Atrial Myxoma

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Background

Atrial myxomas are the most common primary heart tumors. Because of nonspecific symptoms, early diagnosis may be a challenge. Left atrial myxoma may or may not produce characteristic findings on auscultation. Two-dimensional echocardiography is the diagnostic procedure of choice. Most atrial myxomas are benign and can be removed by surgical resection.

Pathophysiology

Myxomas account for 40-50% of primary cardiac tumors. Approximately 90% are solitary and pedunculated, and 75-85% occur in the left atrial cavity. Up to 25% of cases are found in the right atrium. Most cases are sporadic. Approximately 10% are familial and are transmitted in an autosomal dominant mode. Multiple tumors occur in approximately 50% of familial cases and are more frequently located in the ventricle (13% vs 2% in sporadic cases).

Myxomas are polypoid, round, or oval. They are gelatinous with a smooth or lobulated surface and usually are white, yellowish, or brown. The most common site of attachment is at the border of the fossa ovalis in the left atrium, although myxomas can also originate from the posterior atrial wall, the anterior atrial wall, or the atrial appendage. The mobility of the tumor depends upon the extent of attachment to the interatrial septum and the length of the stalk.

Although atrial myxomas are typically benign, local recurrence due to inadequate resection or malignant change has been reported. Occasionally, atrial myxomas recur at a distant site because of intravascular tumor embolization. The risk of recurrence is higher in the familial myxoma syndrome.[1]

Symptoms from a cardiac myxoma are produced by mechanical interference with cardiac function or embolization and more pronounced when the myxomas are left-sided, racemose, and over 5 cm in diameter.[2]  Because the tumors are intravascular and friable, myxomas account for most cases of tumor embolism, which occurs in about 30-40% of patients. The site of embolism is dependent on the tumor location (left or right atrium) and the presence of an intracardiac shunt. A case of multiple peripheral pulmonary artery aneurysms has been reported in association with a right atrial myxoma.[3] Most of the aneurysms had thrombi and became smaller following disappearance of thrombi after resection of the right atrial myxoma. However, some aneurysms became slightly larger.[3]

Ha and associates reported a more frequent occurrence of systemic embolism in polypoid tumors as compared to round (58% vs 0%).[4] Also, polypoid tumors more frequently prolapse into the ventricle. Prolapse of a tumor through the mitral or tricuspid valve may result in the destruction of the annulus or valve leaflets. In one study, 19% of the patients had atrial fibrillation associated with large atrial myxomas. Tumors vary widely in size, ranging from 1 to 15 cm in diameter, with the rate of growth not exactly known. In one case report, right atrial myxomas had a growth rate of 1.36 × 0.03 cm/mo. The myxomas are vascular tumors and may be neovascularized by a branch of a coronary artery.[5] A case of hemorrhage in a left atrial myxoma has been reported.[6]

Myxomas have been demonstrated to produce numerous growth factors and cytokines, including vascular endothelial growth factor, resulting in angiogenesis and tumor growth and an increased expression of the inflammatory cytokine, interleukin-6.[7, 8, 9]

Etiology

Most cases of atrial myxoma are sporadic, and the exact etiology is unknown.

Familial atrial myxomas have an autosomal dominant transmission.

Carney syndrome is genetically heterogenous and is caused by a defect in more than one gene. It is estimated to account for 7% of all atrial myxomas without any predilection for age or sex. Abnormalities in the short arm of chromosome 2 (Carney) and chromosome 12 (Ki-ras oncogene) have been described. In one case report, a frame-shift mutation was found in exon 2 in the causative gene of Carney complex, protein kinase A regulatory subunit 1 alpha (PRKAR1A).[10]

At present, there does not appear to be an association between cardiac myxomas and herpes simplex types 1 and 2.[11]

Epidemiology

United States statistics

Based upon the data of 22 large autopsy series, the prevalence of primary cardiac tumors is approximately 0.02% (200 tumors per million autopsies). About 75% of primary tumors are benign, and 50% of benign tumors are myxomas, resulting in 75 cases of myxoma per million autopsies.

International statistics

Surgical incidence in the Republic of Ireland from 1977-1991 was 0.50 atrial myxomas per million population per year.

Sex- and age-related demographics

Approximately 75% of sporadic myxomas occur in females. In a series of 66 cardiac myxomas, the female-to-male ratio was 2.7:1.[12]  However, female sex predominance is less pronounced in familial atrial myxomas. In a retrospective analysis of 367 patients, there were 28 cases of right atrial myxoma, of which 16 occurred in males and 12 in females.[13]

Myxomas have been reported in patients aged 3-83 years. The mean age for sporadic cases is 56 years; whereas it is 25 years for familial cases. In a retrospective review of 171 patients from India, the mean age of presentation was 37.1 years. Most of these patients were symptomatic; dyspnea was the most common symptom.[14]

Prognosis

Morbidity/mortality

Atrial myxomas are histologically benign but can be dangerous owing to the potential for systemic and cerebral embolism.[15] Factors associated with an increased risk of embolism in those with left atrial myxoma include the presence of atrial fibrillation, an irregular tumor surface, a larger tumor size, and an increased left atrial diameter.[15]

Sudden death may occur in 15% patients with atrial myxoma, typically caused by coronary or systemic embolization or by obstruction of blood flow at the mitral or tricuspid valve.

Morbidity is related to symptoms produced by tumor embolism, heart failure, mechanical valvular obstruction, and various constitutional symptoms.

In a single-center study of 62 patients with cardiac myxoma, actuarial survival was 96.8 ± 1.8% at 10 years. Most patients were asymptomatic following the surgery, without recurrence. Recurrence occurred only in two familial cases of left atrial myxoma. Freedom from reoperation was 98.4 ± 1.3% at 5 years and 96.8 ± 1.8% at 10 years.[16]

Complications

Complications of atrial myxoma include the following:

History

Symptoms of atrial myxomas range from nonspecific and constitutional to sudden cardiac death.[19] In about 20% of cases, myxomas may be asymptomatic and discovered as an incidental finding. Signs and symptoms of mitral stenosis, endocarditis, mitral regurgitation, and collagen vascular disease can simulate those of atrial myxoma. A high index of suspicion aids in diagnosis.

Symptoms of left-sided heart failure include the following:

Symptoms of right-sided heart failure include the following:

Severe dizziness/syncope is experienced by approximately 20% of patients. The most frequent cause in patients with left atrial myxomas is obstruction of the mitral valve. Symptoms may change as the patient changes positions.

Symptoms related to embolization include the following:

Constitutional symptoms that include fever, weight loss, arthralgias, and Raynaud phenomenon are observed in 50% of patients. These symptoms may be related to overproduction of interleukin-6.

Hemoptysis due to pulmonary edema or infarction is observed in up to 15% of patients.

Chest pain is infrequent. If it occurs, it may be due to coronary embolization.

A case report of 5-year history of visual loss, vertigo, ataxia, tinnitus, and bone lesions that resolved after diagnosis and resection of the atrial myxoma has raised a possibility of it causing a paraneoplastic syndrome.[26]

Atrial myxoma can become infected when vegetations may be seen attached to its surface.[27]

Cardiac myxoma in pregnancy is rare, and diagnosis and management may be challenging as fatigue and dyspnea are not uncommon in normal pregnancy. Transthoracic echocardiography can aid in the diagnosis. In most cases, the diagnosis is made in the second trimester and surgical resection performed in the third trimester. Maternal survival is generally excellent.[28]

Physical Examination

The following findings may be noted on physical evaluation of patients with atrial myxomas:

Patients with familial myxoma may have a variety of features known as syndrome myxoma or Carney syndrome,[29]  as follows:

Other described syndromes associated with atrial myxomas include the following:

Laboratory Studies

Laboratory studies are nonspecific and nondiagnostic for atrial myoma. If present, abnormalities may include the following:

Echocardiography

Although transesophageal echocardiography is more sensitive, two-dimensional (2-D) echocardiography is usually adequate for the diagnosis.

Tumor location, size, attachment, and mobility can be assessed with this technique. Because tumors may be in multiple locations, all four chambers should be visualized.

An atrial myxoma must be differentiated from a left atrial thrombus. The thrombus is usually situated in the posterior portion of the atrium and has a layered appearance. Presence of a stalk and mobility favors atrial myxoma.

Doppler echocardiography can show the hemodynamic consequences of atrial myxoma. The findings are consistent with mitral stenosis or regurgitation.

Transesophageal echocardiography (TEE)

TEE has better specificity and 100% sensitivity compared to transthoracic echocardiography (TTE). There is good resolution of both the atria and the atrial septum, and there is better visualization of anatomic details of the tumor and stalk.

This imaging modality reveals smaller (1-3 mm in diameter) vegetations or tumors, visualizes atrial appendages, and detects shunting.

TEE is advisable for myxoma syndrome, as there may be multiple less-common sites (See the image below.)



View Image

Atrial myxoma. This is a transesophageal echocardiogram.

Other Imaging Studies

Radiography

Chest radiographic findings include an abnormal cardiac silhouette, mimicking mitral stenosis; an unusual intracardiac tumor calcification; and pulmonary edema.

Magnetic resonance imaging (MRI)

MRI provides useful information about size, shape, and surface characteristics on T1-weighted images. Cine MR gradient echo (GRE) images can demonstrate the mobility of a tumor. Point of attachment is best visualized by MRI with a postsurgical correlation of 83%. In a small series, MRI was superior to CT scan, which showed only 30% correlation for the site of attachment.

Information about tissue characteristics can be used to differentiate a tumor from a thrombus.

Computed tomography (CT) scanning

Cardiac CT scanning can be used not only to evaluate the coronary arteries and cardiac structures, but this modality can also be used to differentiate the characteristics of the myxoma from intracardiac thrombus and other cardiac pathologies.[31] Myxomas are larger than a thrombus and have typical site of origin, shape, mobility, and occurrence of prolapse.[32]

Degree of attenuation or presence of calcification is not useful to differentiate atrial myxoma from a thrombus.

Nuclear imaging

Fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is not typically indicated in the evaluation for myxoma. Myocardial involvement is rare and only few cases have been reported showing hypermetabolic hypodense areas.[33]

Other Tests

If petechiae are present, a skin biopsy may reveal the presence of elongated or spindle-shaped, myxomatous, endothelial-like cells with round or oval nuclei and prominent nucleoli.

Electrocardiography may show left atrial enlargement, atrial fibrillation, atrial flutter, or conduction disturbances.

In suspected cases of Carney complex, molecular genetic testing for PRKAR1A should be performed to confirm the diagnosis. The family members of the PRKAR1A -positive patients should undergo genetic screening and evaluation for cardiac and extracardiac manifestations of the disease.[34]

Procedures

Cardiac catheterization

Preoperative cardiac catheterization and angiography may be of value to evaluate for neovascularization.[5]

Cardiac catheterization is usually performed to exclude coexistent coronary artery disease in patients older than 40 years.

Atrial myxoma appears as an intracardiac filling defect on angiography. This was the pre-echocardiography method of diagnosis. With current imaging modalities, there is no need for angiography.

Histologic Findings

Histologic studies are characterized by the presence of lipidic cells embedded in a vascular myxoid stroma.[12] Other findings include the following:

Approach Considerations

Conventional treatment of atrial myxoma is surgical removal by median sternotomy. Minithoracotomy with robotically assisted surgery has been reported, resulting in a shorter length of hospital stay, and it is considered a safe and feasible method for atrial myxoma excision.[37] The investigators did not observe any difference in the quality of life between the two strategies.[38]  A case report of total endoscopic robotic resection of a left atrial myxoma in an elderly patient with persistent left superior vena cava also demonstrated good outcome.[39]

Gur and Aykac recommend resection of the myxoma with the surrounding healthy solid tissue in its root to prevent potential complications associated with the tumors, followed postoperatively by annual echocardiography to assess for possible relapse.[40]

Medical Care

Generally, evaluation can be performed on an outpatient basis. Following resection, obtain annual transthoracic echocardiograms to assess for recurrence of the tumor.[40]

A patient with embolic stroke requires hospitalization.

No known medical treatment exists for atrial myxoma. Drug therapy is used only for complications such as congestive heart failure or cardiac arrhythmias.

Consultations

If myxoma is suspected, a cardiologist should be consulted and a cardiothoracic surgical consultation will be required for consideration of resection.

Diet and activity

Patients with atrial myxoma do not require a special diet, and they may engage in activities as tolerated.

Surgical Care

Operative resection of the atrial myxoma is the treatment of choice.

The surgery is associated with an early postoperative mortality of 2.2%. Postoperative atrial fibrillation is seen in 23%-33% of patients.[41, 42] In a series of 91 cases of atrial myxoma, postsurgical neurologic complications were seen in 3% of cases, and reexploration for bleeding was required in 5% of cases.[42]

In a retrospective analysis (2002-2016) of 403 patients who underwent resection of atrial myxoma, long-term outcomes included good survival (5.2% mortality in the follow-up period; mean follow-up was 4.5 years, with a range of 0.5-15 years) as well as late-onset atrial fibrillation.[43]  Independent predictors of outcomes included advanced age, left atrial diameter, and mitral valve surgery.

Because of the risk of tumor fragmentation and embolization, vigorous palpation or manipulation of the myxoma should be performed only after cardioplegia.

Surgery for sporadic atrial myxoma is usually curative. Long-term prognosis is excellent. In a series of 112 patients, only 4 deaths occurred over a median follow-up of 3 years.[44] The recurrence rate is 1%-5%. Recurrence after 4 years is uncommon. The recurrence rate of familial patients is 20%-25%. Primary myxoma occurring at an atypical position is more likely to be associated with recurrence.[45]

In a series of 194 patients, operative mortality was 0.5%, and there was no significant difference in the long-term survival (10, 20, 30 y) when compared to an age-matched general population. Older age at operation was associated with a higher mortality, whereas younger age at diagnosis, smaller tumor dimension, and tumor localized to the ventricles were predictors of recurrence.[46]

Note the following:

Endoscopic cardiac tumor resection

In a study of 27 cases (23 myxomas) of endoscopic cardiac tumor resection using the port access approach, Deshpande et al reported that follow-up did not show any residual or recurrent tumor. This is an alternative approach that has cosmetic appeal and was appreciated by 92% of the patients.[47]

Long-Term Monitoring

In younger patients or patients with suspected Carney complex, the possibility of myxoma recurrence is high and it may be reasonable to obtain a biannual transthoracic echocardiogram to evaluate for recurrence of the tumor. However, in a report of 82 patients with a mean echocardiographic follow-up of 72 months, there were no myxoma recurrences. Therefore, the echocardiographic follow-up in all patients following surgery could be called into question.[48]

Author

Gyanendra K Sharma, MD, FACC, FASE, Professor of Medicine and Radiology, Director, Adult Echocardiography Laboratory, Section of Cardiology, Medical College of Georgia at Augusta University

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven J Compton, MD, FACC, FACP, FHRS, Director of Cardiac Electrophysiology, Alaska Heart Institute, Providence and Alaska Regional Hospitals

Disclosure: Nothing to disclose.

Chief Editor

Richard A Lange, MD, MBA, President, Texas Tech University Health Sciences Center, Dean, Paul L Foster School of Medicine

Disclosure: Nothing to disclose.

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Atrial myxoma. This is a transesophageal echocardiogram.

Atrial myxoma. This is an apical 4-chamber echocardiographic view.

Atrial myxoma. This is a transesophageal echocardiogram.