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Doctors diagnose infective endocarditis (IE) by assembling several kinds of evidence: symptoms and examination findings, risk factors, blood cultures, and heart imaging. The 2023 Duke-ISCVID criteria organize that evidence into definite, possible, or rejected IE categories. No single symptom, blood test, or scan can answer every case.
Blood cultures identify organisms and guide antimicrobial choices, while echocardiography looks for vegetations, valve damage, and nearby complications. Cardiac CT, FDG-PET/CT, pathogen-specific serology, molecular tests, and tissue analysis add evidence when standard tests are inconclusive—particularly when prosthetic material or a transcatheter aortic valve is involved.
What the diagnostic process is trying to establish
IE can produce evidence in different places at once. Microbiology may show a causative organism in the bloodstream; ultrasound or other imaging may show infected valves or structural damage; and the patient’s clinical course may reveal consequences such as heart failure or embolic events. Doctors therefore combine findings rather than treating any one result as decisive.
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The framework most often cited in current practice is the 2023 Duke-ISCVID criteria. They provide a structured way to classify evidence, but clinicians still interpret the criteria in the context of the individual patient.
1. Clinical assessment: symptoms, examination, and risk
Findings that raise suspicion
Doctors first ask about the course of illness and perform a physical examination. Findings that can increase suspicion include prolonged or otherwise unexplained fever, a new heart murmur or new valve dysfunction, new heart failure, embolic or neurologic events, and evidence of glomerulonephritis. These signs may occur for other reasons, so none confirms IE alone.
Risk factors and exposures
The assessment also covers circumstances that make IE more likely or alter which tests are most useful:
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- Prosthetic heart valves or other prosthetic cardiac material
- Cardiac devices, such as implanted leads
- Previous IE
- Congenital or acquired valve disease
- Hemodialysis
- Indwelling vascular catheters
- Immunosuppression
- Relevant exposure history identified by the clinical team
What this step can and cannot show
Symptoms and risk factors set the pre-test suspicion. They help clinicians decide how urgently to obtain cultures and which imaging study is appropriate, but they do not prove that bacteria or another organism is growing on a valve. A patient can have IE without the classic combination of fever and a murmur, and a patient with those findings can have another illness.
2. Blood cultures: identifying the organism
Why cultures are central
Blood cultures look for organisms circulating in the bloodstream. They can identify the cause of infection and allow the clinical team to select antimicrobial therapy that targets that organism. The Duke-ISCVID criteria paper states: “Blood cultures remain the gold standard for diagnosing IE and for directing antimicrobial therapy.”
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How clinicians collect them
For adults with suspected bacteremia, the 2023 criteria paper says that at least two blood-culture sets should be obtained. A set consists of an aerobic and an anaerobic bottle pair drawn at the same time. When possible, separate venipunctures are recommended. Collection is a clinical procedure performed by trained staff; patients should not attempt to arrange or interpret cultures independently.
The 2023 criteria no longer make the older, complex timing and separate-venipuncture rules a condition for satisfying the criteria, although separate draws remain preferable whenever feasible. The team documents how specimens were obtained and interprets the result with the clinical picture.
How a culture becomes diagnostic evidence
A typical IE organism isolated from at least two separate blood-culture sets qualifies as a major microbiologic criterion in the 2023 framework. Other organisms or patterns may carry different weight, which is why the laboratory report is reviewed by clinicians familiar with IE rather than read as a simple positive-or-negative home test.
Why a negative culture does not end the evaluation
Routine cultures do not identify every case. An ISCVID working-group consensus paper published in 2023 estimates that approximately 10% of IE cases in industrialized regions are blood-culture-negative. A negative result therefore has to be considered alongside the symptoms, examination, imaging, prior clinical events, and any prosthetic material or device present.
3. Echocardiography: seeing valves and nearby damage
Echocardiography uses ultrasound to look for vegetations and structural complications. The Duke-ISCVID criteria describe transthoracic echocardiography (TTE) as the first-line imaging method, but transesophageal echocardiography (TEE) is generally more sensitive and answers questions that TTE may not resolve.
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| Test | How it is performed | What it can show | Important limitations or uses |
|---|---|---|---|
| TTE | Ultrasound images obtained through the chest wall | Valve vegetations and some valve or surrounding structural abnormalities | First-line study; smaller lesions or difficult anatomy may not be visible |
| TEE | Ultrasound probe positioned in the esophagus, closer to the heart | More detailed views of valves, prosthetic material, devices, and paravalvular structures | Higher sensitivity than TTE; especially important when prosthetic valves or cardiac devices are involved, or when complications are suspected |
When TEE is particularly important
Clinicians commonly favor TEE when a prosthetic valve or cardiac device is involved, when TTE is nondiagnostic, or when they need to assess suspected leaflet damage, a paravalvular lesion, a fistula, or prosthetic-valve dehiscence. The closer position of the probe can reveal abnormalities hidden by prosthetic material or by the limits of chest-wall imaging.
What a normal echocardiogram means
A normal TTE does not, by itself, rule out IE. The next step depends on the level of suspicion and the question the team still needs to answer. That may mean TEE, another imaging modality, additional microbiology, or observation with reassessment rather than an automatic one-size-fits-all sequence.
4. Cardiac CT and FDG-PET/CT
Cardiac CT
Cardiac CT can add anatomic detail when echocardiography is inconclusive or when a complication is suspected. Findings relevant to the Duke-ISCVID imaging domain include vegetations, leaflet perforation or aneurysm, abscess, pseudoaneurysm, fistula, and prosthetic-valve dehiscence. CT is therefore a targeted follow-up study, not a replacement for initial cultures and echocardiography in every patient.
FDG-PET/CT
FDG-PET/CT detects abnormal metabolic activity. Under the 2023 criteria, activity involving prosthetic material, valves, grafts, or device leads can provide diagnostic evidence in selected cases. The result is interpreted with the patient’s history and other tests; metabolic activity is not automatically synonymous with active IE.
The special challenge of TAVR-associated IE
The AHA’s 2026 summary notes that both TTE and TEE have reduced sensitivity for IE involving a transcatheter aortic valve replacement (TAVR). In that setting, multimodality imaging—particularly FDG-PET/CT—may be needed. This is a specific high-complexity scenario, not a reason to order PET/CT for every person being evaluated for IE.
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5. When blood cultures are negative
Targeted serology
When routine cultures fail to identify an organism, clinicians may order blood tests that look for an immune response to specific pathogens. The 2023 criteria include defined laboratory evidence for Coxiella burnetii, Bartonella species, and Tropheryma whipplei. These tests are selected according to the clinical context and suspected exposure, not used as a universal panel for everyone.
PCR and other nucleic-acid testing
PCR and related molecular assays can detect microbial genetic material when an organism is difficult to grow. The AHA’s scientific statement supports molecular testing when cultures are negative or inconclusive. Sequencing may be considered in specialized settings, with results interpreted by clinicians and microbiology laboratories because contamination and background genetic material can complicate interpretation.
Valve or other tissue analysis
If surgery or another procedure provides an infected valve or related tissue, laboratories can test that specimen with culture, PCR, or sequencing. The 2023 criteria paper describes a study of FISHseq analysis of infected prosthetic valves that increased detection or clarification of causative microorganisms by 30% compared with routine blood and valve cultures. That figure applies to the specific method and study context; it is not a guarantee for every tissue sample.
The AHA’s blood culture-negative endocarditis statement and its 2026 scientific statement describe how these targeted approaches fit into a broader evaluation.
6. How the Duke-ISCVID criteria assemble the evidence
The 2023 Duke-ISCVID system retains three overall categories: definite IE, possible IE, and rejected IE. It uses major and minor clinical criteria rather than a single score from one test.
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| Evidence domain | Examples of what may count |
|---|---|
| Microbiology | Qualifying blood-culture results or specified pathogen-specific laboratory evidence |
| Imaging | Characteristic findings on echocardiography, cardiac CT, or FDG-PET/CT, depending on the situation |
| Clinical features | Predisposing conditions, fever, vascular or immunologic phenomena, and other findings defined by the criteria |
| Surgical evidence | Operative findings recognized as a clinical domain in the updated criteria |
Doctors combine these domains with the patient’s trajectory and their own judgment. The criteria are a classification aid for clinical care and research, not a checklist for self-diagnosis. A person should not count symptoms at home and conclude that IE is present or absent.
How test choices change in common situations
| Clinical situation | Why the evaluation may differ |
|---|---|
| Suspected infection of a native valve | Blood cultures and first-line TTE commonly provide the initial microbiologic and structural evidence; further testing depends on what they show and how strong suspicion remains. |
| Prosthetic valve | TEE is especially important because prosthetic material can obscure lesions; cardiac CT or FDG-PET/CT may add evidence about dehiscence, abscess, or metabolic activity. |
| Cardiac device or lead | TEE and, when appropriate, metabolic imaging help assess structures that TTE may not characterize adequately. |
| TAVR-associated suspicion | Both TTE and TEE can be less sensitive, so a multimodality strategy, particularly FDG-PET/CT, may be required. |
| Blood-culture-negative presentation | Pathogen-specific serology, PCR or other molecular tests, sequencing, and analysis of valve tissue may be considered. |
| Suspected abscess, fistula, perforation, or dehiscence | TEE and cardiac CT can provide complementary views of structural complications. |
These are decision patterns, not a universal order. The treating team chooses tests according to the suspected organism, prosthetic material, device anatomy, initial images, and complications under consideration.
Why an early negative test may not settle the diagnosis
- One negative blood-culture result is not an automatic exclusion. About one in ten IE cases in industrialized regions is estimated to be blood-culture-negative, and targeted testing may be needed.
- A normal TTE is not an automatic exclusion. Lesion size, anatomy, prosthetic material, and the complication being sought affect what ultrasound can detect.
- Different tests detect different evidence. Cultures address organisms; echocardiography and CT address anatomy; FDG-PET/CT addresses abnormal metabolic activity; tissue and molecular tests can identify organisms missed in blood.
- Timing and clinical change matter. If fever, a new murmur, heart failure, embolic findings, or another concerning feature persists, clinicians reassess the evidence and decide whether additional or different testing is justified.
Questions to ask the clinical team
Patients and caregivers can make the diagnostic discussion clearer by asking:
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- Which findings currently raise or lower suspicion for IE?
- How many blood-culture sets were obtained, and did they identify an organism?
- Was the first echocardiogram a TTE, and is TEE needed because of a prosthetic valve, device, or suspected complication?
- Could CT or FDG-PET/CT add information in this particular anatomy?
- If cultures remain negative, which serology or molecular tests are appropriate?
- Which Duke-ISCVID category best describes the evidence now, and what new result would change that assessment?
These questions help explain why doctors may continue evaluating IE after an initially reassuring result, without turning the criteria into a home diagnostic tool.
Quick Recap
Sources and current guidance
- 2023 Duke-ISCVID criteria paper
- AHA 2026 “Top Things to Know” summary
- AHA 2026 scientific statement
- AHA blood culture-negative endocarditis statement
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