Embolism from a left ventricular myxoma presenting with acute limb ischaemia

Abstract

Acute limb ischaemia (ALI) secondary to cardiac myxoma is uncommon. Embolic myxoma should be considered a differential diagnosis in young patients with ALI who do not have apparent cardiovascular risk factors. A multidisciplinary approach and comprehensive care can improve outcomes and optimise the collaborative treatment of ALI. Early referral to a hospital that can provide specialised treatment for ALI helps prevent significant tissue loss and surgical complications, such as amputation.

A man in his 20s presented with bilateral ALI of both lower extremities, and an arterial duplex scan revealed a thrombus occluding all arterial segments of the bilateral lower extremities. An intracardiac mass adherent to the apical and anterior interventricular septum on two-dimensional echocardiography suggested a complex myxoma. The patient was diagnosed with ALI Rutherford category III, and bilateral hip disarticulation was performed. The patient was discharged with an anticoagulant.

Case presentation

A man in his 20s came in with a 1-day onset of bilateral leg paraesthesia, pain and weakness. The patient was previously asymptomatic and had no medical history of embolism, cardiovascular disease or malignancy. He was a non-smoker and did not consume alcohol. The patient was initially admitted to a far-flung hospital and was diagnosed with peripheral arterial occlusive disease. However, there was a progression of pain and violaceous discolouration in the bilateral lower extremities (figure 1). Therefore, the patient was transferred to a tertiary hospital.

Figure 1.

Skin findings at presentation including purpura, retiform patches and discolouration of both lower extremities.

On clinical examination, the patient was conscious, coherent and oriented to time, place and person. Cardiac and pulmonary examination results were unremarkable. No murmurs or audible heart sounds were detected. On examination of the lower extremities, both legs appeared violaceous with mottling. The patient’s legs felt cold and tender to the touch and had absent pulses from the femoral to popliteal, tibialis anterior and dorsalis pedis arteries.

Additionally, there was a note of bilateral foot drop. The patient had 2/5 motor strength in both upper extremities and 0/5 in both lower extremities. Sensory examination revealed 100% sensation in both upper extremities and complete loss of sensation (0%) in both lower extremities. All other physical examination results were typical.

Based on the clinical history, physical examination and imaging findings, the patient was diagnosed with acute limb ischaemia (ALI) Rutherford category III. The patient was immediately started on an intravenous heparin infusion and referred for thoracic and cardiovascular surgery for bilateral hip disarticulation. The patient was urgently transferred to the operating room for emergency bilateral hip disarticulation within 3 hours of admission.

Investigations

An arterial duplex scan revealed hypoechoic intraluminal density in the distal external iliac artery bilaterally, extending to the trifurcation vessels and dorsalis pedis arteries. This finding indicates the presence of a thrombus, leading to a diagnosis of ALI that occludes all arterial segments in both lower extremities.

Two-dimensional echocardiography revealed a dilated, eccentrically hypertrophied left ventricle with mild global hypokinesia and impaired left ventricular systolic function, resulting in an ejection fraction of 46%. An incidental finding of a large, well-circumscribed, pedunculated intracardiac mass adherent to the apical, anterior interventricular septum was observed. The mass measures at least 3.5×2.20 cm and appears cystic with a solid, echo-dense core, suggesting a complex myxoma (figure 2: plax view and figure 3: chamber view).

Figure 2.

Plax view. Echocardiogram presenting an intracardiac mass attached at the apical anterior interventricular septum suggestive of complex myxoma. The arrow indicates the pedunculated mass.

Figure 3.

Chamber view. Echocardiogram presenting an intracardiac mass attached at the apical anterior interventricular septum suggestive of complex myxoma. The arrow indicates the pedunculated mass.

Cardiac MRI

Cardiac MRI is the preferred imaging modality for assessing and evaluating cardiac tumours. MRI is superior in tissue characterisation and can aid in differential diagnosis. MRI has phase and cine contrast sequences that allow clinicians to determine the functional impact of a mass.¹

Workup for antiphospholipid syndrome

Workups for antiphospholipid syndrome were requested, including lupus anticoagulant, antibodies against cardiolipin, antibodies against beta-2 glycoprotein I and JAK2 mutation assay.²

In addition, interleukin 6 is a marker of recurrence. Overproduction of interleukin 6 is responsible for the immunological abnormalities and constitutional symptoms observed in patients with cardiac myxomas.³ However, the patient could not comply due to financial constraints and the unavailability of the test at the institution.

Differential diagnosis

Cardiac tumours may arise from either a primary (benign or malignant) or a secondary (malignant) cause.⁴ The differential diagnoses for right atrial lesions include both benign and malignant lesions. Benign lesions include vegetations, thrombi and myxomas.⁵ Other malignant tumours include primary cardiac lymphoma, primary sarcoma and large B cell lymphoma, which can mimic atrial myxomas.⁶

Approximately 90% of myxomas are sporadic, and 10% are familial.⁷ Familial variety occurs as a part of the Carney complex (CNC), which may include (1) myxomas involving the cardiac, breast and skin; (2) pigmented nevi or lentigines; and (3) endocrine overactivity, including testicular tumours, pituitary adenomas, acromegaly or gigantism, and primary nodular cortical disease with or without Cushing syndrome.⁸

Another possible differential diagnosis for cardiac myxoma is CNC, a rare genetic disorder often associated with multiple endocrine neoplasia syndrome. It affects various glands, such as the pituitary, adrenal and thyroid.⁹

CNC may cause cardiac myxomas, breast myxomatosis, abnormal pigmentation, melanotic schwannomas, testicular tumours and skin myxomas.¹⁰ Clinicians diagnose CNC when two or more cardinal manifestations are present. The workup included biochemical testing, imaging and histology. If a patient demonstrated a mutation in PRKAR1A or had a first-degree relative with CNC, these manifestations were considered sufficient for diagnosis.¹¹

Treatment

Postoperatively, the heparin drip was continued, and the patient was transferred to the intensive care unit. A multidisciplinary team managed the patient, including cardiology, immunology, rheumatology, psychiatry, nephrology, endocrinology, infectious diseases, haematology and rehabilitation therapy.

The patient developed acute renal failure, and creatinine levels increased. The patient required short-term renal replacement therapy in the form of haemodialysis. The patient recovered, and the creatinine level returned to normal. The patient was extubated, treated with enoxaparin and switched to warfarin tablets. The cardiac surgery team assessed the patient and recommended surgical excision of myxoma. However, the patient initially refused surgery.

The patient improved with warfarin and was discharged. Ideally, a cardiac myxoma can be promptly removed after diagnosis.¹² However, in this case, relatives and patients consented to have the myxoma removed after 4 weeks of admission.

Moreover, the institution still needs to have a specialised cardiac centre. Hence, the patient was advised to be transferred to a cardiac centre capable of performing myxoma excision.

Surgery is the mainstay treatment for cardiac myxomas. Long-term follow-up is necessary to monitor for tumour recurrence. Hence, prompt diagnosis and immediate surgical intervention can help reduce morbidity and mortality in these patients.¹³

Outcome and follow-up

The patient was discharged in stable condition. He was discharged on warfarin tablets and advised to maintain an international normalised ratio between 2 and 3. The need for myxoma excision and subsequent follow-up was advised to monitor the progression of the disease. The patient was advised to undergo repeat two-dimensional echocardiography, transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE). TTE had a sensitivity of 95%, whereas TEE had a sensitivity of 100%. MRI and CT can help detect recurrence.¹⁴

The limitation of this study is that the institution only conducted follow-ups for a month; the long-term follow-up was conducted by a cardiologist responsible for the patient.

Discussion

Myxomas are the most common primary benign tumour.¹⁵ These benign tumours are usually incidental findings, with a reported incidence of less than 0.03%.¹⁶ Studies have shown that the average age at clinical presentation is 50 years, ranging from 10 to 79 years. Moreover, in an extensive literature review by Bernatchez et al, three cases of cardiac myxoma presenting as ALI were reported in patients under 30 years of age,¹⁷ which is similar to the patient’s case. With a higher incidence in females, these tumours are commonly found in individuals between the third and sixth decades of life.¹⁸

Pathologically, cardiac myxomas originate from dysregulation of mesenchymal stem cells, resulting in overproliferation.¹⁹ Cardiac myxomas are described as spindle-shaped cells that are embedded in the myxoid vascular stroma. These cells originate from the subendocardium, surrounded by a thin capsule of residual endocardial tissue.²⁰

An extensive review of the literature over the past 50 years revealed 25 cases of acute aortic occlusion secondary to embolisation of an atrial myxoma.²¹ Complete detachment of myxomas is unusual, and 50% of left atrial myxomas may result in systemic embolisation, a rare occurrence in only a few cases.²²

It is often difficult to distinguish between in situ thrombosis and embolic aetiology. However, it is crucial to do so because the different long-term treatment and acute-phase options differ for each. The emboli may tend to lodge at the femoral artery, iliac artery, aorta, popliteal artery and tibioperoneal arteries because the calibre of the vessels decreases, particularly in the lower extremities.^{23 24} In this case, the patient’s thrombus, resulting from ventricular myxoma embolisation, occluded the distal external iliac artery, extending to the trifurcation vessels and dorsalis pedis arteries.

The symptoms of acute arterial occlusion depend on the duration, location and severity of obstruction.²⁵ The classic presentation of ALI can be grouped into six Ps: pallor, paralysis, pain, paraesthesia, poikilothermia and pulse deficit.²⁶ Acute arterial occlusion can lead to intense vascular spasms. The limb may appear ‘marble’ white. The vessels relax for the following hours, and the skin fills with deoxygenated blood, which may lead to a mottled aspect that blanches on pressure.²⁷ Paralysis may also occur with persistent and severe ischaemia.²⁸ In this case, the patient had painful and cold bilateral lower extremities with violaceous discolouration blanched with pressure. The patient may also present with other symptoms such as joint pain, skin rash, weight loss and fever due to the production of growth factors and cytokines (interleukin 6) triggered by myxoma.²⁹

The diagnosis of ALI is usually apparent from its clinical presentation.³⁰ Bedside assessments may include venous and arterial examinations with continuous handheld wave Doppler due to the inaccuracy of pulse palpation.³¹ Echocardiography is helpful in the evaluation of cardiac function and in assessing the existence of embolic sources (vegetation, myxoma and thrombus).³² Two-dimensional echocardiography and arterial duplex scans were performed. Hence, prompt diagnosis and subsequent intervention were carried out.

Echocardiography is the primary diagnostic tool for determining the tumour location, size and relationship with other intracardiac structures. For suspected malignancies, CT and MRI improve diagnostic accuracy.^{33 34}

The severity of ALI was graded according to the Rutherford classification, which assesses the prognosis of the affected limb based on physical examination of skin colour, sensory and motor function, and venous filling (table 1). It also includes the Doppler flow signal in popliteal veins and pedal arteries.³⁵

Table 1.

ALI stages according to the Rutherford classification

Stage	Prognosis	Findings		Doppler signal
		Sensory loss	Muscle weakness	Arterial	Venous
I	Limb viable, not immediately threatened	None	None	Audible	Audible
IIa	The limb is marginally threatened and salvageable if promptly treated	Minimal (toes)	None	Often inaudible	Audible
IIb	The limb is immediately threatened, salvageable with immediate revascularisation	More than toes, pain at rest	Mild or moderate	Inaudible	Audible
III	The limb is irreversibly damaged, and significant tissue loss or permanent nerve damage is inevitable	Profound, anaesthetic	Paralysis (rigour)	Inaudible	Inaudible

ALI, acute limb ischaemia.

The Rutherford ALI classification in table 1 divides an extremity into three categories: viable, threatened or irreversibly damaged.³⁶ For patients with viable (stage I), marginally threatened (stage IIa) and immediately threatened limbs (stage IIb), Doppler ultrasound should be readily available to aid in prompt revascularisation and guide management.¹⁴ All patients with ALI are initially managed with intravenous heparin to prevent recurrent embolism and clot propagation, except when contraindications are present.³⁷

Patients with category I and IIa ischaemia, with a low risk of ischaemic nerve damage or myonecrosis, are often treated with endovascular methods such as catheter-directed thrombolysis.^{38 39} However, category IIb patients require immediate revascularisation with fasciotomy or operative thrombectomy due to an increased risk of permanent tissue damage, nerve injury or muscle necrosis.³,⁴⁰ For patients in category III, such as in the patient’s case, where there is significant tissue loss in the limbs and permanent or inevitable nerve damage, the recommended treatment is amputation.^{2 5}

In a review of reported cases of cardiac myxoma presenting as ALI, a histopathological examination of emboli was performed, and the results were consistent with myxoma (table 2).

Table 2.

Myxoma cases and corresponding intervention

Age/sex	Symptoms	Imaging findings	Management	Histopathological findings	References
50s/female	With sudden pain in right leg Paraesthesia Discomfort in the right popliteal fossa	CT angiogram revealed bilateral popliteal occlusions and bilateral segmental renal infarcts	Heparin infusion Bilateral popliteal embolectomies Single-compartment fasciotomy	Histopathology of the popliteal embolus confirmed a cardiac myxoma with papillary projections and abundant loose myxoid stroma	Ho et al57
Early adolescence/male	Recurrent episodes of syncope Blurring of vision Palpitations Light-headedness	Two-dimensional transthoracic echocardiography The gelatinous masses in the right atrium, right ventricle and left atrium suggest a triple-chamber myxoma	Transoesophageal echocardiogram Bilateral atrial and right ventricular tumours were removed through mitral valve repair	A pathological study of the tumour confirmed the diagnosis of cardiac myxoma	Evangelista26
50s/male	Acute and severe pain in the right lower extremity Paraesthesia Intermittent episodes of dizziness and palpitations for 2 months	CT angiography	Femoral thromboembolectomy by groin cut-down with four-compartment fasciotomy	Histological examination of the embolus showed spindle-shaped cells within a collagenous myxoid stroma, consistent with a myxoma	Mohamed et al58
20s/male	Sudden onset of resting pain pallor and numbness of the right leg	Doppler ultrasonography (acute occlusion of lower extremities in the right leg)	The patient underwent median sternotomy, and cardiopulmonary bypass was performed	Histopathological examination confirmed that the embolus was a myxoma	Zhang et al1

These findings strengthen the diagnosis of tumour embolisation and the need for histopathological confirmation in every case.^{6 41} Hence, the patient was referred to a tertiary hospital for a biopsy of cardiac myxoma because the institution had no capable cardiac centre when admitted.

The management of patients with cardiac myxoma presenting with ALI should include surgical removal of the tumour to prevent embolism recurrence.⁴² If atrial myxomas are surgically excised, they can be cured with an excellent prognosis.⁴³ The survival rate is 85%, and the recurrence rate is 5%.⁴⁴ This incidence was reported in a 22-year treatment study of cardiac myxoma, with a 0.4–5% recurrence rate.

The recurrence of cardiac myxomas is remarkable in young males, a familial form and multifocal cases.⁴⁵ Hence, repeated two-dimensional echocardiography is highly recommended every 5 years.⁴⁶

Complete resection of the entire layer is highly recommended for myxomas occurring at a young age with a ventricular origin, multiple myxomas, positive family history and CNC. This approach has been shown to reduce the recurrence rate.⁴⁷

The surgical approach for myxoma includes cannulation for cardiopulmonary bypass, incision and other concomitant procedures that depend on the size and location of the tumour. The tumours were excised with an acceptable safety margin. The left atrial approach is typically used because of the high incidence and abundance of myxomas in the left atrium with the stalk in the interatrial septum.⁴⁸

The treatment for cardiac myxoma is urgently removing tumours, especially if symptomatic.^{49 50} Tumour recurrence has been reported in approximately 17% of cases and may occur at the original site of myxoma implantation.⁵¹ Complete embolisation of the myxoma to the peripheral vessels is a rare phenomenon that typically occurs with life-threatening and tragic consequences.⁵²

The approach for the excision of myxomas includes left atriotomy, biatrial and right atrial approaches.⁵³ A recent study by Shin et al showed that mini-thoracostomy is an acceptable neurological and clinical outcome for resectioning cardiac myxoma.⁵⁴ The ideal surgical procedure to remove cardiac myxomas remains controversial.⁵⁵

Several surgical techniques to access the left ventricular myxoma include transaortic access through the ascending aorta, transmitral access through the left atrium with video assistance, via small longitudinal left ventriculotomy and trans-septal access through the right atrium. The surgical approach’s choice depends on the tumour’s location within the ventricle.⁵⁶

Learning points.

• Acute limb ischaemia (ALI) secondary to a cardiac myxoma is an unusual presentation. Thus, a high index of suspicion is warranted, particularly in young adults without known comorbidities or risk factors for cardiovascular diseases.

• A multidisciplinary approach and comprehensive care can improve outcomes and optimise the collaborative treatment of patients with ALI.

• Early referral to a hospital that can provide specialised treatment for ALI helps prevent significant tissue loss and surgical complications, such as amputation.

Ethics statements

Patient consent for publication

Obtained.