Infective Endocarditis Complicated by MycoticAneurysm of a Coronary Artery With a Perforated Mitral

Valvular Aneurysm

Kazuaki Negishi, MD, Yohei Ono, MD, Koji Kurosawa, MD, Hiroto Takamatsu, MD, Akihiko Nakano, MD,Akira Hasegawa, MD, Hiroyuki Watanabe, MD, Shuichiro Takanashi, MD,

and Masahiko Kurabayashi, MD, Gunma and Tokyo, Japan

Mycotic aneurysms are well-documented complications of infective endocarditis and occur frequently in theintracranial arteries. However, mycotic aneurysms of the coronary arteries are very rare, and there are fewreports of the management of these lesions. The authors report the case of a 72-year-old woman withcoagulase-negative staphylococcal endocarditis involving a perforated aortic valve, a perforated mitral valveaneurysm, and a large mycotic coronary artery aneurysm. After antimicrobial therapy, the patient underwentopen-heart surgery with mitral and aortic valve replacement, coronary artery bypass, and resection of themycotic coronary aneurysm. The authors present detailed serial echocardiograms of the mycotic coronaryartery aneurysm, which was subsequently confirmed intraoperatively and pathologically. (J Am Soc Echocardiogr2009;22:542.e1-542.e4.)

Keywords: Infective endocarditis, Mycotic coronary aneurysm, Perforatedvalvularaneurysm, Echocardiography

Approximately 2% to 10% of patients with infective endocarditis (IE)have mycotic aneurysms; 1% to 5% of patients with IE develop aneu-rysms of the cerebral vessels.1 Coronary involvement occurs in <10%of all mycotic aneurysms that are due to IE (< 0.5% of all patients withIE).2 Thus, there are few reports on the operative management ofthese lesions. Here, we report a patient with IE with perforated aorticand mitral valves and a mycotic aneurysm of the left circumflex cor-onary artery (LCx), which caused myocardial ischemia. We presentdetailed echocardiograms of these anomalies and of the mycotic cor-onary aneurysm.

CASE REPORT

A 72-year-old, previously healthy Japanese woman was referred toour hospital for evaluation of fever of unknown origin. The patienthad been well and had not been on any regular medication until 5months earlier, when a low-grade fever of 37.0 �C and a loss of appe-tite with weight loss developed and did not resolve, despite courses ofseveral antibiotics. She had no record of any cancer or diabetes mel-litus, including impaired glucose tolerance. Her medical history wasnot significant other than dental caries. Her cardiac examination dem-onstrated no visible heaves and a normal left ventricular impulse. A

From the Department of Medicine and Biological Science, Gunma University

Graduate School of Medicine, Gunma, Japan (K.N., Y.O., K.K., H.T., A.N., A.H.,

M.K.); the Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan

(H.W.); and the Department of Cardiovascular Surgery, Sakakibara Heart

Institute, Tokyo, Japan (S.T.).

Reprint requests: Kazuaki Negishi, MD, Gunma University Graduate School of

Medicine, Department of Medicine and Biological Science, 3-39-22 Showa-cho,

Maebashi, Gunma, 371-8511, Japan (E-mail: kazz.negishi@nifty.com).

0894-7317/$36.00

Copyright 2009 by the American Society of Echocardiography.

doi:10.1016/j.echo.2009.01.020

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normal S1, physiologically split S2, and a harsh, grade IV/VI holosys-tolic murmur with thrill, diastolic rumble (Carly-Coombs murmur),and third heart sounds at the apex were present. Janeway lesionswere seen on both hands and feet. Laboratory data on admission re-vealed a white blood cell count of 11,200/ml, with 82.4% neutrophils,hemoglobin of 8.2 g/dL, and C-reactive protein of 12.2 mg/dl. Resultson chest x-ray were normal, and diuretics were not necessarythroughout the whole hospitalization period, because there wereno symptoms of heart failure.

Transthoracic echocardiography clearly showed hyperkineticcontraction of the left ventricle and normal chamber dimensions.It also clearly demonstrated a heavily thickened mitral valve (41.3� 1.4 cm), with a very mobile mass and perforated mitral valve an-eurysm, which caused severe mitral regurgitation (Figures 1A and1B). It also showed a thickened aortic valve with highly mobile veg-etation and mild to moderate aortic regurgitation. Transesophagealechocardiography (TEE) confirmed the perforated mitral valve an-eurysm. A distinct jet of color Doppler flow across the mitral valveunder the area of the vegetation suggested destructive fenestrationof the infected anterior mitral leaflet (Figures 1C and 1D). TEE alsorevealed a large aneurysm (outer diameter, 21 � 22 mm; inner di-ameter, 11 � 12 mm), with no flow detected by color Doppler, justbeneath the left atrial appendage (Figure 2A). Multidetector com-puted tomography (MDCT) visualized a large coronary aneurysmin the proximal LCx just under the left atrial appendage (Figures2B-2D)

Although repeated blood cultures could not identify the organismcausing IE, the patient was diagnosed as having IE on the basis of 1major criterion (positive echocardiographic results for IE) and 3 minorcriteria (fever, Janeway lesions, and Roth spots). Empiric therapy com-prising ampicillin 12 g/d and gentamicin 80 mg/d was administered.Repeated TEE were performed during her hospitalization. The wall ofthe coronary aneurysm became thinner and echogenicity becamehigher during antimicrobial therapy, implying that this lesion wasa mycotic aneurysm (Figure 3; Videos 1 and 2).

Because of these findings and the risk for rupture of the mycoticcoronary aneurysm, the patient was referred for open-heart surgeryafter infection was controlled. Intraoperatively, an aneurysm just be-neath the left atrial appendage was visualized. Both anterior and pos-terior mitral valve leaflets were thickened, and there was a perforatedaneurysm in the anterior mitral leaflet (Figures 4A and 4B), confirm-ing the findings on TEE. In addition, there was a perforation in thenoncoronary cusp of the aortic valve (Figures 4C and 4D), whilethe other cusps of the aortic valve were thickened and had vegeta-tions (Figure 4D). Microscopic examination demonstrated an inflam-matory infiltrate, partial calcification, and a significant amount offibrosis under the intima of both the mitral and aortic valves. Surgerywas successfully performed, including aortic and mitral valve replace-ment, coronary artery bypass to the distal LCx with a saphenous veingraft, and resection of the mycotic coronary aneurysm. Polymerasechain reaction (PCR) of ribonucleic acid prepared from the resectedspecimen revealed that the pathogen was coagulase-negative Staphy-lococcus. Thus, after the operation, an additional 6-week course of an-timicrobial therapy was administered. The patient was doing well 6months after surgery.

DISCUSSION

Causes of Mycotic Aneurysms

Several pathophysiologic events can be regarded as factors contribut-ing to the development of the mycotic coronary aneurysm in this pa-tient: (1) embolic occlusion and sterile infarction of the vasa vasorum;

Figure 1 Transthoracic (A, B) and transesophageal (C, D) echo-cardiography. (A) Apical long-axis view. The mitral valve is thick-ened (arrow). There are mobile vegetations on the valve. (B)Apical long-axis view with color Doppler. Severe mitral regurgi-tation from perforated anterior mitral leaflet (arrow). (C) Transe-sophageal image of the bulge of the anterior mitral leaflet (dottedcircle). (D) There is turbulent flow from left ventricle to left atriumthrough the perforated anterior mitral leaflet and an extensiveflow convergence area (arrow) at the left ventricular side of theaneurysm, which indicates the location of the perforation.

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(2) direct bacterial invasion of the arterial wall, particularly duringacute endocarditis; and (3) injury due to immune complex deposi-tion.3 Although there was no proven previous cardiac disease, this pa-tient may have been at risk for developing IE because of her advancedage, which predisposes to degenerative valvular disease. If this was thecase, the colonization of a nonbacterial thrombotic lesion during tran-sient bacteremia occurred on the endothelial surface of the valve, andvegetation became progressively enlarged through further depositionof fibrin, platelets, and bacteria. Then, it is likely that the enlarging veg-etation caused septic embolization of the coronary artery or of the

Figure 2 Mycotic coronary aneurysm. (A) Transesophageal0� image. Mycotic aneurysm with thick wall (arrow) is evident.(B) Multiplanar reformation image. There is a very short LCx be-tween the left main trunk of the coronary artery and the mycoticaneurysm (arrow). (C) Volume-rendered image. A mycotic aneu-rysm can be seen just beneath the left atrial appendage (LAA).(D) Maximum-intensity projection image. A mycotic aneurysmthat had formed at the proximal segment of the LCx can beseen. LAD, Left anterior descending artery; RCA, right coronaryartery.

Figure 3 Serial transesophageal echocardiographic images ofmycotic coronary aneurysm (circle). The echogenicity of the an-eurysmal wall gradually increased. The table shows the serialchanges in the internal and external aneurysm maximal diame-ters and measurements of wall thickness.

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arterial vasa vasorum, which initiated proteolysis in the arterial walland dilation of the artery. Arterial branching points favor the impac-tion of emboli and are the most common sites of mycotic aneurysmdevelopment.1 This patient developed a mycotic aneurysm at theproximal LCx, which is very close to the bifurcation of the left anteriordescending coronary artery and the LCx. An eccentric aortic regurgi-tation jet flowing toward the anterior mitral leaflet probably damagedthe endothelium of the anterior mitral leaflet and generated nonbac-terial thrombotic endocarditis, resulting in IE of the mitral valve andthe formation of a valvular aneurysm.

Management

Clinical management remains controversial, because the majority ofreported cases have been documented post mortem. Presumably,most extracranial mycotic aneurysms are prone to rupture if not ex-cised. For the majority of patients, surgical intervention representsthe only hope for a radical cure of extracranial mycotic aneurysmsand survival.1 In addition, Durak4 suggested that aneurysms >1 to2 cm in diameter are unlikely to resolve and can enlarge and eventu-ally rupture, even when the lesions have been rendered sterile withantibiotic therapy.

In this patient, with antibiotic therapy, the wall of the mycoticaneurysm became thinner and showed higher echogenicity. Thismay indicate the resolution of organizing thrombi and progressiveremodeling of the aneurysm, possibly involving the activation of ma-trix metalloproteinases and the subsequent disruption of collagen andelastin within the vessel wall. These changes likely contribute to theincreased risk for coronary artery rupture. The patient underwentdouble valve replacements because of the devastated mitral and aor-

Figure 4 Intraoperative appearance of the infected mitral andaortic valves. (A) A picture of the perforated mitral valves takenduring the operation. The probe comes from the left ventriclethrough the perforated anterior mitral leaflet (AML) (arrow). (B)Resected mitral valve. Both the AML and the posterior mitralleaflet (PML) are heavily thickened. The arrow indicates the per-forated mycotic aneurysm of the mitral valve. (C) A picture of theinfected aortic valve taken during the operation. (D) The re-sected aortic valve. All cusps are thickened. There is a perfora-tion in the right coronary cusp (arrow).

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tic valves. A simultaneous surgical procedure to replace both the in-fected valves and the mycotic coronary artery was planned andperformed.

The timing of surgical intervention was also a challenging problem.Because of the rarity of the condition, limited reports are available.The later the operation is performed, the higher the risk for comorbid-ities, such as embolic events and heart failure. However, the earlier theoperation is performed, the more fragile the surrounding structures ofthe lesions are. We operated on the patient after the infection hadbeen almost fully controlled, because she did not have any complica-tions other than lateral myocardial ischemia.

Despite repeated blood cultures, the previous use of intravenousantibiotics may make it difficult to elucidate the pathogen, even afterthe discontinuance of antibiotics. However, we could identify coagu-lase-negative Staphylococcus as the pathogen in this patient by PCR ofribonucleic acid prepared from the resected culture-negative speci-men. This particular patient underwent an additional 6-week courseof antibiotic therapy after the pathogen had been detected by PCRbecause Staphylococcus bacteremia remains a disease with high mor-tality and morbidity. PCR of the resected tissue may be a very effec-tive way of detecting what the pathogen is, even after patients havebeen treated with antibiotics.5

Diagnosis

To date, only 4 prior cases of mycotic aneurysm of the coronary arterydiagnosed by TEE have been reported in the literature,6-9 eventhough TEE has been performed in most patients with IE, as recom-mended by guidelines.10 Although MDCT can provide clear 3-di-mensional anatomical information, it may cause radio contrastagent–induced nephropathy, especially in patients with renal dys-function, which is known to be one of the major complications ofIE. However, TEE does not need any contrast agent and can be per-formed repeatedly, even in such patients. As was shown by this case,correlating the findings of TEE and MDCT is of prime importance inthe detection of these rare manifestations of IE. Rapid diagnosis, effec-tive treatment, and the prompt recognition of complications are es-sential for good patient outcomes.

CONCLUSION

This case indicates the need to be aware of mycotic aneurysms of thecoronary artery as an uncommon but potentially serious cause ofmyocardial ischemia in patients with IE. Serial TEE can provide accu-rate information about the changes in wall thickness of the aneurysmsthat cannot be obtained by MDCT.

REFERENCES

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2. Reece I, Tareif H, Tolia J, Saeed F. Mycotic aneurysm of the left anterior de-scending coronary artery after aortic endocarditis. Texas Heart Inst J 1994;21:231-5.

3. Weinstein L, Schlesinger JJ. Pathoanatomic, pathophysiologic and clinicalcorrelations in endocarditis (second of two parts). N Engl J Med 1974;291:1122-5.

4. Durak DT. Infective and noninfective endocarditis. In: Hurst JW, editor.The heart, arteries and veins. New York: McGraw-Hill; 1990:1130-57.

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5. Goldenberger D, Kunzli A, Vogt P, Zbinden R, Altwegg M. Moleculardiagnosis of bacterial endocarditis by broad-range PCR amplificationand direct sequencing. J Clin Microbiol 1997;35:2733-9.

6. Tunik P, Slater J, Pasternacl P, Kronzon I. Coronary artery aneurysms:a transesophageal echocardiographic study. Am Heart J 1989;118:176-9.

7. Quinn V, Baloch Z, Chandrasekaran K, Ross J, Karalis D. Coronary arteryaneurysm masquerading as a paracardiac mass on transesophageal echo-cardiography. Am Heart J 1994;127:441-3.

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8. Kapur N, Conte J, Wittstein. Successful management of an unrupturedmycotic coronary aneurysm. J Invas Cardiol 2007;19:E366-8.

9. Kunavarapu C, Olkovsky Y, Lafferty J, Homayuni A, Mohan S, McGinn J.Unusual cardiac complications of Staphylococcus aureus endocarditis.J Am Soc Echocardiogr 2008;21:187.e3-5.

10. Baddour L, Wilson W, Bayer A, Fowler V, Bolger A, Levison M, et al. In-fective endocarditis. Diagnosis, antimicrobial therapy, and managementof complications. Circulation 2005;111:e394-443.

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