runner" was sent from Athens to Sparta, 150 miles (241 km) to seekaid against the ..... arrhythmias can be produced and drugs tested on the spot. It is thought.
UNUSUAL SUDDEN DEATH* JAMES V. WARREN** COLUMBUS
During recent years much attention has been given to the frequent occurrence of sudden unexpected death. Approximately 1000 such episodes take place each day in the United States of America. Careful study of this population indicates that 10-20% are not due to the common cause-arteriosclerotic heart disease. The unusual causes of sudden death occur more frequently in the younger population group, and are caused by a variety of factors no one of which is overwhelming. Taken together they form a significant number of deaths, perhaps 50,000, almost as many as caused by automobile accidents annually in the USA. With the decline in deaths due to coronary artery disease during the past decades, unusual sudden death becomes relatively more important. Because "sudden death" is no longer necessarily a terminal event and even more importantly, because it can be prevented, the unusual causes of sudden death merit new attention. Sudden death is not new. It was recorded in the annals of ancient history. Hippocrates associated sudden death with obesity (1). Even earlier in the writings of Herodotus (2, 3), the famous Greek author, we learn that Pheidippides (or Philippedes) "by birth and practice a trained runner" was sent from Athens to Sparta, 150 miles (241 km) to seek aid against the Persian invasion. He ran the distance in one or two days and then, within the next 24 hours, after participating in the successful battle at Marathon, ran from Marathon to Athens, a distance of 26 miles (42 km), gasped the news of the victory and fell dead. Apocryphal it may be; some say two different runners were involved. Nevertheless, the event is remembered in the Olympic "Marathon" and in a poem by Robert Browning (1879) entitled "Pheidippides". Since then sudden death has struck time and again, perhaps even more evident in the young because of the low mortality rate in our young adults. "Unusual sudden death" results from a mixture of causative factors occurring in age from infancy to the elderly. They are less well defined than the coronary artery disease group and in many the causative factors are unclear. The definition of sudden death is similar to that used in the study of coronary artery disease deaths but in some instances this is not rigidly observed. The greatest interest occurs in truly sudden, perhaps * From the Department of Medicine, The Ohio State University, Columbus, Ohio. ** Address reprint requests to James V. Warren, M.D., Professor of Medicine, The Ohio
State University Medical Center, 1655 Upham Drive, Columbus, OH, 43210. 120
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instantaneous, death. There is little to suggest a logical framework for their classification. Let us look at some of the more common and interesting forms.
SUDDEN INFANT DEATH SYNDROME By far the largest killer during the first year of life is the sudden infant death syndrome commonly spoken of as "crib death" which is probably not a single disorder, but a mixture of several. In the USA it is responsible for 30,000-40,000 deaths per year. Surprisingly enough, despite a great deal of study, the basic answers are not known (4). It was first thought that accidental smothering of the baby was the primary factor, and indeed this is still debated, but it appears to be rather an unusual factor. Attention next turned to the possibility of cardiac malfunction. Electrocardiographic studies in some instances showed prolonged ST intervals and a variety of studies showed suggestive evidence. Further observations including studies on patients with so-called "near miss" episodes indicated that this was not a principal mechanism so attention turned to respiratory factors. It is true that many of the episodes of crib death have the earmarks of so-called sleep apnea and this would appear to be a factor in many cases (5, 6). Surprisingly enough there have been no major studies with combined cardiovascular and respiratory monitoring on a large group of infants upon which one might base a scientific analysis. The problem is, of course, filled with many emotional factors and there is the practical consideration of whether infants in the home should be monitored by some sort of electronic means. It is disappointing to have to say that no clear cut answer is currently available. ANOMALIES OF THE CORONARY ARTERIES A wide variety of congenital anomalies of the coronary arteries have been described. Some may produce stenosis of atresia of the coronary vessels, others coronary artery fistulae. The most interesting situations in terms of unusual sudden death are those instances of anomalous origin of the coronary arteries. In the past these anomalies have been demonstrated at autopsy, but today there is also the potential of making a diagnosis during life when coronary angiography has been carried out. A variety of situations is possible, but as an example Figure 1 illustrates that situation where the coronary artery arises from the right sinus of Valsalva. As the diagram indicates, two potential sites of narrowing result so that under the stress of exercise, for example, ischemia of heart muscle and dysrhythmia may develop causing sudden death. It is unlikely that an otherwise normal young individual would have coronary angiography except on the basis of some other findings. The occurrence of unexplained
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PULMONIC VALVE FIG. 1. Diagrammatic representation of origin of the left coronary artery (LCA) from the right sinus of Valsalva. The anterior chest wall faces the bottom of the page. The LCA subsequently passes leftward and posteriorly between the aorta and right ventricular infundibulum. Two potential sites of narrowing are indicated: 1) the very sharp turn to the left immediately beyond its origin, and 2) the passageway between the aorta and the right ventricufar infundibulum. Narrowing at both these sites might be accentuated by heavy exercise, with increased flow through both the aorta and the main pulmonary artery. (Reprinted by permission of the American Heart Association, Inc. from Levin DC, Fellows, KE, Abrams, HL. Hemodynamically significant primary anomalies of the coronary arteries. Circulation 1978; 58:25.)
syncope in a young individual should cause the physician to undertake a careful clinical evaluation, searching for the various causes of syncope which might be related to those of sudden death. Although benign vasodepressor syncope may occur frequently in the young and overshadow some more serious causes of syncope, usually the clinical story and the identifiable characteristics make it separable on a clinical basis.
SUDDEN DEATH AND CARDIOMYOPATHY Modern cardiology now recognizes multiple types of cardiomyopathy and infiltrative disease of the myocardium. In all of these as indeed is the case in most serious diseases of the heart, sudden death occasionally occurs. Far out of line, however, is the frequent occurrence of sudden death in hypertrophic cardiomyopathy. In 1982, Maron and colleagues reported the clinical profile of 78 patients with hypertrophic cardiomyopathy who died suddenly or who experienced cardiac arrest and survived (8). At the time of the cardiac catastrophe, 71% of the patients were younger than 30 years of age, 54% were without function limitation, and 61% were performing sedentary or minimal physical activity. Nineteen of the 78 patients (24%) were taking propranolol in apparently adequate dosages, indicating that this drug does not provide absolute protection against sudden death. These authors noted that no clinical variable was particularly reliable in identifying patients at risk for sudden death (8). Forty-eight of 62 patients (77%) who died suddenly had a markedly
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increased ventricular septal thickness of 20 mm or more; however, mean septal thickness was similar in patients who died suddenly to those not experiencing sudden death. An abnormal electrocardiogram was equally non-helpful in predicting sudden death. Maron's report is pessimistic about identifying candidates with hypertrophic cardiomyopathy who might die suddenly (8). On the other hand, Goodwin and associates believe that although no definite features predictive of sudden death could be determined, they are of the feeling that young age (14 years or less), a strong family history of sudden death, and progressive symptoms are all features suggesting bad prognosis (9). Medications have not been of great help in preventing sudden death in these patients.
CAFE CORONARIES Acute respiratory obstruction can cause sudden death, but usually the cause is obvious. The one situation that stands out in this area has been called the "cafe coronary". It is so called because it usually occurs in restaurants and simulates an acute coronary event. The profile is relatively consistent. The victim, usually a male having had several alcoholic drinks before dinner, encounters a tough steak and on swallowing in his enthusiasm for the occasion acutely obstructs his airway, becomes blue, cannot talk (an important sign), and rapidly dies unless the obstruction is relieved. First-aid personnel are well versed in the chest compression maneuver which pops the obstructing body out like a champagne cork (10). Similar choking may occur in young children or infants with the occluding material being something as soft as peanut butter. It is a form of the sudden death syndrome that can be aborted or reversed. ALCOHOL AND SUDDEN DEATH Large statistical studies of sudden death such as those by Kuller in Baltimore have shown an important relationship between alcohol consumption and sudden death (11). Many unexplained sudden deaths are accompanied by evidence of acute and chronic alcohol consumption. Following coronary artery disease, alcohol comes up as the second most common categorical area associated with sudden death. There are studies which relate sudden death to enlarged livers (12), cardiomyopathy and other disorders associated with chronic alcoholism. Another interesting report comes from Australia and alludes to the large number of people who have drowned on Sydney's beaches (13). Over 75% have blood alcohol levels indicating significant acute alcohol ingestion. EXERCISE AND SUDDEN DEATH The relationship of exercise to sudden death is a subject of much current discussion primarily due to the popularity of jogging and other
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exercise in both the prevention of coronary artery disease and rehabilitation of patients with that disease. The same factors may be operative in the person who does not have coronary artery disease, but they would appear to be much less common (14). A summary of the present state of knowledge would indicate that there is a beneficial affect of body conditioning through exercise. On the ohter hand, there is evidence that there is somewhat heightened risk of sudden death during the exercise. Although there remains much debate, current opinion indicates that in properly conducted exercise the benefits outweigh the risks. Programs of exercise in patients with coronary disease should be carefully prescribed based on prior careful examination of the cardiovascular system, including exercise testing and the person's clinical status. Sudden death in persons without coronary artery disease and especially in athletes is usually related to underlying diseases such as anomalies of the coronary arteries or cardiomyopathy (see above) (15). DROWNING AND SUDDEN DEATH There has been a worrisome incidence of sudden unexplained death in both amateur and professional underwater divers and swimmers. Many of the reported episodes are unexplained. Some of them clearly relate to mechanical failure of equipment and other identifiable factors. There is a question whether some events begin as syncope in a hostile environment or whether death is the direct event. A number of these events are not simple inability to cope with the aqueous environment. The role of alcohol has already been noted. One identifiable syndrome was pointed out many years ago. This occurs when swimmers in pools attempt to swim a maximum distance under water (16). Their effort involves hyperventilation just before the attempt which blows off carbon dioxide. The swimmer then swims under water to a point of exhaustion. Because the carbon dioxide level has been reduced, the normal warning signs may be absent and the individual falls back on hypoxia as the limiting mechanism. In this situation there is no warning, sudden arrhythmic death may occur, and the person may be found dead in the pool. The moral of these studies is for the individual not to attempt to swim his maximum under water while alone in the swimming pool. There should always be a person in attendance.
PSYCHIC STRESS Through the years there have been numerous reports of death following psychic stress (17, 18). In coronary artery disease sudden death may occur in individuals following emotional stress such as receiving bad news or stress from various causes. In the normal individual, the incidence of such cases must be rare indeed. There have been reports,
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especially in the trench warfare of World War I of people being "scared to death". But these reports are usually unverified and open to question. In primitive cultures, there are described episodes of "voodoo deaths" or death after being "hexed". Most of these deaths are not classifiable as true sudden death. The person dies within a day or two, but there are some descriptions that would fit definitions of sudden death. The nature of these remains a mystery. On the other hand, review of the literature on this subject leads me to believe that "being scared to death" is more a figure of speech than it is an actual event in the normal individual.
SUDDEN DEATH IN SOUTHEAST ASIANS During the last couple of years there have been reports of sudden death occurring in young male Southeast Asians who have come to the United States of America for asylum (19). Males overwhelmingly predominate. The subjects are usually young, often are having difficulties in acclimatization to their new environment and the event usually occurs at night during sleep. It is the custom of Southeast Asians to eat a heavy meal before going to bed at night and this is often the cause. Autopsy studies reported at this time do not reveal any consistent lesions, although it is indicated that more intensive studies on the conduction system are in progress. Actually this is not a new syndrome, in that sudden death of a similar sort has been reported from the Phillipines and other areas of Southeast Asia under different names such as "Bangungut" (20). In a sense this is a form of sleep apnea, but its relationship to these other disorders is not clear at this time. SUDDEN DEATH DURING WEIGHT REDUCTION PROGRAMS There is some evidence that acute weight loss like what occurs during war time may increase the incidence of sudden death (21). Sudden death occurring during severe weight loss in programs for the morbidly obese has brought this syndrome into prominence during the past decade. The so called liquid protein diets which consist of a poor grade of protein were involved in most cases. Weight reduction was usually marked. The subjects, usually young women, had no complicating cardiovascular disorders in most instances. There was only suggestive evidence of electrolyte disturbances such as a loss of potassium. It is said that the more recently used protein supplements of a higher grade of protein, more suitable metabolically, are not accompanied by sudden death. Apparently the metabolic lesson has been learned so that we should not see any further examples of this sort of disorder.
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SUDDEN DEATH IN INDUSTRY Industrial situations may produce toxic gases and chemicals which cause sudden death. Usually the exposure is obvious, but at times it may be hidden. A fascinating example occurred in the earlier part of this century in the case of workers in the dynamite industry (22). These workers were exposed to high concentrations of nitroglycerin and other nitrate compounds, both as gases and by exposure to the skin. Workers in the industry have long recognized that headache and chest pain may result from exposure to these vasodilator compounds. It was usually worse on Monday morning following a weekend away from the industry. There were a number of reports of relatively young industrial workers dying suddenly. On investigation the presumption was that these workers became acclimatized to a high nitrate concentration in the air, or by absorption through their skin. When they left their job on Friday, most of them did not have symptoms nor on Saturday, but by Sunday or Monday morning, symptoms were likely to occur and it was at this time that sudden death occurred. Older workers had learned to put a nitrate compound into their hatbands over the weekend so that they would absorb a small amount and maintain acclimatization. Recognition of this hazard in the industry has been accepted, although not thoroughly proven, and steps have been taken to limit the exposure. The current record in the industry is good. It is an example of preventive medicine being effective in one limited type of unusual sudden death. SUDDEN DEATH AND DRUG USAGE Sudden death may occur as a result of the legitimate use of drugs as well as the missuse, particularly of mood altering compounds. In the former category this has been predominantly noted in two areas: those drugs used in the treatment of arrhythmias in cardiovascular disease and in some mood altering prescription compounds, e.g., the phenothiazines. The former is more apt to occur in patients with coronary artery disease, but the problem is potentially present in all patients with serious arrhythmia regardless of cause. With the current great interest in the risk factors associated with sudden death in coronary disease, there has been a strenuous effort in most patients to eliminate premature ventricular systoles as a precipitating factor for lethal dysrhythmia. Therapeutic trials with drugs have been of mixed benefit, but the important issue in this concept is that the drug not be used so vigorously in an attempt to prevent sudden death so that it causes sudden death. Many cardiologists recommend the use of electrophysiologic studies in patients with alarming dysrhythmia potentials (23). In the electrophysiologic laboratory lethal arrhythmias can be produced and drugs tested on the spot. It is thought by many that this type of effort will control some of the drug produced
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lethal events. There are practical problems about the availability of complex electrophysiologic studies, but at least the potential for more intelligently selecting and prescribing of hazardous drugs is at our disposal. This is another means of preventing sudden death. ET CETERA The examples of unusual sudden death mentioned briefly here are but a few in a long list of reported causes. Many of these other forms are listed in Table 1, but even this list is far from complete. In many, a faulty impulse generating or conducting system in the heart may be the critical factor in precipitating the lethal event. Extensive studies of these factors have been reported in the pioneering work of James and his associates (24, 25). It is an important concept that demands thorough and skillful investigation in any unexplained sudden death. A PHILOSOPHICAL POSTSCRIPT On reviewing the vast literature pertaining to unusual sudden death, one realizes the ubiquity of some of the important precipitating events. Even though most of us do not have anomalies of the coronary arteries or cardiomyopathy, we all have emotions, often severe, or bursts of severe exertion, or extrasystoles at one time or another. Why don't we all fall victim? Why doesn't our engine cough even once? Actually, short pauses with syncope might be expected to be much more frequent in the physically normal person. With the fantastically delicate adjustments needed to give our brain enough oxygen day in and day out, running, emotions and doing our thing, it is, I believe, quite remarkable that we can live decade after decade in blissful ignorance of all of the dire things that might happen. SUMMARY In contrast to usual sudden death seen in the course of coronary artery disease, individuals dying suddenly from other causes form a complex array of situations. In some the causes are readily identifiable. No simple pattern is available to identify the potential candidate, but on review of the many causes some moves by the physician may be helpful. For example, a more complete physical evaluation of young individuals participating in competitive athletics is in order. This is particularly true if the athlete reports an episode of unexplained syncope. This may well be the warning of a propensity towards sudden death under physical and emotional stress. Knowledge of the specific problems in underwater swimming and diving, in high altitude exposure and in various circumstances such as certain weight reduction diets and industrial exposures
TABLE 1 Unusual Sudden Death UNUSUAL SUDDEN DEATH IN HEART DISEASE
A. Anomalies of the Coronary Arteries Coronary Artery Fistulae Origin of the Left Coronary Artery from the Pulmonary Artery Congenital Coronary Stenosis or Atresia Origin of the Left Artery from the Right Sinus of Valsalva B. Sudden Death in Cardiomyopathy Hypertrophic Cardiomyopathy Dilated Congestive Cardiomyopathy Restrictive-Obliterative Cardiomyopathy Amyloid Heart Disease C. Myocarditis D. Valve Disease Mitral Valve Prolapse Sudden Death in Other Valve Diseases E. Sudden Death and Congenital Heart Disease F. Acute Pericardial Tamponade G. Other Rare Causes of Sudden Death Congenital Deafness Associated with Electrocardiographic Abnormalities and Sudden Death UNUSUAL SUDDEN DEATH AND LUNG DISEASE
A. Sudden Death in Primary Pulmonary Hypertension B. Sudden Death in Respiratory Disease Cafe Coronaries C. Sudden Death and Pulmonary Embolism UNUSUAL SUDDEN DEATH AND BRAIN DYSFUNCTION
A. Sudden Death and CNS Disease B. Sudden Death in the Pickwickian Syndrome C. Emotions and Sudden Death UNUSUAL SUDDEN DEATH AND LIVER DISEASE
A. Fatty Liver and Sudden Death B. Sudden Death and Viral Hepatitis UNUSUAL SUDDEN DEATH IN METABOLIC AND CHEMICAL DISORDERS
A. Alcohol and Sudden Death B. Sudden Death and Drugs Anti-Arrhythmic Drugs C. Obesity UNUSUAL SUDDEN DEATH IN ENVIRONMENTAL SITUATIONS
A. Exercise and Sudden Death B. Sudden Death and Drowning C. Sleep Apnea and Sudden Death INFANT AND CHILDREN SUDDEN DEATH
A. Sudden Infant Death Syndrome B. Sudden Unexpected Death in Children MISCELLANEOUS ASSOCIATIONS
A. B. C. D. E. F. G. H. I.
Sudden Death and Medical Procedures Chronobiology and Sudden Death Familial Aspects of Unexpected Sudden Death Sudden Death in Doberman Pinschers and Other Animals Sudden Death and Electrical Shock Sudden Death in Southeastern Asians in USA Insect Bites and Sudden Death Anaphylaxis Unusual Sudden Death in Industry
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may lead to control of some types of unusual sudden death. Clearly, more studies are needed to give answers in so called crib death. As the incidence of usual sudden death falls, these unusual forms of sudden death will represent a more important fraction of sudden death in general. REFERENCES 1. Adams F. The Genuine Works of Hippocrates. Baltimore: The Williams & Wilkins Co.; 1939. 2. Herodotus. History of the Greek and Persian War, Transl Rawlinson G. New York: Washington Square Press, Inc.; 1963: 6: 105. 3. Young D. Sudden death in the athlete. Montefiore Med 1979; 4: 69. 4. James TN. Sudden death in babies. Circulation 1976; 53: 1. 5. Avery ME, Frantz ID. To breathe or not to breathe. What have we learned about apneic spells and sudden infant death? N Engl J Med 1983; 309: 107. 6. Guntheroth WG. Sudden infant death syndrome (crib death). Am Heart J 1977; 93: 784. 7. Levin DC, Fellows KE, Abrams HL. Hemodynamically significant primary anomalies of the coronary arteries. Angiographic aspects. Circulation 1978; 58: 759. 8. Maron BJ, Roberts WC, Epstein SE. Sudden death in hypertrophic cardiomyopathy: a profile of 78 patients. Circulation 1982; 65: 1388. 9. Goodwin JF, Krikler DM. Arrhythmia as a cause of sudden death in hypertrophic cardiomyopathy. Lancet 1976; ii: 937. 10. Heimlich HJ. A life-saving maneuver to prevent food-choking. JAMA 1975; 234: 398. 11. Kuller LH, Lilianfeld A, Fisher R. An epidemiological study and unexpected deaths in adults. Medicine 1967; 48: 341. 12. Randall B. Fatty liver and sudden death. Human Path 1980; 11: 147. 13. Plueckhahn VD. Death by drowning? Geelong 1959 to 1974. Med J Aust 1975; 2: 904. 14. Maron BJ, Roberts WC, McAllister HA, et al. Sudden death in young athletes. Circulation 1980; 62: 218. 15. Roberts WC, Maron BJ. Sudden death while playing professional football. Am Heart J 1981; 102: 1061. 16. Craig AB. Underwater swimming and loss of consciousness. JAMA 1961; 176: 255. 17. Cannon WB. "Voodoo" death. Am Anthrop 1942; 44: 169. 18. Engel GL. Psychologic stress, vasodepressor (vasovagal) syncope, and sudden death. Ann Intern Med 1978; 89: 403. 19. Baron RC, Thacker SB, Gorelkin L, et al. Sudden death among southeast Asian refugees: an unexplained nocturnal phenomenon. JAMA 1983; 250: 2947. 20. Aponte GE: The enigma of "Bangungut". Ann Intern Med 1960; 52: 1258. 21. Wadden TA, Stunkard AJ, Brownell KD. Very low caloric diets: their efficacy, safety and future. Ann Intern Med 1983; 99: 675. 22. Carmichael P, Leiben J. Sudden death in explosive workers. Arch Intern Health 1963; 7: 50. 23. Ruskin JN, McGovern, Garan H, et al. Antiarrhythmic drugs: a possible cause of outof-hospital cardiac arrest. N Engl J Med 1983; 309: 1302. 24. James TN, MacLean WAH. Paroxysmal ventricular arrhythmias and familial sudden death associated with neural lesions in the heart. Chest 1980; 78: 24. 25. James TN, Pearce WN, Givhan EG. Sudden death while driving. Role of sinus perinodal degeneration and cardiac neural degeneration and ganglionitis. Am J Cardiol 1980; 45: 1095.
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Horwitz (Philadelphia): A common cause of sudden death, often misdiagnosed, is pulmonary embolus. The reason for this is that many sudden deaths are assumed to be due to myocardial infarction by pathologists in the coroner's office. These pathologists are primarily interested in being assured that the death was not due to poison or violence and therefore are inclined to use the lable of coronary thrombosis or myocardial infarction unless another diagnosis manifests itself. Such a diagnosis is unlikely to become evident without a most thorough and painstaking postmortem examination. The incidence of pulmonary embolus as a cause of sudden death, then, is probably considerably higher than statistics would lead us to believe. The prophylaxis of sudden death from venous thrombosis and pulmonary embolus is probably more feasible than that from coronary artery disease provided a careful history and physical examination has been performed, including measurements of leg circumferences. Toole (Winston-Salem): We all speak from our own areas of special interest. Following up on Dr. Horwitz's observations, I would like to observe that sudden death can result from causes not detectable by usual autopsy. For example, Stewart Wolf studied the diving reflex which can cause a cardiac arrest of a temporary nature. We later conceived the idea that infants might have a less finely tuned or an over-reactive neuronegative system so that some crib deaths might be the result of this mechanism. My second observation is that unexplained deaths may be the result of the pathologist's inability to detect the pathology. For example, in an unobserved convulsion, the findings at post mortem might be falsely considered to be a cardiac rather than neurological event. Warren: The breathing reflexes are not well developed in utero because they are not needed. This may be a factor in some infants who fall victim to crib death. Brown (Arlington): Louis Hamman wrote a very interesting article years ago on sudden death and mentioned acute meningococcemia in children that just occurred suddenly and nobody picked it up. I was going to comment on Stewart Wolf's work which was mentioned. Perhaps the "pointing of the bone" in the case of the Australian Aborigine that made him drop dead suddenly, and Wolf's parallel studies with animals are pertinent here? Have you looked into that particular aspect of this? Warren: My impression is that most of the so-called voodoo deaths are not, by modern definition, sudden death. They take days or at least hours. Certainly they are not well documented, and are not described in a scientific way. It is hard to make a great deal out of them. Cournand (New York): I am wondering whether the human physiologist should look at the work done by the experimental physiologist and the electrophysiologist. Now there is something which impressed me very much, the fact that with a different test and maximum exercise, there are very often post exercise premature contractions. I just wondered if acute arrhythmia is not one of the mechanisms which cannot be recognized acutely at the crucial moments; but it might play a great role in sudden death. So, I just wondered, Doctor, do you think that the electrophysiologist possibly has the answer which, unfortunately for scientists, is only a hypothesis and one which you could never demonstrate with certainty to be correct? Warren: It is really a privilege to be asked a question by Dr. Andre Cournand who is one of the real father figures for all of us in the cardiovascular field today. Andre, there is some fascinating material which I did not have time to describe. I myself have seen a giraffe fall dead on being chased vigorously. This is an experience of animal catchers in Africa on obtaining animals for zoos. Vigorous exercise may bring very rapid heart rates and later arrhythmias. So that I would have all the up-to-date facts for this talk-I thought somebody would ask me about Swale the famous horse that died suddenly-a consultant from our veterinary school told me that the autopsy was negative. Such horses often develop heart rates of 300 beats per minute or more and often have arrhythmias-so I think what Dr. Cournand suggests has merit.