Metastatic Signet Ring
An Unusual Cause of Cardiac Constriction
ATHER ANIS, M.D., RAJEEV L. NARAYAN, M.D., SURAJ KAPA, M.D., MARC KLAPHOLZ, M.D.,
AND MUHAMED SARIC, M.D., PH.D.
Pericardial constriction secondary to metastatic adenocarcinoma is exceedingly rare. We present the
first recorded case of pericardial constriction secondary to metastatic signet-ring mucinous adenocarci-
noma diagnosed by echocardiography. The cornerstones of echocardiographic diagnosis of constric-
tion are the following: interventricular septal bounce phasic with respiration, M-mode recordings of
the inferior vena cava, and the characteristic Doppler velocity patterns recorded from the mitral valve,
hepatic veins, and mitral annulus.
Key words: Echocardiography, adenocarcinoma, cardiac constriction.
A 59-YEAR-OLD AFRICAN-AMERICAN MAN with a
long history of smoking tobacco and consuming
excessive amounts of ethanol, came to the emer-
gency department complaining of progressive
chest pain, dyspnea, bilateral lower extremity
edema, nausea and vomiting over the preceding
month, along with more recent complaints of
hoarseness and dysphagia.
Physical examination was significant for
prominent jugular venous distension, S4gallop,
dullness over the lung bases, ascites and 2+ pitting
edema of both lower extremities. Laboratory data
revealed iron deficiency anemia and an elevated
serum carcinoembryonic antigen (CEA) level of
98.2 ng/mL (normal <3.0 ng/mL).
After the clinical diagnosis of congestive heart
failure was established, chest radiograph and
transthoracic echocardiogram (TTE) were ob-
tained. Chest radiograph demonstrated bilateral
pleural effusions and an elevated left hemidi-
aphragm. TTE revealed mild left ventricular (LV)
hypertrophy and normal LV systolic function (LV
ejection fraction of 60%). The size and function of
the right heart were normal. Surrounding the epi-
cardial surface of both ventricles and the right
atrium was a 2–3-cm thick band of tissue extend-
ing into the pericardial transverse sinus along the
ascending aorta (Fig. 1). The findings were sug-
© THE MOUNT SINAI JOURNAL OF MEDICINE Vol. 73 No. 6 October 2006
From the Department of Medicine, New Jersey Medical School,
Address all correspondence to Muhamed Saric, M.D., Ph.D.,
F.A.C.C., F.A.S.E., Director, Echocardiography Lab, Division of
Cardiovascular Diseases, New Jersey Medical School, 185 South
Orange Avenue I-538, University Heights, Newark, NJ 07103;
Accepted for publication March 2006.
Fig. 1. Transthoracic echocardiogram in the apical 4-chamber
view at end diastole reveals encasement of the heart by the
signet-cell adenocarcinoma (arrows).
Vol. 73 No. 6
TUMOR-INDUCED PERICARDIAL CONSTRICTION—ANIS
gestive of either an organized pericardial effusion
or a neoplastic invasion.
The presence of an interventricular septal
bounce phasic with respiration was suggestive of
constrictive physiology (1). The diagnosis of con-
striction was confirmed by Doppler velocity pat-
terns of the mitral valve, hepatic veins and mitral
annulus, as well as M-mode recordings of the infe-
rior vena cava (IVC) (2).
Spectral pulsed-wave Doppler recorded at the
mitral valve leaflet tips, showed 66% respiratory
variation in peak velocity of the mitral E wave with
a short deceleration time (<150 msec) (Fig. 2).
In the spectral pulsed-wave Doppler tracing of
the hepatic vein, a marked expiratory enhancement
in the peak velocity of the atrial reversal (AR)
wave was noted (Fig. 3).
Tissue Doppler recordings of the lateral mitral
annulus showed a normal peak velocity of the
early (E’) wave at 17 cm/sec (normal >12 cm/sec)
and an E’/E ratio of 0.44. Both findings were con-
sistent with pericardial constriction but not my-
Inferior Vena Cava
During expiration, the IVC was dilated (diame-
ter = 2.8 cm; normal < 2.5 cm). It collapsed less
than 50% with inspiration (diameter = 1.9 cm) on
M-mode recordings. This is indicative of a
markedly elevated mean right atrial pressure
(15–20 mm Hg), consistent with constrictive phys-
iology. Pulmonary artery systolic pressure was esti-
mated to be mildly elevated (35–40 mm Hg).
A double-contrast barium swallow esopha-
gogram was normal. Five-millimeter axial com-
puted tomography of the chest, abdomen and
pelvis following oral and intravenous contrast ad-
ministration revealed diffuse pericardial thicken-
ing, large bilateral pleural effusions and compres-
sive lung atelectasis. In the abdomen, diffuse he-
patomegaly with passive liver congestion and a
large amount of ascites were noted. These findings
were consistent with constrictive pericardial phys-
iology. No abnormalities of the stomach, small
bowel, colon or pancreas were found.
On surgical pericardiotomy a thickened peri-
cardium with several irregularly shaped nodules in
the pericardial fat were observed; no apparent ab-
normalities of the surrounding lung tissue were
Surgical pathology revealed small-cell, signet-
ring-type metastatic adenocarcinoma in the fibrous
tissue of the pericardium with intralymphatic inva-
sion of the surrounding adipose tissue. Muci-
carmine staining confirmed the presence of a mu-
cinous component and demonstrated CEA im-
The final diagnosis of a signet-ring-type ade-
nocarcinoma of unknown primary location, lead-
ing to pericardial constriction, was established.
While awaiting initiation of oncologic therapy, the
patient had a cardiac arrest with pulseless electri-
cal activity. Since his family refused autopsy, the
immediate cause of death was not established.
Pericardial constriction is characterized by an
intractable encasement of the heart, which uncou-
ples changes in intrapericardial pressures from
Fig. 2. Mitral blood inflow spectral pulsed-wave Doppler ve-
locity tracings reveal a 66% respiratory variation (normal <
25%) in peak velocity of the mitral E wave (Ee= 70 cm/sec
at end expiration; Ei= 42 cm/sec at end inspiration). Also note
a very rapid deceleration of the E wave (<150 msec).
Fig. 3. Hepatic vein spectral pulsed-wave Doppler tracings
demonstrate a marked expiratory enhancement in the peak ve-
locity of the atrial reversal (AR) wave (ARi= 14 cm/sec at end
inspiration; ARe= 26 cm/sec at end expiration). S and D refer
to systolic and diastolic antergrade waves; the subscripts i and
e refer to inspiration and expiration, respectively.
THE MOUNT SINAI JOURNAL OF MEDICINE
those in the pleural space. This can ultimately lead
to heart failure despite preserved systolic and dias-
tolic function of the myocardium.
Historically, tuberculosis was the leading
cause of constrictive pericarditis (3, 4). However,
in the modern era a majority of cases are idiopathic
(42–49%); other causes are post-cardiac surgery
(11–37%), mediastinal radiation (9–31%), con-
nective tissue disorder (3–7%), infections includ-
ing tuberculosis (3–6%), and rarely malignancy,
medications, trauma, sarcoidosis, uremic peri-
carditis or asbestosis (1–10%) (5–7).
The prevalence of pericardial constriction in
patients with metastatic pericardial tumors is about
1–11% (8). As with other cardiac tumors, sec-
ondary tumors of the pericardium are more com-
mon than primary ones (9). Metastatic adenocarci-
nomas are a rare cause of pericardial constriction;
most of them are bronchial in origin (10–12).
In our patient the primary origin of adenocar-
cinoma could not be established although the ele-
vated CEA level pointed toward a primary adeno-
carcinoma of the gastrointestinal tract. Direct
tumor invasion or lymphagitic spread was proba-
bly responsible for the constrictive physiology.
This appears to be the first case recorded in
English of metastatic signet-ring type adenocarci-
noma leading to pericardial constriction diagnosed
by echocardiography. In the only other previously
reported case, bronchial adenocarcinoma metasta-
sized to the pericardium; the diagnosis of constric-
tion was suggested by right heart catheterization,
and echocardiogram was reported to be technically
In pericardial constriction, a rigid pericardium
isolates the heart from normal transmission of in-
trathoracic pressure changes and leads to ventricu-
lar interdependence. Due to pericardial encase-
ment, the normal decrease in intrathoracic pressure
that occurs during inspiration is transmitted only to
the pulmonary and systemic venous systems, but
not to the cardiac chambers.
In constriction, normal negative-pressure in-
spiration leads to a pressure drop in the pulmonary
veins but not in the left ventricle. This in turn re-
sults in a markedly decreased pressure gradient
across the mitral valve, and thus diminished left
ventricular filling. On the contrary, the drop in
pressure in systemic veins enhances venous return
and right ventricular filling.
Since cardiac volume of the constricted heart
is fixed, during inspiration the right ventricle fills
at the expense of the left ventricle, while the oppo-
site occurs during expiration. As a consequence,
during inspiration there is an abrupt posterior mo-
tion (“septal bounce”) of the interventricular sep-
tum (IVS) during early diastole, due to rapid right
heart filling, followed by flattening of IVS in mid-
diastole and an abrupt anterior motion occurring
after atrial contraction (1, 13).
Doppler flow velocity patterns through the mi-
tral and tricuspid valves and hepatic vein not only
provide insight into hemodynamic changes that
occur during respiration in constrictive pericardi-
tis, but also help differentiate it from restrictive
On Doppler echocardiography, the typical pat-
tern of constrictive pericarditis consists of:
1. An inspiratory drop of more than 25% in
the peak velocity of the early left ventricle
diastolic filling wave (mitral E wave);
Deceleration time of mitral E wave less
than 160 milliseconds;
An increase in the left ventricle isovolu-
mic relaxation time with inspiration;
An increase in diastolic flow reversal with
expiration in the hepatic veins (2, 14).
Doppler echocardiography with respiratory
recordings has a sensitivity of 88% for the
diagnosis of constrictive pericarditis (2).
On mitral annular pulsed-wave tissue Doppler
imaging, the peak velocity of the early diastolic
wave (e’ wave) is not diminished in constrictive
pericarditis. This finding distinguishes constrictive
pericarditis from restrictive cardiomyopathy, in
which the diastolic mitral annulus velocities are di-
minished (15, 16). In addition, the restrictive pat-
tern is characterized by a predominantly inspira-
tory increase in diastolic flow reversal in hepatic
Our case underscores the importance of
echocardiography in the diagnosis of cardiac con-
striction, as the clinical presentation may be very
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