Risk Factors for Embolism in Cardiac Myxoma: A Retrospective Analysis

Background

Atrial myxomas are the most common primary heart tumors. Primary tumors of the heart are uncommon, with an incidence ranging between 0.0017% and 0.19% and accounting for nearly half of all benign heart tumors [1,2]. Cardiac myxomas are found in any of the 4 cardiac chambers, with the majority occurring in the left atrium arising in the interatrial septum at the border of the fossa ovalis [3–6]. Cardiac myxomas are initially diagnosed using echocardiography, computed tomography, and magnetic resonance imaging to determine their location, site of pedicle attachment, and size (Figure 1A, 1B). Two-dimensional echocardiography is the diagnostic procedure of choice. Pathological examination is needed for the final diagnosis.

Embolism is a major complication occurring in 30–50% of patients with cardiac myxomas, and is closely associated with cardiac mortality, especially preoperative [7,8]. Despite prompt thrombolytic therapy or embolectomy, sequelae of embolism still remain. Surgical removal is the most effective therapeutic and preventive intervention in cardiac myxoma. However, the specific risk factors contributing to embolism in cardiac myxomas are still unclear. In this retrospective study, we analyzed the clinical data at 3 centers in China over a 16-year period to determine the risk factors of embolism in patients with cardiac myxomas (Figure 1C, 1D).

Material and Methods

PATIENTS:

This is a retrospective study of 162 patients with cardiac myxomas surgically treated between January 1998 and June 2014 at Changzheng Hospital, Changhai Hospital, and Fuzhou General Hospital, in China. Patients with blood diseases prone to thrombosis and those with a history of thrombus were excluded. The diagnosis of cardiac myxomas was confirmed by postoperative pathological examination. This study was approved by our Institutional Review Board.

SURGERY:

The surgical excision of myxoma was performed under the following conditions: 1) Medial sternotomy to open the chest, followed by pericardial incision; 2) Cannulation of caval veins and aorta to establish the bypass system; 3) Moderate hypothermia and cardioplegia using warm blood crystalloids to achieve heart arrest; 4) Partial resection of the endocardium around the tumor base for tumor excision; 5) Avoidance of embolization of tumor fragments; and 6) Valve surgery if indicated by severe valvular regurgitation due to enlarged annulus.

DATA COLLECTION:

Based on clinical presentation and cranial computed tomography, patients were classified into embolic and non-embolic groups. Patients’ clinical profile was retrieved, including sex, age, body surface area, body mass index, history of atrial fibrillation or flutter, concomitant valvular heart disease, pulmonary artery hypertension, coronary artery disease, blood coagulation function, intravascular ultrasound, and characteristic features of the myxomas (size, appearance, location, attachment). Typical myxomas arise from the interatrial septum at the border of the fossa ovalis in the left atrium. Atypical myxomas arise from other sites of the left atrium or in the other cardiac chambers [9]. Macroscopically, the surface of myxomas is classified into 2 types (Figure 2): the irregular type has a surface with a soft consistency and multiple exquisite villous extensions on the surface, and an irregular or villous surface; and the polypoid type has a compact consistency with polypoid appearance and smooth surface [7,10–12].

STATISTICAL ANALYSIS:

Statistical analysis was performed using SAS version 9.3 (SAS Institute Inc, Cary, NC, USA). Continuous variables were reported as means (±SD) or median (range) as appropriate, and the Wilcoxon 2-sample test was used for comparisons. Categorical variables were described as frequencies and percentages, which were compared using chi-square test or Fisher’s exact test. Binary logistic regression was used to identify the independent risk factors of embolic events and the multivariable model was built by stepwise selection. Candidate variables were carefully selected to satisfy the entry criterion of P<0.10 in the univariate analysis. A P value less than 0.05 was considered statistically significant.

Results

PATIENT CHARACTERISTICS:

No significant differences in age, sex, body mass index, or other clinical characteristics were observed between the embolic and non-embolic groups (Table 1). All patients denied a family history of symptomatic cardiac myxomas. Over half of the patients (53.7%) were age 40–60 years. A preponderance of left atrial involvement was observed in 137 patients (84.6%), with 34.3 myxomas arising from the fossa ovalis. In addition, a prevalence of female sex was found (female/male ratio=2.6: 1). Our results are consistent with previous case studies involving populations from France, Germany, the United States, Austria, and Korea [6,13,14].

CLINICAL PRESENTATION:

The embolic group included 33 patients (20.4%) and the non-embolic group included 129 patients (79.6%). Only 1 patient in our study presented both cerebral and peripheral embolism. The embolic group included 25 patients with cerebral infarction. Of these patients, 2 lost vision because of central retinal artery occlusion and 1 patient had internal carotid artery infarction. Six patients presented with pain and dysfunction of the lower extremities caused by acute aortic thrombosis, including 1 patient with aortic thrombus of the external iliac artery. One patient had pulmonary embolism and 1 patient had coronary thrombosis (Table 2).

Among the 129 patients in the non-embolic group, chest pain and discomfort were the most common cardiac symptoms, observed in 79 patients (48.8%). Dyspnea, palpitation, and symptoms of acute heart failure occurred in 47, 36, and 14 patients, respectively. Notably, 1 of these patients presented with cerebral hemorrhage. Nineteen patients (18.6%) were asymptomatic and diagnosed with cardiac myxoma incidentally during examination for other conditions or during physical examination.

LABORATORY RESULTS:

The findings of echocardiography and hematological tests are listed in Table 3. There was no significant difference in platelet count between the 2 groups (250 [IQR 203–311] 109/L vs. 218 [IQR 182–273] 109/L, P=0.0724). The mean platelet volume (MPV) was significantly higher in the embolic group compared with the non-embolic group (10.9 fL [IQR 10.3–11.4 fL] vs. 10.40 fL [IQR 9.7–11.30 fL]; P=0.0384). No significant differences were found in the other hematological parameters between the 2 groups, including blood type, white blood cell count, and granulocyte count. The 2 groups did not differ significantly in echocardiographic parameters such as left atrial volume, left atrial volume index, and left ventricular ejection fraction (Table 3).

HISTOLOGY AND PATHOLOGICAL DATA:

Nearly two-thirds of irregular myxomas were found in the embolic group, but less than half in the non-embolic group. Ten cases presented with blood clots and 3 cases involved mucosubstance adhering to the surface. Round, stellate, or irregular tumor cells were found with myxoid or narrow fibrous matrix in the intercellular region. Eighteen cases showed deposits of hemosiderin and iron salts in the tumor center, 8 cases presented with spotty calcification, and 1 case with ossification. Nearly all the myxomas detected immunohistochemically were positive for Vimentin (46/50). Positivity for CD31 and CD34 was noted in 95.6% (43/45) and 90% (36/40) of cases, respectively (Figure 3).

MYXOMA CHARACTERISTICS:

There were no significant differences in the size of myxomas between the 2 groups (20 cm2 [IQR 10–30 cm2] vs. 18 cm2 [IQR 10–25 cm2]; P=0.3696; Table 4). However, significantly more patients in the embolic group had large myxomas (>25 mm2) than in the non-embolic group (36.4% vs. 17.1%, P=0.0276). Tumor attachment did not differ significantly between the 2 groups (1.0 cm [IQR 0.8–1.5 cm] vs. 1.0 cm [IQR 0.5–1.3 cm]; P=0.1227]. Atypical myxomas were significantly higher in the embolic than in the non-embolic group (45.5% vs. 16.3%, P=0.0303). The irregular surface of myxomas was significantly more common in the embolic group compared with the non-embolic group (63.6% vs. 41.1%, P=0.0337).

PERIOPERATIVE DATA:

No significant differences were observed in perioperative comorbidity, blood products used, total chest tube loss, and operation time between the 2 groups. However, the ventilation time, CCU and total hospital stay were significantly longer in the embolic group compared with the non-embolic group (Table 5). Significantly decreased MPV levels and platelet counts were found after the surgical excision of myxomas in the 2 groups (Table 6).

MULTIVARIATE ANALYSIS:

Table 7 shows the results of logistic regression analyses. Binary logistic regression revealed that the most important risk factor contributing to embolism was the platelet count higher than normal (odd ratio: 2.911; P=0.0356). Atypical location (odd ratio: 2.537; P=0.0477) and irregular surface (odd ratio: 2.701; P=0.0216) of tumor was a significant predictor of embolic complications. MPV was an independent predictor of embolism (odds ratio [OR]: 1.468; 95% confidential interval [CI]: 1.062–2.027; P=0.02) (Table 7).

Discussion

LIMITATIONS:

Owing to the retrospective nature and the long period of data collection, some valuable data were overlooked. For instance, the mobility of myxoma depends on its consistency, the level of attachment, and pedicle length, all of which are related to embolic risks [7,13,15,23]. We found very few cases with pedicle length. The degree of attachment and consistency was not adequate for analysis of myxoma mobility. Our study results are also limited by the different recruitment periods.

Conclusions

The tumor size, location, and macroscopic appearance, along with MPV and platelet count, are closely associated with embolic events in patients with cardiac myxoma. Patients with higher embolic risks should undergo surgical excision promptly, with caution exercised to prevent embolization during the surgery.