Myxomas

A 55-year-old man presents to the cardiology clinic with intermittent chest pain, shortness of breath, and fatigue over the past few months. He reports palpitations and has experienced several syncopal episodes. He also notes an unintentional weight loss of 3 kg over 6 months. Vital signs show a blood pressure of 130/80 mm Hg, pulse rate of 110 beats/min, respiratory rate of 16 breaths/min, and temperature of 97.2 °F. On auscultation, an early diastolic tumor plop followed by a mid-diastolic murmur at the apex is heard, mimicking mitral stenosis. The auscultatory findings vary with body position. Echocardiography reveals a mobile mass attached to the interatrial septum in the left atrium. Diagnosis?

Diagnosis is Atrial myxoma.

1. Definition

Atrial myxoma is the most common primary cardiac tumor in adults and most commonly arises in the left atrium.

Although histologically benign, it can be potentially life-threatening because of intracardiac obstruction, systemic embolization, and other cardiovascular complications.

2. Etiology and Associations

1. Most atrial myxomas are sporadic.
2. A minority are familial or syndromic, most notably in association with Carney complex.
3. Carney complex is frequently associated with germline pathogenic variants in the PRKAR1A gene.
4. Germline PRKAR1A pathogenic variants are characteristic of Carney complex and are not a usual feature of isolated sporadic cardiac myxomas.

3. Pathophysiology

1. The histogenesis of cardiac myxoma is not completely established, but the tumor is thought to arise from primitive multipotent mesenchymal cells.
2. It is typically attached to the interatrial septum near the fossa ovalis.
3. The tumor is often pedunculated and highly mobile.
4. A mobile left atrial myxoma may intermittently obstruct the mitral valve orifice, producing a ball-valve effect.
5. Intermittent mitral inflow obstruction can reduce cardiac output and cause dyspnea, presyncope, or syncope.
6. Tumor fragments or thrombi formed on the tumor surface may enter the systemic circulation and cause arterial embolization, including ischemic stroke.
7. Production of inflammatory cytokines, particularly interleukin-6 (IL-6), contributes to constitutional manifestations such as fever, fatigue, malaise, and weight loss.

4. Clinical Features

4.1 Classic Triad

The clinical manifestations of cardiac myxoma are commonly grouped into three categories:

1. Intracardiac obstruction
2. Embolic phenomena
3. Constitutional symptoms

4.2 Obstructive Features

1. Dyspnea
2. Orthopnea
3. Paroxysmal nocturnal dyspnea
4. Presyncope or syncope
5. Pulmonary congestion or pulmonary edema in severe obstruction
6. Early diastolic tumor plop
7. Mid-diastolic murmur at the apex, which may mimic mitral stenosis
8. Symptoms and auscultatory findings may change with body position because the mobility of the tumor alters the degree of mitral inflow obstruction.

4.3 Embolic Features

1. Systemic embolization occurs in a substantial proportion of patients with left-sided cardiac myxomas.
2. Cerebral embolization may cause transient ischemic attack or ischemic stroke.
3. Peripheral, renal, visceral, coronary, and retinal arterial embolization may also occur.
4. Emboli may consist of tumor fragments, thrombotic material from the tumor surface, or both.

4.4 Constitutional Features

1. Fever
2. Weight loss
3. Fatigue
4. Malaise
5. Myalgia or arthralgia may occur.
6. These manifestations are thought to result largely from cytokine-mediated inflammation, particularly involving IL-6.

5. Diagnosis

5.1 Laboratory Findings

Laboratory abnormalities are nonspecific and may include:

1. Elevated erythrocyte sedimentation rate (ESR)
2. Elevated C-reactive protein (CRP)
3. Anemia, often with an inflammatory pattern
4. Leukocytosis in some patients

Laboratory testing is supportive but is not diagnostic of atrial myxoma.

5.2 Electrocardiography

1. ECG findings are often nonspecific.
2. Atrial arrhythmias or other rhythm disturbances may occur.
3. ECG may also demonstrate findings related to chamber enlargement or associated cardiac disease.

5.3 Echocardiography

1. Transthoracic echocardiography (TTE) is generally the first-line imaging modality.
2. A typical finding is a mobile left atrial mass often attached by a stalk to the interatrial septum near the fossa ovalis.
3. A sufficiently mobile tumor may prolapse through the mitral valve during diastole.
4. Doppler echocardiography can assess the degree of functional mitral inflow obstruction.
5. Transesophageal echocardiography (TEE) provides superior visualization of the atria, tumor attachment, morphology, and relationship to adjacent cardiac structures and is particularly useful when TTE is inconclusive or additional anatomical detail is required.

5.4 Cardiac CT and MRI

1. Cardiac MRI provides detailed tissue characterization and can help differentiate myxoma from thrombus and other cardiac masses.
2. Cardiac CT can define tumor morphology, attachment, calcification, and relationships with surrounding structures.
3. Multimodality imaging is useful when echocardiographic findings are atypical or the diagnosis remains uncertain.

5.5 Histopathology

Definitive pathological confirmation is obtained after surgical excision. Histologically, cardiac myxomas characteristically contain myxoma cells embedded within an abundant myxoid stroma.

5.6 Preoperative Coronary Assessment

Assessment for concomitant coronary artery disease should be individualized according to the patient's age, symptoms, cardiovascular risk factors, and planned surgery.

Coronary CT angiography or invasive coronary angiography may be appropriate when clinically indicated.

Routine invasive coronary angiography solely because a patient is above a particular age should not be presented as a universal contemporary requirement.

6. Management

1. Prompt surgical resection is the definitive treatment.
2. Surgery is generally recommended soon after diagnosis because of the risks of systemic embolization, progressive intracardiac obstruction, and sudden hemodynamic deterioration.
3. Complete excision includes removal of the tumor and its site of attachment when feasible.
4. Prognosis after complete surgical resection is generally excellent.
5. Recurrence is uncommon in sporadic cases but is more frequent in familial disease and Carney complex.
6. Postoperative echocardiographic surveillance is appropriate, with closer and longer surveillance in patients with Carney complex, familial disease, multiple tumors, or previous recurrence.

7. Associated Condition: Carney Complex

Carney complex is an autosomal dominant multiple neoplasia syndrome frequently associated with pathogenic variants in PRKAR1A.

Important manifestations include:

1. Spotty skin pigmentation and lentigines
2. Cardiac myxomas
3. Cutaneous and mucosal myxomas
4. Blue nevi
5. Endocrine tumors or endocrine overactivity
6. Psammomatous melanotic schwannomas

Cardiac myxomas associated with Carney complex tend to occur at a younger age and may be multiple, recurrent, or located in any cardiac chamber.

8. Key Clinical Insight

A mobile left atrial mass attached to the interatrial septum near the fossa ovalis, together with positional symptoms, an early diastolic tumor plop, a mitral stenosis-like murmur, syncopal episodes, constitutional symptoms, and the potential for systemic embolization, is highly characteristic of an atrial myxoma.

References

1. Griborio-Guzman AG, Aseyev OI, Shah H, Sadreddini M. Cardiac myxomas: clinical presentation, diagnosis and management. Heart. 2022;108(11):827-833. doi:10.1136/heartjnl-2021-319479.
2. Saad EA, Mukherjee T, Gandour G, et al. Cardiac myxomas: causes, presentations, diagnosis, and management. Ir J Med Sci. 2024;193(2):677-688. doi:10.1007/s11845-023-03531-2.