INTRODUCTION

Despite being widely known entities by the healthcare community, the prevalence of cardiac masses is less than 0.3%¹, with a cumulative incidence of 13.8 cases per million people per year in the case of primary tumor². The differential diagnosis of these neoplasms includes other cardiac masses, e.g., vegetations, thrombi, or myocardial hypertrophy³, as well as other entities such as vascular neoplasms or intrapericardial cysts.

Cardiac tumors may be primary or secondary (metastases)⁴, , the latter being up to 132 times more frequent than the former⁵. Primary tumors can further be classified as benign (75%)⁶, or malignant⁷. As for benign primary cardiac tumors in adults, most are myxomas and are usually found in the left atrium9, while the most frequently found benign primary tumor in children is rhabdomyoma. Of the 25% malignant ones, the most common are sarcomas and lymphomas⁸.

Cardiac masses affect people mainly between the ages of 30 and 60¹⁰ and some, such as myxomas, are more commonly found in women³. The histopathology of cardiac masses is very diverse. For example, myxomas are gelatinous structures formed by stellate or polygonal spindle cells surrounded by a stroma rich in glycosaminoglycans. These cells are arranged in rings around amorphous capillaries and the tumor surface is surrounded by endothelium^11,12.

The clinical presentation of cardiac masses is determined by their size, anatomical location, and mobility, rather than by their histopathology^7,11. Therefore, symptoms are usually non-specific (chest pain, syncope, murmurs, or arrhythmias)³, , which makes diagnosis difficult as it overlaps with typical presentations of other cardiovascular conditions. However, a high proportion of patients are asymptomatic at diagnosis, with the tumor being found incidentally through imaging tests performed for another reason³. The improvement in the quality and increased use of cardiac imaging techniques in recent years have contributed to increasing the number of diagnoses that are made incidentally.¹³.

According to current recommendations for the diagnosis of cardiac masses, echocardiography is the imaging technique of choice; the study can be completed with other imaging modalities such as computed tomography (CT) or magnetic resonance (MRI)⁸. Despite the great information that these tests provide, the definitive diagnosis must be histological¹¹.

The treatment of cardiac masses is based on surgical excision regardless of their size given the risk of causing lethal complications^3,11.Minimally invasive surgery has allowed patients to achieve increasingly earlier functional recovery¹⁴. In general, cardiac masses have a good prognosis^8,11 and low risk of recurrence (2% in the largest series published to date)¹⁵.

The low prevalence and non-specific symptoms make it difficult to include cardiac masses in the clinical differential diagnosis. Furthermore, the literature focuses primarily on myxomas, and data on other less common cardiac masses are scarce. The objective of this study was to carry out an exhaustive characterization of the symptoms experienced by patients diagnosed with cardiac masses and cysts in our environment, aiming to obtain further data for future diagnoses and provide patients with optimal clinical care.

MATERIAL AND METHODS

Descriptive, retrospective, single-center study. A search was carried out to identify patients who underwent surgery for cardiac tumors and cysts between December 2002 and December 2022 (twenty years) in the database of the Department of Cardiology and Cardiac Surgery of Clínica Universidad de Navarra (Pamplona, Spain).

The following variables were extracted from the medical records:

Likewise, the pathological reports and description of the surgical interventions recorded by the surgical team were consulted.

The specific time of the checkup (in days after surgery), symptoms, imaging techniques used, and data on recurrence and exitus were recorded during the first postoperative checkup (while in the hospital) and in the first checkup following hospital discharge.

This study was conducted in compliance with the Declaration of Helsinki and approved by the Research Ethics Committee of the University of Navarra (project 2023.140). Patient information was coded to protect their identity.

Statistical analysis. The Shapiro-Wilk test, along with the evaluation of skewness and kurtosis, was used to determine whether continuous variables followed the normal distribution. Variables following a normal distribution are presented using arithmetic means (^-x) and standard deviations (SD); otherwise, with medians (P₅₀) and interquartile ranges (IQR). Qualitative variables were presented using frequencies and percentages. The Mann-Whitney U test was used to compare mean postoperative diameters of the masses found in the cardiac chambers according to their anatomical location. Agreements between mean diameters before and after surgery were evaluated using the intraclass correlation coefficient (ICC), together with its 95% confidence interval (95%CI). p-values were two-tailed and statistical significance was set at p <0.05. The analyses were performed with STATA version 15.1 (Stata Corp, College Station, TX, USA) and GraphPad Prism version 9.5.1 (GraphPad Software Inc., San Diego, CA, USA).

RESULTS

Thirteen patients were identified in the search, all of whom were included in the study. In this sample, there was a higher percentage of female patients (76.92%) and the average age was 63.08 years (range: 30-86). Table 1 shows the baseline characteristics of the study patients based on the type of cardiac mass.

Year of diagnosis

The cumulative incidence was non-homogeneous throughout the study period. Halfway through the study (December 2012), only five cases (38.56%) had been diagnosed. Almost half of the patients (53.85%, n = 7) were diagnosed in the first sixteen years (until December 2018).

The cumulative incidence of incidental diagnoses also increased over the years: in the first 10 years, they accounted for 28.57% of diagnoses compared to 66.66% in the following 10 years (and 100% in the last two years) (Fig. 1).

Figure 1. Distribution of diagnosed cases over time according to the type of finding. 

Cardiovascular risk factors

Only one patient (7.69%) had no cardiovascular risk factors, 23.08% (n = 3) had one, 15.38% (n = 2) had two, almost half (46.15%, n = 6), three and one patient had up to four.

Overweight/obesity was the most prevalent cardiovascular risk factor (61.54%, n = 8); five patients having overweight (38.46%), one had type I obesity (7.69%), and two type II obesity (15.38%). The next most frequent cardiovascular risk factors were arterial hypertension (53.85%, n = 7) and dyslipidemia (46.15%, n = 6) (Fig. 2).

BMI: body mass index; CVRF: cardiovascular risk factors; DM: diabetes mellitus; HTN: arterial hypertension.

Figure 2. Risk factors of cardiovascular disease among the study patients. 

DISCUSIÓN

In this study we exhaustively characterize symptoms in patients diagnosed with cardiac masses and cysts in our environment. The general hospital Clínica Universidad de Navarra¹⁶ serves people living in Navarre, as well as patients from other Spanish communities and from abroad. However, only 13 cases with cardiac masses and cysts have been operated in the last 20 years. Probably, a higher number of diagnoses were made at this hospital, but patients decided to undergo treatment at their places of origin or at the Department of Cardiac Surgery of Hospital Universitario de Navarra, the reference public general hospital for the area of Pamplona and the entire Chartered Community of Navarre. This fact responds to the low prevalence of cardiac tumors, less than 0.3%¹. Additional data from similar studies are of great value to help improve future diagnostic performance, understand the condition of this patient population, and provide optimal clinical care.

The most frequently found type of mass in this study is myxoma (the most common benign primary tumor)⁸ , which is in line with other studies. One patient was diagnosed with a leiomyosarcoma, which originates from smooth muscle cells, commonly affecting abdominopelvic organs¹⁹ such as the uterus or the intestine; those that affect the heart are extremely rare and few cases have been described in the literature²⁰. Although cardiac metastases, such as melanoma, breast, lung, or esophageal cancer^17,18, are markedly more common than primary tumors⁵, none of the patients in this study had cardiac metastasis.

As for the location, 85% of the myxomas are reported to be found in the left atrium⁹, very similar to the frequency in this study (88.89%). Although sarcomas commonly affect the right side of the heart³, in this series the mass was found in the left atrium in one patient.

Cardiac tumors must be differentiated from other cardiac masses such as vegetations, thrombi, or myocardial hypertrophy³. In this series, one of the patients had a thrombus. Another patient presented an intimal sarcoma of the pulmonary trunk, an extremely unusual and aggressive cardiovascular tumor, frequently misdiagnosed for the much more common chronic pulmonary thromboembolism²¹. Local invasion or distant metastasis typical of sarcomas causes the patient to die within months or even weeks³.

Average age of the patients in this study was 63.08 years, consistent with the fact that cardiac masses are most common between the third and sixth decades of life¹⁰. Ten per cent of myxomas are a familial variant part of the Carney complex, an endocrine neoplasia syndrome of autosomal dominant transmission caused by a mutation in the PRKAR1A³. While sporadic forms usually appear as isolated entities in the left atrium - adhered to the interatrial septum -, the genetic variant can occur at younger ages, be multiple, and locate in the ventricles. In this series, there is no indication that the cases are of the familial variant, except for the case of the youngest patient (30 years of age); in this latter case, while performing the resection of the myxoma of the left atrium anchored in the interatrial septum, a 1-centimeter myxoma was found in the right atrium attached to the septum. No further information was available, e.g., family history of interest.

EA larger number of cardiac masses are being described with the widespread use of echocardiography as a diagnostic test²². Furthermore, the increase in the quality and use of cardiac imaging techniques in general, have also led to the rise in the diagnosis of incidental cardiac masses¹³. It has been estimated that the incidence of primary cardiac tumors has doubled over the past 50 years²³. The increase in incidence is striking in this study; however, a causal relationship with the rise in the use of imaging techniques cannot be established due to the retrospective nature of the work and the lack of data on the global incidence of cases, as the increase in the incidence of operated cardiac masses should be accompanied by a concomitant increase in diagnoses.

The results of some studies suggest that the most prevalent cardiovascular risk factors in this patient population are smoking and dyslipidemia²⁴, while in our series the risk factors are overweight/obesity and arterial hypertension.

Clinical manifestations are not very specific and may lead to misdiagnosis. Several cases have been described, in which the condition led to a first diagnosis of bronchial asthma²⁵, , as occurred in this series with two cases. The typical clinical presentation for cardiac masses described in the literature is intracardiac obstruction, thromboembolism, and constitutional symptoms^3,8,11,26. It is also very common for cardiac masses to mimic mitral valve disease, both stenosis (due to the prolapse of the tumor in the valve orifice) and insufficiency (due to valve trauma). The detachment of tumor fragments may lead to a thromboembolic phenomenon, and the cytokines they produce can be the cause of constitutional symptoms such as fever, asthenia, or weight loss^3,8.

Patients may present symptoms, although many are asymptomatic at the time of diagnosis and the mass is found incidentally through imaging studies performed for another reason³, as in this series (30.77% asymptomatic and 46.15% incidental diagnoses).

Imaging studies should not only be aimed at making a differential diagnosis but also at evaluating the need of cardiac surgery^3,8. The 2022 European Society of Cardiology (ESC) guidelines on cardio-oncology⁸ establish echocardiography as the preferred imaging technique for these evaluations. Although transthoracic ultrasound is often sufficient, it can be complemented with transesophageal ultrasound, which is more sensitive and specific in cases of smaller tumors or those located at unusual sites^11,27,28. The study can be completed with other imaging modalities such as MRI to characterize the tissue of the mass^8,29, CT or positron emission tomography (PET) to distinguish primary tumors from metastatic disease and benign tumors from malignant ones^8,30. However, CT does not allow differentiating between myxomas and thrombi³¹, although it is the best way to detect calcifications³². In selected cases, such as young patients who present multiple myxomas, echocardiographic screening of first-degree relatives is recommended due to the possibility of a Carney complex³³.

Currently, diagnosis and preoperative evaluation are usually carried out by combining different imaging techniques^3,7, as in the case of 38.46% of the cases in this series.

Imaging studies allow a wide characterization, but the definitive diagnosis must be made by histological examination of the excised mass¹¹. In a recent study that included 265 patients diagnosed with myxoma by echocardiography, only 174 (65.7%) had a pathological diagnosis of this tumor³⁴.

Given their potential to cause serious complications, treatment of cardiac masses is imperative. Regardless of the size of the mass, the only therapeutic option is surgical excision, the result of which is usually curative^3,35,36. The intervention poses very low risk or complications, embolic events being the most common^11,12,37.

Patients who have undergone resection of a myxoma have a very good prognosis^8,11, with a survival of 96% at 10 years³⁸. Malignant tumors, on the other hand, have a poor prognosis. Complete surgical excision is usually impossible, so it is necessary to combine adjuvant radiotherapy or chemotherapy. In this series, two resections were incomplete: the mass located at the intimal sarcoma of the pulmonary trunk and that of the leiomyosarcoma in the left atrium.

Recurrence of cardiac masses is very low: 1-2% in sporadic myxomas (usually due to incomplete tumor resection) and 12-22% in familial cases (due to multifocal lesions initially undetected)³. Thus, follow-up with echocardiography is recommended after the intervention^35,36, although it has not been established for how long. In this series, echocardiography was used in the first outpatient checkup in around half of the patients (58.33%).

There are several limitations to this study. The main one is its retrospective nature, which restricted us from collecting data such as pack years, alcohol consumption, and/or physical activity. Furthermore, its descriptive design and the lack of a comparison group limit the evaluation of the proposed causal relationships. Being a single-center study, the results have limited external validity; however, it should be noted that Clínica Universidad de Navarra serves patients from multiple national and international origins. Finally, the small number of cardiac masses distinct from myxomas should be considered. Possible improvements for future studies should consider prospective designs to avoid loss of information and the participation of multiple centers to increase external validity and detection of less frequent cardiac masses.

In conclusion, in this study, the symptoms in patients diagnosed with cardiac masses and cysts in our environment, most female, are exhaustively characterized. A case of cardiac leiomyosarcoma and a case of intimal sarcoma of the pulmonary trunk are described, two extremely rare types of tumors with limited information available in the literature. Moreover, the most frequent cardiovascular risk factors in these patients are reported. The description of these rare pathologies with such non-specific clinical presentations will help guide future diagnoses and provide optimal clinical care to these patients.