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Lipotamous Cardiac Disorders: Two Unusual Cases and a Review of the Literature
From the Division of Cardiology, Loyola University Medical Center, Maywood, Illinois. The authors report no conflicts of interest regarding the content herein. Manuscript submitted January 16, 2009, provisional acceptance given January 20, 2009, and final version accepted January 22, 2009. Address for correspondence: Ferdinand Leya, MD, Division of Cardiology; Loyola University Medical Center; 2160 South First Avenue; Maywood, IL 60153.
_________________________________________________ ABSTRACT: Tumors involving the heart and surrounding cardiac structures may be benign or malignant and can be classified as primary versus secondary in etiology. Primary cardiac tumors are rare lesions and the vast majority of these are benign neoplasms. More commonly, masses that involve the cardiac structures are secondary in nature. The focus of this manuscript will be those cardiac lesions characterized by a predominance of fatty cells. We present two unusual cases of patients with lipomatous cardiac disorders with extreme imaging and review the current literature on this topic.
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J INVASIVE CARDIOL 2009;21:E65–E69 Tumors involving the heart and surrounding cardiac structures may be benign or malignant and can be classified as primary versus secondary in etiology. Primary cardiac tumors are rare lesions reported only in 0.001 to 0.03 percent of patients in an autopsy series,1 and the vast majority of these are benign neoplasms. More commonly, masses that involve the cardiac structures are secondary in nature1–3 (Table 1). Due to their variation in size and location, patients with cardiac tumors may be asymptomatic or present with local cardiac, embolic or systemic symptoms. The focus of this manuscript will be those cardiac lesions characterized by a predominance of fatty cells. Case Presentations Case 1. A 47-year-old female with hypertension presented to our outpatient cardiology clinic with complaints of recurrent syncope for the past 3 years. She reported these syncopal episodes had occurred at rest or with minimal exertion and were often preceded by diaphoresis, nausea and palpitations, but no chest pain. The patient was taking ramipril and denied tobacco, excessive alcohol or illicit drug use. There was no significant family medical history including early coronary artery disease, heart failure, sudden death or arrhythmias. On examination, the patient was not obese and was in no apparent distress. Cardiopulmonary examination revealed a regular rate and rhythm without a gallop or murmur. Her lungs were clear bilaterally and her peripheral pulses were normal in all extremities. Laboratory evaluation included a normal complete blood count and complete metabolic panel. Her BNP was 16 ug/mL. A chest X-ray revealed moderate enlargement of the cardiac silhouette without evidence of pulmonary venous congestion or pulmonary parenchymal disease. A standard 12-lead electrocardiogram revealed normal sinus rhythm without any repolarization abnormalities. Transthoracic echocardiography (TTE) demonstrated a structurally normal heart with a large homogenous mass occupying the pericardial space without significant pericardial effusion. Cardiac magnetic resonance (MR) imaging further characterized the 3.5 cm circumferential mass as a diffuse fatty infiltration of the pericardial space with increased signal on fat saturation images. There were no pericardial cysts noted (Figure 1). Cardiac catheterization confirmed that there was no hemodynamic abnormality of diastolic filling (Figure 2). Although unique, and not yet described, a pattern of neovascularization arising from the epicardial coronary vessels traversing into the pericardial mass was identified (Ramana-Leya sign) (Figure 3). Tissue needle biopsy obtained via subxiphoid pericardiocentesis revealed mature adipose tissue and immunohistochemical analysis for CD68+ (inflammatory cells), confirming no evidence of an exaggerated inflammatory response in the fatty tissue (Figure 4). A diagnosis of diffuse pericardial lipomatosis (PL) was made. Incidentally, during her workup, the patient experienced recurrence of her symptoms with frank syncope while on telemetry monitoring, showing a prolonged sinus arrest of 5 seconds without an escape rhythm, necessitating a dual-chamber permanent pacemaker implantation. Six months later, the patient was seen in the clinic with complete resolution of her syncopal episodes. Case 2. A 68-year-old male with known coronary artery disease status post coronary artery bypass graft surgery presented to our cardiology clinic with reports of progressive exertional dyspnea and mild lower-extremity edema. He denied any chest pain, palpitations or syncope. The patient was taking aspirin, digoxin, a beta-blocker, a statin and a diuretic. Physical examination revealed a regular heart rate and rhythm without a gallop or murmurs. His lungs were clear bilaterally and his peripheral pulses were mildly decreased in the lower extremities. There was mild pedal edema. Laboratory evaluation included a normal complete blood count and a complete metabolic panel. His BNP was 126 ug/mL. TTE revealed a structurally normal heart with significant (nearly 5 cm thick) lipomatous hypertrophy of the interatrial septum (LHAS) which extended toward the superior vena cava. A subsequent cardiac computed tomographic (CT) angiogram further depicted the severe lipomatous hypertrophy, which spared the fossa ovalis, but impinged upon the lumen of the superior vena cava (SVC) at the SVC-right atrium (RA) junction (Figure 5). Furthermore, this hypertrophy extended from the inferior aspect of the right pulmonary artery, through the interatrial septum and to the base of the heart, extending medially to the coronary sinus and superiorly to abut the proximal ascending aorta. Right- and left-heart cardiac catheterization revealed diffuse native coronary artery disease with widely patent bypass grafts and a 3–4 mmHg dynamic gradient across the SVC-RA narrowing noted only during end-inspiration (Figure 6). Venograms, which opacified the SVC, RA and right ventricle, further depicted the narrowing (Figures 7 and 8). Because no significant gradient or obstructive signs were identified, his symptoms of exertional dyspnea were felt not to be cardiac in etiology and therefore no surgical intervention was indicated. Discussion. We describe 2 patients with unusually severe lipomatous cardiac infiltrations: 1 patient with LHAS, and the other with pericardial lipomatosis (PL). In addition, we are the first to describe via cardiac catheterization and angiography a unique neovascularization process arising from the epicardial coronary vessels traversing into the pericardial lipomatosis tissue (Ramana-Leya sign). Although both our patients had extremely large fatty tissue deposition, neither patient required surgical resection. Benign lipomatous tumors are the second most common primary cardiac tumor. These tumors, which are characterized by a predominance of benign fatty cells, can be further categorized as lipoma/liposarcoma or LHAS based on the degree of encapsulation.4 Cardiac lipomas occur sporadically and have no predilection for gender or age. These tumors commonly develop in the subendocardial region of either the atria or ventricles, but also have been found in intramyocardial and subepicardial regions and rarely on the cardiac valves.5–10 Most lipomas are less than 2 cm in size, but extreme cases of masses larger than 4 kg have been reported.11 Accordingly, the lesions can then result in symptoms of heart failure (obstructive endocardial lesions), arrhythmias (intramyocardial lesions), compression of the heart (larger epicardial lesions), pericardial effusions (epicardial lesions) and valvular insufficiency (valvular lesions).9,12 Primary cardiac liposarcoma is a rare cardiac tumor found in less than 1% of all primary malignant tumors of the heart.3 The majority of these tumors originate from the right atria or ventricle.13 These tumors are further classified based on their pathological appearance: well differentiated, myxoid, round cell and pleomorphic.14 The most common complication of these tumors is mechanical obstruction of blood flow. However, patients may present with symptoms of dyspnea, arrhythmia or signs of congestive heart failure or arterial embolism.13 Rarely is overt compression of the right atrium or tamponade present.15,16 Surgical resection of these tumors is most often reserved for attempts to relieve symptoms or prevent embolic events.14 PL is an extremely rare disorder with very few reported cases.17,18 PL has been compared to diffuse mediastinal lipomatosis (ML) that is characterized by a large amount of nonmalignant, mature adipose tissue and almost always associated with Cushing’s syndrome, long-term steroid use or obesity.17–21 There is little dependable information regarding the clinical presentation of PL due to its extreme infrequency. But of the available literature, it appears that most patients with ML (or PL) are asymptomatic, although some require surgical resection due to the compressive effects of the mass. LHAS is a more common entity seen in approximately 1–2.2% of patients22,23 and is defined as an accumulation of fat tissue > 2 cm in the atrial septum at the level of the fossa ovalis.24,25 The etiology of this condition has yet to be determined, however, it has been suggested that it is due to embryonic mesenchymal cells within the primitive atrial septum that can develop into adipocytes with an appropriate stimulus.26,27 Initial reports correlated LHAS with advanced age, gender and obesity, but more recent studies are conflicting.1,22,24,28 The vast majority of patients with LHAS are asymptomatic, but rarely patients may present with arrhythmias, symptoms from right-heart flow obstruction or even sudden death.7,29 Atrial arrhythmias are the most common type of dysrhythmia, which may be due to underlying atherosclerotic disease or direct disease infiltration leading to interference with the architecture of the atrial myocytes and conducting system.25,28,30 Diagnosis. Lipomas, PL and LHAS are a challenge to diagnose. Since the symptomatology varies widely, diagnosis is often made incidentally during imaging studies ordered to confirm suspicions of other diagnosis.7,8 Two-dimensional echocardiography (both transthoracic and transesophageal) is useful in the initial assessment of tumor size and location, but cannot accurately distinguish between fat and other connective tissues.7,22 In contrast, cardiac CT and MR scans have been instrumental in confirming diagnosis by distinctive fat patterns seen with this type of noninvasive imaging (approximately -25–100 Hounsfield units).3,6–8,31,32 Gross and histopathologic examination of lipomas reveals well-encapsulated masses that are composed of mature fat cells with or without fibrous connective tissue, vacuolated brown fat or calcification.5 Pericardial lipomatosis has a similar histopathologic appearance (Figure 4), although it is not encapsulated.17 Similar examination of LHAS reveal a nonencapsulated accumulation of mature fat and vacuolated adipose cells, hypertrophied myocytes, myocardial fibers and a significant amount of fibrous tissue deposition.1 Treatment. The treatment for cardiac lipomas and PL is most often conservative. Although surgical resection may be necessary if the tumor is causing significant symptoms, the post-operative prognosis is excellent1,33 and the chance of recurrence appears low.34 In contrast, there is only 1 reported case of successful surgical resection of pericardial lipomatosis (which had presented as cardiac tamponade) in a patient who had evidence of neovascularization in the pericardial lipomatosis.35 There is a theoretical periprocedural risk of significant bleeding if a patient has extensive neovascularization arising from the epicardial coronaries, as seen on cardiac angiography (Ramana-Leya sign). LHAS is also treated conservatively, with surgical resection reserved for patients with hemodynamic compromise due to obstruction.22,36 Conclusion. We present 2 unusual cases of severe lipomatous disorders of the heart including the first description of a unique neovascularization process arising from the epicardial coronary vessels to pericardial lipomatosis (Ramana-Leya sign). To date, neither patient has required surgical resection. Primary cardiac and pericardial lipomatous tumors are rare disorders that are most often benign and only require careful monitoring and conservative management. However, we firmly believe that these case presentations, their thorough diagnostic evaluation and their treatment plans are very useful to a practicing invasive or interventional cardiologist. Interventionalists and invasive cardiolgists alike may be the first to encounter these patients during invasive testing in the cardiac catheterization laboratory, and it is very important that these conditions be accurately recognized to avoid unnecessary testing or inappropriate (and/or dangerous) treatment plans. Although these conditions (especially the significant degree of our patients’) are rare, it is essential for practicing cardiologists to recognize and understand their presentations and, when symptomatic and/or severe, the implications for their possible treatment strategies. For example, in patients presenting with diffuse pericardial lipomatosis (Patient #1), it is crucial that a practicing invasive or interventional cardiologist understands the clinical presentation and possible cardiac tamponade, the pathology and therefore ineffectiveness of an attempt at a therapeutic pericardiocentesis due to dense adipose tissue deposition and apparent neovascularization of these masses (first described in our manuscript). Furthermore, in patients presenting with severe IHAS (Patient #2), it is imperative to understand the angiographic appearance as well as the invasive hemodynamic monitoring necessary for a thorough evaluation and determination if surgical therapy is indicated. In addition, patients with this extreme presentation of the disorder would likely be unfit for other invasive procedures (e.g., transseptal puncture and/or atrial-septal occluder device implantation). However, these tumors may infrequently lead to potentially life-threatening consequences of hemodynamic compromise or malignant arrhythmias which may necessitate more aggressive therapy, including surgical resection.
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