Improving the Diagnosis of Intracardiac Infections

Despite advances in culture and molecular diagnostic methods and availability of transesophageal echocardiography at most centers, diagnosis of infective endocarditis (IE) remains challenging. Complications and mortality associated with IE have remained largely unchanged over the last 2 decades.¹ Increasing use of endovascular hardware further limits the sensitivity and specificity of echocardiography, which has been used as the gold-standard imaging modality as part of modified Duke criteria. For this reason, novel imaging modalities have been incorporated into current IE guidelines to improve the diagnosis of IE and associated complications.^2-4

Over the past decade, 18F-fluorodeoxyglucose (18F-FDG) PET/CT has been shown to improve the diagnostic accuracy in patients with suspected prosthetic valve IE and intracardiac device infection. Moreover, 18F-FDG-PET/CT has several advantages over echocardiography, including detection of embolic infectious complications. Here, we discuss the role of 18F-FDG-PET/CT in establishing the diagnosis of IE and associated complications.

18F-FDG-PET/CT

18F-FDG-PET/CT has shown promise as a complementary imaging modality to echocardiography, primarily in prosthetic valve IE and in detection of extracardiac complications. 18F-FDG-PET/CT performs worse in detecting native valve IE than in detecting prosthetic valve IE; this is likely due to the small size of the vegetation, minimal FDG tracer deposition in the valve’s vegetation, and fewer inflammatory cells and fibrosis in native valves compared with prosthetic valves.⁵

A key feature of 18F-FDG-PET/CT in IE evaluation compared with imaging protocols for oncology purposes is patient preparation. Normal myocardium has a great avidity for glucose; therefore, a myocardial suppression diet promotes free fatty acid metabolism and suppresses physiologic glucose metabolism, which is necessary for a successful 18F-FDG-PET/CT.⁶ Current guidelines recommend a low-carbohydrate, high-fat diet for 12 to 24 hours or a fasting period of 12 to 18 hours before imaging with or without the use of intravenous heparin 15 min before FDG administration.^7,8 Patients are also counseled to avoid excessive exertion for 12 to 24 hours before imaging, because increased glucose uptake in the myocardium may lead to higher catecholamine levels, which would lower the quality of the 18F-FDG-PET/CT images.^8,9 Imaging is typically performed 60 minutes following FDG administration. As proposed by Leccisotti et al. following the results of a case series of 27 patients with IE in the transvenous lead of their cardiac implantable electronic device (CIED), another series of delayed images may help to further optimize the visualization of small foci of infection.¹⁰ Image reconstruction with and without attenuation correction is also recommended to enhance image quality and FDG uptake quantification.¹¹ However, an overestimation of FDG avidity is possible, leading to higher rates of false-positive results primarily around prosthetic valves and CIEDs.¹² False-negative findings secondary to elevated blood glucose concentration, prior administration of antimicrobial therapy, and small vegetation size may occur.^3,13

The Role of 18F-FDG-PET/CT in Prosthetic Valve IE

Both the pretest probability of IE and type of prosthetic cardiac material should be taken into account when evaluating patients with suspected IE (Table). In patients with a high level of clinical suspicion for IE, who have a prosthetic valve, and who meet criteria for “possible” or “rejected” IE by modified Duke criteria, an 18F-FDG-PET/CT can be considered because the pooled sensitivity and specificity is high (80.5% and 79%, respectively).¹⁴ Contrary to previous hypotheses, early 18F-FDG-PET/CT changes are not associated with postoperative reactive inflammation following prosthetic valve implantation within the first 3 months.^2,15 During the first year after surgery, “normal” or “negative for infection” is defined as the absence of FDG distribution or a diffuse/homogeneous FDG uptake and a standardized FDG intensity, including a maximum standardized uptake value (SUVmax) ≤5.96/6.46, blood pool SUVmax ≤3.19/3.66, and a valve uptake index ≤0.45/0.41.16 Similar findings were reported in a study that imaged only aortic prosthetic valves.¹⁷ Based on these observations, 18F-FDG-PET/CT is a reasonable option for assessment of early prosthetic valve IE using quantitative measures.

Table

The Role of 18F-FDG-PET/CT in Transcatheter Aortic Valve Implantation Infection

As in prosthetic valve IE, the diagnosis oftranscatheter aortic valve implantation (TAVI) IE can also be challenging, and its presence can be associated with poorer outcomes.¹⁸ Limited data on the utility of 18F-FDG-PET/CT in TAVI-IE diagnosis exist to date based on a theoretical risk of false-positive results caused by the metal stent around the TAVI prosthesis. 18F-FDG-PET/CT could potentially reclassify a “possible” case to either “definite” or “rejected,” especially when used in combination with cardiac CT angiography (CTA).¹⁹ For instance, in a cohort of 22 possible TAVI-IE cases, 5 cases were recategorized as “definitive” and 5 additional cases as “rejected” TAVI-IE. The addition of 18F-FDG-PET/CT and CTA can diagnose up to 78% of TAVI-IE cases that were not visible with echocardiography.¹⁹

The Role of 18F-FDG-PET/CT in CIED Infection

In recent years, rates of CIED insertion and associated infections have significantly increased, resulting in a substantial health care burden.²⁰ CIED infections can be broadly categorized into generator pocket infection and lead infection or lead IE.

18F-FDG-PET/CT has demonstrated a sensitivity (96%) and specificity (97%) for pocket infection diagnosis.²¹ However, in most pocket infection cases, the diagnosis is established based on physical exam findings and the presence of inflammatory changes at the pocket generator site. In contrast, a timely diagnosis of endovascular infection with an intact pocket can be challenging, as a transesophageal echocardiogram cannot reliably distinguish between an infected and noninfected echodensity attached to a device lead.²² Results of a recent meta-analysis including 492 patients showed that the diagnostic accuracy of 18F-FDG-PET/CT was low for lead infections, with pooled sensitivity of 76% and specificity of 83%. The sensitivity increased to 92%, and specificity decreased to 81%, with myocardial suppression protocols.²¹ Thus, when considering the significant complications and the financial burden associated with device removal, the decision to obtain an 18F-FDG-PET/CT should be individualized.

The Role of 18F-FDG-PET/CT in Left Ventricular Assist Device Infection

Figure 1

Similar to CIED implantation, left ventricular assist device (LVAD) use has considerably increased over the past several years.²¹ While LVAD implantation can be a lifesaving procedure, LVAD infections occur in 20% to 40% of patients within approximately 1 to 2 years of the procedure.^20,21

LVAD infections may present as local infection, involving the driveline (most common) or pump pocket, or as an endovascular infection (Figure). 18F-FDG-PET/CT can differentiate and localize the site and extent of infection within the device’s central portion or along the peripheral driveline. Infection in the pump pocket site, which is the central portion, is associated with lower survival, compared with infection along the driveline.²³ A retrospective cohort study addressed the value of 18F-FDG-PET/CT in 31 patients with a high clinical suspicion of LVAD infection the imaging had a sensitivity of 100% and specificity of 80%.²⁴ These results influenced the therapeutic management in 85% (34 of 40) of 18F-FDG-PET/CT examinations.²⁴ Similar results were observed in another study of 35 patients, in which 18F-FDG-PET/CT detected infection in 80% of cases, mainly at the level of the cannula and/or the pump pocket site.²³ In a recent case series and systematic review, the pooled sensitivity and specificity of 18F-FDG-PET/CT in diagnosing LVAD infections was 92% and 83%, respectively.²⁵ However, specificity varied considerably among studies (25% to 100%).²⁵ Both qualitative and quantitative data can provide greater sensitivity and specificity than visual grading alone. Preliminary data showed lower average measured SUVmax values in the absence of infection vs presence of infection (2.3 ± 1.0 to 3.6 ± 1.0 vs 4.0 ± 2.2 to 6.4 ± 3.8).²⁶ The number of patients included in most studies is small,²⁷ and in making a diagnosis, imaging should be an adjunct to the features of clinical presentation and to laboratory diagnostic tools. Moreover, a careful review of each patient’s surgical report could improve the objective assessment of LVAD infection by 18F-FDG-PET/CT.

Conclusions

18F-FDG-PET/CT has high sensitivity and specificity, but it is still considered a diagnostic tool adjunctive to routine clinical evaluation. When interpreting an 18F-FDG-PET/CT, patient preparation (myocardial FDG uptake suppression), surgical technique, and type of material implanted should be carefully considered. The addition of 18F-FDG-PET/CT to the evaluation of possible IE has the potential to improve diagnostic accuracy considerably.

Natalia E. Castillo Almeida, MD, is an assistant professor in the Department of Internal Medicine, Division of Infectious Diseases, at the Mayo Clinic in Rochester, MN.

Zerelda Esquer Garrigos, MD, is an assistant professor and transplant infectious diseases specialist at the University of Mississippi in Jackson, MS.

Maryam Mahmood, MB, ChB, is an assistant professor in the Department of Internal Medicine, Division of Infectious Diseases, at the Mayo Clinic in Rochester, MN.

M. Rizwan Sohail, MD, is a professor of medicine in the Section of Infectious Diseases at Baylor College of Medicine and Medical Director of Faculty Group Practice – Infectious Diseases at Baylor Medicine. He is also section head of Adult Infectious Diseases at Texas Children’s Hospital, Houston, TX.

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