Forensic Aspects of Cardiovascular Pathology

C H A P T E R

20 Forensic Aspects of Cardiovascular Pathology B. Sampson, J.L. Hammers Office of Chief Medical Examiner, City of New York, NY, USA; New York University School of Medicine and Post-Graduate Medical School, New York, NY, USA

O U T L I N E Investigative Information

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General Changes

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Primary Diseases/Injuries of the Heart Trauma Congenital Endocarditis Pericarditis

775 775 779 779 780

Cardiomyopathies, Myocarditis, and Genetic Causes of SCD

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Pulmonary Disease 789 Pulmonary Thromboembolism/Deep Vein Thrombosis 790 Ancillary Studies Histology Toxicology Cultures and Other Studies Genetics

792 792 792 793 793

Sudden Death Following Surgery and Medical Procedures

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Organ and Tissue Harvesting

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Anomalies and Diseases of the Aorta and Coronary Arteries

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Cardiovascular Pathology Consultation

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Diseases of the Cardiac Valves Tumors Immune Disease

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Summary

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References

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INVESTIGATIVE INFORMATION Investigation of sudden cardiac death (SCD), like all other sudden, unexpected or unnatural death relies heavily on a thorough and comprehensive investigation of the circumstances surrounding death, including a scene investigation, interview with family and friends regarding family history and social history, collection of any medical history from a treating physician, review of the medical records. Interviews with friends and family regarding new or changed symptoms identified before death may be key to understanding the pathogenesis of death. Specifically regarding SCDs, a comprehensive report of the activities, complaints and behaviors before and during death are critical. Many causes of SCD have no structural changes at autopsy on gross examination or even upon

Cardiovascular Pathology http://dx.doi.org/10.1016/B978-0-12-420219-1.00020-3

microscopic examination. Sometimes, it is the lack of findings that is significant and identifies the cause of death suspected from the circumstances at death. The scene investigation should document the particulars of the body and the surroundings. The position of the body and any evidence of disruption of the surroundings should be noted. Any medications including dosage, number of pills prescribed and number of pills remaining, drugs and drug paraphernalia, alcohol, and tobacco present at the scene should be thoroughly recorded. Any medical paperwork should be examined for diagnosis and physician information, and family members or friends present at the scene should be questioned about the decedent's medical history and treating physicians. If death occurs in hospital, the pertinent medical records and emergency response reports should be sent

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with the body for review prior to autopsy. A summary of the pertinent events, diagnoses, laboratory testing, radiology imaging, and operative events while in hospital may be very helpful, particularly if the hospitalization course is prolonged. A thorough medical history should be gathered from all available resources, including family, friends, and treating physicians. Asking detailed family history questions, rather than a general query into cardiac death, is likely to illicit the most useful information and give the most helpful clues to identify the cause of death. The social history, including use of drugs, alcohol, and tobacco will identify substances that may play a role in death and may suggest or refute the suspicion of SCD. Certain illicit drugs and prescription medications may elevate blood pressure or incite cardiac rhythm disturbances. Obtaining a comprehensive list of illicit drug use and prescription medication use and misuse will aid in ordering appropriate toxicology testing to identify the presence of these substances in the body at the time of death, understanding the extent of histology sections necessary for establishing a diagnosis and ultimately establishing the cause of death in a timely and accurate manner [1–3].

FIGURE 20.1

Contusions and abrasions over the sternum, resulting from cardiopulmonary resuscitation. Trauma of the underlying soft tissues, sternum, and rib cage may be absent or even extensive, with secondary injuries to the pericardium and heart.

GENERAL CHANGES Many changes and disease processes may be identified at autopsy that do not play a role in death and are not related to the cause of death. Common changes include artifacts related to resuscitative efforts and postmortem changes. Knowledge of the time course of medical intervention, the types of treatment used, and the responses received from the intervention may aid in interpretation of changes identified at autopsy. Likewise, knowledge of position of the body when found as well as the state of decomposition changes, including livor mortis, rigor mortis, and algor mortis, will aid in interpretation of findings at autopsy. Cardiopulmonary resuscitation (CPR) may cause devastating injuries to the chest, including the heart [4–8] (Figures 20.1 and 20.2). Most common are small amounts of serosanguinous fluid in the pericardial space. Petechial hemorrhages may be seen over the pericardium or the epicardial surfaces of the heart as the result of small capillaries bursting from direct and indirect pressure placed on the heart during resuscitation. Contusions, or bruising, to the heart may be identified on the epicardial surface or may involve the full thickness of the myocardium (Figure 20.3). Often contusions involve the anterior aspects of the heart, but may also be seen on the posterior surfaces if resuscitation is aggressive or in patients who are coagulopathic. Histologic examination of the hemorrhagic wall may aid in determining that the hemorrhage is indeed postmortem and related to resuscitation rather than an antemortem myocardial infarct, as changes

FIGURE 20.2

Rectangular contusion on the upper chest where a disposable defibrillator pad previously overlay the skin.

related to resuscitation should lack hypereosinophilia, contraction band necrosis, and infiltration of inflammatory cells. If spontaneous circulation is regained for a short time, contraction bands and hypereosinophilia may be identified but infiltrating inflammatory cells are typically not present. Individuals who survive for hours after resuscitation may show patchy regions of myocardial necrosis, particularly around blood vessels where the reperfusion first occurs. In addition to petechial hemorrhages and contusion, direct damage to the pericardium and heart may be caused by rib or sternal fractures, repetitively displaced

PRIMARY DISEASES/INJURIES OF THE HEART

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decompositional changes in the heart are typically putrefactive changes, brought on by bacterial destruction of tissues. This process results in gross, typically uniform softening and dark discoloration of the heart and vessels. The heart loses its muscular tone as the tissues break down and may appear dilated with a thick left ventricle appearing of more normal thickness. One should be cautious when interpreting cardiac dilatation in a decomposing heart and is best served to interpret such a finding in the context of the prevailing forensic scenario. In addition to softening and discoloration, atherosclerotic plaques particularly in the coronary arteries may putrefy and be difficult to evaluate. A clinical history of atherosclerotic and/or hypertensive cardiovascular disease may aid in determining the cause of death and microscopic examination of myocardium may also be helpful, revealing myocyte hypertrophy and/or perivascular and interstitial fibrosis, suggestive of antemortem hypertension and ischemia [1–3]. FIGURE 20.3 Hemorrhagic contusion of the right atrium following cardiopulmonary resuscitation.

during the physical compressions associated with CPR. Focal and minor to diffuse and extensive lacerations of the pericardium and heart may be present based on the aggressiveness of resuscitation, use of an automated resuscitative device, state of bone density, and resultant fractures of the chest plate. Rib and sternal fractures are most commonly identified in older, osteoporotic patients or in younger patients who are osteopenic from a natural disease process such as cancer or malnutrition. Often lacerations are surrounded by only focal, small amounts of hemorrhage; however, in coagulopathic decedents, the hemorrhage may be extensive [9]. Livor mortis, also known as lividity, is the settling of blood after death in gravity-dependent portions of the body, including in the organs. It is typically not as noticeable in the heart as it is in other organs such as the lungs. When present, it may cause concern for a large region of myocardial ischemia. Identification of discoloration over a broad continuous surface of myocardium should raise suspicion for gravity-dependent lividity and the location on the heart should be correlated with the presence and pattern of lividity identified in the other organs at autopsy, as well as the investigation notes regarding the position in which the body came to rest after death. Status of the lividity, blanching, slightly blanching or nonblanching, at investigation as well as at autopsy, may also be useful. If a question remains in distinguishing lividly from myocardial ischemia, histology sectioning may aid in differentiating the two processes. In lividity, one would expect to see blood confined within the lumen of the blood vessels rather than spreading throughout the myocardium. More advanced

PRIMARY DISEASES/INJURIES OF THE HEART Trauma Penetrating injuries of the heart and cardiac vessels may result from any object that pierces the organ, including fractured ribs, sharp objects such as knives, tools such as a screwdriver or a barbecue fork, and high-velocity blunt objects such as bullets. Stab wounds resulting from any sharp object penetrating into the skin, soft tissues, and organs with the injury deeper than it is wide on the surface of the skin. Such injuries most often result in death from hemorrhage into the pericardial sac with tamponade or from exsanguination due to extensive hemorrhage into the pleural cavities and soft tissues surrounding the pericardium. These injuries may involve the myocardium, the coronary arteries, or the great vessels. The size of the injury as well as the structures injured will determine the speed at which sufficient blood is lost to cause death. Accurate measurements of injury dimension, location, and estimation of depth of penetration are often helpful in assessing the type of object causing the injury. Features of the object injuring the heart are often well preserved in the muscular heart, and often are consistent with or even more precise than measurements on the surface of the skin, which is subject to distortion from Langer's lines (Figure 20.4a and b). Injuries of the blood vessels can result in hemorrhage or introduction of air into the cardiovascular system (Figure 20.5). Gunshot wounds vary in the extent of injury, with smaller caliber bullets causing less damage to the heart than larger caliber bullets, and rifle wounds causing

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(a)

(b)

FIGURE 20.4 (a) Stab wound of the anterior right ventricle with well-preserved features of the knife apparent on the epicardial surface, with a blunt edge of the knife situated superior and a sharp edge inferior. (b) Stab wound of the anterior left ventricle that is slightly irregular on the epicardial surface with a curved edge (arrow), consistent with movement of the knife while within the heart.

FIGURE 20.5

X-ray of the chest from a decedent who stabbed himself in the neck many times to commit suicide. Note the radiolucent region within the right heart (arrow) indicating a large air embolus. Injuries to the vessels, particularly of the neck, may allow air to enter the circulatory system. The air can travel to the heart if circulation persists and can embolize in the right heart, causing death. To identify an air embolus in the heart, it is helpful to X-ray the decedent before performing an autopsy.

much more extensive injury than handguns. The damage to the heart is a result of the amount of energy the traveling bullet releases into the tissue as it passes through. The more gunpowder in a bullet, the more energy the bullet has to transfer to the tissues, and the greater the damage. A handgun typically causes a small- to medium-sized perforation in the heart while a rifle will cause pulpification of the myocardium (Figure 20.6). Shotgun wounds of the heart vary based on how close the shotgun is fired to the body. The closer the shotgun is to the body when fired, the tighter the pellets are, and the more they travel together as one object causing a large defect with a smooth to scalloped margin. The further away from the body when fired, the more spread out

FIGURE 20.6 Gunshot wound of the left atrium (arrow) with surrounding epicardial hemorrhage. Note the small size of the gunshot wound defect. This wound was caused by ammunition from a handgun.

the pellets become and the pattern of injury will be smaller, punctate defects approximating the size of the pellets [10]. Injuries of the blood vessels can occur from direct perforation or secondary damage from a bullet passing close to the vessel (Figures 20.7 and 20.8). Blunt force trauma of the heart and vessels results from direct impact or acceleration-deceleration forces [11]. Direct impact injuries may be from an object striking the chest, such as a baseball, or from the torso impacting a hard object or surface, such as steering wheel. Acceleration-deceleration injuries occur when the body, moving at a high velocity, strikes a fixed object. Resultant trauma, causing injury or even death, may be as minimal as no gross or microscopic evidence of injury, as in a commotio cordis, or as extensive as rupture of the heart or transection of the aorta [12]. Occasionally, the heart may even be expelled from the chest when gaping lacerations of the skin and chest wall are present. Such extensive

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FIGURE 20.7 Gunshot perforation of the lower thoracic aorta. Note the stellate, jagged lacerations around a larger central defect.

FIGURE 20.10

Extensive lacerations and pulpification of the heart from blunt force trauma deceleration forces and penetrating injuries from pieces of debris from an aerial impact between two small aircrafts.

FIGURE 20.8 Multiple stretch lacerations of the intimal surface of the right iliac artery following a gunshot wound which tracked very close to the external surface of the artery but did not perforate the artery. The adjacent vein was tied off at the hospital, as it was transected by the bullet.

FIGURE 20.9

Extensive laceration with transection of the apex of the heart resulting from blunt force trauma deceleration forces in the driver of a motorcycle that crashed while traveling at a high speed.

injuries are most often seen in high-speed motor vehicle and motorcycle crashes where there are extensive blunt force injuries (Figure 20.9). Additionally, small aircraft collisions may result in extensive injuries of the heart and vessels, both from impact and from fragments of penetrating debris (Figure 20.10). Contusions of the heart result from direct impact or compression of the heart and may occur on the anterior or posterior surface of the heart. Concurrent injury to the skin, soft tissues, and bones need not be present. Contusion may be present on the epicardial surface, through

the full thickness of the myocardial wall or on the endocardial surface [13]. However, endocardial hemorrhages are more commonly associated with reperfusion injury. Care should be taken to microscopically examine such lesions when related to the cause of death. Contusion may cause pain simulating angina pectoris or myocardial infarction, but may remain undetected and without symptom. Microscopic examination of the contusion reveals abundant interstitial hemorrhage with variable findings, including contraction band necrosis and damage to muscle bundles. Similar to a resolving myocardial infarct, healing of a contusion renders the wall weak from necrotic softening and prone to rupture with resultant hemopericardium and cardiac tamponade. Replacement fibrosis is the end result of a healed cardiac contusion and if large, a post-traumatic aneurysm may form [14–16]. Falls or jumps from great heights, such as off of tall buildings, often lead to extensive fractures of the ribs, sternum, and vertebral column which may displace and cause secondary injuries including hemorrhage of the soft tissues, contusion of the myocardium, and puncture lacerations of the heart and vessels. The deceleration forces may also cause primary lacerations to the pericardium, heart, and great vessels [17]. Lacerations may be small and focal or large and gaping (Figure 20.11). The vast majority of aortic lacerations and transections occur in the thoracic segment 2-3 cm past the origin of the left subclavian artery at the aortic isthmus. It is at this location where the aorta is most fixed by the ligamentum arteriosum, resulting in a focus of increased stress during deceleration. The second most common site of aortic laceration

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FIGURE 20.11 Large lacerations of the myocardium resulting from blunt force trauma deceleration forces when a construction worker fell 20 stories.

is just proximal to the innominate artery in the ascending aorta, another relative point of fixation. A partial thickness laceration of the intima or media may lead to a post-traumatic aneurysm which may remain undetected while contained by pressure from surrounding anatomic structures or continue to expand, causing pain as it presses on surrounding structures. Margins of aneurysm located at the site of the laceration may cause a coarctation and disrupt blood flow past this site [18,19]. A partial thickness laceration with maintained circulation may also result in retrograde or antegrade dissection of the aortic wall, causing occlusion of the intimal lining of the aorta or coronary artery and sudden death [20–22]. Injuries similar to those discussed in the aorta can occur in the branches of the aorta or in the peripheral arteries, with similar pathologic sequelae [23]. Injuries to peripheral veins often lead to thrombotic occlusion with infarction of dependent tissues and organs [24,25]. Nonpenetrating blunt trauma may also damage the coronary arteries and cardiac valves [26–28]. Lacerations of the intima and media may lead to local thrombosis or dissection resulting in myocardial ischemia. The left anterior descending coronary artery is most commonly involved, likely due to a location of vulnerability to blunt impact at the anterior chest. Lacerations of the cardiac valve leaflets and avulsion at points of attachment, as well as rupture of the chordae tendineae and papillary muscles, may lead to valvular insufficiency and even infective endocarditis (IE) [29–31]. The aortic valve most commonly experiences lacerations and avulsion of the leaflet attachments while the chordae tendineae and papillary muscles of the mitral valve tend to suffer damage. Both native valves and mechanical and bioprosthetic valves may suffer blunt impact damage [32]. Identifying death from commotio cordis is heavily dependent on documentation of witnessed or circumstantial blunt impact to the chest without gross or

FIGURE 20.12

Normal heart, anterior view.

FIGURE 20.13

Normal heart, posterior view.

microscopic injury of the heart identified at autopsy (Figures 20.12 and 20.13). Typically injuries to the soft tissues and bone of the chest are absent to minimal and should never be extensive enough to cause death [33]. A thorough scene investigation may make the difference between determining death due to commotio cordis and an undetermined cause of death. Details surrounding death should be thoroughly documented, particularly extensive explanation of the activities before and after collapse. Multiple witness accounts should be gathered when a decedent was engaged in a sporting activity during collapse, particularly those with hard objects such as baseballs, lacrosse balls, and hockey pucks [34,35]. Decedents involved in motor vehicle crashes where there is possible chest impact should be examined for signs of cardiac activity after death. A lack of blood at the scene in a decedent with injuries that would be expected to bleed should raise suspicion for a sudden loss of cardiac

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Congenital

FIGURE 20.14 This decedent was a nonseat belted driver involved in a head-on motor vehicle collision. External examination showed superficial abrasions of the chest and upper abdomen consistent with an impact with a steering wheel. Internal examination revealed no injuries of the chest wall, heart, lungs, and abdominal organs. Additionally, this decedent had a deep gaping laceration beneath each knee. There was a striking lack of blood at the scene and on the jeans. Histology sections revealed no pathologic changes in the organs. The toxicology evaluation revealed the decedent was intoxicated with alcohol at nearly three times the legal driving limit. Given the scene investigation and the negative findings at autopsy, the cause of death was determined to be commotio cordis.

activity and the possibility of commotio cordis. A sudden collapse during horseplay or wrestling should also raise suspicion for commotio cordis. Correlating negative autopsy findings, including histopathology and toxicology, with a blow to the chest will allow one to confidently make the diagnosis of commotio cordis (Figure 20.14). Chest impacts leading to commotio cordis typically occur to the anterior chest wall over the heart and must occur at a very specific point in the cardiac cycle to cause ventricular fibrillation and death. Pig studies have shown that chest impacts with a baseball-type object caused commotio cordis if the impact occurred during a 30 ms window on the upslope of the T-wave, just before the peak. This represents the repolarization phase of the cardiac cycle. The most common cardiac dysrhythmia experienced is ventricular fibrillation [36]. Cardiac dysrhythmias from witnessed chest impacts followed by unresponsiveness may be reversed with quick use of automated external defibrillator (AED) devices. AEDs are most effective when utilized within 3 min of collapse and readily available AEDs at sporting events has become the rule rather than the exception. While resuscitation was once believed to be futile, survival is now reported in 35% of reported cases [1–3,37,38].

With current medical advances, most cardiac congenital anomalies are identified at a very young age and are successfully treated. In those who die from the anomalies, their deaths typically do not fall under the jurisdiction of the coroner or medical examiner, as the cause of death is natural and related to their diagnosed congenital heart disease. In cases of sudden unexpected death, congenital defects are typically readily identified at autopsy. However, more subtle or rare anomalies may be identified only upon consultation to a cardiac pathologist. Occasionally, death occurs suddenly and unexpectedly after a period of time following successful repair of a known congenital defect from which long-term survival was expected. In such cases, the death typically does fall under the jurisdiction of the local coroner or medical examiner and an autopsy should be performed to determine the cause of death. It is often helpful to review operative reports and if possible, to have the surgeon present for evaluation of the heart, to better understand the procedure, and receive immediate feedback regarding the state of the repair [39,40]. Once out of the adolescent period, sudden death due to a congenital cardiac anomaly is rare, though ventricular and atrial septal defects may be identified in older adults who have managed to remain undiagnosed and compensate for the defect until the heart becomes enlarged and a cardiac dysrhythmia occurs, causing sudden death [41,42]. The threshold to consult a cardiac pathologist for gross or microscopic examination should be low, particularly in cases of complex congenital anomalies or rare genetic disease processes.

Endocarditis The four cardiac valves and endocardial surfaces of the heart should be carefully examined at each forensic examination. IE is readily apparent in most cases and should be considered particularly in cases of death among intravenous drug abusers (IVDAs), who are at increased risk for endocarditis typically infecting the tricuspid valve [43] (Figure 20.15). Sudden death in a person complaining of viral type symptoms after recent dental manipulation should also raise concern for endocarditis [44]. Endocarditis can be seen in both native valves and prosthetic valves. Histologic examination of the infected cardiac valve with special stains should be performed as well as bacterial culture to identify the responsible organism. In cases where endocarditis is grossly identified and no history is known, identification of a specific organism may lead to a likely underlying cause. Septic emboli phenomena to organs, including the kidney and brain, may be seen in some cases. Antemortem complaints may include fever, loss of appetite, flu-like symptoms, and weight loss. External signs of endocarditis may give clues to possible infection

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[46]. Prolapsed mitral valves seen at autopsy should be thoroughly inspected for infection [47]. The microscopic appearance of acute bacterial endocarditis shows no evidence of repair (fibroblasts), many polymorphonuclear leukocytes, necrosis, and bacteria. Untreated IE is generally fatal. Occasionally, patients undergoing surgical repair for IE, particularly when myocardial abscess is present may die during surgery, particularly if infection is more extensive than expected and repair of friable tissue is not possible [48]. Similar infections following pacemaker implantation can involve the pacemaker pocket or the pacemaker leads [49]. FIGURE 20.15

Endocarditis of the tricuspid valve, often seen in intravenous drug abusers. Note the nodules of infection on the valve cusp and the resulting deformity of the valve.

before the start of the autopsy. Subungual splinter hemorrhages, maculae on the palms and soles, and hemorrhagic nodules on the pads of the fingers may be seen [45]. While native valve endocarditis is most often due to Streptococci, IVDAs are more susceptible to methicillin-resistant and sensitive Staphylococcus aureus. Recent dental procedures or gingivitis can cause infection due to Streptococcus viridans. Appropriate medical and social history should be taken into consideration and shared with the microbiology laboratory to aid in organism identification. Valvular disease may erode into the valve ring and even into the adjacent myocardium causing abscess formation. Rupture of leaflets, papillary muscles, and chordae tendineae may occur (Figure 20.16). Infection of the valves may lead to significant valvular insufficiency and resultant congestive heart failure. Recent mechanical or bioprosthetic valve implantation should prompt careful evaluation for infection. Replacement valves in the mitral position are more likely to become infected than those in the aortic position

Pericarditis Pericarditis is readily apparent at the time of autopsy (Figure 20.17). The epicardial surface is covered by a yellow-green shaggy exudate and the pericardial fluid is murky yellow. Histologic evaluation reveals fibrin and acute inflammation with polymorphonuclear leukocytes and vascular congestion. Bacterial cultures should be performed to rule out an infectious process, but most cases of pericarditis are due to uremia. Other causes include acute myocardial infarct, radiation, trauma, surgery, infection, tumor, rheumatoid arthritis, or systemic lupus erythematous. The presence of pericarditis in combination with sudden death should prompt a more extensive investigation into the medical history. Treatment with immunosuppressant medications such as steroids and infections causing an immunocompromised state

FIGURE 20.17 Fibrinous pericarditis with a shaggy green layer of FIGURE 20.16

Aortic valve endocarditis. Abscess formation may be present within the adjacent myocardium and if extensive, can make repair difficult to impossible. Patients undergoing repair may die during surgery if the amount of infected tissue is extensive.

fibrin on the epicardial surface. This decedent was being treated with chronic corticosteroids following bilateral adrenalectomies for removal of pheochromocytomas performed 1 year prior. She died in her bed without complaint prior to death.

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are risk factors for the development of pericarditis. The most common symptom of pericarditis is chest pain with fever, night sweats, and weight loss as common symptoms [1,50]. Hemorrhagic pericarditis should raise suspicion for tuberculosis infection or neoplasm [51]. Pericardiocentesis may be performed and a blind pericardial percutaneous puncture may result in a cardiac defect, bleeding, and lead to death. Pericardial fluid can be evaluated to identify the cause of pericarditis.

CARDIOMYOPATHIES, MYOCARDITIS, AND GENETIC CAUSES OF SCD Cardiomyopathies are covered at great length elsewhere in this book, but here we highlight the most common causes of sudden and unexpected cardiac death related to cardiomyopathies [52–54]. Dilated and hypertrophic cardiomyopathies are the most prevalent types identified in SCD. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a less commonly identified cardiomyopathy, but should be excluded in all cases of SCD. Dilated cardiomyopathies alter the normal muscular function of the heart leading to a variety of physiologic compensatory changes and death typically results from dysrhythmia, conduction system abnormalities, or secondary effects of heart failure [55,56]. Identification of cases in which saving genetic material may be helpful can be complex, but in sudden death where a cardiomyopathy in the decedent is known, a family history of cardiomyopathy is known, or autopsy finding suggest a genetic cardiomyopathy, samples should be collected. It is best to collect material for potential studies in more deaths than may be necessary. Dilated cardiomyopathies are commonly identified at forensic autopsy. Death may be seen at any stage of the progressive process of cardiac enlargement, ventricular chamber enlargement, thinning of the left ventricular wall, and contractile dysfunction. The heart enlarges primarily from systolic failure, though diastolic failure also occurs. Dilatation can lead to progressive dysfunction of the tricuspid and mitral valves, manifesting as regurgitation. Despite efforts to compensate for the dysfunction, the heart becomes more damaged until it cannot sustain. A variety of underlying etiologies for dilatation are well known but in the forensic population of sudden death, alcohol and hypertension are the most commonly identified underlying etiologies (Figure 20.18). Dilatation from unreported or undiagnosed remote myocarditis is also seen. Much less common are genetic mutations leading to familial dilated cardiomyopathy [57]. Given that little information may be known about a decedent's history at the time of autopsy, one should have a low threshold for collecting samples for possible future genetic testing. Occasionally, antemortem symptoms are

FIGURE 20.18

Cross-section of the heart showing a concentrically thickened left ventricle with dilatation of the ventricle chamber. This decedent experienced sudden death following many years of known clinical hypertension.

reported including fatigue, dyspnea on exertion, and edema. Often, there is no history of such symptoms and clues must be gathered during the external examination and examination of the body cavities and organs at the time of autopsy. Lower extremity edema, pulmonary edema, and increased serous fluid in body cavities can be observed at autopsy. A thorough medicolegal investigation may reveal a history of known cardiomyopathy, the presence of alcohol containers in quantity sufficient to raise concern for chronic alcoholism, or the presence of medications suggestive of treatment for congestive heart failure, including angiotensin-converting enzyme inhibitors, angiotensin II receipt blockers, beta-blockers, diuretics, and vasodilators. Investigation may also reveal medications indicating a possible underlying etiology of the cardiomyopathy. For example, folate and vitamin B12 are often prescribed to alcoholics. Antihypertensive medications may be identified at the scene. Thorough examination of the organs at autopsy may reveal clues for underlying etiologies. Identification of hepatosteatosis or hepatic cirrhosis at autopsy would support ethanol as the underlying etiology. Arteriolonephrosclerosis suggests a history of hypertension (Figure 20.19). The presence of a billowing mitral valve with myxoid degeneration is consistent with mitral valve prolapse (MVP). Fibrosis and thickening of the valve and chordae tendineae indicate long-standing prolapse (Figure 20.20). Histopathologic examination may reveal patchy fibrosis suggestive of a remote viral myocarditis. Because alcohol is cardiotoxic, its cardiac effects in addition to cardiomyopathy include arrhythmias, hypertension, and stroke. Binge drinking has been shown to cause myocardial inflammation. While chronic alcoholism is identified more in men than women, female alcoholics tend to suffer the cardiotoxic effects of alcohol more than men, despite drinking less quantity than men. Cardiomyopathy from

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FIGURE 20.19 External surface of the right kidney showing pitting, granularity, and few cortical cysts, consistent with arteriolonephrosclerosis and degeneration from hypertensive cardiovascular disease.

vascular disease, starvation, endocrine diseases, drugs such as cocaine, heavy metals, granulomatous disease such as sarcoidosis, neuromuscular disorders, and the peripartum period. A complete medicolegal investigation combined with findings from a complete and through autopsy will often allow for identification of these underlying etiologies. Occasionally, despite extensive efforts, a likely cause may not be identified [61]. Hypertrophic cardiomyopathy (HCM) is a widely recognized cause of sudden death in the preadolescent, adolescent, and young adult population, often without antemortem symptoms or diagnosis. While both males and females may be affected, the typical forensic scenario is a teenage male participating in a vigorous sporting activity when he suddenly collapses and cannot be resuscitated. Most patients are asymptomatic and the first presentation of disease is sudden death. When present in females, the disease presents at a younger age, with symptoms, and is medically evaluated. At autopsy, the heart is enlarged and the interventricular septum is typically disproportionately enlarged in comparison to the left ventricular free wall. Cutting the heart to show a four chamber view will allow for the most obvious identification of this discrepancy [62]. Occasionally, the free wall and the interventricular septum may be symmetrically thickened or the free wall may even be thicker than the interventricular septum (Figure 20.21). The risk of sudden death in HCM patients is high, even if the left ventricular wall and interventricular septum thickness is not marked. Extensive

FIGURE 20.20

Fibrous thickening of the mitral valve and chordae tendineae in a decedent with long-standing mitral valve prolapse.

chronic alcoholism and sudden death may still occur in persons abstinent from alcohol if they have suffered irreversible or progressing myocardial damage from past alcohol consumption. Lack of a present overconsumption of alcohol or presence of alcohol containers upon medicolegal investigation should not exclude alcohol as the underlying etiology of the cardiomyopathy. In such cases, a history of past alcoholism provides sufficient evidence [58]. Rarely, the cause of the dilated cardiomyopathy cannot be identified [59]. Acute viral myocarditis with active infection can lead to death during the symptomatic period. However, symptoms may be vague and not reported. At autopsy, the heart may appear grossly dusky, softened, and dilated. Histopathologic examination reveals patchy to diffuse involvement. The heart should be adequately sampled in suspected cases or in cases of unexplained SCD so that death from a focal myocarditis can be excluded. Dilated cardiomyopathy may result in persons who survive a viral myocarditis and the resultant damage may be extensive enough to compromise cardiac function [60]. Less common causes of cardiomyopathy include doxorubicin chemotherapy treatment, collagen-

FIGURE 20.21

Sudden death occurred in this young man while playing basketball with friends. He had no past medical history or complaints before his sudden collapse. The heart was grossly enlarged and the left ventricle was palpably thick. After formalin fixation, the heart was cut to show the four chambers and revealed a markedly thickened left ventricle and interventricular septum. Microscopic examination revealed myocyte disarray in the interventricular septum consistent with hypertrophic cardiomyopathy. Of note, the left ventricular and interventricular septum are nearly symmetrically thickened.

ANOMALIES AND DISEASES OF THE AORTA AND CORONARY ARTERIES

histologic sections should be taken to identify myocyte disarray. Microscopic examination reveals myocyte disarray or disorganization, particularly in the interventricular septum, but disarray may also be identified in the left ventricular free wall. Fibrosis is often present and may be identified both grossly and microscopically. Intramural coronary arteries with a thickened wall and reduced lumen may also be identified [63]. Subendocardial fibrosis from ischemia may be identified. While consultation with a cardiac pathologist is not necessary, benefit may be gained from an extensive evaluation of the coronary vessels and structural documentation of the heart. Since HCM is a genetic disorder known to have a high incidence of sudden death and living relatives may also be affected, material should be collected and saved for potential future genetic testing. Identification of HCM at autopsy may prompt testing of relatives for HCM and if identified, lives can be prolonged through medication, medical intervention, and adjustment in activities of daily living [53,64]. ARVC manifests with gross or microscopic fibrofatty replacement of the right ventricular myocardium. ARCV can manifest with sudden unexpected death from postadolescence to age 50. At autopsy, the right ventricle may exhibit extensive fibrofatty replacement of the right ventricle such that the wall is translucent when held to light. However, cases may be missed exclusively on gross examination. Thorough sectioning of the heart including sections of the right ventricle in cases of sudden death when routine investigation, toxicology, and histology do not illicit an underlying cause of death may help to identify grossly unapparent cases of ARVC [65–67]. Cardiac channelopathies are an emerging set of congenital or acquired genetic disorders manifesting with disruption of cardiac ion channel function leading to altered electrical function and predisposition to dysrhythmia and sudden death. Some of the common channelopathies include Brugada syndrome, short QT syndrome, long QT syndrome, and catecholamine polymorphic ventricular tachycardia [68,69]. A cardiac channelopathy should be considered in all cases of sudden unexpected death appearing to be from a cardiac cause without an identified reason after a complete autopsy, including sufficient histopathologic examination and toxicologic testing. Cardiac channelopathies are without structural and microscopic abnormality. The cardiac conduction system should be grossly and microscopically evaluated for evidence of fibrosis and inflammation, which might help explain a cardiac death that might otherwise remain undetermined [70]. Death from channelopathies is most common in infants, children, and young athletes but can be seen into adulthood and presents as cardiac death without identifiable cause [71]. Some deaths previously classified as sudden infant death syndrome may actually be deaths related to cardiac channelopathies [72,73]. Likewise, previously determined cardiac deaths of unknown cause may be related to

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cardiac channelopathies. Identification of a cardiac channelopathy at death is important for relatives of the decedent, who may suffer from the same or a similar genetic mutation and who, with appropriate therapy, may avoid an SCD. Additionally, identification of a cardiac channelopathy responsible for death of young siblings may absolve caretakers of suspicion in the deaths. Channelopathies are discussed at length elsewhere in this book. Channelopathies should be explored, particularly in sudden infant death, when extensive testing, including histology, toxicology, and cultures, at autopsy is negative. New genetic mutations are being researched and identification of additional genes related to channelopathies will allow for greater identification of the cause of death. While the capabilities of current genetic testing may not reveal mutation known to cause death, collection of blood or tissue for future testing may allow for more extensive investigation when additional mutations are identified [66]. While antemortem symptoms are often not known or reported, death from a channelopathy should be suspected in a decedent who has experienced syncopal episodes without an identified structural cause or has a family history of syncopal episodes or unexplained cardiac death. Targeted medicolegal interviews with family members will assist with gathering necessary history. Medication information should also be gathered and the list should be reviewed for the presence of medications known to alter the QT interval. Referral of family members to a genetic counselor or a cardiovascular genetics center will allow for evaluation of sudden death risk for family members [74–76].

ANOMALIES AND DISEASES OF THE AORTA AND CORONARY ARTERIES Coarctation of the aorta is rarely identified at autopsy as symptoms typically lead to diagnosis and treatment during life. When present at autopsy, the narrowing of the aorta is just distal to the origin of the left subclavian artery and is easily observed. Aortic aneurysms and dissections are known complications and histologic evaluation of the site of dissection may reveal changes in the intima and media suggestive of a coarctation that may be difficult to grossly appreciate [77,78]. Careful cross-sectioning of the coronary arteries at 1.0 cm or less intervals and along the entire length before the heart is opened along the lines of blood flow will allow for the identification of coronary artery anomalies [53] and pathologies that can explain sudden death [79]. Anomalies such as high take-off of the coronary ostium [80], a single coronary ostium (Figure 20.22), acute angle take-off of a coronary artery (Figure 20.23) [81], and a bridging (sometimes also referred to as tunneling) (Figure 20.24) [82,83] of a coronary artery must be taken into consideration within the prevailing forensic scenario.

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

FIGURE 20.22 Single coronary ostium. This was an incidental finding in a person who died from an acute drug intoxication.

In general, a coronary artery take-off is high if positioned >0.2-0.3 cm above the sinotubular junction. A person who is acutely intoxicated with a substance known to cause death, such as heroin, is likely not dying suddenly from a coronary artery anomaly, while an anomaly may be of great significance in a driver dying in a motor vehicle crash with no explanation for the crash. Likewise, a myocardial bridge that extends into the myocardium 0.2-0.3 cm deep over at least a similar length with overlying myocardium is considered to be significant [84]. Again, the importance this finding plays in the cause of death must be evaluated within the context of the circumstances of death. A person who is struck on the head by a falling object at a work site and suffers extensive blunt force injuries is likely not dying a SCD despite the presence of a myocardial bridge; however, a person who is a strong swimmer who is found drowned without explanation may be dying as a result of a this anomaly [85–89]. An acute thrombus occluding the lumen is most often identified in decedents with pre-existing coronary artery atherosclerosis and occurs when an atherosclerotic plaque ruptures and causes hemorrhage that thromboses and occludes the arterial lumen. This blockage can cause myocardial ischemia or infarct of great enough significance to cause sudden death (Figure 20.25). Such cases are often seen in middle-aged men [90,91]. Thrombus of the coronary artery lumen should be examined with great care at the time of autopsy and microscopically to exclude a spontaneous coronary artery dissection. Displacement of the intimal layer of the arterial wall can usually be visualized grossly on cross-section, though occasionally microscopic examination may be necessary (Figure 20.26). Coronary artery dissections may result

FIGURE 20.23 Acute angle take-off of the left coronary artery, demonstrated by the probe within the artery.

FIGURE 20.24

Bridging of the left anterior descending coronary artery. Notice that the center of the vessel lumen is located 0.5 cm below the myocardial surface.

FIGURE 20.25 Cross-section of the left anterior descending coronary artery with an acute thrombus, leading to a sudden unexpected death. Microscopic examination should be performed to identify the cause of the thrombus. Commonly a ruptured atherosclerotic plaque will lead to acute thrombus but the thrombus may also result from a coronary artery dissection.

ANOMALIES AND DISEASES OF THE AORTA AND CORONARY ARTERIES

785

(a)

(b) FIGURE 20.27 (a) Patchy moderate atherosclerosis of the abdomiFIGURE 20.26 Cross-section of left anterior descending coronary artery with spontaneous coronary artery dissection (right). Note the separation of the inner layers of the artery wall from the outer layers in the section on the right (arrow).

from extension of an aortic dissection that travels retrograde to the coronary ostia and along the coronary arteries. Coronary artery dissections typically occur in females without underlying atherosclerosis and are typically found in a younger population, particularly in the peripartum or postpartum period. Histologic examination should be performed to identify the presence of any underlying disease process of the artery, particularly vasculitis or an isolated eosinophilic coronary arteritis [92,93]. Atherosclerosis of the arteries may be systemic but is most commonly seen in the coronary arteries and the aorta. In the aorta, the most common location where atherosclerosis is identified is above the bifurcation, inferior to the renal arteries. Atherosclerosis may be slight or marked with ulcerated plaques and may be regional or diffuse (Figure 20.27a and b). The presence and degree of aortic atherosclerosis often does not correlate with that present in the coronary arteries [94,95]. Likewise, atherosclerosis of the coronary arteries often varies drastically. Sometimes, there is calcification of the artery wall which makes sectioning difficult but does not compromise the lumen. More commonly, there is actual stenosis due to atherosclerosis, with or without calcification (Figure 20.28a and b). Identification of coronary artery dominance is important when assessing the significance of blood flow compromise to the myocardium. A 75% stenosis of the right coronary in a right dominant heart is more likely to cause sudden death than a similar stenosis identified in the left circumflex. In general, a stenosis of greater than 75% of a coronary artery is sufficient to cause

nal aorta near the bifurcation. Of note, there are some scattered fatty streaks. (b) Aorta with marked atherosclerosis, ulcerated plaques, and thrombus in both common iliac arteries resulting from plaque rupture.

(a)

(b) FIGURE 20.28 (a) In situ cross-section of the proximal left anterior descending coronary artery exhibiting marked atherosclerotic stenosis. This decedent died suddenly and unexpectedly. He had no known past medical history. (b) Cross-section of markedly stenosed coronary artery, removed from the myocardium.

death if no other prevailing cause of death is identified through autopsy and investigation. Typically, death is seen when multiple coronary arteries are stenotic or when there is marked (>75%) stenosis of the proximal to mid-

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

left anterior descending coronary artery [96–99]. Factors that accelerate the formation of atherosclerosis, such as diabetes mellitus and tobacco use, should be considered as contributing factors to death due to atherosclerotic cardiovascular disease. If death occurs quickly from a myocardial infarct due to compromised blood flow where a coronary artery is stenosed, examination of the myocardium is likely to be unremarkable for ischemic changes such as hypereosinophilia, contraction bands, edema, or necrosis. As time progresses, hemorrhage can be seen within the myocardium (Figure 20.29) and the infarct passes through the stages of healing. While healing, the wall weakens before forming a fibrous scar. It is during the healing process when the wall is most vulnerable to rupture with resultant cardiac tamponade and death. Gross findings in these cases typically show a large infarct comprised of soft yellow necrotic myocardium with hemorrhagic margins where the rupture occurs (Figure 20.30a and b). Persons are typically found dead unexpectedly, often at home. Once a fibrous scar forms,

the wall is typically thinner than the remaining ventricle; however, the likelihood for rupture is decreased unless the wall forms an aneurysm, where it may rupture at the margin (Figure 20.31) [100,101]. Hypertensive disease is often found in combination with atherosclerotic disease at the autopsy of a SCD. The extent of structural and microscopic changes varies but can include gross cardiac hypertrophy, concentric left ventricular hypertrophy (Figure 20.32a and b), fibrosis (Figure 20.33) and arteriolonephrosclerosis and the presence of myocyte hypertrophy, perivascular and interstitial cardiac fibrosis, and arteriolo- and arteriolarnephrosclerosis on histopathologic examination. Presence of gross and microscopic findings sufficient to support hypertension without an alternative cause of death should allow certification of death as hypertensive cardiovascular disease. Often, decedents are reported to have well-controlled clinical hypertension and their death may come as a surprise to the family or treating physician. This does not preclude them from death due to a cardiac dysrhythmia in the setting of hypertension. Hypertensive cardiovascular disease may also cause sudden death due to disease processes secondary to elevated blood pressure, including rupture of a cerebrovascular

FIGURE 20.29 Multiple foci of recent hemorrhage in the left ventricular wall and interventricular septum, identified as acute myocardial infarcts on microscopic examination.

FIGURE 20.31 Cross-section of the heart with a thin, fibrotic left ventricular wall, the end result of a healed large infarct. A large region of thin fibrosis can form an aneurysm.

(a)

(b)

FIGURE 20.30 (a) Rupture through the full thickness of the left ventricular wall at the site of an organizing myocardial infarct. This man was found deceased in his chair at home when he did not show up for work and his co-workers came to check on him. He had no reported complaints when last seen alive, but was noted to be a heavy smoker. The rupture resulted in hemopericardium and cardiac tamponade. (b) A closer photograph of the ruptured left ventricular wall. The yellow necrotic myocardium is more apparent in this photograph, indicating an organizing myocardial infarct.

DISEASES OF THE CARDIAC VALVES

(a)

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(b)

FIGURE 20.32 (a) Cross-section of the heart located near the tips of the papillary muscles, showing a concentrically thickened left and a somewhat thickened right ventricle. (b) A closer look at the left ventricular wall to evaluate the wall thickness, which measured 1.8 cm. The left ventricular wall thickness should normally not exceed 1.4 cm and should be measured at the exclusion of the papillary muscles, chordae tendineae and epicardial fat.

FIGURE 20.33 Focal fibrosis within the left ventricular wall, indicating a region of prior myocardial ischemia.

aneurysm leading to subarachnoid hemorrhage, a hemorrhagic infarct in the cerebrum, cerebellum, or brainstem (Figure 20.34a–c), or an aortic dissection with rupture and hemorrhage or even hemopericardium (Figure 20.35a–d). Given the prevalence of hypertension in the population, performance of a complete autopsy will allow for the most specific determination of the immediate cause of death, although the underlying cause of death will remain hypertensive cardiovascular disease [102,103].

DISEASES OF THE CARDIAC VALVES The four cardiac valves are typically smooth and translucent though it is quite common to see small plaques of cholesterol deposition within the valve cusps, even at a young age (Figure 20.36a and b). Significant atherosclerosis can deform the valve and compromise function, leading to regurgitation and secondary cardiac effects. The most common valvular abnormality is MVP, and therefore, the role it plays in death must be carefully considered

when identified autopsy. Evaluation of the valve for billowing and the extent of myxomatous degeneration and collagen fragmentation as well as examination of the lungs for changes secondary to regurgitation, are all important observations to make in understanding the significance of MVP in death. Examination of the chordae tendineae may reveal rupture which increases the extent of regurgitation. Decedents may have a known history of prolapse, but many do not. In the postmortem setting, one cannot quantify the extent of regurgitation but secondary changes in the heart and lungs may give clues to the physiologic significance during life [104]. The aortic valve should be examined for the number of cusps, as any deviation from the normal tricuspid valve makes the valve subject to abnormal hemodynamics and increased pathology [105–108]. While a bicuspid aortic valve may be completely unremarkable, it is more subject to pathologic processes, including atherosclerosis. Calcification of the leaflets with progressive obstruction of the valve orifice is the cause of most aortic stenosis and is identified in persons over age 65 (Figure 20.37a and b). Those with a bicuspid aortic valve may have manifestations of aortic stenosis at a younger age due to premature atherosclerosis of the valve [109–111]. Postinflammatory or rheumatic aortic valve stenosis is rare in the Western world but is still the most common cause of aortic valve stenosis worldwide [111]. Gathering history regarding country of birth and spent time abroad as well as risk factors for atherosclerosis, including tobacco use and elevated low-density lipoprotein cholesterol, may be useful in differentiating the underlying cause. Investigation of antemortem symptoms including dyspnea, syncope, and angina will allow for a greater understanding of the significance the aortic valve stenosis had in causing death.

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

(a)

(c)

(b)

FIGURE 20.34 (a) Very large cerebral artery aneurysm located that the posterior communicating artery in the fresh state. This aneurysm ruptured (arrow), causing extensive diffuse subarachnoid hemorrhage and sudden unexpected death. (b) Small, ruptured cerebral artery aneurysm of the internal carotid artery. This decedent experienced sudden death following rupture with subarachnoid hemorrhage extending over the base of the brain, cerebellum, and brainstem. (c) Recent diffuse thin to thick subarachnoid hemorrhage resulting from a ruptured cerebral artery aneurysm. A pre-existing aneurysm may rupture from weakening of the wall but rupture may also result from hypertension, both chronic elevations from systemic disease and transient elevations during exercise or use of stimulatory drugs such as cocaine and amphetamines.

(a)

(c)

(b)

(d)

FIGURE 20.35 (a) Transverse view of the ascending aorta with an acute dissection, evidenced by separation of the layers of the artery wall (arrow). (b) Tense pericardium with apparent dark discoloration beneath from hemopericardium. (c) Hemopericardium evident with the pericardium now reflected. A very focal separation of the blood (arrow) reveals the heart. (d) Defect of the right coronary artery with hemorrhage into the adjacent epicardial fat. The defect is a site of rupture resulting from an aortic dissection that traveled retrograde to the coronary artery where the rupture caused sudden death resulting from hemopericardium with tamponade.

DISEASES OF THE CARDIAC VALVES

(a) FIGURE 20.36

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(b)

(a) Bicuspid aortic valve. Note the focal fatty deposits of the aorta. (b) Anomaly of the pulmonary valve with four leaflets.

Tumors Theoretically, any neoplasm can metastasize, though rarely, to the heart. Given the infrequent nature of cardiac neoplastic lesions and the need to differentiate tumors from non-neoplastic granulomatous processes such as sarcoidosis, histologic examination is useful. Differentiating a metastatic tumor from sarcoidosis or lymphoma can be difficult on gross examination (Figure 20.38a–d). Primary tumors of the heart are quite rare and typically easily separated from metastasis based on location and distribution [113–115].

(a)

(b) FIGURE 20.37 (a) Aortic valve with marked calcification of the leaflets, causing aortic stenosis. This decedent exhibited long-term cardiac changes from stenosis resulting in ventricular and atrial dilatation. (b) Aortic valve with calcification of leaflets causing aortic stenosis.

The tricuspid valve leaflets should be carefully inspected for gross evidence of IE, especially in the death of an intravenous drug user. Additionally, the valve position and leaflets should be inspected for Ebstein malformation which can lead to valve incompetence or stenosis. Ebstein malformation has a known association with supraventricular tachyarrhythmia and possible sudden death [112].

Immune Disease Immunologic disease processes affecting the cardiovascular system typically manifest as vasculitis or granulomas and often, histopathology sections are needed for identification. In a sudden, apparently natural death of a person with a known history of immunologic disease, standard microscopic examination of organs, as well as small- and medium-sized blood vessels may help confirm the pathologic process and understand the extent of disease. When disease is not known, histopathology may be helpful in identification of a previously undiagnosed immunologic disease process.

Pulmonary Disease Pulmonary hypertension may cause long-term effects on the heart, beginning with thickening of the right ventricle with failure and progressive thickening of the left ventricular wall. A fibrotic plaque may be seen in the pulmonary artery. Care should be taken at autopsy and on microscopic examination to identify cardiac pathology and lung pathology that might help identify if the pulmonary hypertension is the cause of the cardiac disease or if it is the result of cardiac disease. Disease processes of the left ventricle, either within the myocardium or the mitral valve, can lead to passive pulmonary hypertension.

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

(a)

(b)

(c)

(d)

FIGURE 20.38 (a) View of the endocardium of the left ventricle showing white patches throughout the left ventricular wall. (b) A cross-section of a heart with similar white patches. Histologic examination revealed metastatic squamous cell carcinoma. Lymphoma can present with similar gross lesions in the heart. (c) Cross-section of the heart showing multiple white patches throughout the left and right ventricular walls. Histologic examination revealed the patches to be sarcoidosis. (d) Microscopic view of the white patches seen in (a) and (b) showing squamous cell carcinoma.

Likewise, pulmonary hypertension may be caused by emphysema or pulmonary fibrosis, disease processes which destroy or compress the lung vasculature. Likewise, blockage of pulmonary arteries by a thromboembolus can lead to pulmonary hypertension [116].

Pulmonary Thromboembolism/Deep Vein Thrombosis When autopsying sudden deaths, one must always be vigilant to examine the pulmonary arteries for the presence of pulmonary thromboemboli. Without careful attention at dissection, thrombi that are not attached to the vessel wall can displace, and the cause of death may be missed. Sudden death from pulmonary embolism (PE) typically results from a deep vein thrombus from the lower extremity dislodging and moving to the lungs where it blocks enough blood supply to cause death [117] (Figure 20.39). Often decedents complain of shortness of breath or chest pain before death, but occasionally decedents are found dead without known antemortem

FIGURE 20.39 Measurement of the calf circumference in a decedent found to have a pulmonary thromboembolism at autopsy. Note the enlarged left calf diameter (45 cm on the left compared to 41.5 cm on the right). An organizing thrombus was identified within a deep vein of the left lower leg.

DISEASES OF THE CARDIAC VALVES

(a)

(c)

791

(b)

(d)

FIGURE 20.40 (a) In situ saddle pulmonary thromboembolus identified in the pulmonary trunk upon removal of the heart from the chest. (b) Lung with large saddle pulmonary thromboembolus removed from the vessel of the opposite lung. (c) Pulmonary thromboembolus removed from the pulmonary trunk. Some regions show more organization (arrows) than others. (d) Section of the lung near the hilum showing a thromboembolus within a medium-sized blood vessel (arrow).

complaint [118]. At autopsy, these tend to be large, saddle emboli spanning the left and right vessels (Figure 20.40a–d). The thrombi are not adherent to the wall of the pulmonary arteries and do not take the shape of the vessel, but rather are an organizing strand of thrombus more consistent with the caliber of the vessels of the lower extremity now lodged within the pulmonary arteries. The thrombus can be easily removed from the pulmonary vessels and should be sectioned to evaluate the degree of organization. The veins of the lower extremities should be dissected to look for deep vein thrombus, which is often present at the level of the calf or popliteal fossa but may be present in the thigh or pelvic veins (Figure 20.41a and b). Decedents with large abdominal masses including leiomyoma or pelvic tumors such as ovarian or soft tissue tumors are at increased risk for formation of pelvic thrombi due to local pressure on the pelvic veins. Extensive history for risk factors should be gathered either before or after autopsy. Families, friends, and physicians can add important information to understanding relevant risk factors for thrombus formation. The formation of deep vein thrombi and subsequent pulmonary thromboembolism is typically multifactorial.

Obesity is one of the most common risk factors for formation of deep vein thrombosis (DVT) but there is not a specific body mass index above which risk is inferred. Often, obesity is the only identified risk factor in cases of pulmonary thromboemboli due to deep vein thrombus. Decedents with a history of decreased mobility from prolonged travel, illness, use of restraints limiting mobility in hospitalized patients, substance abuse, particularly opioid use, or sedentary life style are at risk for lower extremity deep vein thrombi as a result of stasis. Adding to these risk factors is a state of dehydration, which often occurs during all of the previously described circumstances. Other important risk factors include trauma of the lower extremities, use of oral contraceptive birth control pills, particularly those with high estrogen, and tobacco use. Vasculitis is a rare but important risk factor to consider [119,120]. A family history of clotting issues including history of miscarriages or deep vein thrombus is important to note, as this may indicate a genetic predisposition to the formation of thrombi. The most commonly examined genetic mutations are for Factor V Leiden gene mutation, Prothrombin gene mutation, and Homocysteine gene mutation [121]. If testing is

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

the relative dehydration that accompanies the ketosis. Evaluation of vitreous electrolytes including glucose levels should be performed in decedents with a history of diabetes mellitus. While diabetic patients typically die of diseases secondary to prolonged hyperglycemia, it is not uncommon, particularly for insulin-dependent diabetics, or even for persons not clinically diagnosed as diabetics to experience ketoacidosis and sudden death. Common complaints before death included feeling unwell, lethargy, and flu-like symptoms. Evaluating vitreous electrolytes will also aid in identifying a state of dehydration before death and will identify an additional risk factor [123].

ANCILLARY STUDIES

(a)

Histology

(b) FIGURE 20.41 (a) In situ cross-section of a deep vein in the lower leg that is filled with an organizing thrombus. (b) Deep veins of the lower extremity filled with organizing thrombus, removed from the surrounding soft tissues so that microscopic examination can be performed.

possible for these genetic mutations, they should be performed, as identification of a genetic mutation may mean living relatives are at an increased risk for thrombus formation. Families should be made aware if significant genetic mutations are identified and should be encouraged to consult with their personal physician, who can advise them of appropriate follow-up in the context of their overall health. Given the multiple risk factors for DVTs and PEs, a complete autopsy should be performed and should include histologic examination of the pulmonary thromboembolus as well as the deep vein thrombus with surrounding vessel, soft tissues, and muscles. Histologic sections may reveal trauma or vasculitis, as well as confirmation that the thrombus was present antemortem and allow for aging of the thrombi. Toxicology may help identify an increased risk for DVTs. Opiate intoxication may lead to prolonged immobility or even prolonged direct pressure on an extremity leading to venous stasis and thrombus formation [122]. A less commonly known risk factor for deep vein thrombus formation is diabetic ketoacidosis. A ketotic state is prothrombotic as well as

The threshold for taking histologic sections of cardiac deaths should be low, particularly in persons lacking a clinical cardiac history or obvious findings at autopsy. While no definitive number of sections exists to adequately examine the heart and vessels, one should examine enough sections as not to miss a disease process which may be focal, such as myocarditis. Typically, two sections of the right ventricle and six to eight sections of the left ventricle, including the various aspects of the free wall and interventricular septum, will suffice. Additionally, sections of coronary arteries are often useful in cases of a negative autopsy and toxicology when investigation suggests a SCD. Cases of coronary artery dissections and isolated eosinophilic coronary arteritis have been identified when gross examination fails to reveal any pathology. If extensive histology of the myocardium reveals no significant pathologic process, one should consider histologic examination of the conduction system. While examination often reveals no significant pathology, examination is part of a thorough and extensive evaluation of sudden unexplained cardiac death and identification of pathology will allow for determination of cause of death.

Toxicology Toxicology testing is an essential part of the investigation of sudden and unexpected death. While toxicology evaluation may reveal a cause of death resulting from a single drug or combination of substances, the presence of certain drugs and medications may contribute to an SCD in decedents with underlying cardiac pathology. Use of drugs and medications that elevate the blood pressure and cause increased cardiac demand, such as amphetamines and cocaine, may lead to a cardiac dysrhythmia, particularly in persons with underlying heart disease. Likewise, identification of medications known

SUDDEN DEATH FOLLOWING SURGERY AND MEDICAL PROCEDURES

to cause dysrhythmias, such as digoxin, may be of public health importance. In these instances, it is important to obtain a quantitative level of the medication to determine if antemortem levels were in the therapeutic or toxic range. Identification of the presence of medications that prolong the QT interval may also be helpful in identifying cause of death. Many medications may prolong the QT interval including Class IA and Class III antiarrhythmic agents, the antipsychotics haloperidol and phenothiazines, some atypical antipsychotics, tricyclic antidepressants, and fluoroquinolone antibiotics.

Cultures and Other Studies Cultures to identify viral proteins and bacterial and other microorganisms should be a routine part of an infant or young child autopsy. Significant illnesses in this age group are often grossly unapparent at the time of autopsy and failure to collect cultures may result in a missed cause of death. Typical specimens collected for viral testing can include nasopharyngeal swabs, oropharyngeal and tracheal swabs, cerebrospinal fluid, and stool. Bacterial and microorganism cultures can be performed on any tissue or fluid collected at the time of autopsy. Blood, cerebrospinal fluid, urine, and lung tissue are samples often collected. Sampling any grossly purulent tissue or fluid will aid in the identification of the causative organism and will allow for a more specific cause of death statement on the death certificate, as the infection will play a role in the cause of death. It is helpful to provide the laboratory with a brief clinical history or a list of suspected organisms when requesting testing. Testing for human immunodeficiency virus and hepatitis virus infections may allow for identification of an underlying cause of infection or pathology identified on histopathologic examination. Samples should be collected at the time of autopsy to ensure the best outcome.

Genetics Blood and nonfixed tissue may be collected at autopsy in anticipation of future cardiac molecular genetics testing. Typically, formalin fixed tissue is not sufficient, as testing for genetic causes of SCD requires whole gene sequencing and requires large segments of DNA rather than smaller fragments that are useful for identification testing. A full purple top ethylenediaminetetraacetic acid tube of blood or fresh tissue that is quickly frozen or placed into a preservative solution after collection will allow for testing at a later date, if necessary. It is ideal to collect multiple specimens to ensure adequate specimen quality and DNA quantity. From a forensic perspective, it is wise to consider a potential genetic cause for SCD at the time of autopsy in all decedents under the age of 40 without a sufficient cause of death, based on

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the investigative information or at the conclusion of the autopsy. Additionally, cardiac changes suggestive of an underlying genetic process or a strong family history of sudden death at a young age are clues that saving samples for genetic testing is prudent. Additionally, unexpected sudden death in persons performing activities that would not typically cause death should raise suspicion for a possible genetic cause. For example, if a person who knows how to swim drowns, he may be experiencing a cardiac dysrhythmia from an underlying cardiac genetic cause. Likewise, a person driving a motor vehicle who crashes without obvious reason may crash following a cardiac rhythm disturbance and collection of blood or tissue for potential genetic studies may prove useful once the crash investigation is complete and all additional studies are completed. Typically, it is useful to wait for and review the toxicology results, histopathology slides, and gather additional investigative, medical, and social history before ordering genetic testing. If all initial studies are unremarkable and an SCD is still suspected, evaluation of the conduction system may prove useful before genetic studies are performed. Given the expense of genetic testing and the possibility of a genetic mutation not being identified, it is wise to perform all possible testing before ordering genetic studies. Additionally, the utility of genetic testing in the deceased individual may best be determined with the aid of a genetic counselor following a comprehensive family pedigree. The family may ultimately benefit more from genetic testing of the living family members rather than the deceased. However, informing families of the importance of seeking out genetic counseling is an important role for the medical examiner or coroner and may be key to preventing the death of relatives.

SUDDEN DEATH FOLLOWING SURGERY AND MEDICAL PROCEDURES As life expectancy increases and medical technology advances, surgery is being performed more often and with greater success on older patients who often have significant underlying disease processes, particularly cardiac disease. Any surgery is not without risk and deaths during or after surgical procedure do occur. These deaths are often reported to the local coroner or medical examiner for consideration of jurisdiction. By and far, jurisdiction is mostly declined, as one assumes a certain risk when choosing to undergo a surgical procedure, particularly in the setting of known underlying cardiac disease. However, there are instances when it is appropriate for the medical examiner or coroner to investigate the death and even perform an autopsy. Death during or following a minor procedure with little risk, such as a colonoscopy, or in a healthy patient without significant underlying disease will likely prompt a medicolegal investigation into

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20. FORENSIC ASPECTS OF CARDIOVASCULAR PATHOLOGY

death. A complete autopsy should be performed to document all underlying disease processes which may be significant. A thorough targeted examination of the surgical site and the path along which medical manipulation took place should be performed, examining the tissues for disease, injury, hemorrhage, and infection, and evaluating the status of sutures, clips and placed therapies [124–127] (Figure 20.42). It is helpful to document abnormalities with photographs as well as a written description. Retaining tissue from the local region of interest may also be helpful. Occasionally, patients with known or unknown cardiac disease die during or shortly after surgery with no evidence of untoward circumstances related to the surgical procedure (Figure 20.43). In these cases, patients are

FIGURE 20.42 Greenfield filter that dislodged from the inferior vena cava and traveled to the right heart, where it embolized to the inflow tract at the superior vena cava.

FIGURE 20.43

Green discoloration of the myocardium that presented over a short amount of time following sectioning. This discoloration developed in all of the organs a short time after sectioning. The discoloration results from antemortem treatment with methylene blue used in diagnostic and surgical procedures.

typically suffering a cardiac dysrhythmia from the stress that the surgical process places on the already functionally compromised heart [127].

ORGAN AND TISSUE HARVESTING The forensic pathologist is often called upon to grant permission for organ and tissue donation in deaths resulting from apparent SCD. Balancing the great benefit to the living and the risk of losing probative evidence or the ability to determine the cause of death must be carefully considered within the prevailing forensic scenario of each death. Permission for donation of a whole heart for transplant is typically granted, as the benefit is greatest and the heart is still functioning and less likely the cause of death. Harvesting of the whole heart for valves after death is a common request. Following valve harvesting, the heart is examined by the cardiac pathologist consultant and their report as well as the residual heart tissue and recuts of histopathology slides can be returned to the forensic pathologist for independent review. The report should contain extensive documentation of disease processes and the examination may reveal a sufficient explanation of death. Often, permission is granted for harvesting of the aorta and iliac vessels or vessels of the lower extremities. Vessels with grossly apparent trauma at harvesting should not be removed. Photographs taken during the harvesting procedure may aid in understanding the state of tissues and organs prior to harvesting. Since pulmonary thromboembolism is a common cause of sudden death, care must be taken when granting permission for harvesting of the heart for valves, lungs, and lower extremity vessels when there is a high suspicion of pulmonary thromboembolus or DVT. Thrombus present with the pulmonary arteries during removal of the heart should be collected and submitted to the forensic pathologist for evaluation. Thrombi identified within harvested vessels of the legs render the vessel nontransplantable and the tissue may be discarded. Pulmonary thromboemboli identified at autopsy in a decedent who has had harvesting of the lower extremity vessels should prompt a discussion with the organ procurement team to investigate if thrombus was identified within the vessels. If a thrombus is identified, the tissue can be returned to the autopsy pathologist for examination. Likewise, a request can be made to the organ donor network to notify the forensic pathologist that a thrombus is identified after harvesting so that arrangements can be made for return of the vessel. In both instances, subsequent gross and microscopic examination by the autopsy pathologist is part of a thorough investigation into the risk factors leading to thrombus formation. Artifacts in the remaining tissues may be produced during tissue and organ harvesting (Figure 20.44). To

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FIGURE 20.44

Partial thickness laceration of the lower thoracic aorta from cross clamping of the aorta during organ donor harvesting.

the inexperienced, these changes may be difficult to differentiate from antemortem injuries. When abdominal organs are harvested, the aorta is cross clamped to stop the flow of blood. The clamp may cause a partial or full thickness defect to the wall of the aorta that may appear similar to an aortic laceration or transection caused by blunt force trauma. Loosening of fascia and soft tissue connections as well as hemorrhage into these tissues may be difficult to differentiate from blunt force injury; however, the history related to the death and the report or photographs from the transplant surgeon or harvesting technicians should be helpful in excluding injuries present prior to procurement.

CARDIOVASCULAR PATHOLOGY CONSULTATION The cardiac pathologist may serve an important role as a consultant in the forensic setting. Evaluation of the heart and major vessels by an expert allows for thorough identification of pre-existing pathology, accurate documentation of complex surgical procedures both recent and remote, and exploration of recent changes to the tissues. Accurate documentation of these factors will assist in identifying the mechanism which led to death. Additionally, this important information can help confirm reported events surrounding death. The medical examiner/coroner will take the information from the cardiac pathology consultation into account with the circumstances surrounding death including other autopsy findings, toxicology results, witness statements, police reports, and scene investigation. Assimilation of all information will allow for determination of the cause and manner of death. While a decedent may have very significant cardiovascular pathology, this underlying disease may play no role in the cause and manner of death. For example, a person with significant coronary artery atherosclerotic stenosis may suffer a gunshot wound to the

head during an argument and die. Though the underlying cardiac disease made that person susceptible to SCD, the gunshot wound was a significant event that clearly led to his death, unrelated to his existing heart disease. Some deaths, however, require more investigation of the pre-existing cardiac disease, and highlight the benefits of cardiac pathology consultation. If this same person were to crash his car while driving, and sustain injuries which may or may not be extensive enough to cause death, the medical examiner or coroner would rely heavily on the cardiac pathology consultation to understand the extent of the long-standing pathology, if there was a more acute pathologic process either independent of or related to the pre-existing pathology, or if there is evidence of trauma to the tissues. Understanding these factors can allow for an understanding of the mechanism of death. Based on the examination, the medical examiner or coroner can determine the significance that these findings play in the death. Significant trauma to the heart or major vessels indicates that the death was likely related to the motor vehicle crash. Identification of an acute pathologic process with the absence of significant injury would indicate that the crash was likely a secondary result of the acute pathology and the medical examiner would have to determine if the injuries from the crash were significant enough to have contributed to death. Identification of significant long-standing cardiac pathology may indicate the crash was caused by some acute event that cannot be documented at autopsy, such as a dysrhythmia or rapidly fatal myocardial infarct; however, other circumstances may have led to the crash, such as driver error, mechanical issues, or dangerous driving conditions such as icy roads. The exact cause for the crash may not be definitively determined in such cases but utilizing information from accident reconstruction investigators can aid in the ultimate determination.

SUMMARY The most important aspect of determining the cause and manner of death in SCDs is a thorough investigation, including the circumstances surrounding death as well as a comprehensive medical, social, and family history. Without the investigation, the specific cause of a SCD may go undiagnosed. Often at the time of autopsy, little of this information is known. However, additional information can be gathered in the days to weeks following the autopsy while awaiting histopathology slides and toxicology results. Asking family members and friends specific questions in an effort to gather significant family and social history, a list of recent complaints and medications, and a report of the circumstances at the time of death will elucidate much of the needed information to aid in the determination of the cause of a SCD and will

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allow for the most specific and useful cause of death statement, benefiting the family and the public in disease prevention and treatment [128].

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