- Email: [email protected]
Spontaneous coronary artery dissection associated with cocaine use: A case report and brief review
Cardiovascular Pathology 10 (2001) 141 – 145
Spontaneous coronary artery dissection associated with cocaine use: A case report and brief review Jon R. Steinhauer, James B. Caulfield* Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, 523 Kracke Building, Birmingham, AL 35233-6823, USA Received 13 February 2001; received in revised form 23 April 2001; accepted 27 April 2001
Abstract Isolated, spontaneous dissection of the coronary arteries in the absence of trauma is an unusual but well-documented occurrence. Fewer than 50 cases have been reported in males in the English language literature, and only one case, nonfatal, was associated with cocaine use. We present the second overall and the first fatal case of cocaine-associated spontaneous coronary artery dissection and a brief review of the literature on coronary dissection and the cardiovascular effects of cocaine use. The mechanism of cocaine’s toxicity on the heart and vasculature is complex, multifactorial, and predominantly related to cocaine’s adrenergic properties. The increased arterial blood pressure from cocaine’s inotropic and chronotropic effects combined with its direct vasoconstrictive effect leads to increased shear forces on the coronary endothelium. This elevated stress may be responsible for the formation of an intimal tear and the subsequent dissection of the coronary artery. If the dissected portion of the arterial wall is displaced enough to significantly occlude the true lumen, infarction can result. In light of this possibility, coronary artery dissection must be considered in young patients presenting with symptoms of cardiac ischemia and a history of cocaine use. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Spontaneous coronary artery dissection; Cocaine use
1. Introduction
2. Case report
Spontaneous, nontraumatic dissection of the coronary arteries is a rare occurrence first described by Pretty in 1931 [1]. In a 1999 review, Elming and Kober [2] identified 142 cases of spontaneous coronary artery dissection, only 39 of which occurred in men. Including our own case, we identified nine additional incidences of spontaneous coronary dissection in men [2 – 12] for a total of 48. Only one reported case of isolated coronary artery dissection has been associated with cocaine use [9]. That patient survived following bypass surgery. Presented below is what we believe to be the first fatal case of cocaine-associated coronary artery dissection and the first case of cocaine-associated left anterior descending artery dissection.
A 23-year-old male with a history of intravenous drug abuse and hepatitis C was found unconscious on the ground near a motorcycle. There were no external signs of trauma and no witnesses. He was transported to an outlying medical center where he was hypoxic and hypotensive, requiring pressors and mechanical ventilation. A urine drug screen was positive for cocaine metabolites, benzodiazepines, and opiates. Because of concern for intracranial hemorrhage, he was transferred to the University of Alabama Hospital. Upon arrival, his systolic blood pressure was 70 –80 mmHg, and he was tachycardic with an SpO2 of 70– 80% on full ventilatory support. A CT scan of the head showed no evidence of hemorrhage. A CT scan of the chest showed bilateral infiltrates and no evidence of cardiac or pulmonary contusion. An electrocardiogram showed marked ST elevation with low voltage in leads V3 – V6, and a large myocardial infarction was suspected. On the day of admission, cardiac troponin I was greater than 500 ng/ml, and the MB fraction of creatine kinase was 1092 ng/ml with a relative index of 8.9%. An echocardiogram indicated severe hypo-
* Corresponding author. Tel.: +1-205-934-4555; fax: +1-205-9757094. E-mail address: [email protected] (J.B. Caulfield).
1054-8807/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII: S 1 0 5 4 - 8 8 0 7 ( 0 1 ) 0 0 0 7 4 - 6
142
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
Fig. 1. Proximal left anterior descending coronary artery completely occluded by dissecting aneurysm (43 ).
kinesis with a left ventricular ejection fraction of 10% and global dysfunction. His ejection fractions deteriorated to less than 5%, bilaterally, during his hospital course. Subsequently, he became septic, developed multiorgan system failure, and expired on the seventh hospital day. An unlimited postmortem examination was performed using an infectious disease protocol, and principal findings related to the cause of death included dissection of the left anterior descending artery with thrombosis of the false lumen and complete occlusion of the true lumen (Fig. 1). An intimal tear was identified (Fig. 2). The right coronary artery was completely occluded by a thrombus, but it was not dissected, and no other vascular abnormalities were identified. Nearly transmural, circumferential myocardial necrosis of the left ventricle was also evident (Fig. 3). Bands of pale yellow myocardium surrounded by a deep red hyperemic zone contain areas of fibroblastic proliferation representing necrosis of 5 –7 days in age. Adjacent
Fig. 2. Intimal tear identified in left anterior descending artery (30 ).
Fig. 3. Ventricular myocardium with circumferential myocardial necrosis. Left ventricle averages 1.0 cm in thickness. Bands of deep red to pale yellow myocardium represent necrosis ranging from 5 to 7 days in age.
hyperemic, deep red colored zones represent more acute necrosis exhibiting extensive contraction band necrosis on microscopic examination (Fig. 4). Additional findings included deep venous thromboses in the internal iliac veins and the jugular veins and thromboemboli occluding many of the small branch pulmonary arteries. Multiple pulmonary infarctions and diffuse alveolar damage were also identified. Pertinent negative findings were the absence of coronary or aortic atherosclerosis or cystic medial necrosis, the absence of coronary adventitial inflammation, and the absence of myocardial hypertrophy and peripheral vascular disease. No evidence of traumatic injury was identified.
3. Discussion Coronary artery dissection is a well-documented, traumatic complication of coronary catheterization up to 0.3% of the time [13] and is also a known sequela of blunt chest
Fig. 4. Contraction band necrosis in left ventricular wall (300 ).
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
trauma [14,15]. The pathophysiology of spontaneous coronary dissection, however, remains unclear, and the mechanism probably varies between subsets of patients. About three-quarters of all reported cases of spontaneous coronary dissection have occurred in women, and nearly one third of those were pregnant or peripartum [2]. This strong female predominance and association with pregnancy may be due to vascular changes secondary to increased estrogen production and hemodynamic changes associated with both gestation and delivery. Other cases have been reported in association with eosinophilic [16 – 18], lymphocytic, or histiocytic vasculitides [19 – 21], and may have been related to vascular damage from inflammatory substances, though some propose the inflammation to be reactive in nature rather than causative [21]. At least one case has been associated with cystic medial necrosis [18,21 – 23]. Including our own case, we reviewed 48 cases of spontaneous, nontraumatic coronary artery dissection in men [2 – 12]. Out of those, 16 (33%) were under the age of 40 years. Ten (63%) of the patients under 40 experienced dissection in the left coronary circulation, and none had coronary artery disease or hypertension. One young patient suffered from Marfan’s syndrome [20]. In the over-40 age group, dissection of the right coronary artery was most common (66%), and coronary artery atherosclerosis or hypertension was present in up to two-thirds of cases [2]. Sudden death was relatively less common (7% vs. 20%) in the older population, however [2]. Prior to our case, cocaine-associated spontaneous coronary dissection has been reported only once previously in a 27-year-old male with normal coronary arteries [9]. Dissection occurred in the right coronary circulation, and he suffered a myocardial infarction, but survived following emergent bypass surgery. Adverse cardiovascular effects of cocaine are well recognized and extensively studied, but not completely understood. Chest pain, myocardial ischemia and necrosis, and aortic dissection are all well-recognized consequences of acute cocaine intoxication, even in individuals without predisposing risk factors. Mittleman et al. [24] reported a 23.7fold relative risk of myocardial infarction in the first hour following cocaine use. The mortality from such infarctions, however, has been reported as low as 0% by Hollander et al. [25] in 130 patients. Dissection of the thoracic aorta, while also rare, has been reported several times in the last two decades in relation to cocaine use and has been associated with a high rate of sudden death [26 –29]. It has been asserted that elevated blood pressure increases shear stress on the aortic intima, leading to separation from the media. Data do not conclusively support aortic vasoconstriction as a significant effect of cocaine use [30]. The mechanisms by which cocaine exerts its toxicity on the myocardium and the coronary vasculature are multifold, and it is most likely that a combination of direct and indirect effects are responsible for coronary artery dissection, as well as other cardiac complications of cocaine intoxication.
143
Cocaine’s acute effects on the cardiovascular system have been shown to include positive and negative inotropism, coronary vasoconstriction, rhythm and conduction abnormalities, and hypertension and tachycardia in conscious subjects [31 – 36]. The combination of these effects increases myocardial oxygen demand and reduces coronary blood flow, most likely contributing to the myocardial ischemia and necrosis that has been observed following acute cocaine use. It is a combination of the same effects that probably contributes to dissection of the aorta and the coronary arteries, and there are multiple toxic mechanisms believed responsible for these effects. Cocaine’s sodium channel blocking properties are responsible for a local anesthetic effect that is clinically useful when topically applied. Systemically, the same mechanism has been shown to be responsible for depression of left ventricular contractility and cardiac arrhythmias [34]. While this effect may contribute to myocardial ischemia and necrosis, it does not appear to contribute to the forces believed responsible for coronary artery dissection. Secondly, cocaine induces increased catecholamine release in the central and peripheral [37] nervous system and impaired presynaptic reuptake of dopamine and norepinephrine [38]. The result of this is markedly increased concentrations of catecholamines at the synapse, leading to increased a- and b-adrenergic stimulation, raising the heart rate, blood pressure, and contractility in conscious subjects and causing coronary vasospasm [36]. The elevated arterial blood pressure in combination with vasoconstriction may induce sharp increases in the shear stress on the arterial wall, leading to atherosclerotic plaque rupture in those with coronary disease and an increased risk of dissection even in those with normal coronary arteries. Additionally, this adrenergism is believed to compliment a direct mechanism that increases calcium ion influx into the myocyte, increasing contractility, and according to some, leading to contraction band necrosis and further impairment of left ventricular function [39]. Animal studies have also shown cocaine to cause calcium ion influx into vascular smooth muscle, possibly leading to vasoconstriction [40,41]. Many cases of cocaine-associated myocardial necrosis and ischemia have been reported in young, normotensive men with normal coronary arteries [24,25,36,42], suggesting acute coronary vasospasm coupled with increased oxygen demand may be responsible. While the association between arterial dissection and cocaine use is extremely rare and has not been well studied, it has been suggested that severe vasospasm secondary to cocaine’s a-adrenergic effects leads to separation of the intima from the media or the media from the adventitia. Angiographic experiments have demonstrated reduced coronary caliber in response to cocaine administration [43 –45], and experiments on isolated animal arteries have also documented vasoconstriction in response to acute cocaine exposure [46]. Conflicting results have been reported [30,47 – 49], however, and it is likely that cocaine’s effects on the vasculature are a complex
144
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
interaction of factors that have yet to be precisely defined. Furthermore, what predisposes some individuals to coronary dissection and why it has not been reported in animal studies has yet to be addressed in the literature. It also seems peculiar that coronary artery dissection has not been more frequently associated with cocaine use in populations seemingly at higher risk for dissection, such as pregnant women or those with Marfan’s syndrome or coronary arteritis. The rarity of coronary dissection and ethical issues surrounding cocaine use in human subjects may preclude practical investigation of these subjects.
4. Conclusion The realization that cocaine use can be associated with dissection of the coronary arteries is important. In the case presented, the extent of myocardial damage at the time of presentation was already extensive, and more intensive therapy would not likely have changed the outcome. In practice, however, it is reasonable to assume that acute coronary dissection can present early, at a stage at when therapeutic intervention can be beneficial and life saving. Dissection of the coronary arteries has been successfully treated with angioplasty [50], stenting [51], and with coronary artery bypass surgery [52]. Thrombolysis, however, is thought to have aggravated dissections in some patients [2]. Because of the high rate of survival in effectively treated patients, coronary dissection should be suspected in individuals presenting with coronary symptoms and a history of recent cocaine use.
References [1] Pretty HC. Dissecting aneurysm of coronary artery in a woman aged 42: rupture. Br Med J 1931;1:667. [2] Elming H, Kober L. Spontaneous coronary artery dissection. Scand Cardiovasc J 1999;33:175 – 9. [3] Ichiba N, Shimada K, Hirose M, et al. Plaque rupture causing spontaneous coronary artery dissection in a patient with acute myocardial infarction. Circulation 2000;101:1754 – 5. [4] Vara Manso J, Barriales Alavarez V, Moris de la Tassa C. Spontaneous coronary artery dissection. Int J Cardiol 1998;67:263 – 4. [5] Vale PR, Baron DW. Coronary artery stenting for spontaneous coronary artery dissection: a case report and review of the literature. Catheter Cardiovasc Diagn 1998;45:780 – 6. [6] Koga T, Sakamoto A, Nakamura Y, et al. Circumferential spontaneous coronary artery dissection in an elderly man: a case report. Angiology 1998;49:83 – 6. [7] Singh RS, Pannu HS, Agarwal R, Prasad VS, Cherian KM. Spontaneous double vessel coronary artery dissection. A case report and surgical management. Scand Cardiovasc J 1997;31:181 – 3. [8] Cohen DE, Strimike CL. A case of multiple spontaneous coronary artery dissections. Catheter Cardiovasc Interventions. 2000; 49:318 – 20. [9] Jaffe BD, Broderick TM, Leier CV. Cocaine-induced coronary artery dissection. N Engl J Med 1994;330(7):510 – 1. [10] DeJunco JE, Hamby RI, Vega M. Spontaneous dissection of the right coronary artery. NY State J Med 1985;85:485.
[11] Palank EA, Dawson JT, Cowen GD, Tysinger JR. Primary dissecting aneurysm of the right coronary artery. Chest 1977;72:774 – 6. [12] Forker AD, Rosenlof RC, Weaver WF, Carveth SW, Reese HE. Primary dissecting aneurysm of the right coronary artery with survival. Chest 1973;64:656 – 8. [13] Cripps TR, Morgan JM, Rickards AF. Outcome of extensive coronary artery dissection during coronary angioplasty. Br Heart J 1991;66: 3 – 6. [14] Baker PB, Keyhani-Rofagha S, Graham RL, Sharma HM. Dissecting hematoma (aneurysm) of coronary arteries. Am J Med 1986;80: 317 – 9. [15] Greenberg J, Salinger M, Weschler F, Edelman B, Williams R. Circumflex coronary artery dissection following waterskiing. Chest 1998;113:138 – 40. [16] Robinowitz M, Virmani R, McAllister H. Spontaneous coronary artery dissection and eosinophilic inflammation: a cause and effect relationship. Am J Med 1982;72:923 – 8. [17] Koller PT, Cliffe CM, Ridley DJ. Immunosuppressive therapy for peripartum-type spontaneous coronary artery dissection: case report and review. Clin Cardiol 1998;21:40 – 6. [18] Basso C, Morgagni GL, Thiene G. Spontaneous coronary artery dissection: a neglected cause of acute myocardial ischaemia and sudden death. Heart 1996;75:451 – 4. [19] Chu KH, Menapace FJ, Blankenship JC, Hausch R, Harrington T. Polyarteritis nodosa presenting as acute myocardial infarction with coronary dissection. Catheter Cardiovasc Diagn 1998;44: 320 – 4. [20] Bateman AC, Gallagher PJ, Vincenti AC. Sudden death from coronary artery dissection. J Clin Pathol 1995;48:781 – 4. [21] Dowling GP, Buja LM. Spontaneous coronary artery dissection occurs with and without periadventitial inflammation. Arch Pathol Lab Med 1987;111:470 – 2. [22] Kaufman G, Engelbrecht JW. Haemorrhagic intramedial dissection of coronary artery with cystic medial necrosis. Am J Med. 1969; 24:409 – 13. [23] Conraads VM, Vorlat A, Colpaert CG, et al. Spontaneous dissection of three coronary arteries subsequent to cystic medial necrosis. Chest 1999;116:1473 – 5. [24] Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation 1999;99:2737 – 41. [25] Hollander JE, Hoffman RS, Burstein JL, Shih RD, Thode HC. Cocaine-associated myocardial infarction: mortality and complications. Arch Intern Med 1995;155:1081 – 6. [26] Perron AD, Gibbs M. Thoracic aortic dissection secondary to crack cocaine ingestion. Am J Emerg Med 1997;15:507 – 9. [27] Cohle SD, Lie JT. Dissection of the aorta and coronary arteries associated with acute cocaine intoxication. Arch Pathol Lab Med 1992; 116:1239 – 41. [28] Gadaleta D, Hall MH, Nelson RL. Cocaine-induced acute aortic dissection. Chest 1989;96:1203 – 6. [29] Barth CW, Bray M, Roberts WC. Rupture of the ascending aorta during cocaine intoxication. Am J Cardiol 1986;57:496. [30] Eisenberg MJ, Yakel DL, Mendelson J, Redberg RF, Jones RT, Foster E. Immediate effects of intravenous cocaine on the thoracic aorta and coronary arteries. Chest 1996;110:147 – 54. [31] Morcos NC, Fairhust A, Henry WL. Direct myocardial effects of cocaine. Cardiovasc Res 1993;27:269 – 73. [32] Vitullo JC, Karam R, Mekhail N, Wicker P, Engelmann GL, Khairallah PA. Cocaine-induced small vessel spasm in isolated rat hearts. Am J Pathol 1989;135:85 – 91. [33] Shannon RP, Mathier MA, Shen YT. Coronary vascular response to short term cocaine administration on conscious baboons compaired with dogs. J Am Coll Cardiol 2000;35:1347 – 54. [34] Fraker TD, Temesy-Armos PN, Brewster PS, Wilkerson RD. Mechanism of cocaine-induced myocardial depression in dogs. Circulation 1990;81:1012 – 6.
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145 [35] Hayes SN, Moyer TP, Morley D, Bove AA. Intravenous cocaine causes epicardial coronary vasoconstriction in the intact dog. Am Heart J 1991;121:1639 – 48. [36] Lange RA, Cigarro RG, Yancy CW, et al. Cocaine-induced coronary artery vasoconstriction. N Engl J Med 1989;321:1557 – 62. [37] Billman GE. Mechanisms responsible for the cardiotoxic effects of cocaine. FASEB J 1990;4:2469 – 75. [38] Langer SZ. Presynaptic regulation of release of catecholamines. Pharmacol Rev 1981;32:337 – 62. [39] Pitts WR, Vongpatanasin W, Cigarroa JE, Hillis LD, Lange RA. Effects of intracoronary infusion of cocaine on left ventricular systolic and diastolic function in humans. Circulation 1998;97:1270 – 3. [40] Zhang A, Cheng TP, Altura BT, Altura BM. Acute cocaine results in rapid rises in intracellular free calcium concentration in canine cerebral vascular smooth muscle cells: possible relation to etiology of stroke. Neurosci Lett 1996;215:57 – 9. [41] He GQ, Zhang A, Altura BT, Altura BM. Cocaine-induced cerebrospasm and its possible mechanism of action. J Pharmacol Exp Ther 1994;268:1532 – 9. [42] Moliterno DJ, Williard JE, Lange RA, et al. Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both. N Engl J Med 1994;330:454 – 9. [43] Ascher EK, Stauffer JCE, Gaasch WH. Coronary artery spasm, cardiac arrest, transient electrocardiographic Q waves and stunned myocardium in cocaine-associated acute myocardial infarction. Am J Cardiol 1988;61:939 – 41.
145
[44] Mathias DW. Cocaine-associated ischemia: review of clinical and angiographic findings. Am J Med 1986;81:675 – 8. [45] Minor RL, Scott BD, Brown DD, Winniord MD. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med 1991;115:797 – 806. [46] Vitullo JC, Karam R, Mekhai N, Wicker P, Engelmann GL, Khairallah PA. Cocaine-induced small vessel spasm in isolated rat hearts. Am J Pathol 1989;135:85 – 91. [47] Zimring HJ, Fitzgerald RL, Engler RL, Ito BR. Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function. Circulation 1994;89:1819 – 28. [48] Gillis RA, Hernandez YM, Erzouki HK, et al. Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug. Drug Alcohol Depend 1995;37:217 – 30. [49] Daniel WC, Lange RA, Landau C, Willard JE, Hillis LD. Effects of the intracoronary infusion of cocaine on coronary artery dimensions and bloodflow in humans. Am J Cardiol 1996;98:288 – 91. [50] Gonzalez JL, Hill JA, Conti RC. Spontaneous coronary artery dissection treated with percutaneous transluminal angioplasty. Am J Cardiol 1989;63:385 – 6. [51] Klutstein MW, Tzivoni D, Bitran D, Mendzelevski B, Ilan M, Almagor Y. Treatment of spontaneous coronary artery dissection: report of three cases. Catheter Cardiovasc Diagn 1997;40:372 – 6. [52] Thayer J, Healy R, Maggs P. Spontaneous coronary artery dissection. Ann Thorac Surg 1987;44:97 – 107.
Spontaneous coronary artery dissection associated with cocaine use: A case report and brief review Jon R. Steinhauer, James B. Caulfield* Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, 523 Kracke Building, Birmingham, AL 35233-6823, USA Received 13 February 2001; received in revised form 23 April 2001; accepted 27 April 2001
Abstract Isolated, spontaneous dissection of the coronary arteries in the absence of trauma is an unusual but well-documented occurrence. Fewer than 50 cases have been reported in males in the English language literature, and only one case, nonfatal, was associated with cocaine use. We present the second overall and the first fatal case of cocaine-associated spontaneous coronary artery dissection and a brief review of the literature on coronary dissection and the cardiovascular effects of cocaine use. The mechanism of cocaine’s toxicity on the heart and vasculature is complex, multifactorial, and predominantly related to cocaine’s adrenergic properties. The increased arterial blood pressure from cocaine’s inotropic and chronotropic effects combined with its direct vasoconstrictive effect leads to increased shear forces on the coronary endothelium. This elevated stress may be responsible for the formation of an intimal tear and the subsequent dissection of the coronary artery. If the dissected portion of the arterial wall is displaced enough to significantly occlude the true lumen, infarction can result. In light of this possibility, coronary artery dissection must be considered in young patients presenting with symptoms of cardiac ischemia and a history of cocaine use. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Spontaneous coronary artery dissection; Cocaine use
1. Introduction
2. Case report
Spontaneous, nontraumatic dissection of the coronary arteries is a rare occurrence first described by Pretty in 1931 [1]. In a 1999 review, Elming and Kober [2] identified 142 cases of spontaneous coronary artery dissection, only 39 of which occurred in men. Including our own case, we identified nine additional incidences of spontaneous coronary dissection in men [2 – 12] for a total of 48. Only one reported case of isolated coronary artery dissection has been associated with cocaine use [9]. That patient survived following bypass surgery. Presented below is what we believe to be the first fatal case of cocaine-associated coronary artery dissection and the first case of cocaine-associated left anterior descending artery dissection.
A 23-year-old male with a history of intravenous drug abuse and hepatitis C was found unconscious on the ground near a motorcycle. There were no external signs of trauma and no witnesses. He was transported to an outlying medical center where he was hypoxic and hypotensive, requiring pressors and mechanical ventilation. A urine drug screen was positive for cocaine metabolites, benzodiazepines, and opiates. Because of concern for intracranial hemorrhage, he was transferred to the University of Alabama Hospital. Upon arrival, his systolic blood pressure was 70 –80 mmHg, and he was tachycardic with an SpO2 of 70– 80% on full ventilatory support. A CT scan of the head showed no evidence of hemorrhage. A CT scan of the chest showed bilateral infiltrates and no evidence of cardiac or pulmonary contusion. An electrocardiogram showed marked ST elevation with low voltage in leads V3 – V6, and a large myocardial infarction was suspected. On the day of admission, cardiac troponin I was greater than 500 ng/ml, and the MB fraction of creatine kinase was 1092 ng/ml with a relative index of 8.9%. An echocardiogram indicated severe hypo-
* Corresponding author. Tel.: +1-205-934-4555; fax: +1-205-9757094. E-mail address: [email protected] (J.B. Caulfield).
1054-8807/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII: S 1 0 5 4 - 8 8 0 7 ( 0 1 ) 0 0 0 7 4 - 6
142
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
Fig. 1. Proximal left anterior descending coronary artery completely occluded by dissecting aneurysm (43 ).
kinesis with a left ventricular ejection fraction of 10% and global dysfunction. His ejection fractions deteriorated to less than 5%, bilaterally, during his hospital course. Subsequently, he became septic, developed multiorgan system failure, and expired on the seventh hospital day. An unlimited postmortem examination was performed using an infectious disease protocol, and principal findings related to the cause of death included dissection of the left anterior descending artery with thrombosis of the false lumen and complete occlusion of the true lumen (Fig. 1). An intimal tear was identified (Fig. 2). The right coronary artery was completely occluded by a thrombus, but it was not dissected, and no other vascular abnormalities were identified. Nearly transmural, circumferential myocardial necrosis of the left ventricle was also evident (Fig. 3). Bands of pale yellow myocardium surrounded by a deep red hyperemic zone contain areas of fibroblastic proliferation representing necrosis of 5 –7 days in age. Adjacent
Fig. 2. Intimal tear identified in left anterior descending artery (30 ).
Fig. 3. Ventricular myocardium with circumferential myocardial necrosis. Left ventricle averages 1.0 cm in thickness. Bands of deep red to pale yellow myocardium represent necrosis ranging from 5 to 7 days in age.
hyperemic, deep red colored zones represent more acute necrosis exhibiting extensive contraction band necrosis on microscopic examination (Fig. 4). Additional findings included deep venous thromboses in the internal iliac veins and the jugular veins and thromboemboli occluding many of the small branch pulmonary arteries. Multiple pulmonary infarctions and diffuse alveolar damage were also identified. Pertinent negative findings were the absence of coronary or aortic atherosclerosis or cystic medial necrosis, the absence of coronary adventitial inflammation, and the absence of myocardial hypertrophy and peripheral vascular disease. No evidence of traumatic injury was identified.
3. Discussion Coronary artery dissection is a well-documented, traumatic complication of coronary catheterization up to 0.3% of the time [13] and is also a known sequela of blunt chest
Fig. 4. Contraction band necrosis in left ventricular wall (300 ).
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
trauma [14,15]. The pathophysiology of spontaneous coronary dissection, however, remains unclear, and the mechanism probably varies between subsets of patients. About three-quarters of all reported cases of spontaneous coronary dissection have occurred in women, and nearly one third of those were pregnant or peripartum [2]. This strong female predominance and association with pregnancy may be due to vascular changes secondary to increased estrogen production and hemodynamic changes associated with both gestation and delivery. Other cases have been reported in association with eosinophilic [16 – 18], lymphocytic, or histiocytic vasculitides [19 – 21], and may have been related to vascular damage from inflammatory substances, though some propose the inflammation to be reactive in nature rather than causative [21]. At least one case has been associated with cystic medial necrosis [18,21 – 23]. Including our own case, we reviewed 48 cases of spontaneous, nontraumatic coronary artery dissection in men [2 – 12]. Out of those, 16 (33%) were under the age of 40 years. Ten (63%) of the patients under 40 experienced dissection in the left coronary circulation, and none had coronary artery disease or hypertension. One young patient suffered from Marfan’s syndrome [20]. In the over-40 age group, dissection of the right coronary artery was most common (66%), and coronary artery atherosclerosis or hypertension was present in up to two-thirds of cases [2]. Sudden death was relatively less common (7% vs. 20%) in the older population, however [2]. Prior to our case, cocaine-associated spontaneous coronary dissection has been reported only once previously in a 27-year-old male with normal coronary arteries [9]. Dissection occurred in the right coronary circulation, and he suffered a myocardial infarction, but survived following emergent bypass surgery. Adverse cardiovascular effects of cocaine are well recognized and extensively studied, but not completely understood. Chest pain, myocardial ischemia and necrosis, and aortic dissection are all well-recognized consequences of acute cocaine intoxication, even in individuals without predisposing risk factors. Mittleman et al. [24] reported a 23.7fold relative risk of myocardial infarction in the first hour following cocaine use. The mortality from such infarctions, however, has been reported as low as 0% by Hollander et al. [25] in 130 patients. Dissection of the thoracic aorta, while also rare, has been reported several times in the last two decades in relation to cocaine use and has been associated with a high rate of sudden death [26 –29]. It has been asserted that elevated blood pressure increases shear stress on the aortic intima, leading to separation from the media. Data do not conclusively support aortic vasoconstriction as a significant effect of cocaine use [30]. The mechanisms by which cocaine exerts its toxicity on the myocardium and the coronary vasculature are multifold, and it is most likely that a combination of direct and indirect effects are responsible for coronary artery dissection, as well as other cardiac complications of cocaine intoxication.
143
Cocaine’s acute effects on the cardiovascular system have been shown to include positive and negative inotropism, coronary vasoconstriction, rhythm and conduction abnormalities, and hypertension and tachycardia in conscious subjects [31 – 36]. The combination of these effects increases myocardial oxygen demand and reduces coronary blood flow, most likely contributing to the myocardial ischemia and necrosis that has been observed following acute cocaine use. It is a combination of the same effects that probably contributes to dissection of the aorta and the coronary arteries, and there are multiple toxic mechanisms believed responsible for these effects. Cocaine’s sodium channel blocking properties are responsible for a local anesthetic effect that is clinically useful when topically applied. Systemically, the same mechanism has been shown to be responsible for depression of left ventricular contractility and cardiac arrhythmias [34]. While this effect may contribute to myocardial ischemia and necrosis, it does not appear to contribute to the forces believed responsible for coronary artery dissection. Secondly, cocaine induces increased catecholamine release in the central and peripheral [37] nervous system and impaired presynaptic reuptake of dopamine and norepinephrine [38]. The result of this is markedly increased concentrations of catecholamines at the synapse, leading to increased a- and b-adrenergic stimulation, raising the heart rate, blood pressure, and contractility in conscious subjects and causing coronary vasospasm [36]. The elevated arterial blood pressure in combination with vasoconstriction may induce sharp increases in the shear stress on the arterial wall, leading to atherosclerotic plaque rupture in those with coronary disease and an increased risk of dissection even in those with normal coronary arteries. Additionally, this adrenergism is believed to compliment a direct mechanism that increases calcium ion influx into the myocyte, increasing contractility, and according to some, leading to contraction band necrosis and further impairment of left ventricular function [39]. Animal studies have also shown cocaine to cause calcium ion influx into vascular smooth muscle, possibly leading to vasoconstriction [40,41]. Many cases of cocaine-associated myocardial necrosis and ischemia have been reported in young, normotensive men with normal coronary arteries [24,25,36,42], suggesting acute coronary vasospasm coupled with increased oxygen demand may be responsible. While the association between arterial dissection and cocaine use is extremely rare and has not been well studied, it has been suggested that severe vasospasm secondary to cocaine’s a-adrenergic effects leads to separation of the intima from the media or the media from the adventitia. Angiographic experiments have demonstrated reduced coronary caliber in response to cocaine administration [43 –45], and experiments on isolated animal arteries have also documented vasoconstriction in response to acute cocaine exposure [46]. Conflicting results have been reported [30,47 – 49], however, and it is likely that cocaine’s effects on the vasculature are a complex
144
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145
interaction of factors that have yet to be precisely defined. Furthermore, what predisposes some individuals to coronary dissection and why it has not been reported in animal studies has yet to be addressed in the literature. It also seems peculiar that coronary artery dissection has not been more frequently associated with cocaine use in populations seemingly at higher risk for dissection, such as pregnant women or those with Marfan’s syndrome or coronary arteritis. The rarity of coronary dissection and ethical issues surrounding cocaine use in human subjects may preclude practical investigation of these subjects.
4. Conclusion The realization that cocaine use can be associated with dissection of the coronary arteries is important. In the case presented, the extent of myocardial damage at the time of presentation was already extensive, and more intensive therapy would not likely have changed the outcome. In practice, however, it is reasonable to assume that acute coronary dissection can present early, at a stage at when therapeutic intervention can be beneficial and life saving. Dissection of the coronary arteries has been successfully treated with angioplasty [50], stenting [51], and with coronary artery bypass surgery [52]. Thrombolysis, however, is thought to have aggravated dissections in some patients [2]. Because of the high rate of survival in effectively treated patients, coronary dissection should be suspected in individuals presenting with coronary symptoms and a history of recent cocaine use.
References [1] Pretty HC. Dissecting aneurysm of coronary artery in a woman aged 42: rupture. Br Med J 1931;1:667. [2] Elming H, Kober L. Spontaneous coronary artery dissection. Scand Cardiovasc J 1999;33:175 – 9. [3] Ichiba N, Shimada K, Hirose M, et al. Plaque rupture causing spontaneous coronary artery dissection in a patient with acute myocardial infarction. Circulation 2000;101:1754 – 5. [4] Vara Manso J, Barriales Alavarez V, Moris de la Tassa C. Spontaneous coronary artery dissection. Int J Cardiol 1998;67:263 – 4. [5] Vale PR, Baron DW. Coronary artery stenting for spontaneous coronary artery dissection: a case report and review of the literature. Catheter Cardiovasc Diagn 1998;45:780 – 6. [6] Koga T, Sakamoto A, Nakamura Y, et al. Circumferential spontaneous coronary artery dissection in an elderly man: a case report. Angiology 1998;49:83 – 6. [7] Singh RS, Pannu HS, Agarwal R, Prasad VS, Cherian KM. Spontaneous double vessel coronary artery dissection. A case report and surgical management. Scand Cardiovasc J 1997;31:181 – 3. [8] Cohen DE, Strimike CL. A case of multiple spontaneous coronary artery dissections. Catheter Cardiovasc Interventions. 2000; 49:318 – 20. [9] Jaffe BD, Broderick TM, Leier CV. Cocaine-induced coronary artery dissection. N Engl J Med 1994;330(7):510 – 1. [10] DeJunco JE, Hamby RI, Vega M. Spontaneous dissection of the right coronary artery. NY State J Med 1985;85:485.
[11] Palank EA, Dawson JT, Cowen GD, Tysinger JR. Primary dissecting aneurysm of the right coronary artery. Chest 1977;72:774 – 6. [12] Forker AD, Rosenlof RC, Weaver WF, Carveth SW, Reese HE. Primary dissecting aneurysm of the right coronary artery with survival. Chest 1973;64:656 – 8. [13] Cripps TR, Morgan JM, Rickards AF. Outcome of extensive coronary artery dissection during coronary angioplasty. Br Heart J 1991;66: 3 – 6. [14] Baker PB, Keyhani-Rofagha S, Graham RL, Sharma HM. Dissecting hematoma (aneurysm) of coronary arteries. Am J Med 1986;80: 317 – 9. [15] Greenberg J, Salinger M, Weschler F, Edelman B, Williams R. Circumflex coronary artery dissection following waterskiing. Chest 1998;113:138 – 40. [16] Robinowitz M, Virmani R, McAllister H. Spontaneous coronary artery dissection and eosinophilic inflammation: a cause and effect relationship. Am J Med 1982;72:923 – 8. [17] Koller PT, Cliffe CM, Ridley DJ. Immunosuppressive therapy for peripartum-type spontaneous coronary artery dissection: case report and review. Clin Cardiol 1998;21:40 – 6. [18] Basso C, Morgagni GL, Thiene G. Spontaneous coronary artery dissection: a neglected cause of acute myocardial ischaemia and sudden death. Heart 1996;75:451 – 4. [19] Chu KH, Menapace FJ, Blankenship JC, Hausch R, Harrington T. Polyarteritis nodosa presenting as acute myocardial infarction with coronary dissection. Catheter Cardiovasc Diagn 1998;44: 320 – 4. [20] Bateman AC, Gallagher PJ, Vincenti AC. Sudden death from coronary artery dissection. J Clin Pathol 1995;48:781 – 4. [21] Dowling GP, Buja LM. Spontaneous coronary artery dissection occurs with and without periadventitial inflammation. Arch Pathol Lab Med 1987;111:470 – 2. [22] Kaufman G, Engelbrecht JW. Haemorrhagic intramedial dissection of coronary artery with cystic medial necrosis. Am J Med. 1969; 24:409 – 13. [23] Conraads VM, Vorlat A, Colpaert CG, et al. Spontaneous dissection of three coronary arteries subsequent to cystic medial necrosis. Chest 1999;116:1473 – 5. [24] Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation 1999;99:2737 – 41. [25] Hollander JE, Hoffman RS, Burstein JL, Shih RD, Thode HC. Cocaine-associated myocardial infarction: mortality and complications. Arch Intern Med 1995;155:1081 – 6. [26] Perron AD, Gibbs M. Thoracic aortic dissection secondary to crack cocaine ingestion. Am J Emerg Med 1997;15:507 – 9. [27] Cohle SD, Lie JT. Dissection of the aorta and coronary arteries associated with acute cocaine intoxication. Arch Pathol Lab Med 1992; 116:1239 – 41. [28] Gadaleta D, Hall MH, Nelson RL. Cocaine-induced acute aortic dissection. Chest 1989;96:1203 – 6. [29] Barth CW, Bray M, Roberts WC. Rupture of the ascending aorta during cocaine intoxication. Am J Cardiol 1986;57:496. [30] Eisenberg MJ, Yakel DL, Mendelson J, Redberg RF, Jones RT, Foster E. Immediate effects of intravenous cocaine on the thoracic aorta and coronary arteries. Chest 1996;110:147 – 54. [31] Morcos NC, Fairhust A, Henry WL. Direct myocardial effects of cocaine. Cardiovasc Res 1993;27:269 – 73. [32] Vitullo JC, Karam R, Mekhail N, Wicker P, Engelmann GL, Khairallah PA. Cocaine-induced small vessel spasm in isolated rat hearts. Am J Pathol 1989;135:85 – 91. [33] Shannon RP, Mathier MA, Shen YT. Coronary vascular response to short term cocaine administration on conscious baboons compaired with dogs. J Am Coll Cardiol 2000;35:1347 – 54. [34] Fraker TD, Temesy-Armos PN, Brewster PS, Wilkerson RD. Mechanism of cocaine-induced myocardial depression in dogs. Circulation 1990;81:1012 – 6.
J.R. Steinhauer, J.B. Caulfield / Cardiovascular Pathology 10 (2001) 141–145 [35] Hayes SN, Moyer TP, Morley D, Bove AA. Intravenous cocaine causes epicardial coronary vasoconstriction in the intact dog. Am Heart J 1991;121:1639 – 48. [36] Lange RA, Cigarro RG, Yancy CW, et al. Cocaine-induced coronary artery vasoconstriction. N Engl J Med 1989;321:1557 – 62. [37] Billman GE. Mechanisms responsible for the cardiotoxic effects of cocaine. FASEB J 1990;4:2469 – 75. [38] Langer SZ. Presynaptic regulation of release of catecholamines. Pharmacol Rev 1981;32:337 – 62. [39] Pitts WR, Vongpatanasin W, Cigarroa JE, Hillis LD, Lange RA. Effects of intracoronary infusion of cocaine on left ventricular systolic and diastolic function in humans. Circulation 1998;97:1270 – 3. [40] Zhang A, Cheng TP, Altura BT, Altura BM. Acute cocaine results in rapid rises in intracellular free calcium concentration in canine cerebral vascular smooth muscle cells: possible relation to etiology of stroke. Neurosci Lett 1996;215:57 – 9. [41] He GQ, Zhang A, Altura BT, Altura BM. Cocaine-induced cerebrospasm and its possible mechanism of action. J Pharmacol Exp Ther 1994;268:1532 – 9. [42] Moliterno DJ, Williard JE, Lange RA, et al. Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both. N Engl J Med 1994;330:454 – 9. [43] Ascher EK, Stauffer JCE, Gaasch WH. Coronary artery spasm, cardiac arrest, transient electrocardiographic Q waves and stunned myocardium in cocaine-associated acute myocardial infarction. Am J Cardiol 1988;61:939 – 41.
145
[44] Mathias DW. Cocaine-associated ischemia: review of clinical and angiographic findings. Am J Med 1986;81:675 – 8. [45] Minor RL, Scott BD, Brown DD, Winniord MD. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med 1991;115:797 – 806. [46] Vitullo JC, Karam R, Mekhai N, Wicker P, Engelmann GL, Khairallah PA. Cocaine-induced small vessel spasm in isolated rat hearts. Am J Pathol 1989;135:85 – 91. [47] Zimring HJ, Fitzgerald RL, Engler RL, Ito BR. Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function. Circulation 1994;89:1819 – 28. [48] Gillis RA, Hernandez YM, Erzouki HK, et al. Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug. Drug Alcohol Depend 1995;37:217 – 30. [49] Daniel WC, Lange RA, Landau C, Willard JE, Hillis LD. Effects of the intracoronary infusion of cocaine on coronary artery dimensions and bloodflow in humans. Am J Cardiol 1996;98:288 – 91. [50] Gonzalez JL, Hill JA, Conti RC. Spontaneous coronary artery dissection treated with percutaneous transluminal angioplasty. Am J Cardiol 1989;63:385 – 6. [51] Klutstein MW, Tzivoni D, Bitran D, Mendzelevski B, Ilan M, Almagor Y. Treatment of spontaneous coronary artery dissection: report of three cases. Catheter Cardiovasc Diagn 1997;40:372 – 6. [52] Thayer J, Healy R, Maggs P. Spontaneous coronary artery dissection. Ann Thorac Surg 1987;44:97 – 107.