Download Mitral Stenosis at Autopsy - JOURNAL of the Louisiana State

Journal of the Louisiana State Medical Society
Pathology Image of the Month
Mitral Stenosis at Autopsy
Harry Porterfield, DO; Meaghen Ashby, MD;
William P. Newman, MD; and Robin McGoey, MD
A 52-year-old woman decedent was presented to the
hospital autopsy service for a coroner authorized complete
autopsy following an admit urine toxicology screen that
was positive for cannabinoids. Prior to admission, she
was found unresponsive at home after a two month history
of increasingly progressive shortness of breath. She was
transported to the emergency department and resuscitated
after prolonged arrest. She was then admitted to the
intensive care unit and subsequently was documented to
have significant anoxic brain injury. Care was withdrawn
by the family and death was declared on hospital day five.
Medical history was reported for type 2 diabetes
mellitus, and bipolar schizoaffective disorder with multiple
prior psychiatric admissions. Her medical record review
revealed a transthoracic echocardiogram two months prior
to admission that documented mild mitralregurgitation,
moderate mitral valve stenosis and a thickened valvular
and subvalvular mitral apparatus with restricted motion of
the posterior leaflet. Left atrial enlargement was marked,
left ventricular hypertrophy was moderate, and pulmonary
hypertension was graded as severe. The ejection fraction
was estimated at 70 percent. She was discharged with
outpatient follow-up to the cardiology department but was
noncompliant with recommendations.
At autopsy, the heart exam confirmed a markedly
dilated left atrial chamber with a slightly raised, broad
fibrous plaque along the atrial endocardial surface. The
mitral valve circumference was small at 8.0 cm (8.2-9.1cm)
and the leaflets were thickened. The mitral valve chordae
tendinae were notably short and thick with evident fusion at
multiple sites. A gross photo across the left atrioventricular
axis and mitral valve is seen in Figure 1. Additional findings
at autopsy included cardiomegaly at 720 gm (234-390
gm), bilateral pulmonary edema containing hemosiderin
laden macrophages, congestive hepatosplenomegaly
and plexogenic arteriopathy on pulmonary microscopic
examination.
Figure 1: The left atrioventricular view of the heart through the mitral
valve at autopsy showing left atrial dilatation, a left atrial endocardial
raised plaque, as well as short and thick chordae with chordal fusion.
What is the underlying clinical diagnosis
in this case and what is the most likely cause of death?
Answer is on p. 145
144 J La State Med Soc VOL 167 May/June 2015
Journal of the Louisiana State Medical Society
DIAGNOSIS:
Chronic rheumatic mitral
valvulitis and heart failure
DISCUSSION
Rheumatic heart disease (RHD) is the result of valvular
damage caused by an abnormal immune response to group
A streptococcal (GAS), Streptococcus pyogenes infection,
usually during childhood, and typically after pharyngitis.1
Although nearly eradicated in developed nations, RHD
continues to be a major health challenge in developing
nations where it remains the leading cause of heart failure
in children and young adults, accounting for approximately
250,000 deaths annually.2 Despite the potentially significant
morbidity and mortality associated with RHD and the
predicted rise in the number of people at risk for RHD
over the next 20 years, the disease draws little attention
from the medical community as evidenced by a paucity of
publications on the topic.1
GAS pharyngitis leads to acute rheumatic fever (ARF)
in less than 3 percent of cases. However, when it does
appear, it occurs within three weeks following the initial
infection.3 The incidence worldwide of ARF in children
between 5 and 14 years of age is reported to be 350,000 cases
annually; though some populations report endemic numbers
of cases.1,3 In 1944, Jones described the main clinical features
of ARF, which have subsequently been modified, revised
and expanded by the World Health Organization (WHO)4
into diagnostic criteria based on a variety of combinations
of clinical features, termed major and minor (Table).
Cardiac involvement has been documented in up to 50
percent of those diagnosed with ARF. The cardiac hallmark
of acute RF is mitral regurgitation of variable severity
and, in one series utilizing echocardiographic evaluation
of ARF, prolapse of the anterior leaflet.5,6 Pericarditis is
also common in ARF and can accompany the valvular
pathology. The valvulopathy of ARF can either resolve
or can progress into rheumatic heart disease (RHD) which
has recently been reported to affect nearly 20 million
people worldwide.1 The pathogenesis and risk factors for
progression are not widely understood though research does
suggest progression occurs more frequently in females.7
RHD may be diagnosed in an individual known to have
had prior ARF. Usually RHD is diagnosed in patients who
were previously asymptomatic or who cannot recall being
affected with ARF or GAS.
In the acute phase of RF, cardiac pathology reveals a
mixed inflammatory cell pancarditis involving the epi-,
myo- and endocardium. A nodular lesion, termed the
Aschoff body, may be identifiable microscopically within the
myocardium (mainly of the left atrium) or in the pericardium.
The Aschoff body, at its pathognomoic phase, is a fusiform
nodular aggregate of spindle shaped cells admixed with
Table: 2002-3002 WHO criteria for diagnosis of rheumatic fever and rheumatic heart disease (based on revised Jones Criteria)4
Diagnostic Categories
Criteria
Primary episode of RF
2 Major or
1 Majora and 2 Minorb plus evidence of
preceding GAS infectionc
Recurrent RF in patient without RHD
2 Majora or
1 Majora and 2 Minorb plus evidence of
preceding GAS infectionc
Recurrent RF in patient with RHD
2 Minorb plus evidence of preceding GAS infectionc
Chronic rheumatic valvulitis (patients presenting for
first time with pure mitral stenosis or mixed mitral valve
disease and/or aortic valve disease)
Do not require any other criteria to be
diagnosed as having RHD
a
Major Criteriaa: carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules
Minor Criteriab: clinical (fever, polyarthralgia), laboratory (elevated acute phase reactants)
Evidence of preceding GAS Infectionc: electrocardiogram (prolonged PR interval), elevated or rising antistreptolysin-O or other streptococcal antibody, or positive
throat culture or rapid antigen test for GAS, or recent scarlet fever
145 J La State Med Soc VOL 167 May/June 2015
Journal of the Louisiana State Medical Society
chronic inflammatory cells and fibroconnective tissue.
Larger mononuclear cells called Anitschkow cells may be
seen within the nodule and, on cut section, bear an owl-eye
appearance. Aschoff bodies, thought to be manifestations
of the inflammatory response to RF, regress and disappear
within 3-4 months. Grossly, cardiac pathology in the ARF
phase may also reveal a fibrinous pericarditis as well as
finely nodular, uniformly sized, verrucous, vegetations
along the lines of closure of, primarily, the mitral valve.8
Chronic RHD, either from repeated attacks of RF or
from progression of ARF takes on a strikingly different
histopathologic form; and mitral valvulopathy is the primary
problem. Gross features are characterized by mitral valve
stenosis due to commissural fusion, leaflet thickening and
subvalvular disease with shortened, thickened, and often
fused, chordae tendineae. From the left atrial projection, the
valve is said to take on a ‘fish mouth’ appearance. The aortic
valve also can show commissure fusion and calcification of
the cusps. The tricuspid and pulmonic valves are affected
less frequently. Further features can include dilatation
of the left atrial chamber and raised map-like plaques
(MacCallum patch) along the atrial endocardium due to
mitral regurgitation.8-10
The autopsy case presented here of a relatively young
female with a several month history of apparent heart failure
and recent echo diagnosis of mitral stenosis illustrates the
highly characteristic mitral valvulopathy of chronic RHD.
Further histopathologic examination of the raised left
atrial lesion demonstrated the characteristic features seen
in a MacCallum plaque, or mitral regurgitation jet lesion,
of bland, loose subendocardial fibrosis.10 The postmortem
diagnosis of RHD was, not surprisingly, made in this female
individual unbeknownst to have had prior ARF.
There is no specific nonsurgical treatment for RHD
other than for its complications including heart failure,
atrial fibrillation, ischemic embolic events and infective
endocarditis. Prevention strategies are postulated to be the
most sustainable method for disease control in developing
nations.1 Surveillance of RHD patients is most often via
echocardiography and clinical exam. The prognosis of RHD
largely relates to clinical progression of the valvulopathy
into left ventricular systolic dysfunction. Most often, the
mitral stenosis is indolent and slowly progressive with a
latency period as long as 20-40 years between initial infection
and onset of symptoms. However, rheumatic valvulopathy
progresses far more rapidly in developed countries such
as the US. Mortality in untreated RHD is most often
attributable to heart failure in 60-70 percent of patients.
It can also be vascular embolism in 20-40%; endocarditis
in 1-5%. If pulmonary hypertension is superimposed as
evidenced in the current case, the mean survival time falls to
less than three years.11 With no evidence of thromboemboli
or endocarditis in the current case along with the autopsy
findings of congestive splenomegaly and plexogenic
arteriopathy in the pulmonary vascular system coupled with
antemortem historical evidence of recent shortness of breath,
the decedent’s proximate cause of death was presumably
146 J La State Med Soc VOL 167 May/June 2015
heart failure due to chronic rheumatic mitral valvulopathy.
REFERENCES
1. Marijon E, Mirabel M, Celermajer DS, et al. Rheumatic heart disease.
Lancet. 2012;379:953-964.
2. Carapetis JR, Steer AC, Mulholland ED, et al. The global burden of
group A streptococcoal diseases. Lancet Infect Dis. 2005;5:685-694.
3. Essop MR and Peters F. Contemporary issues in rheumatic fever and
chronic rheumatic heart disease. Circulation. 2014;130:2181-2188.
4. WHO. Rheumatic Fever and Rheumatic Heart Disease: Report of a
WHO Expert Consultation. Geneva 29 Oct-1 Nov 2001. Geneva,
Switzerland: WHO; 2004.
5. Kinsley RH, Pocock WA. Rheumatic fever and rheumatic heart
disease.In: Barlow JB, ed. perspectives on the mitral valve.
Philadelphia, PA: FA Davis Company; 1987:227–245.
6. Marcus RH, Sareli P, Pocock WA, et al. Functional anatomy of severe
mitral regurgitation in active rheumatic carditis. Am J Cardiol.
1989;63:577–584.
7. Carapetis JR, Wolff DR, Currie BJ. Acute rheumatic fever and
rheumatic heart disease in the top end of Australia’s Northern
Territory. Med J Aust. 1996; 164: 146–149.
8. Burke AP. Pathology of rheumatic heart isease. Sep 9, 2013;
Available from: Medscape Reference [serial online]. Accessed
March 16, 2015. Available at http://emedicine.medscape.com/
article/1962779-overview#a1
9. Chopra P, Gulwani H. Pathology and pathogenesis of rheumatic
heart disease. Ind J Pathol Microbiol. 2007;50:685-697.
10. Shivakumarswamy U, Sinhasan SP, Purushotham R, et al.
MacCallum Plaque of the Heart: A Medicolegal Case. Heart
Views. 2010;11:71-73.
11. Ward C, Hancock BW. Extreme pulmonary hypertension caused
by mitral valve disease: natural history and results of surgery. Br
Heart Journal.1975;37:74–78.
All authors are affiliated with the Department of Pathology at Louisiana
State University School of Medicine in New Orleans. Dr. Porterfield
is a third year pathology resident, Dr. Ashby is a first year pathology
resident, Dr. Newman is a professor of pathology and Dr. McGoey
is an associate professor of athology and residency program director.
Acknowledgements: The authors would like to gratefully
acknowledge the support of the Orleans Parish Coroner’s Office for
providing the case material for this report.