Introduction

Primary cardiac tumors are rare, occurring in about 0.001-0.3% of autopsies.¹ The clinical incidence of these tumors is about 1 in every 500 cardiac surgical cases in large centers. For primary cardiac tumors, about 75% are benign and 25% are malignant. Of the malignant tumors, about 75% are sarcoma.¹ Most cardiac surgeons and cardiologists will have minimal experience with primary cardiac malignancy. The purpose of this paper is to summarize our experience with the evaluation and treatment of primary malignant cardiac tumors.

Primary malignant cardiac tumors tend to occur in young patients with a mean age of 44 years and are evenly divided between the sexes.² In a 17-year retrospective study of primary cardiac and non-cardiac soft tissue sarcomas in the SEER (Surveillance, Epidemiology, and End Results) database, Hamidi et al. found 210 primary cardiac sarcomas and 24,404 non-cardiac soft tissue sarcomas.³ The median overall survival for patients with cardiac sarcoma was 6 months and for non-cardiac soft tissue sarcoma was 96 months. Patients with cardiac sarcoma having surgery had a median survival of 12 months, whereas those who did not have surgery had a median survival of 1 month. Surgical series have emphasized both the rarity of this condition as well as the need for complete surgical resection for optimal survival. The Mayo Clinic reviewed a 32-year period and found 34 patients who had undergone surgical resection of primary cardiac sarcoma; the median survival time of 12 months was extended to 17 months in the event of R0 resection.⁴ Patients who had an R1 resection had a median survival time of 6 months. The combined series from MD Anderson Cancer Center and the Texas Heart Institute found 21 patients over a 25-year period; those patients had an actuarial survival rate of 14% at 2 years.⁵ Those who underwent an R0 resection had a median survival time of 24 months, whereas those who underwent an R1 resection had a median survival time of 10 months, which emphasizes both the aggressiveness of this disease and the importance of complete resection in these patients. We recently reviewed our experience with the surgical treatment of 96 primary cardiac sarcomas over a 25-year period for the Houston Methodist Hospital/MD Anderson Cancer Center combined multidisciplinary cardiac tumor group.²

We divide primary cardiac sarcoma into three clinical groups based on their site of presentation: right heart sarcomas, left heart sarcomas, and pulmonary artery (PA) sarcomas. We have previously discussed our management of this disease based on this classification and will discuss our current recommendations.^6-8

Evaluation

Presenting symptoms of primary cardiac sarcomas can be non-specific, and the most common method of initial diagnosis is echocardiography. Left atrial tumors are often thought initially to be myxomas, but careful review almost always reveals broad based or abnormally located tumors that should raise the suspicion for malignancy. Right heart sarcomas are generally large and broad based when first found and not usually confused with a benign process. Ventricular tumors are the least common and generally lead to extensive evaluation prior to any treatment. Suspicion of malignancy leads to both careful local evaluation of the tumor and its extent and the search for systemic involvement. We perform cardiac magnetic resonance angiography, chest and abdominal computed tomography, as well as a whole body positron emission tomography on all patients suspected of primary malignant cardiac tumors. We also get coronary angiography on all left and right heart suspected sarcomas to evaluate coronary involvement in case coronary resection is needed as well as to evaluate for paraganglioma, which can mimic sarcoma and always has large feeding vessels on coronary angiography. Histologic diagnosis should be established when possible for consideration of neoadjuvant therapy when possible.

Left Heart Sarcoma

The clinical presentation of patients with primary left heart sarcoma depends on the anatomic location and extent of the tumor and is not influenced by histology. The most common presenting symptoms for left heart sarcoma, in our experience, are shortness of breath and dyspnea on exertion, both consistent with congestive heart failure and arising from the obstruction of intracardiac blood flow. Over half of our patients had New York Heart Association Functional Classification III or IV congestive heart failure symptoms at presentation. Most primary left heart sarcomas are reported to occur in the left atrium, and this is supported by our experience in which 22 of 24 (92%) occurred in the left atrium and 2 of 24 (8%) occurred in the left ventricle. When treated without surgical resection, the survival is 9-12 months.⁹ The most effective therapy for primary cardiac sarcoma and the greatest determinant of survival is complete surgical resection. Complete removal is mainly determined by the anatomic location of the tumor and the structures it involves. The left atrium and left ventricle present unique and difficult problems for the surgeon in attempting complete resection of these often-large tumors. The earlier literature on left heart sarcoma showed a high rate of local recurrence.^10,11 It was our opinion that the high rate of local recurrence was related to the difficulty in anatomically exposing and removing the entire left atrium, resulting in incomplete resection and rapid local recurrence. Cardiac surgeons typically approach left atrial tumors through the interatrial groove. This is generally satisfactory for benign or small tumors but usually provides inadequate exposure for large and malignant tumors. Complete cardiectomy and orthotopic transplantation can be done. Most medical review boards, however, will not approve donor hearts for active malignancy, and previous series of orthotopic transplantation for sarcoma have shown a median survival of only 12 months.¹² Similarly, left ventricular tumors can be approached through the aortic valve, through the mitral valve, or using a left ventriculotomy. Approach through the aortic valve has been used successfully for benign tumors¹³ but is not adequate for compete resection of malignant tumors. Exposure via the mitral valve with the heart in situ is similarly inadequate, and left ventriculotomy through viable muscle is not appealing to most surgeons. Our approach to this difficult surgical problem is cardiac autotransplantation: cardiac excision, ex vivo resection and reconstruction, and cardiac re-implantation. Cardiac autotransplantation was first attempted by Cooley in 1984 for a left atrial paraganglioma.¹⁴ It was first successfully used for left atrial sarcoma in 1998 by our group¹ and in 2006 for left ventricular sarcoma.¹⁵ Our most recent publication for cardiac autotransplantation for malignant and complex tumors in 2014 had 35 autotransplants, of which 26 were for primary cardiac sarcoma. Of these cases, 19 were isolated autotransplants and 7 were autotransplants combined with a pneumonectomy due to extensive tumor involvement.¹⁶ The 30-day mortality for primary cardiac sarcoma with autotransplantation alone was 11% with 1- and 2-year survival of 58% and 32%. The 30-day mortality for autotransplant and pneumonectomy was 57%. Every death was due to extensive coagulopathy and bleeding into the pneumonectomy space, requiring multiple transfusions, which led to unilateral pulmonary edema, right heart failure, and death. Consequently, we currently carefully screen for pulmonary vein involvement, and if pneumonectomy appears likely, we decline surgical intervention. We currently have done 51 cardiac autotransplants and recommend post-resection chemotherapy in all cases.

Right Heart Sarcoma

We have found right heart sarcomas to be bulkier and more exophytic than left heart or PA sarcomas. They tend to present with less heart failure due to intracardiac obstruction and more non-specific symptoms, often delaying the diagnosis. Distant metastatic disease also appears more commonly with right heart sarcomas.² We originally looked at our experience with 21 primary right heart sarcomas and compared these with 36 patients collected from the literature. In our patients, those with R0 resection had a significantly better median and 5-year survival rate than those with an R1 resection (27 vs. 4 months and 36 vs. 0%).¹⁷ In this series, our R0 resection rate was only 38%, which compared to an R0 resection rate in our collected literature of 42%.¹⁷ Based on this, our group began a protocol of histologic diagnosis for all potentially malignant right heart tumors. This allowed us to identify and treat appropriately non-sarcoma malignant tumors such as lymphoma and plasmacytomas¹⁸ and begin neoadjuvant chemotherapy for all primary sarcomas to attempt to shrink margins and improve R0 resection rates and survival. All patients without overt heart failure that might force an early surgery are started on neoadjuvant chemotherapy, doxorubicin hydrochloride (75 mg/m2), and ifosfamide (10gm/m2) in an attempt to cytoreduce the tumor bulk and sterilize the infiltrative, microscopic fingers of disease that tend to invade the margins of even wide resections. This chemotherapy is continued as long as a positive response is obtained or until the patient reaches tolerance. If the patient has obtained a significant response and metastatic disease is controlled, surgical resection is considered. If the patient fails to respond to neoadjuvant chemotherapy or metastatic disease is not controlled, then only definitive chemotherapy and radiotherapy are considered. The current study incudes 44 patients treated with this protocol who were compared to our patients who did not receive neoadjuvant chemotherapy (manuscript under review at Annals of Thoracic Surgery). The mean age was 41 years with a range of 15-67 years. The right coronary artery was involved and required resection and replacement in 1/3 of the cases. The 30-day mortality was 5% in both groups, and the median survival for neoadjuvant chemotherapy versus none was 20 versus 9.5 months. The median survival for R0 resection versus R1 was significantly better at 53.5 versus 9.5 months (p = 0.004).

Pulmonary Artery Sarcoma

PA sarcomas are extremely rare, with less than 250 cases reported in the world literature when we last reported this disease.¹⁹ We first reported our group's experience with this disease in 2009 when we reported 9 cases of primary PA sarcoma, which we compared to cases collected from the literature.⁶ These patients most commonly presented with shortness of breath and often constitutional symptoms consistent with a number of more common pulmonary conditions such as pulmonary emboli (PE), pulmonary hypertension, fibrosing mediastinitis, lung tumor, and PA stenosis. This is further highlighted by the average time from symptom onset to diagnosis being 3-12 months, with 50% of patients having metastatic disease when diagnosed.²⁰ Obtaining tissue histology can be difficult, and symptoms often demand urgent surgical intervention. Fortunately, cardiac magnetic resonance imaging can help differentiate tumor from chronic PE by the presence of perfusion in PA sarcoma but not in chronic PE. These tumors tend to begin on the dorsal surface of the pulmonary root and often involve the pulmonary valve.²¹ It generally extends distally along the artery but does not often penetrate the artery wall, which allows for complete resection. We replace the pulmonary root with allograft and use Dacron graft to extend this out to the first PA bifurcation. We had no operative mortality in our series and found a median survival of 71 versus 18 months in the case from the literature. We believe this is because a large number of the reported cases were misidentified as chronic PE and treated with thromboendarterectomy, which we believe to be an inadequate oncologic operation.

Complex Ventricular Tumors not Resectable by Standard Technique

We have occasionally found large ventricular sarcoma that are not technically resectable by normal techniques. We have not considered orthotopic transplantation in the face of active disease. Our group has begun to explore the possibility of complete cardiac excision and mechanical replacement as a bridge to chemotherapy and possible transplantation if longer-term disease-free survival can be obtained. We have used both external support ventricular assist devices²² and SynCardia Total Artificial Heart (SynCardia Systems, LLC; Tucson, AZ).²³

Conclusion

Primary cardiac sarcoma is a rare and deadly disease. We use a multidisciplinary approach to all primary cardiac sarcomas with careful evaluation for local tumor extent as well as metastatic involvement. We use neoadjuvant therapy based on histologic tissue diagnosis for all right heart sarcomas and believe this approach should be considered for left heart and PA sarcomas when possible.

References

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Keywords: Allografts, Aortic Valve, Atrial Fibrillation, Autografts, Autopsy, Cardiac Surgical Procedures, Constriction, Pathologic, Coronary Angiography, Coronary Vessels, Disease-Free Survival, Doxorubicin, Dyspnea, Echocardiography, Endarterectomy, Heart Atria, Heart Failure, Heart Neoplasms, Heart Ventricles, Heart, Artificial, Hypertension, Pulmonary, Ifosfamide, Incidence, Lung Neoplasms, Lymphoma, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Mediastinitis, Mitral Valve, Myxoma, Neoadjuvant Therapy, Paraganglioma, Physical Exertion, Pneumonectomy, Polyethylene Terephthalates, Positron-Emission Tomography, Protestantism, Pulmonary Artery, Pulmonary Edema, Pulmonary Valve, Pulmonary Veins, Retrospective Studies, Sarcoma, Surgeons, Survival Rate, Thoracic Surgery, Transplantation, Autologous, Cardiotoxins, Cardiotoxicity

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