Cardiac Neoplasms, Primary

Synonyms and related keywords: primary cardiac neoplasms, cardiac tumor, myxoma, Carney complex, atrial myxoma, intracardiac tumor mass, primary neoplasm, rhabdomyoma, fibroma, fibroelastoma, hemangioma, lipoma, teratoma, hamartoma, malignant tumor, benign tumor


INTRODUCTION

Background: The most common primary cardiac tumor is the atrial myxoma, which accounts for 40-50% of all these neoplasms. The remainder of the pathological spectrum includes benign and malignant cell types. Although the overall incidence of the disease is low (0.0001-0.5% in autopsy series), it provides unique diagnostic and therapeutic challenges.

The clinical symptoms caused by cardiac tumors generally are secondary to their mass effect, local invasion, embolization, or constitutional symptoms. An intracardiac tumor mass may obstruct blood flow, compromise valve function, or induce neurological catastrophe secondary to tumor embolization. The location of the tumor determines the type of symptoms produced, which can include syncope, angina, dyspnea, edema, ascites, depression of pump function, cardiomyopathy, and pulmonary hypertension. Some tumors produce no symptoms and are found incidentally as a consequence of secondary symptoms, eg, stroke or evidence of peripheral embolization.

Most benign tumors can be resected completely with excellent outcomes. Consider heart transplantation in those instances when the benign tumor is too large to resect. Resection is the treatment of choice for malignant cardiac tumors; however, long-term results are dismal, even with the addition of adjuvant therapy.

Pathophysiology: Several types of tumors can arise in the heart, depending upon the tissues and structures involved. Primary neoplasms may arise from endocardium, valvular structures, primitive tissue rests, and the conduction system. Secondary or metastatic neoplasms arise from hematologic spread of the originating tissue. The physiologic derangements induced by the tumor are dependent upon the location of the mass and the tissue from which it arises.

Frequency:

• In the US: Incidence depends upon tumor cell type. Overall incidence of the disease is 0.0001-0.5% in autopsy series. Myxomas account for 40-50% of primary cardiac tumors in patients aged 30-60 years.

• Internationally: Rates of cardiac tumors in other countries parallel rates in the United States.

Mortality/Morbidity:

• Myxomas: The mortality rate of patients after myxoma removal does not differ significantly from that of the general population.

• Rhabdomyoma, fibroma, fibroelastoma, hemangioma, lipoma, teratoma, and hamartoma: These are benign tumors, and mortality rates in patients with these tumors do not differ significantly from that of the general population.

• Malignant tumors: These tumors generally are sarcomatous in nature. In spite of resections (complete or incomplete), median survival duration ranges from 10-24 months.

Race: Primary cardiac tumors appear to occur equally in all races, unless their presence is connected directly with underlying genetic disorders that demonstrate a race predilection.

Sex: The frequencies of these tumors in males and females are the same.

Age: Cardiac tumors can occur in all age groups.

• Cardiac myxoma, lipomatous septal hypertrophy, paraganglioma, and sarcoma tumors occur primarily in adults.

• Rhabdomyoma, fibroma, teratoma, hamartoma, and Purkinje tumors occur primarily in children.

• Papillary fibroelastoma, hemangioma, and lipoma occur in all age groups.

CLINICAL

History: Myxomas often are asymptomatic, but these tumors can produce symptoms by releasing substances that lead to inflammatory signs, including fever, tachycardia, and tachypnea. Myxomas also present as acute vascular insufficiency of the extremities from embolization. If myxomas are large, they will cause intracardiac obstruction manifested as dyspnea, syncope, or congestive heart failure.

• Rhabdomyoma arises from the ventricles of atrioventricular (AV) valves and regress spontaneously. It presents with atrial arrhythmias and heart block. Approximately 80% of rhabdomyomas are associated with tuberous sclerosis. Although most rhabdomyomas are small, large ones may cause intracardiac obstruction.

• Fibroma, hemangioma, and lipoma are accompanied by signs and symptoms that are attributable to the mass effect of the tumor. Depending upon the location, these tumors may obstruct the right or left ventricular outflow, resulting in dyspnea, hepatic congestion, peripheral edema, and syncope. Arrhythmias may occur when the tumor is located at the ventricular septum.

• Papillary fibroelastomas typically arise from the aortic or mitral valves; they may be asymptomatic or may be detected secondary to an embolic event. These typically are found incidentally on echocardiography.

• Lipomatous septal hypertrophy and hamartoma or Purkinje tumors generally present with arrhythmias. In the former case, atrial arrhythmias and heart block are common. In the latter case, incessant ventricular tachycardia in an infant is indicative of the presence of a tumor.

• Teratoma and paraganglioma tumors directly compress the heart, causing tamponade symptoms (ie, hypotension, fatigue, dyspnea). These tumors may present with superior vena cava obstructive symptoms. Paraganglioma also may produce systemic symptoms such as hypertension, headache, flushing, and palpitations.

• Of pheochromocytomas occurring as a cardiac tumor, 50% secrete catecholamines, producing the characteristic symptoms of hypertension, arrhythmias, anxiety, palpitations, and perspiration.

• For sarcomatous tumors, pain suggests malignancy. Dyspnea, pericardial effusions, right heart failure, and syncope are common.

Physical: Often, examination of patients with cardiac tumors yields no abnormal physical findings unless the tumor is large or produces substances that may cause secondary symptoms or findings.

• Patients with cardiac myxoma may present with an acutely ischemic extremity and absent pulses due to embolization.

• In a similar fashion, tumor emboli may produce neurological signs of stroke.

• Patients with large prolapsing myxomas may have an early diagnostic sound termed the tumor plop. This sound results from the impact of the tumor against the endocardial wall. If the tumor is present in the left ventricle and compromises the mitral valve, the murmur of mitral stenosis may be heard.

• In a similar fashion, masses producing ventricular compromise may manifest signs such as peripheral edema, hepatic enlargement, cyanosis, or clubbing.

• Tumors that compress the heart may be manifested by the classic physical findings of cardiac tamponade, ie, jugular venous distention, muffled heart tones, and pulsus paradoxus.

• Notably, no classic physical examination finding defines the presence of a cardiac tumor in a patient.

Causes: No distinct cause of cardiac tumors is known.

DIFFERETIALS

Carney Complex


WORKUP

Lab Studies:

• Erythrocyte sedimentation rate (ESR) is a nonspecific test that may be elevated in the presence of a cardiac tumor.

Imaging Studies:

• Chest radiograph may demonstrate an enlarged cardiac silhouette or atrial enlargement.

• MRI of the chest will demonstrate intracardiac pathology in the form of a mass.

• Transesophageal echocardiography (TEE) is the test of choice. TEE delineates the position of the tumor and details the integrity or involvement of the septal and valvular structures. (Seventy-five percent of cardiac myxomas arise from the fossa ovalis on the left atrial side.)

• Perform fetal ultrasonography if the diagnosis is suspected in utero.

• Cardiac catheterization is necessary only if other processes are strongly suspected.

• Perform metaiodobenzylguanidine (MIBG) radionuclide scan for suspected paraganglioma. This scan uses a radioactive guanidine that is taken up preferentially by neuroendocrine cells.

Other Tests:

• ECG is ordered to detect potential arrhythmias that may be associated with tumors. These arrhythmias include atrial fibrillation, paroxysmal atrial tachycardia, and ventricular arrhythmias.

Histologic Findings: Myxomas are gelatinous in nature with rests of spindle cells. If DNA tetraploidy is present, suspect malignancy. Fibroelastomas are composed of endocardium, fibrous tissue, elastic fibers, and smooth muscle cells arranged in a central stock of collagen and a covering of hyperplastic endothelial cells.

Staging: No particular staging exists for cardiac tumors.

TREATMENT

Medical Care: For those tumors presenting with cardiac arrhythmias, standard medical management of the arrhythmia is warranted until the diagnosis is established and definitive therapy undertaken. In the case of paragangliomas, treat hypertension with beta-blockade until resection is undertaken.

Surgical Care: When possible, treatment of choice for cardiac tumors is complete resection. In patients whose tumors are determined to be malignant, adjuvant therapy (ie, chemotherapy, radiation) after resection did not affect the outcome. Cardiac transplantation has been used for benign and malignant tumors. Series using this therapy have been too small to use in predicting outcomes.

MEDICATION

For patients who present with paraganglioma, hypertension, or arrhythmias, beta-blockade is the medical treatment of choice until surgical intervention can be undertaken.

Drug Category: Beta-blockers -- This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have anti-arrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Drug Name	Metoprolol (Lopressor) -- Selective beta1 adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG.
Adult Dose	12.5-50 mg PO tid; increase at 1-wk intervals prn to total of 450 mg/d if necessary
Pediatric Dose	1-5 mg/kg/d PO divided bid
Contraindications	Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities; chronic obstructive lung disease
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives may increase toxicity; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG

Drug Name	Carvedilol (Coreg) -- Nonselective beta-adrenoreceptor blocker with alpha-adrenergic blocking activity of equal potency. No intrinsic sympathomimetic activity has been documented.
Adult Dose	3.125-12.5 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; bradycardia; hypotension; severe cardiomyopathy; second- or third-degree heart block; chronic obstructive lung disease; symptomatic hepatic disease
Interactions	Interaction with other anti-arrhythmics and antihypertensives may potentiate clinical effect; may increase blood levels of cyclosporine and digoxin; may diminish hyperglycemic action of glucagon; may alter response to hypoglycemic agents (ie, sulfonylureas); fluoxetine and paroxetine may increase blood level; rifampin may decrease blood level; NSAIDs may blunt antihypertensive effect
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor BP and pulse before taking; use with caution in CHF with slowed AV conduction, peripheral vascular disease, hyperthyroidism, or diabetes mellitus; discontinue if hepatic dysfunction occurs; avoid abrupt withdrawal; discontinue over 1-2 wk

Drug Name	Atenolol (Tenormin) -- Selectively blocks beta1 receptors with little or no effect on beta2 receptors.
Adult Dose	25-50 mg PO bid
Pediatric Dose	1-2 mg/kg PO qd
Contraindications	Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without pacemaker)
Interactions	Aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor BP and pulse before taking; beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG

FOLLOW-UP

Further Outpatient Care:

• Annually follow up with patients who have undergone resection for cardiac tumors with echocardiography in order to assess for recurrences. With the more aggressive malignant tumors, follow up every 3-6 months.

Complications:

• Complications encountered after resection of cardiac tumors can include valvular insufficiency, complete heart block requiring pacemaker insertion, atrial and ventricular arrhythmias, and stroke.

Prognosis:

• Prognosis for benign tumors is excellent, matching that of the healthy population. Malignant tumors carry a dismal prognosis even in the face of complete resection. An occasional sarcoma can be resected completely, resulting in long-term survival.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Although primary cardiac tumors are uncommon, the diagnosis must be entertained in any patient presenting with peripheral arterial embolization.

• In order to avoid missing the diagnosis, always send embolectomy specimens for pathologic examination, and carefully review the results of the examination.

• If operative intervention is warranted once the diagnosis of an intracardiac tumor is made, undertake the procedure expeditiously. Delaying an intervention can invite complications from embolization of the tumor, including limb loss and stroke.

• Carefully instruct the patient and family that in spite of resection, these tumors might recur even though they are not malignant in most cases. In this regard, careful education will help eliminate the question of incomplete resection if recurrences arise.

Special Concerns:

• Patient and family counseling about the disease process is important.

• For benign tumors cured by complete resection, the discussion is fairly straightforward. Explain the operative risk, complications, and alternatives, as with any cardiac operation.

• With rhabdomyomas, the common association with tuberous sclerosis requires careful discussion of the ramifications of this underlying condition. In addition, the presence of these tumors does not mandate resection unless associated with severe cardiac symptoms.

• Mesotheliomas of pericardial origin usually are malignant, while those of the AV node are not malignant.

• The degree of malignancy of pheochromocytomas often cannot be defined histologically but is determined by degree of invasion and by development of metastases. Thus, some uncertainty is introduced into the discussion with the patient with this type of tumor.