Background
Cardiac tumors, whether benign or malignant, are relatively rare among oncological diseases, with an overall prevalence of no more than 0.33% [
1]. Cardiac tumors can also be classified as primary or metastatic, depending on their origin. The frequency of primary cardiac tumors is approximately 1.38/100000, and a recent study has shown that 90% of primary cardiac tumors are benign, with most being myxomas [
2]. Metastatic cardiac tumors are described as being approximately 22 to 132 times more common than primary cardiac tumors [
3‐
5]. However, the incidence of cardiac metastases reported in the literature is diverse, ranging from 2.3% to 18.3% (average incidence of 7.1%) among autopsies of cancer patients [
6,
7]. The symptoms of cardiac tumors are nonspecific and can mimic the manifestations of many other heart diseases, making them difficult to diagnose and cure [
8]. Twelve percent of oncology patients with uncomfortableness in the heart were found to have tumor metastases in the heart or pericardium at autopsy [
9]. The occurrence of cardiac metastases often means that the tumor has progressed to a terminal stage, and whether continued treatment benefits the patient is worth studying [
10]. When treatment is continued, whether a valid cardiac response associated with an increase in patient survival also needs to be indicated. Currently, most clinical studies of cardiac metastatic tumors have been case reports [
11‐
15]. The overviews of the clinical features as well as the prognosis of patients with cardiac metastatic tumors are limited. This study reviewed the clinical data of cancer patients diagnosed in Fujian Cancer Hospital and Fujian Provincial Hospital from 2007 to 2022, exploring the clinical features and prognosis of cardiac metastatic tumors.
Materials and methods
A retrospective analysis was conducted on patients with malignancies who were admitted to Fujian Cancer Hospital and Fujian Provincial Hospital from January 2007 to September 2022, and the follow-up period ended in March 2023. Patients with malignancies were diagnosed through detailed medical history, complete physical examination and pathologic results. Cardiac metastases were confirmed by imaging examinations (echo, cardiac CT, cardiac MRI, etc.), and all tumors had metastasized to the heart and/or invaded the pericardium from external sources. Both patients who continued treatment and those who withdrew from treatment were included. This study obtained only clinical information (medical history, clinical examinations and prognosis) and was carried out in accordance with the standards of the Declaration of Helsinki. Informed consent was obtained from all patients or their legal guardians. This study was approved by the Ethics Committee of Fujian Cancer Hospital and the Ethics Committee of Fujian Provincial Hospital.
Efficacy evaluation of antitumor treatments for primary tumors and metastases was performed. For solid tumors, it was based on Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) [
16]; for lymphohematopoietic tumors, it was based on Lugano 2014 standard [
17]. Efficacy grades were divided as follows: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The cardiac response is defined as an evaluation of the efficacy of the cardiac metastases as PR or CR after treatment. In echocardiography data, the left ventricular ejection fraction (LVEF) reflects cardiac systolic function, and the early diastolic transmitral flow velocity/early diastolic mitral annular velocity (E/e’) ratio reflects cardiac diastolic function.
All statistical analyses were performed using SPSS v27.0. Continuous variables are presented as the mean ± SD when normally distributed and as the median (interquartile range) otherwise. Descriptive parameters such as frequencies and percentages were calculated for categorical data. For normally distributed continuous variables, between-group differences were performed with independent-sample t tests; for nonnormally distributed data, Wilcoxon rank-sum tests were used. The 1-, 3-, 6-, and 12-month survival outcomes were examined, and comparisons were evaluated by Kaplan‒Meier curves and log-rank statistics. The survival of the following groups was compared: continued treatment versus discontinued treatment and cardiac response versus no cardiac response. All survival data were right-censored. All tests were 2-sided, and an alpha value of 0.05 was used to define statistical significance.
Discussion
Cardiac tumors are rarely seen clinically and are more likely to be found postmortem, mainly because the symptoms of metastatic cardiac tumors are insidious and are not focused on in daily treatment. In this study, we collected, summarized and analyzed the clinical data of 41 patients with cardiac metastases to preliminarily describe the clinical features and treatment outcomes of these tumors. One-fourth of the patients had cardiac metastasis at the time when the primary tumor was diagnosed. More than half of the patients had cardiac metastasis within 6 months after the primary tumor diagnosis. Some of the patients with primary tumors evaluated as PD were found to have cardiac metastasis at the same time. When the primary tumor is evaluated as PD, an assessment of the heart may help to recognize cardiac metastasis in the early stage, although more samples are needed to confirm this recommendation.
The pathological types of cardiac metastases are diverse and depend on the nature of the primary tumor. In this study, one-fourth (10 of 41) of patients were observed to have lymphoma as the primary tumor. The second most common type of primary tumor was lung cancer (7 of 41), followed by esophageal cancer, cervical cancer, renal cancer, melanoma, colorectal cancer, osteosarcoma, soft tissue tumors and other unclassified primary tumors. As lymphoma is a non-solid tumor of lymph-hematopoietic origin, it has been reported that the heart seems to be more often involved in non‐Hodgkin's lymphomas, and the pericardium is more often infiltrated in Hodgkin's lymphoma [
18,
19]. Thus, whether lymphomas are more likely than other tumor types to spread to the heart through the bloodstream should be of greater concern. For solid tumors, it has been reported that up to 10% of bronchogenic tumors have atrial invasion, and lung cancer is the most common solid primary tumor that spreads to the heart [
7,
15,
20]. In this study, lung cancer still accounted for the most frequent histologic types of cardiac metastases that were observed, which was consistent with previous literature. The number of cardiac metastases and their sites were also recorded. The majority of them were solitary, located in the ventricles or invading the pericardium, which was similar to the current reports [
7,
20]. However, there is no association between cardiac symptoms and the sites or number of cardiac metastases. Instead, all patients with pericardial effusion after cardiac metastases had cardiac symptoms. Furthermore, a history of cardiovascular disease and cardiovascular risk factors did not seem to be associated with the development of cardiac metastases.
Echocardiography is a common method for assessing cardiac function. Echocardiographic imaging may show a thickened myocardium, an abnormal myocardial structure and abnormal contractility after cardiac metastasis [
19,
20]. Although cardiac function after cardiac metastasis has been reported in the literature [
21], preserved systolic function was found in carcinoid metastasis patients. However, little is known about the changes in cardiac function before and after cardiac metastasis. In the present study, pre- and postmetastatic echocardiography data were collected in some patients. In these data, although there was one patient with an increased heart rate after cardiac metastasis, there was no marked difference in heart rate overall. The volume of the heart could not be compared effectively because it varies according to the site of the metastatic tumor. All patients who had echocardiography showed valve regurgitation. Valves are an unusual target for metastases due to the lack of vessels and constant cusp motion [
22]. However, intracavitary masses can impede blood flow and cause valvular dysfunction [
23], which may explain why patients with cardiac metastasis have valve regurgitation. Cardiac metastases occurred with different sizes in any part of the heart, and myocardial thickening and valvular regurgitation were also observed under echocardiography, but findings on hemodynamic changes were not apparent. The LVEF in cardiac metastasis patients was in the normal range, which was similar to the results of Pandya et al. [
21]. The E/e’ ratio can reflect cardiac diastolic function, and a value above 12 is considered abnormal diastolic function [
24,
25]. Compared with echocardiography data before cardiac metastases, three patients displayed E/e’ > 12 after cardiac metastasis but normal ejection fraction, which suggested the potential possibility of diastolic insufficiency. Altogether, the impact on cardiac function seems to be compensable in the early stage of cardiac metastasis.
Prolonging the survival of oncology patients has always been a common goal. The occurrence of cardiac metastasis indicated that the tumor was in the terminal stage. The 2022 ESC guidelines on cardio-oncology hold the view that systemic chemotherapy is needed for the treatment of cardiac metastases, but a lack of evidence to support its benefits and not much explanation is given in the guidelines [
10]. To the knowledge, this is the first study to focus on the response of cardiac metastases and prognosis after continued antitumor treatment. In this study, survival analysis showed that patients who continued treatment after developing cardiac metastases had remarkably improved survival compared with those who withdrew from treatment, regardless of the treatment regimen. Notably, half of the patients received chemotherapy alone, but this study could not evaluate which type of treatment most effectively prolonged patient survival. Although there was no significant association between cardiac metastasis response and survival after treatment, the median survival time was longer in patients whose cardiac metastasis responded to treatment. Generally, it is beneficial for oncology patients to continue treatment after developing cardiac metastases.
Of the patients who had efficacy evaluations, when primary tumors appeared to recede, there were corresponding remissions or stabilization of the cardiac metastases and other metastases. When the primary tumors stabilize or progress, cardiac metastases and other metastases also appear to stabilize or progress. Thus, it was tentatively concluded that when cardiac metastases responded to a therapeutic regimen, their responses were accompanied by primary tumor responses. Among patients with cardiac metastases, there were 5 in whom the efficacy of treatment was evaluated as CR; 4 of these patients had lymphoma. The primary tumors were also evaluated as achieving CR or PR. For lymphoma patients, active chemotherapy after cardiac metastasis can still achieve good results. Therefore, after cardiac metastasis occurs, systemic therapy to address the primary tumors remains important, and a cardiac response can lead to favorable curative effects and prolong the survival period.
Theoretically, myocardial replacement with tumor cells may eventually cause heart failure [
26]. The death of tumor patients after cardiac metastasis has also been speculated; there were 3 patients with high levels of NT-proBNP who presented chest tightness and shortness of breath and died of heart failure. There was a concern that some patients who showed symptoms of heart failure and elevated NT-proBNP but normal ejection fraction had the possibility of ejection fraction-preserved heart failure, but none of them received preventive heart failure treatment. According to the 2022 AHA Guidelines on Heart Failure [
27], for patients with cancer-related cardiac risk, cardiac function assessment before therapy and cardiac function monitoring are highly recommended, but the benefits from pharmaceutical prevention with β-blockers and ACEIs/ARBs need more evidence. In cancer patients with cardiac metastases, cardiac function assessment and monitoring are needed for the early recognition of heart failure, along with low cardiotoxicity medications. Pharmaceutical prevention to reduce death from cardiovascular events still deserves more practice and investigation. Unfortunately, due to the concealed symptoms of cardiac metastasis and the incompleteness of existing NT-proBNP data, the risk of cancer patients dying from heart failure after cardiac metastasis needs further research.
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