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Eur J Cardiothorac Surg 2002;22:971-977
© 2002 Elsevier Science NL
a Department of Surgery, Division of Cardiac Surgery, Karl Franzens University Graz, Graz, Austria
b Division for Cardiology, Karl Franzens University Graz, Graz, Austria
c Clinical Immunology and Jean Dausset Laboratory, Karl Franzens University Graz, Graz, Austria
Received 19 April 2002; received in revised form 10 September 2002; accepted 11 September 2002.
* Corresponding author. Tel.: +43-316-385-2730; fax: +43-316-385-4671
e-mail: keelingi{at}medscape.com
| Abstract |
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Key Words: Cardiac myxoma Immunology Cardiac surgery
| 1. Introduction |
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| 2. Patients and methods |
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Preoperative routine laboratory investigations in myxoma patients showed elevated levels of C-reactive protein (CRP) in 57.1% and an acceleration of the erythrocyte blood sedimentation rate (BSR) in 86.1% of the patients (Table 2). The following immunologic features were studied in patients with cardiac myxoma: complement activation; cellular activation; OKT4/8 ratio; serum levels of immunoglobulins, Ig subgroups,
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chains of immunoglobulins, lymphocyte subpopulations, ß-2 microglobulin (ß-2 MG), interleukin 2R (Il-2R), intracellular adhesion molecule (ICAM), Fc epsilon receptor II (CD 23), tissue necrosis factor receptor (TNFR); anti-streptolysine titer (ASL), rheumatoid factor (RF); white blood cell count (WBCC); and serum protein electrophoresis (SPEP). Long-term survivors after resection of a myxoma still exhibited various immunologic anomalies (Table 3). Furthermore, the immunologic status changed again in patients with recurrent disease (Fig. 1)
. A familial occurrence of the disease was excluded in first-grade relatives of our patients.
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2.3. Statistical methods
Follow-up of the survivors was accomplished by means of questionnaires, telephone calls, clinical and laboratory examination, and TTE or TEE. For comparison of patients with and without embolization of the myxoma, a two-tailed Fisher's exact test or
2 test were applied. Estimations of the risk for tumor embolization were performed using logistic regression. Alterations of immunologic parameters were analyzed using the one-sided unpaired Student's t-test. Causes of death were ascertained from the National Cause of Death Register. Survival rates were calculated using the KaplanMeier method, with significance levels of P<0.05. SAS® was used for computation.
| 3. Results |
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3.2. Mortality
The follow-up period after resection of a myxoma ranged between 6 days and 24 years. Four of the 49 myxoma patients died postoperatively. One patient died on day 6 after the operation due to low cardiac output and subsequent multiorgan failure. Another patient died 8 months postoperatively after having developed an apallic syndrome from intraoperative embolization of the myxoma. In two other patients cardiac insufficiency from coronary artery disease developed many years after myxoma resection. There has been no intra- or perioperative death due to myxoma during the past 24 years. Early mortality was 2.0% due to one patient dying 6 days after operation. Late mortality was 6.1% due to three patients dying 8177 months postoperatively. The overall survival rate was 74% at 24 years.
3.3. Early postoperative results
Nonfatal early complications were found in 21 patients (42.9%) and are listed in Table 4. Cardiac and respiratory complications represented typical conditions after open-heart surgery and included postcardiotomy syndrome, pericardial effusion, prolonged healing of the sternal wound, bradycardia necessitating pacemaker implantation, atrial flutter, atrial fibrillation, respiratory insufficiency, bronchopulmonary infection, and pneumothorax. One patient developed an ileus. Cerebral complications were found in three patients, one with infarction in the area supplied by the posterior cerebral artery, one with reversible hemiparese and the other with transient disorientation syndrome.
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From TTE and TEE examinations, a recurrence of the myxoma was suspected in one patient 72 months after his first operation for a myxoma. At that time, 21 out of our 49 patients were at risk for a recurrence of the disease (Fig. 2) . The rate of recurrence of the myxoma was 2.0% after 24 years. A symptomatic patient, a 45-year-old man, had three small myxomas that were resected in an uneventful reoperation; he is without symptoms since. Thus, the rate of reoperation for a cardiac myxoma in our patients was 2.0%. The actuarial freedom from recurrence of the disease was 95% at 24 years of follow-up (Fig. 2). Other conditions found with TTE or TEE were: mild to moderate mitral insufficiency in three patients, prolapse of the posterior mitral valve leaflet in one patient, dilation of both the left atrium and ventricle in two patients, aortic insufficiency grade II in one patient, and a massive incompetence of the left ventricle in one patient (Table 5). Because one myxoma recurred during a total observation period of 344 patient-years, the linearized recurrence rate was 0.29 per 100 patient-years.
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Out of 21 postoperative immunologic examinations, 15 patients (71.4%) presented abnormal values in terms of fluorescence-activated cell sorter (FACS) analysis, whereas five patients (23.8%) had normal values (Table 3). Abnormal ICAM values were found for 11 patients (52.4%).
In one case of a recurrent myxoma, immunologic alterations were examined and pre- and postoperative data were compared (Fig. 1). Preoperatively, serum CRP was elevated. FACS analysis revealed an impressive modification of the cell composition with an increased number of suppressor cells and thus a decreased helper/suppressor cell ratio of 0.8. C3 was elevated, while Il-2R, T8, and IgA were lower than normal. Immediately postoperatively, most immunologic parameters were altered due to the use of extracorporeal circulation. After 1 month, however, CRP had decreased to normal levels and the helper/suppressor cell ratio had normalized. C3, Il-2R, and T8 were normal, while IgA was borderline. Il-6 levels were normal.
| 4. Discussion |
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A higher risk of embolization has also been reported and events occur in 3043% of the patients [2,3]. Embolization from a mitral valve myxoma might occur more often than from an atrial myxoma due to motion of the valve leaflets. In addition, the high pressure within the left ventricle during systole seems to give rise to embolizations more frequently from the left than from the right side of the heart [3]. Embolizations occur more often from polypoid tumors floating in the blood stream than from solid round tumors [12]. Tumor size may play an additional role in embolization [13]. We report in this study that patients presenting two certain characteristics were identified as having a significantly increased pre- and postoperative risk for tumor embolization.
Asymptomatic cases were rare. This important fact may have an impact on screening methods for such patients. Our data seem to indicate that screening for myxoma is important in those cases of familial occurrence, in complex myxoma, or Carney disease in particular [14]. In myxoma families, additional immunologic and genetic screening can identify family members at risk for the disease or for a possible recurrence of disease.
Significant immunological alterations in myxoma patients seem to occur pre- and postoperatively for BSR, SPEP, CRP, FACS, Il-2R, and ICAM (Tables 2 and 3). After surgical removal of the myxoma they return to normal. In cases of recurrence of the disease, these parameters may undergo a change again. We found alterations of ICAM, but not of the OKT4/8 ratio or S, also in up to 66.6% of the long-term survivors after resection of a cardiac myxoma without recurrence of the disease. The preoperative presence and the postoperative diminution of antibodies to fresh heart muscle has been demonstrated in some myxoma patients. Therefore, it is speculated that patients may have an immune response reaction to the neoplasm or to the heart muscle mediated by the presence of neoplasm, and the reaction leads to constitutional symptoms [15]. Immunological changes due to medication, intercurrent diseases, high age, and the use of the heartlung machine can interfere with immunological screening for myxomas and should therefore be considered when interpreting immunological results. The patient from whom the data for Fig. 1 were derived was a 41-year-old male, who received none of these drugs around the pre- and postoperative examination days. When the 21 long-term patients underwent the postoperative immunological examination, some were treated with drugs, which could have altered their immune system. However, their measured values did not significantly differ from those measured in patients, who did not receive potentially immunomodulating drugs.
Differential diagnoses include thrombotic lesions, other cardiac tumors, and also but rarely neoplastic invasion of the inferior caval vein, for example, by a pheochromocytoma. MRI, in addition, allows the determination of the tissue density and may be used to distinguish myxomas from calcified and fatty tumors. Recently, calretinin, a new immunohistochemical marker, has been investigated and found to be highly specific in differentiating cardiac myxoma and mural myxoid thrombi [16]. Echocardiography, especially two- or three-dimensional TEE [12,17], is useful for estimating the risk for tumor embolization. Specifically, the risk seems to depend upon the shape, morphology, and mobility of the myxoma. Furthermore, both methods seem very helpful in planning the access for operation on valve tumors.
The surgical access to the myxoma may vary depending on the tumor location. Myxoma excision by way of aortotomy may be feasible in most cases. This approach facilitates the exposure of the left-ventricular-sided aspect of the mitral valve apparatus. In all the cases presented here, and in most cases presented in the literature, the originally compromised mitral, tricuspid, or aortic valves and the interventricular septum were completely preserved, and the patients were treated by resection of the tumor alone. Closure of an atrial septal defect (ASD) due to tumor resection was performed in one case. In those rare instances in which the tumor arises from an atrioventricular valve (AV) valve, the valve occasionally requires valvuloplasty or even replacement. Special care must be taken to avoid intraoperative systemic or pulmonary embolization of the myxoma. With systolic prolapse of some tumors into the left ventricular outflow tract, patients are at a higher risk of intraoperative embolization. For these reasons we decided to remove the tumor through the aortic root. A transventricular or minimally invasive approach, using the Heart-Port system, can be used as an alternative [18,19].
The prognosis for patients with solitary myxomas after surgical resection has been excellent. Postoperative complications were comparable to other cardiac operations (Table 4). Usually, the hospital mortality after the removal of an atrial myxoma is about 4% [2]. All current surgical techniques seem to provide low recurrence rates. Late recurrences have been reported to occur in 0.45% of surgically treated patients from up to 22 years after operation [2]. However, 40% of patients with familial myxoma experience recurrence of the myxoma [7]. Cardiac myxomas seem to recur more often in young males, or in patients with multifocal origins, and in those who have a family history of the tumor [2,7]. Therefore, it is necessary to perform routine echocardiography frequently throughout a patient's life. Except for patients with multifocal, atypical, or familial myxomas, echocardiography at 5-year intervals for several years should be adequate.
The TEE follow-up at 12 months was uneventful in 81% of our patients (Table 5). Trivial (grade I) mitral valve dysfunction without evidence of tumor recurrence was the most common abnormal finding in 7% of the patients. As the recurrence rate is higher in patients who already had a relapse, these patients demand special attention at follow-ups.
The courses of our patients indicate that the many risks inherent in this disease may be kept very low with immediate surgical treatment after early diagnosis with a particular focus on familial occurrence. As this disease may mimic a huge variety of other cardiac diseases, a possible myxoma should always be considered since relatively low risk cardiac surgical treatment is performable for most patients, and its postoperative prognosis is excellent.
| References |
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