ORIGINAL ARTICLE

Sudden Cardiac Death Look Closely at the Coronaries for Spontaneous Dissection Which Can Be Missed. A Study of 9 Cases Saral Desai, MD, FRCPath,* and Mary N. Sheppard, FRCPath*†

Abstract: Spontaneous coronary artery dissection is a rare cause of death seen largely in young women, with many cases occurring in the early postpartum period. Nine cases with this condition were examined from our histopathology records comprising 6 women and 3 men with an age range of 26 to 47 years. All deaths were sudden, and only one patient complained of chest pain and she was 8 weeks postpartum. All cases showed dissection macroscopically, though 4 of the 6 cases, which were sent for a second opinion, were described as having normal coronaries by the referring pathologists. One heart seemed to have postmortem coronary artery thrombus and dissection was difficult to discern on gross examination. All cases were examined histologically and confirmed acute dissection of the coronary arteries, with more than 2 arteries affected in 2 cases. Histologic features of myocardial ischemia/infarction were noted in 4 cases so the explanation for the sudden death in the other 4 cases remains a possible fatal arrhythmia. The macroscopic changes in the heart of acute coronary artery dissection can be difficult to detect and can be easily mistaken for postmortem clot or a thrombus overlying an atheromatous plaque. All such cases with thrombus in the arteries, even the normal-looking coronary arteries, in young adults should be examined microscopically for dissection. Key Words: spontaneous coronary artery dissection, sudden cardiac death young (Am J Forensic Med Pathol 2010;31: 000 – 000)

symptoms, history of pregnancy (where applicable), drug history, and family history were accrued. Where the whole heart was sent for referral, the macroscopic finding of all the chambers, the great vessels, the valves, and the coronaries were noted. All the measurements, including valve circumference and ventricular wall thickness at the midventricular level, were taken. The coronary arteries, including the left main stem, and their branches were transsected perpendicular to their long axis at less than 2 mm intervals. Histologic sections of the atria, right ventricle, the right ventricular outflow tract, the interventricular septum, all the walls of the left ventricle, the coronary arteries, the conduction system, and the aorta were taken. The sections were stained with hematoxylin and eosin and Elastic van Geison stain. Cases of arterial dissection were identified on the basis of a fissure in the outer media of the artery filled with blood and fibrin, together with an acute or chronic inflammatory reaction in the media. The coronaries were examined for other changes namely vasculitis, atherosclerosis, myxoid medial degeneration, and abnormalities in elastic and collagen fibers. The myocardium was examined for changes of acute ischemia (contraction bands in myocytes, myocyte swelling, and early mild neutrophilic infiltrate), established infarction (dense neutrophilic infiltrate with eosinophilic anuclear swollen myocytes), healing infarction (macrophages, and vascular granulation tissue), and healed ischemia in the form of fibrous scarring.

C

oronary artery dissection is a rare but well-known cause of death, occurring largely as a consequence of instrumentation of the coronary arteries1 and rarely as a primary event, especially in postpartum young women.2 We find a large number of “normallooking” hearts in cases of sudden cardiac death in young adults.3 In a selection of these normal looking hearts sent for a second opinion, we found coronary artery dissection, which prompted us to look at our database and identify all our cases with spontaneous coronary artery dissection. This study revealed that macroscopic changes in the coronary arteries could be subtle and easily overlooked. We wish to highlight this rare cause of sudden death in young adults that can potentially be missed at autopsy.

MATERIALS AND METHODS Our CRY (Cardiac Risk in the Young) pathology database was searched for cases with coronary artery dissection. Clinical data were obtained from the referral letters and the coroner’s officer’s reports. In particular, the information on previous cardiac signs/

Manuscript received June 10, 2009; accepted January 5, 2010. From the *Department of Histopathology, Royal Brompton Hospital, London, United Kingdom; †CRY Centre for Cardiac Pathology, National Heart and Lung Institute, Imperial College, London, United Kingdom. Correspondence: Saral Desai, Royal Brompton Hospital, Sydney Street, London, UK SW3 6NP. E-mail: [email protected]. Copyright © 2010 by Lippincott Williams & Wilkins ISSN: 0195-7910/10/3103-0001 DOI: 10.1097/PAF.0b013e3181e29598

RESULTS A total of 9 cases with coronary artery dissection were identified over a period of 16 years (1992–2008). All cases of spontaneous coronary artery dissection were postmortem cases, autopsied either at our hospital (1 case) or referred (8 cases). The patients comprised 6 women and 3 men with an age range of 26 to 47 years (mean age ⫽ 36.8 years). Case 1 was a 40-year-old woman who entered hospital with chest pain and her ECG showed an anterior myocardial infarct. She arrested shortly after admission. Case 2 was a 26-year-old man who had a history of mental illness and drug abuse. He was completely asymptomatic and was found dead in bed. Case 3 was a 39-year-old man with history of fever and dyspnea. He had a history of mental illness and had self inflicted burns to skin 1 week before his sudden death. Case 4 was a 39-year-old woman who was 8 weeks postpartum. She had complained of chest pain, palpitations, and dyspnea over 4 days prior to her death. She was found dead at home while breast-feeding. Case 5 was a 38-year-old man with pain in the left arm and feeling of indigestion 4 to 6 hours prior to his sudden death in General Practice (GP) surgery. Case 6 was a 35-year-old woman with sore throat and general malaise who was sent home from work and was found dead, slumped at wheel of her parked car.

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Desai and Sheppard

TABLE 1. Comparing the Macroscopic Findings of the Referring Pathologist With Those Noted by Us Dissection Noted

Case Case Case Case Case Case Case Case Case

1 2 3 4 5 6 7 8 9

Infarction/ Fibrosis Noted

Referring Pathologist

Us

Referring Pathologist

Us

NA* Not known No No No Yes No No Yes

Yes Yes NA† Yes Yes NA† Thrombus Yes NA†

NA* No Not known No No Yes No No No

Yes No NA† Yes No NA† No No NA†

*Examined at our hospital only. † Whole heart not available for study. Us indicates authors; NA, not applicable.

FIGURE 2. Dissection of the coronary arteries mimicking a thrombus (left) and an atherosclerotic plaque (right). TABLE 2. Coronary Arteries Showing Dissection Case Case Case Case Case Case Case Case Case

1 2 3 4 5 6 7 8 9

RCA

LMS

LAD

LCA

Yes Yes Yes No No No No No No

No No No No Yes No Yes No No

No No No Yes Yes Yes Yes Yes Yes

No No No No No No Yes No No

RCA indicates right coronary artery; LMS, left main stem; LAD, left anterior descending; LCA, left circumflex artery.

FIGURE 1. Blood clot in the wall of the coronary artery, pushing the inner layers to one side.

Case 7 was a 34-year-old woman with chest pain a week prior to her death. She died suddenly with terminal seizures and vomiting while collecting her children from school. Case 8 was a 43-year-old woman who had a 40 minute episode of chest pain and collapse 2 weeks prior to her death. She had a cardiological examination, including exercise tolerance test, ECG and Chest X-ray which were declared normal on the very day of her death. She was found dead at home in her bedroom. Case 9 was 47-year-old woman who was found dead at home. She had complained of chest pain earlier in the day. None of these cases had any family history of cardiac disease. All toxicological results were negative. Six hearts were available for macroscopic examination and in 3 of the remaining cases, the gross findings noted by the referring pathologist were available. The macroscopic findings of the referring pathologists and our own are compared in Table 1, with the dissection of the coronary artery illustrated in Figure 1, showing thrombus within the lumen and the media typically pushed to one side. In 4 of the 8 referred cases, the referring pathologists did not 2 | www.amjforensicmedicine.com

comment on any pathology in the coronaries, dissection was noted in 2 cases and in the remaining 2 cases, the coronaries had not been examined with pathologist wishing us to do this. Looking at 1 LAD, the thrombus was displaced and the apposed walls of the vessel give a false impression of atheromatous plaque (Fig. 2). In one of our cases (case 6), we saw what appeared to be thrombus within the coronaries and were not sure of its significance and had to rely on microscopy for confirmatory diagnosis. The distribution of dissection within the coronary arterial system is shown in Table 2. More than one vessel was affected in 2 cases. Of the 3 men, 2 had right coronary artery dissection, while the right coronary artery was involved in only 1 of the 6 women. On histology, the media of the artery showed a split with blood and fibrin within the fissure (Fig. 3, top). The wall of the artery surrounding the dissection showed an inflammatory reaction including neutrophils, lymphocytes, macrophages, and occasional eosinophils (Fig. 3, bottom). The intensity of the infiltrate was variable with only a few cells at 1 end of the spectrum to numerous at the other, almost mimicking vasculitis. In 3 cases, the eosinophils were a major component of the inflammatory infiltrate. No features to suggest myxoid degeneration, vasculitis, or atherosclerosis were seen. The portion of the myocardium supplied by the dissected coronaries showed acute early ischemic changes in 4 cases while established fibrosis indicating previous ischemic injury was seen in © 2010 Lippincott Williams & Wilkins

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FIGURE 3. Blood dissecting through the media of the coronary artery (top) with the wall of the vessel showing inflammatory infiltrate, including eosinophils (bottom). 2 cases. Three cases did not show any ischemic damage on extensive sampling of the heart. The myocardium did not show any evidence of cardiomyopathy, myocarditis, granuloma formation, or malignancy. Sections of the cardiac valves and the conduction system did not show any abnormality.

DISCUSSION Spontaneous dissection of the coronary arteries has been described largely in young adults,4,5 especially in postpartum females.2,6 –9 The findings in our series are consistent with this as the mean age of the patients was 37.9 years, but only one of the patients was a woman who was postpartum. This condition has been described in young women on oral contraceptive pills,10,11 patients with collagen vascular disease,12–14 and in persons with history of drug abuse.15,16 This study highlights that it can also occur in young males and a history of drug abuse especially cocaine must be looked for (1 of our cases had a history of drug abuse but had negative toxicology findings). Spontaneous coronary artery dissection has also been noted in patients with disorder of soft tissues viz. ElherDanlos syndrome,17 Marfan syndrome,6,18 and Osler-Weber-Rendu disease.19 Cases with spontaneous coronary artery dissection occurring after intense exercise or exertion have been described in the literature,20 –23 but most of our cases died at rest. Two patients had © 2010 Lippincott Williams & Wilkins

Cardiac Death Case Study

mental health problems but there is no established link to coronary dissection. It is interesting that symptoms ranged from none to chest pain 2 weeks prior to death so the time course is highly variable. Clinical findings can also vary from established infarction in 1 patient to a normal ECG in the other investigated case. Some authors have described cases of dissection with associated coronary artery dysplasia.24,25 We feel that these cases might possibly represent old healed dissection. The difficulty in assessing the coronaries has been borne out by the fact that 4 hearts were referred with coronaries not being commented on and presumed normal. Sometimes, the thrombosis within the dissected fissure can be mistaken for postmortem thrombosis or the thrombus may be displaced and the apposed walls of the vessel give an impression of thrombosis overlying an atheromatous plaque. Thus, histology is essential in all such cases. Failure to examine the main stem of the left coronary artery as it lies deep within fat or the right coronary artery deep in the atrioventricular groove will miss cases of dissection. It is not uncommon to see involvement of more than 1 coronary and dissection in all the coronaries has been described.26 In all sudden young deaths under the age of 40, the heart and the coronaries should be examined in detail and histology taken. Histologically, it is necessary to distinguish coronary artery dissection from artificial tearing of the media during necropsy. When the dissection has occurred during life, the blood is mixed with fibrin and there is an inflammatory cell infiltrate, which can be variable and subtle, lining the plane of dissection within media. This vital reaction is absent in cases where the tear has occurred as a result of postmortem handling. Vasculitis will not have a plane of dissection containing thrombus within the vessel and the inflammation in dissection is confined to the plane of dissection. Other areas of the coronary circulation free of dissection will not contain inflammation. Our series illustrates that the macroscopic findings can be subtle with only thrombus being noted, and the histology provides the ultimate proof of this condition. It does not matter if the coronaries appear normal; taking histology is essential, especially in young adults. Coronary dissection does occur, and not necessarily in females only. It is a diagnosis that can be missed and is missed by pathologists. We believe it is under-diagnosed in sudden cardiac death. This study also highlights the fact that ischemic damage in the ventricles may be absent in the presence of acute coronary dissection. This is similar to the findings of acute coronary thrombosis overlying ruptured plaque in which ventricular infarction is not found and the patient has died of a lethal arrhythmia or patient surviving out of hospital cardiac arrest without coronary artery disease.27 ACKNOWLEDGMENTS The authors thank Cardiac Risk in the Young, UK, which has enabled us to carry out this work. REFERENCES 1. Dunning DW, Kahn JK, Hawkins ET, et al. Iatrogenic coronary artery dissections extending into and involving the aortic root. Catheter Cardiovasc Interv. 2000;51:387–393. 2. Satoda M, Takagi K, Uesugi M, et al. Acute myocardial infarction caused by spontaneous postpartum coronary artery dissection. Nat Clin Pract Cardiovasc Med. 2007;4:688 – 692. 3. Fabre A, Sheppard MN. Sudden adult death syndrome and other nonischaemic causes of sudden cardiac death. Heart. 2006;92:316 –320. 4. Desseigne P, Tabib A, Loire R. An unusual cause of sudden death: spontaneous dissection of coronary arteries. Apropos of 2 cases 关in French兴. Arch Mal Coeur Vaiss. 1992;85:1031–1033. 5. Kearney P, Singh H, Hutter J, et al. Spontaneous coronary artery dissection:

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Desai and Sheppard

6. 7.

8. 9.

10.

11.

12.

13.

14.

15.

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a report of three cases and review of the literature. Postgrad Med J. 1993;69:940 –945. Bateman AC, Gallagher PJ, Vincenti AC. Sudden death from coronary artery dissection. J Clin Pathol. 1995;48:781–784. Cosson S, Guyon P, Halphen C, et al. Myocardial infarction due to spontaneous coronary dissection during the postpartum period 关in French兴. Arch Mal Coeur Vaiss. 1998;91:883– 886. Coulson CC, Kuller JA, Bowes WA Jr. Myocardial infarction and coronary artery dissection in pregnancy. Am J Perinatol. 1995;12:328 –330. Mortensen UM, Nielsen-Kudsk JE, Andersen HR, et al. Spontaneous dissection of the left main coronary arteries in three women 关in Danish兴. Ugeskr Laeger. 2001;163:6919 – 6920. Muretto P. Images in pathology. Spontaneous coronary artery dissection as cause of sudden cardiac death in a young woman with oral contraceptive use. Int J Surg Pathol. 2006;14:331. Evangelou D, Letsas KP, Korantzopoulos P, et al. Spontaneous coronary artery dissection associated with oral contraceptive use: a case report and review of the literature. Int J Cardiol. 2006;112:380 –382. Sharma AK, Farb A, Maniar P, et al. Spontaneous coronary artery dissection in a patient with systemic lupus erythematosis. Hawaii Med J. 2003;62:248 – 253. Kothari D, Ruygrok P, Gentles T, et al. Spontaneous coronary artery dissection in an adolescent man with systemic lupus erythematosus. Intern Med J. 2007;37:342–343. Reed RK, Malaiapan Y, Meredith IT. Spontaneous coronary artery dissection in a female with antiphospholipid syndrome. Heart Lung Circ. 2007;16:120 – 122. Steinhauer JR, Caulfield JB. Spontaneous coronary artery dissection associated with cocaine use: a case report and brief review. Cardiovasc Pathol. 2001;10:141–145.

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16. Garcia Garcia C, Casanovas N, Recasens L, et al. Spontaneous coronary artery dissection in ergotamine abuse. Int J Cardiol. 2007;118:410 – 411. 17. Athanassiou AM, Turrentine MA. Myocardial infraction and coronary artery dissection during pregnancy associated with type IV Ehlers-Danlos syndrome. Am J Perinatol. 1996;13:181–183. 18. Angiolillo DJ, Moreno R, Macaya C. Isolated distal coronary dissection in Marfan syndrome. Ital Heart J. 2004;5:305–306. 19. Mieghem CA, Ligthart JM, Cademartiri F. Images in cardiology. Spontaneous dissection of the left main coronary artery in a patient with Osler-WeberRendu disease. Heart. 2006;92:394. 20. Kalaga RV, Malik A, Thompson PD. Exercise-related spontaneous coronary artery dissection: case report and literature review. Med Sci Sports Exerc. 2007;39:1218 –1220. 21. Marijon E, Fressonnet R, Haggui A, et al. Spontaneous coronary dissection of the left main stem after intense physical activity—regression under conservative strategy. Int J Cardiol. 2008;128:e16 – e18. 22. Tac¸oy G, Sahinarslan A, Timurkaynak T. Spontaneous multivessel coronary artery dissection in a wrestler. Anadolu Kardiyol Derg. 2007;7:193–195. 23. Justice LT, Dauterman K, Smedira NG, et al. Left main dissection and thrombosis in a young athlete. Cardiol Rev. 2005;13:260 –262. 24. Censori B, Agostinis C, Partziguian T, et al. Spontaneous dissection of carotid and coronary arteries. Neurology. 2004;63:1122–1123. 25. Ritzenthaler T, Derex L, Cakmak S, et al. Spontaneous dissections of the carotid arteries in a patient with recent coronary artery dissection. Eur Neurol. 2008;59:324 –326. 26. Harikrishnan S, Ajithkumar VK, Tharakan JM. Spontaneous coronary artery dissection of all major coronary arteries. Can J Cardiol. 2007;23:313–314. 27. Rosman HS, Goldstein S, Landis JR, et al. Clinical characteristics and survival experience of out-of-hospital cardiac arrest victims without coronary heart disease. Eur Heart J. 1988;9:17–23.

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