Chapter 62. Cardiac Neoplasms

Neoplasms of the heart can be divided into primary cardiac tumors arising in the heart and secondary cardiac tumors from metastasis. Primary cardiac tumors can be further stratified into benign and malignant tumors. Between 10 and 20% of patients dying of disseminated cancer have metastatic involvement of the heart or pericardium.1,2 Surgical resection is seldom possible or advisable for these tumors, and intervention usually is limited to drainage of malignant pericardial effusions and/or diagnostic biopsies.

The incidence of primary cardiac neoplasm ranges between 0.17 and 0.19% in unselected autopsy series.3-5 Seventy-five percent of primary cardiac tumors are benign, and 25% are malignant.2,6 Fifty percent of the benign tumors are myxomas, and 75% of malignant tumors are sarcomas.2,6 The clinical incidence of these tumors is 1 in 500 cardiac surgical patients. With the exception of myxomas, most surgeons will rarely encounter primary cardiac tumors. The purpose of this chapter is to summarize useful information for the evaluation and management of patients with cardiac tumors and to provide a reference for additional study.

A primary cardiac neoplasm was first described by Realdo Colombo in 1559.7 Alden Allen Burns of Edinburgh described a cardiac neoplasm and suggested valvular obstruction by an atrial tumor in 1809.8 A series of six atrial tumors, with characteristics we now recognize as myxoma, was published in 1845 by King.9 In 1931, Yates reported nine cases of primary cardiac tumor and established a classification system similar to what we use today.10 The first antemortem diagnosis of a cardiac tumor was made in 1934 when Barnes diagnosed a cardiac sarcoma using electrocardiography and biopsy of a metastatic lymph node.11 In 1936, Beck successfully resected a teratoma external to the right ventricle,12 and Mauer removed a left ventricular lipoma in 1951.13 Treatment of cardiac tumors was profoundly influenced by two events: the introduction of cardiopulmonary bypass in 1953 by John Gibbon, which allowed a safe and reproducible approach to the cardiac chambers, and the introduction of cardiac echocardiography, which allowed safe and noninvasive diagnosis of an intracardiac mass. The first echocardiographic diagnosis of an intracardiac tumor was made in 1959.14 An intracardiac myxoma was diagnosed by angiography in 1952 by Goldberg, but attempts at surgical removal were unsuccessful.9 A large right atrial myxoma was removed by Bhanson in 1952 using caval inflow occlusion, but the patient died 24 days later.15 Crafoord in Sweden first successfully removed a left atrial myxoma in 1954 using cardiopulmonary bypass,16 and Kay in Los Angeles first removed a left ventricular myxoma in 1959.17 By 1964, 60 atrial myxomas had been removed successfully, with improved results owing to the increasing safety of cardiopulmonary bypass and use of echocardiography for detection. Operations are currently performed routinely on patients with atrial myxoma with minimal mortality.6,18–21 Primary malignant tumors, however, continue to represent a challenge.

A pathologic classification is listed in Table 62-1. Mural thrombus is listed as a pseudotumor, although not really a cardiac tumor, its presentation may mimic myxoma clinically and pathologically. Most mural thrombi are associated with underlying valvular disease, myocardial infarction, dysfunction, or atrial fibrillation.22 Mural thrombi also have been noted in hypercoagulable syndromes, particularly antiphospholipid syndrome.23 With increasing use of long-term central catheters, we have seen several right atrial masses that were difficult to define and upon removal were mural thrombi.

Heterotopias and tumors of ectopic tissue include cystic tumors of the atrioventricular node consisting of multiple benign cysts in the region of the atrioventricular node that can cause heart block or sudden death. Most are diagnosed at autopsy, but a biopsy diagnosis of atrioventricular nodal tumor has been reported.24 Germ cell tumors of the heart usually are teratomas, occurring within the pericardial sac, but yolk sac tumors have been described in infants and children.25 Ectopic thyroid tissue may occur within the myocardium and is referred to as struma cordis. Right ventricular outflow track obstruction may be present, but most patients are asymptomatic.

Most of the remaining tumors arise in the mesenchymal, fat, fibrous, neural, or vascular cells of the heart, with myxoma representing a tumor of undetermined histogenesis. Primary cardiac lymphoma, mesothelioma, and metastatic tumors to the heart represent the remaining pathologic categories that comprise the greater part of this chapter.

Myxoma

Myxomata comprise 50% of all benign cardiac tumors in adults and 15% of such tumors in children. Occurrence during infancy is rare (Tables 62-2 and 62-3). A vast majority of myxomas occur sporadically and tend to be more common in women.4,21 The peak incidence is between the third and sixth decades of life, and 94% of tumors are solitary.26 Approximately 75% occur in the left atrium28 and 10 to 20% occur in the right atrium. The remaining proportion are equally distributed between the ventricles.2 The deoxyribonucleic acid (DNA) genotype of sporadic myxomas is normal in 80% of patients.27 Myxomas are unlikely to be associated with other abnormal conditions and have a low recurrence rate.4,28

About 5% of myxoma patients show a familial pattern of tumor development based on autosomal dominant inheritance.29,37,38 These patients and 20% of those with sporadic myxoma have an abnormal DNA genotype chromosomal pattern.27 In contrast to the "typical" sporadic myxoma profile, familial patients are more likely to be younger, equally likely to be male or female, and more often (22%) have multicentric tumors originating from either the atrium or ventricle.30-34 Although familial myxomas have the same histology, they have a higher recurrence rate after surgical resection (21 to 67%).28,35 Approximately 20% of familial patients have associated conditions such as adrenocortical nodule hyperplasia, Sertoli cell tumors of the testes, pituitary tumors, multiple myxoid breast fibroadenomas, cutaneous myomas, and facial or labial pigmented spots.26,35 These conditions often are described as complex myxomas within the group of familial myxoma.27 A familial syndrome with autosomal X-linked inheritance characterized by primary pigmented nodular adrenocortical disease with hypercortisolism, cutaneous pigmentous lentigines, and cardiac myxoma is referred to as Carney's complex.26,35

Pathology

Both biatrial and multicentric myxomas are more common in familial disease. Biatrial tumors probably arise from bidirectional growth of a tumor originating within the atrial septum.36 Atrial myxomas generally arise from the interatrial septum at the border of the fossa ovalis but can originate anywhere within the atrium, including the appendage.4 In addition, isolated reports confirm that myxomas can arise from the cardiac valves, pulmonary artery and vein, and vena cava.37,38 Right atrial myxomas are more likely to have broad-based attachments than left atrial tumors; they also are more likely to be calcified,32 and thus visible on chest radiographs. Ventricular myxomas occur more often in women and children and may be multicentric.2,39 Right ventricular tumors typically arise from the free wall, and left ventricular tumors tend to originate in the proximity of the posterior papillary muscle.

Grossly, about two-thirds of myxomas are round or oval tumors with a smooth or lobulated surface (Fig. 62-1).21 Most are polypoid, compact, pedunculated, mobile, and not likely to fragment spontaneously.2,4 Mobility depends on stalk length, the extent of attachment to the heart, and the amount of tumor collagen.4 Most are pedunculated with a short, broad base, and sessile forms are unusual.2,40 Less common villous or papillary myxomas are gelatinous and fragile and prone to fragmentation and embolization, occurring about one-third of the time.21,41 Myxomas are white, yellow, or brown in color, and are frequently covered with thrombus.2 Focal areas of hemorrhage, cyst formation, or necrosis may be seen in cut section. The average size is about 5 cm in diameter, but growth to 15 cm in diameter and larger has been reported.4 Myxomatous tumors appear to grow rapidly, but growth rates vary, and occasionally, tumor growth arrests spontaneously.4 Weights range from 8 to 175 g, with a mean between 50 and 60 g.5

Histologically, myxomas are composed of polygonal-shaped cells and capillary channels within an acid mucopolysaccharide matrix. 4 The cells appear singularly or in small clusters throughout the matrix, and mitoses are rare.42,51 The matrix also contains occasional smooth muscle cells, reticulocytes, collagen, elastin fibers, and a few blood cells. Cyst, areas of hemorrhage, and foci of extramedullary hematopoiesis are also found.35,41 Ten percent of the tumors have microscopic deposits of calcium and metastatic bone deposits, as well as sometimes glandular-like structures.35,41 The base of the tumor contains a large artery and veins that connect with the subendocardium but do not typically extend deep beyond the subendocardium.35 A coronary angiography in our own institution revealed a large feeding vessel and was suspected originally of being an angiosarcoma but on histology proved to be a typical benign myxoma. Myxomas tend to grow into the overlying cardiac cavity rather than into the surrounding myocardium. Myxomas arise from the endocardium and are considered derivative of the subendocardial multipotential mesenchymal cell.43,44,45 This accounts for the occasional presence of hematopoietic tissue and bone in these tumors. Interestingly, myxomas have developed after cardiac trauma, including repair of atrial septal defects and trans-septal puncture for percutaneous dilatation of the mitral valve.

Clinical Presentation

The classic clinical presentation of a myxoma is intracardiac obstruction with congestive heart failure (67%); signs of embolization (29%); systemic or constitutional symptoms of fever (19%); weight loss or fatigue (17%); and immunologic manifestations of myalgia, weakness, and arthralgia (5%).21 Cardiac rhythm disturbances and infection occur less frequently.

Constitutional Symptoms

Nearly all myxoma patients admit to a variety of constitutional symptoms. These complaints may be accompanied by a leukocytosis, elevated erythrocyte levels and sedimentation rate, hemolytic anemia, thrombocytopenia, and elevated C-reactive protein. Immunoelectrophoresis may reveal abnormal immunoglobulin levels with increased circulating IgG.46 The recent discovery of elevated levels of interleukin-6 in patients with myxoma has been linked to a variety of associated conditions, including lymphadenopathy, tumor metastasis, ventricular hypertrophy, and development of constitutional symptoms.39,47,48 Other less frequent complaints include Raynaud's phenomenon, arthralgias, myalgias, erythematous rash, and clubbing of the digits.4,49

Possible etiologies of such varied complaints and symptoms include tumor embolization with secondary myalgias and arthralgias and elevated immunoglobulin response.50 Circulating antibody–tumor antigen complexes with complement activation also may play a role.51 Such symptom complexes tend to resolve following surgical resection of the tumor.52

Obstruction

Obstruction of blood flow in the heart is the most common cause of acute presenting symptoms. The nature of these symptoms is determined by which of the chambers is involved and the size of the tumor. Myxomas in the left atrium tend to mimic mitral disease. These produce positional dyspnea and other signs and symptoms of heart failure associated with elevated left atrial and pulmonary venous pressures. Clinically, mitral stenosis often is suspected and leads to echocardiography and diagnosis of myxoma. Syncopal episodes occur in some patients and are thought to result from temporary occlusion of the mitral orifice.32,53 Right atrial myxomas can produce a clinical picture of right-sided heart failure with signs and symptoms of venous hypertension, including hepatomegaly, ascites, and dependent edema and can cause tricuspid valve stenosis by partially obstructing the orifice.32,53 If a patent foramen ovale is present, right-to-left atrial shunting may occur with central cyanosis, and paradoxical embolization has been reported.54 Large ventricular myxomas may mimic ventricular outflow obstruction. The left ventricular myxoma may produce the equivalent of subaortic or aortic valvular stenosis,54,55 whereas right ventricular myxomas can simulate right ventricular outflow track or pulmonic valve obstruction.

Embolization

Systemic embolization is the second most common mode of myxomatous presentation, occurring in 30 to 40% of patients.2,4,32 Because the majority of myxomas are left-sided, approximately 50% of embolic episodes affect the central nervous system owing to both intra- and extracranial vascular obstruction. The neurologic deficits following embolization can be transient but are often permanent.56 Specific central nervous system consequences include intracranial aneurysms, seizures, hemiparesis, and brain necrosis.57–59 Retinal artery embolization with visual loss has occurred in some patients.60

Embolic myxomatous material has been found blocking iliac and femoral arteries.61–62 Other sites of tumor embolization include abdominal viscera and the renal and coronary arteries.63 Histologic examination of surgically removed peripheral myxoma that has embolized provides the diagnosis of an otherwise unsuspected tumor.32 Renal artery specimens from a nephrectomy have shown viable enlarging embolic myxoma after excision of the primary tumor. Right-sided myxomatous emboli mainly obstruct pulmonary arteries and cause pulmonary hypertension and even death from acute obstruction.4,54

Infection

Infection arising in a myxoma is a rare complication and produces a clinical picture of infectious endocarditis.64,65 Infection increases the likelihood of systemic embolization,4 and an infected myxoma warrants urgent surgical resection.

Diagnosis

Clinical Examination

Findings at the time of clinical assessment of a patient with cardiac myxoma vary according to the size, location, and mobility of the tumor. Left atrial myxomas may produce auscultatory or clinical findings similar to mitral disease. The well-described "tumor plop" can be confused with a third heart sound,66 occurring just after the opening snap of the mitral valve created from contact between the tumor and endocardial wall.66 Left atrial myxomas that cause partial obstruction of left ventricular filling may result in elevated pulmonary vascular pressures with augmentation of the pulmonary component of the second heart sound.67

Right atrial myxomas may produce similar auscultatory findings as left atrial myxomas with the exception that they are best heard along the lower right sternal border rather than at the cardiac apex. In addition, right atrial hypertension may produce a large a wave in the jugular venous pulse and, when severe, may mimic superior vena caval syndrome.

Chest Radiograph and Electrocardiogram

The findings on chest roentgenogram may include generalized cardiomegaly, individual cardiac chamber enlargement, and pulmonary venous congestion. More specific rare findings are density within the cardiac silhouette caused by calcification within the tumor (see Fig. 62-3) occurring more often with right-sided myxomas.4

Electrocardiographic Findings

Nonspecific abnormalities such as chamber enlargement, cardiomegaly, bundle-branch blocks, and axis deviation can be found.68 Fewer than 20% of patients have atrial fibrillation.39 Evaluation of nonspecific electrocardiographic abnormalities occasionally leads to an incidental diagnosis of myxoma most electrocardiograms are not helpful in establishing a diagnosis.

Echocardiography

Cross-sectional echocardiography is the most useful test employed for the diagnosis and evaluation of myxoma. The sensitivity of two-dimensional (2-D) echocardiography for myxoma is 100%, and this imaging technique largely has supplanted angiocardiography.69 However, coronary angiography usually is performed in myxoma patients more than 40 years of age to rule out significant coronary disease. Transesophageal echocardiography (TEE) provides the best information concerning tumor size, location, mobility, and attachment.70

Transesophageal echocardiograms detect tumors as small as 1 to 3 mm in diameter.71 Most surgeons obtain a transesophageal echocardiogram in the operating room before the operation (Fig. 62-2). We particularly evaluate the posterior left atrial wall, atrial septum, and right atrium, which often are not well displayed on transthoracic examination, to exclude the possibility of biatrial multiple tumors. Additionally, post operative TEE ensures a normal echocardiogram before leaving the operating room.

Computed Tomography and Magnetic Resonance Imaging

Although myxomas have been identified using computed tomography (CT),69,72 this modality is most useful in malignant tumors of the heart because of its ability to demonstrate myocardial invasion and tumor involvement of adjacent structures.68 Similarly, magnetic resonance imaging (MRI) has been employed in the diagnosis of myxomas and may yield a clear picture of tumor size, shape, and surface characteristics.68–72 MRI is particularly useful in detecting intracardiac and pericardial extension, invasion of malignant secondary tumors, and the evaluation of ventricular masses that occasionally turn out to be myxoma. Both CT and MRI detect tumors as small as 0.5 to 1.0 cm and provide information regarding the composition of the tumor.4 Neither CT nor MRI is needed for atrial myxomas if an adequate echocardiogram is available. The exception is the occasional right atrial myxoma that extends into one or both caval or tricuspid orifices. CT or MRI should be reserved for the situation in which the diagnosis or characterization of the tumor is unclear after complete echocardiographic evaluation.

Surgical Management

Surgical resection is the only effective therapeutic option for patients with cardiac myxoma and should not be delayed because death from obstruction to flow within the heart or embolization may occur in as many as 8% of patients awaiting operation.73 A median sternotomy approach with ascending aortic and bicaval cannulation usually is employed. Manipulation of the heart before initiation of cardiopulmonary bypass is minimized in deference to the known friability and embolic tendency of myxomas. In the event of preoperative known cerebral embolization without hemorrhage, the tumor should be resected approximately seven days after the event to prevent further embolization and yet allow time for stabilization of the brain for cardiopulmonary bypass. For left atrial myxomas, the venae cavae are cannulated through the right atrial wall, with the inferior cannula placed close and laterally to the inferior vena cava–right atrial junction. Caval snares are always used to allow opening of the right atrium, if necessary. If extensive exposure of the left atrium is needed or a malignant left atrial tumor is suspected, we mobilize and directly cannulate the superior vena cava, which allows it to be transected if necessary for additional exposure. Body temperature is allowed to drift down, but there is no attempt to induce systemic hypothermia unless the need for reduced perfusion flow is anticipated. Modern cardioplegic techniques yield a quiet operative field and protect the myocardium from ischemic injury during aortic cross-clamping. Cardiopulmonary bypass is started, and the aorta is clamped before manipulation of the heart.

Exposure of left atrial myxomas is maximized by using several principles from mitral valve repair surgery. The surgeon desires the right side of the heart to rotate up and the left side of the heart to rotate down. Therefore, stay sutures are placed low on the pericardium on the right side, and no pericardial stay sutures are placed on the left before placing the chest retractor. This rotates the heart for optimal exposure of both the right and, particularly, the left atrium (Fig. 62-3). For left atrial tumors, the superior vena cava is mobilized extensively, as is the inferior vena cava–right atrial junction, allowing increased mobility and exposing the left atrial cavity. Left atrial myxomas can be approached by an incision through the anterior wall of the left atrium anterior to the right pulmonary veins (Fig. 62-4). This incision can be extended behind both cavae for greater exposure (Fig. 62-5). Exposure and removal of large tumors attached to the interatrial septum may be aided by a second incision parallel to the first in the right atrium. This biatrial incision allows easy removal of tumor attached to the fossa ovalis with a full-thickness Ro (margin-negative) excision at the site of attachment and easy patch closure of the atrial septum if necessary (Fig. 62-6).

Right atrial myxomas pose special venous cannulation problems, and intraoperative echocardiography may be beneficial. Both venae cavae may be cannulated directly. When low- or high-lying tumor pedicles preclude safe transatrial cannulation, cannulation of the jugular or femoral vein can provide venous drainage of the upper or lower body. In general, we always can cannulate the superior vena cava distal enough from the right atrium to allow adequate tumor resection, but occasionally femoral venous cannula drainage has been necessary. If the tumor is large or attached near both caval orifices, peripheral cannulation of both jugular and femoral veins may be used to initiate cardiopulmonary bypass and deep hypothermia. After the aorta is cross-clamped and the heart is arrested with antegrade cardioplegia, the right atrium may be opened widely for resection of the tumor and reconstruction of the atrium during a period of circulatory arrest if this is needed for a dry field. Resection of large or critically placed right atrial myxomas often requires careful preoperative planning, intraoperative TEE, and special extracorporeal perfusion techniques to ensure complete removal of the tumor, protection of right atrial structures, and reconstruction of the atrium. Because myxomas rarely extend deep in the endocardium, it is not necessary to resect deeply around the conduction tissue. The tricuspid valve and the right atrium, as well as the left atrium and ventricle, should be inspected carefully for multicentric tumors in patients with right atrial myxoma. Regardless of the surgical approach, the ideal resection encompasses the tumor and a portion of the cardiac wall or interatrial septum to which it is attached (Fig. 62-7). Our policy is to perform a full thickness resection whenever possible. However, partial-thickness resection of the area of tumor attachment has been performed when anatomically necessary without a noted increase in recurrence rate.74,75

Ventricular myxomas usually are approached through the atrioventricular (AV) valve76 or by detaching the anterior portion of the AV valve for exposure and resection and reattachment after resection. Occasional small tumors in either outflow tract can be removed through the outflow valve.76 If necessary, the tumor is excised through a direct incision into the ventricle, but this is unusual and the least preferred approach. It is not necessary to remove the full thickness of the ventricular wall because no recurrences have been reported with partial-thickness excisions. As with right atrial myxoma, the presence of ventricular myxoma prompts inspection for other tumors because of the high incidence of multiple tumors.

Every care should be taken to remove the tumor without fragmentation. Following tumor removal from the field, the area should be liberally irrigated, suctioned, and inspected for loose fragments. There are rare instances of distant metastases from myxoma many years after tumor resection, and these reports raise the issue of potential intraoperative dissemination of tumor.77 Cardiotomy suction can be used during the operation, but wall suction should strictly be used during the brief time that the tumor is exposed. The low malignant potential of the vast majority of myxomas and the rarity of metastasis support the author's current policy of retaining rather than discarding blood, and we believe that most cases of metastatic implantation of myxoma represent a preoperative embolic event.

Minimally Invasive Approaches to Surgical Removal

Minimally invasive approaches are being applied with increasing frequency in all areas of cardiac surgery, and cardiac tumors are no exception. Experience is confined to benign tumors and is quite limited. Approaches have included right parasternal or partial sternotomy exposure with standard cardioplegic techniques,78 right submammary incision with femoral-femoral bypass and nonclamped ventricular fibrillation,79 and the right submammary port access method with antegrade cardioplegia and ascending aortic balloon occlusion.80 Thoracoscopic techniques have been used to aid in visualization and removal of ventricular fibroelastomas81,82 (Fig. 62-8). Myxoma removal is possible via thoracoscopy.83 Results in this limited number of selected patients have been good, but more experience and longer follow-up are needed before this can be recommended as a standard approach.

Results

Removal of atrial myxomas carries an operative mortality rate of 5% or less.21 Operative mortality is related to advanced age or disability and comorbid conditions. Excision of ventricular myxomas can carry a higher risk (approximately 10%). Our experience over the last 15 years with 85 myxomas shows no operative or hospital mortality.

Recurrence of nonfamilial sporadic myxoma is approximately 1 to 4%.4,74,75 Many large series report no recurrent tumors.74,83–86 The 20% of patients with sporadic myxoma and abnormal DNA have a recurrence rate estimated at between 12 and 40%.4 The recurrence rate is highest in patients with familial complex myxomas, all of whom exhibit DNA mutation, and this is estimated to be about 22%.4 Overall, recurrences are more common in younger patients. The disease-free interval averages about 4 years and can be as brief as 6 months.75 Most recurrent myxomas occur within the heart, in the same or different cardiac chambers, and may be multiple.19,32,87 Extra-cardiac recurrence after resection of tumor, presumably from embolization and subsequent tumor growth and local invasion, has been observed.19,87,88 The biology of the tumor, dictated by gene expression rather than histology, may be the only reliable factor predicting recurrence. DNA testing of all patients with cardiac myxoma may prove to be the best predictor of the likelihood of recurrence.89

Myxomas generally classified as "malignant" are often found on subsequent review to be sarcomas with myxoid degeneration.90 However, this issue also remains unsettled because of reports of metastatic growth of embolic myxoma fragments in the brain, arteries, soft tissue, and bones.56,88,91–97 Symptomatic lesions of possible metastatic myxoma should be excised if feasible.56,91

The extent to which patients should be subjected to long-term echocardiographic surveillance after myxoma resection is not standardized. It would seem prudent to closely follow patients who are treated initially for multicentric tumors, those whose tumors are removed from unusual locations in the heart, all tumors believed to have been incompletely resected, and all tumors found to have an abnormal DNA genotype. Patients undergoing resection of tumors thought to be myxomas but with malignant characteristics at pathologic examination should have long-term, careful follow-up.

Other Benign Cardiac Tumors

As shown in Table 62-2, myxomas comprise approximately 41% of benign cardiac tumors, with three other tumors (ie, lipoma, papillary fibroelastoma, and rhabdomyoma) together contributing a similar proportion. A number of rarely encountered tumors account for the remainder.

Lipoma

Lipomas are well-encapsulated tumors consisting of mature fat cells that may occur anywhere in the pericardium, subendocardium, subepicardium, and intra-atrial septum.2 They may occur at any age and have no sex predilection. Lipomas are slow growing and may attain considerable size before producing obstructive or arrhythmic symptoms. Many are asymptomatic and are discovered incidentally on routine chest roentgenogram, echocardiogram, or at surgery or autopsy.98,99 Subepicardial and parietal lipomas tend to compress the heart and may be associated with pericardial effusion. Subendocardial tumors may produce chamber obstruction. The right atrium and left ventricle are the sites affected most often. Lipomas lying within the myocardium or septum can produce arrhythmias or conduction abnormalities. Large tumors that produce severe symptoms should be resected. Smaller, asymptomatic tumors encountered unexpectedly during cardiac operation should be removed if excision can be performed without adding risk to the primary procedure. These tumors are not known to recur.

Lipomatous Hypertrophy of the Interatrial Septum

Nonencapsulated hypertrophy of the fat within the atrial septum is known as lipomatous hypertrophy.2 This abnormality is more common than cardiac lipoma and usually is encountered in elderly, obese, or female patients as an incidental finding during a variety of cardiac imaging procedures.84 Various arrhythmias and conduction disturbances have been attributed to its presence.85,100 The main difficulty is differentiating this from a cardiac neoplasm on echocardiography.101 After the demonstration of a mass by echocardiography, the typical T1 and T2 signal intensity of fat on MRI usually can establish a diagnosis.102,103 Arrhythmias and heart block are considered by some as indications for resection, but data are lacking as to the long-term benefits from resection.104

Papillary Fibroelastoma of the Heart Valves

Papillary fibroelastomas are tumors that arise characteristically from the cardiac valves or adjacent endocardium.105 These tumors are described as resembling sea anemones with frondlike projections in gross description (Fig. 62-9). The AV and semilunar valves are affected with equal frequency. It is now known that these are capable of producing obstruction of flow, particularly coronary ostial flow, and may embolize to the brain and produce stroke.106–115 They are usually asymptomatic until a critical event occurs. Papillary fibroelastomas of the cardiac valve should be resected whenever diagnosed, and valve repair rather than replacement should follow the resection of these benign tumors whenever technically feasible (Fig. 62-10). Cytomegalovirus has been recovered in these tumors, suggesting the possibility of viral induction of the tumor and chronic viral endocarditis.111

Rhabdomyoma

Rhabdomyoma is the most frequently occurring cardiac tumor in children. It usually presents during the first few days after birth. It is thought to be a myocardial hamartoma rather than a true neoplasm.116 Although rhabdomyoma appears sporadically, it is associated strongly with tuberous sclerosis, a hereditary disorder characterized by hamartomas in various organs, epilepsy, mental deficiency, and sebaceous adenomas. Fifty percent of patients with tuberous sclerosis have rhabdomyoma, but more than 50% of patients with rhabdomyoma have or will develop tuberous sclerosis.117 More than 90% of rhabdomyomas are multiple and occur with approximately equal frequency in both ventricles.118 The atrium is involved in fewer than 30% of patients. Pathologically, these tumors are firm, gray, and nodular and tend to project into the ventricular cavity. Micrographs show myocytes of twice normal size filled with glycogen, containing hyperchromatic nuclei and eosinophilic-staining cytoplasmic granules.2,119 Scattered bundles of myofibrils can be seen within cells by electron microscopy.118

Clinical findings may mimic valvular or subvalvular stenosis. Arrhythmias, particularly ventricular tachycardia and sudden death, may be a presenting symptom.119 Atrial tumors may produce atrial arrhythmias.119 The diagnosis is made by echocardiography. Rarely, no intramyocardial tumor is found in a patient with ventricular arrhythmias, and the site of rhabdomyoma is located by electrophysiologic study.119

Early operation is recommended in patients who do not have tuberous sclerosis before 1 year of age.86 The tumor usually is removed easily in early infancy, and some can be enucleated.86 Unfortunately, symptomatic tumors often are both multiple and extensive, particularly in patients with tuberous sclerosis, who, unfortunately, have a dismal long-term outlook. In such circumstances, surgery offers little benefit.

Fibroma

Fibromas are the second most common benign cardiac tumor, with more than 83% occurring in children. These tumors are solitary, occur exclusively within the ventricle and the ventricular septum, and affect the sexes equally. Fewer than 100 tumors have been reported, and most are diagnosed by age 2 years. These tumors are not associated with other disease, nor are they inherited. Fibromas are nonencapsulated, firm, nodular, gray-white tumors that can become bulky. They are composed of elongated fibroblasts in broad spiral bands and whirls mixed with collagen and elastin fibers. Calcium deposits or bone may occur within the tumor and occasionally are seen on roentgenography (Figs. 62-11 and 62-12).

Most fibromas produce symptoms through chamber obstruction, interference with contraction, or arrhythmias. Depending on size and location, such a tumor may interfere with valve function, obstruct flow paths, or cause sudden death from conduction disturbances in up to 25% of patients.114 Intracardiac calcification on chest roentgenograms suggests the diagnosis, which is confirmed by echocardiogram.

Surgical excision is successful in some patients, particularly if the tumor is localized, does not involve vital structures, and can be enucleated.86,120–122 However, it is not always possible to remove the tumor completely, and partial removal is only palliative, although some patients have survived many years.86,121 Operative mortality may be high in infants. Most cases are in adolescents and adults.186,120,121 Successful, complete excision is curative.120,121 Children with extensive fibromas have been treated with cardiac transplantation.122,123

Mesothelioma of the AV Node

Mesothelioma of the AV node, also termed polycystic tumor, Purkinje tumor, or conduction tumor. It is a relatively small, multicystic tumor that arises in proximity to the AV node and may extend upward into the interventricular septum and downward along the bundle of His.2 Mesothelioma is associated with heart block, ventricular fibrillation,124 and sudden death. Cardiac pacing alone does not prevent subsequent ventricular fibrillation. Surgical excision has been reported.24

Pheochromocytoma

Cardiac pheochromocytomas arise from chromaffin cells of the sympathetic nervous system and produce excess amounts of catecholamines, particularly norepinephrine. Approximately 90% of pheochromocytomas are in the adrenal glands. Fewer than 2% arise in the chest. Only 32 cardiac pheochromocytomas had been reported by 1991.125 The tumor predominantly affects young and middle-aged adults with an equal distribution between the sexes. Approximately 60% occur in the roof of the left atrium. The remainders involve the interatrial septum or anterior surface of the heart. The tumor is reddish brown, soft, lobular, and consists of nests of chromatin cells.

The patients usually present with symptoms of uncontrolled hypertension or are found to have elevated urinary catecholamines. The tumor usually is located by scintigraphy using [I131] metaiodobenzylguanidine126 and CT or MRI.126 Cardiac catheterization with differential blood chamber sampling sometimes is necessary in addition to coronary angiography.125 After the tumor is located, it should be removed using cardiopulmonary bypass with cardioplegic arrest. Patients require preanesthetic alpha and beta blockade and careful intraoperative and immediate postoperative monitoring. Most tumors are extremely vascular, and uncontrollable operative hemorrhage has occurred.126 Resection may require removal of the atrial and/or ventricular wall or a segment of a major coronary artery.135 Explantation of the heart to allow resection of a large left atrial pheochromocytoma has been attempted.127 Transplantation has been performed for unresectable tumor and complete excision produces cure.121–123

Paraganglioma

Paragangliomas are endocrine tumors that can secrete catecholamines. As a result, their presentation is often similar to that of pheochromocytomas. When found within the thoracic cavity, they are located most often in the posterior mediastinum. Paragangliomas typically present with atypical chest pain.128,129 On echocardiography, they are often large and highly vascular tumors.130 On cardiac catheterization, they may be intimately associated with the coronary arteries (Fig. 62-13). If they involve the left atrium, the technique of cardiac autotransplantation may be used to completely resect them131 (Fig. 62-14).

Hemangioma

Hemangiomas of the heart are rare tumors (24 clinical cases reported), affect all ages, and may occur anywhere within the heart.132,133 These are vascular tumors composed of capillaries or cavernous vascular channels. Patients usually develop dyspnea, occasional arrhythmias, or signs of right-sided heart failure.134 Diagnosis is difficult, and echocardiography or cardiac catheterization can establish a diagnosis of cardiac tumor by showing an intracavity filling defect.135 CT and MRI show axial T2-weighted MRI should show a high signal mass owing to vascularity (Fig. 62-15). Coronary angiography typically shows a tumor blush and maps the blood supply to the tumor. During resection, meticulous ligation of feeding vessels is required to prevent postoperative residual arteriovenous fistulas or intracavity communications. Partial resections have produced long-term benefits.132 Tumors rarely resolve spontaneously.136

Teratoma

Cardiac teratoma is a rare tumor that typically presents in infants and young children.137 About 80% of the tumors are benign.138 These tumors are discovered by echocardiography after a variety of symptoms lead to cardiac or mediastinal evaluation. There is little experience with surgical removal, which should be possible.

Castleman Tumor

Castleman disease is a poorly understood lymphoproliferative disorder. The disease was first described by Castleman and colleagues in 1956.139 It typically presents as a solitary lesion in the mediastinum. The most common histologic type is hyaline vascular, which accounts for approximately 90% of cases and often behaves in a benign fashion. The more aggressive subgroups are the plasma and mixed-cell types, which have a more malignant behavior.140 Patients may have a localized or multicentric disease with lymph node involvement, typically in the mediastinum. These tumors typically present as well-circumscribed masses. There have been reports of Castleman disease with myocardial and coronary artery invasion or development of a coronary pseudoaneurysm.141 In these more aggressive cases, cardiac assist devices have been used as a bridge to recovery141 (Figs. 62-16 and 62-17). CT imaging of the lesions reveals atypical or target-like enhancement that corresponds to various degrees of degeneration, necrosis, and fibrosis. Technetium-99m tetrofosmin and [I123] beta-methyliodophenyl pentadecanoic acid (BMIPP) imaging may aid in the diagnosis. On BMIPP, these tumors show reduced uptake compared with the surrounding normal myocardium.142 Complete surgical resection is considered curative.143

Primary cardiac malignancy is very uncommon, with only 21 surgically treated cases noted in a 25-year surgical experience from 1964 to 1969, combining the experience of two large institutions, the Texas Heart Institute and the M. D. Anderson Cancer Center in Houston.144 Additional current reports from the Texas Medical Center include a series from the Methodist Debakey Heart and Vascular Center and M. D. Anderson Cancer Center of 27 patients selected from 1990 to 2006.144 Approximately 25% of primary cardiac tumors are malignant, and of these, about 75% are sarcomas. McAllister's survey of cardiac tumors found the most common to be angiosarcomas (31%), rhabdomyosarcomas (21%), malignant mesotheliomas (15%), and fibrosarcomas (11%),2 see Table 62-4.

Rather than histologic classification of cardiac sarcoma, we propose a classification system based on anatomic location. Histology does not greatly affect treatment or prognosis as much as anatomic location.144,145 The revised classification system divides primary cardiac sarcomas into right heart sarcomas, left heart sarcomas and pulmonary artery sarcomas, and these are the categories that will be used in the discussion to follow.

Right heart sarcomas tend to metastasize early, present as bulky masses (Fig. 62-18), and are characteristically infiltrative.145 Right heart sarcomas often occupy much of the right atrium growing largely in an outward pattern, and often avoid heart failure until the latest stage of presentation. This presentation often allows time for neoadjuvant chemotherapy in an attempt to shrink the tumor and sterilize the infiltrating edges to increase chances of obtaining a resection with microscopically negative margins.

Left heart sarcomas tend to be more solid with less infiltration than right heart sarcomas and tend to metastasize later in the course of disease.187 Left-sided sarcomas are most often located in the left atrium, and tend to grow into the wall. Diminution of blood flow quickly results in life-threatening heart failure. Neoadjuvant chemotherapy can rarely be used because of this presentation. Most left atrial sarcomas are initially clinically diagnosed as mxyomas, have a positive resection margin, rapidly recur, and require repeat resection.

Primary malignant cardiac tumors arise sporadically, showing no inherited linkage. Although they may span the entire age spectrum, they usually occur in adults more than 40 years of age. The patients usually present with symptoms of congestive heart failure, pleuritic chest pain, malaise, anorexia, and weight loss.137,146 The most common symptom has been dyspnea147 (Table 62-5). Some develop refractory arrhythmias, syncope, pericardial effusion, and tamponade.147 The chest x-ray may be abnormal and even show a mass lesion, but the definite diagnosis usually is made with cardiac echocardiography.146,148 Right atrial lesions are more frequently malignant (usually angiosarcoma) than left-sided lesions (usually myxoma but, when malignant, often malignant fibrous histiocytoma). If malignancy is suspected, chest CT or MRI may suggest histology and provide detailed anatomy and help in staging and assessing resectability. The current status of positron-emission tomographic (PET) scans in evaluating these patients remains controversial. We perform cardiac catheterization on all patients older than 40 years of age presenting with intracardiac masses and on all patients with large right atrial masses. Malignancy may be suggested and coronary involvement suspected by tumor blush. This is not pathognomic because we have seen a large feeding vessel and tumor blush in a histologically confirmed myxoma.

Unfortunately, primary cardiac malignancy may grow to a large size before detection and involve portions of the heart not amenable to resection. Some of these patients have been considered for transplantation and will be discussed later. Otherwise, palliative medical therapy can be attempted with radiation therapy, although success in both symptom relief and longevity has been somewhat limited. Whether the tumor is primary or secondary, the decision to resect is based on tumor size and location and an absence of metastatic spread seen on complete evaluation. Unfortunately, most primary cardiac malignancies that have been referred to our center were considered to be benign initially and were resected incompletely at presentation. If malignancy is suspected or confirmed, and if the lesion appears anatomically resectable and there is no metastatic disease, then resection should be considered. If complete resection is possible, surgery provides better palliation and potentially can double survival.149 After resection, we recommend adjuvant chemotherapy and believe that this can improve survival.138,149 Complete resection will depend on the location of the tumor, the extent of involvement of the myocardium and/or fibrous skeleton of the heart, and histology.

Angiosarcoma

Angiosarcomas are two to three times more common in men than in women and have a predilection for the right side of the heart. Eighty percent arise in the right atrium.147,150,151 These tumors tend to be bulky and aggressively invade adjacent structures, including the great veins, tricuspid valve, right ventricular free wall, interventricular septum, and right coronary artery150 (Fig. 62-19). Obstruction and right-sided heart failure are not uncommon. Pathologic examination of resected specimens demonstrates anastomosing vascular channels lined with typical anaplastic epithelial cells. Unfortunately, most of these tumors have spread by the time of presentation, usually to the lung, liver, and brain.147 Without resection, 90% of the patients are dead within 9 to 12 months of diagnosis despite radiation or chemotherapy.22,147 We have seen carefully selected patients without evidence of spread on metastatic evaluation who have undergone complete surgical resection with subsequent chemotherapy (Fig. 62-20). In addition to surgical resection of the right atrium, right coronary bypass and even tricuspid valve repair or replacement may be undertaken (Fig. 62-21). We have had no hospital mortality in this small group, and most patients die from metastasis rather than recurrence at the local site.152

Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults. Its occurrence as a cardiac primary malignancy has been relatively recently accepted as a specific entity. It is characterized histologically by a mixture of spindle cells in a storiform pattern, polygonal cells resembling histiocytes, and malignant giant cells. The cell of origin is the fibroblast or histioblast.148,153 It usually occurs in the left atrium and often mimics myxoma. In fact, every left atrial MFH referred to our institution has been previously incompletely resected when thought to represent a myxoma. The tendency to metastasize early is not as prominent as with angiosarcoma. Several reports document rapid symptomatic recurrence after incomplete resection despite chemotherapy. These patients often die of local cardiac disease before the development of metastases. We believe that if complete resection can be obtained (particularly if the malignant nature is recognized and complete resection can be done at the original operation) and adequate chemotherapy can be provided, we may improve survival in this otherwise dismal disease.

Rhabdomyosarcoma

Rhabdomyosarcomas do not evolve from rhabdomyomas and occur equally in the sexes. The tumors are multicentric in 60% of patients and arise from either ventricle. These tumors frequently invade cardiac valves or interfere with valve function because of their intracavitary bulk. Microscopically, tumor cells demonstrate pleomorphic nuclei and spidery, wispy, streaming eosinophilic cytoplasm, usually in a muscle-like pattern.

The tumors are aggressive and may invade pericardium. Surgical excision of small tumors may be rational, but local and distant metastases and poor response to radiation or chemotherapy limit survival to less than 12 months in most of these patients.120,137,138,149,154

Other Sarcomas and Mesenchymal-Origin Tumors

McAllister and Fenoglio found that malignant mesotheliomas arising from the heart or pericardium and not from the surrounding pleura were the third most common malignant cardiac tumors and that fibrosarcomas were fourth.2 However, in the two decades since their work, clinicians have rarely encountered these tumors. This apparent decrease in incidence may be related to changes in histologic criteria for classifying primary malignant neoplasms since their study.5,132,138,147–149,154–155

The histology of these tumors can be ambiguous and difficult. These neoplasms can resemble other sarcomas, and some might be deemed fibrous histiocytomas today. The behavior of these tumors is more important, and as with other cardiac sarcomas, resection of small tumors in the absence of known metastasis perhaps is justified, but data are scarce.22,147,149,154 This being said, it is important to rule out more diffuse thoracic involvement with mesothelioma before considering resection of an isolated cardiac or pericardial mesothelioma. A PET scan may be considered, and any suspicious pleural thickening or effusion should be evaluated carefully both radiographically and histologically.

Myosarcoma, liposarcoma, osteosarcoma, chondromyxosarcoma, plasmacytoma, and carcinosarcoma arising from the heart all have been reported,155–158 but by the time diagnosis is made, only palliative therapy usually can be offered, and surgery is indicated only occasionally. Regardless of therapy, it is unusual for patients with these diagnoses to survive more than a year.

Right-Sided Cardiac Sarcomas

The prognosis without surgery for right heart sarcoma is dismal, and surgical resection is the only treatment modality shown to increase survival. Complete surgical resection is complicated both by the bulky infiltrative nature of right heart sarcoma and the high incidence of metastatic disease at presentation. The author's current approach to right heart sarcomas has been to begin with neoadjuvant chemotherapy once a definitive tissue diagnosis of sarcoma is made using a right heart catheterization biopsy. Occasionally, a diagnosis of lymphoma or other tumor is made. Multidisciplinary treatment planning based on the correct diagnosis is imperative. After 4 to 6 rounds of chemotherapy (with repeat imaging every other cycle to assess for tumor response), the patient is evaluated for surgical resection. This treatment regimen aims to improve on the current microscopic complete resection rate of 33%. The initial diagnostic test for right heart sarcomas is transthoracic echocardiography, which rarely misses these usually large tumors. Unlike large left atrial masses that are usually benign myxomas, the majority of large right atrial masses are typically malignant (Fig. 62-22). The majority of right heart sarcomas referred to our specialty center have yet to undergo attempted resection, unlike left-sided heart tumors which are typically resected under the presumption they are benign mymomas. The primary reason for local failure of a right heart sarcoma is incomplete resection, typically because of surgical hesitancy to achieve complete resection because of involvement of the right coronary artery.

Most right heart sarcomas are angiosarcomas.2 (Fig. 62-23) These tumors may occur in the right atrium (Fig. 62-24) or the right ventricle but far more commonly arise from the right atrium. They replace the right atrial wall and frequently grow into the cardiac chamber and into adjacent tissues. Right heart tumors tend to be infiltrative and form microscopic "fingers" of tumor extending beyond the margins of gross disease. Diffuse pericardial involvement, right ventricular involvement, or encasement of great vessels or veins often precludes surgical resection. The tricuspid valve, right coronary artery, and up to about 30% of the right ventricular muscle mass may be resected and replaced or reconstructed with reasonable risk to achieve a complete resection. Thus, all patients are evaluated preoperatively with coronary arteriography. In patients treated without surgical resection, the survival is approximately 10% at 12 months.159 A microscopically negative surgical resection margin has been shown to extend survival149 and remains standard therapy. Although some patients having a radical resection still locally recur, the leading cause of death is distant metastatic disease. Complete resection followed by adjuvant chemotherapy has been shown to extend survival.149,159

Patients with even limited metastatic disease that did not respond well to chemotherapy or who developed new metastatic disease while on treatment are not considered candidates for surgery. Patients with widely metastatic disease are not considered candidates unless palliative surgery because of severe symptoms is recommended. Every patient should be referred to oncology for potential continuation of chemotherapy after recovery from surgery.

Based on the anatomic extent of tumor and the needed margins for resection, venous cannulation for cardiopulmonary bypass must be carefully planned and individualized to each patient. Directly cannulating the high superior vena cava (SVC) for upper body drainage and cannulating directly into the inferior vena cava (IVC) at the diaphragm usually allows adequate exposure for complete inferior resection, but occasionally femoral cannulation aids in exposing the more caudal structures of the right heart. Aortic cannulation is standard, as it is distant from the tumor. The right atrium can be completely resected and replaced with Bovine pericardium. If the resection involves the SVC or IVC, a vascular stapler can be used to staple lengthwise creating a tube from Bovine pericardium to recreate the vein segment (Fig. 62-25). One particular area of danger is at the right atrial junction with the root of the aorta, as overzealous resection in this area will result in damage to the fibrous skeleton of the heart, which is characteristically difficult to repair. Incomplete resection leaving gross disease rapidly leads to regrowth of the tumor and should be avoided if at all possible. When right coronary artery involvement is suspected, mobilization of the right internal mammary artery is performed at the beginning of the operation. Right ventricular wall can be simply partially replaced with Bovine pericardium or incorporated into a prosthetic tricuspid valve used for valve replacement. For an illustration of the steps involved in the resection and later reconstruction of a right heart sarcoma, please refer to Fig. 62-26.

Left-Sided Cardiac Sarcomas

Surgical resection is the most effective therapeutic option for patients with malignant left-sided cardiac tumors. Delay can result in death from obstruction to flow within the heart or embolization, which may occur in as many as 8% of patients awaiting operation. The clinical presentation of patients with primary left heart sarcoma depends on the anatomic location and extent of the tumor and is not influenced by histology. Most primary left heart sarcomas are reported to occur in the left atrium, a concept supported by the author's experience; 22/24 (92%) occurred in the left atrium and 2/24 (8%) occurred in the left ventricle. Most left atrial masses seen by cardiac surgeons are mistaken to be benign myxomas. Every left atrial sarcoma patient referred to our center previously underwent resection for a presumed myxoma that was later found to be a cardiac sarcoma. Each of these cases had rapid reappearance of the left atrial tumor at the site of resection likely representing regrowth of persistent incompletely resected sarcoma. Intracavitary left ventricular tumors are very uncommon and are rarely mistaken for a simple cardiac myxoma. Heart failure caused by obstruction of intracardiac blood flow is the most common and concerning presenting symptom. Heart block from local invasion, arrhythymia, pericardial effusion, distal embolus, fever, weight loss, and malaise are also seen. The mean age of presentation is reported to be 40 years of age.148 Transthoracic echocardiography is the most common initial diagnostic test. Transesophageal echocardiography is specifically recommended for in all left-sided cardiac tumors because of increased resolution of left-sided structures. Cardiac MRI and PET/CT scans are also obtained in patients known or suspected to have sarcoma.

Once diagnosed, primary cardiac sarcoma patients have an often dismal prognosis. When medically treated, the survival at 12 months is less than 10%.159 Most reports in the literature are either autopsy series or individual case reports or small case series. Operative mortality usually exceeds 20 percent, and the mean survival is typically around 12 months.160–162 Many published series focus on primary cardiac sarcoma in general without regard to anatomic location. The Mayo Clinic reported 34 patients over 32 years with a median survival of 12 months.163 A combined series from the Texas Heart Institute and the MD Anderson Cancer Center reported an actuarial survival of 14% at 2 years in 21 patients over a 26-year period.156 The authors have previously reported a combined multimodality approach, and found a median survival of 23.5 months in 27 patients over 16 years with survival of 80.9% at one year and 61.9% at two years.146 Subsequent analyses show histologic type does not influence survival or treatment approach.164 The major determinant of clinical presentation and surgical approach is anatomic location. Currently, these tumors are grouped based on location, such as pulmonary artery sarcomas, right heart sarcomas, or left heart sarcomas.165

The high rate of local recurrence and secondary resections reported in the literature166 indicate the left atrium and ventricle present unique anatomic exposure challenges. Complete resection and reconstruction is complicated because of the left heart proximity to vital structures. Often, a surgeon's inability to adequately visualize vital structures and reconstruct leads to an inadequate resection with rapid regrowth of tumor. Typically, left atrial tumors are approached through the interatrial groove. The interatrial groove is often an adequate approach for benign tumors, but is limited for malignant tumors that are often larger and require a more generous margin of resection. We have considered complete cardiectomy and orthotopic cardiac transplantation for complete removal of these tumors. Although feasible, this approach requires the availability of a donor and postoperative immunosuppression; both of which present potential problems in cancer patients. Additionally series using orthotopic cardiac transplantation for this purpose have only shown a median survival of 12 months.167 Left ventricular tumors can be approached through the aortic valve, the mitral valve or through a ventriculotomy. A transaortic valve approach works nicely for benign tumors82 but is inadequate for malignant tumors because of their size and the amount of resection needed. A ventriculotomy through normal ventricular muscle is possible, but not ideal. The author's group adopted the approach of cardiac explantation, ex vivo tumor resection, cardiac reconstruction, and reimplantation of the heart (cardiac autotransplantation), which permits a radical tumor resection and accurate reconstruction.

Cardiac Autotransplantation

The technique of cardiac autotransplantation was introduced for cardiac tumors by Cooley in 1985 to deal with a large left atrial pheochromocytoma.127 Although this case was not successful, it introduced the senior author (MJR) to the technique and its potential use for cardiac tumors. The author's group did the first successful cardiac auto transplant for cardiac sarcoma in 1998,153 also reporting this for left atrial sarcoma and left ventricular sarcoma.168 Working closely with the MD Anderson Cancer Center, the Methodist Hospital has now performed 28 cardiac auto transplants, with 23 of these for primary cardiac sarcoma.

Cardiac auto transplantation has several fundamental differences from standard orthotopic heart transplantation.169 In orthotopic heart transplantation, unless a domino procedure is being done, the explanted heart is not to be used and any damage to its structures is inconsequential. For a complete video of an autotransplant including replacement of the mitral valve, please refer to the movie attached to this chapter. Therefore, the cardiectomy can be performed leaving a wide margin of remaining tissue to use in tailoring the heart to be implanted without regard to cutting critical structures such as the coronary sinus. Similarly, the donor heart can usually be harvested with extra tissue at its margins to be used to help tailor the implantation unlike traditional orthotopic heart transplant surgery. The heart must be excised in cardiac autotransplantation in a manner that does not damage any structures that cannot be repaired, replaced, or are vital to cardiac function. Additionally, if the heart is simply excised and reimplanted, loss of workable tissue makes reimplantation more challenging than orthotopic heart transplantation. Cannulation techniques must take into consideration planned explantation. The aorta can be cannulated distally in the transverse arch. Venous cannulation must be directly into the SVC and IVC just below the right atrial junction. This requires greater exposure and mobilization of the SVC and IVC. After commencing CPB, further mobilization of the SVC and IVC is performed until each is completely free and surround with umbilical tapes on a tourniquet. Wide mobilization of the interatrial groove and circumferential mobilization of the ascending aorta and pulmonary artery follows cannulation. This facilitates both accurate excision of the heart and reimplantation. The ascending aorta is cross-clamped and antegrade cold blood potassium cardioplegia is given (10 cc/kg) to achieve cardiac arrest. The left atrium is opened at the beginning of cardioplegia, and a sump drain placed to decompress the heart. After cardioplegia and cardiac quiescence, the left atrium is opened to confirm pathology and appropriateness of autotransplantation. The SVC first divided beyond the right atrial junction. This is followed by IVC division which should be transected near the right atrial and SVC junction. For each transection, it is important to note the rim of tissue being left behind retracts substantially towards the venous cannulae and an extraordinarily wide rim must be left or reimplantation at the IVC can be exceedingly difficult. The ascending aorta is divided about 1 cm distal to the sinotubular junction and the pulmonary artery is divided just proximal to its bifurcation. The left atrium transection is then completed, dividing the atrium just anterior to the pulmonary veins and on the left side equal distant between the pulmonary veins and the mitral valve and left atrial appendage. This allows complete removal of the heart which is placed into a basin of ice slush (Fig. 62-27). The posterior left atrium is then inspected, and any tumor is widely excised (Fig. 62-28). Bovine pericardium is used for reconstruction, and the pulmonary veins may be individually reimplanted into new orifices cut in the bovine pericardium or left as a cuff, if pathology permits. The anterior left atrium can be entirely removed, including the mitral valve, leaving only a mitral annulus.

Bovine pericardial reconstruction starts with cutting a hole to match the mitral annulus opening. Mitral valve replacement using pledgeted 2-0 ticron sutures begins with pledgets placed on the left ventricular side of the annulus, passing thru the annulus, through the bovine pericardium, and then through the prosthetic mitral valve. When the sutures are tied, the neo atrial wall is sealed to the valve and annulus. The anterior and posterior bovine pericardium can then be tailored by cutting darts and sewing them together before reanastomosis. Reimplantation is similar to standard cardiac transplantation, beginning with the left atrium anastomosis. The right atrium is then attached to the IVC, and then the right atrium to the SVC. If either of these anastomoses appear to be under excess tension, an interposition graft of Gore-Tex, Dacron, or crafted pericardial tube graft can be used to bridge the defect successfully (Fig. 62-29). The pulmonary artery and aorta are reanastomosed in a standard fashion using Prolene suture, warm-blood potassium cardioplegia is given antegrade, and the aortic cross-clamp is removed. The procedure for left ventricular tumors is similar, and occasionally requires mitral valve excision or partial excision of the interventricular septum (Fig. 62-30). The interventricular septum can be reconstructed with bovine pericardium and valve replacement is typically done with a tissue valve. Although these patients are young, a tissue valve is often chosen to avoid anticoagulation. Issues with structural valve deterioration are of less concern because survival is counted now in years rather than decades.

Because of poor survival, lesions requiring a pneumonectomy in addition to cardiac autotransplant should be considered a contraindication to surgery. This can usually be determined preoperatively with cardiac MRI to evaluate restriction of blood flow through the pulmonary veins.

Lymphomas

Lymphomas may arise from the heart, although this is rare.170 Most of these tumors respond to radiation and chemotherapy, and surgical resection is rarely indicated.152 Even when complete resection is not possible, incomplete resection has been performed to relieve acute obstructive systems and, when followed with radiation and chemotherapy, has allowed for extended survival in selected patients.

Pulmonary Artery Sarcomas

Most pulmonary artery sarcomas are classified as. The most frequent presenting symptom is shortness of breath and peripheral edema from concomitant right-sided heart failure.171 The diagnostic modalities of choice for both the initial evaluation and monitoring for recurrence after resection for pulmonary artery sarcomas are chest CT or MRI (Figs. 62-31, 62-32, and 62-33).

Pulmonary artery sarcomas are very rare tumors that are often confused with acute or chronic pulmonary embolus. This confusion has led to both delay in diagnosis and many being treated with a tumor thromboendarterectomy approach rather than radical resection. These tumors usually are discovered after they have grown to considerable size (Fig. 62-34). Pulmonary artery sarcoma can present with cough, dyspnea, hemoptysis and chest pain that may mimic pulmonary embolus (PE). Constitutional symptoms often present include fever, anemia and weight loss which are more consistent with malignancy than PE and these mass lesions will not decrease in size with anticoagulation. These tumors tend to arise from the dorsal surface of the main pulmonary artery just beyond the pulmonary valve.172 They form from multipotential mesenchymal cells from the muscle remnant of the bulbus cordis173 in the intimal and subintimal surfaces.164 The tumor then tends to grow distally along the artery, rarely penetrating the actual wall of the artery but rather distending it (Fig. 62-35). This characteristic is important to note when planning surgical resection. Distal extension can go to the lung parenchyma itself as emboli, infarction, or metastasis.174 Although survival difference based on cell histology is found in limited cases, that has not been our experience in cardiac sarcoma in general.171 Surgical resection remains the primary method of treatment in patients with PA sarcoma and the only method shown to increase survival. A staging system has been developed to further classify these patients and determine who should be offered surgical therapy (Table 62-6).

Resection often requires replacement of a portion of the pulmonary root and branch pulmonary arteries using a pulmonary homograft with or without artificial graft. Pneumonectomy may be required to resect the tumor completely. Because exposure of the right main pulmonary artery may require division of the aorta and possibly the SVC, we plan surgical cannulation for cardiopulmonary bypass by using dual venous cannulation with direct SVC cannulation and normal IVC cannulation via the right atrium. Arterial cannulation via the ascending aorta is routine. Both SVC and IVC are isolated with tourniquets to control blood flow into the right heart. Cardiopulmonary arrest is achieved with cold potassium blood cardioplegia. Fortunately, these tumors rarely penetrate the pulmonary artery wall, allowing reasonable mobilization. The main pulmonary artery has always been involved in our experience and the pulmonary valve is involved 30% of the time.171 The main pulmonary arteries can be resected out to their first branch points on each side from a median approach. In cases where one pulmonary artery is relatively free and the other is involved deep into the lung, a pneumonectomy may be required. In this case, the pulmonary veins and main bronchus are dissected and divided before CPB is instituted to avoid bleeding while heparinized. The branch PAs and main pulmonary artery are mobilized, CPB is instituted, and the involved main PA is divided. In such cases, the involved lung with little blood flow once resected may result in improved hemodynamics; especially after removal of tumor obstructing the contralateral pulmonary artery. Once each pulmonary artery has been divided or in the case of pneumonectomy the lung and main PA removed, the main PA trunk can be assessed for pulmonary valve involvement. If the pulmonary valve is involved, the entire PA trunk must be removed and replaced by a pulmonary allograft. Removal of the entire PA trunk and replacement by an allograft is similar to mobilization and replacement techniques for a Ross procedure.174 If the resection of the right and/or left main PA is limited, then the allograft branches may be adequate to span the defect. When tumor extension is too distal for this, a Gore-Tex (ePTFE) graft can be used to interpose between the distal right PA resection point to distal left PA resection point and then implantation of the pulmonary allograft into the side of the ePTFE graft is performed. Despite the extensive nature of the resection, separation from CPB has not been difficult. The surgery relieves the patient of severe PA obstruction that is present preoperatively.

The authors have successfully resected pulmonary artery sarcomas in 10 patients, three of whom required concomitant pneumonectomy. There were no in-hospital or 30-day deaths, and all patients were discharged home. Our longest survivor currently has lived more than 100 months and has no known disease. In most cases, adjuvant chemotherapy is used, even in the face of clear surgical margins. Radical PA resection is both safe and appears to prolong survival compared to minimal or palliative resection. Resection in conjunction with chemotherapy also appears to prolong survival. Currently, recommendations to record such rare tumors in a national registry may allow better analysis of long-term outcomes.

Heart Transplantation

Malignant primary cardiac tumors may grow to a large size before detection. Additionally, extensive myocardial involvement or location affecting the fibrous trigone of the heart may make complete resection impossible. Because complete resection yields better results than incomplete resection, orthotopic cardiac transplantation has been considered as a treatment option. Reports of transplantation for a number of cardiac tumors, including sarcoma,174–177 pheochromocytoma,170 lymphoma,171 fibroma,133 and myxoma have appeared. However, the long-term results are uncertain because some patients die from recurrent metastatic disease despite transplantation.170,171,173 As of 2000, 28 patients had been reported involving orthotopic transplantation for primary cardiac tumors, and of these, 21 had malignant tumors.173 The mean survival for patients with primary cardiac malignancy was 12 months. Although technically feasible in some cases, orthotopic transplantation is hindered by a scarcity of donor organs and coupled with an extensive recipient list of patients without cancer. In addition, the large size of the tumor when diagnosed often necessitates rapid intervention for progressive congestive heart failure. Finally, the effect of immunosuppression on any remaining malignancy is unknown. In most cases, orthotopic transplantation is reserved for unresectable benign tumors, such as cardiac fibroma.

Approximately 10% of metastatic tumors eventually reach the heart or pericardium, and almost every type of malignant tumor has been known to do so.2,7 Secondary neoplasms are 20 to 40 times more common than primary.4,174 Up to 50% of patients with leukemia develop cardiac lesions. Other cancers that commonly involve the heart include breast cancer, lung cancer, lymphoma, melanoma, and various sarcomas.2,175,176 Metastases involving the pericardium, epicardium, myocardium, and endocardium roughly follow that order of frequency2,7 as well (Table 62-7).

The most common means of spread, particularly for melanoma, sarcoma, and bronchogenic carcinoma, is hematogenous and ultimately via coronary arteries. In addition, metastasis can reach the heart through lymphatic channels; through direct extension from adjacent lung, breast, esophageal, and thymic tumors; and from the subdiaphragmatic vena cava. The pericardium is involved most often by direct extension of thoracic cancer; the heart is the target of hematologous and/or retrograde lymphatic metastasis.5 Cardiac metastases rarely are solitary and nearly always produce multiple microscopic nests and discrete nodules of tumor cells2,7 (Fig. 62-36). Cardiac metastases produce clinical symptoms in only about 10% of afflicted patients.177,178 The most common symptom is pericardial effusion or cardiac tamponade. Occasionally, patients develop refractory arrhythmias or congestive heart failure. Chest radiographs and electrocardiograms tend to show nonspecific changes, but echocardiography is particularly useful for diagnosis of pericardial effusion, irregular pericardial thickening, or intracavity masses interfering with blood flow.

Surgical therapy is limited to relief of recurrent pericardial effusions or, occasionally, cardiac tamponade. In most instances, these patients have widespread disease with limited life expectancies. Surgical therapy is directed at providing symptomatic palliation with minimal patient discomfort and hospital stay. This is most readily accomplished via subxiphoid pericardiotomy, which can be accomplished under local anesthesia if necessary with reliable relief of symptoms, a recurrence rate of about 3%, and little mortality.176 Alternatively, a large pericardial window in the left pleural space can be created using thoracoscopy, but we would recommend this only under unusual circumstances.179 This can be accomplished with minimal patient discomfort but does require general anesthesia with single-lung ventilation and may be poorly tolerated by patients with hemodynamic deterioration secondary to large effusions.

Abdominal and pelvic tumors on occasion may grow in a cephalad direction via the inferior vena cava to reach the right atrium. Subdiaphragmatic tumors are frequently renal carcinomas, although hepatic, adrenal, and uterine tumors occasionally have exhibited this behavior. Up to 10% of renal cell carcinomas invade the inferior vena cava, and nearly 40% of these reach the right atrium.188 Radiation and chemotherapy are not effective in relieving the obstruction of blood flow. If the kidney can be fully removed, as well as the tail of the tumor thrombus, survival can approach 75% at 5 years.96,182

Renal cell tumors with atrial extension typically are resected with abdominal dissection to ensure resectability of the renal tumor. Initially, we performed a concomitant median sternotomy and often used cardiopulmonary bypass with hypothermic circulatory arrest when treating these patients. However, we have changed our approach and now work closely with our liver transplant surgeons who have extensive experience in the area of the retrohepatic vena cava. We have found that we can expose the vena cava up to the right atrium through an abdominal incision. With ligation of the arterial inflow, the tumor tail often shrinks below the diaphragm, and in almost all circumstances, this can be removed without the use of cardiopulmonary bypass. Occasionally venovenous bypass as used in hepatic transplantation is necessary to occlude inflow through the inferior vena cava, but this is unusual. If the tumor is too complex for this maneuver, then a median sternotomy is performed, and cardiopulmonary bypass with hypothermic circulatory arrest can be used to remove the tumor from the cardiac chambers down into the inferior vena cava. Perfusion can be restarted, followed by removal of the rest of the tumor. Although it leads to adequate exposure, significant problems with coagulopathy are often apparent after cardiopulmonary bypass and profound hypothermia.

A 5-year survival rate of 75% has been achieved following nephrectomy with resection of right atrial tumor extension.181,182 Other subdiaphragmatic tumors with atrial extension that have been resected successfully include hepatic and adrenal carcinoma, as well gynecologic tumors.183–186,192

This is an exciting time for investigators involved in the search for novel therapies for tumors such as many of those discussed in this chapter. A "new biology" is being developed in laboratories around the world working in these areas, and this is supplanted by the knowledge that is being obtained from the concerted Human Genome Project and the subsequent development of proteomics.187 It is incumbent on the thoracic surgeon involved in the care of patients with cardiac tumors to have some degree of familiarity with the terms and promise of these advances because significant additional improvement in survival of many of these patients is unlikely to result from further advances in surgical technique.

Interestingly, many sarcomas demonstrate reproducible translocations that allow for the production of novel chimeric genes that may code for a variety of fusion proteins. Many of these proteins have been found to engender cellular phenotypic malignant changes, resistance to apoptosis, and unfettered growth.188 Although not associated with cardiac involvement, the fusion proteins EWS-FL11 and EWS-ERG are noted in Ewing's sarcoma. When full-length antisense oligonucleotide constructs are used to target the mRNA of these proteins, protein expression is downregulated, and an eightfold increase in apoptosis sensitivity is noted.180 These fusion proteins have been noted in some forms of rhabdomyosarcoma, and the most common is PAX3-FKHR. This oncoprotein combines components of two strong transcriptional activators and may increase the production of the downstream antiapoptotic protein BCL-XL. Antisense oligonucleotides directed at this oncoprotein mRNA have led to apoptosis in rhabdomyosarcoma cells.189,190 A similar translocation and fusion protein have been noted in fibrosarcoma. This translocation [t(12;15)(p13q25)] brings together genes from chromosomes 12 and 15, which combines a transcription factor with a tyrosine kinase receptor. The resulting fusion protein is a tyrosine kinase that has oncogenic potential.191 Reproducible translocations and fusion proteins with downstream effectors of malignant behavior have not been described for angiosarcoma, but they are actively being sought.192 Antisense treatment has been maligned in the past owing to problems with both delivery and stability of therapeutic constructs. However, sophisticated biochemical alteration of these molecules has improved stability, and two recent solid tumor trials using antisense therapy for salvage have demonstrated positive results.193 Additional methods of delivering antisense to tumor cells, including viral vector delivery, have been developed. Finally, in addition to antisense methods, small molecule inhibition of many of these fusion proteins should be possible.

Angiosarcoma is an obvious target for therapies based on antiangiogenesis. The weak antiangiogenic properties of interferon-alpha are presumed to be the mechanism that accounts for responses to this agent in this tumor.194 Multiple new antiangiogenic agents are being evaluated currently in phase I and II trials, and a number of noncardiac angiosarcoma patients have been treated at our institution on this basis. We have noted several to develop stabilized disease, but no definitive data are yet published. Certainly, the use of these agents in these vascular-origin tumors is theoretically attractive.

Viral vector–mediated gene therapy has been evaluated for various sarcomas in the preclinical setting. A number of potential targets exist for these sorts of therapies. Although p53 is not commonly mutated or absent, mdm-2 is often overexpressed in many sarcomas, including angiosarcoma. This gene is a known oncogene that is able to directly induce cellular transformation. Importantly, when overexpressed, it binds to and inhibits p53 activity, even though expression of p53 may appear normal. Overexpression of mdm-2 also has been associated with VEGF overproduction and angiogenesis.194 Preclinical studies of adenoviral vector p53 transduction of sarcoma in SCID mice have demonstrated growth delay, tumor regression, and decreases in VEGF expression.195 Many other targets for this approach, including inhibition of NF-κB expression using an adenoviral-dominant negative Iκ-βα construct and prodrug-mediated gene therapy using a doxorubicin prodrug and adenoviral transfer of a metabolizing enzyme in sarcoma cells, have been shown to be effective.183 Unfortunately, the application of viral-mediated gene therapy paradigms to this tumor suffers the same problems of targeting, transgene expression durability, and immune response that are problematic for the field in general.

In regard to molecular diagnosis, there are no reproducible familial patterns for development of most malignant tumors. However, familial cardiac myxoma, rhabdomyoma, and fibroma may exhibit reproducible genetic abnormalities that lend themselves to the development of genetic testing to identify individuals at risk. Familial myxoma syndrome, or Carney complex, has been associated with mutations in the 17q24 gene PRKAR1a that codes for the R1a regulatory subunit of cAMP-dependent protein kinase A (PKA).195 Although not widely available, genetic diagnosis of this syndrome is now technically achievable.196 Reproducible mutations in the TSC-1 and TSC-2 genes in patients with tuberous sclerosis and cardiac rhabdomyoma, as well as mutations in the PTC gene of patients with the Gorlin syndrome and cardiac fibroma, have been noted.197–200 It is hoped that in the near future we will be able to predict who is at particular risk for these and other cardiac tumors. This could allow for more intense surveillance, earlier detection, and a higher rate of surgical or multimodality cure for these patients.

• Complete excision and radical resection is recommended to prevent local recurrence of cardiac tumors.
• All benign cardiac tumors are potentially curable with current surgical techniques.
• Multimodality therapy and multidisciplinary planning should be incorporated into the care of cardiac tumor patients.
• Cardiac sarcomas are best classified by anatomic location rather than histologic subtype, and the former dictates their presentation, treatment, and prognosis.
• Right heart sarcomas tend to be more bulky, infiltrative, metastasize earlier, and are usually amenable to neoadjuvant chemotherapy.
• Left heart sarcomas tend to be more solid, less infiltrative, and metastasize later.
• Pulmonary artery sarcomas usually present with obstruction, right heart failure, and tend to grow distally within the confinement of the pulmonary artery.
• Cardiac tumors located in the anterior left atrial wall may require autotransplantation for complete excision of the tumor, reconstruction, and reimplantation.
• Cardiac autotransplant and concomitant pneumonectomy carries an unacceptable 50% mortality rate.