CASE REPORTEuropean Heart Journal - Case Reports
doi:10.1093/ehjcr/ytz171

Cardiac imaging

Shiro Miura

1*, Masanao Naya

2

, Takehiro Yamashita

1, and Youhei Ohkawa

3

1
Department of Cardiology, Hokkaido Ohno Memorial Hospital, 2-1-16-1 Miyanosawa, Nishi-ku, Sapporo 063-0052, Japan; 2Department of Cardiovascular Medicine, Hokkaido,
University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan; and 3Department of Thoracic and Cardiovascular Surgery, Hokkaido Ohno Memorial
Hospital, 2-1-16-1 Miyanosawa, Nishi-ku, Sapporo 063-0052, Japan

Received 19 March 2019; first decision 20 May 2019; accepted 17 September 2019

Background

Prosthetic valve endocarditis (PVE) is a life-threatening systemic infection involving a high mortality rate and severe
complications, including perivalvular abscess. Early diagnosis and detection of PVE continue to be challenging in clinical settings.

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Case summary A 64-year-old man with a history of mechanical aortic valve implantation 12 years prior was referred to our hos-pital with a major complaint of high fever and was admitted. Although results of three blood culture tests at
admission were negative, transthoracic echocardiography, and transoesophageal echocardiography (TOE) were
performed to exclude the possibility of PVE; both, however, were inconclusive. Subsequently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was performed; revealing intense
hyper-metabolism above the aortic valve prosthesis with a greater intensity at the posterior end, confirming a diagnosis of aortic PVE complicated with perivalvular abscess.

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Discussion
Considering the intermediate suspicion of PVE despite negative TOE and negative blood culture tests, 18F-FDG
PET/CT can play a central role in diagnosing PVE. However, this new imaging modality often fails to differentiate
thrombi, soft atherosclerotic plaques, or foreign body reactions on the surface of prosthetic valves. In this report,
we have successfully enhanced the diagnostic accuracy of 18F-FDG PET/CT by focusing on perivalvular involvement,
which could be a key finding, because intense 18F-FDG uptake surrounding the aortic annulus was consistent withthe thickened area within the aortic annular region observed in the TOE examinations.
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Keywords

Case report • Endocarditis • Perivalvular abscess • Positron emission tomography* Corresponding author. Tel: þ81 11 665 0020, Fax: þ81 11 665 0242, Email: s.miura@ohno-kinen.or.jp
Handling Editor: Timothy C. Tan
Peer-reviewers: Didem Oguz, Marco De Carlo, and Dejan Milasinovic
Compliance Editor: Mohammed Majid Akhtar
Supplementary Material Editor: Ross Thomson
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
V

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestrictedreuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Usefulness of 18F-fluorodeoxyglucose positronemission tomography/computed tomography
angiography in a patient with blood
culture-negative prosthetic valve
endocarditis complicated withperivalvular abscess: a case report

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S. Miura et al.

Learning points
echocardiography, particularly in patients with low-to-intermediate probability for PVE based on the modified Duke criteria.

• We describe a case of PVE complicated by perivalvular abscess where the combination of 18F-fluorodeoxyglucose positron emission tomography and computed tomography angiography aided in the diagnosis of PVE and its complications, shedding light on the additional rolesof the new imaging modalities.

Introduction
Definitive diagnosis of prosthetic valve endocarditis (PVE) is clinically challenging because of its varying clinical presentation, microorganisms involved and patient profile. Prosthetic valve
endocarditis entails high initial mortality and morbidity rates witha high risk of complications, including perivalvular abscess and fistulae during follow-up and often requires surgical intervention.1
Therefore, the diagnosis and management of PVE necessitates acollaborative approach involving cardiologists, infectious disease
physicians, cardiac imaging specialists, cardiovascular surgeons,and microbiologists.2
Recently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been
advocated as an alternative diagnostic imaging modality for PVE,
particularly when echocardiography and blood culture results
are inconclusive in reaching a definitive PVE diagnosis. 3
Furthermore, 18F-FDG PET/CT can detect distant emboli, metastatic infections and perivalvular involvement along with coronary anatomy when combined with CT coronary angiography. 4
Additionally, complementary information obtained from less invasive tests are vital for patients with PVE who require early surgery. Herein, we present a challenging case of PVE complicatedwith perivalvular abscess.

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Case presentation
A 64-year-old man presented to our outpatient clinic with complaints of general fatigue and high fever (>38 C) at night that persisted for 3 days. He had previously undergone 25-mm mechanicalaortic valve implantation (St. Jude Medical Regent; St. Jude Medical,
Inc., St. Paul, MN) 12 years prior because of severe aortic regurgitation. Upon examination, no focus of infection could be identified, andhe was admitted to our heart centre to exclude the possibility of
PVE. After three sets of blood culture were obtained, intravenous
ceftriaxone (2 g/day) was empirically initiated. Initial transthoracic
echocardiography (TTE) revealed no dysfunction of the mechanicalaortic prosthesis, and whole-body CT revealed no embolic events.
The patient recovered to a low-grade fever (37–38 C) 48 h after the
initial antibiotics therapy and showed improved C-reactive protein
level (from 13 to 6.3 mg/dL) in the first 5 days. Subsequently, transoesophageal echocardiography (TOE) performed on the 5th day of
hospitalization revealed a 6–11 mm mobile echogenic mass attachedto the prosthetic valve and a thickened area within the posterior annular region with a low echogenic appearance at the level of the noncoronary sinus of Valsalva (Figure 1). At this point, the patient met
two minor diagnostic criteria (predisposing heart condition of prior
prosthetic valve implantation and high fever) in the modified Duke
diagnostic criteria for infective endocarditis because the TOE findings
were considered inconclusive. Subsequently, combined 18F-FDG
PET/CT and CT coronary angiography revealed intense hypermetabolism above the aortic valve prosthesis with greater intensity atTimeline

12 years before admission
3 days before admission

25-mm mechanical aortic valve implantation owing to severe aortic regurgitation.
Fever at night and general fatigue initiated.

Day of admission

Initial transthoracic echocardiography revealed no dysfunction of the mechanical aortic prosthesis, and no embolic
events were detected on the whole-body computed tomography (CT). Three blood culture tests were performed
and intravenous antibiotic therapy with ceftriaxone (2 g/day) was initiated.

Hospital Day 5

Transoesophageal echocardiography was inconclusive and fever persisted.

Hospital Day 8

All blood culture tests were negative. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT revealed considerable uptake of 18F-FDG surrounding the aortic annulus; intensive antibiotic therapy was initiated with intraven-

Hospital Day 14

The infected prosthetic valve was surgically replaced with a 25-mm bioprosthesis with extensive debridement of perivalvular abscess.

Hospital Day 51

The patient was discharged well.

6 months after discharge

A 6-month of outpatient oral antibiotic therapy with amoxicillin (750 mg/day) was completed without any recurrences.

ous ampicillin (8 g/day) and gentamicin (180 mg/day).

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• Prosthetic valve endocarditis (PVE) can often be a major diagnostic challenge owing to the difficulties in the interpretation of conventionalUsefulness of 18F-FDG PET/CT angiography in a patient

the posterior end and absence of obstructive coronary artery, thereby confirming the diagnosis of aortic PVE complicated with perivalvular abscess (Figure 2). Following a comprehensive discussion with theendocarditis team, including an infectious disease specialist, a microbiologist (pathologist) and cardiovascular surgeons, we decided toswitch from intravenous ceftriaxone to appropriate antibiotic therapy [intravenous ampicillin (8 g/day) and gentamicin (180 mg/day)] forblood culture-negative patients with PVE based on the current ESC
guideline5 and withheld specific serological tests or polymerase chain
reaction (PCR) assays for unusual but potential microorganisms aslong as the patient’s clinical course was not out of track and the antibiotics therapy appeared clinically effective. Following 1 week of intensive antibiotic treatment, we finally decided to perform surgery
mainly because the PVE was complicated with perivalvular abscess, asevidenced by 18F-FDG PET/CT with all negative blood culture tests.
On the 14th day of hospitalization, prosthetic valve was surgicallyreplaced with a 25-mm bioprosthesis (25A TrifectaTM; St. Jude
Medical, Inc., St. Paul, MN, USA) with extensive debridement of theinfected and necrotic tissues surrounding the aortic annulus (Figure
3A and B). Surgically excised tissue was subjected to microbiologicaland pathological analysis; however, no evidence of bacterial organisms was found (Figure 3C and D) and blood culture tests were negative. Post-operative TTE revealed a normally functioning aortic valve,and he was discharged on the 51st day. Based on the internationalguideline,5 antibiotic therapy was continued for 6 weeks until hospitaldischarge, although gentamicin was discontinued in the first 3 weeks
because of nephrotoxicity. Furthermore, intravenous antibiotic treatment was followed by 6-month outpatient oral antibiotic therapy
with amoxicillin (750 mg/day) without any recurrences.

Discussion
The modified Duke criteria have been recommended for PVE diagnosis since its proposal by Durack et al.6 Notwithstanding the presence

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of well-established clinical criteria, PVE diagnosis poses some challenges. There is a common concern regarding the interpretation of
echocardiographic findings, despite TTE or TOE being the primary
diagnostic approach.7 As observed in the patient in this study, echocardiographic findings can often be inconclusive, which can be primarily attributed to the similar appearance of both the thrombus andpannus on the prosthetic valves, which cannot be distinguished fromvegetation.7 This inconclusive diagnosis can lead to difficulty or delay
in surgical decisions, particularly in patients with low-to-intermediate
likelihood of PVE, such as those with negative blood culture tests.
18
F-fluorodeoxyglucose positron emission tomography/computed
tomography is an established diagnostic modality in patients with suspected PVE that is used when conventional diagnostic tools fail toprovide a definitive diagnosis.5 In the present patient, perivalvular involvement was a key observation because intense 18FDG uptake
confined to the aortic annulus above the prosthesis as revealed by
18
F-FDG PET/CT images was compatible with the thickened area
within the aortic annular region observed in TOE examinations,
implying perivalvular abscess formation. Additionally, detecting perivalvular involvement by utilizing 18F-FDG PET/CT allowed us to improve the diagnostic accuracy of PVE.
As a preoperative risk assessment, CT angiography is more advantageous and safer than invasive coronary angiography in PVE cases
involving the aortic valve because invasive coronary angiography potentially involves risks of vegetation embolization or haemodynamic
decompensation. Also, CT angiography can provide further information on the valve size, anatomy, and calcification of aortic valve, which
are essential for surgical planning.8 Furthermore, compared with the
TOE findings, the combination of PET and CT angiography enhances
the accuracy of identification of the infected location, in addition to
the delineation of coronary anatomy and detection of fistulae and abscess, distal embolic complications and infected aneurysms at othersites.4
Another important case discussion was on how to manage theblood culture-negative patient with PVE with appropriate antibiotic
therapy and/or surgical intervention if needed. The patient was initially treated with ceftriaxone in empirical therapy for unexplained fever
following three sets of blood culture tests. Although the patient’s
condition stabilised in the first week, with improvement in fever andgeneral appearance, we switched ceftriaxone to intravenous ampicillin and gentamicin because the findings of 18F-FDG PET/CT imaging
were highly suggestive of PVE. These antibiotic regimens for initial
empirical treatment of late PVE were determined based on the current ESC guideline5 and consultation with the endocarditis team. In a
recent review,9 Viridans group streptococci, coagulase-negative staphylococci (CNS), Enterococcus spp. and Streptococcus bovis were reported
to be the most common pathogens in patients with PVE. We carefully selected a combination of ampicillin and gentamicin to mainly treat
staphylococci, streptococci, and enterococci. We assumed that thepatient’s clinical course was relatively subacute and less destructivewith no major complications such as heart failure and systematic embolism and ceftriaxone seemed to be clinically effective. Considering
this, PVE triggered by Staphylococcus aureus or CNS was slightly lesslikely to occur in the patient. Blood culture-negative infective endocarditis (BCNIE) can be caused by fungi or fastidious slow-growing
bacteria, notably obligatory intracellular bacteria.1 Among them,

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Figure 1 Transoesophageal echocardiography showing a thickened area along the aortic root behind the non-coronary sinus of
Valsalva (arrowheads) and a mobile echogenic mass attached to theprosthetic valve leaflet (arrow).

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S. Miura et al.

Figure 3 (A) Visualization of the mobile vegetation attached to the aortic mechanical prosthesis (arrow). (B) Surgical view of an aortic perivalvularabscess (arrow). (C) Haematoxylin–eosin (H&E)-stained histological section of the mobile vegetation attached to the aortic mechanical prosthesis
showing fibrin-rich thrombi and infiltration of neutrophils and macrophages without any evidence of bacteria or tumour tissue. (D) Magnified H&Estained section of mobile vegetation (square in C) showing microorganisms that were absent in the thrombotic vegetation.

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Figure 2 (A) 18F-fluorodeoxyglucose positron emission tomography/computed tomography showing significant 18F-fluorodeoxyglucose uptake(arrowheads) at the level of the mechanical aortic valve with inhibition of the rest of the cardiac metabolism, indicating perivalvular abscess. (B) The
combination of 18F-fluorodeoxyglucose positron emission tomography and computed tomography angiography provides additional information
regarding the accurate location of the vegetation behind the valve surface (arrow) and distribution of the affected perivalvular tissue (arrowheads), in
addition to characterizing the coronary arteries, aortic valve, root, and ascending aorta. LMCA, left main coronary artery; RCA, right coronary artery.

Usefulness of 18F-FDG PET/CT angiography in a patient..
.. Supplementary material..
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.. Supplementary material is available at European Heart Journal - Case.. Reports online.
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.. Slide sets: A fully edited slide set detailing this case and suitable for..
.. local presentation is available online as Supplementary data.
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.. Consent: The author/s confirm that written consent for submission.. and publication of this case report including image(s) and associated..
.. text has been obtained from the patient in line with COPE guidance.
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.. Conflict of interest: none declared.
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Lead author biography
Dr Shiro Miura is working as a chiefinterventional cardiologist at one of
the most outstanding cardiovascular
centers in Hokkaido in Japan named
Hokkaido Ohno Memorial Hospitalwith remarkable achievements specializing in interventions on ischemic
heart diseases and structural heartdisease in the management of inpatients and outpatients with heart
failure following the postgraduate
course named ‘MSc Statistics with Applications in Medicine’ in
University of Southampton in the UK where I was rewarded the
Dean’s List Awards for exceptional performance for both the regularterm exams and final dissertation.

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nutritionally variant Streptococcus spp. and HACEK (Haemophilus,
Aggregatibacter, Cardiobacterium, Eikenella, and Kingella) could be
the potential causative microbes in the present case; therefore, we
selected a combination of ampicillin and gentamicin for treatment
based on the local epidemiology. Indeed, we were ready to performsystemic serological testing for less common microorganisms in
BCNIE patients, such as Coxiella burnetii, Bartonella spp., Aspergillus
spp., Mycoplasma pneumonia, Brucella spp., and Legionella pneumophila,
followed by specific PCR assays. However, we kept the samples anddid not perform these tests because the patient’s condition had gradually recovering after the initiation of intravenous ampicillin and gentamicin during the whole hospital stay, including the perioperative
period. Additionally, both the blood and tissue PCR tests, which are
not covered by Japan’s national health insurance, generally take a considerable amount of time and cost. A 6-month outpatient oral antibiotic therapy was completed because we emphasized on theremarkable findings: PVE was complicated with perivalvular abscessformation and unidentified microorganisms.
In summary, we report a case regarding a patient with blood
culture-negative PVE complicated with perivalvular abscess, with alow-to-intermediate likelihood of PVE based on the modified Duke
criteria, in whom 18F-FDG PET/CT successfully provided a definitive
diagnosis of perivalvular abscess and infective endocarditis, leading tosubsequent surgical intervention within an appropriate timeframe.

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