J Forensic Sci, September 2015, Vol. 60, No. 5 doi: 10.1111/1556-4029.12768 Available online at: onlinelibrary.wiley.com
PAPER PATHOLOGY/BIOLOGY
Yang Li,1 Ph.D.; Ling Li,2 M.D.; Hong-Shu Mu,3 M.D.; Shuan-Liang Fan,1 Ph.D.; Fang-Gang He,2 Ph.D.; and Zhen-Yuan Wang,1 Ph.D.
Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31 Forensic Autopsy Cases
ABSTRACT: Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospec-
tive study of 31 sudden unexpected deaths caused by AAD was conducted at Xi’an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female = 6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.
KEYWORDS: forensic science, forensic autopsy, aortic dissection, sudden death, medical tangle, medicolegal investigation Acute aortic dissection, a serious life-threatening medical emergency was first recognized in 1600s (1,2), has been studied for decades. Although the clinical diagnosis and treatment of this devastating disease has been greatly improved in the past two decades (3–5), deaths from acute aortic dissection due to missed diagnosis or misdiagnosis is still a major health concern because of poor recognition of this great “masquerader” by physicians in China. Our institute has investigated a total of 31 medical malpractice litigation cases related to deaths due to missed diagnosis or misdiagnosis of aortic dissection from 2001 to 2012. We present this article to show that a forensic autopsy is not only essential for the determination of cause of death in sudden death cases but can also help physicians have a better understanding of acute aortic dissection in their practice. In addition, the literature is reviewed, and pathogenesis, clinical presentations, and detailed forensic autopsy findings are discussed.
Materials and Methods Data Selection and Collection A retrospective study of forensic autopsy cases at the Medicolegal Center of Xi’an Jiaotong University (MC-XJU) was conducted. A total of 31 sudden unexpected deaths caused by aortic 1 School of Forensic Medicine, Xi’an Jiaotong University, Shaanxi, 710061, China. 2 Office of the Chief Medical Examiner, 900 West Baltimore Street, Baltimore, MD 21223. 3 Xian’yang Wei-cheng Public Security Bureau, Shaanxi, 712000, China. Received 20 April 2014; and in revised form 14 July 2014; accepted 18 July 2014.
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dissection were collected for the study over a 12-year period between 2001 and 2012. Deaths due to traumatic and iatrogenic aortic dissection were excluded. In all the study cases, scene investigation reports, medical history, and autopsy findings were reviewed. Stanford classification was used to divide the aortic dissection into two groups depending on whether the ascending aorta was involved: Dissections involving the ascending aorta proximal to the brachiocephalic artery were termed type A (see Fig. 1), whereas those not involving the ascending aorta were referred to as type B dissections (type B without ascending aorta involvement) (see Fig. 2). All the procedures followed were in accordance with the ethical standards of Xi’an Jiaotong University. Statistical Analysis All continuous data were present as mean SD. Univariate analyses were used to calculate proportion, distribution of demographic variables among the cases. Pearson’s chi-square test and Fisher’s exact test were used to evaluate the statistical significance of frequency distributions of two types of aortic dissection. Unpaired Student’s t-test was used to compare mean values between two groups. A measure probability value of p < 0.05 was considered significant. Statistical evaluation was carried out by SPSS 16.0 software (IBM, Chicago IL, USA).
Results Demographics The general demographic characteristics of the 31 cases were summarized in Table 1. With regard to gender, 27 cases (87.1%) were male, with male to female ratio = 6.7:1. Of the 31 cases, 24 deaths © 2015 American Academy of Forensic Sciences
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The detailed clinical presentation and physical examination findings were recorded in 23 of the 31 cases (Table 4). Data presented in Table 4 showed positive findings in clinical examinations. A total of 26 ECG reports were recorded with abnormalities: nine cases with ST-segment elevation, 5 with ST-segment depression, 2 with pathological Q wave, 2 with arrhythmia, and one with hypertrophy. Only 2 of 31 patients had an X-ray image. Abdominal ultrasound was performed on 14 cases, of which 4 showed cholelithiasis and 3 showed renal/urinary calculi. Fifteen cases had serological/biochemical tests. Of the 15 cases, 10 had elevated CK-MB level and 9 had elevated D-dimer level. Autopsy Findings
FIG. 1––Forensic autopsy of type A aortic dissection photograph of a heart and an autopsied aorta of a decedent with type A aortic dissection: a false lumen formed from the aortic root (arrow).
FIG. 2––Forensic autopsy of type B aortic dissection photograph of an aorta of a decedent with type B aortic dissection: the entry tear at the proximal of the descending aorta with a 1.0 cm dissection (ellipse-shaped dashed line); a false lumen (arrow); atherosclerotic spots in the intima of the aorta (rectangle-shaped dashed line).
(77.4%) were due to type A dissection. Overall, the age distribution of aortic dissection ranged from 20 to 64 years, with a mean age of 44.2 years. The mean ages of decedents with type A and type B aortic dissection were about the same with type A = 44.4 years and type B = 43.6 years (p > 0.05). Nineteen cases (61.3%) were under the age of 50 years old. Of the 31 cases, type A aortic dissection occurred in individuals with body mass index (BMI) of 26.68 1.7 and type B aortic dissection with BMI of 26.95 1.27. Clinical History and Presentation Analysis of data revealed 17 cases (54.8%) had onset symptoms occurring in the morning hours between 0600 and 1200 (Table 2). Sixteen of 31 cases (51.6%) occurred in the winter. Table 3 shows that of the 31 cases, 26 patients were clinically misdiagnosed with acute myocardial infarction (9 cases), coronary artery disease (6 cases), cholecystitis (4 cases), acute gastroenteritis (3 cases), renal/urinary calculi (3 cases), and acute pancreatitis (1 case). The other five patients died in a short time window without an identified clinical diagnosis. Among the 26 misdiagnosed cases, 22 cases were type A aortic dissection (84.6%) and 4 cases (15.4%) were type B aortic dissection (p < 0.05).
Autopsy findings are summarized in Table 5. Overall, the heart weights ranged from 342 g to 640 g with an average of 460.8 78.7 g. Of the 31 cases, individuals with type A aortic dissection had a larger heart (478 72 g) than those with type B aortic dissection (402 74 g, p = 0.04). Moreover, 21 of 24 cases (87.5%) with type A aortic dissection had heart weight more than 400 g compared to only 2 individuals (28.6%) with type B aortic dissection who had heart weight more than 400 g. The aortic root diameter was measured at the level of sinuses of Valsalva. In this study, aortic root was considered dilated when its diameter at the sinuses of Valsalva exceeded 4.0 cm in both women and men (6,7). The average dimension of individuals with type A aortic dissection was greater than those of individuals with type B aortic dissection (42.54 8 mm vs. 33.71 5 mm, p < 0.01). Of the 24 type A aortic dissection cases, 15 (62.5%) had aortic root diameter >4.0 cm while only 1 of the 7 (14.3%) type B aortic dissection cases had aortic root diameter >4.0 cm. Cardiac tamponade due to a rupture of the dissected channel into the pericardial sac was the most frequent cause of death (28 cases, 90.3%). Twenty cases had entry sites of dissection found in the ascending aorta, whereas the entry site in the arch of aorta was found in eight cases, all of which were confirmed with a type A dissection. Only in four cases, an entry tear was found in descending aorta, including one case with a type A dissection. The exit sites in the adventitia of the aorta were also identified. There were 24 cases with an exit tear found in the ascending aorta. Four cases had an exit tear in the arch of aorta, including 2 type A dissection cases with descending aorta involved. Three cases had an exit tear in the descending aorta, with 1 type A dissection case. There were 18 (58.1%) cases in which the thrombus took less than 50% space of the false lumen (15 cases with type A aortic dissection versus three cases with type B aortic dissection) and 13 (41.9%) cases with more than half of the false lumen filled by thrombus, including 9 type A aortic dissection cases and 4 type B aortic dissection cases. Microscopic examination was performed on all the 31 cases. Of the 31 cases, moderate atherosclerosis was found in 26 cases (83.9%), in the coronary arteries and in the aorta near the intimal tears. There were 9 cases (29.0%) that had decreased and fragmented elastic fibers in the media of the aorta. The medial cystic degeneration was confirmed in only two cases, both of which were type A dissection. Discussion Aortic dissection is a catastrophic cardiovascular disease, which is associated with high mortality if undiagnosed and untreated. The aortic dissection mortality rate is still high with
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JOURNAL OF FORENSIC SCIENCES TABLE 1––Demographic characteristics.* Dissection Type A & B (n = 31) No. (%)
Age distribution 14–29 30–39 40–49 50–59 60–69 Sex Male Female Age [Mean SD] Body mass index (BMI†)
6 3 10 9 3
Type A (n = 24) No (%)
(19.4) (9.7) (32.1) (29) (9.7)
5 1 9 6 3
27 (87.1) 4 (12.9) 44.23 12.21 26.74 1.6
(20.8) (4.2) (37.5) (25) (12.5)
21 (87.5) 3 (12.5) 44.42 12.79 26.68 1.7
Type B (n = 7) No. (%) 1 2 1 3 0
(14.3) (28.6) (14.3) (42.9) (0.0)
6 (85.7) 1 (14.3) 43.57 10.80 26.95 1.27
p Value
0.233
0.901 0.8744 0.708
*Age and BMI were compared by student’s t test, all other data were compared by Pearson’s chi-square test. BMI: weight in kilograms divided by height in meters squared.
†
TABLE 2––Clinical history and presentations. Total Cases (n = 31) No (%)
Type A (n = 24) No.(%)
The time of onset 0000–0600 5 (16.1) 0600–1200 17 (54.8) 1200–1800 5 (16.1) 1800–2400 4 (13.0) The season Spring 4 (13.0) Summer 3 (9.7) Autumn 8 (25.8) Winter 16 (51.6)
Type B (n = 7) No.(%)
p Value
5 12 4 3
(20.8) (50) (16.7) (12.5)
0 5 1 1
(0.0) (71.4) (14.3) (14.3)
0.563
3 3 7 11
(12.5) (12.5) (29.2) (45.8)
1 0 1 5
(14.3) (0.0) (14.3) (71.4)
0.365
TABLE 3––Clinical misdiagnosed cases.
Clinical Diagnoses Total cases Coronary artery disease Acute myocardial infarction Acute gastroenteritis Stroke Renal/urinary lithiasis Cholecystitis
Total Cases
Type A, No. (%)
Type B, No. (%)
26 6 9
22 (84.6) 6 (27.3) 8 (36.4)
4 (15.4) 0 (0) 1 (25)
0.03
1 0 1 1
0.674
3 1 3 4
2 1 2 3
(9.1) (4.5) (9.1) (13.6)
(25) (0) (25) (25)
p Value
an increase of 1–2% per hour despite of advancements in diagnostic and therapeutic modalities. The aim of the clinical or medicolegal measurements is to lower the mortality of this deadly disease. Several risk factors such as hypertension, atherosclerosis, Marfan syndrome, bicuspid aortic valve, male gender, advanced age have been reported to be associated with acute aortic dissection (6–9). In patients with characteristics of inherited diseases or having classical clinical signs and symptoms, the aortic dissection can be recognized directly and easily (10). However, some patients may have nonspecific clinical symptoms or a rapid deterioration. The clinical diagnosis of aortic dissection could be missed or misdiagnosed. In such cases, the diagnosis of aortic dissection was usually made after death during forensic autopsy examination. In any sudden unexpected death, an autopsy examination is necessary to determine the cause of death. In cases of medical
tangle or medical malpractice litigation, forensic investigation is imperative not only to determine the exact cause of death but also to clarify the relation among the variables of direct cause of death, contributory factor(s) or underlying cause(s) of death, and medical intervention. According to the data from the International Registry of Acute Aortic Dissection, males are a greater proportion (66.7%) of patients suffering aortic dissection (1). Our data also indicated 87.1% cases were male. There was no significant difference between the mean ages of patients with type A dissection (44.42 12.79 years) or type B (43.57y 10.8) dissection in our study, but the proportion of the cases with the age under 50 years was higher (63.3%) than those whose age was more than 50 years (36.7%). The onset of the acute aortic dissection was exhibited in a chronobiological fashion. Mehta et al. reported that the frequency of the complication of aortic dissection was significantly increased during the time from 0600 to 1200 (11). Manfredini et al. also has reported that a relatively high mortality incidence of aortic dissection occurred during early hour of the morning (12). Furthermore, there were two peaks, in later winter and autumn. In this report, we uncovered that 54.8% of patients had an onset in the morning, and more than 50% cases occurred in the winter. It is well recognized that the heart weights can be used as collaborative evidence of hypertension and other cardiac diseases, such as atherosclerotic cardiovascular disease, valvular heart diseases, and cardiomyopathy (13–17). Bailey, Duflou, and Puranik have found that aortic atherosclerosis and hypertension were the major modifiable risk factors for aortic dissection (18). Our study showed 23 of 31 cases (74.2%) had cardiomegaly, which could be a collaborative evidence of hypertension. The cardiomegaly is diagnosed if the heart weight is >95% confidence interval for body height and weight based on the Mayo Clinic criteria (19). In the current study, patients with type A aortic dissection were much more likely having cardiomegaly than the patients with type B aortic dissection. According to the 2010 Guidelines on Thoracic Aortic Disease, genetic syndromes such as Marfan syndrome, Loeys–Dietz syndrome, Ehlers–Danlos syndrome type IV, Turner syndrome, and familial thoracic aortic aneurysms and dissections (TAAD), are strongly associated with the formation of aortic dissection (15). Although in our study, only one case was diagnosed with Marfan syndrome, investigation of blood relatives, especially in
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TABLE 4––Clinical presentations of misdiagnosed cases.
Category Described symptoms Any pain described Abrupt onset Abdominal pain Chest pain Throat pain Headache Radiating/migrating Chest distress/short breath Neurological symptoms Hematemesis Abdominal distension feeling Blood pressure Hypertension ((SBP≧120 mmHg) Normotension (SBP80-120 mmHg) Hypotension ((SBP ≤80 mmHg) Laboratory examination ECG ST-segment elevation ST-segment depression Pathological Q wave Arrhythmia Hypertrophy Abdominal type B ultrasound Cholelithiasis Renal/urinary calculi Serological/biochemical test Elevated CK-MB Elevated D-dimers* Imaging test (X-ray) Absence/none performed
Recorded Cases (23) No.(%) 21 17 9 4 3 1 7 3 2 2 2
(91.3) (73.9) (39.1) (17.4) (13.0) (4.3) (30.4) (13.0) (8.7) (8.7) (8.7)
Type A (19), No.(%) 17 13 6 3 3 1 6 3 2 2 2
(89.5) (68.4) (31.6) (15.8) (15.8) (5.3) (31.6) (15.8) (10.5) (10.5) (10.5)
Type B (4), No. (%) 4 4 3 1 0 0 1 0 0 0 0
(100) (100) (75) (25) (0) (0) (25) (0) (0) (0) (0)
6 (26.1)
5 (26.3)
1 (25)
12 (52.2)
10 (52.6)
2 (50)
5 (21.7)
4 (21.1)
1 (25)
21 9 5 2 2 4 14 4 3 15 10 9 2 4
(91.3) (39.1) (21.7) (8.7) (8.7) (17.4) (60.9) (17.4) (13) (65.2) (43.5) (39.1) (8.7) (17.4)
18 8 5 2 1 4 11 3 1 12 9 9 2 4
(94.7) (42.1) (26.3) (10.5) (5.3) (21.1) (57.9) (15.8) (5.3) (63.2) (47.4) (47.4) (10.5) (21.0)
3 1 0 0 1 0 3 1 2 3 1 0 0 0
(75) (25) (0) (0) (25) (0) (75) (25) (50) (75) (25) (0) (0) (0)
p Value, Type A vs. B 0.7 0.3 0.1 0.7 0.6 0.9 0.8 0.6 0.7 0.7 0.7
0.9
0.8
0.6 0.7 0.7 0.5
ECG, electrocardiography; SBP, systolic blood pressure. *500 lg/L as cutoff line.
younger patients, those with aortic valve disease, and those with inherited disease should be considered by forensic pathologists. While diagnosis and therapeutic considerations of aortic dissection predominate clinical medicine, forensic pathologist may find themselves in the unique position of reporting genetic implications to the family of the decedent. We also recorded the interplay of thrombus and aortic dissection because the thrombus formed in the aortic dissection is significantly related to the accuracy of diagnosis. If the false lumen was occupied by thrombus completely, false or negative interpretation of the physical examination could be made so that patients might not be diagnosed promptly (20). On the other hand, the thrombus in aortic dissection could compress the true channel leading to death (21,22). According to our findings, 24 decedents with a type A aortic dissection had more thrombus in the false lumen than those in the false channel of the other seven cases with type B aortic dissection (58.3% vs. 42.9%), which suggested people suffering the type A aortic dissection have a higher possibility of thrombus formation in the dissection and a higher risk to suffer a sudden cardiac death. The diagnosis of aortic dissection remains clinically challenging and the outcomes from this disease are often fatal (18). Patel and Arora have reported that a range of both benign and potentially lethal conditions are commonly confused with aortic dissections and may not be considered in the initial differential diagnosis in as many as 39% of cases (8). It has also reported that 30% of acute aortic dissection was initially misdiagnosed
and distracting physicians’ attention to other lethal diseases because aortic dissection’s clinical signs and symptoms are diverse and overlap with a broad high risk of conditions (23– 26). Our data showed a total of 31 patients who died of clinically unrecognized acute aortic dissection, including 26 misdiagnosed patients with acute myocardial infarction (9 cases), coronary artery disease (6 cases), cholecystitis (4 cases), acute gastroenteritis (3 cases), renal/urinary lithiasis (3 cases), and stroke (1 case). Clinically, acute aortic dissection is difficult to accurately distinguish from conditions such as acute coronary artery syndrome, pericarditis, pulmonary thromboembolism, or even cholecystitis/pancreatitis. Survival rate is directly related to prompt diagnosis and precise treatment. Typical symptom of acute aortic dissection is sudden chest to back pain, which is present in 75% of patient (27). But this typical symptom can either be masked in the presence of neurological symptoms or even misinterpreted (28). In our study, one patient presented obvious neurologic manifestations including hemiplegic paralysis and was diagnosed as stroke. Autopsy examination, however, revealed that the patient had ruptured aortic dissection with luminal thrombus formation. In addition, a focal fresh infarct was noted in the patient’s brain and kidney. It is believed that the thrombus in the aortic dissection formed thromboemboli which caused infarcts in the brain and kidney. Chest radiography and electrocardiography may provide the first clues of aortic dissection. The widened mediastinum or abnormal aortic contour is a frequent finding in acute aortic
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JOURNAL OF FORENSIC SCIENCES TABLE 5––Autopsy findings.
Heart weights (g) ≤400 >400 Diameter of aortic root (mm) ≤40 >40 Hemorrhage Mediastinum Pleural cavity Pericardial cavity Location of the entry site Ascending aorta Arch of aorta Descending aorta Location of the exit site Ascending aorta Arch of aorta Descending aorta Thrombus in false lumen ≤50%* >50% Microscopic findings Atherosclerosis Decrease and fracture of elastic fibers Medial mucinous degeneration
p Value, Type A vs. B
Total Cases No.(%)
Type A, No.(%)
Type B, No.(%)
8 (25.8) 23 (74.2)
478 72 3 (12.5) 21 (87.5) 42.54 8
402 74 5 (71.4) 2 (28.6) 33.71 5
0.04 0.006
9 (37.5) 15 (62.5)
6 (85.7) 1 (14.3)
0.037
3 (9.7) 1 (3.2) 28 (90.3)
3 (12.5) 0 (0.0) 22 (91.7)
0 (0.0) 1 (14.3) 6 (85.7)
0.33 NA 0.9
20 (64.5) 8 (25.8) 3 (9.7)
16 (66.7) 8 (33.3) 1 (4.1)
4 (57.1) 0 (0) 2 (28.6)
0.09
24 (77.4) 4 (12.9) 3 (9.7)
21 (87.5) 2 (8.3) 1 (4.1)
3 (42.9) 2 (28.6) 2 (28.6)
0.1
18 (58.1) 13 (41.9)
15 (62.5) 9 (37.5)
3 (42.9) 4 (57.1)
0.357
26 (83.9) 9 (29)
21 (87.5) 6 (25)
5 (71.4) 3 (42.9)
0.39 0.36
2 (6.5)
2 (8.3)
0 (0.0)
0.43
dissection patients. The ECG can also exhibit ST-segment change, suggesting acute aortic dissection (29). However, chest X-ray and ECG have a low sensitivity and specificity in diagnosing an acute aortic dissection. Biomarkers may provide the first clue for physicians to diagnose aortic dissection. Using D-dimer as a positive biomarker for aortic dissection diagnosis has been suggested in several studies (29–32). The elevated D-dimer may help physicians considering the possibility of acute aortic dissection. The D-dimer, however, may not always elevate in patients with acute aortic dissection if there is a lack of communication between true and false lumen (33,34). In our study, 23 patients had recorded Ddimer test. Of the 23 patients, only 9 showed elevated D-dimer. The negative D-dimer levels gave a false-negative result for physicians to rule out the acute aortic dissection, which lead to a devastating effect on the outcomes of treatments. Our data indicate the likelihood of negative D-dimer in acute aortic dissection cannot be overlooked. The other biomarker, such as smoothmuscle myosin heavy-chain protein (35,36), shows diagnostic assurance to some extent, but its use as a recommendation to confirm aortic dissection is yet to be fully accepted due to lack of large prospective studies. CT and MRI are high sensitive tools for correct diagnosis of aortic dissection (37,38). However, the use of CT and MRI usually is usually delayed or not ordered because they are time-consuming. In our study, CT scan or MRI was not performed in all the 31 cases. A high index of clinical suspicion is required, and a CT or MRI scan should be undertaken as soon as possible in cases of suspected aortic dissection. Conclusion Acute aortic dissection can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. A high index of clinical suspicion, rapid patient evaluation, and initiation of prompt
0.008
treatment are essential for survival of acute aortic dissection patients. Authors believe that the lack of high suspicious index, the absence of rapid, efficient and appropriate clinical evaluation, and atypical onset with a short time window prior to death are the key elements for the missed diagnosis of acute aortic dissection. The medicolegal issues surrounding missed diagnosis of acute aortic dissection remain significant in China. Forensic autopsy examination is often requested by family members when a patient’s clinical diagnosis is in question. The medicolegal death investigation can help physicians have a better understanding of acute aortic dissection. While diagnosis and therapeutic considerations of aortic dissection predominate clinical medicine, forensic pathologist may find themselves in the unique position of reporting genetic implications to the family of the decedent, as familial association of thoracic aortic dissection is known. Acknowledgment Funded by the Council of National Natural Science Foundation of China (No.81072509 & 81273335). References 1. Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000;283(7):897–903. 2. Tsai TT, Trimarchi S, Nienaber CA. Acute aortic dissection: perspectives from the International Registry of Acute Aortic Dissection (IRAD). Eur J Vasc Endovasc Surg 2009;37(2):149–59. 3. Clouse WD, Hallett JW Jr, Schaff HV, Spittell PC, Rowland CM, Ilstrup DM, et al. Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 2004;79 (2):176–80. 4. Fann JI, Smith JA, Miller DC, Mitchell RS, Moore KA, Grunkemeier G, et al. Surgical management of aortic dissection during a 30-year period. Circulation 1995;9(Suppl):II113–21.
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24. Hansen MS, Nogareda GJ, Hutchison SJ. Frequency of and inappropriate treatment of misdiagnosis of acute aortic dissection. Am J Cardiol 2007;99(6):852–6. 25. Spittell PC, Spittell JA Jr, Joyce JW, Tajik AJ, Edwards WD, Schaff HV, et al. Clinical features and differential diagnosis of aortic dissection: experience with 236 cases (1980 through 1990). Mayo Clin Proc 1993;68(7):642–51. 26. Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: part II: therapeutic management and follow-up. Circulation 2003;108(6):772–8. 27. Pineault J, Ouimet D, Pichette V, Vallee M. A case of an aortic dissection in a young adult: a refresher of the literature of this “great masquerader”. Int J Gen Med 2011;4:889–93. 28. Perry SM, Conley JW. Dissecting aortic aneurysm with bizarre neurologic and vascular aspects. Calif Med 1951;74(6):434–5. 29. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010;122(2):184–8. 30. Akutsu K, Sato N, Yamamoto T, Morita N, Takagi H, Fujita N, et al. A rapid bedside D-dimer assay (cardiac D-dimer) for screening of clinically suspected acute aortic dissection. Circ J 2005;69(4):397–403. 31. Marill KA. Serum D-dimer is a sensitive test for the detection of acute aortic dissection: a pooled meta-analysis. J Emerg Med 2008;34(4):367– 76. 32. Sodeck G, Domanovits H, Schillinger M, Ehrlich MP, Endler G, Herkner H, et al. D-dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. Eur Heart J 2007;28(24):3067– 75. 33. Paparella D, Malvindi PG, Scrascia G, de Ceglia D, Rotunno C, Tunzi F, et al. D-dimers are not always elevated in patients with acute aortic dissection. J Cardiovasc Med (Hagerstown) 2009;10(2):212–4. 34. Suzuki T, Distante A, Zizza A, Trimarchi S, Villani M, Salerno Uriarte JA, et al. Diagnosis of acute aortic dissection by D-dimer: the International Registry of Acute Aortic Dissection Substudy on Biomarkers (IRAD-Bio) experience. Circulation 2009;119(20):2702–7. 35. Suzuki T, Katoh H, Watanabe M, Kurabayashi M, Hiramori K, Hori S, et al. Novel biochemical diagnostic method for aortic dissection. Results of a prospective study using an immunoassay of smooth muscle myosin heavy chain. Circulation 1996;93(6):1244–9. 36. Suzuki T, Katoh H, Tsuchio Y, Hasegawa A, Kurabayashi M, Ohira A, et al. Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study. Ann Intern Med 2000;133(7):537–41. 37. Nienaber CA, von Kodolitsch Y, Nicolas V, Siglow V, Piepho A, Brockhoff C, et al. The diagnosis of thoracic aortic dissection by noninvasive imaging procedures. N Engl J Med 1993;328(1):1–9. 38. Shiga T, Wajima Z, Apfel CC, Inoue T, Ohe Y. Diagnostic accuracy of transesophageal echocardiography, helical computed tomography, and magnetic resonance imaging for suspected thoracic aortic dissection: systematic review and meta-analysis. Arch Intern Med 2006;166(13):1350–6. Additional information and reprint requests: Zhenyuan Wang, Ph.D. School of Forensic Science and Medicine Xi’an Jiaotong University No.76 Yanta West Road, Yanta District Xi’an, Shaanxi, 710061 China E-mail: [email protected]
PAPER PATHOLOGY/BIOLOGY
Yang Li,1 Ph.D.; Ling Li,2 M.D.; Hong-Shu Mu,3 M.D.; Shuan-Liang Fan,1 Ph.D.; Fang-Gang He,2 Ph.D.; and Zhen-Yuan Wang,1 Ph.D.
Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31 Forensic Autopsy Cases
ABSTRACT: Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospec-
tive study of 31 sudden unexpected deaths caused by AAD was conducted at Xi’an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female = 6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.
KEYWORDS: forensic science, forensic autopsy, aortic dissection, sudden death, medical tangle, medicolegal investigation Acute aortic dissection, a serious life-threatening medical emergency was first recognized in 1600s (1,2), has been studied for decades. Although the clinical diagnosis and treatment of this devastating disease has been greatly improved in the past two decades (3–5), deaths from acute aortic dissection due to missed diagnosis or misdiagnosis is still a major health concern because of poor recognition of this great “masquerader” by physicians in China. Our institute has investigated a total of 31 medical malpractice litigation cases related to deaths due to missed diagnosis or misdiagnosis of aortic dissection from 2001 to 2012. We present this article to show that a forensic autopsy is not only essential for the determination of cause of death in sudden death cases but can also help physicians have a better understanding of acute aortic dissection in their practice. In addition, the literature is reviewed, and pathogenesis, clinical presentations, and detailed forensic autopsy findings are discussed.
Materials and Methods Data Selection and Collection A retrospective study of forensic autopsy cases at the Medicolegal Center of Xi’an Jiaotong University (MC-XJU) was conducted. A total of 31 sudden unexpected deaths caused by aortic 1 School of Forensic Medicine, Xi’an Jiaotong University, Shaanxi, 710061, China. 2 Office of the Chief Medical Examiner, 900 West Baltimore Street, Baltimore, MD 21223. 3 Xian’yang Wei-cheng Public Security Bureau, Shaanxi, 712000, China. Received 20 April 2014; and in revised form 14 July 2014; accepted 18 July 2014.
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dissection were collected for the study over a 12-year period between 2001 and 2012. Deaths due to traumatic and iatrogenic aortic dissection were excluded. In all the study cases, scene investigation reports, medical history, and autopsy findings were reviewed. Stanford classification was used to divide the aortic dissection into two groups depending on whether the ascending aorta was involved: Dissections involving the ascending aorta proximal to the brachiocephalic artery were termed type A (see Fig. 1), whereas those not involving the ascending aorta were referred to as type B dissections (type B without ascending aorta involvement) (see Fig. 2). All the procedures followed were in accordance with the ethical standards of Xi’an Jiaotong University. Statistical Analysis All continuous data were present as mean SD. Univariate analyses were used to calculate proportion, distribution of demographic variables among the cases. Pearson’s chi-square test and Fisher’s exact test were used to evaluate the statistical significance of frequency distributions of two types of aortic dissection. Unpaired Student’s t-test was used to compare mean values between two groups. A measure probability value of p < 0.05 was considered significant. Statistical evaluation was carried out by SPSS 16.0 software (IBM, Chicago IL, USA).
Results Demographics The general demographic characteristics of the 31 cases were summarized in Table 1. With regard to gender, 27 cases (87.1%) were male, with male to female ratio = 6.7:1. Of the 31 cases, 24 deaths © 2015 American Academy of Forensic Sciences
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The detailed clinical presentation and physical examination findings were recorded in 23 of the 31 cases (Table 4). Data presented in Table 4 showed positive findings in clinical examinations. A total of 26 ECG reports were recorded with abnormalities: nine cases with ST-segment elevation, 5 with ST-segment depression, 2 with pathological Q wave, 2 with arrhythmia, and one with hypertrophy. Only 2 of 31 patients had an X-ray image. Abdominal ultrasound was performed on 14 cases, of which 4 showed cholelithiasis and 3 showed renal/urinary calculi. Fifteen cases had serological/biochemical tests. Of the 15 cases, 10 had elevated CK-MB level and 9 had elevated D-dimer level. Autopsy Findings
FIG. 1––Forensic autopsy of type A aortic dissection photograph of a heart and an autopsied aorta of a decedent with type A aortic dissection: a false lumen formed from the aortic root (arrow).
FIG. 2––Forensic autopsy of type B aortic dissection photograph of an aorta of a decedent with type B aortic dissection: the entry tear at the proximal of the descending aorta with a 1.0 cm dissection (ellipse-shaped dashed line); a false lumen (arrow); atherosclerotic spots in the intima of the aorta (rectangle-shaped dashed line).
(77.4%) were due to type A dissection. Overall, the age distribution of aortic dissection ranged from 20 to 64 years, with a mean age of 44.2 years. The mean ages of decedents with type A and type B aortic dissection were about the same with type A = 44.4 years and type B = 43.6 years (p > 0.05). Nineteen cases (61.3%) were under the age of 50 years old. Of the 31 cases, type A aortic dissection occurred in individuals with body mass index (BMI) of 26.68 1.7 and type B aortic dissection with BMI of 26.95 1.27. Clinical History and Presentation Analysis of data revealed 17 cases (54.8%) had onset symptoms occurring in the morning hours between 0600 and 1200 (Table 2). Sixteen of 31 cases (51.6%) occurred in the winter. Table 3 shows that of the 31 cases, 26 patients were clinically misdiagnosed with acute myocardial infarction (9 cases), coronary artery disease (6 cases), cholecystitis (4 cases), acute gastroenteritis (3 cases), renal/urinary calculi (3 cases), and acute pancreatitis (1 case). The other five patients died in a short time window without an identified clinical diagnosis. Among the 26 misdiagnosed cases, 22 cases were type A aortic dissection (84.6%) and 4 cases (15.4%) were type B aortic dissection (p < 0.05).
Autopsy findings are summarized in Table 5. Overall, the heart weights ranged from 342 g to 640 g with an average of 460.8 78.7 g. Of the 31 cases, individuals with type A aortic dissection had a larger heart (478 72 g) than those with type B aortic dissection (402 74 g, p = 0.04). Moreover, 21 of 24 cases (87.5%) with type A aortic dissection had heart weight more than 400 g compared to only 2 individuals (28.6%) with type B aortic dissection who had heart weight more than 400 g. The aortic root diameter was measured at the level of sinuses of Valsalva. In this study, aortic root was considered dilated when its diameter at the sinuses of Valsalva exceeded 4.0 cm in both women and men (6,7). The average dimension of individuals with type A aortic dissection was greater than those of individuals with type B aortic dissection (42.54 8 mm vs. 33.71 5 mm, p < 0.01). Of the 24 type A aortic dissection cases, 15 (62.5%) had aortic root diameter >4.0 cm while only 1 of the 7 (14.3%) type B aortic dissection cases had aortic root diameter >4.0 cm. Cardiac tamponade due to a rupture of the dissected channel into the pericardial sac was the most frequent cause of death (28 cases, 90.3%). Twenty cases had entry sites of dissection found in the ascending aorta, whereas the entry site in the arch of aorta was found in eight cases, all of which were confirmed with a type A dissection. Only in four cases, an entry tear was found in descending aorta, including one case with a type A dissection. The exit sites in the adventitia of the aorta were also identified. There were 24 cases with an exit tear found in the ascending aorta. Four cases had an exit tear in the arch of aorta, including 2 type A dissection cases with descending aorta involved. Three cases had an exit tear in the descending aorta, with 1 type A dissection case. There were 18 (58.1%) cases in which the thrombus took less than 50% space of the false lumen (15 cases with type A aortic dissection versus three cases with type B aortic dissection) and 13 (41.9%) cases with more than half of the false lumen filled by thrombus, including 9 type A aortic dissection cases and 4 type B aortic dissection cases. Microscopic examination was performed on all the 31 cases. Of the 31 cases, moderate atherosclerosis was found in 26 cases (83.9%), in the coronary arteries and in the aorta near the intimal tears. There were 9 cases (29.0%) that had decreased and fragmented elastic fibers in the media of the aorta. The medial cystic degeneration was confirmed in only two cases, both of which were type A dissection. Discussion Aortic dissection is a catastrophic cardiovascular disease, which is associated with high mortality if undiagnosed and untreated. The aortic dissection mortality rate is still high with
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JOURNAL OF FORENSIC SCIENCES TABLE 1––Demographic characteristics.* Dissection Type A & B (n = 31) No. (%)
Age distribution 14–29 30–39 40–49 50–59 60–69 Sex Male Female Age [Mean SD] Body mass index (BMI†)
6 3 10 9 3
Type A (n = 24) No (%)
(19.4) (9.7) (32.1) (29) (9.7)
5 1 9 6 3
27 (87.1) 4 (12.9) 44.23 12.21 26.74 1.6
(20.8) (4.2) (37.5) (25) (12.5)
21 (87.5) 3 (12.5) 44.42 12.79 26.68 1.7
Type B (n = 7) No. (%) 1 2 1 3 0
(14.3) (28.6) (14.3) (42.9) (0.0)
6 (85.7) 1 (14.3) 43.57 10.80 26.95 1.27
p Value
0.233
0.901 0.8744 0.708
*Age and BMI were compared by student’s t test, all other data were compared by Pearson’s chi-square test. BMI: weight in kilograms divided by height in meters squared.
†
TABLE 2––Clinical history and presentations. Total Cases (n = 31) No (%)
Type A (n = 24) No.(%)
The time of onset 0000–0600 5 (16.1) 0600–1200 17 (54.8) 1200–1800 5 (16.1) 1800–2400 4 (13.0) The season Spring 4 (13.0) Summer 3 (9.7) Autumn 8 (25.8) Winter 16 (51.6)
Type B (n = 7) No.(%)
p Value
5 12 4 3
(20.8) (50) (16.7) (12.5)
0 5 1 1
(0.0) (71.4) (14.3) (14.3)
0.563
3 3 7 11
(12.5) (12.5) (29.2) (45.8)
1 0 1 5
(14.3) (0.0) (14.3) (71.4)
0.365
TABLE 3––Clinical misdiagnosed cases.
Clinical Diagnoses Total cases Coronary artery disease Acute myocardial infarction Acute gastroenteritis Stroke Renal/urinary lithiasis Cholecystitis
Total Cases
Type A, No. (%)
Type B, No. (%)
26 6 9
22 (84.6) 6 (27.3) 8 (36.4)
4 (15.4) 0 (0) 1 (25)
0.03
1 0 1 1
0.674
3 1 3 4
2 1 2 3
(9.1) (4.5) (9.1) (13.6)
(25) (0) (25) (25)
p Value
an increase of 1–2% per hour despite of advancements in diagnostic and therapeutic modalities. The aim of the clinical or medicolegal measurements is to lower the mortality of this deadly disease. Several risk factors such as hypertension, atherosclerosis, Marfan syndrome, bicuspid aortic valve, male gender, advanced age have been reported to be associated with acute aortic dissection (6–9). In patients with characteristics of inherited diseases or having classical clinical signs and symptoms, the aortic dissection can be recognized directly and easily (10). However, some patients may have nonspecific clinical symptoms or a rapid deterioration. The clinical diagnosis of aortic dissection could be missed or misdiagnosed. In such cases, the diagnosis of aortic dissection was usually made after death during forensic autopsy examination. In any sudden unexpected death, an autopsy examination is necessary to determine the cause of death. In cases of medical
tangle or medical malpractice litigation, forensic investigation is imperative not only to determine the exact cause of death but also to clarify the relation among the variables of direct cause of death, contributory factor(s) or underlying cause(s) of death, and medical intervention. According to the data from the International Registry of Acute Aortic Dissection, males are a greater proportion (66.7%) of patients suffering aortic dissection (1). Our data also indicated 87.1% cases were male. There was no significant difference between the mean ages of patients with type A dissection (44.42 12.79 years) or type B (43.57y 10.8) dissection in our study, but the proportion of the cases with the age under 50 years was higher (63.3%) than those whose age was more than 50 years (36.7%). The onset of the acute aortic dissection was exhibited in a chronobiological fashion. Mehta et al. reported that the frequency of the complication of aortic dissection was significantly increased during the time from 0600 to 1200 (11). Manfredini et al. also has reported that a relatively high mortality incidence of aortic dissection occurred during early hour of the morning (12). Furthermore, there were two peaks, in later winter and autumn. In this report, we uncovered that 54.8% of patients had an onset in the morning, and more than 50% cases occurred in the winter. It is well recognized that the heart weights can be used as collaborative evidence of hypertension and other cardiac diseases, such as atherosclerotic cardiovascular disease, valvular heart diseases, and cardiomyopathy (13–17). Bailey, Duflou, and Puranik have found that aortic atherosclerosis and hypertension were the major modifiable risk factors for aortic dissection (18). Our study showed 23 of 31 cases (74.2%) had cardiomegaly, which could be a collaborative evidence of hypertension. The cardiomegaly is diagnosed if the heart weight is >95% confidence interval for body height and weight based on the Mayo Clinic criteria (19). In the current study, patients with type A aortic dissection were much more likely having cardiomegaly than the patients with type B aortic dissection. According to the 2010 Guidelines on Thoracic Aortic Disease, genetic syndromes such as Marfan syndrome, Loeys–Dietz syndrome, Ehlers–Danlos syndrome type IV, Turner syndrome, and familial thoracic aortic aneurysms and dissections (TAAD), are strongly associated with the formation of aortic dissection (15). Although in our study, only one case was diagnosed with Marfan syndrome, investigation of blood relatives, especially in
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TABLE 4––Clinical presentations of misdiagnosed cases.
Category Described symptoms Any pain described Abrupt onset Abdominal pain Chest pain Throat pain Headache Radiating/migrating Chest distress/short breath Neurological symptoms Hematemesis Abdominal distension feeling Blood pressure Hypertension ((SBP≧120 mmHg) Normotension (SBP80-120 mmHg) Hypotension ((SBP ≤80 mmHg) Laboratory examination ECG ST-segment elevation ST-segment depression Pathological Q wave Arrhythmia Hypertrophy Abdominal type B ultrasound Cholelithiasis Renal/urinary calculi Serological/biochemical test Elevated CK-MB Elevated D-dimers* Imaging test (X-ray) Absence/none performed
Recorded Cases (23) No.(%) 21 17 9 4 3 1 7 3 2 2 2
(91.3) (73.9) (39.1) (17.4) (13.0) (4.3) (30.4) (13.0) (8.7) (8.7) (8.7)
Type A (19), No.(%) 17 13 6 3 3 1 6 3 2 2 2
(89.5) (68.4) (31.6) (15.8) (15.8) (5.3) (31.6) (15.8) (10.5) (10.5) (10.5)
Type B (4), No. (%) 4 4 3 1 0 0 1 0 0 0 0
(100) (100) (75) (25) (0) (0) (25) (0) (0) (0) (0)
6 (26.1)
5 (26.3)
1 (25)
12 (52.2)
10 (52.6)
2 (50)
5 (21.7)
4 (21.1)
1 (25)
21 9 5 2 2 4 14 4 3 15 10 9 2 4
(91.3) (39.1) (21.7) (8.7) (8.7) (17.4) (60.9) (17.4) (13) (65.2) (43.5) (39.1) (8.7) (17.4)
18 8 5 2 1 4 11 3 1 12 9 9 2 4
(94.7) (42.1) (26.3) (10.5) (5.3) (21.1) (57.9) (15.8) (5.3) (63.2) (47.4) (47.4) (10.5) (21.0)
3 1 0 0 1 0 3 1 2 3 1 0 0 0
(75) (25) (0) (0) (25) (0) (75) (25) (50) (75) (25) (0) (0) (0)
p Value, Type A vs. B 0.7 0.3 0.1 0.7 0.6 0.9 0.8 0.6 0.7 0.7 0.7
0.9
0.8
0.6 0.7 0.7 0.5
ECG, electrocardiography; SBP, systolic blood pressure. *500 lg/L as cutoff line.
younger patients, those with aortic valve disease, and those with inherited disease should be considered by forensic pathologists. While diagnosis and therapeutic considerations of aortic dissection predominate clinical medicine, forensic pathologist may find themselves in the unique position of reporting genetic implications to the family of the decedent. We also recorded the interplay of thrombus and aortic dissection because the thrombus formed in the aortic dissection is significantly related to the accuracy of diagnosis. If the false lumen was occupied by thrombus completely, false or negative interpretation of the physical examination could be made so that patients might not be diagnosed promptly (20). On the other hand, the thrombus in aortic dissection could compress the true channel leading to death (21,22). According to our findings, 24 decedents with a type A aortic dissection had more thrombus in the false lumen than those in the false channel of the other seven cases with type B aortic dissection (58.3% vs. 42.9%), which suggested people suffering the type A aortic dissection have a higher possibility of thrombus formation in the dissection and a higher risk to suffer a sudden cardiac death. The diagnosis of aortic dissection remains clinically challenging and the outcomes from this disease are often fatal (18). Patel and Arora have reported that a range of both benign and potentially lethal conditions are commonly confused with aortic dissections and may not be considered in the initial differential diagnosis in as many as 39% of cases (8). It has also reported that 30% of acute aortic dissection was initially misdiagnosed
and distracting physicians’ attention to other lethal diseases because aortic dissection’s clinical signs and symptoms are diverse and overlap with a broad high risk of conditions (23– 26). Our data showed a total of 31 patients who died of clinically unrecognized acute aortic dissection, including 26 misdiagnosed patients with acute myocardial infarction (9 cases), coronary artery disease (6 cases), cholecystitis (4 cases), acute gastroenteritis (3 cases), renal/urinary lithiasis (3 cases), and stroke (1 case). Clinically, acute aortic dissection is difficult to accurately distinguish from conditions such as acute coronary artery syndrome, pericarditis, pulmonary thromboembolism, or even cholecystitis/pancreatitis. Survival rate is directly related to prompt diagnosis and precise treatment. Typical symptom of acute aortic dissection is sudden chest to back pain, which is present in 75% of patient (27). But this typical symptom can either be masked in the presence of neurological symptoms or even misinterpreted (28). In our study, one patient presented obvious neurologic manifestations including hemiplegic paralysis and was diagnosed as stroke. Autopsy examination, however, revealed that the patient had ruptured aortic dissection with luminal thrombus formation. In addition, a focal fresh infarct was noted in the patient’s brain and kidney. It is believed that the thrombus in the aortic dissection formed thromboemboli which caused infarcts in the brain and kidney. Chest radiography and electrocardiography may provide the first clues of aortic dissection. The widened mediastinum or abnormal aortic contour is a frequent finding in acute aortic
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JOURNAL OF FORENSIC SCIENCES TABLE 5––Autopsy findings.
Heart weights (g) ≤400 >400 Diameter of aortic root (mm) ≤40 >40 Hemorrhage Mediastinum Pleural cavity Pericardial cavity Location of the entry site Ascending aorta Arch of aorta Descending aorta Location of the exit site Ascending aorta Arch of aorta Descending aorta Thrombus in false lumen ≤50%* >50% Microscopic findings Atherosclerosis Decrease and fracture of elastic fibers Medial mucinous degeneration
p Value, Type A vs. B
Total Cases No.(%)
Type A, No.(%)
Type B, No.(%)
8 (25.8) 23 (74.2)
478 72 3 (12.5) 21 (87.5) 42.54 8
402 74 5 (71.4) 2 (28.6) 33.71 5
0.04 0.006
9 (37.5) 15 (62.5)
6 (85.7) 1 (14.3)
0.037
3 (9.7) 1 (3.2) 28 (90.3)
3 (12.5) 0 (0.0) 22 (91.7)
0 (0.0) 1 (14.3) 6 (85.7)
0.33 NA 0.9
20 (64.5) 8 (25.8) 3 (9.7)
16 (66.7) 8 (33.3) 1 (4.1)
4 (57.1) 0 (0) 2 (28.6)
0.09
24 (77.4) 4 (12.9) 3 (9.7)
21 (87.5) 2 (8.3) 1 (4.1)
3 (42.9) 2 (28.6) 2 (28.6)
0.1
18 (58.1) 13 (41.9)
15 (62.5) 9 (37.5)
3 (42.9) 4 (57.1)
0.357
26 (83.9) 9 (29)
21 (87.5) 6 (25)
5 (71.4) 3 (42.9)
0.39 0.36
2 (6.5)
2 (8.3)
0 (0.0)
0.43
dissection patients. The ECG can also exhibit ST-segment change, suggesting acute aortic dissection (29). However, chest X-ray and ECG have a low sensitivity and specificity in diagnosing an acute aortic dissection. Biomarkers may provide the first clue for physicians to diagnose aortic dissection. Using D-dimer as a positive biomarker for aortic dissection diagnosis has been suggested in several studies (29–32). The elevated D-dimer may help physicians considering the possibility of acute aortic dissection. The D-dimer, however, may not always elevate in patients with acute aortic dissection if there is a lack of communication between true and false lumen (33,34). In our study, 23 patients had recorded Ddimer test. Of the 23 patients, only 9 showed elevated D-dimer. The negative D-dimer levels gave a false-negative result for physicians to rule out the acute aortic dissection, which lead to a devastating effect on the outcomes of treatments. Our data indicate the likelihood of negative D-dimer in acute aortic dissection cannot be overlooked. The other biomarker, such as smoothmuscle myosin heavy-chain protein (35,36), shows diagnostic assurance to some extent, but its use as a recommendation to confirm aortic dissection is yet to be fully accepted due to lack of large prospective studies. CT and MRI are high sensitive tools for correct diagnosis of aortic dissection (37,38). However, the use of CT and MRI usually is usually delayed or not ordered because they are time-consuming. In our study, CT scan or MRI was not performed in all the 31 cases. A high index of clinical suspicion is required, and a CT or MRI scan should be undertaken as soon as possible in cases of suspected aortic dissection. Conclusion Acute aortic dissection can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. A high index of clinical suspicion, rapid patient evaluation, and initiation of prompt
0.008
treatment are essential for survival of acute aortic dissection patients. Authors believe that the lack of high suspicious index, the absence of rapid, efficient and appropriate clinical evaluation, and atypical onset with a short time window prior to death are the key elements for the missed diagnosis of acute aortic dissection. The medicolegal issues surrounding missed diagnosis of acute aortic dissection remain significant in China. Forensic autopsy examination is often requested by family members when a patient’s clinical diagnosis is in question. The medicolegal death investigation can help physicians have a better understanding of acute aortic dissection. While diagnosis and therapeutic considerations of aortic dissection predominate clinical medicine, forensic pathologist may find themselves in the unique position of reporting genetic implications to the family of the decedent, as familial association of thoracic aortic dissection is known. Acknowledgment Funded by the Council of National Natural Science Foundation of China (No.81072509 & 81273335). References 1. Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000;283(7):897–903. 2. Tsai TT, Trimarchi S, Nienaber CA. Acute aortic dissection: perspectives from the International Registry of Acute Aortic Dissection (IRAD). Eur J Vasc Endovasc Surg 2009;37(2):149–59. 3. Clouse WD, Hallett JW Jr, Schaff HV, Spittell PC, Rowland CM, Ilstrup DM, et al. Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 2004;79 (2):176–80. 4. Fann JI, Smith JA, Miller DC, Mitchell RS, Moore KA, Grunkemeier G, et al. Surgical management of aortic dissection during a 30-year period. Circulation 1995;9(Suppl):II113–21.
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