Evaluation of CV Inflammation and Infection

Abstract

Early diagnosis of endocarditis has an important prognostic value because a delay in antibiotic therapy and cardiac surgery may adversely affect clinical outcome. However, its diagnosis remains a challenging one.

Early diagnosis of endocarditis has an important prognostic value because a delay in antibiotic therapy and cardiac surgery may adversely affect clinical outcome. However, its diagnosis remains a challenging one.

Clinical diagnosis of infective endocarditis (IE) is based on the modified Duke criteria, which are mainly related to the results of blood cultures; echocardiography, either transthoracic or transesophageal, and clinical findings. According to these criteria the probability of IE is classified as definite, possible, or rejected. However, in clinical practice, the modified Duke criteria show a low diwagnostic accuracy for early diagnosis of IE, especially in presence of device-related IE (prosthetic valve and implantable pacemaker/defibrillator devices), for which echocardiography is quite frequently normal or inconclusive. Moreover, when IE is suspected, the use of a whole-body modality of imaging is recommended to identify the presence of a possible extra-cardiac primary infection focus, as well as to assess the spread of infection (infective embolism).

Recently, the European Society of Cardiology incorporated ¹⁸F-FDG PET/CT findings in its guidelines as major criteria in the diagnostic algorithm of patients with suspected device-related IE in order to reduce the rate of misdiagnosed IE, classified in the “Possible IE” category.

The rationale behind the use of PET/CT is related to the increased ¹⁸F-FDG uptake in presence of elevated glucose metabolism (infected cells, activated leucocytes, monocytes, macrophages, CD4+ T-lymphocytes).

In order to optimize ¹⁸F-FDG PET/CT findings, some aspects need to be pointed out:

• The use of ¹⁸F-FDG PET/CT in subjects with suspected IE of native valve remains questionable due to low accuracy of the test.

• Images acquired after surgery must be carefully evaluated due to possible post-operative inflammation phenomena. For this reason, a delay of at least 3 months after surgery is recommended before a PET/CT scan is performed.

• Biological glue during surgery may induce an inflammatory response and must be considered in interpreting ¹⁸F-FDG PET/CT images.

• Antibiotic therapy can decrease the sensitivity of ¹⁸F-FDG PET/CT and, when clinically possible, PET should be performed before therapy starts.

• To avoid the physiological uptake of FDG in the myocardium, patients must receive an adequate preparation. A high-fat/low-carbohydrate diet for 24/72 h, followed by a fast of at least 8–10 h must be observed. An intravenous administration of 50 IU/kg heparin 15 min before tracer injection can be considered.

• To reduce false positive results, PET/CT images must always be interpreted after an accurate evaluation of the non-attenuation corrected images.

• Semiquantitative assessment of ¹⁸F-FDG uptake by using maximal standardized uptake value (SUVmax) and ratio between uptake in the affected valve area and in the blood pool (SUV ratio) may add support to visual evaluation.

FormalPara Further Reading

• Habib G, Lancellotti P, Iung B. 2015 ESC Guidelines on the management of infective endocarditis: a big step forward for an old disease. Heart. 2016 Jul 1;102(13):992–4. https://doi.org/10.1136/heartjnl-2015-308791. Epub 2016 May 11.

• Mahmood M, Kendi AT, Ajmal S, Farid S, O’Horo JC, Chareonthaitaweeet P, al. Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis. J Nucl Cardiol 2019;26: 922–35.

• Tlili G, Amraoui S, Mesguich C, Rivière A, Bordachar P, Hindié E, Bordenave L. et al. High performances of 18F-fluorodeoxyglucose PET-CT in cardiac implantable device infections: A study of 40 patients. J Nucl Cardiol 2015; 22: 787–98.

• Juneau D1, Erthal F, Alzahrani A, Alenazy A, Nery PB, Beanlands RS, et al. Systemic and inflammatory disorders involving the heart: the role of PET imaging. Q J Nucl Med Mol Imaging. 2016 Dec;60(4):383–96. Epub 2016 Sep 9.

• Roque A, Pizzi MN, Fernández-Hidalgo N, Permanyer E, Cuellar-Calabria H, Romero-Farina G, et al. Morpho-metabolic post-surgical patterns of non-infected prosthetic heart valves by [18F] FDG PET/CTA: “normality” is a possible diagnosis. Eur Heart J Cardiovasc Imaging. 2020 Jan 1;21(1):24–33. https://doi.org/10.1093/ehjci/jez222.

4.1 Patient Preparation for Assessing Inflammation/Infection

The role of FDG PET/CT for diagnosing inflammation involving implanted structures such as intracardiac devices (ICD) and prosthetic valves, or other conditions such as inflammatory cardiomyopathies or cardiac sarcoidosis, has been already recognized.

However, due to the physiologic myocardial FDG uptake, the difficulty is to identify areas of pathological uptake at cardiac level. To this purpose, specific patient preparation is requested to ideally suppress cardiac glucose metabolism while enhancing contrast to inflammatory FDG deposits and identify areas of active inflammation and/or granulomatous disease.

One strategy is to instruct patients to undergo a preparation rich in fat and low in carbohydrates, eating one fatty meal prior to the exam and fast the day of the procedure.

Further Reading

• Blankstein R, Lundbye J, Heller G. Proceedings of the ASNC cardiac PET summit meeting, May 12 2014, Baltimore MD. J Nucl Cardiol. 2015;22:720–9.

• Blankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol. 2014;21:166–74.

• Demeure F, Hanin FX, Bol A, Vincent MF, Pouleur AC, Gerber B, et al. A randomized trial on the optimization of 18F-FDG myocardial uptake suppression: Implications for vulnerable coronary plaque imaging. J Nucl Med. 2014;55:1629–35.

• Osborne MT, Hulten EA, Murthy VL, MD, Skali H, Taqueti VR, et al. Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. J Nucl Cardiol. 2017 Feb; 24(1): 86–99.

4.2 Suspected Prosthetic Valve Endocarditis (PVE)

4.2.1 False Positive (with and w/o AC)

Case 61

History

• 85-year-old female with chronic atrial fibrillation and pacemaker implantation.

• She had a recent fall with displacement of the left hip and peri-trochanteric hematoma.

• She was being evaluated for fever of unknown origin (FUO) and positive blood culture for staphylococcus aureus.

• Transesophageal echocardiography was negative for endocarditis.

• Referred for ¹⁸F-FDG PET/CT for identification of possible infection foci (Figs. 4.1, 4.2, and 4.3).

PET/CT Images

Fig. 4.1

Coronal FDG PET image demonstrating intense glucose uptake around the left hip

Fig. 4.2

PET/CT images demonstrating intense focal FDG uptake around the pacemaker lead (arrow, Top Panel), which persists in the non-attenuation corrected images (arrow, Lower Panel)

Fig. 4.3

PET/CT images showing intense FDG accumulation in the area corresponding to intense mitral annular calcification (arrow, Top Panel), which appears non-significant in the non-attenuation corrected images (arrow, Lower Panel)

Findings

• The ¹⁸F-FDG PET/CT showed high tracer uptake in the left hip suggestive for peri-trochanter infection.

• There is a second focus of focal FDG uptake at the level of the left subclavian vein, corresponding to the pacemaker lead. This is present in both the attenuation-corrected and uncorrected PET images.

• There is an additional focus of intense FDG accumulation in the area of dense mitral annular calcification, which almost completely disappears in the uncorrected PET images.

Differential Diagnosis

• Infection.

• Non-specific inflammation.

• Artifact.

Management

• The presence of focal FDG uptake in the pacemaker lead that persisted in the uncorrected PET images in the clinical context of a patient with fever and bacteremia with positive blood cultures is consistent with an infected pacemaker lead.

• The pacemaker lead was removed. Culture of the device was positive for staphylococcus aureus.

• Systemic broad-spectrum antibiotic therapy was initiated.

• The FDG focus around the dense mitral annular calcification was an attenuation correction artifact.

Teaching Points

• FDG PET/CT is a useful imaging technique in the evaluation of patients with FUO. It is considered highly sensitive, but specificity is moderate. In equivocal cases, radiolabeled white blood cell imaging can be considered.

• Dense calcification and metal can lead to artificially high FDG uptake. It is always recommended that both the attenuation corrected and non-attenuation corrected images be evaluated.

Further Reading

• Kouijzer I, Mulders-Manders C, Bleeker-Rovers C, Oyen W. Fever of Unknown Origin: the Value of FDG-PET/CT. Seminars in Nuclear Medicine. 2018;48:100–107.

• Diemberger I, Bonfiglioli R, Martignani C, Graziosi M, Biffi M, Lorenzetti S, et al. Contribution of PET imaging to mortality risk stratification in candidates to lead extraction for pacemaker or defibrillator infection: a prospective single center study. European Journal of Nuclear Medicine and Molecular Imaging. 2018;46:194–205.

4.2.2 Focal Abscess Before and After Antibiotic Therapy

Case 62

History

• 65-year-old female with a history of bicuspid aortic valve and thoracic aortic aneurysm status post bioprosthetic aortic valve replacement and aneurysm graft repair 6 years ago, presented with lactobacillus bacteremia.

• Transesophageal echocardiogram (TEE) was non-diagnostic for prosthetic valve endocarditis.

• The patient was referred for ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT imaging (Figs. 4.4 and 4.5) to assess for prosthetic valve endocarditis (PVE).

• The study was repeated after antibiotic therapy (Figs. 4.6 and 4.7).

18F-FDG PET/CT

Fig. 4.4

Baseline FDG PET/CT study showing intense uptake at the level of the bioprosthetic valve

Fig. 4.5

FDG PET images with and without attenuation correction

Fig. 4.6

Follow-up FDG PET/CT study, after antibiotic therapy, showing substantial decrease of the intensity of the focal uptake area

Fig. 4.7

Follow-up FDG PET images with and without attenuation correction

Findings

• Baseline study

  • There is intense FDG uptake along the anterior and left lateral aspect of the bioprosthetic aortic valve. This is evident on both the attenuation-corrected and -uncorrected PET images. The SUVmax was 8.2.

• Follow-up study (12 weeks after initiation of antibiotic therapy)

  • There is substantial decrease in the intensity and extent of FDG uptake along the bioprosthetic aortic valve, which is minimal on the non-attenuation corrected images. The SUVmax was 4.1.

Differential Diagnosis

• None

Correlative Imaging

• None

Management

• The imaging findings are consistent with a focus of infection around the prosthetic aortic valve.

• The patient was treated with a prolonged course of antibiotics with good clinical response on repeat ¹⁸F-FDG PET/CT imaging performed after 3 months following initiation of antibiotic therapy.

Teaching Points

• ¹⁸F-FDG PET/CT is a useful modality to evaluate patients with suspected acute prosthetic valve endocarditis with high sensitivity and reasonable specificity for diagnosis of infection.

• Infection is suspected when FDG uptake is focal and intense (as opposed to mild and diffuse) around the prosthetic valve, as shown in this case.

• Like in case # 60, it is useful to evaluate both the attenuation-corrected and non-attenuation corrected images in the setting of prosthetic valves to ensure that the focus of uptake persists.

• FDG PET/CT is also useful to assess response to antibiotic therapy.

Further Reading

• Pizzi M, Roque A, Fernández-Hidalgo N, Cuéllar-Calabria H, Ferreira-González I, Gonzàlez-Alujas M, et al. Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18 F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography. Circulation. 2015;132:1113–1126.

• Swart L, Gomes A, Scholtens A, Sinha B, Tanis W, Lam M, et al. Improving the Diagnostic Performance of 18 F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis. Circulation. 2018;138:1412–1427.

4.3 Device Infection

4.3.1 Generator Pocket and Lead Infection

Case 63

History

• 74-year-old male with previous pacemaker/ICD implant admitted with fever underwent FDG PET/CT for suspected infective endocarditis (Fig. 4.8).

PET/CT Images

Fig. 4.8

Coronal, sagittal, and axial FDG PET/CT images (left and middle panels), non-attenuation corrected axial (right upper panel) and MIP PET image (right lower panel), showing a focus of intense FDG uptake in the pacemaker generator pocket

Findings

• There is a focus of intense FDG uptake (SUVmax: 4.8) in the pacemaker generator pocket, which persists in the non-attenuation corrected images.

• The diffuse cardiac uptake is due to inadequate patient preparation and limits the assessment for associated valvular endocarditis.

Differential Diagnosis

• Pacemaker generator pocket infection

• Non-specific inflammation in pacemaker pocket

Management

• The focality and intensity of the FDG uptake was considered indicative of an infection focus in the pacemaker generator pocket. The patient started antibiotic therapy and a pocket surgical revision was considered.

Teaching Points

• FDG PET is the most useful technique to evaluate pacemaker infection, especially within the pacemaker generator pocket.

• The diagnostic accuracy of PET/CT is very high in generator pocket infection, in which inflammatory changes after implantation do not usually extend beyond 6 weeks and are easily differentiated from infection after this period. The accuracy is nearly 100% for diagnosis of infection of the generator pocket and for the extra-cardiac segment of the leads.

• It is always recommended that patients be prepared adequately with high-fat/protein low-carbohydrate diet before imaging to maximize the benefit of PET/CT imaging for evaluation of possible associated foci of infection in the heart.

Further Reading

• Arnon-Sheleg E, Israel O, Keidar Z. PET/CT Imaging in Soft Tissue Infection and Inflammation—An Update. Seminars in Nuclear Medicine. 2020;50:35–49.

• Chen W, Sajadi M, Dilsizian V. Merits of FDG PET/CT and Functional Molecular Imaging Over Anatomic Imaging With Echocardiography and CT Angiography for the Diagnosis of Cardiac Device Infections. JACC: Cardiovascular Imaging. 2018;11:1679–1691.

4.3.2 Device Infection in Patient with Amyloidosis

Case 64

History

• 87-year-old female with a previous pacemaker implant for heart block presenting with fever and cachexia.

• Transthoracic echocardiography was non-diagnostic for infective endocarditis but showed LV hypertrophy and a pattern consistent with cardiac amyloidosis.

• She underwent planar and SPECT ^99mTc-DPD imaging (Fig. 4.9) and FDG PET/CT (Figs. 4.10 and 4.11).

Fig. 4.9

Planar and SPECT ^99mTc-DPD imaging. The planar images demonstrate intense tracer uptake in the left and right ventricles which is greater than ribs (Perugini grade 3). The SPECT images show that uptake is predominantly in the mid to basal segments

Fig. 4.10

PET/CT images demonstrating intense focal FDG uptake associated with the section of the pacemaker lead in the right ventricle. No FDG uptake is noted in the pacemaker generator pocket

Fig. 4.11

PET images without attenuation correction which demonstrate persistence of intense focal FDG uptake associated with the pacemaker lead in the right ventricle

Findings

• The planar ^99mTc DPD images demonstrate intense tracer uptake in the left and right ventricles which is greater than ribs (Perugini grade 3). The SPECT images show that DPD uptake is predominantly in the mid to basal segments. This confirms the presence of transthyretin amyloidosis.

• PET/CT images demonstrate intense focal FDG uptake associated with the section of the pacemaker lead in the right ventricle, which persisted in the non-attenuation corrected images. There was no FDG uptake in the pacemaker pocket.

Management

• The images are consistent with an infected intracardiac section of the pacemaker lead.

• The patient was started on broad-spectrum antibiotic therapy and transferred to a rehabilitation center.

Teaching Points

• FDG PET is a powerful diagnostic tool for excluding/documenting device infection.

• FDG PET/CT is highly specific when tracer uptake is identified in the pacemaker/ICD leads. However, a negative result does not completely exclude the presence of small foci of infection with low metabolic activity owing to limitations related to partial volume effect.

Further Reading

• Arnon-Sheleg E, Israel O, Keidar Z. PET/CT Imaging in Soft Tissue Infection and Inflammation—An Update. Seminars in Nuclear Medicine. 2020;50:35–49.

• Chen W, Sajadi M, Dilsizian V. Merits of FDG PET/CT and Functional Molecular Imaging Over Anatomic Imaging With Echocardiography and CT Angiography for the Diagnosis of Cardiac Device Infections. JACC: Cardiovascular Imaging. 2018;11:1679–1691.

4.4 Vasculitis

4.4.1 Diagnosis and Response to Therapy

Case 65

History

• 63-year-old female with a history of pulmonary sarcoidosis admitted to the general medicine service for fever, vomiting, and headache.

• She was referred for ¹⁸F-FDG PET/CT to assess for vasculitis, before (Fig. 4.12) and after therapy (Fig. 4.13).

PET/CT Images

Fig. 4.12

Whole-body PET/CT images during the index admission showing multiple foci of intense FDG uptake in the mediastinum and hilar regions (arrows) and in the abdominal aorta and iliac arteries (arrows)

Fig. 4.13

Follow-up whole-body PET/CT images obtained 9 and 18 months after the initial scan demonstrate complete resolution of FDG uptake in the thorax and markedly reduced but still active inflammation in the abdominal aorta and proximal iliac arteries

Findings

• The whole-body PET/CT images confirmed multiple areas of active inflammation including mediastinal and hilar lymph nodes consistent with her history of known sarcoidosis, and vascular inflammation involving the abdominal aorta and iliac arteries.

• The 9- and 18-month follow-up whole-body PET/CT images demonstrate interval resolution of inflammatory foci in the chest and marked improvement in the abdominal aorta and iliac arteries.

Management

• The patient was initiated on immunosuppressive therapy with corticosteroids. Tocilizumab was added after the 9-month FDG PET/CT study.

Correlative Imaging (Fig. 4.14)

• Whole-body contrast CT angiography was performed during initial hospital admission. It showed dilation of the abdominal aorta with aneurysm of the right iliac artery and several ulcerations.

Fig. 4.14

Contrast CT angiography showing dilation of the abdominal aorta with aneurysm of the right iliac artery and several ulcerations

Differential Diagnosis

• Pulmonary sarcoidosis

• Takayasu’s arteritis

• Giant cell arteritis

• Sarcoid vasculitis

Teaching Points

• FDG PET/CT is a very effective tool for monitoring treatment response in inflammatory diseases including sarcoidosis and vasculitis.

Further Reading

• Piekarski E, Benali K, Rouzet F. Nuclear Imaging in Sarcoidosis. Seminars in Nuclear Medicine. 2018;48:246–260.

• Versari A, Pipitone N, Casali M, Jamar F, Pazzola G. Use of imaging techniques in large vessel vasculitis and related conditions. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2018;62:34–39.

4.4.2 Large Vessel Vasculitis

Case 66

History

• 65-year-old female with a history of diabetes and hypertension presented with sudden onset renal dysfunction secondary to bilateral renal artery stenosis for which she underwent bilateral renal artery angioplasty with subsequent improvement of renal function.

• She underwent thoracic, abdominal, and pelvic CT angiography and FDG PET/CT (Fig. 4.15).

Fig. 4.15

FDG PET (top), CT angiography (middle), and fused limited whole-body PET/CT images

Findings

• The CT angiogram demonstrates diffuse thickening of the thoracic and abdominal aorta.

• The PET images demonstrate increased FDG uptake throughout the thoracic and abdominal aorta and iliac arteries.

Differential Diagnosis

• Takayasu’s arteritis

• Giant cell arteritis

Management

• The patient was started on immunosuppression with good clinical response. No follow-up imaging was available.

Teaching Points

• FDG PET/CT is useful to assess the presence and extent of arterial inflammation and provides important information that can inform initiation and monitoring of treatment as discussed in Case 64.

Further Reading

• Tezuka D, Haraguchi G, Ishihara T, Ohigashi H, Inagaki H, Suzuki J, et al. Role of FDG PET-CT in Takayasu Arteritis. JACC: Cardiovascular Imaging. 2012;5:422–429.

• Slart R, et al. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC. European Journal of Nuclear Medicine and Molecular Imaging. 2018;45:1250–1269.

• Prieto-González S, Depetris M, García-Martínez A, Espígol-Frigolé G, Tavera-Bahillo I, Corbera-Bellata M, et al. Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case–control study. Annals of the Rheumatic Diseases. 2014;73:1388–1392.