Sixty-seven articles pertaining to PCA met the inclusion criteria. Evidence was provided in various research formats, including 43 case studies,4,9,10–49 12 case series,50–61 7 literature reviews,62–68 and 5 narrative reviews.5,69–72 Sixty-six subjects identified in the articles met the diagnostic criteria for malignant PCA. Males were diagnosed 1.25 times more frequently than females, with the greatest prevalence in the fourth decade of life for both genders (Figure 3). Race was reported for 5 subjects, including 2 individuals identified as African American and 3 individuals identified as White.4,10,11
A total of 35 presenting symptoms from either the primary tumor or a metastasis at initial diagnosis were recorded in 56 of the cases (Table 1). The 4 most common presenting symptoms were dyspnea (n = 22), chest pain (n = 18), breathlessness (n = 10), and pericardial effusion (n = 10). The authors recognize that the symptoms identified in this review of cases are not unique to the diagnosis of a PCA. Given the rarity of this diagnosis, it is understandable that symptoms may favor a differential diagnosis of more common ailments. However, unsuccessful remediation of symptoms after appropriate medical intervention should give health care providers justification to conduct appropriate testing to rule out this diagnosis.
Physical therapy intervention for cough and right anterior chest pain prior to diagnosis was reported in 1 case. The individual was reported to be under the care of a PT for 2 weeks; however, no description regarding the frequency, duration, or type of interventions provided was available. It was noted that the cough was resolved, but the chest pain became pleuritic in nature after the physical therapy intervention and a 2-week course of antibiotic medication.17
Inconsistencies in follow-up times and number of follow-up visits led to variability in the survival status reporting available to the investigators. Of the 32 cases for which longevity was available, medical follow-up ranged from 4 to 32 months. Thirteen patients were reportedly still living at that time, whereas 19 were reported as deceased. Because of these inconsistencies in follow-up reporting, correlations between survival, lifestyle risk factors, and physical activity levels could not be analyzed.
A review of case studies and series describing individuals with a diagnosis of PCA revealed a paucity of evidence with regard to possible risk factors. In addition, documentation specific to the effect of physical therapy during various stages of treatment or a correlation between physical activity and tumor development was not present. Lack of evidence regarding prevention strategies, inclusive of prior physical activity levels, limited the authors' ability to garner whether care thwarted malignant cell conversion in this population. Further research with intention toward capturing this data is warranted to improve prevention and early detection efforts.
In agreement with current literature, this review indicated a higher incidence of PCA diagnosis in males than in females.16 The results also indicated that the highest rate of diagnosis occurred in the fourth to fifth decades of life, which paralleled the current accepted demographic of PCA.5 Race was reported only in 5 cases, thereby limiting diagnostic patterns for this variable. Furthermore, this literature review did not reveal a comprehensive historical description of the individual with a diagnosis of PCA. This includes details of the medical history, lifestyle risk factors that include physical activity, or diagnostic/prognostic data.
Standardization for reporting of these data in future case series and reports may provide sufficient data to achieve this review's purpose of identifying trends and correlations. In addition, an understanding of potential characteristics or variables that may contribute to an increased risk of developing this form of cancer would be beneficial. Specifically, smoking tobacco is a widely accepted risk factor for various types of cancer but it is still unknown whether it is a risk factor for PCA. Furthermore, strong evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal.73 Underlying mechanisms linking obesity to the development of cancer include chronic inflammation, oxidative stress, cross talk between tumor cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and functional defeat of the immune function.73 While it can be hypothesized that vascular tissue cells, such as cardiac endothelial cells, are susceptible to these adverse effects preceding cancer development, the absence of data in the reported case histories cannot yet support this suggestion.
The findings of this literature review generated incomplete evidence or description of the role of a PT in the prevention or treatment of PCA. To the authors' knowledge, this is the first literature review attempting to seek correlation between lifestyle factors and the presence of PCA. Physical therapy is the professional authority that synthesizes examination and evaluation to provide evidence-based interventions with the purpose of optimizing movement to improve the human experience.74 Therefore, understanding signs, symptoms, and common risk factors that may be modified prior to disease onset will save lives. A component of the physical therapy examination and evaluation process involves the assessment of patient exercise tolerance, health promotion and wellness risk factors, and functional activities of daily living.8 This type of assessment places PTs at the forefront for identifying symptoms such as dyspnea, chest pain, and fatigue, as well as the effects of these symptoms on quality of life. Unfortunately, these symptoms are not unique to PCA. Thus, differential diagnosis is not possible using these factors alone. Because of the rarity of the disease and the poor outcomes reported in the literature, which may be due to late-stage diagnosis and limited treatment options, PT referrals are scarce. With this review, the authors seek to provide 2 avenues for awareness among health care providers and opportunities for increased intervention. First, information gleaned from this review may provide PTs with increased knowledge to share within the profession. Second, this review suggests a potential for further education about the benefits of physical therapy in both prehabilitation and rehabilitation.
Because surgical intervention was the most common medical intervention provided to individuals with a diagnosis of PCA, pre- and postoperative exercise should be considered. While there is limited evidence related to the benefits of exercise training specific to this diagnosis, it has been reported in common malignancies. For example, Jones et al75 completed a single group study of 25 individuals with suspected operable lung cancer. Exercise consisted of 5 endurance cycle ergometry sessions per week at varying intensities. Participants underwent cardiopulmonary exercise testing, Six-Minute Walk Test, and pulmonary function testing at baseline, immediately before, and 30 days after surgical resection. Analyses indicated that presurgical exercise capacity decreased postsurgery but did not decrease beyond baseline values. The researchers concluded that prehabilitation was beneficial in improving cardiorespiratory fitness prior to pulmonary tumor resection. This evidence leads to the following question: “Could prehabilitation for pulmonary tumor translate to benefits for PCA?”
Published research that included comprehensive lifestyle risk factors and physical activity data was limited. Sadly, the questions that initiated the authors' desire to examine the literature are unable to be answered or even considered with the evidence currently available in the scientific community. Further research to capture causative factors, medical history, prediagnosis lifestyle, and risk factors among individuals with PCA is warranted to improve prevention and early detection efforts. Prospective studies with an emphasis on the effect of a PT's role in prehabilitation, secondary prevention, postoperative recovery, and symptoms management necessitate further investigation.
This specific investigation review revealed a paucity of evidence regarding characteristics, lifestyle risk factors, or physical activity levels of individuals with a diagnosis of PCA. The authors' quest to understand whether muscle physiology may be a contributor to the rarity of primary malignant cardiac tumor is just beginning. Furthermore, the literature was limited with regard to case histories inclusive of lifestyle and behavior risk factors that would be amenable to physical therapy prevention strategies. The authors' aspire to initiate dialogue within the physical therapy profession as well as within the health care community about the need for more evidence regarding the factors that may be contributing to the rare occurrence of primary cardiac tumors. The 35 presenting symptoms and past medical history reported in this literature are certainly not exclusive to PCA but may provide a basis for correlation with other genetic and epigenetic factors to explore along our journey for answers. The physical therapy profession is well positioned to promote healthy behaviors and to provide patient education that reduce risk factors and prevent and treat noncommunicable diseases consistent with a biopsychosocial paradigm.8
The authors aspire to continue examination of rare cancers that may exhibit unique characteristics in partnership and in parallel to other researchers with similar scholarly ambitions. Continued efforts are warranted to examine both unique characteristics of cardiac muscle physiology and cancer risk factors that may be amenable to PT prevention strategies and interventions.
The authors thank Dr Julia Rodriguez, for her mentorship in conducting the literature review and in securing the articles for analysis, and Sherry Wynn Purdue, for her editorial assistance.
1. Henonen I. The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Turku, Finland: Painosalama Oy, University of Turku; 2010.
2. Hojman P, Gehl J, Christensen JF, Pedersen BK. Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metab. 2018;27(1):10–21.
3. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Bio Med. 2010;49(11):1603–1616.
4. Nakamura-Horigome M, Koyama J, Eizawa T, et al Successful treatment of primary cardiac angiosarcoma with docetaxel and radiotherapy. Angiology. 2008;59(3):368–371.
5. Patel SD, Peterson A, Bartczak A, et al Primary cardiac angiosarcoma—a review. Med Sci Monit. 2014;20:103–109.
6. Green BN, Johnson CD, Adams A. Writing narrative literature reviews for peer-reviewed journals: secrets of the trade. J Chiropr Med. 2006;5(3):101–117.
7. Von Elm E, Altman DG, Egger M, et al The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344–349.
8. Bezner J. Promoting health and wellness: implications for physical therapist practice. Phys Ther. 2015;95:1433–1444.
9. Pourmand A, Boniface K. Incidental identification of right atrial mass using bedside ultrasound: cardiac angiosarcoma. West J Emerg Med. 2011;12(4):478–480.
10. Dong Y, Zhu D, Dong L, Ren L. Primary cardiac angiosarcoma with pulmonary and lumbar metastases presenting as unexplained pericardial effusion in a 41 year-old man. Heart Lung Circ. 2014;23(5):e145–e146.
11. Romero-Farina G, Candell-Riera J, Beltran-Ror A, Gonzalez-Moreno JB, Bigalli D, Stratta A. Primary cardiac angiosarcoma: diagnostic utility of computed tomography and cardiac magnetic resonance. Rev Esp Cardiol. 2004;57(12):1234–1237.
12. Wong CW, El-Jack S, Edwards C, Patel H. Primary cardiac angiosarcoma: morphologically deceptive benign appearance and potential pitfalls in diagnosis. Heart Lung Circ. 2010;19(8):473–475.
13. Jain A, Simon S, Elangovan I. (18)F-fluoro-deoxyglucose positron emission tomography-computed tomography in initial assessment and diagnosis of right atrial angiosarcoma with widespread visceral metastases: a rare case report and review of the literature. Indian J Nucl Med. 2015;30(1):51–54.
14. Tang K, Shang Q, Zhou Q, Zhou J, She X, Zhang M. Primary cardiac angiosarcoma with spontaneous ruptures of the right atrium and right coronary artery. Echocardiography. 2013;30(6):E156–E160.
15. Bouma W, Lexis CP, Willems TP, et al Successful surgical excision of primary right atrial angiosarcoma. J Cardiothorac Surg. 2011;6:47.
16. Chang JH, Kim JH, Hong SH, et al Angiosarcoma presenting with spontaneous hydropneumothorax: report of a case and review of the literature. Open Respir Med J. 2014;8:48–54. doi:10.2174/1874306401408010048.
17. Laws JW, Annes GP, Bogren HG. Primary malignant tumors of the heart. Calif Med. 1973;118(4):11–17.
18. Bellitti R, Buonocore M, De Rosa N, Enrico Covino F, Casale B, Sante P. Primary cardiac angiosarcoma in a 25-year-old man: excision, adjuvant chemotherapy, and multikinase inhibitor therapy. Tex Heart Inst J. 2013;40(2):186–188.
19. Ho CK, Wang E, Au WK, Cheng LC. Primary cardiac angiosarcoma of left atrium. J Card Surg. 2009;24(5):524–525.
20. Ranga U, Aiyappan SK, Veeraiyan S. An unusual case of hemoptysis. Lung India. 2014;31(2):190–192.
21. Toledano FJ, Mesa D, Ortiz MR, Leon C. Large mass in left atrium by transesophageal echocardiography: an unusual case of cardiac angiosarcoma mimicking a cystic mass. Echocardiography. 2010;27(10):E137–E138.
22. Kodali D, Seetharaman K. Primary cardiac angiosarcoma. Sarcoma. 2006;2006:39130. doi:10.1155/SRCM/2006/39130.
23. Kim DM, Hong JH, Kim SY, et al Primary cardiac angiosarcoma presenting with cardiac tamponade. Korean Circ J. 2010;40(2):86–89.
24. Antonuzzo L, Rotella V, Mazzoni F, et al Primary cardiac angiosarcoma: a fatal disease. Case Rep Med. 2009;2009:591512.
25. Aoka Y, Kamada T, Kawana M, et al Primary cardiac angiosarcoma treated with carbon-ion radiotherapy. Lancet Oncol. 2004;5(10):636–638.
26. Cardoso ME, Canale LS, Ramos RG, Salvador Junior Eda S, Lachtermacher S. Cardiac angiosarcoma. Case Rep Cardiol. 2011;2011:340681.
27. Dhull VS, Sharma P, Mukherjee A, Jana M, Bal C, Kumar R. 18
F-FDG PET-CT for evaluation of cardiac angiosarcoma: a case report and review of literature. Mol Imaging Radionucl Ther. 2015;24(1):32–36.
28. Gong J, Tian J, Xiao Y. Right atrial angiosarcoma and electrocardiogram-gated cardiac computed tomography: a case report. Chin Ger J Clin Oncol. 2009;8(4):242–244.
29. Hori Y, Funabashi N, Miyauchi H, et al Angiosarcoma in the right atria demonstrated by fusion images of multi-slice computed tomography and positron emission tomography using F-18-fluoro-deoxyglucose. Int J Cardiol. 2007;123(1):e15–e17.
30. Khanji M, Lee E, Ionescu A. Blushing primary cardiac angiosarcoma. Heart. 2014;100(3):266.
31. Ohri SK, Nihoyannopoulos P, Taylor KM, Keogh BE. Angiosarcoma of the heart causing cardiac rupture: a rare cause of hemopericardium. Ann Thorac Surg. 1993;55(2):525–528.
32. Pezzuto A, Gencarelli G, Martone L, Bruno P, Mariotta S. Primary cardiac angiosarcoma in a young woman. Case Rep Oncol. 2010;3(1):24–29.
33. Rao U, Curtin J, Ryding A. Primary angiosarcoma of the heart. Heart. 2013;99(24):1878–1879.
34. Hsieh PL, Lee D, Chiou KR, et al Echocardiographic features of primary cardiac sarcoma. Echocardiography. 2002;19(3):215–220.
35. Castilla E, Pascual I, Roncales F, Aguirre E, Del RA. Transient response of cardiac angiosarcoma to paclitaxel. Eur J Cancer Care. 2010;19(5):699–700.
36. Riles E, Gupta S, Wang DD, Tobin K. Primary cardiac angiosarcoma: a diagnostic challenge in a young man with recurrent pericardial effusions. Exp Clin Cardiol. 2012;17(1):39–42.
37. Amonkar GP, Deshpande JR. Cardiac angiosarcoma. Cardiovasc Pathol. 2006;15(1):57–58.
38. Burjonroppa SC, Reardon MJ, Swafford J. Images in cardiology: right atrial mass: primary angiosarcoma. Heart. 2005;91(10):1271.
39. Park WK, Jung SH, Lim JY. Cardiac angiosarcoma on the right atrium: two cases. Korean J Thorac Cardiovasc Surg. 2012;45(2):120–123.
40. Hoffmeier A, Schmid C, Scheld HH. Reply: “Ex situ resection of primary cardiac tumors.” Thorac Cardiovasc Surg. 2004;52(2):125.
41. Tokmak H, Demir N, Dimirkol MO. Cardiac angiosarcoma: Utility of [18
F]fluorodeoxyglucose positron emission tomography–computed tomography in evaluation of residue, metastases, and treatment response. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085334
. Published 2015. Accessed August 26, 2015.
42. Benassi F, Maiorana A, Melandri F, Stefanelli G. A case of primary cardiac angiosarcoma: extensive right atrial wall reconstruction with autologous pericardium. J Card Surg. 2010;25(3):282–284.
43. Park KS, Song BG, Ok KS, et al Primary cardiac angiosarcoma treated by complete tumor resection with cardiac reconstruction. Heart Lung. 2011;40(3):e41–e43.
44. Pigott C, Welker M, Khosla P, Higgins RS. Improved outcome with multimodality therapy in primary cardiac angiosarcoma. Nat Clin Pract Oncol. 2008;5(2):112–115.
45. Puppala S, Hoey ET, Mankad K, Wood AM. Primary cardiac angiosarcoma arising from the interatrial septum: magnetic resonance imaging appearances. Br J Radiol. 2010;83(995):e230–e234.
46. Yang HS, Sengupta S, Umland MM, Chandrasekaran K, Mookadam F. Primary cardiac angiosarcoma evaluated with contrast two-dimensional and real-time three-dimensional echocardiography. Eur J Echocardiogr. 2008;9(5):733–738. doi:10.1093/ejechocard/jen164.
47. Kontogiorgi M, Exarchos D, Charitos C, et al Primary right atrium angiosarcoma mimicking pericarditis. Word J Surg. 2007;5:120. doi:10.1186/1477-7819-5-120.
48. Fernandes CP, Oliveira FA, Cost FW, et al Clinical, histological, and immunmohistochemical features of a mandibular metastasis from a primary cardiac angiosarcoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(2):e121–e127. doi.org/10.1016/j.oooo.2012.12.017.
49. Kumar N, Agarwal S, Ahuja A, Das P, Airon B, Ray R. Spectrum of cardiac tumors excluding myxoma: experience of a tertiary center with review of the literature. Pathol Res Pract. 2011;207(12):769–774.
50. Jain G, Mukhopadhyay S, Kurien S, Yusu J, Tyagi S, Jain R. Ruptured cardiac angiosarcoma with pulmonary metastases: a rare disease with a common (mis)diagnosis. Indian Heart J. 2012;64:603–606.
51. Garcia JM, Gonzalez R, Silva JM, et al Mutational status of K-ras and TP53 genes in primary sarcomas of the heart. Br J Cancer. 2000;82(6):1183–1185.
52. Zhang PJ, Brooks JS, Goldblum JR, et al Primary cardiac sarcomas: a clinicopathologic analysis of a series with follow-up information in 17 patients and emphasis on long-term survival. Hum Pathol. 2008;39(9):1385–1395.
53. Hanssens M, De Scheerder I, De Buyzere M, Clement DL. Primary cardiac tumors: retrospective evaluation of 15 consecutive patients. Acta Cardiol. 1988;43(1):21–29.
54. Mayer F, Aebert H, Rudert M, et al Primary malignant sarcomas of the heart and great vessels in adult patients—a single-center experience. Oncologist. 2007;12(9):1134–1142.
55. Kosuga T, Fukunaga S, Kawara T, et al Surgery for primary cardiac tumors. Clinical experience and surgical results in 60 patients. J Cardiovasc Surg (Torino). 2002;43(5):581–587.
56. Molina JE, Edwards JE, Ward HB. Primary cardiac tumors: experience at the University of Minnesota. Thorac Cardiovasc Surg Suppl. 1990;38(2):183–191.
57. Bossert T, Gummert JF, Battellini R, et al Surgical experience with 77 primary cardiac tumors. Interact Cardiovasc Thorac Surg. 2005;4(4):311–315.
58. Kamiya H, Yasuda T, Nagamine H, et al Surgical treatment of primary cardiac tumors: 28 years' experience in Kanazawa University hospital. Jpn Circ J. 2001;65(4):315–319.
59. Gruber HP, Fraedrich G, Kasper W, Schindler M, Schlosser V. Primary cardiac tumors: a twenty-year review. Vasc Surg. 1992;26(7):573–579.
60. Simpson L, Kumar SK, Okuno SH, et al Malignant primary cardiac tumors: review of a single institution experience. Cancer. 2008;112(11):2440–2446.
61. Bakaeen FG, Reardon MJ, Coselli JS, et al Surgical outcome in 85 patients with primary cardiac tumors. Am J Surg. 2003;186(6):641–647.
62. Sarjeant JM, Butany J, Cusimano RJ. Cancer of the heart: epidemiology and management of primary tumors and metastases. Am J Cardiovasc Drugs. 2003;3(6):407–421.
63. Bendel EC, Maleszewski JJ, Araoz PA. Imaging sarcomas of the great vessels and heart. Semin Ultrasound CT MRI. 2011;32(5):377–404.
64. Davila AD, Rodriguez-Ospina L. Primary cardiac and pericardial tumors. Bol Asoc Med P R. 2008;100(4):48–54.
65. Reardon MJ, Walkes JC, Benjamin R. Therapy insight: malignant primary cardiac tumors. Nat Clin Pract Cardiovasc Med. 2006;3(10):548–553.
66. Maraj S, Pressman GS, Figueredo VM. Primary cardiac tumors. Int J Cardiol. 2009;133(2):152–156.
67. Roberts WC. Primary and secondary neoplasms of the heart. Am J Cardiol. 1997;80(5):671–682.
68. Becker RC, Loeffler JS, Leopold KA, Underwood DA. Primary tumors of the heart: a review with emphasis on diagnosis and potential treatment modalities. Semin Surg Oncol. 1985;1(4):161–170.
69. Ostrowski S, Marcinkiewicz A, Kosmider A, Jaszewski R. Sarcomas of the heart as a difficult interdisciplinary problem. Arch Med Sci. 2014;10(1):135–148.
70. Butany J, Nair V, Naseemuddin A, Nair GM, Catton C, Yau T. Cardiac tumours: diagnosis and management. Lancet Oncol. 2005;6:219–228.
71. Habertheuer A, Laufer G, Wiedemann D, et al Primary cardiac tumors on the verge of oblivion: a European experience over 15 years. Cardiothorac Surg. 2015;10(1):56.
72. Castillo JG, Silvay G. Characterization and management of cardiac tumors. Semin Cardiothorac Vasc Anesth. 2010;14(1):6–20.
73. De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013;2013:291546.
74. American Physical Therapy Association. Vision statement for the physical therapy profession and guiding principles to achieve the vision. http://www.apta.org/Vision
. Updated January 9, 2017. Accessed May 31, 2018.
75. Jones LW, Peddle CJ, Eves ND, et al Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer. 2007;110(3):590–598. doi:10.1002/cncr.22830.
* References 10, 15, 17-19, 25, 26, 29, 37, 42, 48, 50, 51.