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Bicuspid aortic and pulmonary valves complicated by acute aortic dissection in a highly trained athlete – Case report and review of the literature

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Abstract

Acute aortic dissection is typically seen in the middle aged and elderly population, the majority of the cases are related to systemic hypertension and atherogenic process. In contrast, aortic dissection-related deaths in the young are rare and are mainly associated with genetically based disorders and congenital cardiac anomalies. One of the most recognized congenital risk factors that predispose to aortic dissection is the bicuspid aortic valve. This report describes an illustrative case of acute aortic dissection in a 29-year-old athlete secondary to previously unrecognized congenital bicuspid aortic valve. Moreover, further cardiac autopsy disclosed bicuspid pulmonary valve -an exceedingly rare congenital valvular anomaly. The authors characterize and discuss, with emphasis on medicolegal approach, the mechanisms and interactions between these pathologic entities that led to the athlete's sudden unexpected death.
Rom J Leg Med [22] 167-172 [2014]
DOI: 10.4323/rjlm.2014.167
© 2014 Romanian Society of Legal Medicine
167
Bicuspid aortic and pulmonary valves complicated by acute aortic dissection
in a highly trained athlete – Case report and review of the literature
Martin Janík1,*, František Novomeský1, Lubomír Straka1, Jozef Krajčovič1, František Štuller1, Petr Hejna2
_________________________________________________________________________________________
Abstract: Acute aortic dissection is typically seen in the middle aged and elderly population, the majority of the cases are
related to systemic hypertension and atherogenic process. In contrast, aortic dissection-related deaths in the young are rare and
are mainly associated with genetically based disorders and congenital cardiac anomalies. One of the most recognized congenital
risk factors that predispose to aortic dissection is the bicuspid aortic valve. is report describes an illustrative case of acute aortic
dissection in a 29-year-old athlete secondary to previously unrecognized congenital bicuspid aortic valve. Moreover, further
cardiac autopsy disclosed bicuspid pulmonary valve - an exceedingly rare congenital valvular anomaly. e authors characterize
and discuss, with emphasis on medicolegal approach, the mechanisms and interactions between these pathologic entities that led
to the athletes sudden unexpected death.
Key Words: aortic dissection, bicuspid aortic valve, bicuspid pulmonary valve, athlete.
1) Institute of Forensic Medicine and Medicolegal Expertises, Jessenius Faculty of Medicine, Comenius University,
University Hospital, Martin, Slovak Republic
* Corresponding author: M.D., PhD., Institute of Forensic Medicine and Medicolegal Expertises, Jessenius Faculty of
Medicine, Comenius University, 036 59 Martin, Slovak Republic, EU, Tel. +042908902998, Fax +042434132770,
Email: janik.mato@gmail.com
2) Department of Forensic Medicine, Faculty of Medicine, Charles University and University Hospital, Hradec Kralove,
Czech Republic
Acute aortic dissection, in routine autopsy
caseloads, is typically seen in the middle aged
and elderly population. Most cases in the adult are related
to systemic hypertension and atherogenic process. In
contrast, aortic dissection-related deaths in the young are
rare, mainly associated with genetically based disorders
and hereditary genetic syndromes such as Marfan,
Ehlers-Danlos, Loeys-Dietz, or Turner syndromes [1–
4]. One of the most recognized congenital risk factors
that predispose to aortic dissection is the bicuspid (or
bileaet) aortic valve (BAV). Bicuspid aortic valve is
the most frequent congenital cardiac anomaly in adults,
aecting approximately 1% to 2% of the population, and
is responsible for more deaths and complications than
the combined eects of all the other congenital cardiac
defects [5, 6]. Bicuspid aortic valve is heritable and has
been shown to be genetically heterogeneous [7]. One of
the most common associated nding in cases of BAV
is proximal ascending aorta dilatation, called bicuspid
aortopathy, with increased risk of aortic dissection and
rupture [8]. Other well-recognized complications may
include aortic stenosis and regurgitation, or infective
endocarditis [9, 10]. According to a recent autopsy study
of congenital cardiac malformations, BAV was found in 24
out of 64 autopsied cases (37,5 %). Interestingly, there was
only one case of sudden death caused by aortic dissection
and no case of BAV-related infective endocarditis [11].
Bilateral congenitally bicuspid aortic and
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Janík M. et al Bicuspid aortic and pulmonary valves complicated by acute aortic dissection in a highly trained athlete
pulmonary valves are very rare and are found in
approximately 0.03% of the population and may be
associated with trisomy 18, tetralogy of Fallot, absent
conal septum, and coarctation of the aorta [12, 13].
In this paper, we present and discuss an
illustrative autopsy case of a sudden unexpected death in
a young athlete due to acute aortic dissection secondary to
previously undiagnosed bicuspid aortic valve. Moreover,
at cardiac autopsy we discovered bicuspid pulmonary
valve - an exceedingly rare congenital valvular anomaly.
CASE REPORT
A 29-year-old male presented with severe tearing
chest pain with immediate onset and collapsed suddenly
at work. He was unresponsive to resuscitation eorts and
was pronounced dead at the scene. Information obtained
prior to autopsy revealed that the decedent was a highly
trained triathlete. Additionally, he had complained
of progressive weakness and mild febrile illness for
the several days prior to death. His family history was
noncontributory.
Postmortem examination of the well-nourished
athletic male showed unremarkable external ndings
except for marks produced by the resuscitation procedure.
His height was 188 cm, and his weight was 90 kg.
Macroscopically, the lungs showed congestion and mild
edema with multiple, subpleural petechial hemorrhages.
Sectioning of the brain demonstrated diuse cerebral
swelling. Autopsy revealed no traumatic stigmata either
recent or remote. No pathological conditions or other
abnormalities were identied grossly in any visceral
organs except as described below. A comprehensive
blood and urine toxicologic assay was negative.
Cardiac autopsy
Upon opening an apparently enlarged
pericardium, approximately 970 mL of clotted and
nonclotted blood was collected within the pericardial
space. In situ inspection of the heart revealed full-thickness
rupture (measuring 3 x 2.5 cm) of the aortic aneurysm
with adjacent adventitial hemorrhage. On transverse
slices, the myocardium showed mildly hypertrophied
le ventricular walls, 2.4 cm in thickness (heart weight
435 g; dimensions 14 x 12 x 6.4 cm) and some dilatation
of the right ventricle with no infarctions either acute or
remote. Further dissection of the heart showed, directly
above the aortic opening, a wide, transversely oriented,
Figure 1. (A) bicuspid aortic valve with equal-sized leaets and two commissures (asterisks); an apparent intimal tear directly
above the aortic opening; (B) both coronary ostia arising from one sinus (asterisks); (C) bicuspid pulmonary valve with two
commissures (asterisks); (D) aneurysmatic dilatation of the ascending aorta (blue arrows).
A B
D
C
Romanian Journal of Legal Medicine Vol. XXII, No 3(2014)
169
T-shaped intimal tear (Fig. 1 A, B) with dissecting,
blood-lled channel extending peripherally to the
aortic arch (DeBakey I). At the level of 1.5 cm distally
from the above-described tear, dissection ruptured
externally into the pericardial sac. e aneurysmatic
ascending aorta measured 5.6 cm in diameter (Fig. 1 D).
Further examination of the aorta showed a localized
mild narrowing of the lumen of the aortic arch distal to
the origin of the le subclavian artery as well as patchy
orange brolipid atherosclerotic plaques. Dissection of
the valvular heart apparatus revealed both congenitally
bicuspid aortic and pulmonary valves (Fig. 1 A, C).
Equally-sized and shaped aortic cusps were apparently
enlarged, focally thickened, with two commissures and
no raphe between the undeveloped le and right coronary
cusps (Fig. 1 A, B).
e aortic valve circumference measured 7.9 cm.
ere was evidence of mild aortic valve insuciency.
Macroscopically, smooth, mildly edematous valvular
endocardium showed focal areas of yellowish brolipid
deposits. Both coronary ostia arose from one sinus,
distribution and dimensions were normal (Fig. 1 B). e
examination of the right ventricular outow tract revealed
the presence of the bicuspid pulmonary valve (Fig. 1 C).
e pulmonary leaets were equally-sized, thin, with two
commissures. e pulmonary valve circumference was
5.6 cm. No other congenital heart defects, valvular vitia,
or major vessels abnormalities were present.
Microscopic examination of the aortic leaet,
both periaortic and aortic perivalvular broadipose
tissue showed reactive inammatory process to the
dissection that had invaded into the adjacent aortic wall
(Fig. 2 A-C). Focal microcystic medial degeneration,
bers disorganization, and aortic intramural hematomas
were also identied (Fig. 2 D). Other cardiac structures or
aortic segments were not microscopically compromised.
e cause of death, based on the above-described
autopsy ndings, was massive hemopericardium
resulting from ruptured aortic dissection sustained as a
complication of bicuspid aortic valve.
DISCUSSION
e estimated incidence of aortic dissection has
been found to vary from 5 to 30 per million individuals per
year. From a morphological viewpoint, aortic dissection
is dened as the splitting of aortic wall between the outer
and middle portion of the tunica media either with or
A B
C D
Figure 2. (A) perivalvular tissue with acute reactive inammatory inltrate and focal hemorrhage (H&E, x10); (B) periaortic
adventitial tissue with acute inammatory process that invades into the adjacent aortic medial wall (H&E, x10); (C) dense
inammatory reaction to the dissection (H&E, x10); (D) aortic intramural hematoma (H&E, x10).
170
Janík M. et al Bicuspid aortic and pulmonary valves complicated by acute aortic dissection in a highly trained athlete
without intimal tear. e latter type of aortic dissection is
rarer and is called bloodless dissection [14, 15]. In both
types of aortic dissection, the process rarely involves the
whole circumference of the aorta.
In most cases, nevertheless, dissection of the
aorta originates and propagates owing to an intimal
tear. In such a scenario, blood from the aortic lumen
penetrates through the intimal tear into the vessel wall
and causes separation of layers of the tunica media. e
resulting spreading of dissection is possible owing to
the pulse-dependent pressure of bloodstream, either in
a backward or forward pattern. Dissection may re-enter
the aortic lumen, creating a “double-barrel” aorta or may,
through adventitial tear, give rise to hemopericardium,
hemothorax, or even hemoretroperitoneum.
Secondary dissection-associated complications
commonly include peripheral ischemia due to
obstruction/compression of aortic tributaries or severe
aortic regurgitation (the second most common cause
of death, aer aortic rupture in persons with aortic
dissections) [16].
Recently, Hostiuc et al. reported two cases of
aortic dissection associated with dissection and rupture
of the pulmonary artery [17].
Etiologically, several aortic wall-related diseases,
including atherosclerosis, systemic hypertension,
hereditary connective tissue diseases, syphilis, Erdheim-
Gsell cystic degeneration of media, and infective aortitis
are predispositions for the development of aortic
dissection or rupture [18, 19]. Additionally, cocaine and
amphetamine abuse, the pregnancy/postpartum period,
and iatrogenically related aortic wall injuries such as
cardiopulmonary resuscitation, catheter-based diagnostic
and therapeutic interventions have been recognized as a
precipitating factors of aortic wall dissection or rupture
[20–26]. Lastly, fatal aortic tear may occur in the setting
of congenital cardiac diseases with the most recognized
being bicuspid aortic valve and aortic coarctation [27].
e bicuspid valve is usually composed of two
unequally sized cusps, with the presence of a central
raphe that results from fusion of the commissures. e
morphological conguration of the bicuspid valve depends
on which commissures have fused. e most common
manifestation involves a fusion of the right and le cusps,
followed by fusion of the right and noncoronary cusps.
e least common pattern comprises fusion of the le
and noncoronary cusps. In rare instances, the leaets are
symmetrical and rapheless (as demonstrated in our case).
Although bicuspid aortic valve is primarily
a valvular disorder, it is important to realize that this
anomaly also plays a role in development of aortic wall
abnormalities, with aortic dilatation and risk of aortic
dissection with rupture. From a histopathological
viewpoint, brosis, elastin fragmentation, and cystic
degeneration of media have been found upon examination
of the aorta in persons who died of a dissecting aneurysm
[28, 29]. However, Larson and Edwards found a
prevalence of aortic medial degeneration in only 18%
of 161 persons with aortic dissections among 21,105
autopsies [30]. More specically, bicuspid valve studies
have reported structural abnormalities of thoracic aortic
tissue, including decreased brillin, elastin fragmentation,
matrix disruption, and apoptosis [10].
ough the mechanism of bicuspid semilunar
valves remains obscure, it is thought to originate
from an endocardial cushion defect which may be
due to abnormal cell migration, signaling pathways
and, lastly, by genetic predisposition (NOTCH1 gene)
[31]. More recent experimental studies have shown
that metalloprotease ADAMTS5 deciency blocks the
excavation of endocardial cushions during aortic and
pulmonary valve development [32].
Aortic dissection usually occurs at a younger age
and in previously asymptomatic persons with BAV. e
incidence of fatal aortic dissection in individuals with
BAV is approximately 5%, while the risk of dissection is
highest when the aortic diameter is more than 5 cm and
with concomitant systemic hypertension [33].
Besides the BAV-associated aortic stenosis/
insuciency, it is acknowledged that the aortic bicuspid
valve is a well-recognized substrate for bacterial
endocarditis, predominantly in children and young
adults. e valvular inammatory process is highly
destructive and may be associated with bacterial aortitis
as the bacterial elements invade into the aortic wall.
Approximately 10-30% of individuals with bicuspid
aortic valve develop endocarditis. Microbiologically, the
most frequent microorganisms are Staphylococcus spp.
and Streptococcus viridans. Saint-Martin et al. reported
a case, where a ruptured subaortic pseudoaneurysm
caused sudden death [34]. e decedent in that case
report had a history of bicuspid aortic valve with recent
Staphylococcal endocarditis.
While the bicuspid pulmonary valve is commonly
associated with other congenital heart diseases, isolated
bicuspid pulmonary valve is extremely rare, with less than
10 cases reported in the literature. e true incidence of
bicuspid pulmonary valve, however, remains unknown
perhaps due to fact that the clinical course is usually
benign [35]. Recently, Luk et al. reported autopsy case
of a 70-year-old man with bilateral congenitally bicuspid
aortic and pulmonary valves [36]. Both valves showed
multifocal nodular thickening and brosis. ere was
markedly greater dilatation of the pulmonary artery,
compared to the aorta, as well as an absence of symptoms.
A functionally normal bicuspid aortic valve is clinically
asymptomatic and does not usually represent a limitation
for physical activity. e stress of regular and intense
exercise on an abnormal aortic valve may, however,
accelerate the development of complications and sudden
Romanian Journal of Legal Medicine Vol. XXII, No 3(2014)
171
death is an appreciable risk, whether the individual
is symptomatic or asymptomatic [37]. erefore,
identifying and accurate staging of the bicuspid aortic
valve in athletes, through strict cardiological follow-up,
is of vital importance in order to prevent the potential
adverse consequences of training [38, 39]. Athletes with
bicuspid valve who develop aortic valve insuciency
and aortic dilatation should completely avoid vigorous
sporting activities, given the increased risk of aortic
rupture [37]. Furthermore, because the aortic dilatation
rate may signicantly dier between individual patients,
only specic follow-up measurements can determine
individual size-dependent aortic risk [8].
In the postmortem assessment, cardiac
imaging modalities such as computed tomography, CT
angiography, and MRI have proven to be benecial,
particularly in cases of suspected aortic dissection,
endocarditis, or myocardial infarction [40–42]. In
sudden cardiac deaths of young, previously healthy
individuals, detection of primary underlying pathology
may have tremendous implications for cardiologists,
genetic counselors and families such as aortic dissections
associated with congenital and genetically based
diseases. In such cases, conventional organ-by-organ
dissection, augumented with various ancillary laboratory
studies such as histopathology, imunohistochemitry,
microbiologic cultures, and molecular diagnostic
evaluation are warranted and highly recommended.
In summary, we have reported an illustrative
autopsy case of acute aortic dissection complicated by
massive hemopericardium in the setting of previously
unrecognized bicuspid aortic valve. Moreover, pathologic
ndings included mild le ventricular hypertrophy and
aortic coarctation, additional bicuspid aortic valve-related
comorbidities and precipitating factors in producing
aortic dissection and/or rupture. Apart from above
mentioned le-sided cardiac abnormalities, autopsy
showed an uncommon congenital bicuspid pulmonary
valve, although this nding did not play a role in the
mechanism of death.
References
1. Hirani R, Koszyca B, Byard RW. Marfan syndrome and sudden death within a family – Aetiologic, molecular and diagnostic issues at
autopsy. J Forensic Leg Med 2008;15:205–9.
2. Shields LB, Rolf CM, Davis GJ, Hunsaker 3rd JC. Sudden and unexpected death in three cases of Ehlers-Danlos syndrome type IV. J
Forensic Sci 2010;55:1641–5.
3. Power T, Langlois NE, Byard RW. e forensic implications of Turner´s syndrome. J Forensic Sci 2014; 59:671–5.
4. Ripperger T, Tröger HD, Schmidtke. e genetic message of a sudden, unexpected death due to thoracic aortic dissection. Forensic Sci Int
2009;187:1–5.
5. Homan JI, Kaplan S. e incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890–1900.
6. Verma S, Siu SC. Aortic dilatation in patients with bicuspid aortic valve. N Engl J Med 2014;370:1920–9 .
7. Cripe L, Andelnger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. J Am Coll Cardiol 2004;44:138–43.
8. Detaint D, Michelena HI, Nkomo VT, Vahanian A, Jondeau G, Sarano ME. Aortic dilatation patterns and rates in adults with bicuspid
aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy. Heart 2014;100:126–34.
9. Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol 2010;55:2789–2800.
10. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve.
Circulation 2002;106:900–4.
11. Hamilton LE, Lew EO, Matshes EW. "Grown-up" congenital heart disease and sudden death in a medical examiner's population. J Forensic
Sci 2011;56:1206–12.
12. Jashari R, Van Hoeck B, Gon Y, Vanderkelen A. e incidence of congenital bicuspid or bileaet and quadricuspid or quadrileaet
arterial valves in 3,861 donor hearts in the European Homogra Bank. J Heart Valve Dis 2009;18:337–44.
13. Sughimoto K, Nakano K, Gomi A, Nakatani H, Nakamura Y, Sato A. Pulmonary artery aneurysm with ascending aortic aneurysm
concomitant with bilateral bicuspid semilunar valves. Ann orac Surg 2006; 82:2270–2.
14. Schyma C, Hagemeier L, Madea B. Bloodless aortic dissection. Forensic Sci Med Pathol 2013;9:221–4.
15. Dettmeyer R, Schmidt P, Madea B. Two cases of unexpected sudden death due to cystic medionecrosis of the aorta associated with bloodless
aortic dissection. Forensic Sci Int 1998;94:161–6.
16. Khan AI, Nair CK. Clinical, diagnostic, and management perspectives of aortic dissection. Chest 2002;122:311–28.
17. Hostiuc S, Dermengiu D, Ceauşu M, Capatina CO, Luca L, Hostiuc M. Sudden death due to dissection of the thoracic aorta associated with
dissection and rupture of the pulmonary artery: report of two cases. Forensic Sci Int 2014;236:e9–13.
18. Tsokos M. Syphilitic aortic aneurysm rupture as cause of sudden death. Forensic Sci Med Pathol 2012;8:325–6.
19. Gary T, Seinost G, Hafner F, Gorkiewicz G, Brodmann M. Cystic medial necrosis Erdheim Gsell as a rare reason for spontaneous rupture
of the ascending aorta. Vasa 2011;40:147–9.
20. Palmiere C, Burkhardt S, Staub C, Hallenbarter M, Paolo Pizzolato G, Dettmeyer R, La Harpe R. oracic aortic dissection associated with
cocaine abuse. Forensic Sci Int 2004;141:137–42.
21. Monteiro FN, Bhagavath P, Rao L, Pai ND, Kanchan T, Menezes RG, Priyadarshini NA, Pradeep Kumar G. Descending thoracic aortic
aneurysm rupture during postpartum period. J Forensic Sci 2011;56:1054–7.
22. Srettabunjong S. Spontaneous rupture of acute ascending aortic dissection in a young pregnant woman: A sudden unexpected death.
Forensic Sci Int 2013;232:5–8.
23. Ventura F, Landolfa MC, Portunato F, De Stefano F. Sudden death due to aortic dissection in pregnancy: case report. Rom J Leg Med
2011;19:17–22.
172
Janík M. et al Bicuspid aortic and pulmonary valves complicated by acute aortic dissection in a highly trained athlete
24. Patterson RH, Burns WA, Jannotta FS. Complications of external cardiac resuscitation: a retrospective review and survey of the literature.
Med Ann Dist Columbia 1974;43:389–94.
25. Swalwell CI, Davis GG. Methamphetamine as a risk factor for acute aortic dissection. J Forensic Sci 1999;44:23–6.
26. Marella GL, Furnari C, Perfetti E, Arcudi G. Aortic dissection and cocaine use. J Forensic Leg Med 2011;18:329–31.
27. Lynch MJ, Woodford NW, Dodd MJ. Sudden death due to aortic rupture complicating undiagnosed coarctation of the aorta in a teenager
- a case report and review of the literature. J Forensic Leg Med 2008;15:443–6.
28. Bode-Jänisch S, Schmidt A, Günther D, Stuhrmann M, Fieguth A. Aortic dissecting aneurysms—histopathological ndings. Forensic Sci
Int 2012;214:13–7.
29. Dermengiu S, Ceausu M, Hostiuc S, Curca GC, Dermengiu D, Turculet C. Spontaneous aortic dissection due to cystic medial degeneration.
Report of a sudden case and literature review. Rom J Leg Med 2009;17:89–96.
30. Larson EW, Edwards WD. Risk factors for aortic dissection: a necropsy study of 161 cases. Am J Cardiol 1984;53:849–55.
31. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D. Mutations in NOTCH1 cause aortic valve
disease. Nature 2005;437:270–4.
32. Dupuis LE, Osinska H, Weinstein MB, Hinton RB, Kern CB. Insucient versican cleavage and Smad2 phosphorylation results in bicuspid
aortic and pulmonary valves. J Moll Cell Cardiol 2013;603:50–9.
33. Roberts CS, Roberts WC. Dissection of the aorta associated with congenital malformation of the aortic valve. J Am Coll Cardiol
1991;17:712–16.
34. Saint-Martin P, Rogers C, Carpenter E, Fishbein MC, Lau S, Sathyavagiswaran L. Subaortic pseudoaneurysm of the le ventricle
complicating staphylococcal endocarditis. J Forensic Sci 2009;54:930–2.
35. Mordi I, Tzemos N. Bicuspid aortic valve disease: a comprehensive review. Cardiol Res Pract 2012;196037.
36. Luk A, Morales K, Butany J. Bilateral congenitally bicuspid aortic and pulmonic valves: a rare entity. Cardiovasc Pathol 2013;22:27–8.
37. Sheppard MN. e ttest person in the morgue? Histopathology 2012;60:381–96.
38. DeMozzi P, Longo UG, Galanti G, Maulli N. Bicuspid aortic valve: a literature review and its impact on sport activity. Br Med Bull
2008;85:63–85.
39. Zeppilli F, Bianco M, Bria S, Palmieri V. Bicuspid aortic valve: an innocent nding or a potentially life-threatening anomaly whose
complications may be elicited by sports activity? J Cardiovasc Med (Hagerstown) 2006;7:282–7.
40. Filograna L, Hatch G, Ruder T, Ross SG, Bolliger SA, ali MJ. e role of post-mortem imaging in a case of sudden death due to ascending
aorta aneurysm rupture. Forensic Sci Int 2013;228:76–80.
41. Schwendener N, Mund M, Jackowski C. Type II DeBakey dissection with complete aortic rupture visualized by unenhanced postmortem
imaging. Forensic Sci Int 2013;225:67–70.
42. Jackowski C, Schweitzer W, ali M, Yen K, Aghayev E, Sonnenschein M, Vock P, Dirnhofer R. Virtopsy: postmortem imaging of the
human heart in situ using MSCT and MRI. Forensic Sci Int. 2005; 149:11–23.
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Bicuspid or bifoliate aortic valve (BAV) results in two rather than three cusps and occurs in 1-2% of the population placing them at higher risk of developing progressive aortic valve disease. Only NOTCH-1 has been linked to human BAV, and genetically modified mouse models of BAV are limited by low penetrance and additional malformations. Here we report that in the Adamts5(-/-) valves, collagen I, collagen III, and elastin were disrupted in the malformed hinge region that anchors the mature semilunar cusps and where versican, the ADAMTS5 proteoglycan substrate, accumulates. ADAMTS5 deficient prevalvular mesenchyme also exhibited a reduction of α-smooth muscle actin and filamin A suggesting versican cleavage may be involved in TGFβ signaling. Subsequent evaluation showed a significant decrease of pSmad2 in regions of prevalvular mesenchyme in Adamts5(-/-) valves. To test the hypothesis that ADAMTS5 versican cleavage is required, in part, to elicit Smad2 phosphorylation we further reduced Smad2 in Adamts5(-/-) mice through intergenetic cross. The Adamts5(-/-);Smad2(+/-) mice had highly penetrant BAV and bicuspid pulmonary valve (BPV) malformations as well as increased cusp and hinge size compared to the Adamts5(-/-) and control littermates. These studies demonstrate that semilunar cusp malformations (BAV and BPV) can arise from a failure to remodel the proteoglycan-rich provisional ECM. Specifically, faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. Further studies using the Adamts5(-/-);Smad2(+/-) mice with highly penetrant and isolated BAV, may lead to new pharmacological treatments for valve disease.
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Pregnancy is a well-known risk factor for aortic dissection and half of the cases reported in women under 40 years of age have been estimated to occur during pregnancy, usually during the third trimester. The authors present a case of unexpected maternal death due to acute aortic dissection in a woman at the 41st week of gestation with silent clinical history. In the case reported the patient had no previous medical history when she delivered her first full-term baby, neither connective congenital abnormalities nor other morbid states that could potentially cause cardiovascular accidents. The dissecting aneurysm was due to pregnancy. In this case, early diagnosis would have allowed early intervention which would have prevented the death of the patient, although she did not present a striking clinical situation. Under these circumstances, it is clearly of the utmost importance not to underestimate seemingly trivial symptoms that may conceal unexpected fatal clinical situations.
Article
The autopsy findings from two rare cases of sudden death concerning a 31- and a 44-year-old woman are reported. Autopsy and morphological examination revealed a dissection of the aorta but no rupture into the pericardial sac. In both cases mucoid deposits in all layers of the media and rarefication of the elastic fibers were found, rendering cystic medionecrosis as the cause of the aortic dissection. In these unusual cases, only a very small intimal tear was present, but no blood in the dissected aortic wall. Evidence of left ventricular hypertrophy and a history of hypertension were reported in both cases. No extension of the aortic dissections into the left or right coronary artery and no other clinical or pathological findings associated with aortic dissection were present. Cystic medionecrosis was the cause of the aortic dissection in these cases. The mechanism of death in both cases is discussed.
Article
BICUSPID AORTIC VALVE IS THE MOST COMMON CONGENITAL HEART DEFECT in adults, affecting 1.3% of the population worldwide, and is responsible for more deaths and complications than the combined effects of all the other congenital heart defects. 1,2 Although aortic stenosis and regurgitation are the most common complications of a bicuspid aortic valve, dilatation of any or all segments of the proximal aorta from the aortic root to the aortic arch, called bicuspid aortopathy, is also present in approximately 50% of affected persons.(1-4) Accumulating evidence suggests that the pattern of aortic dilatation in persons with a bicuspid aortic valve is diverse, possibly reflecting heterogeneity in molecular, rheologic, and clinical features.(4-9) This article provides a brief overview of the basic principles, recent advances, and recommendations for the treatment of adults with bicuspid aortopathy.
Article
Turner's syndrome, the most common sex chromosome disorder of females, is caused by complete or partial loss of one X chromosome and is associated with a wide range of internal and external manifestations and increased mortality rates (three to nine times the background population). While individuals with Turner's syndrome may survive for many decades, premature and unexpected deaths can occur that bring decedents to the attention of forensic examiners. Causes of death in Turner's syndrome are often linked to underlying cardiovascular conditions such as aortic dissection, congenital cardiovascular disease, ischemic heart, and cerebrovascular disease, but deaths due to noncardiac causes also occur with increased frequency. The latter include epilepsy, diabetes mellitus, chronic renal disease, pneumonia, chronic liver disease, and malignancy. Thus, the autopsy evaluation of these cases requires careful examination of all major organ systems, with the consideration of confirmatory cytogenetic testing.
Article
Acute aortic dissection (AAD) in pregnancy is a rare phenomenon. Usually, it occurs during the third trimester, resulting in a catastrophic outcome for both mother and fetus and thus requiring a high level of clinical suspicion and a prompt multidisciplinary approach. There have been numerous such reports published in clinical literatures, yet there is little documentation in forensic literatures. Nearly all the reported cases have been associated with underlying risk factors for aortic pathology, predominantly connective tissue disorders. The author reports a sudden unexpected death due to a ruptured AAD in a 32-year-old pregnant woman with no cardiovascular risk factors at 37 weeks' gestational age. The ascending aortic wall showed a longitudinal intimal tear measured 0.6cm in length and a longitudinal external tear measured 6cm in length. Pre-eclampsia superimposed on chronic hypertension was solely possible cause of ruptured AAD in this case. The present case not only illustrates the association of AAD and pregnancy with a resultant fetal-maternal death but also raises awareness of possible such cases.
"Bloodless aortic dissection" is a rare cause of sudden death due to an aortic dissection without intimal tears and with no blood present within the dissected aortic wall. The first case was described in 1993. Death was considered to be caused by acute myocardial ischemia from dissection involving the left coronary artery. Further cases have been described where death was thought to originate from increasing hypertension during progressive extension of the dissection followed by a sudden irritation of the subendothelially localized conduction system of the heart. The presented case involves a rapidly fatal aortic dissection in a 64 year old man without any intimal tears and no blood in the dissected aortic wall, although the dissection involved the entire aorta. Death was considered due to myocardial ischemia since the dissection had reached the aortic root and the origins of the coronary arteries.