CardioNerds meet with fellows from The Christ Hospital, Drs. Hanad Bashir, Hyunsoo Chung, and Dalia Aziz to discuss the following case that highlights angioleiomyoma:

A 60-year-old woman with a past medical history significant for breast cancer (on tamoxifen) presented as a transfer to our facility for a clot-in-transit. She had initially presented to the outside hospital after progressive dyspnea on exertion and recent syncope. She was found on an echocardiogram to have a right atrial mass spanning into the right ventricle. CTA of the chest and abdomen/pelvis demonstrated extensive thrombus burden spanning from the IVC into the right ventricle. She was transferred to our facility for intervention.

Endovascular attempts were unsuccessful, at which point she underwent surgical thrombectomy. Gross examination of the mass revealed a cylindrical shape, homogeneous tan color, rubbery soft tissue, measuring 25.5 cm in length and 2.3 cm in diameter. Histology confirmed the presence of angioleiomyoma. A second, smaller mass (5.2cm long and 4mm in diameter) was removed from under the tricuspid valve, with histology consistent with leiomyoma. Estrogen receptor and progesterone receptor staining were strongly positive, leading to the discontinuation of tamoxifen. Given the presence of uterine fibroids identified on the CT scan, there was concern about a uterine origin. A hysterectomy is planned for her in the near future.

Expert commentary is provided by Dr. Wojciech Mazur. Episode audio was edited by student Dr. Adriana Mares.

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Case Media – The Tall Tail Heart: Angioleiomyoma – The Christ Hospital



Pearls – The Tall Tail Heart: Angioleiomyoma – The Christ Hospital

1. Although evaluation of cardiac mass by echocardiography can provide information such as size, location, and morphology, adjunctive cross-sectional imaging may be used depending on the need for further temporal resolution (CT) or tissue characterization via cardiac MRI (CMR). If suspicious for elevated metabolic activity, there should be consideration of FDG-PET.
   
   
2. Tamoxifen (a selective estrogen receptor modulator) is an agent used for breast cancer therapy. However, its use has been associated with endometrial hyperplasia, uterine fibroids, endometrial and uterine malignancy. Increased risk of malignancy has been seen more often in post-menopausal women and is dose and time-dependent.
   
   
3. Clot in transient is a mobile thrombus, typically within the right heart structures. It is estimated to occur in 4-18% of patients with pulmonary embolism and is associated with elevated morbidity and mortality. Treatment includes surgical embolectomy, endovascular embolectomy, systemic thrombolysis, catheter-directed thrombolysis, or systemic anticoagulation.
   
   
4. Angioleiomyoma is a rare benign pericystic tumor that most commonly affects the extremities. There are case reports of other affected sites, including the uterus. Invasion into the cardiac structures is exceedingly rare.
   
   
5. The only established treatment for angioleiomyoma is surgical resection.
   

Show Notes – The Tall Tail Heart: Angioleiomyoma – The Christ Hospital

Syncope

• Syncope is a transient loss of consciousness secondary to reduced blood flow to the brain. Often, certain presentations are mislabeled as syncope, such as seizure disorders, posttraumatic loss of consciousness, and cataplexy.
  
• An organized diagnostic approach should be used to reduce hospital admissions and medical costs and increase diagnostic accuracy.
  
• Syncope can be divided into five general subgroups.
  

1) Neurally mediated reflex syncope (carotid sinus syndrome, vasovagal)

2) Orthostatic syncope

3) Cardiac arrhythmias

4) Structural cardiac and pulmonary causes

5) Cerebrovascular disorders.

• Initial evaluation should include thorough H&P, including orthostatic vitals and ECG. If diagnosis remains uncertain after initial evaluation, patients’ syncope should be risk stratified into three groups: high, intermediate, and low risk.
  
• Additionally, the 2017 ACC/AHA/HRS guidelines stratify patient risk based on short-term (<30 days) and long-term (>30 days) morbidity and mortality based on initial examination and history.
  
• Patients presenting with high-risk and short-term syncope features should be immediately hospitalized for further diagnostic testing and treatment. High-risk features are usually indicative of underlying cardiovascular causes that could lead to sudden death; this includes but is not limited to life-threatening arrhythmias and acute coronary syndrome.
  
• Risk stratification also determines the selection of diagnostic tests. When underlying cardiac etiology is suspected, diagnostic tests such as echocardiography, CT angiography, cardiac magnetic resonance, electrophysiology study, exercise stress testing, and coronary angiography may be valuable in establishing timely diagnosis in high-risk patients.
  
• Choice of study modality varies greatly based on patient presentation and risk factors. In contrast to patients presenting with high-risk syncope, low-risk patients are discharged home with re-assurance and follow-up.
  

Strategy for Intracardiac Masses

• First, take into account the patient’s age at the time of presentation, as certain medical conditions like rhabdomyomas and fibromas are more commonly observed among pediatric patients.
  
• Second, assess the likelihood from an epidemiological perspective and consider the clinical probability. For instance, if a patient has recently experienced an anterior wall myocardial infarction and exhibits an akinetic ventricular apex, the presence of a cardiac mass during echocardiography could indicate the possibility of an intracardiac thrombus.
  
• Third, factor in the location of the tumor. If the mass is detected on the valves, potential diagnoses to consider include thrombus or vegetation. While masses within the heart chambers might still indicate thrombus, it’s also important to contemplate other possibilities, such as myxomas, lymphomas, and metastases.
  
• Fourth, delve into the tissue characteristics of the mass using additional diagnostic imaging methods like cardiac magnetic resonance imaging.
  

Imaging Modalities for Intracardiac Masses

• Transthoracic echocardiography (TTE) is readily available and non-invasive. Transesophageal echocardiography (TEE) offers insights into size, shape, attachment site, extension, and hemodynamic effects. Ultrasound-enhancing agents in echocardiography help differentiate various masses. Thrombi and benign tumors display a non or low-enhancing pattern. Malignancies and highly vascular tumors display a hyperenhancing pattern. Doppler velocities aid in assessing the hemodynamic impact.
  
• Cardiac MRI (CMR) is invaluable in the assessment of cardiac masses. In addition to anatomy, dimensions, and mass consistency, using different signal sequences like T1, T2, early and late gadolinium enhancement differentiate tissue characteristics and unveil fatty presence, necrosis, bleeding, inflammation, and vascularity within a mass.
  
• Cardiac CT provides high spatial and temporal resolution, multiplanar image reconstruction, and rapid acquisition. The broad field of view allows for the evaluation of the chest, lung tissue, vascular structures, and potential masses within the chest. Cardiac CT can be used to detect calcifications within the mass, although it has less soft tissue resolution compared with CMR.
  
• FDG-PET/CT can help gauge tumors’ metabolic activity. When CT alone doesn’t decisively determine benign or malignant nature, PET/CT steps in, aiding in malignancy diagnosis and guiding biopsy locations, staging, and cancer therapy planning.
  

Cardiac tumors

• Cardiac tumors can be categorized into primary and secondary tumors.
  
• Secondary tumors, arising from metastasis, are more prevalent and often stem from cancers like melanoma, breast, or lung cancer.
  
• Secondary tumors can lead to issues like pericardial effusion with or without cardiac tamponade, myocardial infiltration, obstruction, or embolization. Primary tumors include benign (about 80%) and malignant (about 20%) types.
  
• Malignant tumors are mainly sarcomas, such as angiosarcomas and rhabdomyosarcomas.
  
• Benign tumors encompass myxomas, gelatinous masses with scattered myxoma cells; papillary fibroelastomas, frond-like masses typically on valves; lipomas, composed of fat cells; fibromas, containing fibroblasts and mostly found in the left ventricle; and rhabdomyomas, made of maldeveloped cardiac myocytes and often seen in ventricles. Other rare tumors include Purkinje cell tumors. However, the latter three mentioned are more common in children.
  

Clot-in-transit

• Clot-in-transit (CIT) is the presence of mobile echogenic material in the right atrium or ventricle as seen on ultrasound.
  
• Right heart clots are classified into three types based on their morphology:
  
  • Type A (common and carries a high risk of pulmonary embolization)
    
  • Type B (assumed to originate from the atrium or ventricle)
    
  • Type C (rare and migratory, resembling cardiac myxomas)
    
  
  
• Intervention options for CIT include catheter-based thrombolysis, systemic (IV) thrombolysis, surgical/endovascular embolectomy, and anticoagulation therapy.
  
• Catheter-based thrombolysis involves high-frequency ultrasound exposure, catheter-directed thrombolysis, mechanical thrombectomy, and endovascular clot suction. It has a high success rate but may not work for bulky thrombi.
  
• Surgical embolectomy is recommended for hemodynamically unstable patients with CIT and provides an opportunity to address right-to-left heart communication. It requires substantial surgery and cardiopulmonary bypass.
  
• In cases of concomitant CIT and pulmonary embolism (PE), simultaneous treatment is essential to prevent further PE episodes.
  
• Anticoagulants are an option for patients in whom surgery is contraindicated, but they do not affect existing clots and may lead to bleeding or thrombus fragmentation.
  
• Systemic thrombolysis can improve right ventricular function, reduce pulmonary hypertension, and dissolve clots in multiple locations but carries a risk of thrombus embolization as well as bleeding complications.
  
• Management plans for CIT should consider individual patient factors like hemodynamic stability, right heart function, patent foramen ovale (PFO), and malignancy.
  
• There are no definitive guidelines. As a result, treatment decisions should be made on a case-by-case basis. An algorithm for CIT treatment may be helpful in clinical decision-making. PE response teams (PERT) are invaluable for complex decision making.
  

Angioleiomyoma

• These are rare, benign tumors that are classified as pericytic (perivascular) soft tissue tumors.
  
• There appears to be no consensus on incidence and prevalence, though there have been reports of this tumor accounting for around 5% of benign soft tissue tumors. Women are more affected than men. The age of diagnosis tends to be in the 4th to 6th decade.
  
• They typically arise in the extremities, particularly the lower extremities. However, the prevalence of uterine, cardiac, and major vascular deposition (IVC) is unknown.
  
• Typically, when present in the extremities, patients complain of discomfort due to the nodules. That said, location and size will determine symptoms. Pulmonary angioleiomyomas causing dyspnea have been reported. If involving the uterus, patients may present with menorrhagia, abdominal pain, and abdominal mass. Those masses can be submucosal, intramural, subserosal. As in this case, excessive burden in the IVC and right heart can lead to hemodynamic limitations, ultimately leading to symptoms of dyspnea and syncope.
  
• There is no agreement on the pathophysiology of this tumor. However, there are hypotheses, including trauma to the area, venous stasis, and hormonal factors causing the propagation of abnormal cell growth. Proposed histological types include capillary type (narrow vessels interlaced with thick fascicles of smooth muscles), venous type (thick vessels interspersed with fascicles of smooth muscle), and cavernous type (widened vessels with less smooth muscles).
  
• Although echo, CT, and MRI imaging could help evaluate the characteristics of this mass, pathology is required for a definitive diagnosis.
  
• The mainstay treatment is surgical excision of the tumor. This has been effective in preventing recurrence. However, in this case, the treating team should be cognizant of any potential medications leading to the proliferation of this tumor.
  

Benign metastasizing leiomyoma

• The origins of the tumor are typically uterine leiomyomas. These are inherently mitotically inactive smooth muscle cells without atypia, which have migrated to extra-uterine sites. 
  
• Although rare, these are mostly seen in patients of reproductive age and frequently involve the lungs, whereby it is called pulmonary benign metastasizing leiomyoma.
  
• Patients may present with incidental extra-uterine leiomyoma found on exam. If there is hemodynamic change in the cardiac chambers or if involving the lungs,  patients may present with symptoms including dyspnea, cough, and chest discomfort.
  
• There is evidence to suggest chromosome deletions, particularly in 19q and 22q, may predispose leiomyomas to metastatic potential. 
  
• When present in the lung, this needs to be differentiated from pulmonary lymphangioleiomyomatosis (LAM), which on histology demonstrates perivascular epithelioid cells along bronchial interstitium.
  
• Leiomyomas beyond the uterus have been classified as intravenous, benign metastasizing, diffuse peritoneal, retroperitoneal, and parasitic. Incidence is approximately 0.25% to 0.4% for those with leiomyomas.
  
• For patients with symptomatic disease, resection of the leiomyoma, anti-hormonal agents, and anti-angiogenesis agents can be used for tumor treatment.
  

References –

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