Cardiac myxoma in pregnancy: a comprehensive review

Objective Cardiac myxoma in pregnancy is rare and the clinical characteristics of this entity have been insufficiently elucidated. This article aims to describe the treatment options and the risk factors responsible for the maternal and feto-neonatal prognoses. Methods A comprehensive search of the literature of cardiac myxoma in pregnancy was conducted and 44 articles with 51 patients were included in the present review. Results Transthoracic echocardiography was the most common diagnostic tool for the diagnosis of cardiac myxoma during pregnancy. Cardiac myxoma resection was performed in 95.9% (47/49); while no surgical resection was performed in 4.1% (2/49) patients (P=0.000). More patients had an isolated cardiac myxoma resection in comparison to those with a concurrent or staged additional cardiac operation [87.2% (41/47) vs. 12.8% (6/47), P=0.000]. A voluntary termination of the pregnancy was done in 7 (13.7%) cases. In the remaining 31 (60.8%) pregnant patients, cesarean section was the most common delivery mode representing 61.3% and vaginal delivery was more common accounting for 19.4%. Cardiac surgery was performed in the first, second and third trimester in 5 (13.9%), 14 (38.9%) and 17 (47.2%) patients, respectively. No patients died. In the delivery group, 20 (76.9%) neonates were event-free survivals, 4 (15.4%) were complicated and 2 (7.7%) died. Neonatal prognoses did not differ between the delivery modes, treatment options, timing of cardiac surgery and sequence of cardiac myxoma resection in relation to delivery. Conclusion The diagnosis of cardiac myxoma in pregnancy is important. Surgical treatment of cardiac myxoma in the pregnant patients has brought about favorable maternal and feto-neonatal outcomes in the delivery group, which might be attributable to the shorter operation duration and non-emergency nature of the surgical intervention. Proper timing of cardiac surgery and improved cardiopulmonary bypass conditions may result in even better maternal and feto-neonatal survivals.


INTRODUCTION
Cardiovascular disorders during pregnancy have become a more and more attracting issue concerning both mother and child in terms of their prognoses [1] . Cardiac surgery during pregnancy remains a tough problem due to the fact that cardiopulmonary bypass jeopardizes fetuses more than mothers [2] . The overall feto-neonatal mortality was 18.6% among the pregnant patients with a cardiac operation [1] . The fetal deaths were apparently associated with cardiac surgery during early pregnancy as well as the use of cardiopulmonary bypass [3] . Cardiac myxoma in pregnancy is one of the cardiovascular disorders that warrant a surgical resection without delay [1] . However, the clinical features of cardiac myxomas in the pregnant patients have not been sufficiently elaborated, and the risk factors influencing the maternal and feto-neonatal outcomes remain uncertain. In order to highlight these aspects, a comprehensive literature review of pregnant cardiac myxoma is conducted.

METHODS
Publications in all languages reporting on cardiac myxoma during pregnancy until November 2014 were retrieved from MEDLINE, Highwire Press, Google and Yahoo! search engines, Chinese Medical Citation Index (CMCI) and LI-LACs. The search terms "cardiac myxoma" and "pregnancy" were searched. In addition, "left atrial", "right atrial", "left ventricular", "right ventricular", "mitral valve", "tricuspid valve" and "aortic valve" were also used in the search strategy to find articles containing cardiac myxomas.

CMCI
Chinese Medical Citation Index QUOROM Quality of Reporting of Meta-Analyses Primary exclusion criteria included articles describing cardiac myxoma diagnosed postpartum, other types of cardiac tumors, undetermined nature of intracardiac mass, or myxoma of the other organs of the pregnant patients, fetal cardiac myxoma, or cardiac myxoma of animals. Papers with no complete data of the pregnant patients were excluded for the statistical analyses. Table 1 shows the results of literature retrieval. Data were carefully extracted for details of the patient population, demographics, diagnosis, clinical features of cardiac myxomas, associated disorders/comorbidities, cardiac surgical procedures, delivery modes, timing of cardiac myxoma and delivery, follow-up length and survival, complication and mortality of both mother and baby, etc. This rare condition was only reported in sporadic single case or small series without larger patient population, comparative, or randomized studies. Accordingly, the qualitative analysis of the collective data from the retrieved articles constituted a systematic review, as suggested in the Quality of Reporting of Meta-Analyses (QUOROM) recommendations [4] .
Quantitative data were presented as mean ± standard deviation along with range and median values, and intergroup differences were compared by unpaired t-test. Comparisons of frequencies were made by Fisher's exact test and P<0.05 was considered statistically significant.

Prognosis
In the delivery group, delivery mode was not given in 16 cases. Among the 26 deliveries with either cesarean section or vaginal delivery, 20 (76.9%) were event-free survivals, 4 (15.4%) were complicated and 2 (7.7%) died. Neonatal prognoses did not differ between delivery modes, treatment options, timing of cardiac surgery and sequence of cardiac myxoma in relation to delivery (Tables 4-7).

DISCUSSION
Cardiac myxoma is rare in pregnant patients. The diagnosis and management can be challenging in terms of the nature of the intracardiac mass, timing of delivery, necessity of cardiac surgery and risks of subsequent treatment [36] . The clinical manifestations of a cardiac myxoma can be one or more of the Goodwin's triad [51] . Patients may present with fatigue and dyspnea, which, however, can be misinterpreted as asthma or normal fatigue associated with pregnancy [39] . Echocardiography remains the standard non-invasive diagnostic modality, particularly in the pregnant patient [52] . In some patients, atrial thrombi may have a stalk and may be mistaken for myxomas, leading to unnecessary and potential harmful surgery [53] . A left intraatrial mass can be diagnosed as thrombus if associated with atrial fibrillation, dilated left atrium, mitral or tricuspid stenosis, low ejection fraction, prosthetic mitral or tricuspid valves, or spontaneous atrial contrast echoes [54] . Moreover, in the pregnant patients, cardiovascular magnetic resonance imaging is indicated for visualizing coarctation, aortitis, aortic dissection and atrial myxoma [52] .
Surgical management of cardiac myxoma is similar to that of the valvular disorders in the pregnant patients, even with minimally invasive cardiac surgical techniques [55] .
Nevertheless, surgical indications of both conditions can be somehow different from each other. Congestive heart failure as a consequence of rheumatic mitral stenosis is always a contraindication of pregnancy. But it may be curable to percutaneous inteventional therapy, however, carrying the risk of fetal teratogenicity by manipulation under X-ray. Or else, an urgent valvular operation is warranted in the presence of infective endocarditis, intramural thrombus, paravalvular leakage, stuck prosthetic valve or thrombus formation. Meanwhile, the indications for cardiac myxoma resection are the potential embolic events and sudden death caused by myxoma-obstructed valve orifice [2] . Wang et al. [2] reported three pregnant patients with a cardiac myxoma, two of which were complicated with cerebral infarctions and an urgent cardiac myxoma resection with later curettage was performed. Liu et al. [6] described a pregnant patient with a cardiac myxoma presented with both cerebral infarction and central retinal artery occlusion, and a cardiac surgical resection was performed without delay. As for the potential of cardiogenic embolic events and possible preterm delivery due to hemodynamic changes, a timely surgical resection of cardiac myxoma can be indispensable during pregnancy.
The favorable maternal and fetal outcomes suggest that there might be a subset of pregnant patients with intracardiac masses who may benefit from non-surgical management [36] . Open heart surgery as well as the use of cardiopulmonary bypass may cause premature labor and endanger the baby [49] . The surgical resection of cardiac myxoma may be associated with a 30% baby loss rate, or postnatal physical or developmental disabilities [39] . It is encouraging that maternal survival rate was 100% in the pregnant patients with a cardiac myxoma, superior to that of the pregnant patients with infective endocarditis [3] . This might be interpreted as the results of the advantaged cardiopulmonary bypass techniques including high flow rate, high perfusion pressure and pulsatile flow applied in cardiac surgery during pregnancy [30] . By comparison, infective endocarditis and acute aortic dissection might be more dangerous to the pregnant patients than cardiac myxoma as for the infective nature of the former and the use of profound hypothermic circulatory arrest for the operation of the latter [3,56] . The present study also revealed that timing of delivery other than the delivery mode (by excluding early termination of pregnancy) and time sequence of cardiac surgery and delivery was closely related to feto-neonatal mortality. Cardiac surgery under cardiopulmonary bypass should be avoided in the first trimester, particularly after six weeks, due to the risk of teratogenesis [50] . The pregnant patients may wait for a few weeks [13] , or take weekly thyrotropin-releasing hormone and ß-methasone therapies for fetal lung maturation [35] . Precautions during cardiac operation include using blood priming solution, normothermic cardiopulmonary bypass and high perfusion pressure [38] .
Possible bias may be generated in present patient setting due to limited data available from the literature for the statistical analysis. Therefore, more abundant information of such patients is necessary for further precise results.

CONCLUSIONS
Cardiac myxoma is rare in pregnant patients. In most cases, the cardiac myxoma is diagnosed in the second trimester and is resected in the third. Cesarean section was the most frequent delivery mode. The 100% maternal survival of this patient setting is encouraging. A delivery at early gestation was closely related to an increased feto-neonatal mortality. A delivery postponed to late pregnancy until fetal maturity may improve the feto-neonatal survival. In brief, embolic potential and hemodynamic deterioration are indications for an urgent cardiac myxoma resection. Otherwise, cardiac surgery should be avoided in the first trimester and be postponed until fetal pulmonary maturation or after delivery.