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STRUCTURE — FUNCTION CORRELATIONS IN CARDIOVASCULAR AND PULMONARY DISEASES (CPC)
STRUCTURE - FUNCTION CORRELATIONS IN CARDIOVASCULAR AND PULMONARY DISEASES (CPC) Death in the Disco* Frank C. Brosius, Ill, M.D.; Brian D. Blackhoume, M.D.; and William C. Roberts, M.D., F.C.C.P.
Dr. WiUiam C. Roberts: Herein we discuss findings in a young man who died while dancing ina disco.
Dr. Brosius will present the patient.
Dr. Frank C. Brosius: A 31-year-old white man, who died July 29, 1979, had been healthy until age 25 when he had a transient episode of substernal chest pain with radiation to the left arm. Although not hospitalized, a diagnosis of "pericarditis" was made. An ECG and chest roentgenogram performed at age 26 were normal. The total serum cholesterol level, however, was 360 mg/100 ml. At age 29, transient, substernal chest pain, for which he did not seek medical care, again occurred, and occasional substernal and left arm pain with extreme exertion was noted periodically thereafter. At age 29, an ECG (employment examination) was normal, and the total serum cholesterol level was 380 mg/l00 mI. At age 31, a few weeks before death, the total serum cholesterol level was 450 mg/l00 ml and the serum biglyceride level, 128 mg/lOO mI. The low density lipoprotein (LDL) serum cholesterol level was 356 mg/l00 mI, and the very low density lipoprotein (VLDL) level was 26 mg/l00 mI. Both his brother and his father had elevated serum cholesterol levels. The patient smoked about 40 cigarettes daily. About two weeks before his sudden death, he began taking phendimetrazine to lose weight. During the afternoon of death, he ate a large picnic meal at which time he told his friends that he "did not feel well," but he expressed no specific complaints. Later that evening, he reportedly inhaled substantial amounts of butyl nitrite, which he had used often in the past year. While dancing in the disco, he collapsed and could not be resuscitated. ·From the Pathology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, and The District of Columbia Medical Examiner's OlBee, Washington, D.C. Reprint requesta: Dr. Robem, Building lOA, Room 3E30, NIH, Bethesda roms
CHEST, 78: 2, AUGUST, 1980
D1'. Roberts: Dr. Blaekboume, will you present your
findings at necropsy?
Dr. Brian D. Blackboume: At necropsy, the heart weighed 430 g. A healed transmural infarct was present in the posterior wall of left ventricle and it extended from apex to base. No foci of myocardial necrosis were present. The lumens of the four major coronary arteries were severely narrowed by atherosclerotic plaques. Each of the four major epicardial coronary arteries were divided into 5-mm long segments, and a histologic section was prepared and examined from each segment. Greater than 75 percent cross-sectional area narrowing by atherosclerotic plaque was present in 9 of 14 5-mm segments of the right coronary artery,!in 11 of 11 of the left anterior descending, and in 5 of the 5 of the left circumHex (Fig 1). In addition, numerous yellow atherosclerotic plaques were present in the ascending aorta.
D1'. Roberts: Although only 31 years of age, our
patient had fatal coronary atherosclerosis ("sudden coronary death"), familial hypercholesterolemia, namely type II hyperlipoproteinemia (hyperbetalipoproteinemi'a), for which he never received therapy, previous acute myocardial infarction, probably at age 25, as evidenced by a transmural left ventricular scar at necropsy, and unrecognized periodic angina pectoris thereafter. Among the risk factors to premature symptomatic atherosclerosis, hypercholesterolemia Is clearly the most important. Of 181 patients with familial hypercholesterolemia reported by Jensen and associates,' symptomatic coronary heart disease occurred before age 40 years in 19 percent of the men (25 percent of the women), and before age 50 years in 45 percent of the men (75 percent of the women). Of the patients with familial hypercholesterolemia reported
DEATH IN THE DISCO 321
FiGURE 1. Photomicrographs at sites of maximal narrowing of the right (R), left anterior descend ing (LAD), and left circumflex (LC) coronary arteries. All three are severely narrowed, (all are Movat stains, original magnification X 16).
by Slack,' 24 percent of the men had evidence of coronary heart disease by age 40 years and 85 percent by age 50 years. The mean age of development of symptomatic coronary heart disease in the men with hypercholesterolemia reported by Harlan and associates' was 42 years. Of the male patients with type II hyperlipoproteinemia described by Stone and associates.' nearly 10 percent had clinical evidence of coronary heart disease by age 30 years, 16 percent (1 in 6) by age 40 years, and 52 percent by age 50 years. In contrast, among the male patients of similar age but with normal serum lipoprotein patterns, the risk of a fatal or nonfatal coronary event by age 40 was less than 1 percent and by age 50, 13 pereent.s Thus, type II hyperlipoproteinemia appears to accelerate the development of symptomatic coronary heart disease among American men by more than 20 years. The amount of coronary arterial narrowing in our 31-year-old patient was extreme. Of 30 5-mm segments of major coronary artery examined histologically, 25 (83 percent) were narrowed greater than 75 percent in cross-sectional area by atherosclerotic plaques. This degree of narrowing is more than is usually observed at necropsy in victims of "sudden coronary death."5 Among 31 previously reported personally studied necropsy patients with sudden coronary death, examination of histologic sections from each 5-mm segment of the four major (right, left main, left anterior descending and left circumflex) coronary arteries (50 5-mm segments per patient) disclosed that 36 percent were narrowed 76 percent to 100 percent in cross-sectional area by atherosclerotic plaque; 34 percent, 51 percent to 75 percent; 23 percent, 26 percent to 50 percent, and only 7 percent were narrowed 25 percent or less.Ii Thus, the atherosclerotic process in victims of "sudden coronary death" is diffuse and 322 BROSIUS, BLACKBOURNE, ROBERTS
severe, but usually not as severe as in the present patient Depending on how "sudden coronary death" is defined, histologic evidence of myocardial necrosis mayor may not be present. H the definition includes death up to six hours after the sudden change in the symptomatic state, then myocardial necrosis is nearly always absent. 5 H the definition of "sudden coronary death" is up to 24 hours, a definition utilized by the World Health Organization, left ventricular myocardial necrosis may be observed or expected in the victims dying in the time period 12 to 24 hours. Our patient, who died nearly instantaneously, had no myocardial necrosis. Although never knowingly taking medication for his unrecognized cardiac disease, our patient frequently sniffed butyl nitrite. Dr. Brosius, can you enlighten us about this volatile nitrite? Dr. Brosius: Butyl nitrite has been popular in the drug culture as an aphrodisiac.S? especially among homosexual men." Amyl nitrite has been used for such purposes for several years, but its availability is legally restricted. The butyl congener, in contrast, is sold over the counter, marketed as a "room odorizer," and its stimulation is derived by sniffing the compound directly from the bottle. Recently, it has been documented that butyl nitrite inhalation can cause subclinical methemoglobinemia in normal persons, and theoretically, if the nitrite exposure were intense or inadequate time were allowed between nitrite dnhalations for methemoglobin reduction, obvious clinical manifestations of methemoglobinemia could occur," Increased intraocular pressure and severe hypotension also have been reported as side eHects of chronic nitrite use." Although potentially dangerous in the normal individual, butyl nitrite in our patient with extremely narrowed coroCHEST, 78: 2, AUGUST, 1980
nary arteries was at least potentially beneficial because of its vasodilator effects. In addition, it may have served to counteract the vasopressor effects .of both his antiobesity medication and his cigarette smoking. In contrast to the pleasurable effects described from use of the volatile nitrites in the drug abusers, the giddiness, light headedness, mild disinhibitory action, and "orgasm expander"-effects are virtually never described in patients with angina pectoris. Instead, the coronary patients complain of the odor; the pounding, pulsating headache, or the feeling of fullness behind the eyes. There are no reports of psychological dependence on the volatile nitrites by coronary patients. REFERENCES
1 Jensen J, Blankenhorn D, Kornemp V: Coronary disease in familial hypercholesterolemia. Circulation 1967; 36:77-82
CHEST, 78: 2, AUGUST, 1980
2 Slack J: Risks of ischaemic heart disease in familial hyperlipoproteinemic states. Lancet 1969; 2: 1380-1382 3 Harlan WR, Graham JB, Estes EH: Familial hypercholesterolemia: a genetic and metaboUc study. Medicine 1966; 45:77-110 4 Stone NJ, Levy HI, Fredrickson DS, Verter J: Coronary artery disease in 116 kindred with familial type n hyperlipoproteinemia. Circulation ·1974; 49 :476-488 5 Roberts WC, Jones AA: Quantitation of coronary arterial narrowing at necropsy in sudden coronary death: analysis of 31 patients and comparison with 25 control subjects. Am J Cardioll979; 44:39-45 6 Everett GM: Effects of amyl nitrite (Poppers') on sexual experience. Med Aspects Hum Sexual 1972; 6:146-151 7 Cohen S: The volatile nitrites. JAMA 1979; 241:2077-
2078
8 Goode E, Troiden RR: Amyl nitrite use among homosexual men. Am J Psychiatr 1979; 136:1067-1069 9 Home MK, Waterman MR, Simon LM, et al: Methemoglobinemia from snifBng butyl nitrite. Ann Intern Med 1979; 91 :416-418
DEATH IN THE DISCO 323
Dr. WiUiam C. Roberts: Herein we discuss findings in a young man who died while dancing ina disco.
Dr. Brosius will present the patient.
Dr. Frank C. Brosius: A 31-year-old white man, who died July 29, 1979, had been healthy until age 25 when he had a transient episode of substernal chest pain with radiation to the left arm. Although not hospitalized, a diagnosis of "pericarditis" was made. An ECG and chest roentgenogram performed at age 26 were normal. The total serum cholesterol level, however, was 360 mg/100 ml. At age 29, transient, substernal chest pain, for which he did not seek medical care, again occurred, and occasional substernal and left arm pain with extreme exertion was noted periodically thereafter. At age 29, an ECG (employment examination) was normal, and the total serum cholesterol level was 380 mg/l00 mI. At age 31, a few weeks before death, the total serum cholesterol level was 450 mg/l00 ml and the serum biglyceride level, 128 mg/lOO mI. The low density lipoprotein (LDL) serum cholesterol level was 356 mg/l00 mI, and the very low density lipoprotein (VLDL) level was 26 mg/l00 mI. Both his brother and his father had elevated serum cholesterol levels. The patient smoked about 40 cigarettes daily. About two weeks before his sudden death, he began taking phendimetrazine to lose weight. During the afternoon of death, he ate a large picnic meal at which time he told his friends that he "did not feel well," but he expressed no specific complaints. Later that evening, he reportedly inhaled substantial amounts of butyl nitrite, which he had used often in the past year. While dancing in the disco, he collapsed and could not be resuscitated. ·From the Pathology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, and The District of Columbia Medical Examiner's OlBee, Washington, D.C. Reprint requesta: Dr. Robem, Building lOA, Room 3E30, NIH, Bethesda roms
CHEST, 78: 2, AUGUST, 1980
D1'. Roberts: Dr. Blaekboume, will you present your
findings at necropsy?
Dr. Brian D. Blackboume: At necropsy, the heart weighed 430 g. A healed transmural infarct was present in the posterior wall of left ventricle and it extended from apex to base. No foci of myocardial necrosis were present. The lumens of the four major coronary arteries were severely narrowed by atherosclerotic plaques. Each of the four major epicardial coronary arteries were divided into 5-mm long segments, and a histologic section was prepared and examined from each segment. Greater than 75 percent cross-sectional area narrowing by atherosclerotic plaque was present in 9 of 14 5-mm segments of the right coronary artery,!in 11 of 11 of the left anterior descending, and in 5 of the 5 of the left circumHex (Fig 1). In addition, numerous yellow atherosclerotic plaques were present in the ascending aorta.
D1'. Roberts: Although only 31 years of age, our
patient had fatal coronary atherosclerosis ("sudden coronary death"), familial hypercholesterolemia, namely type II hyperlipoproteinemia (hyperbetalipoproteinemi'a), for which he never received therapy, previous acute myocardial infarction, probably at age 25, as evidenced by a transmural left ventricular scar at necropsy, and unrecognized periodic angina pectoris thereafter. Among the risk factors to premature symptomatic atherosclerosis, hypercholesterolemia Is clearly the most important. Of 181 patients with familial hypercholesterolemia reported by Jensen and associates,' symptomatic coronary heart disease occurred before age 40 years in 19 percent of the men (25 percent of the women), and before age 50 years in 45 percent of the men (75 percent of the women). Of the patients with familial hypercholesterolemia reported
DEATH IN THE DISCO 321
FiGURE 1. Photomicrographs at sites of maximal narrowing of the right (R), left anterior descend ing (LAD), and left circumflex (LC) coronary arteries. All three are severely narrowed, (all are Movat stains, original magnification X 16).
by Slack,' 24 percent of the men had evidence of coronary heart disease by age 40 years and 85 percent by age 50 years. The mean age of development of symptomatic coronary heart disease in the men with hypercholesterolemia reported by Harlan and associates' was 42 years. Of the male patients with type II hyperlipoproteinemia described by Stone and associates.' nearly 10 percent had clinical evidence of coronary heart disease by age 30 years, 16 percent (1 in 6) by age 40 years, and 52 percent by age 50 years. In contrast, among the male patients of similar age but with normal serum lipoprotein patterns, the risk of a fatal or nonfatal coronary event by age 40 was less than 1 percent and by age 50, 13 pereent.s Thus, type II hyperlipoproteinemia appears to accelerate the development of symptomatic coronary heart disease among American men by more than 20 years. The amount of coronary arterial narrowing in our 31-year-old patient was extreme. Of 30 5-mm segments of major coronary artery examined histologically, 25 (83 percent) were narrowed greater than 75 percent in cross-sectional area by atherosclerotic plaques. This degree of narrowing is more than is usually observed at necropsy in victims of "sudden coronary death."5 Among 31 previously reported personally studied necropsy patients with sudden coronary death, examination of histologic sections from each 5-mm segment of the four major (right, left main, left anterior descending and left circumflex) coronary arteries (50 5-mm segments per patient) disclosed that 36 percent were narrowed 76 percent to 100 percent in cross-sectional area by atherosclerotic plaque; 34 percent, 51 percent to 75 percent; 23 percent, 26 percent to 50 percent, and only 7 percent were narrowed 25 percent or less.Ii Thus, the atherosclerotic process in victims of "sudden coronary death" is diffuse and 322 BROSIUS, BLACKBOURNE, ROBERTS
severe, but usually not as severe as in the present patient Depending on how "sudden coronary death" is defined, histologic evidence of myocardial necrosis mayor may not be present. H the definition includes death up to six hours after the sudden change in the symptomatic state, then myocardial necrosis is nearly always absent. 5 H the definition of "sudden coronary death" is up to 24 hours, a definition utilized by the World Health Organization, left ventricular myocardial necrosis may be observed or expected in the victims dying in the time period 12 to 24 hours. Our patient, who died nearly instantaneously, had no myocardial necrosis. Although never knowingly taking medication for his unrecognized cardiac disease, our patient frequently sniffed butyl nitrite. Dr. Brosius, can you enlighten us about this volatile nitrite? Dr. Brosius: Butyl nitrite has been popular in the drug culture as an aphrodisiac.S? especially among homosexual men." Amyl nitrite has been used for such purposes for several years, but its availability is legally restricted. The butyl congener, in contrast, is sold over the counter, marketed as a "room odorizer," and its stimulation is derived by sniffing the compound directly from the bottle. Recently, it has been documented that butyl nitrite inhalation can cause subclinical methemoglobinemia in normal persons, and theoretically, if the nitrite exposure were intense or inadequate time were allowed between nitrite dnhalations for methemoglobin reduction, obvious clinical manifestations of methemoglobinemia could occur," Increased intraocular pressure and severe hypotension also have been reported as side eHects of chronic nitrite use." Although potentially dangerous in the normal individual, butyl nitrite in our patient with extremely narrowed coroCHEST, 78: 2, AUGUST, 1980
nary arteries was at least potentially beneficial because of its vasodilator effects. In addition, it may have served to counteract the vasopressor effects .of both his antiobesity medication and his cigarette smoking. In contrast to the pleasurable effects described from use of the volatile nitrites in the drug abusers, the giddiness, light headedness, mild disinhibitory action, and "orgasm expander"-effects are virtually never described in patients with angina pectoris. Instead, the coronary patients complain of the odor; the pounding, pulsating headache, or the feeling of fullness behind the eyes. There are no reports of psychological dependence on the volatile nitrites by coronary patients. REFERENCES
1 Jensen J, Blankenhorn D, Kornemp V: Coronary disease in familial hypercholesterolemia. Circulation 1967; 36:77-82
CHEST, 78: 2, AUGUST, 1980
2 Slack J: Risks of ischaemic heart disease in familial hyperlipoproteinemic states. Lancet 1969; 2: 1380-1382 3 Harlan WR, Graham JB, Estes EH: Familial hypercholesterolemia: a genetic and metaboUc study. Medicine 1966; 45:77-110 4 Stone NJ, Levy HI, Fredrickson DS, Verter J: Coronary artery disease in 116 kindred with familial type n hyperlipoproteinemia. Circulation ·1974; 49 :476-488 5 Roberts WC, Jones AA: Quantitation of coronary arterial narrowing at necropsy in sudden coronary death: analysis of 31 patients and comparison with 25 control subjects. Am J Cardioll979; 44:39-45 6 Everett GM: Effects of amyl nitrite (Poppers') on sexual experience. Med Aspects Hum Sexual 1972; 6:146-151 7 Cohen S: The volatile nitrites. JAMA 1979; 241:2077-
2078
8 Goode E, Troiden RR: Amyl nitrite use among homosexual men. Am J Psychiatr 1979; 136:1067-1069 9 Home MK, Waterman MR, Simon LM, et al: Methemoglobinemia from snifBng butyl nitrite. Ann Intern Med 1979; 91 :416-418
DEATH IN THE DISCO 323