Annals of Oncology 15: 375381, 2004

Review DOI: 10.1093/annonc/mdh086

2004 European Society for Medical Oncology
Metastases to the heart
K. Reynen*, U. Kckeritz & R. H. Strasser
*Correspondence to: Dr K. Reynen, Heart Center Dresden, Fetscherstrasse
76, 01307 Dresden, Germany. Tel: +49-3514-501331;
Fax: +49-3514-501512; E-mail: Kardiologie@mailbox.tu-dresden.de
Department of Internal Medicine II, University of Dresden, Heart Center Dresden, Dresden, Germany
Received 11 August 2003; revised 6 September 2003; accepted 17 September 2003
Primary tumors of the heart are rare, occurring at a frequency of
0.02% in pooled autopsy series [1]. Histologically, three-quarters
of primary heart tumors turn out to be benign, almost half of them
being myxomas [2]. Whether benign or malignant, the majority of
primary cardiac tumors are intracavitary and preferentially
develop in the left atrium, thereby leading to left ventricular
inflow obstruction. Embolism is also common. Secondary or
metastatic heart tumors occur comparatively more frequently,
with an at least 100 times higher incidence than primary tumors of
the heart [3]. Intracavitary growth of secondary heart tumors,
however, is unusual. Therefore, despite their frequency, meta-
static heart tumors only rarely gain clinical attention. However,
signs of cardiac involvement are often overlooked, since the
symptoms of disseminated tumor disease prevail. Thus, like pri-
mary tumors of the heart, metastases may imitate valvular heart
disease or cause cardiac failure, ventricular or supraventricular
heart rhythm disturbances, conduction defects, syncope, embolism,
or, quite often, pericardial effusion. Not infrequently, cardiac
tumor invasion contributes to the mechanism of death in affected
patients [4]. Today, two-dimensional echocardiography makes
the detection of cardiac involvement in neoplastic diseases much
easier.
Definition
Neoplasms of the heart may be primary or secondary. Secondary
or metastatic tumors are per se malignant. Carcinomas of the heart
are, by definition, metastatic. Sarcomas or mesotheliomas have to
be considered metastatic if an extracardiac tumor site has already
been or will be revealed by clinical examination, by diagnostic
procedures, or post-mortem.
Incidence
Reflecting the age distribution of malignant diseases, cardiac
metastases predominantly occur in patients in the sixth and seventh
decade of life. There is no sex preference. Cardiac metastases
mostly appear in patients with disseminated tumor disease; solitary
metastases to the heart are very rare. The frequency of cardiac
metastases is generally underestimated: varying from series to
series, cardiac metastases were found in up to 25% of post-
mortem patients who had died of malignancies [319]. Better
diagnostic tools and aggressive treatment of localized malignant
tumors by surgery and/or radiotherapy has led to longer survival
of tumor patients; in tumors with a high propensity to spread meta-
stases, however, this is with the downside of a higher probability
that the patient finally goes through diffuse tumor disease. There-
fore, the incidence of cardiac metastases has increased during
recent decades [319]. Furthermore, metastases to the heart,
whether microscopic or macroscopic, are increasingly taken into
account nowadays, and are looked for thoroughly during post-
mortem examinations [11, 15, 20].
Tumors of origin
In principle, every malignant tumor can metastasize to the heart.
To date, only tumors of the central nervous system have not been
proven to develop cardiac metastases. The most common tumors
with cardiac metastatic potential are carcinomas of the lung, the
breast and the esophagus, malignant lymphoma, leukemia, and
malignant melanoma [38, 1317, 19, 21, 22]. Owing to their high
propensity to generalized hematogenous spread, malignant
melanomas frequently metastasize to the heart, and represent the
tumor with the highest rate of cardiac metastases (in more than
half the cases) [20]. This rate is increasingly lower in carcinomas
of the lung, breast, thyroid gland, kidney and esophagus, and
malignant lymphomas. Cardiac infiltrates are also identified in
about one-third of patients that die of leukemia. Figure 1 shows
the relative incidence of cardiac metastases in four large post-
mortem series classified by the tumor of origin.
Morphology and topography
Cardiac metastases are usually small and multiple; however,
single large tumor lesions are also observed. In carcinomas, meta-
static deposits may lead to diffuse thickening of the pericardium.
Focal as well as diffuse tumor infiltration of the pericardium and/
or myocardium and/or endocardium have been observed in hemato-
logical malignancies: in contrast to leukemic infiltration, lympho-
matous deposits are usually grossly discernible. Although it is
assumed that the right side of the heart is more frequently involved
than the left [6, 20, 23], there are numerous cases where left-sided
involvement is found [4, 5, 7, 9, 24]. In most cases, diffuse bilateral
spread is found. In descending order of frequency, pericardium,
myocardium and endocardium are involved [4, 5, 810, 1719].
Whether pericardial or myocardial metastases develop depends
on the preferential metastatic pathway of the tumor of origin.

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376
Metastatic pathways
Metastases may reach the heart via the lymphatic or hemato-
genous route, or by direct or transvenous extension. Lymphatic
spread tends to give rise to pericardial metastases, hematogenous
spread preferentially gives rise to myocardial metastases. Only
rarely are endocardial tumor deposits found. Tumors such as the
bronchial or esophageal carcinoma, which develop near the heart,
may expand by direct extension into the heart, but these tumors
predominantly attain to the heart by the lymphatics. Similar obser-
vations were made for carcinomas of the breast. Via mediastinal
lymph nodes, tumor cells invade at first the epicardial, and then
the myocardial lymphatic system [12]. Owing to their topography
and prevalence, carcinomas of lung and breast are the most
common tumors originating cardiac metastases. Owing to their
preferred metastatic pathway, both preferentially affect the peri-
cardium. Cardiac metastases of infradiaphragmatic tumors are
markedly less frequent. Malignant melanoma, lymphoma, leuke-
mia, soft tissue and bone sarcoma usually spread hematogenously.
Secondary heart tumors that have partial or total intracavitary
growth are very rare; when they do occur, they are often covered
by thrombotic material [2540]. Even more rare are clusters of
tumor cells on heart valves. This type of tumor infiltration has led
to heart valve stenosis or regurgitation only in isolated cases [20,
4143].
Extracardiac tumors may also reach the atria and even the
chambers of the heart by transvenous extension. Intraluminal
growth of renal cell carcinoma (hypernephroma) through the vena
renalis and vena cava inferior into the right atrium (in 1% of these
tumors) has been reported [29, 4447]. Furthermore, hepatocellular
carcinoma [48], leiomyoma of the uterus [49, 50], nephro-
blastoma (Wilms tumor) [51, 52], pheochromocytoma [53] and
carcinoma of the adrenal cortex [5456] have been observed to
extend through the inferior, and carcinoma of the lung and thyroid
gland [57, 58] through the superior vena cava into the right atrium.
Rarely, bronchial carcinoma spreads through the pulmonary veins
into the left-side heart cavities [59, 60].
Symptomatology
Since the clinical picture is chiefly dominated by generalized
tumor spread, cardiac metastases usually remain clinically silent,
particularly as the vast majority of cardiac metastases are small.
Frequently, cardiac involvement is not noticed until after death. In
retrospective studies, only about one-tenth of patients who died of
tumor disease and showed cardiac spread as identified at post-
mortem examination presented with symptoms or findings indica-
tive of cardiac involvement [7, 11]. Obviously, there is no strong
correlation between the extent of cardiac involvement and clinical
manifestations. Not infrequently, post-mortem findings reveal
cardiac involvement to be more extensive than clinical findings
have suggested.
At the time when malignant disease is diagnosed, cardiac meta-
stases are the clinically prevailing finding in a few single cases
only [13, 26, 29, 61, 62]. Occasionally, however, metastases to the
heart are detected during initial tumor staging. On the other hand,
they may not become apparent clinically until many years after
cancer diagnosis, if at all. For example, heart metastases of
sarcomas have caused clinical symptoms not before 11 and 25 years
after resection of the original tumor, respectively, just as meta-
stases of malignant melanomas not before 14 and 22 years,
respectively [6367]. Heralds of metastases to the heart are a rapid
increase in heart size by pericardial effusion, new signs of heart
failure or valve disease, conduction defects, and atrial or ven-
tricular heart rhythm disturbances [3, 5, 10, 11, 13, 20, 21, 28].
Symptoms such as dyspnea or tachypnea, and clinical findings
such as systolic heart murmur, peripheral edema, pleural or peri-
Figure 1. Relative incidence of metastatic heart tumors in autopsy studies for frequent primary neoplasms. Shown is a summary of four large series: white
shading, Burke and Virmani [3]; light gray shading, Davies [13]; dark gray shading, Hanfling [10]; hatched shading, Scott and Garvin [5].

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377
cardial effusion, or ascites, however, may also be the result of
tumor-associated anemia and hypoproteinemia, or of lung meta-
stases.
It is less the histological type than the localization of metastases
that determines the symptomatology. Pericardial involvement can
lead to pericarditis with pericardial effusion, which can be sero-
sanguineous or hemorrhagic and may lack hemodynamic com-
promise. However, in cases of rapid increase in pericardial fluid
and low compliance of the pericardium, cardiac tamponade can
result and necessitate immediate pericardiocentesis [5, 9, 18, 20,
29, 62, 6871]. Cardiac output can only be maintained as long as
the reduction in stroke volume due to increasing pericardial pres-
sure can be compensated for by tachycardia and peripheral vaso-
constriction. Hypotension, dyspnea and peripheral cyanosis,
pulsus paradoxus (systolic blood pressure decreases by more than
10 mmHg during inspiration), and venous congestion are also
hallmarks of clinical diagnosis. Venous congestion is manifested
by distended neck veins and paradoxical increase in venous pres-
sure during inspiration (Kussmauls sign), as well as epigastric
pain caused by hepatic congestion. In cases of a slow increase in
pericardial fluid, the pericardium may stretch and the pericardial
sac may take in more than 3 l. In these cases, pericardial effusion
can remain asymptomatic for a long time. Pericardial tumor
growth itself can cause constriction of the heart in the same way
[10, 22, 25, 68, 70, 71]. Other causes of heart failure in patients
with cardiac metastases may be replacement of myocardium and,
in cases of intracavitary growth, the obliteration of heart chambers
or the obstruction of the ventricular inflow or outflow tract sug-
gestive of valvular heart disease [5, 10, 20, 2528, 3537]. An
association between tumor infiltration and myocardial rupture has
been reported only in isolated cases [72, 73].
Cardiac metastases can provoke atrial and ventricular heart
rhythm disturbances, as well as conduction defects. These include
complete atrioventricular block by invasion of the cardiac con-
duction system or of the providing coronary artery [5, 711, 20,
25, 28, 41, 68, 69, 74, 75]. Syncope and sudden death have been
reported [9, 10, 20, 25, 28, 36, 68, 75]. Angina pectoris and myo-
cardial infarction can be the result of coronary embolism, but also
of invasion or compression of a coronary artery [3, 1012, 20, 22,
41, 63, 65]. Alternatively, retrosternal pain may be due to peri-
carditis. Furthermore, intracavitary right-sided heart metastases
can lead to pulmonary, and left-sided heart metastases to systemic
embolism [26, 27, 29, 30, 47, 63]. However, this occurs less
frequently than in cases of the benign myxoma.
The most common tumors of origin, carcinoma of the lung and
breast, metastasize preferentially to the pericardium, thereby lead-
ing to pericardial effusion. Therefore, when signs and or symptoms
of cardiac dysfunction are present, the vast majority results from
pericardial, and only rarely from myocardial or intracavitary,
metastases.
Diagnosis
There are no physical or laboratory examinations that specifically
detect cardiac metastases in diffuse tumor disease. In cases of
intracavitary metastases, systolic and or diastolic murmurs can
occur in relation to their location, size and mobility [10, 33]. The
nature of the murmur in mobile tumors may change with body
position. Diastolic murmurs reflect tumor-related obstruction of
the left or right ventricular filling, and systolic murmurs the inter-
ference with the closure of atrioventricular valves or the narrow-
ing of the ventricular outflow tract. In cases of heart failure, gallop
rhythm can develop; in cases of pericarditis, pericardial friction;
and in cases of larger pericardial effusion, heart sounds often
diminish [7, 8, 11].
Electrocardiographic recordings are usually unspecific but may
document possible ventricular or supraventricular arrhythmias, or
conduction defects. Pericarditis is rarely accompanied by the
typical ST-segment elevations. Not infrequently, only non-specific
ST-segment changes are found. Pericardial effusion can cause low
voltage and electrical alternans [5, 711, 20, 68, 69, 71, 74, 75].
Q-waves can occur as residues of tumor-related myocardial
infarction; an electrocardiographic picture of infarction can also
result from infiltration or displacement of myocardium by the
tumor [7, 11, 65, 71].
Chest radiography may reveal an increase in cardiac silhouette
through pericardial effusion or peri- and/or paracardial tumor
growth, as well as a pleural effusion resulting from heart failure or
a lung tumor [79, 76]. Because they contain bone, cardiac meta-
stases of the rare osteogenic sarcomas can be visualized by radio-
graphy [28].
In cases of larger size only, intracavitary tumors may appear as
filling defects under radionuclide or contrast medium angiography
[25, 39, 77]. Probing of the tumor-bearing heart chamber, how-
ever, should be avoided, since tumor fragments or tumor-adherent
thrombotic material may be embolized. Nevertheless, in individual
cases, diagnosis of intracardiac metastasis has been established by
catheter biopsy, usually under fluoroscopic guidance [61, 65, 78].
Biopsy of intracardiac lesions has also been performed with the
help of transthoracic or transesophageal echocardiography [79,
80]. Tumor vessels can be dyed in cases in which coronary arterio-
graphy is included in the diagnostic procedure.
The method of choice to detect cardiac metastases and their
complications, however, is two-dimensional echocardiography
[27, 29, 31, 37, 81, 82]. Echocardiography can show dense peri-
cardial bands reflecting the pericardium being thickened by
inflammation or tumor infiltration. Pericardial effusion can be
proven quickly, with high sensitivity. Pericardial metastases may
project in a cauliflower-like pattern into the fluid-filled pericardial
space [83]. Pericardiocentesis can be performed under ultrasound
guidance, and thereby more safely and accurately. Tumor cells
within the pericardial fluid may verify diagnosis of metastatic
pericardial involvement [10, 29, 6871]. Negative cytologic find-
ings, however, do not exclude a malignant origin of the effusion,
and pericardial biopsy might then be necessary. Because sono-
graphic examination is comfortable for the patient and inexpen-
sive, it is appropriate for the follow-up of pericardial effusions. In
cases of larger myocardial metastases, regional wall motion
abnormalities can be revealed by ultrasound. Intracavitary lesions
can also be detected with high sensitivity. In cases of peri- or
paracardial lesions, the transesophageal approach is superior to
the transthoracic approach [81, 84].

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Supplemental diagnostic imaging methods are computer tom-
ography and magnetic resonance imaging. These two methods
provide sections of cardiac, mediastinal, pulmonic and thoracic
structures in any desired plane, without overlapping. Thus, size
and extension of paracardial or transpericardial tumor growth can
be determined more precisely than by sonography. In addition,
and in contrast to ultrasound, tissue differentiation is partly
possible between solid, liquid, hemorrhagic or fatty lesions [64,
81, 82, 85, 86], and myocardial metastases can be better demar-
cated.
In cases in which a malignant tumor was resected many years
before detection of a cardiac tumor mass, exploratory thoracotomy
and open biopsy might be necessary to confirm the diagnosis of
metastasis [76].
Differential diagnosis
The differential diagnosis of intracavitary mass lesions includes
benign and malignant primary cardiac tumors. Since an intra-
cardiac lesion is detected by ultrasound, the differential diagnosis
must include thrombus, vegetation and a foreign body. However,
intracardiac metastases, even though rare, should also be included
in the differential diagnosis, as well as infectious and non-bacterial
thrombotic or marantic endocarditis. Intramural metastases
should be considered in the differential diagnosis of myocardial
infarction and pericardial metastases in the differential diagnosis
of pericardial effusion. However, myocardial or pericardial
damage can also be caused by radio- or chemotherapy. Thus, peri-
carditis with effusion, pericarditis constrictiva, myocardial or
valvular fibrosis may be attributable to radiotherapy, and cardio-
myopathy to anthracyclines such as doxorubicin and dauno-
rubicin.
Treatment
In the vast majority of cases, cardiac metastases manifest in
patients with advanced tumor disease, with the heart being
involved in the generalized tumor spread. At this stage of the dis-
ease, many patients will already have undergone surgical treat-
ment for the tumor of origin, or radio- or chemotherapy. Cardiac
treatment is mostly confined to palliative measures. Surgical
resection is only indicated in exceptional cases of solitary intra-
cavitary heart metastases, leading to obliteration of cardiac cham-
bers or valve obstruction if the tumor of origin was surgically
resected in toto and the patient appears to have a good prognosis
[32, 63, 64, 66, 77, 87, 88]. Frequently, however, complete
resection fails, and postoperative mortality is high [89, 90]. Coil
embolization of the supplying coronary branch may be an altern-
ative option in circumscribed intracardiac masses [91]. Tumors
invading the right atrium by the transvenous route, however, have
been successfully removed surgically in a large number of cases
[4447, 49, 52, 53, 55, 56, 89]. Mitral valve replacement because
of high-grade mitral insufficiency due to tumor infiltration has
been reported casuistically [42]. Furthermore, tumor-related com-
plete AV-block has been managed by pacemaker implantation
[75]. Tumor-related AV-block, however, may occasionally be
rescinded by radiotherapy [10]. Usually, cardiac infiltrates in
leukemia and lymphoma respond well to radio- or chemotherapy
[10, 69].
Not infrequently, pericardial involvement requires specific
efforts. Malignant pericardial effusion may be diminished by local
radiotherapy or systemic chemotherapy [10, 69, 71]. Cardiac
tamponade, however, makes percutaneous pericardiocentesis
necessary as soon as possible [6871]. The immediate success rate
is high (>95%) and complications are rare, and include puncture
of a coronary artery or the myocardium, rhythm disturbances or
pneumothorax [92]. Nearly half of effusions can be definitely
controlled by this approach [92]. If not, chemotherapeutics or
radioisotopes may be instilled through the catheter to prevent
recurrence of the effusion (by direct cytostatic and/or by slerosing
activity with adhesion of the visceral and the parietal pericardium
as a result of inflammatory reactions) [70, 71, 9295]. For this
purpose in particular, bleomycin sulfate [9698], cisplatin
[99102], mitoxantrone [103], thiotepa [104, 105], mitomycin C
[106], 5-fluorouracil [100, 107] and tetracycline derivates [94, 96,
98, 100] (see also Table 1), as well as chromic phosphate
32
P for a
dose of 185 to 370 MBq [108, 109], were evaluated. Among the
chemotherapeutics, cisplatin seems to be the most efficacious,
especially in lung cancer patients [100, 102]. However, instilla-
tion of antitumor agents or tertacyline derivates can result in
severe pain, arrhythmias and bone marrow toxicity, and in unpre-
dictable sclerotic processes. Radioisotopes have been shown to be
safe, without noteworthy side effects and of high efficacy, but the
technical expenditure is high [92, 108, 109]. In cases of failure to
control pericardial effusion by pericardiocentesis, alternatively,
percutaneous balloon pericardiostomy can be considered [110,
111]. Today, more invasive procedures, such as open surgical
drainage through a subxiphoid pericardial window or anterolateral
thoracotomy with pericardiectomy, in these terminally ill patients
are only rarely performed.
Symptomatic improvement, however, is not infrequently lessened
by cardiopulmonary side effects: radiotherapy may lead to fibro-
sis of the lung or myocardium, and the latter may be associated
with disturbance of the conduction system. Frequently, radio-
therapy is accompanied by pericarditis. Cardiotoxic side effects
well known for the chemotherapeutic agents doxorubicin, dauno-
rubicin and cyclophosphamide (in high doses) may induce recal-
citrant myocardial failure.
Summary
Secondary heart tumors are common in patients with metastatic
tumor disease, afflicting up to one-quarter of them. Clinically,
secondary heart tumors usually remain silent. However, ultra-
sound examination of the heart should be performed as soon as
symptoms of heart failure, angina pectoris, embolism or rhythm
disturbances develop, or a new heart murmur becomes audible, or
as soon as heart size increases radiologically. Additional informa-
tion may be obtained by computer tomography or nuclear magnetic
resonance imaging. To note cardiac involvement does not only
have prognostic implications: even if only exceptionally curative

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therapy may be available, palliative measures may improve the
quality of life of affected patients.
Acknowledgements
We are indebted to Eugene Braunwald, MD, for review of this
manuscript.
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Table 1. Substances used for pericardial sclerosis treatment, and their doses and side effects
a
Previous instillation of 100 mg lidocaine intrapericardially advisable.
Substance Single dose Frequency of application Side effects
Tetracycline derivates
[94, 96, 98, 100]
15 mg/kg body weight (5001000 mg)
a
in 2050 ml normal saline solution
15 Fever >38.5C, thoracic pain,
atrial arrhythmia
Bleomycin sulfate
[9698]
560 mg in 1020 ml normal saline
solution
12 Fever
Cisplatin
[99102]
10 mg in 20 ml normal saline solution;
or
15 Pain, nausea, myocardial ischemia,
atrial arrythmia
30 mg/m
2
in 100 ml normal saline
solution
1
Thiotepa
[104, 105]
15 mg in 20 ml sterile water;
or
3 Leukopenia, thrombocytopenia
30 mg in 20 ml sterile water 1
Mitomycin C
[106]
8 mg in 10 ml normal saline 13 Pericardial constriction
Mitoxantrone
[103]
1020 mg 13 None
5-Fluorouracil
[100, 107]
250 mg in 20 ml normal saline 1 Neutropenia

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