Atrial Myxoma

Introduction
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 are produced by mechanical interference with cardiac function or embolization. Being intravascular and friable, myxomas account for most cases of tumor embolism. Embolism occurs in about 30-40% of patients. The site of embolism is dependent upon the location (left or right atrium) and the presence of an intracardiac shunt.

Jong-Won Ha and associates reported a more frequent occurrence of systemic embolism in polypoid tumors as compared to round (58% vs 0%).2 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 myxoma. Left atrial myxomas produce symptoms when they reach about 70 g. Right atrial myxomas grow to approximately twice this size before becoming symptomatic. Tumors vary widely in size, ranging from 1-15 cm in diameter. Rate of growth is not exactly known. In one case report, right atrial myxoma had a growth rate of 1.36 x 0.03 cm/month.

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-6.3,4,5

Frequency
United States

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

Surgical incidence in the Republic of Ireland from 1977-1991 was 0.50 atrial myxomas per million population per year.
Mortality/Morbidity
Sudden death may occur in 15% patients with atrial myxoma. Death is 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.
Sex
Approximately 75% of sporadic myxomas occur in females.
Female sex predominance is less pronounced in familial atrial myxomas.
Age
Myxomas have been reported in patients aged 3-83 years.
The mean age for sporadic cases is 56 years. 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.6
The mean age for familial cases is 25 years.
Clinical
History

Symptoms range from nonspecific and constitutional to sudden cardiac death. In about 20% of cases, myxoma 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
Dyspnea on exertion (75%) that may progress to orthopnea, paroxysmal nocturnal dyspnea, and pulmonary edema is observed.
Symptoms are caused by obstruction at the mitral valve orifice. Valve damage may result in mitral regurgitation.
Symptoms of right-sided heart failure
Patients experience fatigue and peripheral edema.
Abdominal distension due to ascites is rare; however, it is more common in slowly growing right-sided tumors.
These symptoms are also observed in the later stage of progressive heart failure associated with left atrial myxomas.
Severe dizziness/syncope
This 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
Systemic or pulmonary embolization may occur from left- or right-sided tumors.
Left-sided symptoms are produced from the infarction or hemorrhage of viscera.
Embolization to the central nervous system may result in transient ischemic attack, stroke, or seizure. In an analysis of 113 cases of atrial myxoma with neurologic presentation, 83% of patients presented with ischemic stroke, most often in multiple sites (43%). Twelve percent of patients presented with seizures. In a retrospective review of 74 patients with atrial myxoma, 12% had neurologic manifestations.7 Cerebral infarction was present in 89% of the cases and most myxomas (89%) demonstrated a mobile component on transesophageal echocardiography. Other complications include myxoma-induced cerebral aneurysm and myxomatous metastasis that can mimic vasculitis or endocarditis.
Involvement of the retinal arteries may result in vision loss.
Systemic embolization that causes occlusion of any artery, including coronary, aortic, renal, visceral, or peripheral, may result in infarction or ischemia of the corresponding organ.
On the right side, embolization results in pulmonary embolism and infarction.
Multiple, recurrent small emboli may result in pulmonary hypertension and cor pulmonale.
Presence of an intracardiac shunt (atrial septal defect or patent foramen ovale) may result in a paradoxical embolism.
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.

Physical
Jugular venous pressure may be elevated, and a prominent A wave may be present.
A loud S1 is caused by a delay in mitral valve closure due to the prolapse of the tumor into the mitral valve orifice (mimicking mitral stenosis).
P2 may be delayed. Its intensity may be normal or increased, depending on the presence of pulmonary hypertension.
In many cases, an early diastolic sound, called a tumor plop, is heard. This sound is produced by the impact of the tumor against the endocardial wall or when its excursion is halted.
An S3 or S4 may be audible.
A diastolic atrial rumble may be heard if the tumor is obstructing the mitral valve.
If there is valve damage from the tumor, mitral regurgitation may cause a systolic murmur at the apex.
A right atrial tumor may cause a diastolic rumble or holosystolic murmur due to tricuspid regurgitation.
General examination may reveal fever, cyanosis, digital clubbing, rash, or petechiae.
Patients with familial myxoma may have a variety of features called syndrome myxoma or Carney syndrome8 , as follows:
Myxomas in breast, skin, thyroid gland, or neural tissue
Spotty pigmentation such as lentigines (ie, flat brown discoloration of skin), pigmented nevi, or both
Endocrine hyperactivity such as Cushing syndrome
Multiple cerebral fusiform aneurysms may be seen in patients with Carney syndrome.9
Other described syndromes associated with atrial myxomas include the following:
NAME syndrome features nevi, atrial myxoma, myxoid neurofibroma, and ephelides (ie, freckles [tanned macules found on the skin]).
LAMB syndrome features lentigines, atrial myxoma, and blue nevi.
Causes
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. Abnormalities in the short arm of chromosome 2 (Carney) and chromosome 12 (Ki-ras oncogene) have been described. In a recent 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).

http://emedicine.medscape.com/article/151362-overview