesion, then one of two circumstances is likely to be responsible: (1) The ventricular rate has been excessively high over long periods of time. (2) Mural thrombi have broken off and lodged in one or several of the many critical points in the body. Control of these two potentially harmful circumstances becomes the physician's challenge as he confronts an afflicted patient. Rapid ventricular rate commonly can be reduced to levels compatible with efficient ventricular function by administration of appropriate amounts of digitalis. However, I can recall one man in the early portion of his seventh decade whose ventricular rate remained in excess of 120 beats per minute after daily administration of 0.6 mg. of digitoxin for many days. He was given quinidine, 3 grains (0.2 gm.) four times daily for a few days, his rhythm converted to a sinus type and his ventricular rate fell to levels between 60 and 75 beats per minute. In this clinical experience is found support for a flexible attitude with regard to the treatment of auricular fibrillation by pharmacologic means. Digitalis and quinidine are drugs sufficiently divergent in mode of action that when one fails to effect solution of a problem, the other may work promptly and well. Except when lack of cooperation by the patient has proved an insurmountable obstacle to effective treatment, control of ventricular rate in cases of auricular fibrillation has proved, in my experience, less of a problem than that presented by the imponderable hazard of systemic embolization. Inasmuch as the danger of embolization is less if sinus rhythm can be restored and maintained, an effort to accomplish this end by administration of quinidine is justified. However, fatalities reasonably ascribed to the pharmacologic effects of quinidine even at small to moderate levels of dosage continue to enter
Cardiac Arrhythmia and Cardiac Death
891
medical experience in frequency sufficient to produce a source of deep concern in regard to the welfare of any patient treated with this drug. Because of this concern, my colleagues and I prefer to institute quinidine therapy with the patient in the hospital. An extended preliminary period of anticoagulant therapy would be ideal but may not be practicable. Before each dose of quinidine is administered, the patient is checked for symptoms or signs of toxic reaction to the drug. An electrocardiogram is recorded daily and studied for evidences of impaired atrioventricular or intraventricular conduction. The total dosage of quinidine is not carried to more than 3 gm. in 24 hours unless all has gone well at lower dosages and the justification for pushing on to higher levels is exceptionally great. If sinus rhythm has not been restored with quinidine or if reversion to atrial fibrillation occurs promptly in spite of continued treatment with the drug, then consideration must be given to long-term treatment with anticoagulants. Justification for such an undertaking is found on review of the following clinical case. CASE IV. In 1935, a 43-year-old man presented himself for examination and treatment. He was found to have atrial fibrillation attended by a ventricular rate of 128 beats per minute. Treatment with quinidine was administered and sinus rhythm temporarily was restored. Reversion to atrial fibrillation occurred within 1 month in spite of continued treatment with quinidine. Use of quinidine was discontinued, and treatment with digitalis was begun and continued throughout the remainder of the patient's life. In 1947, examination disclosed hypertension, the systolic pressure being 182 mm. of mercury and the diastolic 118 mm., and a nonfunctioning left kidney. In February, 1953, pain in the right flank, hematuria and anuria developed and the patient died in uremia. The findings at necropsy included splenic, cerebral and bilateral renal infarcts with atrophy of the left kidney. The renal findings are pictured in Figure 90, a. That the atrophic left kidney played a role in development of this patient's hypertension seems likely; infarction of the right kidney was attended by failure of renal function and death. Examination of the heart disclosed no valvular disease (Fig. 90, b) and minimal coronary atherosclerosis. Microscopic study of the left atrial wall revealed the site of origin of a recently dislodged mural thrombus.
This patient, I think, could have been spared the complications leading to his death by properly administered anticoagulant therapy. The feasibility of such a program of anticoagulant therapy when adequate laboratory facilities are available is well established. We have under continued observation at the Clinic one patient who has been maintained almost constantly at accepted levels of therapeutically effective prothrombin deficiency over a period of 12 years. Currently his prothrombin time is being checked once a month, and in the past year the prothrombin time has been maintained between the range of 29 and 40 seconds. Although the hazards of long-term anticoagulant therapy are not to ~be minimized, my colleagues and I have the impression that careful
892
Raymond D. Pruitt
Fig. 90 (Case IV). a, Kidneys, ureters, and aorta of a man, aged 61 years, who had had idiopathic auricular fibrillation for 18 years prior to his death and who succumbed in uremia (for details, see text). A thrombus was present in the left renal artery and the kidney was atrophic. A more recent thrombus was present in the right renal artery and infarction of the right kidney was noted. b, The heart. Note normal appearance of mitral valve. An organized thrombus was present in the dilated left atrium but is not pictured here.
cooperation of physician, patient, and laboratory renders this program superior in the protective sense in certain patients to one in which reliance is placed on efforts to establish and maintain sinus rhythm by use of quinidine. Such an anticoagulant program is obviously justified in the patient who has atrial fibrillation and has recently experienced systemic embolization. Its use must be considered carefully for younger patients with persistent atrial fibrillation when no established contraindications to such therapy exist. In this latter group, final decisions will rest on such
Cardiac Arrhythmia and Cardiac Death
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individual considerations as the availability of proper laboratory facilities and the intelligence and cooperativeness of the patient. SUMMARY An increased awareness of the role of certain cardiac arrhythmias in the development of major and sometimes lethal complications of cardiac disease is an essential prelude to more determined, effort to improve rnethods of treatment which may avert these disasters. Ventricular arrest, ventricular tachycardia, and ventricular fibrillation are the most sinister among the cardiac arrhythmias and on them attention has been centered in this discussion. An attempt has been made to identify the nature of current therapeutic measures and the dilemmas encountered in application of such measures in the treatment of these arrhythmias. Case histories have been presented illustrating the benignancy even of complete heart block and ventricular tachycardia in certain patients having no other evidences of heart disease. Atrial fibrillation unattended by other evidences of heart disease becomes a hazardous disturbance of the cardiac rhythm primarily when a rapid ventricular rate is inadequately controlled over a long period, or when mural thrombi develop in the fibrillating atria and embolization ensues. The role of digitalis, quinidine, and anticoagulant therapy in treatment of these complications is considered. REFERENCES 1. Achor, R. W. P., Futch, W. D., Burchell, H. B. and Edwards, J. E.: The Fate of
Patients Surviving Acute Myocardial Infarction: A Study of Clinical and Necropsy Data in Two Hundred Fifty Cases. Arch. Int. Med. 98: 162-174 (Aug.) 1956. 2. Bellet, S.: The rrreatment of Stokes-Adams Seizures. Mod. Concepts Cardiovas. Dis. 26: 393-397 (June) 1957. 3. Zoll, P. M., Linenthal, A. J., Gibson, W., Paul, M. H. and Norman, L. R.: Termination of Ventricular Fibrillation in Man by Externally Applied Electric Countershock. New England J. Med. 254: 727-732 (April 19) 1956. 4. Zoll, P. M., Linenthal, A. J., Norman, L. R., Paul, M. H. and Gibson, W.: Treatment of Unexpected Cardiac Arrest by Electric Stimulation of the Heart. New England J. Med. 254: 541-546 (March 22) 1956.