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Current diagnosis and management of cardiac myxomas Expert Rev. Cardiovasc. Ther. 13(4), 369–375 (2015)

Sonia Jain1, Joseph J Maleszewski1,2, Christopher R Stephenson3 and Kyle W Klarich1 1 Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA 2 Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA 3 Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA *Author for correspondence: Tel.: +1 507 284 1226 Fax: +1 507 284 3968 [email protected]

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Cardiac myxoma is the most common cardiac neoplasm. In the majority of cases, it is isolated (non-syndromic) and located in the left atrium. In up to 10% cases, it is seen in syndromic association with the Carney complex where it is encountered in younger patients, with atypical and multiple locations, such as the right atrium or ventricles, and carries a high risk of recurrence. Imaging is pivotal in the diagnosis, management guidance and surveillance. Surgical excision is the established definitive treatment. Further research should address management strategies in incidentally discovered small myxomas in asymptomatic patients and the role of genetic testing and screening in syndromic myxomas. KEYWORDS: cardiac tumor . Carney complex . diagnosis . echocardiography . heart neoplasms . myxoma . pathology .

prognosis

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therapy

Cardiac myxoma (CM) is a benign neoplasm with not so benign clinical implications. Although, primary cardiac neoplasms are rare, myxomas are widely felt to be the most common benign tumor. Most busy echocardiographic laboratories will identify a myxoma, approximately 1 in 5000 studies [1]. Myxomas have a wide array of clinical symptoms and implications. It is important to determine the etiology, either isolated or familial, as this has significant management implications. The reported incidence of cardiac neoplasms was less than 0.1% in a large unselected autopsy series in 1993 [2] and 0.02% in a subsequent analysis of pooled autopsy series in 1996 [3]. A large echocardiographic series from 1991 identified 30 cardiac tumors in 20,305 consecutive patients, corresponding to a prevalence of 0.0015% or 1 cardiac tumor per 676 studies performed [4]. Three-quarters of primary cardiac neoplasms are benign, of which approximately half are CMs. CMs are currently considered the most common benign cardiac neoplasms in adults, although unpublished data from the Mayo Clinic suggests that papillary fibroelastoma is more common, although its neoplastic nature is questionable. The first published description of a left atrial myxoma was by King in 1845 [5] in the autopsy findings of an 80-year-old distinguished British

10.1586/14779072.2015.1024108

general who suffered syncope and sudden death. He described ‘a semi-fluid substance seen in the region of the heart’ probably referring to the typical gelatinous mass of a myxoma. The first successful surgical excision of a left atrial myxoma was performed by Swedish cardiovascular surgeon Clarence Crafoord [6] in 1954 and today CM is the most commonly resected neoplasm of the heart at many major heart centers. Whereas initial descriptions were largely based on postmortem series, in contemporary practice, CMs are largely identified antemortem by non-invasive imaging, including echocardiography (echo), computed tomography or MRI. Epidemiology

CMs are commonly diagnosed between 30 and 60 years of age, with a mean age of diagnosis of 50–55 years. CMs are very rare in children under the age of 10 years, but when they do, it is often in a syndromic context (see below). They occur about twice as frequently in women, though the reason for this female sex predilection is not clear [7–9]. The majority (>90%) of myxomas are isolated and nonsyndromic [10]. In 3–10% cases, CMs are inherited, usually in the context of the socalled Carney complex (CNC) or myxoma syndrome.

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Figure 1. Characteristic spotty mucocutaneous pigmentation of the face, eyelids, mouth and vermillion border of the lips in a patient with Carney complex. Photo courtesy of Dr. J. Aidan Carney, Mayo Clinic, Rochester, MN.

Carney complex

CNC was first described as ‘the syndrome of myxomas, spotty pigmentation and endocrine overactivity’ by Carney et al. [11] at the Mayo Clinic in 1985. CNC is an autosomal dominant multiple neoplasia syndrome, characterized by myxomas (cardiac or other endocrine, neural and skin neoplasms), endocrinopathy (Cushing syndrome and acromegaly) and spotty mucocutaneous pigmentation, particularly on the vermillion border of the lips (FIGURE 1) [12]. There are important differences between the syndromic and non-syndromic CMs. CNC-associated CM has an earlier age of onset (mean age 26 years), demonstrates no gender or racial predilection, has atypical and multifocal tumor locations, and carries a significantly higher risk of recurrence [13–16]. Two-thirds of the patients with CNC have a mutation in the PRKAR1A gene on chromosome 17q22-24, which encodes the regulatory subunits I–K of the protein kinase A (PKA), the primary mediator of cAMP signaling in mammals [12,17]. In a recent study of 110 cases of CM, Maleszewski et al. [18] noted that up to 32% of non-syndromic CMs have aberrant PRKAR1A protein expression, with at least one-third of these harboring identifiable mutations in the PRKAR1A gene. Therefore, abnormal tumor PRKAR1A expression does not appear to be a reliable discriminator of syndromic and non-syndromic CMs. Pathology

Myxoma (New Latin, from Greek myxa) is a benign neoplasm, aptly named given its common gelatinous or mucus-like appearance (FIGURE 2A). Grossly, CMs can range from a slimy, 370

friable lesion to one that is firm or sometimes calcified (so-called lithomyxoma). They may have a smooth or villous surface, the latter of which is thought to have a greater potential for embolic complications. CMs can be sessile, arising from a broad base, or emanate from a stalk or pedicle. The tumors are typically variegated, often having intratumoral hemorrhage owing to their vascularity. Surface thrombi, either organized or fresh, can sometimes be seen and are also thought to contribute to the associated embolic phenomena [7,9]. CMs can range in size from 2 mm to upwards of 15 cm (mean 5–6 cm) [7,9,19]. Histologically, CMs are characterized by a proliferation of bland, spindle- or stellate-shaped cells (so-called myxoma or lepidic cells) in a myxoid, proteoglycan-rich background (FIGURE 2B) [7,19,20]. The cells are often situated around blood vessels, forming perivascular ring structures. The constant motion experienced by these intracardiac tumors can cause traumatic rupture of the tumor’s blood vessels, resulting in intratumoral hemorrhage that manifests as either fresh blood within the tumor or hemosiderosis. CMs may have unusual histological features, by virtue of their likely primitive multipotential mesenchymal origin. Some of these include ossification (with or without extramedullary hematopoiesis) and gland formation. The latter of these can cause diagnostic concern for a metastatic adenocarcinoma. Rare reports have documented Epstein–Barr virus-associated large B-cell lymphomas arising within otherwise prototypical CMs [21–23]. This finding, and the need to treat such lymphoproliferative processes, underscores the importance of careful histopathologic evaluation of these lesions following surgical resection. Location

CMs occur most commonly in the left atrium (75%), followed by the right atrium (15–20%) and then the ventricles [24]. CMs in biatrial, biventricular and atrioventricular locations have been reported. When located in the atria, most tumors are pedunculated, and arise on the atrial septum, in the region of the fossa ovalis. Large CMs can prolapse across the mitral or tricuspid valve, resulting in obstruction to blood flow. Other sites of attachment include the anterior or posterior atrial wall, atrial appendage, and mitral annulus or the atrial aspect of the mitral valve leaflets. A non-left atrial location should raise suspicion for a tumor arising in a syndromic setting and prompt clinical evaluation for other features of CNC (see above). While most CMs arise in an isolated and singular fashion, multiple synchronous tumors can also occur. Again, the latter finding is far more common in the setting of CNC. Clinical presentation

The clinical presentation of patients with CMs is quite variable and can range from profound heart failure to being asymptomatic, and the lesion is found incidentally on imaging. Despite their histopathologic benignity, the precarious location of CMs can cause malignant consequences. Like other cardiac tumors, CMs can produce symptoms by virtue of their size, their intracardiac site and the tumor character (embolic potential and Expert Rev. Cardiovasc. Ther. 13(4), (2015)

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cytokine production). It is interesting to A B note that no single feature can accurately predict their clinical behavior. In general, right atrial myxomas are less frequently symptomatic than those arising in the left atrium. Cardiovascular symptoms are the most common presenting features. In a large retrospective review of 112 patients with CM, cardiac symptoms were identified as the presenting complaint in 67% of patients [9]. Heart failure, chest pain 1 cm unrelated to exercise, palpitations, syncope and myocardial infarction were reported. Similarly, another series of Figure 2. Pathologic features of cardiac myxomas. (A) Grossly, cardiac myxomas are 91 patients with cardiac tumors, includgelatinous lesions that typically have a smooth surface. Areas of red hemorrhage may be ing CMs, found presenting symptoms of seen and attest to the high vascularity in these lesions. (B) Histologically, the lesions are heart failure (52%), dyspnea (51%), palcharacterized by bland, spindle-shaped, ‘myxoma’ cells within a myxoid background pitations (37%) and angina (20%) (hematoxylin & eosin, original magnification  600). because of a combination of obstruction, distortion of valvular anatomy, direct invasion of the tumor of a multimodality imaging protocol in the diagnosis and surgical planning for tumor resection [32]. into cardiac conduction tissues and local irritation [8]. Non-specific constitutional symptoms, such as fever, malaise, fatigue, weight loss, arthralgia, Raynaud phenomena, arthralgias Imaging and myalgias are the next most frequent, seen in 13–34% of Echocardiography patients [8,9]. CMs are known to have the potential to elaborate Echo is the primary imaging modality for both the initial diagIL-6, which is thought to be responsible for such constitutional nosis and follow-up surveillance of CM. A comprehensive 2D symptoms [25–27]. Serum levels of IL-6 seem to have some correla- transthoracic echo evaluation should be performed on all tion with tumor size, with larger tumors associated with higher patients with suspected or known CM. Schattenberg [33] first levels [28]. Reported laboratory abnormalities, which may also be described the echocardiographic features of left atrial myxoma. attributed to IL-6 production, associated with CMs include ane- Echo can readily visualize tumor location, shape, size, number mia, increased erythrocyte sedimentation rate and hypergamma- and morphological characteristics and detect pertinent hemodyglobulinemia. Constitutional symptoms tend to abate, with namic consequences (FIGURE 3). Two distinct morphological types normalization of serum IL-6 levels, following tumor resection [29]. have been identified: a round type with a smooth surface Embolization of the tumor fragments or surface thrombi can appearance and a polypoid type with an irregular surface that is result in devastating neurologic or systemic infarction. This is more commonly associated with embolic phenomena [34]. A meticulous study should be performed to avoid misdiagillustrated by a series of 74 consecutive patients with atrial nosis of normal anatomic variants and tumor mimics or other myxoma from the Mayo Clinic, 9 (12%) of whom had embolic central nervous system complications [30]. For seven of tumors [35]. Differential diagnosis includes thrombus, other carthese nine patients, stroke was the initial presenting symptom diac tumors, such as sarcoma, papillary fibroelastoma, rhabdoand the embolic risk was reflected by the mobility, rather than myoma (primarily in children) and metastatic tumors or size, of the myxoma. The incidence of neurologic sequela infrequent findings, such as a blood cyst or hemangioma. Echo reported in the literature range from 12 to 30% [8,9,30]. The features that help distinguish CM from thrombus or other vasreported incidence of systemic embolization to limbs, splanch- cular tumors include the characteristic pedunculated attachment to the atrial septum, lobulated appearance, and the absence of nic and coronary circulations ranges from 4.1 to 23% [8,9,31]. extension into vessels or myocardial infiltration. If the tumor is large enough, it can cause mechanical obstruction of the atrioDiagnosis While imaging can provide important clues to the diagnosis, ventricular valvular orifice and valvular dysfunction. Doppler definitive diagnosis must be rendered on gross and microscopic hemodynamics can provide an objective assessment of transmiexamination of the tumor itself. As mentioned, CMs can come tral or transtricuspid flow obstruction with diastolic mean to clinical attention because of symptoms directly related to the gradient (FIGURE 3D), and estimated right ventricular systolic prestumor or incidentally during routine imaging workup for other sure. Color flow imaging helps assess valvular integrity, particureasons. Echocardiography (echo) is the mainstay of diagnostic larly in cases of tumor attachment to mitral valve leaflets. imaging but cardiac computed tomography and MRI can pro- Contrast echocardiography perfusion imaging can be useful in vide additional data and are increasingly being utilized as part differentiating CM from vascular tumors and thrombi. informahealthcare.com

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A

B

C

D

Figure 3. Transthoracic echocardiography showing the typical appearance of a large left atrial myxoma attached to the atrial septum (yellow arrow). (A) Parasternal long axis view (arrow). (B) Apical four chamber view. (C) Color Doppler shows flow turbulence suggesting transmitral flow obstruction. (D) Doppler evaluation demonstrates mechanical obstruction resulting in a mean mitral diastolic gradient of 5 mmHg (heart rate 68 bpm). A

B

Kirkpatrick et al. [36] demonstrated both qualitative and quantitative differences in perfusion imaging in a series of 16 cardiac masses – highly vascular or malignant tumors hyperenhanced in comparison to surrounding myocardium, myxomas partially enhanced, whereas thrombi failed to enhance. Transesophageal echocardiography (TEE) provides superior visualization compared with transthoracic echo (FIGURE 4), and is useful to rule out multiple tumors and distinguish from thrombi [37]. Most centers employ intraoperative TEE during surgical excision of CMs. Real-time 3D echocardiography, particularly 3D TEE, has an incremental role in visualization of tumor morphology and its spatial relation to surrounding cardiac structures, thereby aiding in diagnosis and surgical planning (FIGURE 4C) [38–40]. Cardiac computed tomography

On computed tomography imaging, a left atrial mass with a narrow attachment to the atrial septum and a heterogeneous low attenuation is highly consistent with a CM [41]. However, computed tomography is probably most useful in differentiating CM from malignant tumors and identifying associated mediastinal lymphadenopathy and tumor extension. Cardiac MRI

C

Cardiac MRI allows for better characterization of tumor shape and density, tissue signal intensity with reference to normal myocardium and perfusion. CMs are typically heterogeneous in cine imaging because of interspersed calcification- or hemosiderin-related artefacts, hyperintense in T2 weighted and isointense in T1-weighted MR imaging [42,43]. Treatment

Figure 4. Transesophageal echocardiography. (A) A large myxoma with its characteristic attachment to the atrial septum (yellow arrow). (B) A right atrial myxoma at the junction of the right atrium and superior vena cava (yellow arrow). (C) 3D face view of the myxoma from the left atrial perspective. SVC: Superior vena cava; RA: Right atrium.

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Surgical excision is the only definitive treatment and is highly efficacious. Upon diagnosis, prompt surgical excision is recommended to prevent systemic embolization and cardiovascular complications. Surgical excision is typically performed via a standard median sternotomy and bicaval cardiopulmonary bypass. The CM, in its usually left atrial location, is approached through a right atriotomy Expert Rev. Cardiovasc. Ther. 13(4), (2015)

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Cardiac myxomas

and the fossa ovalis is excised around the attachment of the myxoma, which is then carefully removed while taking precautions to prevent tumor fragmentation and spillage (FIGURE 5). Meticulous attention has to be paid to tumor handling to prevent embolization complications and tumor seeding with consequent recurrence. The atrial septum is repaired with a pericardial patch. Intraoperative TEE is used to evaluate for residual tumor. In the largest contemporary series, Garatti et al. [44] describe the management and outcomes of 98 patients undergoing open myxoma excision. They reported low operative mortality (3%) because of low cardiac output state in two emergently operated patients and cerebrovascular accident in one patient. Similarly, tumor recurrence was infrequent at 1%, occurring in one patient at the left atrial free wall 68 months after the index surgery and attributed to probable intraoperative seeding at the time of removal of the initial tumor that was attached to the fossa ovalis. Depending on tumor location, concurrent mitral or tricuspid valve repair or replacement may be required. Postoperative complications include low cardiac output hemodynamics requiring inotropic support; electrophysiological abnormalities, such as transient atrial fibrillation and complete heart block necessitating pacemaker implantation; hydropneumothorax; tumor fragmentation and embolization; and cerebrovascular accident [44–46]. In one large series, transient atrial arrhythmias were seen in 26% patients but permanent pacemaker was necessary in only 2% patients [9]. There have been reports of minimally invasive surgical techniques employing minithoracotomy [47–49]. While this approach is less invasive, there is insufficient short- and long-term follow-up data. The first case report of percutaneous removal of a right atrial myxoma was recently published [50]. Prognosis

Overall, the prognosis in patients with CM is excellent. Recurrence rates are between 1 and 5% [9,44]. Reasons for recurrence include incomplete resection (most commonly), intraoperative tumor seeding and tumor multifocality. For recurrent disease, different strategies have been described, including simple reexcision, reexcision with intraoperative cryoablation and cardiac autotransplantation with ex-vivo radical bi-atrial resection and reconstruction [48,51]. A large series from the Mayo Clinic reports the risk of recurrence increasing linearly for the first 4 years after surgical excision and then reaching a plateau [12]. Based on this, yearly surveillance echocardiography is recommended for the first 4 years at least. In the familial variant, long-term periodic echocardiographic surveillance is essential for timely relapse detection and treatment. As mentioned above, Epstein–Barr virus-associated large B-cell lymphomas can rarely arise in the setting of CM. Given the rarity of reported cases of Epstein–Barr virus-positive lymphoproliferative processes arising in the setting of myxoma, the prognostic implications of such are not definitively known. However, based on the information in the reports hitherto, the informahealthcare.com

Review

Figure 5. Open surgical excision of a left atrial myxoma via a right atriotomy.

lesion appears to have a generally favorable prognosis with long-term survival demonstrated even in those not treated with systemic chemotherapy [52]. Likewise, although the prognosis for primary cardiac lymphomas is typically very poor, lymphomas associated with CMs and intracardiac devices appear to behave in a more indolent fashion [53]. Because of the familial implications of a diagnosis of CNC, every patient with a CM should be screened for additional manifestations of such. If any ambiguity exists, serum molecular genetic testing can be performed. It is worth reiterating that the absence of an identifiable mutation does not preclude the diagnosis of CNC. Expert commentary

Although the majority of CMs are isolated (non-syndromic), it is important to recognize a less common syndromic manifestation in patients with CNC. Discerning between the two variants has important implications for patient management and surveillance. Two-thirds of CNC-associated CMs have been shown to exhibit inactivating genetic mutations of PRKAR1A and it was generally accepted that this would be a reliable means of distinguishing between isolated and syndromic neoplasms. However, a recent publication demonstrated that loss of PRKAR1A protein expression is also seen in up to 32% of isolated myxomas. Further research in this area is urged. Echocardiography is the optimal imaging modality because of its extensive availability, lack of radiation exposure and relative cost–effectiveness. Integrated multimodality imaging with 2D and 3D echo, cardiac computed tomography or MRI can be helpful in patients with inconclusive echocardiographic findings, atypical features, multiple masses or to delineate neighboring anatomical detail for surgical planning. Five-year view

As the use and sensitivity of cardiac imaging increases, myxomas are likely to be more readily identified. Current literature is limited to retrospective case series and single center experiences. Prospectively, enrolling national and international registries 373

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would be a valuable and practical resource to expand the evidence base. Important questions remain to be answered – the role of genetic testing, the optimal management strategy in asymptomatic patients with incidentally identified myxoma, the optimal interval and total duration of surveillance in syndromic and isolated forms and discerning the role of myxoma in sudden death.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Key issues .

Cardiac myxomas are the most commonly identified primary cardiac neoplasms.

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Most myxomas are isolated. In 3–10% cases, they are inherited in the syndromic context of the autosomal-dominant Carney complex.

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Distinguishing between the isolated and syndromic variants of myxoma is essential as it has significant implications for patient management, prognosis and family screening.

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Two-thirds of patients with Carney complex-associated myxomas have inactivating mutations of the PRKAR1A gene.

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Recent data suggests that loss of PRKAR1A protein expression may also play a role in isolated myxoma tumorigenesis.

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The clinical presentation is heterogeneous, varying from incidental discovery to devastating complications, such as embolic stroke, pulmonary embolus and visceral infarctions.

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Echocardiography is the first-line imaging modality for both initial diagnosis and subsequent scrutiny.

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Computed tomography and MRI can provide complementary and incremental imaging detail.

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Left atrial location with a characteristic attachment to the atrial septum is an important diagnostic clue.

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Surgical removal is the definitive therapy. Minimally invasive and possibly, percutaneous techniques are emerging.

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Because of the small but real risk of recurrence, we recommend long term, interval echocardiographic surveillance in all patients with a history of cardiac myxoma.

References

7.

Papers of special note have been highlighted as: . of interest .. of considerable interest

Reynen K. Cardiac myxomas. N Engl J Med 1995;333:1610-17

8.

Centofanti P, Di Rosa E, Deorsola L, et al. Primary cardiac tumors: early and late results of surgical treatment in 91 patients. Ann Thorac Surg 1999;68:1236-41

1.

2.

Tamin SS, Khan SK, Maleszewski JJ, et al. Papillary fibroelastoma: an unexpectedly common cardiac mass. Presented at Rapid Fire Oral Abstracts: Valvular Heart Disease. American Society of Echocardiography 23rd Annual Scientific Sessions. 30 June 2012– 3 July 2012. Maryland, USA Lam KY, Dickens P, Chan AC. Tumors of the heart. A 20-year experience with a review of 12,485 consecutive autopsies. Arch Pathol Lab Med 1993;117:1027-31

3.

Reynen K. Frequency of primary tumors of the heart. Am J Cardiol 1996;77:107

4.

Sutsch G, Jenni R, von Segesser L, Schneider J. [Heart tumors: incidence, distribution, diagnosis. Exemplified by 20,305 echocardiographies]. Schweiz Med Wochenschr 1991;121:621-9

5.

6.

King G. Observations on the Inquest Held on the Late General Dick, and on the Cause of Death. Prov Med Surg J 1845;9: 650-1 Chitwood WR Jr. Clarence Crafoord and the first successful resection of a cardiac myxoma. Ann Thorac Surg 1992;54:997-8

374

9.

Pinede L, Duhaut P, Loire R. Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases. Medicine 2001;80:159-72

10.

Jain D, Maleszewski JJ, Halushka MK. Benign cardiac tumors and tumorlike conditions. Ann Diagn Pathol 2010;14: 215-30

11.

Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine 1985;64:270-83

12.

Stergiopoulos SG, Stratakis CA. Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease!. FEBS Lett 2003;546: 59-64

13.

Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 2001;86:4041-6

14.

Boikos SA, Stratakis CA. Carney complex: pathology and molecular genetics. Neuroendocrinology 2006;83:189-99

15.

McCarthy PM, Piehler JM, Schaff HV, et al. The significance of multiple, recurrent, and ‘complex’ cardiac myxomas. J Thorac Cardiovasc Surg 1986;91:389-96

16.

Vidaillet HJ Jr, Seward JB, Fyke FE 3rd, et al. ‘Syndrome myxoma’: a subset of patients with cardiac myxoma associated with pigmented skin lesions and peripheral and endocrine neoplasms. Br Heart J 1987;57:247-55

17.

Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000;26:89-92

18.

Maleszewski JJ, Larsen BT, Kip NS, et al. PRKAR1A in the development of cardiac myxoma: a study of 110 cases including isolated and syndromic tumors. Am J Surg Pathol 2014;38:1079-87

..

New research demonstrating loss of PRKAR1A protein expression is also seen in isolated, non-syndromic myxomas.

19.

Pucci A, Gagliardotto P, Zanini C, et al. Histopathologic and clinical characterization of cardiac myxoma: review of 53 cases from

Expert Rev. Cardiovasc. Ther. 13(4), (2015)

Cardiac myxomas

a single institution. Am Heart J 2000;140: 134-8 20.

Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Karolinska Institutet University Library on 04/14/15 For personal use only.

21.

22.

23.

24.

Tazelaar HD, Locke TJ, McGregor CG. Pathology of surgically excised primary cardiac tumors. Mayo Clin Proc 1992;67: 957-65 Svec A, Rangaiah M, Giles M, et al. EBV+ diffuse large B-cell lymphoma arising within atrial myxoma. An example of a distinct primary cardiac EBV+ DLBCL of immunocompetent patients. Pathol Res Pract 2012;208:172-6 Bartoloni G, Pucci A, Giorlandino A, et al. Incidental Epstein-Barr virus associated atypical lymphoid proliferation arising in a left atrial myxoma: a case of long survival without any postsurgical treatment and review of the literature. Cardiovasc Pathol 2013;22:e5-10 Aguilar C, Beltran B, Quinones P, et al. Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus? Cardiovasc Pathol 2015;24:60-4 Burke AP, Virmani R. Cardiac myxoma. A clinicopathologic study. Am J Clin Pathol 1993;100:671-80

25.

Seino Y, Ikeda U, Shimada K. Increased expression of interleukin 6 mRNA in cardiac myxomas. Br Heart J 1993;69:565-7

26.

Kanda T, Umeyama S, Sasaki A, et al. Interleukin-6 and cardiac myxoma. Am J Cardiol 1994;74:965-7

27.

28.

29.

Sakamoto H, Sakamaki T, Sumino H, et al. Production of endothelin-1 and big endothelin-1 by human cardiac myxoma cells–implications of the origin of myxomas. Circ J 2004;68:1230-2 Yokomuro H, Yoshihara K, Watanabe Y, et al. The variations in the immunologic features and interleukin-6 levels for the surgical treatment of cardiac myxomas. Surg Today 2007;37:750-3 Mendoza CE, Rosado MF, Bernal L. The role of interleukin-6 in cases of cardiac myxoma. Clinical features, immunologic abnormalities, and a possible role in recurrence. Tex Heart Inst J 2001;28:3-7

30.

Lee VH, Connolly HM, Brown RD Jr. Central nervous system manifestations of cardiac myxoma. Arch Neurol 2007;64: 1115-20

.

A retrospective study of neurological manifestations of myxoma.

informahealthcare.com

Review

31.

Keeling IM, Oberwalder P, Anelli-Monti M, et al. Cardiac myxomas: 24 years of experience in 49 patients. Eur J Cardiothorac Surg 2002;22:971-7

43.

Motwani M, Kidambi A, Herzog BA, et al. MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology 2013;268:26-43

32.

Bhattacharyya S, Khattar RS, Gujral DM, Senior R. Cardiac tumors: the role of cardiovascular imaging. Expert Rev Cardiovasc Ther 2014;12:37-43

44.

33.

Schattenberg TT. Echocardiographic diagnosis of left atrial myxoma. Mayo Clin Proc 1968;43:620-7

Garatti A, Nano G, Canziani A, et al. Surgical excision of cardiac myxomas: twenty years experience at a single institution. Ann Thorac Surg 2012;93: 825-31

..

Large, contemporary single center study of surgical outcomes of myxoma excision.

45.

Samanidis G, Perreas K, Kalogris P, et al. Surgical treatment of primary intracardiac myxoma: 19 years of experience. Interact Cardiovasc Thorac Surg 2011;13:597-600

46.

Patil NP, Dutta N, Satyarthy S, et al. Cardiac myxomas: experience over one decade. J Card Surg 2011;26:355-9

47.

Ko PJ, Chang CH, Lin PJ, et al. Video-assisted minimal access in excision of left atrial myxoma. Ann Thorac Surg 1998;66:1301-5

48.

Rathore KS, Hussenbocus S, Stuklis R, Edwards J. Novel strategies for recurrent cardiac myxoma. Ann Thorac Surg 2008;85:2125-6

49.

Yu S, Xu X, Zhao B, et al. Totally thoracoscopic surgical resection of cardiac myxoma in 12 patients. Ann Thorac Surg 2010;90:674-6

50.

Konecny T, Reeder G, Noseworthy PA, et al. Percutaneous ablation and retrieval of a right atrial myxoma. Heart Lung Circ 2014;23:e244-7

.

First case report of percutaneous excision of a right atrial myxoma.

51.

Gammie JS, Abrishamchian AR, Griffith BP. Cardiac autotransplantation and radical bi-atrial resection for recurrent atrial myxoma. Ann Thorac Surg 2007;83:1545-7

52.

Aguilar C, Beltran B, Quinones P, et al. Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus? Cardiovasc Pathol 2015;24:60-4

53.

Gruver AM, Huba MA, Dogan A, Hsi ED. Fibrin-associated large B-cell lymphoma: part of the spectrum of cardiac lymphomas. Am J Surg Pathol 2012;36:1527-37

34.

Ha JW, Kang WC, Chung N, et al. Echocardiographic and morphologic characteristics of left atrial myxoma and their relation to systemic embolism. Am J Cardiol 1999;83:1579-82; A1578

35.

Peters PJ, Reinhardt S. The echocardiographic evaluation of intracardiac masses: a review. J Am Soc Echocardiogr 2006;19:230-40

36.

.

37.

38.

Kirkpatrick JN, Wong T, Bednarz JE, et al. Differential diagnosis of cardiac masses using contrast echocardiographic perfusion imaging. J Am Coll Cardiol 2004;43: 1412-19 A study that suggest echocardiographic contrast perfusion imaging is useful in differentiating cardiac neoplasms. Reeder GS, Khandheria BK, Seward JB, Tajik AJ. Transesophageal echocardiography and cardiac masses. Mayo Clin Proc 1991;66:1101-9 Mehmood F, Nanda NC, Vengala S, et al. Live three-dimensional transthoracic echocardiographic assessment of left atrial tumors. Echocardiography 2005;22:137-43

39.

Plana JC. Added value of real-time threedimensional echocardiography in assessing cardiac masses. Curr Cardiol Rep 2009;11: 205-9

40.

Zaragoza-Macias E, Chen MA, Gill EA. Real time three-dimensional echocardiography evaluation of intracardiac masses. Echocardiography 2012;29:207-19

41.

Araoz PA, Mulvagh SL, Tazelaar HD, et al. CT and MR imaging of benign primary cardiac neoplasms with echocardiographic correlation. Radiographics 2000;20:1303-19

42.

Fussen S, De Boeck BW, Zellweger MJ, et al. Cardiovascular magnetic resonance imaging for diagnosis and clinical management of suspected cardiac masses and tumours. Eur Heart J 2011;32:1551-60

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Current diagnosis and management of cardiac myxomas.

Cardiac myxoma is the most common cardiac neoplasm. In the majority of cases, it is isolated (non-syndromic) and located in the left atrium. In up to ...
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