Infective endocarditis: Beyond the usual tests

Cleveland Clinic Journal of Medicine. 2019 August;86(8):559-567 | 10.3949/ccjm.86a.18120
August 1, 2019|Cleveland Clinic Journal of Medicine
Nkemdilim Mgbojikwe, MD;Steven R. Jones, MD;Thorsten M. Leucker, MD, PhD;Daniel J. Brotman, MD
Author and Disclosure Information

Nkemdilim Mgbojikwe, MD
Assistant Professor of Medicine, Johns Hopkins University School of Medicine; Assistant Director of Clinical Operations, Hospitalist Program, The Johns Hopkins Hospital, Baltimore, MD

Steven R. Jones, MD
Associate Professor of Medicine, Johns Hopkins University School of Medicine; Director, Inpatient Cardiology, Johns Hopkins Heart and Vascular Institute, Baltimore, MD

Thorsten M. Leucker, MD, PhD
Assistant Professor of Medicine, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine; Director of Basic and Translational Vascular Biology Research within the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD

Daniel J. Brotman, MD
Professor of Medicine, Johns Hopkins University School of Medicine; Director, Hospitalist Program, The Johns Hopkins Hospital, Baltimore, MD

Address: Nkemdilim Mgbojikwe, MD, Hospitalist Program, Division of General Internal Medicine, Johns Hopkins Hospital, 600 N. Wolfe Street/ Meyer 8-134B, Baltimore, MD 21287; nmgboji1@jhmi.edu

Dr. Brotman has disclosed consulting for Portola Pharmaceuticals.

Release date: August 1, 2019
Expiration date: July 31, 2020
Estimated time of completion: 1 hour

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ABSTRACT

Infective endocarditis remains a diagnostic challenge. Although echocardiography is still the mainstay imaging test, it misses up to 30% of cases. Newer imaging tests—4-dimensional computed tomography (4D CT), fluorodeoxy­glucose positron emission tomography (FDG-PET), and leukocyte scintigraphy—are increasingly used as alternative or adjunct tests for select patients. They improve the sensitivity of clinical diagnosis of infective endocarditis when appropriately used, especially in the setting of a prosthetic valve.

KEY POINTS

  • Echocardiography can produce false-negative results in native-valve infective endocarditis and is even less sensitive in patients with a prosthetic valve or cardiac implanted electronic device.
  • 4D CT is a reasonable alternative to transesophageal echocardiography. It can also be used as a second test if echocardiography is inconclusive. Coupled with angiography, it also provides a noninvasive method to evaluate coronary arteries perioperatively.
  • Nuclear imaging tests—FDG-PET and leukocyte scintigraphy—increase the sensitivity of the Duke criteria for diagnosing infective endocarditis. They should be considered for evaluating suspected infective endocarditis in all patients who have a prosthetic valve or cardiac implanted electronic device, and whenever echocardiography is inconclusive and clinical suspicion remains high.

CARDIAC CT

For patients who have inconclusive results on echocardiography, contraindications to TEE, or poor sonic windows, cardiac CT can be an excellent alternative. It is especially useful in the setting of a prosthetic valve.

Synchronized (“gated”) with the patient’s heart rate and rhythm, CT machines can acquire images during diastole, reducing motion artifact, and can create 3D images of the heart. In addition, newer machines can acquire several images at different points in the heart cycle to add a fourth dimension—time. The resulting 4D images play like short video loops of the beating heart and allow noninvasive assessment of cardiac anatomy with remarkable detail and resolution.

4D CT is increasingly being used in infective endocarditis, and growing evidence indicates that its accuracy is similar to that of TEE in the preoperative evaluation of patients with aortic prosthetic valve endocarditis.6 In a study of 28 patients, complementary use of CT angiography led to a change in treatment strategy in 7 (25%) compared with routine clinical workup.7 Several studies have found no difference between 4D CT and preoperative TEE in detecting pseudoaneurysm, abscess, or valve dehiscence. TEE and 4D CT also have similar sensitivities for detecting infective endocarditis in native and prosthetic valves.8,9

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Figure 1A. Transesophageal echocardiography in a 73-year-old man with a bioprosthetic aortic valve who presented with 2 months of fevers, chills, and night sweats. He had several negative blood cultures and 2 negative transesophageal echocardiograms over 1 month. No mass, vegetation, paravalvular abscess, or significant valve dysfunction was noted.
Figure 1B. Cardiac computed tomographic (CT) angiography with iodinated contrast, including 4D reconstruction, in the same patient, however, shows an 11-mm vegetation on the bioprosthetic aortic valve leaflets (arrow).
Figure 1C. Fluorodeoxyglucose positron emission tomography (FDG-PET) in the same patient confirms the diagnosis, showing a 13-mm hypermetabolic focus on the prosthetic valve (arrow), yielding the diagnosis of infectious endocarditis.

Coupled with CT angiography, 4D CT is also an excellent noninvasive way to perioperatively evaluate the coronary arteries without the risks associated with catheterization in those requiring nonemergency surgery (Figure 1A, B, and C).

4D CT performs well for detecting abscess and pseudoaneurysm but has slightly lower sensitivity for vegetations than TEE (91% vs 99%).9

Gated CT, PET, or both may be useful in cases of suspected prosthetic aortic valve endocarditis when TEE is negative. Pseudoaneurysms are not well visualized with TEE, and the atrial mitral curtain area is often thickened on TEE in cases of aortic prosthetic valve infective endocarditis that do not definitely involve abscesses. Gated CT and PET show this area better.8 This information is important in cases in which a surgeon may be unconvinced that the patient has prosthetic valve endocarditis.

Limitations of 4D cardiac CT

4D CT with or without angiography has limitations. It requires a wide-volume scanner and an experienced reader.

Patients with irregular heart rhythms or uncontrolled tachycardia pose technical problems for image acquisition. Cardiac CT is typically gated (ie, images are obtained within a defined time period) to acquire images during diastole. Ideally, images are acquired when the heart is in mid to late diastole, a time of minimal cardiac motion, so that motion artifact is minimized. To estimate the timing of image acquisition, the cardiac cycle must be predictable, and its duration should be as long as possible. Tachycardia or irregular rhythms such as frequent ectopic beats or atrial fibrillation make acquisition timing difficult, and thus make it nearly impossible to accurately obtain images when the heart is at minimum motion, limiting assessment of cardiac structures or the coronary tree.4,10

Extensive coronary calcification can hinder assessment of the coronary tree by CT coronary angiography.

Contrast exposure may limit the use of CT in some patients (eg, those with contrast allergies or renal dysfunction). However, modern scanners allow for much smaller contrast boluses without decreasing sensitivity.

4D CT involves radiation exposure, especially when done with angiography, although modern scanners have greatly reduced exposure. The average radiation dose in CT coronary angiography is 2.9 to 5.9 mSv11 compared with 7 mSv in diagnostic cardiac catheterization (without angioplasty or stenting) or 16 mSv in routine CT of the abdomen and pelvis with contrast.12,13 In view of the morbidity and mortality risks associated with infective endocarditis, especially if the diagnosis is delayed, this small radiation exposure may be justifiable.

Bottom line for cardiac CT

4D CT is an excellent alternative to echocardiography for select patients. Clinicians should strongly consider this study in the following situations:

  • Patients with a prosthetic valve
  • Patients who are strongly suspected of having infective endocarditis but who have a poor sonic window on TTE or TEE, as can occur with chronic obstructive lung disease, morbid obesity, or previous thoracic or cardiovascular surgery
  • Patients who meet clinical indications for TEE, such as having a prosthetic valve or a high suspicion for native valve infective endocarditis with negative TTE, but who have contraindications to TEE
  • As an alternative to TEE for preoperative evaluation in patients with known infective endocarditis.

Patients with tachycardia or irregular heart rhythms are not good candidates for this test.

FDG-PET AND LEUKOCYTE SCINTIGRAPHY

FDG-PET and leukocyte scintigraphy are other options for diagnosing infective endocarditis and determining the presence and extent of intra- and extracardiac infection. They are more sensitive than echocardiography for detecting infection of cardiac implanted electronic devices such as ventricular assist devices, pacemakers, implanted cardiac defibrillators, and cardiac resynchronization therapy devices.14–16

The utility of FDG-PET is founded on the uptake of 18F-fluorodeoxyglucose by cells, with higher uptake taking place in cells with higher metabolic activity (such as in areas of inflammation). Similarly, leukocyte scintigraphy relies on the use of radiolabeled leukocytes (ie, leukocytes previously extracted from the patient, labelled, and re-introduced into the patient) to allow for localization of inflamed tissue.

The most significant contribution of FDG-PET may be the ability to detect infective endocarditis early, when echocardiography is initially negative. When abnormal FDG uptake was included in the modified Duke criteria, it increased the sensitivity to 97% for detecting infective endocarditis on admission, leading some to propose its incorporation as a major criterion.17 In patients with prosthetic valves and suspected infective endocarditis, FDG-PET was found in one study to have a sensitivity of up to 91% and a specificity of up to 95%.18

Both FDG-PET and leukocyte scintigraphy have a high sensitivity, specificity, and negative predictive value for cardiac implanted electronic device infection, and should be strongly considered in patients in whom it is suspected but who have negative or inconclusive findings on echocardiography.14,15

In addition, a common conundrum faced by clinicians with use of echocardiography is the difficulty of differentiating thrombus from infected vegetation on valves or device lead wires. Some evidence indicates that FDG-PET may help to discriminate between vegetation and thrombus, although more rigorous studies are needed before its use for that purpose can be recommended.19