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Doctors diagnose infective endocarditis (IE) by assembling evidence from the patient’s symptoms and examination, blood cultures, echocardiography, and—when needed—CT, FDG-PET/CT, molecular tests, serology, or tissue analysis. No single symptom or scan is enough in every case. The 2023 Duke-ISCVID criteria organize the evidence into definite, possible, or rejected IE categories, but clinicians still interpret those categories in the context of the individual patient.
This is a hospital-based evaluation, not a condition that can be confirmed with a home kit. A negative early culture or a normal first echocardiogram may lower suspicion without ending the workup, particularly when prosthetic valves, cardiac devices, or transcatheter aortic-valve replacement (TAVR) are involved.
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What the diagnostic process is trying to establish
Infective endocarditis is an infection of the heart’s inner lining, usually involving a valve or implanted cardiac material. The evaluation has several different targets:
- Clinical assessment looks for a pattern of illness and risk factors that makes IE more or less likely.
- Blood cultures seek organisms circulating in the bloodstream and help clinicians choose antimicrobial treatment.
- Echocardiography looks for vegetations, valve damage, and complications around a valve.
- CT and FDG-PET/CT can reveal structural damage or abnormal activity involving prosthetic material when ultrasound is inconclusive.
- Serology, molecular testing, sequencing, and tissue analysis can identify an organism when routine cultures are negative or unclear.
The 2023 Duke-ISCVID criteria provide a structured framework. They use major and minor clinical criteria and retain the categories definite, possible, and rejected IE. The criteria support clinical judgment; they are not a self-diagnosis checklist.
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IE can be life-threatening. The American Heart Association’s 2026 summary cites nearly 40% one-year mortality, a disease-burden figure rather than a measure of any individual test’s accuracy.
1. Clinical assessment raises or lowers suspicion
The process begins with a history and physical examination. Clinicians look for combinations of findings rather than a single “classic” symptom.
Symptoms and examination findings
- Prolonged or otherwise unexplained fever
- A new heart murmur or a change in valve function
- New or worsening heart failure
- Embolic or neurologic events, which can occur when infected material travels from the heart
- Findings such as glomerulonephritis, an inflammatory kidney injury associated with some cases
These findings are clues, not proof. Fever can have many causes, and some people with IE do not have every expected sign. The clinician decides how urgently to obtain cultures and imaging based on the whole presentation.
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Suspicion is higher when symptoms occur in someone with a prosthetic valve, a cardiac device, previous IE, congenital or acquired valve disease, hemodialysis, an indwelling catheter, or immunosuppression. Selected exposure history may also matter. These factors change the starting probability of IE; they do not establish the diagnosis on their own.
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2. Blood cultures identify organisms and guide treatment
Blood cultures look for bacteria or fungi growing from blood samples. The Duke-ISCVID authors state that “Blood cultures remain the gold standard for diagnosing IE and for directing antimicrobial therapy.” A positive result can provide both a major diagnostic criterion and the information needed to tailor antimicrobial treatment.
How clinicians collect cultures
Collection is performed by healthcare professionals. For adults with suspected bacteremia, the 2023 criteria paper says at least two blood-culture sets should be obtained. A set consists of an aerobic and an anaerobic bottle drawn at the same time. Whenever possible, separate venipuncture is recommended. The criteria no longer make the older complex timing and separate-venipuncture rules a prerequisite for applying the diagnostic criteria, so patients should not try to manage timing or collection themselves.
What a positive result means
The organism and the number of independently obtained positive sets matter. Under the 2023 criteria, a typical IE organism isolated from at least two separate sets is major microbiologic evidence. The result is interpreted alongside imaging, examination findings, and the patient’s clinical course; a culture result is not read in isolation.
What a negative result means
A negative culture does not automatically exclude IE. Routine cultures fail to identify the causative organism in approximately 10% of IE cases in industrialized regions, according to the 2023 ISCVID working-group consensus. If suspicion remains, clinicians may repeat or extend the evaluation and use tests designed for organisms that routine cultures do not reveal.
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3. Echocardiography shows valves and nearby structures
Echocardiography uses ultrasound to look for vegetations and structural complications. The two main forms answer similar questions from different positions.
| Test | How it is performed | What it can show | Important limitations or uses |
|---|---|---|---|
| TTE (transthoracic echocardiography) | Ultrasound images are obtained through the chest wall. | Valve motion, possible vegetations, regurgitation, chamber function, and some complications. | First-line imaging in the Duke-ISCVID framework. Smaller lesions or structures that are difficult to visualize may be missed. |
| TEE (transesophageal echocardiography) | An ultrasound probe is placed in the esophagus, closer to the heart. | More detailed views of valves, prosthetic material, device leads, and tissue around the valve. | Generally more sensitive than TTE. Especially important with a prosthetic valve or cardiac device, or when leaflet damage, a paravalvular lesion, fistula, or prosthetic-valve dehiscence is suspected. |
Why a normal TTE may not settle the question
TTE is a sensible first look because it is noninvasive, but image quality and anatomy vary. A small vegetation, an early infection, or a lesion hidden by prosthetic material may not be visible. If the clinical suspicion remains significant, clinicians may proceed to TEE or another imaging modality rather than treating a normal TTE as a definitive exclusion.
When TEE is particularly valuable
TEE places the transducer close to the heart and usually provides better sensitivity. It is especially useful for prosthetic-valve IE, device-associated infection, and suspected complications such as tissue destruction beside a valve. The decision depends on the patient’s risks and the specific question the team needs answered.
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4. CT and FDG-PET/CT add information in selected cases
Cardiac CT
Cardiac CT can contribute structural evidence when echocardiography is inconclusive or when complications need clearer anatomic definition. Findings relevant to the diagnostic criteria can include vegetations, leaflet perforation or aneurysm, abscess, pseudoaneurysm, fistula, and prosthetic-valve dehiscence. CT is therefore complementary to ultrasound: it supplies cross-sectional detail rather than replacing blood cultures or echocardiography.
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FDG-PET/CT
FDG-PET/CT detects areas of increased metabolic activity and combines that information with CT anatomy. Under the Duke-ISCVID framework, abnormal activity involving prosthetic material, valves, grafts, or cardiac-device leads can provide diagnostic evidence in the appropriate setting. The test is targeted; it is not a routine scan for every person with fever.
The special challenge of TAVR-associated IE
Infection involving a transcatheter aortic-valve replacement can be difficult to see on echocardiography. The AHA’s 2026 summary notes reduced sensitivity of both TTE and TEE in TAVR-associated IE and says multimodality imaging—particularly FDG-PET/CT—may be needed. That is a selected scenario, not a reason for every suspected case to undergo PET/CT.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.5. What doctors do when cultures are negative
When blood cultures remain negative but the clinical and imaging picture still suggests IE, clinicians may order targeted tests. The choice depends on the suspected organism, exposures, implanted material, and whether a specimen can be obtained safely.
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Organism-specific serology can detect an immune response that routine blood culture misses. The 2023 criteria include specific laboratory evidence for Coxiella burnetii, Bartonella species, and Tropheryma whipplei. PCR and other nucleic-acid tests can look directly for microbial genetic material. The AHA’s scientific statement supports molecular testing when cultures are negative or inconclusive.
Sequencing and tissue analysis
If valve surgery or another procedure yields infected tissue, laboratories can analyze that specimen. Sequencing approaches may clarify an organism that standard cultures did not recover. In one study described in the 2023 ISCVID criteria paper, FISHseq analysis of infected prosthetic valves increased detection or clarification of causative microorganisms by 30% compared with routine blood and valve cultures. That percentage belongs to the specific method and study context; it is not a guaranteed improvement for every patient.
6. How the Duke-ISCVID criteria combine the evidence
The criteria prevent the evaluation from becoming a decision based on one isolated result. Major evidence can include qualifying blood-culture findings, selected pathogen-specific laboratory tests, and characteristic imaging. Minor clinical criteria capture other features that raise suspicion, while surgical evidence is also included as a clinical domain.
| Classification | What it means in practice |
|---|---|
| Definite IE | The combined major and minor evidence, or qualifying surgical evidence, reaches the criteria’s threshold for established infection. |
| Possible IE | Evidence is suggestive but does not yet meet the threshold for definite disease; further observation, cultures, imaging, or specialist assessment may be needed. |
| Rejected IE | The available evidence supports another explanation or fails to sustain IE under the criteria. |
These labels are classification aids, not substitutes for bedside judgment. A clinician may continue investigating a patient who remains very concerning despite an initially non-diagnostic result, especially when prosthetic material or a device makes imaging harder.
Why one negative test may not end the evaluation
Each test examines a different part of the disease process. Blood cultures can miss an organism; TTE can miss a small or obscured lesion; CT may show anatomy without identifying the organism; PET/CT can show metabolic activity without providing a complete microbiologic answer. Because the tests are not interchangeable, clinicians combine them and select follow-up studies according to the unresolved question.
- Negative cultures but persistent suspicion: targeted serology, PCR, sequencing, or tissue analysis may be considered.
- Normal or unclear TTE: TEE or cross-sectional imaging may provide a better view.
- Prosthetic valve, cardiac device, graft, or TAVR: the threshold for advanced or multimodality imaging is often lower because implanted material can hide or mimic disease.
- Evidence of a complication: CT or TEE may be chosen to define an abscess, fistula, dehiscence, perforation, or related structural damage.
What a patient can expect during an evaluation
The exact order is individualized, but a hospital evaluation commonly follows this logic:
- History and examination: the team reviews fever and other symptoms, heart findings, embolic or neurologic events, kidney findings, prior valve disease, devices, procedures, and relevant exposures.
- Blood cultures: clinicians obtain the recommended sets before interpreting microbiology alongside the rest of the evidence.
- Initial echocardiography: TTE is commonly the first cardiac imaging study.
- Focused follow-up: TEE is considered when TTE is insufficient, prosthetic material or a device is present, or complications are suspected.
- Advanced imaging or laboratory testing: CT, FDG-PET/CT, serology, molecular tests, sequencing, or tissue analysis are selected to answer the remaining diagnostic question.
- Formal classification and clinical decision-making: the team applies the Duke-ISCVID framework while considering the patient’s trajectory and alternative diagnoses.
This sequence is not a universal checklist. Timing and test selection change with the suspected organism, prior results, anatomy, complications, and the urgency of the illness.
Questions that clarify the workup
Patients and caregivers can ask the treating team:
- What findings make IE more or less likely in this case?
- How many blood-culture sets were obtained, and did they grow an organism?
- Was TTE sufficient, or is TEE needed to examine a valve, device, or complication more closely?
- If cultures are negative, which serology or molecular test fits the suspected organisms?
- Is prosthetic material or TAVR making the ultrasound images harder to interpret?
- Which Duke-ISCVID category best describes the evidence now, and what result would change that assessment?
These questions help explain the reasoning without turning the criteria into a home diagnostic tool. Suspected IE requires prompt professional assessment because delays can allow valve damage, heart failure, embolic events, or other complications to progress.
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