Atrial Myxomas

Epidemiology and General Characteristics

• Atrial myxomas are rare overall but remain the most frequent primary cardiac tumour in adults.
• They are most commonly located in the left atrium, typically arising from the interatrial septum at the border of the fossa ovalis.
• Less frequently, they may originate in the right atrium or, rarely, in the ventricles.
• These tumours are usually solitary and pedunculated, but variations in morphology and attachment are recognised.
  
  

Diagnostic Challenge

• The clinical presentation is often nonspecific, contributing to diagnostic delay.
• Symptoms may mimic those of valvular heart disease, heart failure, or systemic illness.
• Early recognition is crucial, as complications such as systemic emboli or sudden obstruction of blood flow can be life-threatening.

Sporadic Myxomas

• The majority of atrial myxomas arise as isolated cases, representing the non-familial form.
• These tumours develop without clear hereditary patterns or associated syndromes.

Familial Myxomas

• Fewer than 10% of atrial myxomas are familial in nature.
• They follow an autosomal-dominant pattern of inheritance.
• Familial cases may occur in isolation or as part of a broader syndrome.

Carney’s Complex

• Some familial atrial myxomas form a component of Carney’s complex, a rare autosomal-dominant condition.
• This syndrome is characterised by:
  • Myxomas occurring at multiple sites, including cardiac and extracardiac locations.
  • Endocrine tumours, such as adrenal, pituitary, or testicular neoplasms.
  • Cutaneous manifestations, including spotty skin pigmentation and lentigines.

Cellular Origin

• Immunohistochemical studies indicate that atrial myxomas arise from multipotent mesenchymal cells.
• These cells have the capacity for both neural and endothelial differentiation, suggesting a pluripotent cellular origin.

Macroscopic Features

• Atrial myxomas are usually pedunculated, though sessile tumours also occur. Around 85% are attached to the interatrial septum at the border of the fossa ovalis.
• They vary in size from 1 cm to 15 cm in diameter, with weights between 15 g and 180 g.
• Macroscopically, they appear gelatinous and polypoid, with surfaces that may be smooth, lobulated, friable, or villous.
• Smooth tumours tend to be larger and present predominantly with obstructive symptoms, whereas friable or villous tumours, with fragile extensions, are more prone to embolisation.
• Their colour ranges from whitish to yellow-brown, and they are often covered with thrombus.

Growth and Attachment

• Tumour mobility is determined by the site and extent of stalk attachment to the interatrial septum.
  
  
• They are vascular lesions, occasionally receiving neovascular supply from a coronary artery branch.
  
  
• Growth rates are not well defined, but individual reports suggest gradual enlargement over months. Rarely, haemorrhage into the tumour mass has been described.
  
  

Cellular Composition and Origin

• Histologically, myxomas consist of a heterogeneous mixture of myxoma (lepidic) cells, smooth muscle cells, endothelial cells, and undifferentiated mesenchymal elements.
  
  
• These cells are embedded in a myxoid stroma composed of acid mucopolysaccharides, and the surface is covered by endothelium.
  
  
• The most accepted hypothesis is that they originate from multipotent mesenchymal or subendocardial stem cells capable of differentiating along neural, endothelial, or muscular lineages.
  
  

Functional and Clinical Consequences

• Symptoms arise primarily from mechanical interference with intracardiac blood flow, systemic or pulmonary embolisation, and constitutional manifestations.
  
  
• Embolic events occur in approximately 30–40% of patients, particularly with friable or polypoid tumours. Systemic emboli are more common in left-sided myxomas, whereas right atrial lesions may cause pulmonary embolism and, rarely, pulmonary artery aneurysms.
  
  
• Polypoid tumours prolapsing into the ventricles can damage valve leaflets or annuli. Large atrial myxomas are also associated with atrial fibrillation.
  
  
• Constitutional symptoms, including fever, malaise, weight loss, and raised ESR, are attributed to the release of cytokines and growth factors, especially interleukin-6.
  
  

Molecular and Cytokine Activity

• Atrial myxomas secrete vascular endothelial growth factor (VEGF), promoting angiogenesis and tumour expansion.
  
  
• Other cytokines and inflammatory mediators, including interleukin-6, have been implicated in systemic inflammatory responses and tumour progression.

General Incidence

• Primary cardiac tumours are rare, with autopsy series estimating a prevalence of about 0.02% (200 per million autopsies).
• Approximately 75% of primary cardiac tumours are benign, and of these, half are atrial myxomas. This corresponds to around 75 cases per million autopsies.
• Myxomas account for nearly 50% of all benign cardiac tumours in adults, but they are less common in children, where they represent only about 15% of cases.

Location

• Between 75–85% of myxomas originate in the left atrium, typically attached to the interatrial septum.
• About 20–25% are located in the right atrium.
• Less frequently, myxomas arise in the ventricles: approximately 2% in sporadic cases compared with 13% in familial cases.
• Around 90% of myxomas are solitary and pedunculated, although multiple lesions may occur, particularly in the familial form.

Demographic Distribution

• Sporadic atrial myxomas show a strong female predominance, with 70–75% of cases occurring in women. The reported female-to-male ratios vary between 2:1 and 3:1.
• Right atrial myxomas demonstrate a less consistent sex predilection, with some series suggesting a slight male predominance.
• Sporadic myxomas are usually diagnosed between the fourth and sixth decades of life, with a mean age around 56 years.
• Familial cases present much earlier, with mean age in the mid-20s, and can be seen in children as young as 3 years old.

Familial vs Sporadic Cases

• About 90% of myxomas are sporadic and isolated.
• Approximately 10% are familial, with autosomal-dominant inheritance.
• Multiple tumours are found in around 50% of familial cases, and these are more likely to occur in ventricular locations compared with sporadic forms.

Geographic and International Data

• A surgical incidence study in the Republic of Ireland (1977–1991) reported an annual rate of 0.50 atrial myxomas per million population.
• In India, a retrospective study of 171 patients found a younger mean age of presentation at 37 years, with dyspnoea being the most common presenting symptom.

Obstructive Symptoms

Left-Sided Myxomas

• Mimic mitral valve obstruction or regurgitation, producing exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, pulmonary oedema, and signs of left-sided heart failure.
• Symptoms may worsen with postural changes due to tumour mobility, leading to dizziness, syncope, or sudden shortness of breath.
• Recurrent pulmonary oedema and atrial fibrillation are common with larger tumours.

Right-Sided Myxomas

• Present similarly to tricuspid stenosis and right heart failure.
• Symptoms include exertional dyspnoea, peripheral oedema, abdominal swelling due to ascites, and hepatomegaly.
• Slowly growing right atrial tumours may produce gradually progressive right-sided failure.

Thromboembolic Symptoms

Left Atrial Myxomas

• High risk of systemic embolisation, especially in the brain, retina, spleen, kidneys, and peripheral arteries.
• Presentations include transient ischaemic attacks, hemiplegia, seizures, or acute vision loss.
• Embolic risk is higher in friable, irregular, or villous tumours, and in patients with atrial fibrillation.

Right Atrial Myxomas

• Can cause pulmonary embolism, presenting with tachycardia, hypoxia, pulmonary infarction, or even sudden death.
• In patients with an atrial septal defect or patent foramen ovale, paradoxical systemic emboli can occur.
• Recurrent small emboli may produce pulmonary hypertension and cor pulmonale.

Constitutional Symptoms

Systemic Manifestations

• Up to 50% of patients report fever, fatigue, anorexia, arthralgia, weight loss, myalgia, Raynaud’s phenomenon, or pallor due to anaemia.
• These nonspecific features are related to tumour secretion of interleukin-6 and other inflammatory cytokines.
• Symptoms often mimic autoimmune disease, endocarditis, or systemic malignancy, leading to diagnostic confusion.

Anaemia and Inflammatory Features

• Anaemia occurs in 15–49% of cases, often associated with elevated ESR.
• Intermittent fever is reported in 20–32% of patients.
• Raynaud’s phenomenon may be present as part of the cytokine-mediated systemic response.

Other Symptoms and Associations

Carney’s Complex

• Familial atrial myxomas may occur as part of Carney’s complex.
• Associated features include cutaneous lentigines, endocrine tumours (adrenal, pituitary, testicular, thyroid), and recurrent multifocal cardiac myxomas.

Neurological Complications

• Neurological effects include embolic stroke, seizures, and cognitive changes.
• Rare associations include myxoma-related cerebral aneurysms or metastasis-like lesions mimicking vasculitis.

Respiratory and Cardiac Features

• Haemoptysis can occur secondary to pulmonary infarction or pulmonary oedema.
• Chest pain, though infrequent, may reflect coronary artery embolisation.
• Multiple small emboli may contribute to progressive pulmonary hypertension.

Rare Presentations

• Some patients remain asymptomatic, with tumours detected incidentally.
• Case reports describe paraneoplastic-like syndromes with longstanding neurological or musculoskeletal complaints resolving after tumour removal.
• Infections of the tumour with attached vegetations have been described.
• During pregnancy, atrial myxoma may mimic normal physiological dyspnoea and fatigue, delaying diagnosis. Most are detected in the second trimester, with surgical resection performed safely in the third.

General Findings

• Jugular venous pressure may be elevated, often with a prominent A wave in right atrial tumours.
• Cyanosis, clubbing, petechiae, and rash may be present in advanced disease or when embolic or constitutional processes are prominent.
• Fever and pallor can indicate tumour-related systemic inflammation or anaemia.

Cardiac Auscultation

Left-Sided Myxomas

• A loud S1 caused by delayed closure of the mitral valve due to tumour prolapse.
• Early diastolic “tumour plop” in up to 15% of cases, representing abrupt tumour movement against the endocardial surface.
• A diastolic atrial rumble similar to mitral stenosis when the mitral orifice is obstructed.
• Systolic murmur at the apex may suggest mitral regurgitation from tumour-induced valve damage.
• Additional heart sounds (S3 or S4) can be heard in some patients.

Right-Sided Myxomas

• A diastolic rumble may indicate obstruction of the tricuspid valve.
• A holosystolic murmur may occur due to tricuspid regurgitation.
• Right atrial tumours may also delay P2, with its intensity depending on the degree of pulmonary hypertension.

Pulmonary and Systemic Embolic Signs

• Signs of neurological deficit (stroke, seizures, transient ischaemic attacks) may be detected following cerebral emboli.
• Visual loss may reflect retinal arterial occlusion.
• Evidence of pulmonary embolism includes hypoxia, tachycardia, haemoptysis, or signs of right heart strain.
• Peripheral emboli may cause limb ischaemia, abdominal pain, or signs of organ infarction (renal, splenic).

Constitutional Manifestations

• Weight loss, arthralgia, fever, fatigue, or Raynaud’s phenomenon may be apparent on systemic review.
• These reflect cytokine-driven systemic inflammation, particularly mediated by interleukin-6.

Syndromic Associations

Carney’s Complex

• Spotty pigmentation (lentigines, blue naevi, pigmented naevi).
• Endocrine hyperactivity including Cushing’s syndrome, thyroid or gonadal tumours, and pituitary adenomas (sometimes leading to acromegaly).
• Extracardiac myxomas in skin, breast, or thyroid tissue.
• Predisposition to recurrent and multifocal atrial myxomas despite surgical resection.

Related Syndromes

• NAME syndrome: nevi, atrial myxoma, myxoid neurofibroma, and ephelides (freckles).
• LAMB syndrome: lentigines, atrial myxoma, and blue naevi.

Neurological Associations

• Multiple cerebral aneurysms have been described in patients with Carney’s complex or long-standing myxomas.
• Rare cases mimic systemic vasculitis or endocarditis due to embolic or inflammatory mechanisms.

Laboratory Studies

• Nonspecific abnormalities may be present and include anaemia (15–49% of patients), leukocytosis, thrombocytopenia, raised ESR, and elevated C-reactive protein.
• Increased serum gamma globulin levels can occur, with abnormalities in protein electrophoresis in up to 45% of cases.
• Serum interleukin-6 may be elevated, reflecting tumour activity and recurrence risk.
• Haemolytic anaemia can arise due to mechanical red cell destruction.

Echocardiography

Transthoracic Echocardiography (TTE)

• First-line investigation in suspected cases.
• Can determine size, location, attachment, and mobility of the mass.
• Differentiates myxomas from left atrial thrombi, with stalk and mobility favouring a myxoma.
• Doppler evaluation may reveal haemodynamic effects mimicking mitral stenosis or regurgitation.

Transoesophageal Echocardiography (TEE)

• Higher resolution and 100% sensitivity compared to TTE.
• Identifies smaller vegetations or tumours (as small as 1–3 mm).
• Essential in patients with suspected multiple lesions or in the context of myxoma syndromes.

Cardiac Magnetic Resonance Imaging (MRI)

• Provides detailed anatomical definition including size, surface, and attachment site.
• Cine MR gradient echo images demonstrate tumour mobility.
• T1- and T2-weighted sequences allow characterisation of the tumour microenvironment.
• Superior to CT in defining tumour attachment (83% correlation with surgical findings).

Computed Tomography (CT)

• Useful when MRI is not available or contraindicated.
• Defines size, origin, and tissue density, and helps distinguish myxomas from thrombi or other cardiac masses.
• Provides assessment of extracardiac structures and preoperative planning.
• Calcification may be visible but is not a reliable differentiating feature.

Nuclear Imaging

• FDG-PET is rarely used but may identify hypermetabolic foci in rare cases of myocardial involvement.
• Can help differentiate tumour recurrence or malignant transformation from benign pathology.

Coronary Angiography and Cardiac Catheterisation

• Performed preoperatively in patients >40 years or with cardiovascular risk factors to exclude concomitant coronary artery disease.
• Defines tumour vascularisation and may reveal feeding vessels from coronary arteries.
• Previously used for diagnosis, now reserved mainly for operative planning.

Biopsy and Histology

• Biopsy is rarely indicated due to risk of embolisation and is reserved for cases where noninvasive imaging is inconclusive.
• Histology shows polygonal to stellate myxoma cells embedded in a vascular myxoid stroma.
• Necrosis occurs in ~8%, calcification in 10–20%, and haemorrhage may be present.
• Immunohistochemistry demonstrates expression of interleukin-6 and, in some cases, abnormal DNA content.

Additional Studies

• Chest X-ray may reveal cardiomegaly, pulmonary oedema, or occasionally intracardiac calcification.
• Electrocardiography may show atrial fibrillation, flutter, left atrial enlargement, or conduction abnormalities.
• Skin biopsy in patients with petechiae may reveal spindle-shaped myxomatous cells.
• Genetic testing for PRKAR1A mutations is indicated in suspected Carney complex, with screening of first-degree relatives recommended.

Thrombus versus Myxoma

• Atrial mural thrombi represent the most important differential for atrial myxomas, as both can share overlapping clinical and imaging features.
• Histopathological appearances may also be similar, particularly with myxoid stroma.
• Immunohistochemistry is often unhelpful, but the calretinin marker has diagnostic value, being specific for myxomas and absent in mural thrombi.
• Thrombi are commonly associated with atrial fibrillation, low cardiac output states, or the presence of intracardiac catheters, and are typically located in the posterior atrium.

Other Primary Cardiac Tumours

• Primary sarcomas, particularly angiosarcomas, may mimic atrial myxomas in presentation and location.
• Primary cardiac lymphomas, including diffuse large B-cell lymphoma, can present with intracardiac masses resembling myxomas.
• Distinction requires histological evaluation and, at times, advanced imaging or biopsy.

Valvular Heart Disease

Mitral Stenosis

• Both mitral stenosis and left atrial myxoma may produce exertional dyspnoea, orthopnoea, haemoptysis, and a diastolic murmur.
• ECG often reveals left atrial hypertrophy in mitral stenosis.
• Echocardiography distinguishes the two by demonstrating a fixed obstruction in mitral stenosis versus a mobile mass in atrial myxoma.

Mitral Regurgitation

• Can present with dyspnoea, fatigue, and systolic murmurs at the apex, overlapping with findings in myxomas.
• Differentiation is achieved through echocardiography, which shows leaflet prolapse, chordal rupture, or annular dilation.

Tricuspid Valve Disease

• Tricuspid stenosis and regurgitation may mimic right atrial myxomas with features of right heart failure, hepatomegaly, and ascites.
• Echocardiography differentiates valvular disease from a mass obstructing the tricuspid orifice.

Pulmonary Conditions

Pulmonary Embolism

• Both pulmonary embolism and right atrial myxoma can present with dyspnoea, chest pain, hypoxia, and signs of right heart strain.
• In pulmonary embolism, imaging demonstrates intravascular thrombus rather than a pedunculated atrial mass.

Idiopathic Pulmonary Arterial Hypertension

• Shares clinical features of exertional dyspnoea, fatigue, and signs of right ventricular strain.
• Diagnosis confirmed with right heart catheterisation showing raised pulmonary artery pressures without evidence of obstruction.

Infective Endocarditis

• Fever, splenomegaly, petechiae, or a history of drug use or prosthetic valves may point to endocarditis rather than myxoma.
• Echocardiography reveals valvular vegetations rather than an atrial mass.
• Blood cultures provide microbiological confirmation.

Connective Tissue Diseases

• Fatigue, arthralgia, and vasculitic skin manifestations may mimic constitutional symptoms of myxoma.
• Positive antinuclear antibodies or other autoantibodies help distinguish connective tissue disease.

Other Considerations

• Rare cardiac tumours or metastatic lesions can appear radiographically similar to myxomas.
• Imaging with MRI or CT provides better delineation of tissue characteristics and sites of origin.

General Approach

• The only definitive treatment for atrial myxoma is surgical excision, and this should be undertaken as soon as the diagnosis is confirmed.
• Timing of surgery depends on patient stability, comorbidities, and surgical expertise availability.
• While awaiting surgery, or in cases where surgery is contraindicated, associated complications such as heart failure, arrhythmias, and embolic events are managed medically.

Surgical Management

Conventional Excision

• Standard treatment is removal via median sternotomy under cardiopulmonary bypass and cardioplegic arrest.
• Surgical access is determined by tumour location: right or left atriotomy, or combined atriotomy for larger or complex tumours.
• Associated procedures may be performed concurrently, such as valve repair or replacement, or coronary artery bypass grafting.
• To prevent recurrence, excision should include the tumour base with adjacent endocardium; a pericardial or synthetic patch may be used to repair the septal defect.
• Some centres use adjuncts such as laser photocoagulation to destroy residual pretumorous cells at the stalk site.
• Operative mortality ranges from 0.5–2.2%, with major postoperative complications including atrial fibrillation (23–33%), neurological events (≈3%), and re-exploration for bleeding (≈5%).

Minimally Invasive and Robotic Surgery

• Minimally invasive approaches, including mini-thoracotomy and totally endoscopic robotic resection, have been reported as feasible and safe alternatives.
• Benefits include reduced hospital stay, smaller incisions, and good cosmetic results, with patient satisfaction exceeding 90% in some series.
• Outcomes, including survival and recurrence rates, are comparable to conventional surgery.

Long-Term Surgical Outcomes

• Surgery for sporadic atrial myxomas is usually curative, with an excellent prognosis.
• Recurrence is rare in sporadic cases (1–5%) but higher in familial forms (20–25%).
• Risk factors for recurrence include incomplete excision, multiple tumour foci, ventricular localisation, and younger age at presentation.
• Long-term survival following resection is comparable to the general population, though advanced age and concomitant valve surgery predict poorer outcomes.

Medical Management

• No medical therapy eradicates myxoma; drug therapy is limited to complications:
  • Arrhythmias: managed with antiarrhythmic medications until surgery.
  • Heart failure: treated with standard therapies such as beta-blockers, ACE inhibitors, and diuretics.
  • Embolic events: anticoagulation or antiplatelet therapy may be considered, though surgery remains definitive.
• In patients with severe comorbidities or poor surgical prognosis, conservative management is pursued, though outcomes are poor.

Management of Embolic Phenomena

• Embolic complications depend on the vascular territory involved.
• Unlike thrombotic occlusion, embolic masses from myxoma are poorly responsive to thrombolysis or percutaneous interventions.
• Surgical excision of the tumour is the definitive therapy to prevent recurrence of embolisation.

Postoperative Follow-Up

• Annual transthoracic echocardiography is generally recommended to monitor for recurrence; some advocate biannual imaging in high-risk groups (e.g., familial myxoma, Carney complex, young patients).
• However, recurrence after complete excision is uncommon, and the necessity of lifelong frequent imaging remains debated.
• Patients with Carney complex require closer follow-up due to higher recurrence risk and association with extracardiac tumours.

Overall Outlook

• Atrial myxomas are histologically benign, but clinical consequences can be severe due to obstruction, embolisation, or constitutional symptoms.
• Surgical resection offers an excellent prognosis, with operative mortality typically below 5% and rapid postoperative recovery.
• Long-term outcomes are highly favourable, with most patients becoming asymptomatic following excision and experiencing sustained survival.

Morbidity and Mortality

• Despite their benign histology, atrial myxomas carry risks of systemic and cerebral embolism, heart failure, arrhythmias, and sudden death.
• Sudden death occurs in up to 15% of patients, most often from coronary or systemic embolisation or acute obstruction at the mitral or tricuspid valve.
• Factors increasing embolic risk include atrial fibrillation, large tumour size, irregular or friable tumour surface, and left atrial enlargement.
• In a single-centre study of 62 patients, actuarial survival at 10 years was 96.8%, with the majority asymptomatic and free from recurrence.

Recurrence

• Recurrence rates vary depending on clinical subtype:
  • Sporadic cases: 1–3%.
  • Familial cases: up to 12%.
  • Carney complex and atypical myxomas: up to 20–25%.
• Reported recurrence rates across series range from 1.5–5%, with familial disease carrying the highest risk.
• Causes of recurrence include incomplete excision, multifocal origin, or implantation of tumour fragments.
• Preventive surgical measures include wide excision margins, minimal tumour manipulation, and inspection of all cardiac chambers during surgery.

Long-Term Outcomes

• Large series demonstrate excellent survival following surgery:
  • In 153 surgically treated patients, recurrence occurred in only 3.3% over a mean follow-up of 5.2 years, with in-hospital mortality of 0.7%.
  • In 403 patients followed for a median of 4.5 years, recurrence occurred in 1.5% and early in-hospital mortality was 0.7%.
  • Another long-term follow-up study reported overall survival of 87% at 13 years post-surgery.
• Predictors of adverse outcomes include advanced age, larger tumour size, associated mitral valve disease, and familial predisposition.

Complications

• Congestive heart failure.
• Cardiac arrhythmias.
• Systemic or pulmonary embolisation.
• Neurological events such as stroke.
• Sudden death from acute obstruction or embolism.
• Infective endocarditis involving the tumour surface.
• Rarely, rupture or myocardial infarction secondary to embolic occlusion.

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