Download Occurrence of left-sided heart valve involvement before right

European Journal of Echocardiography (2011) 12, E18
doi:10.1093/ejechocard/jeq171
Occurrence of left-sided heart valve involvement
before right-sided heart valve involvement in
carcinoid heart disease
Vidyasagargoud Marupakula, Karyne L. Vinales, Mohammad Q. Najib,
Louis A. Lanza, Howard R. Lee, and Hari P. Chaliki *
Division of Cardiovascular Diseases and Division of Cardiovascular and Thoracic Surgery, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, 85259 AZ, USA
Received 28 September 2010; accepted after revision 3 November 2010; online publish-ahead-of-print 17 December 2010
Carcinoids are rare neuroendocrine tumours that occur primarily in the gastrointestinal tract. Carcinoid heart disease is characterized by
fibrous plaque deposition on the endocardial surface of the cardiac valves and chambers. It affects the right heart valves in 85% of cases
and the left heart valves in 15%. We present an unusual case of a patient with metastatic carcinoid heart disease in whom typical carcinoid
aortic and mitral valve lesions developed 2 years prior to the development of severe right-sided carcinoid valvular heart disease.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Aortic valve insufficiency † Carcinoid heart disease † Mitral valve
Introduction
Carcinoids are rare neuroendocrine tumours, with an incidence in
the general population of 1.2 –2.1/100 000.1 About 55% of primary
carcinoid tumours occur in the gastrointestinal tract, mostly in the
small intestine.2 The next most common sites are the rectum
(20%), appendix (16%), and colon (11%).3 Common sites of metastasis are the liver and regional lymph nodes, but the propensity of
carcinoid tumours to metastasize correlates mainly with the
primary tumour size and location.3
Carcinoid heart disease affects the right side of the heart in 85%
of patients, but left-sided involvement has been reported in up to
15% of patients.2,4 We present a case of carcinoid heart disease
that primarily involved the aortic and mitral valves 2 years
before the development of right-sided valvular disease.
Case report
A 76-year-old woman with no prior exposure to anorexigens who
had an established diagnosis of carcinoid disease from an external
institution presented with liver metastasis. She originally sought
treatment for diarrhoea and flushing and was found to have a
caecal mass that ultimately resulted in a diagnosis of carcinoid
disease. Subsequently, she underwent partial resection of the
distal small bowel and the proximal large bowel. One year later,
she had a total hysterectomy and bilateral salpingo-oophorectomy.
Over the next 10 years, her health was relatively good; then she
began losing weight and had increasing symptoms of diarrhoea
and fatigue. Further evaluation by computed tomography scans
of the abdomen and pelvis and an octreotide nuclear scan of the
patient revealed metastatic carcinoid tumours not only in the
liver but also in the pelvis and the head of the pancreas; the concentration of urinary 5-hydroxyindoleacetic acid (5-HIAA) was
38 mg/24 h. An echocardiogram showed preserved left and right
ventricular systolic function. However, the mitral valve was
thickened, with restriction of the posterior mitral valve leaflet
and minimal regurgitation but no stenosis (Figure 1A). The aortic
valve was also thickened, with slight doming of the right coronary
cusp during systole with mild regurgitation (Figure 1B and C, and
see Supplementary data online, Movie 1). Although the pulmonary
valve was not well visualized, Doppler imaging did not show any
pulmonary valve stenosis or regurgitation (Figure 2). The tricuspid
valve had minimal thickening without regurgitation (Figure 3 and
see Supplementary data online, Movie 2). Echocardiographic
imaging during agitated saline contrast injection confirmed the
existence of a patent foramen ovale.
Over the next 2 years, the patient experienced progressive shortness of breath, ascites, and marked deterioration in functional
capacity. Echocardiography showed normal left ventricular systolic
function but moderate right ventricular systolic dysfunction and
enlargement. The right atrium was found to be severely enlarged,
* Corresponding author. Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: [email protected]
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V. Marupakula et al.
Figure 1 (A) Initial echocardiogram shows thickened mitral valve leaflets as seen from the apical four-chamber view. Image also shows posterior
leaflet (arrow) motion being restricted in diastole. (B) Parasternal long-axis view showing thickened aortic valve leaflets (arrow). (C) Doppler colour
flow imaging from apical long-axis view showing aortic regurgitation. Ao indicates aorta; LA, left atrium; LV, left ventricle; RV, right ventricle.
Figure 2 Initial echocardiogram shows Doppler velocity profile from the pulmonary valve and the absence of significant stenosis or regurgitation (peak velocity of only 1 m/s).
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Carcinoid heart disease
and the mitral valve was thickened, resulting in the restriction of the
posterior mitral valve leaflet. The aortic valve was also thickened and
had doming of the leaflets during systole, with mild regurgitation.
Both the aortic valve and the mitral valve appeared to show progressive thickening since they had been last examined 2 years
earlier (see Supplementary data online, Movie 3). Unlike its appearance on the previous echocardiogram, the tricuspid valve was markedly thickened, with nearly immobile tricuspid valve leaflets
(Figure 4A and see Supplementary data online, Movie 4) and severe
tricuspid valve regurgitation (Figure 4B and see Supplementary data
online, Movie 4). The dagger-shaped tricuspid regurgitation signal
was consistent with severely elevated right atrial pressure indicated
by a large V-wave (Figure 4C). The pulmonary valve was thickened
(Figure 5A), with significant regurgitation (Figure 5B), and the
Doppler signal showed minimal stenosis of the pulmonary valve
(Figure 5C and see Supplementary data online, Movie 4). Specifically,
pulmonary valve regurgitation showed rapid deceleration, which
indicated clinically significant pulmonary regurgitation and elevated
right ventricular diastolic pressure. Urinary 5-HIAA increased to
49 mg/24 h, compared with 38 mg/24 h noted 2 years earlier. The
patient subsequently underwent cardiac surgery that consisted of
closure of the patent foramen ovale and replacement of both the tricuspid valve and the pulmonary valve with tissue valves. The
explanted tricuspid valve was observed to be markedly thickened
and fibrotic (Figure 6), as was the pulmonary valve.
Discussion
Figure 3 Initial echocardiogram showing apical four-chamber
view of minimally thickened tricuspid valve (arrow) without
dilation of right atrium (RA) or right ventricle (RV). LA indicates
left atrium; LV, left ventricle.
Carcinoid heart disease is characterized by plaque-like deposits of
fibrous tissue that commonly occur on the endocardial surfaces of
the valve cusps, leaflets, and cardiac chambers. The diagnosis is
suspected when echocardiography shows thickening, shortening,
and retraction of the tricuspid valve leaflets with severe tricuspid
Figure 4 (A) Subsequent echocardiogram 2 years later shows markedly thickened and retracted tricuspid valve leaflets (arrow) with dilated
right atrium (RA) and right ventricle (RV). LA indicates left atrium; LV, left ventricle. (B) Doppler colour flow imaging from apical four-chamber
view showing severe tricuspid regurgitation. (C) Doppler imaging of tricuspid regurgitation showing dagger-shaped signal (arrows) due to severe
tricuspid regurgitation with elevated right atrial pressure.
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V. Marupakula et al.
Figure 5 Subsequent echocardiogram 2 years later. (A) Parasternal short-axis view shows thickened pulmonary valve leaflets (arrow). AV
indicates aortic valve; RVOT, right ventricular outflow tract. (B) Doppler colour flow imaging shows clinically significant pulmonary regurgitation. (C) Doppler velocity profile demonstrates minimal pulmonary valve stenosis (peak velocity of only 1 m/s) and rapid deceleration due to
significant pulmonary regurgitation (arrows).
Figure 6 Gross pathology of the tricuspid valve shows
thickened leaflets (arrows denote the edges of the leaflets).
regurgitation with or without stenosis.3 The pulmonary valve is
also thickened and retracted, resulting in regurgitation and/or stenosis. When there is left-sided valvular involvement, the mitral
valve appears thickened, with a reduction in excursion of the leaflets, as was observed in our patient. The severity of the mitral
regurgitation varies, depending on the extent of the valvular
involvement. Observable aortic valve thickening and doming,
like that seen in our patient, are the result of the deposition of
carcinoid plaque on the aortic valve. Similar echocardiographic
findings are also found in patients with drug-induced valvular
heart disease, radiation-induced valve disease, and even rheumatic
heart disease.5
In carcinoid heart disease, the presence of hepatic metastases
plays a permissive role in allowing high quantities of tumour products, such as serotonin and other vasoactive amines, to be available
and carried directly to the right heart.4,6 However, the left heart is
less involved due to the protective mechanism of the lung. As
blood passes through the lungs, serotonin is degraded to
5-HIAA, which substantially reduces serotonin levels capable of
inducing left heart fibrosis.7 Nonetheless, the presence of
primary bronchial carcinoid, high-circulating vasoactive substances,
and an atrial right-to-left shunt such as a patent foramen ovale may
facilitate involvement of the left heart.8 In the case of our patient,
the presence of elevated vasoactive peptides and a patent foramen
ovale paved the way for earlier involvement of the left-sided valves
before the clinically significant right-sided valvular involvement.
This case illustrates the relatively less common manifestation of
carcinoid heart disease in that aortic and mitral valve abnormalities
due to carcinoid heart disease preceded the development of more
common right-sided valvular heart disease. This finding underscores the need for close surveillance of patients with carcinoid
tumours.9
Supplementary data
Supplementary data are available at European Journal of Echocardiography online.
Carcinoid heart disease
Conflict of interest: The authors have no conflicts of interest to
disclose.
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