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Infective Endocarditis and Cardiovascular Implantable Electronic Device Infection

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Radionuclide Imaging of Infection and Inflammation

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Abstract

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient’s management, as early treatment improves the prognosis. Cardiovascular infections are difficult to diagnose on the basis of a single symptom, sign, or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices, while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. This chapter describes the main epidemiological, clinical, and diagnostic challenges in infective endocarditis and infections associated with cardiovascular implantable electronic devices, with particular regard to the role of WBC SPECT/CT and [18F]FDG PET/CT in each diagnostic algorithm. In addition, the needs of proper hybrid equipment, dedicated imaging acquisition protocols, specific expertise for imaging reading and imaging interpretations in this field are discussed, emphasizing the need of a specific reference framework within a cardiovascular multidisciplinary team approach.

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Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

    Martina Sollini

  2. Humanitas Clinical and Research Center - IRCCS, Rozzano, Italy

    Martina Sollini

  3. Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

    Francesco Bandera

  4. Cardiology University Department, Heart Failure Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

    Francesco Bandera

  5. Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy

    Francesco Bartoli, Roberta Zanca & Paola Anna Erba

  6. Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy

    Elena Lazzeri & Paola Anna Erba

Authors
  1. Martina Sollini
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  2. Francesco Bandera
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  3. Francesco Bartoli
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  4. Roberta Zanca
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  5. Elena Lazzeri
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  6. Paola Anna Erba
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Corresponding author

Correspondence to Paola Anna Erba .

Editor information

Editors and Affiliations

  1. Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy

    Elena Lazzeri

  2. Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University of Rome, Roma, Italy

    Alberto Signore

  3. Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy

    Paola Anna Erba

  4. Nuclear Medicine Department, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

    Napoleone Prandini

  5. Nuclear Medicine, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Annibale Versari

  6. Nuclear Medicine Department, Private Hospital “PIO XI”, Roma, Italy

    Giovanni D´Errico

  7. Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy

    Giuliano Mariani

Clinical Cases

Clinical Cases

9.1.1 Case 9.1

9.1.1.1 Background

A 52-year-old man was hospitalized for deep vein thrombosis of the right lower limb presenting as acute compartment syndrome, and underwent emergency fasciotomy. This treatment failed, and right limb amputation had to be subsequently performed. About 3 years prior to this acute episode, the patient had been submitted to the replacement of the aortic valve and ascending aorta. After the amputation, he experienced raise of C-reactive protein (CRP) and fibrinogen (10.4 mg/dL and 648 mg/dL, respectively); pro-calcitonin was in the normal range, and blood cultures were negative. TTE did not show any abnormality. Despite negativity of blood cultures and TTE, empiric antimicrobial treatment was started based on the high clinical suspicious of infection, and TEE was planned, which showed mild aortic valve regurgitation. Since the patient presented one major and one minor criteria, he was classified as possible IE with persisting high suspicious of infection; as recommended by the latest ESC 2015 Guidelines, he was therefore referred for molecular imaging. [18F]FDG PET/CT (Fig. 9.4) confirmed the suspicious of IE, showing high tracer uptake on the prosthetic aortic valve. Empiric antimicrobial treatment was continued and after 2 months, when both CRP and fibrinogen were in the normal range, he underwent a follow-up [18F]FDG PET/CT scan (Fig. 9.5) during therapy. The 2-month follow-up scan confirmed the presence of prosthetic valve endocarditis and showed additional infection involving soft tissues of the right amputation stump.

Fig. 9.4
figure 4

[18F]FDG PET/CT in a patient with prosthetic valve endocarditis. The MIP image (a) shows increased [18F]FDG uptake in the mediastinum and at the right amputation stump. (b) Transaxial fused PET/CT sections. (c) Coronal sections (PET left; CT middle; fused PET/CT right). Intense [18F]FDG uptake at the prosthetic valve is clearly detectable indicating IE. The moderate and diffuse tracer uptake at the right amputation stump suggests post-surgical inflammation

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Fig. 9.5
figure 5

Follow-up [18F]FDG PET/CT scan in the same patient as in Fig. 9.4, with prosthetic valve endocarditis and infection of amputation stump. (a) The MIP image shows increased [18F]FDG uptake in the mediastinum and in the lateral side of the right amputation stump. The transaxial fused PET/CT (b) and coronal (c) images (PET, left; CT, middle; fused, right) confirm intense [18F]FDG uptake at the prosthetic valve, almost unchanged from the previous examination. The focal area of increased [18F]FDG uptake in the lateral side of the right amputation stump suggests spread of infection to the soft tissues of the knee, as shown by axial fused images (d). The moderately increased tracer uptake at the right groin (indicated by “asterisk”) is related to muscular uptake

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9.1.1.2 Suspected Site of Infection

PVIE.

9.1.1.3 Radiopharmaceutical Activity

[18F]FDG, 295 MBq.

9.1.1.4 Imaging

The acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

9.1.1.5 Conclusion/Teaching Point

[18F]FDG PET/CT identified the presence of IE, was helpful to monitor response to treatment, and identified an additional, unexpected site of infection. [18F]FDG PET/CT is highly sensitive also during antimicrobial treatment.

9.1.2 Case 9.2

9.1.2.1 Background

A 60-year-old obese woman with aortic valve prosthesis went to the emergency department for chest pain and fever. IE was suspected due to the presence of fever associated to relevant cardiac risk factors (prosthetic valve). Blood cultures were positive for Staphylococcus epidermidis. TEE showed a doubtful image on the prosthetic valve, suspected for IE but inconclusive. [18F]FDG PET/CT (Fig. 9.6) showed an area of focal tracer uptake at the aortic valve prosthesis, and a large lesion in the spleen characterized by a “hot” rim surrounding a “cold” core. Overall, these findings were suggestive for prosthetic valve endocarditis with splenic septic embolism.

Fig. 9.6
figure 6

The [18F]FDG PET/CT MIP image (a) shows an area of mildly increased focal uptake in the cardiac region and a lesion in the spleen. Axial fused sections (b) confirm an area of focal uptake which involves the aortic valve prosthesis, indicating IE. (c) Axial (PET, upper; CT, middle; fused PET/CT, bottom) and (d) coronal (PET, left; CT, middle; fused PET/CT, right) sections show a large lesion in the spleen characterized by a “hot” rim surrounding “cold” core, suggesting septic embolism (abscess)

Full size image

9.1.2.2 Suspected Site of Infection

Prosthetic valve endocarditis.

9.1.2.3 Radiopharmaceutical Activity

[18F]FDG, 347 MBq.

9.1.2.4 Imaging

The acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

9.1.2.5 Conclusion/Teaching Point

[18F]FDG PET/CT identified the presence of IE with associated splenic septic embolism.

9.1.3 Case 9.3

9.1.3.1 Background

A 70-year-old woman with aortic and mitral valve prosthesis went to the emergency department for persistent fever unresponsive to antimicrobial treatment. Lab tests raised the suspicion of infection, with high C-reactive protein (38 mg/dL), and fibrinogen (521 mg/dL). Blood cultures were negative. TTE was negative. A doubtful image suspected for vegetation at the aortic valve was detected on TEE. Accordingly, the patient was referred for [18F]FDG PET/CT (Fig. 9.7), which showed increased tracer uptake at both prosthetic valves. A 99mTc-HMPAO-labeled-WBC scintigraphy (Fig. 9.8) confirmed with the presence of IE involving both the aortic and the mitral prosthetic valves. Nonetheless, the disease burden identified by 99mTc-HMPAO-WBC scintigraphy was lower compared to [18F]FDG PET/CT.

Fig. 9.7
figure 7

The [18F]FDG PET/CT MIP image (a) shows two ring-like areas of increased the tracer uptake in the cardiac region. Transaxial fused PET/CT sections (b) demonstrates involvement of both the aortic and the mitralic valve prosthesis

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Fig. 9.8
figure 8

(a) 99mTc-HMPAO-WBC planar images (anterior views in the left panels, posterior views in the right panels) of the thorax at 30 min, 4 h, and 20 h (from top to bottom), showing a mild time-dependent increase of radioactivity accumulation in the lower third of the sternum. Fused transaxial SPECT/CT sections acquired at 4 h (b) and at 20 h (c), showing increased WBC accumulation at both the aortic and the mitral valve prosthesis

Full size image

9.1.3.2 Suspected Site of Infection

Prosthetic valve endocarditis.

9.1.3.3 Radiopharmaceutical Activity

[18F]FDG, 202 MBq; 99mTc-HMPAO-WBC, 740 MBq.

9.1.3.4 Imaging

The PET/CT acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

99mTc-HMPAO-WBC scintigraphy: planar images of the thorax acquired at 30 min, 4 h and 20 h. SPECT/CT imaging of the thorax at 4 h and 20 h, with 3D reconstruction.

9.1.3.5 Conclusion/Teaching Point

Both [18F]FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT allow identification of blood culture-negative prosthetic valve endocarditis. 99mTc-HMPAO-WBC scintigraphy requires SPECT/CT acquisition in suspected cardiovascular infection. As expected, 99mTc-HMPAO-WBC scintigraphy is more accurate than [18F]FDG PET/CT for defining the infection burden.

9.1.4 Case 9.4

9.1.4.1 Background

An 81-year-old man had been submitted to ICD implant several years before being referred to the emergency department because of dyspnea and fever. Lab tests showed increased C-reactive protein (1.2 mg/dL, normal value <0.5 mg/dL) and erythrocyte sedimentation rate (85 mm/h, normal value <30 mm/h). Blood cultures were positive for Staphylococcus aureus, but both transthoracic and TEE excluded the presence of vegetation or any other signs of IE. Because of high clinical suspicion of ICD-related IE, the patient was referred for [18F]FDG PET/CT (Fig. 9.9), which showed high [18F]FDG uptake at the ICD generator pocket, along the EC, and in the right lung; this pattern was consistent with CIED infection with lung embolism. Small bilateral axillary lymph nodes exhibited faint, nonspecific tracer uptake.

Fig. 9.9
figure 9

The [18F]FDG PET/CT MIP image (a) shows increased tracer uptake in the upper region of the left hemithorax. (b) Coronal sections (PET, left; CT, middle; fused PET/CT, right) show intense and diffuse [18F]FDG uptake at the ICD pocket, in the left hemithorax. (c) Transaxial fused sections confirm the presence of ICD pocket infection, EC involvement and a hot spot in the upper lobe of right lung, classified as lung embolism; faint [18F]FDG uptake is detectable also in small bilateral axillary lymph nodes, as for nonspecific inflammation. (d) Selected transaxial sections (PET, left; CT, middle; fused PET/CT, right) showing in the same plane the pocket infection in the left hemithorax and the septic embolism in right lung. (e) The area of focal [18F]FDG uptake at the posterior right greater trochanter is due to nonspecific muscular uptake

Full size image

9.1.4.2 Suspected Site of Infection

Cardiac device.

9.1.4.3 Radiopharmaceutical Activity

[18F]FDG, 291 MBq.

9.1.4.4 Imaging

The acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

9.1.4.5 Conclusion/Teaching Point

[18F]FDG PET/CT identified the presence of ICD pocket infection, with associated septic lung embolism.

9.1.5 Case 9.5

9.1.5.1 Background

A 73-year-old man had been submitted ICD positioned for heart failure about 3 years before being referred to the emergency department for persistent fever unresponsive to antimicrobial treatment. Lab tests showed increased C-reactive protein (2.5 mg/dL, normal value <0.5 mg/dL), and erythrocyte sedimentation rate (96 mm/h, normal value <30 mm/h). Blood cultures were positive for Streptococcus dysgalactiae. TTE did not show any abnormality, while TEE was doubtful for a vegetation along the lead of ICD. Because of the high clinical suspicion for infection together with uncertain TEE findings, [18F]FDG PET/CT was performed (Fig. 9.10), which showed increased tracer uptake along the lead of ICD, thus confirming the doubtful TEE findings; in addition a focus of increased [18F]FDG uptake was noted in the soft tissues of the sacral region.

Fig. 9.10
figure 10

[18F]FDG PET/CT in a patient with cardiac device infection. (a) Transaxial section on a selected plane (PET, left; CT, middle; fused PET/CT, right). (b) Coronal section on a selected plane (PET, left; CT, middle, fused PET/CT, right). The images show increased [18F]FDG uptake along the lead of the ICD, thus confirming the doubtful TEE findings as due to infection. (c) Transaxial sections on a selected plane (PET, top; CT, middle; fused PET/CT, bottom), demonstrating a focus of increased [18F]FDG uptake in the soft tissues of the sacral region

Full size image

9.1.5.2 Suspected Site of Infection

Cardiac device.

9.1.5.3 Radiopharmaceutical Activity

[18F]FDG, 239 MBq.

9.1.5.4 Imaging

The acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

9.1.5.5 Conclusion/Teaching Point

[18F]FDG PET/CT identified ICD-related infection and also identified the probable portal of entry for bacteria.

9.1.6 Case 9.6

9.1.6.1 Background

A 74-year-old obese man with prior implantation of ICD went to the emergency department for dyspnea and persistent fever unresponsive to antimicrobial treatment. Lab tests indicated very high level of C-reactive protein (22 mg/dL) and mildly increased pro-calcitonin (1.8 ng/dL), but still in the range of sepsis uncertainty (0.5–2 ng/dL). Blood cultures were positive for Staphylococcus aureus. While TTE was negative, at TEE two faint vegetations were seen along the lead of ICD and at the tricuspid valve, respectively. [18F]FDG PET/CT was performed to confirm/exclude infection based on the high clinical suspicious (cardiac risk factors, lab tests, bacteremia, and suspected, even if uncertain, TEE findings). The PET/CT scan (Fig. 9.11) showed increased [18F]FDG uptake along the intracardiac portion of the lead of ICD and at the pericardium of the right atrium. In addition, lung embolisms were detected.

Fig. 9.11
figure 11

(a) [18F]FDG PET/CT MIP image. (b) Coronal sections (PET, left; CT, middle; fused PET/CT, right). The images show increased [18F]FDG uptake at the intracardiac portion of the ICD lead, associated with intense and diffuse tracer uptake involving the pericardium of the right atrium. (c) Transaxial sections (PET, left; CT, middle; fused PET/CT, right), showing focal sites of [18F]FDG uptake consistent with embolisms in the upper lobe of left lung

Full size image

9.1.6.2 Suspected Site of Infection

Infection of device.

9.1.6.3 Radiopharmaceutical Activity

[18F]FDG, 367 MBq.

9.1.6.4 Imaging

The acquisition included scout view (120 kV, 10 mA), whole-body CT scan (140 kV, 80 mA), and PET (3D, 3 min/FOV). Images were reconstructed with and without attenuation correction using the low-dose transmission CT scan.

9.1.6.5 Conclusion/Teaching Point

[18F]FD-PET/CT identified the presence of ICD infection, associated with pericarditis and lung septic embolisms.

9.1.7 Case 9.7

9.1.7.1 Background

An 80-year-old man with ICD went to the emergency department for persistent fever unresponsive to antimicrobial treatment. Lab tests supported the clinical suspicion of infection, with increased C-reactive protein (14 mg/dL, normal value <0.5 mg/dL) and increased fibrinogen (486 mg/dL, normal range 150–400 mg/dL). Blood cultures were negative. TTE was negative. TEE identified a doubtful image suspected for vegetation along the lead. The patient underwent a 99mTc-HMPAO-WBC scintigraphy (Fig. 9.12), which identified device-related infection based on the presence of time-dependent radioactivity accumulation increase at the ICD pocket and along the intravascular portion of the ICD lead.

Fig. 9.12
figure 12

99mTc-HMPAO-WBC scintigraphy. (a) Anterior and posterior planar whole-body images acquired at 30 min, confirming a normal biodistribution pattern of the radiolabeled WBC. (b) Planar spot views of the thorax (anterior, left panel; posterior, right panel) acquired at 4 h (top) and at 20 h (bottom), showing no abnormalities. (c) Transaxial SPECT/CT sections (SPECT, left; CT, middle; fused SPECT/CT, right) acquired at 4 h, showing increased WBC accumulation at the deep component of the ICD pocket and at the intravascular portion of the ICD lead

Full size image

9.1.7.2 Suspected Site of Infection

Cardiac device.

9.1.7.3 Radiopharmaceutical Activity

99mTc-HMPAO-WBC, 740 MBq.

9.1.7.4 Imaging

Planar images of the thorax acquired at 30 min, 4 h, and 20 h. SPECT/CT imaging of the thorax at 4 h and 20 h, with 3D reconstruction.

9.1.7.5 Conclusion/Teaching Point

99mTc-HMPAO-WBC scintigraphy identified the presence ICD infection.

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Sollini, M., Bandera, F., Bartoli, F., Zanca, R., Lazzeri, E., Erba, P.A. (2021). Infective Endocarditis and Cardiovascular Implantable Electronic Device Infection. In: Lazzeri, E., et al. Radionuclide Imaging of Infection and Inflammation. Springer, Cham. https://doi.org/10.1007/978-3-030-62175-9_9

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