Infected Cardiac Myxoma: an Updated Review

OBJECTIVE This study aims to present an updated clinical picture of the infected cardiac myxoma. Revankar & Clark made a systematic review of infected cardiac myxoma based on the literature before 1998. Since then, there has not been any updated information describing its recent changing trends. METHODS A comprehensive literature search of infected cardiac myxoma was conducted on MEDLINE, Highwire Press and Google between 1998 and 2014. RESULTS In comparison with Revankar & Clark's series, the present series disclosed a significantly decreased overall mortality. It is believed that refinement of the prompt diagnosis and timely management (use of sensitive antibiotics and surgical resection of the infected myxoma) have resulted in better outcomes of such patients. CONCLUSION The present series of infected cardiac myxoma illustrated some aggravated clinical manifestations (relative more occasions of high-grade fever, multiple embolic events and the presence of refractory microorganisms), which should draw enough attention to careful diagnosis and treatment. In general, the prognosis of infected cardiac myxoma is relatively benign and the long-term survival is always promising.


INTRODUCTION
Cardiac myxomas are rare. The classical clinical manifestations of cardiac myxomas can be a triad with constitutional, obstructive and embolic symptoms [1] . The infected cardiac myxoma is a very rare condition with only sporadic cases reported in the literature. In 1998, Revankar & Clark [2] presented a complete literature collection of infected cardiac myxoma with a total of 40 cases, with detailed descriptions of the clinical features of this rare condition. They found no clear distinction between infected and uninfected cardiac myxomas, however, the infected myxomas are associated with more febrile symptoms and a higher risk of embolic events. In order to highlight the recent trends of infected cardiac myxoma, an updated review is made based on a renewed literature collection.

METHODS
A comprehensive literature search was conducted on MEDLINE, Highwire Press and Google between 1998 and 2014. The search terms included "myxoma", "heart", "heart valve", "endocarditis", "infected", "bacteremia", "blood culture" and "sepsis". Data were extracted from the text, figures and tables, with details of the study population, demographics, onset symptom, duration of disease, risk factor, complication, microorganism, antibiotic use and surgical treatment, timing of surgical operation, follow-up duration and main outcomes including survival, postoperative complication, requirement of further surgical procedure and mortality. DOI: 10.5935/1678-9741.20140112 Reference values of white blood cell count, hemoglobin, erythrocyte sedimentation rate and C-reaction protein were 4.0-10.0×10 9 /L, >12 g/dL (>11 g/dL for females), <20 mm/h and 0-1 mg/dL, respectively.
Quantitative data were presented as mean±standard deviation with range and median values, and intergroup differences were compared using the unpaired t test. Frequencies were compared using Fisher's exact test. Results with P<0.05 were considered statistically significant.

Risk factors
Recent dental procedures, recent infections, previous invasive procedures and immunocompromised conditions were the risk factors that led to a cardiac myxoma infected. No predominance was noted between the above risk factors. No significant difference was found in each risk factor between the present series and the series of Revankar & Clark [2] (Table 2).

Clinical features
The onset symptoms and signs of the 37 patients (2 patients' symptoms were not reported) with infected cardiac myxoma were listed in Table 3. Fever was the most common symptom accounting for 97.3% of all cases. The fever nature was persistent in 2 (5.6%), recurrent in 1 (2.8%), intermittent in 1 (2.8%) and with a fever of unknown origin in 3 (8.3%) patients. In general, constitutional symptoms were more frequent than obstructive or neurological symptoms. The duration of symptoms before admission was 1.6±1.7 (range, 0.1-6; median, 1) months (n=21).

Microorganisms
All 39 patients had microbiological evidence confirmed by one or more investigations including blood culture, culture of resected myxoma, histopathological inspection for bacteria or confirmation by polymerase chain reaction. Blood culture for microbiological isolation was positive in 37, negative in 1 and unstated in 1. Cultures of resected myxoma tissues were done in 15 patients: 9 (60%) were positive and 6 (40%) were negative. Histopathological studies of the resected myxomas were performed in 30 patients. They were histopathologically inspected for bacteria in 14 patients: 13 (92.9%) were positive and 1 (7.1%) was negative. The 41 bacteria of 39 patients were summarized in Table 4.

Treatment
Thirty-eight of 39 patients received a surgical treatment of infected cardiac myxoma and the reason that only patient did not undergo any surgical procedure was due to rapid deterioration leading to death. Of the 38 surgical operations, 30 were isolated cardiac myxoma resections, 5 were cardiac Gram-positive cocci 2  The timing for surgical operation was reported in 26 patients, 4 of them were operated on an urgent basis and 22 had a delay of 18±13.5 (range, 3-42; median, 14) days (n=21) after admission for the purpose of sufficient preoperative antibiotic treatment and stabilization of patients' conditions. Preoperative antibiotic treatment was described in 26 patients. The frequently used antibiotics included vancomycin (7 patients), penicillin (4 patients) and ampicillin (3 patients). Sometimes, they were used along with gentamicin (80 mg every 8 h). Other antibiotics were imipenem, meropenem, peperacillin, trimethoprim/ sulfamethoxazole, oxicillin, ampicillin, nafcillin, teicoplanin, azitromicine, ceftriaxone, clindamycin and amoxicillin-clavulanic acid.

Outcomes
During a follow-up period of 11.1±14.5 (0.1-58; median, 8.5) months (n=16), 37 (92.6%) patients survived and 2 (7.4%) died. Of the 37 survived patients, 35 (94.6%) were eventfree and 2 (5.4%) were complicated with ruptured saccular abdominal aortic aneurysm with renal infarct and septic emboli requiring aortoiliac bypass in one patient, and increased cerebral hematoma requiring craniotomy in another. One patient died of rupture of a right lung abscess 3 weeks after admission and the other died of disseminated intravascular coagulation on postoperative day 10. The overall mortality was 5.1% and the operative mortality was 2.6%, with a significantly reduced overall mortality in comparison with that of the patient series of Revankar & Clark (overall mortality: 5.1% vs. 21%, x 2 =4.0, P=0.047; operative mortality: 3% vs. 2.6%, x 2 =1.4, P=0.239). The overall survival rate was 92.6% (Figure 1). The survival rates of the surgical and non-surgical patients were 96.2% and 0%, respectively ( Figure 2).
The diagnosis of infected cardiac myxoma can be a challenge. The time interval from symptom onset to establishment of the diagnosis varied from 0 to 126 (median, 4) months [40] . Pathogens can be evidenced by blood culture, culture or staining of resected myxoma, and occasionally confirmation by polymerase chain reaction is helpful. The transthoracic or transesophageal echocardiography is a reliable means for the detection of a cardiac myxoma. Only in patients with rapid deterioration leading to sudden death was the diagnosis of a cardiac myxoma established by autopsy.
Comparisons between the two series revealed that the present series were characterized by few occasions of moderategrade fever (while more occasions of high-grade fever in spite of lack of a statistical significance) and abnormal heart sound, but more uncommon microorganisms and more severe complications --multiple embolic events. Other clinical features of the two patient series did not differ from each other. The somehow aggravated situations may contribute to the presence of refractory microorganisms, such as Gram-negative bacteria, fungus and actinomyce.
In comparison with Revankar & Clark's [2] series, the present series disclosed a significantly decreased overall mortality. It is believed that refinement of the prompt diagnosis and timely management (use of sensitive antibiotics and surgical resection of the infected myxoma) have resulted in better outcomes of such patients.

CONCLUSION
In conclusion, the present series of infected cardiac myxoma illustrated somehow aggravated clinical manifestations (relative more occasions of high-grade fever, multiple embolic events and the presence of refractory microorganisms), which should draw sufficient attention to be careful in the diagnosis and treatment. In general, the prognosis of infected cardiac myxoma is relative benign and now the long term survival is always promising.