Integration of ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Diagnostic Algorithm of Prosthetic Valve Endocarditis: A Case Report and Review of Literature

Introduction

Prosthetic valve endocarditis (PVE) is a potentially life-threatening complication with an annual incidence of 0.3%–1.2% and accounting for about 25% of all cases of infective endocarditis (IE).[1] Aortic valve is most commonly involved (66.5%), followed by mitral (40.7%), tricuspid (2.9%), and multiple valves (7.2%).[2] PVE is usually bacterial, with fungal infection accounting for only 4% cases.[3] ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography- computed tomography (PET-CT) has shown utility in diagnosis of IE, especially PVE.[4] Positive ¹⁸F-FDG PET-CT has been inducted as a major criterion for IE diagnosis in the European Society of Cardiology (ESC) guidelines.[5] We present a case of fungal PVE, where ¹⁸F-FDG PET-CT played an important role in management and review the available literature in this regard.

Case Report

A 58-year-old man presented at our hospital with palpitation and chest discomfort. There was no fever. He had a history of mitral valve replacement with a bioprosthetic valve, 9 years back. He was diabetic and hypertensive, relatively well controlled with oral medications. Blood tests showed normal total leukocyte count (5400/ml, normal: 4000–10,000), raised C-reactive protein (1.7 mg/L, normal <0.5), raised serum procalcitonin (1.3 ng/ml, normal <0.5), and elevated brain natriuretic peptide (845.7 pg/ml, normal <100). Electrocardiogram showed atrial fibrillation. Transthoracic echocardiography (TTE) showed post mitral valve replacement status, with some suspicion of vegetations, mild pulmonary arterial hypertension, and normal cardiac function (ejection fraction 60%). Transesophageal echocardiography (TEE) was then performed which showed multiple mobile masses attached to the bioprosthetic mitral valve with out-of-phase motion and severe mitral stenosis. With suspicion of IE, multiple aerobic and anaerobic blood cultures were sent, all were negative. Based on Duke Criteria,[6] a diagnosis of possible PVE was made (one major and one minor criteria). The cardiologist then advised cardiac ¹⁸F-FDG PET-CT for further evaluation. The patient was prepared with a combination of 24 h of low carbohydrate and fat rich diet, 12 h fasting and intravenous unfractionated heparin (50 IU/kg, 15 min before ¹⁸F-FDG), to suppress physiological myocardial ¹⁸F-FDG uptake.[7] Cardiac PET-CT [Figure 1, arrows] showed a focal area of increased ¹⁸F-FDG uptake in the region of the prosthetic valve (SUV_max 5.3, blood pool 2.0). No periannular uptake was seen. The uptake was not visually different on nonattenuation corrected PET images. As the patient did not have any features of septic embolism, whole body imaging was not performed. Based on ¹⁸F-FDG PET-CT findings and ESC 2015 guidelines,[5] a diagnosis of PVE was made. The patient underwent a redo mitral valve replacement with mosaic porcine bioprosthesis. Culture of the removed prosthetic valve showed growth of Candida albicans, sensitive to amphotericin and fluconazole. The patient was given 2 weeks of intravenous amphotericin B and then discharged in stable condition on oral fluconazole. He was doing fine with a 3 years' follow-up.

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Figure 1 Transaxial (a), coronal (b) and sagittal (c) noncontrast computed tomography images show the mitral prosthetic valve (arrow). On transaxial (d), coronal (e) and sagittal (f) positron emission tomography, and transaxial (g), coronal (h), and sagittal (i) fused positron emission tomography-computed tomography images, focal increased ¹⁸F-fluorodeoxyglucose uptake is seen in the prosthetic valve (arrow, SUV_max 5.3), suggestive of prosthetic valve endocarditis. Post removal culture from the prosthetic valve showed growth of Candida albicans

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Discussion

PVE is a dreaded complication of valve replacement. Although data are conflicting, risk of PVE is considered higher for bioprosthetic valves compared to mechanical valves.[8] PVE is classified into two temporal groups, early PVE, occurring within 1 year (usually 2 months) of replacement, usually caused by nosocomial microbes such as Staphylococci, Gram-negative bacilli, and Candida, and late PVE, occurring beyond 1 year, usually caused by Streptococci, Staphylococcus aureus, Enterococci, and Fastidious Gram-negative bacteria.[3] The former is associated with infection of surrounding tissue, causing perivalvular abscess and paravalvular leak. The latter is associated with formation of platelet-fibrin thrombi on the valve leaflet, later seeded with microbes.[9] Therefore, differentiation of bland thrombi from infected vegetation is important from a clinical perspective, even more so, if classical pictures of IE are absent and blood cultures are negative, as was in the present case.[10] PVE caused by Candida is more sinister, has subacute presentation, large vegetations, poor yields from blood culture and needs aggressive management with redo valve replacement and antifungals.[11] The same management strategy was followed in the present case.

A positive blood culture along with suggestive imaging, forms the basis for PVE diagnosis.[1] Blood culture is positive in a large proportion of PVE patients, but can be negative in early disease, after antibiotic therapy, or if caused by fastidious bacteria and fungus, as in the present case. The imaging modalities for PVE include TTE, TEE, CT, and PET-CT.[3] While TTE is safe, cheap and widely available, it is dependent on the operator and imaging window, and has overall poor sensitivity, but high specificity. TEE is also relatively safe and widely available, has high sensitivity and specificity, and is usually the preferred imaging for PVE. Unfortunately, it also suffers from the drawbacks of operator and imaging window dependence. Multislice CT is moderately sensitive and specific for PVE, and allows assessment of coronary arteries in the same setting, but is costlier and also entails radiation exposure, unlike TTE or TEE. It can also show artefacts because of the valve.

¹⁸F-FDG PET-CT is an important supplementary diagnostic method in cases of PVE.[12] A detailed overview of available literature pertaining to the role of ¹⁸F-FDG PET-CT in PVE is presented in Table 1.[1314151617181920212223242526272829] A recent meta-analysis by Wang et al.[30] showed a pooled sensitivity of 80.5% (95% confidence interval [CI] 74.1%–86.0%) and specificity of 73.1% (95% CI 63.8–81.2%) in PVE. In addition, if the whole body PET-CT is performed it can pick up additional extra-cardiac septic foci in about 17% of patients.[3132] Abnormal focal ¹⁸F-FDG uptake at the site of prosthetic valve (implanted more than 3 months before) is now a major criterion, which significantly increases the sensitivity of the modified Duke Criteria from 70% to 97% without changing the specificity.[13] It is especially useful in the category of “possible IE.” While semi-quantitative analyses have been performed by many authors, visual analysis of PET-CT is as accurate and should be compared with the cardiac blood pool, traditionally in the right atrium. Care must be taken for adequate preparation of patients with different combinations of fasting, carbohydrate restricted fat rich diet and heparin, so as to optimally suppress the physiological myocardial ¹⁸F-FDG uptake, which can interfere with image interpretation in PVE. Familiarity with patterns of ¹⁸F-FDG uptake in normal prosthetic valves is also essential.[33] Normal uptake is usually mild to moderate, homogeneous, periannular, and less marked in non-attenuation corrected PET images. Intense normal uptake can be seen around recently implanted valves, up to 3 months. The barriers to routine use of ¹⁸F-FDG PET-CT in PVE are its limited availability, higher cost and risk of radiation exposure. Apart from ¹⁸F-FDG, a wide array of radiopharmaceuticals have been used for infection imaging [Table 2].[34] Of particular interest in PVE is leukocyte imaging.[15] The advantages of leukocyte imaging over ¹⁸F-FDG PET-CT are its high specificity for the diagnosis of infective foci and lack of confounding physiological uptake in myocardium. On the negative side radiolabeling of leukocytes is a laborious and time consuming process, carries risk of handling blood products, and total imaging time is very long. In addition, the low spatial resolution of gamma imaging compared to PET is also a drawback reducing sensitivity, though that can be overcome using ¹⁸F-FDG labeled leukocytes.

In conclusion, ¹⁸F-FDG PET-CT shows high accuracy for diagnosis of PVE and should be integrated in the diagnostic algorithms. It is especially useful in cases where other tests are equivocal and those with diagnosis of “possible IE” based on Duke Criteria.