Surgical treatment of primary cardiac tumors in the contemporary era: A single‐centre analysis

Abstract Background Primary cardiac tumors (PCT) are rare lesions but have the potential to cause significant morbidity if not timely treated. We reviewed our single‐center experience in the surgical treatment of PCT with a focus on the long‐term outcome. Methods From 2001 to 2020, 57 consecutive patients underwent surgical resection of PCT at our Institution. Data including the demographic characteristics, tumor histology, surgical procedure, and postoperative outcomes were collected and analyzed. Results Mean age at presentation was 63.6 ± 11.2 years, and 33 (57.9%) of the patients were female. A total of 55 (96.5%) subjects were diagnosed with benign cardiac tumor, while the remaining had malignant tumors. The most common histopathological type was myxoma. All patients survived to hospital discharge. Main postoperative complications were: acute kidney injury (n = 3), sepsis (n = 3), and stroke (n = 2). Mean follow‐up time was 9 ± 5.9 years. Long‐term mortality was 22.8% (13/57). No tumor recurrence was observed among survivors. There was a significant relationship between mortality and pathological characteristics of the tumor, and myxomas had higher survival rates. Conclusion Surgical treatment of PCT is a safe and highly effective strategy associated with excellent short‐term outcomes. Long‐term survival remains poor for primary malignant tumors of the heart.


| INTRODUCTION
Primary cardiac tumors (PCT) are a rare disease, with reports of prevalence from autopsy series ranging from 0.001% to 0.3%. 1,2 However, they constitute a major diagnostic and therapeutic challenge. Recently, considerable advances in cardiac imaging have made the diagnosis of heart neoplasms accurate and readily available.
Hence, the clinical interest on PCT has been progressively increasing.
Usually, over 75% of these tumors are benign, with atrial myxomas being the most common. 3 Cardiac sarcoma represents the most frequent primary malignant tumor of the heart. 4 Surgical resection is the most common and effective therapy for both benign and malignant PCT. Because of the rarity of PCT occurrence, only few studies have been published describing the presentation and outcomes after surgical management. Moreover, the majority of these reports focus on patients submitted to tumor resection in the past half century. The aim of the present study was to review our experience in the surgical treatment of PCT over the last two decades, with a focus on the longterm outcomes.

| MATERIALS AND METHODS
We conducted an observational retrospective study of adult (>18 years old) patients with pathological confirmation of PCT undergoing surgical resection at our institution between January 1, 2000 and December 31, 2020. Subjects with metastatic tumors of the heart, and those in whom a primary cardiac origin was not clear, were excluded from the analysis. Preoperative diagnosis was established using transthoracic echocardiogram (TTE) or other cardiac imaging techniques such as computed tomography (CT) or magnetic resonance (MRI). Information including demographics, comorbidities, symptoms, tumor location, pathological findings, operation information, and in-hospital outcomes were collected from the hospital database. Data about postdischarge death was obtained from the Regional Institutional Health Database System. All survivors were contacted via telephone to assess late functional status and tumor recurrence. The study was conducted in accordance with the principles of the declaration of Helsinki and the study protocol was approved by the institution ethical committee (nr. 164/2020).

| Statistical analysis
Categorical data were described as numbers and percentages, while continuous variables were presented as mean ± SD or median and interquartile range. Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. Statistical analysis was performed with SPSS for Windows, version 23 (IBM Corporation). A value of p < .05 was considered to be statistically significant.

| Patient demographics and tumor characteristics
A total of 57 patients underwent surgical rection for PCT during the study period. Baseline characteristics are shown in Table 1 Table 2.

| Postoperative outcomes and survival analysis
Postoperative outcomes are reported in  Figure 2. Analysis revealed that patients with papillary fibroelastoma had poorer long-term survival when compared to subjects who underwent myxoma resection, however this trend did not reach statistical significance (p = .41).

| DISCUSSION
Despite the increase availability of several cardiac imaging modalities, cardiac tumors remain an exceptionally rare entities, representing the cause of only 0.3%-0.85% of all open-heart surgeries. 1,5 Our study corroborates previous observations suggesting that PCTs occur more often in the middle-aged population, and the morbidity is higher in female. 6 Atrial myxomas are confirmed to be the most common PCT. Note: Data are shown as mean ± SD (%) as appropriate.

Characteristics Value
Early outcomes Although significantly less frequent, papillary fibroelastoma is the second-most common primary tumor of the heart. As previously described, 6 In patients with benign cardiac neoplasms or in those with resectable primary malignant disease and no evidence of metastasis, surgery is generally indicated to improve prognosis. 11 For selected subjects, other approaches such as heart transplantation 12  After surgical resection, the main difference between benign and malignant tumors is the survival rates. 6,17,18 In our series, surgical resection of PCT has good short and long-term results; conversely, the prognosis of malignant types is poor. The median survival of patients with malignant tumors was less than 2 years. These findings are consistent with a previous report that documented survival of 16.5 months. 19 Primary cardiac sarcomas possess the highly aggressive local growth and metastatic spreads are relative common. The prognosis of patients is primarily related with tumor histology, complete or incomplete resection and distant organ metastasis at initial diagnosis. 20 Clinical presentation of heart sarcoma may vary depending on location. Studies have found that right-sided cardiac sarcomas tend to be bulky, are more infiltrative and metastasize earlier; 21 thus, clinical symptoms are commonly nonspecific.
In contrast, left-sided cardiac sarcomas are less invasive, more circumscribed, and usually cause heart failure early in the disease process. 21 Sarcomas that originate in the pulmonary arteries are the rarest group, and generally present with symptoms related to intraluminal obstruction such as dyspnea. Our approach to malignant PCT is conservative and consists of surgical removal without extensive cardiac resection. While some have advocated for highly aggressive procedures including cardiomyoplasty and autotransplantation for the resection of complex heart tumors, 13,22 it is currently unknown whether these approaches result in superior survival outcomes. As such, malignant PCT present the greatest challenge to cardiac surgeons.
In accord with previous studies, 6,8 we found that individuals with papillary fibroelastoma had poorer long-term results compared with subjects diagnosed with myxoma, albeit not statistically significance.
This could be explained through the fact that the patients with fibroelastoma were older (64 vs. 62 years old) and had more CVAs at the time of surgical intervention (27% vs. 11%). The increased occurrence of CVA in subjects with fibroelastoma is not a novel findings; we have found previous observations in studies by Tamin et al. 23 and Gowda et al. 24 Indeed, the rate of concomitant surgical procedures was greater in patients underwent fibroelastoma excision (63% vs. 18%). Thus, it was a sicker group than myxoma group and, not surprisingly, had a different postoperative long-term survival.
Overall, the patient population presented in this study showed acceptable postoperative course with results comparable to the other nontumor cardiac surgical patients, However, we observed a slightly higher incidence of postoperative complications (e.g., stroke, AKI, atrial fibrillation), when compared with previous publications on this topic. 8,25 This may be because of the higher rate of concomitant procedures performed in addition to tumor resection in our experience. Noticeably, performing concomitant procedures during tumor have a negative effect on postoperative morbidity.

| Limitations
The major limitations of the current study were the retrospective design and its small sample size because of the rarity of PCT. Moreover, we only evaluated patients underwent surgical resection; conservatively managed heart tumors were not considered. Because of the unavailability of data on cause of death, only all-cause mortality was assessed. We had no tumor recurrences at follow-up, however, recurrence was assessed only in survivors due to failed in obtaining deceased patients' medical records.
Last, since the current study was not designed to detect confounders that impact survival, it is important to note that our results only described the association with long-term survival rather than causation.

| CONCLUSION
PCT are challenging because they are extremely are. The firstchoice treatment is surgical excision, which must be performed as early as possible to reduce the risk of embolic events. Surgical F I G U R E 2 Kaplan-Maier's survival analysis: myxomas versus fibroelastomas. Analysis showed that after a relative equal survival between myxomas and fibroelastomas in the first year of follow-up, patients with papillary fibroelastoma had poor long-term survival when compared to subjects who underwent myxoma excision; however, this trend did not reach statistical significance (p = .41) resection of benign tumors is safe and, especially for myxomas, provides excellent long-term prognosis. On the contrary, patients with malignant tumors have a dismal prognosis.