Download Bicuspid aortic and pulmonary valves complicated by acute aortic

Rom J Leg Med [22] 167-172 [2014]
DOI: 10.4323/rjlm.2014.167
© 2014 Romanian Society of Legal Medicine 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. 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.
Key Words: aortic dissection, bicuspid aortic valve, bicuspid pulmonary valve, athlete.
A
cute 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
bileaflet) aortic valve (BAV). Bicuspid aortic valve is
the most frequent congenital cardiac anomaly in adults,
affecting approximately 1% to 2% of the population, and
is responsible for more deaths and complications than
the combined effects 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 finding 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
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: [email protected]
2) Department of Forensic Medicine, Faculty of Medicine, Charles University and University Hospital, Hradec Kralove,
Czech Republic
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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.
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 diffuse cerebral
swelling. Autopsy revealed no traumatic stigmata either
recent or remote. No pathological conditions or other
abnormalities were identified grossly in any visceral
organs except as described below. A comprehensive
blood and urine toxicologic assay was negative.
CASE REPORT
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
left 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,
A 29-year-old male presented with severe tearing
chest pain with immediate onset and collapsed suddenly
at work. He was unresponsive to resuscitation efforts 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 findings
A
B
D
C
Figure 1. (A) bicuspid aortic valve with equal-sized leaflets 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).
168
Romanian Journal of Legal Medicine T-shaped intimal tear (Fig. 1 A, B) with dissecting,
blood-filled 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. The 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 left subclavian artery as well as patchy
orange fibrolipid 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 left and right coronary
cusps (Fig. 1 A, B).
The aortic valve circumference measured 7.9 cm.
There was evidence of mild aortic valve insufficiency.
Macroscopically, smooth, mildly edematous valvular
endocardium showed focal areas of yellowish fibrolipid
deposits. Both coronary ostia arose from one sinus,
distribution and dimensions were normal (Fig. 1 B). The
examination of the right ventricular outflow tract revealed
the presence of the bicuspid pulmonary valve (Fig. 1 C).
Vol. XXII, No 3(2014)
The pulmonary leaflets were equally-sized, thin, with two
commissures. The 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 leaflet,
both periaortic and aortic perivalvular fibroadipose
tissue showed reactive inflammatory process to the
dissection that had invaded into the adjacent aortic wall
(Fig. 2 A-C). Focal microcystic medial degeneration,
fibers disorganization, and aortic intramural hematomas
were also identified (Fig. 2 D). Other cardiac structures or
aortic segments were not microscopically compromised.
The cause of death, based on the above-described
autopsy findings, was massive hemopericardium
resulting from ruptured aortic dissection sustained as a
complication of bicuspid aortic valve.
DISCUSSION
The 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 defined 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 inflammatory infiltrate and focal hemorrhage (H&E, x10); (B) periaortic
adventitial tissue with acute inflammatory process that invades into the adjacent aortic medial wall (H&E, x10); (C) dense
inflammatory reaction to the dissection (H&E, x10); (D) aortic intramural hematoma (H&E, x10).
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Janík M. et al
Bicuspid aortic and pulmonary valves complicated by acute aortic dissection in a highly trained athlete
without intimal tear. The 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. The
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, after 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, ErdheimGsell 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].
The bicuspid valve is usually composed of two
unequally sized cusps, with the presence of a central
raphe that results from fusion of the commissures. The
morphological configuration of the bicuspid valve depends
on which commissures have fused. The most common
manifestation involves a fusion of the right and left cusps,
followed by fusion of the right and noncoronary cusps.
The least common pattern comprises fusion of the left
and noncoronary cusps. In rare instances, the leaflets 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, fibrosis, elastin fragmentation, and cystic
degeneration of media have been found upon examination
170
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 specifically, bicuspid valve studies
have reported structural abnormalities of thoracic aortic
tissue, including decreased fibrillin, elastin fragmentation,
matrix disruption, and apoptosis [10].
Though 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 deficiency 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. The
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/
insufficiency, it is acknowledged that the aortic bicuspid
valve is a well-recognized substrate for bacterial
endocarditis, predominantly in children and young
adults. The valvular inflammatory 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]. The 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. The 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 fibrosis. There 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. The 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 death is an appreciable risk, whether the individual
is symptomatic or asymptomatic [37]. Therefore,
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 insufficiency
and aortic dilatation should completely avoid vigorous
sporting activities, given the increased risk of aortic
rupture [37]. Furthermore, because the aortic dilatation
rate may significantly differ between individual patients,
only specific 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 beneficial,
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
Vol. XXII, No 3(2014)
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
findings included mild left 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 left-sided cardiac abnormalities, autopsy
showed an uncommon congenital bicuspid pulmonary
valve, although this finding did not play a role in the
mechanism of death.
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