Why diagnosis is difficult

Endocarditis is a serious heart infection that can be hard to detect. The condition often mimics other illnesses with vague symptoms like fatigue, fever, or joint pain, making accurate diagnosis challenging. Some people don't show obvious symptoms until the infection has progressed, and complications have already set in.

Early and accurate diagnosis is critical because untreated endocarditis can result in heart valve damage, heart failure, stroke, or even death. Thankfully, medical imaging, laboratory tests, and clinical evaluations have greatly improved diagnostic accuracy.

When doctors suspect endocarditis

Physicians may begin to suspect endocarditis based on a patient’s history, risk factors, and symptoms. Common red flags include:

  • Persistent fever without a clear source

  • New or changed heart murmurs

  • Unexplained fatigue or weight loss

  • Evidence of embolic events (like stroke or blood in urine)

  • Skin signs like petechiae, Osler’s nodes, or Janeway lesions

If any of these signs are present—especially in someone with a prosthetic heart valve, congenital heart defect, or history of endocarditis—a diagnostic workup will usually be initiated right away.

Initial clinical evaluation

The diagnostic process begins with a physical examination and thorough medical history. Your doctor will check for:

  • Abnormal heart sounds using a stethoscope

  • Swollen joints or extremities

  • Skin changes or lesions

  • Signs of emboli in eyes, nails, or mucosa

  • Symptoms of heart failure, such as fluid in the lungs

Medical history includes recent dental work, surgeries, IV drug use, or chronic illnesses like diabetes or autoimmune conditions that can increase infection risk.

Blood cultures

The most important first step in confirming endocarditis is performing blood cultures. This involves taking several samples of blood (typically three sets) from different veins over time—ideally before antibiotics are started.

These cultures help:

  • Identify the specific bacteria or fungus causing the infection

  • Guide doctors in choosing the right antibiotic

  • Confirm ongoing bacteremia (bacteria in the blood)

A positive blood culture, especially with organisms commonly linked to endocarditis (e.g., Staphylococcus aureus, Streptococcus viridans), is one of the strongest indicators.

Complete blood count (CBC)

A CBC test checks the levels of different cells in the blood, which helps reveal infection and inflammation. In endocarditis:

  • White blood cell count may be elevated

  • Anemia (low red blood cells) is often present

  • Platelet counts can vary depending on the severity of infection or complications

Though not specific to endocarditis, CBC supports the overall clinical picture.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)

These are inflammatory markers that help measure the body’s response to infection:

  • ESR (sed rate): measures how quickly red blood cells settle at the bottom of a test tube; elevated in chronic inflammation

  • CRP: a protein produced by the liver in response to inflammation; rises more rapidly than ESR

High levels of either (or both) are commonly found in patients with endocarditis and can help track treatment progress.

Urinalysis

Even though endocarditis is a heart condition, a urinalysis is often performed. Why? Because emboli or immune complexes from the infected heart valve can affect the kidneys.

Possible findings include:

  • Hematuria (blood in the urine)

  • Proteinuria (protein in the urine)

  • White blood cells or casts (indicating kidney inflammation)

These results are indirect evidence that the infection is impacting other organs.

Electrocardiogram (ECG)

An ECG (EKG) is not used to diagnose endocarditis directly, but it helps rule out other cardiac issues and detect complications. It records the electrical activity of the heart.

ECG can reveal:

  • Arrhythmias (irregular heartbeats)

  • Heart block, especially if the infection spreads to the heart’s conduction system

  • Signs of previous or ongoing myocardial damage

Repeated ECGs are often performed during hospitalization to monitor for changes.

Chest X-ray

A chest X-ray is helpful in evaluating how the infection is affecting the lungs and heart. It can show:

  • Enlarged heart (sign of heart failure)

  • Fluid in the lungs (pulmonary edema)

  • Signs of pneumonia or septic emboli (infected clots in the lungs)

This imaging is commonly used in both initial evaluation and treatment monitoring.

Transthoracic echocardiogram (TTE)

A TTE is the first-choice non-invasive imaging tool in suspected endocarditis. It uses ultrasound waves to create images of the heart and valves.

TTE can detect:

  • Vegetations (infected masses) on heart valves

  • Valve dysfunction or leaking

  • Abscesses or structural damage

  • Fluid accumulation around the heart

However, it might miss small vegetations or those in hard-to-see locations, especially in obese patients or those with chest deformities.

Transesophageal echocardiogram (TEE)

When a TTE doesn’t provide clear answers, a TEE is usually the next step. This test involves passing a probe down the esophagus to get closer, clearer images of the heart.

TEE is better at:

  • Detecting small vegetations or abscesses

  • Evaluating prosthetic heart valves

  • Spotting perivalvular leaks or fistulas

TEE is considered the gold standard for imaging in endocarditis and is often repeated during treatment to assess changes.

CT and MRI scans

In complex or severe cases, CT (computed tomography) or MRI (magnetic resonance imaging) may be used to:

  • Detect embolic events in the brain, kidneys, spleen, or lungs

  • Evaluate complications such as aortic root abscesses or aneurysms

  • Plan for surgical intervention

MRI is especially useful for evaluating the brain when embolic strokes or abscesses are suspected.

Cardiac MRI

Though not routine for all endocarditis cases, cardiac MRI can provide detailed 3D imaging of the heart and blood vessels. It helps:

  • Evaluate extent of structural damage

  • Identify myocardial inflammation

  • Detect periannular complications

Its role is increasing in advanced heart centers for complex or recurrent cases.

Nuclear medicine scans

In patients with prosthetic valves or unclear diagnoses, nuclear imaging (like PET-CT or tagged white blood cell scans) can help identify hidden infections.

These scans show metabolic activity and highlight infected tissue that may not be visible on echocardiography or CT.

Duke criteria

To formally diagnose endocarditis, doctors often rely on the Modified Duke Criteria, which classify findings into major and minor criteria:

Major Criteria

  • Positive blood cultures with typical organisms

  • Evidence of endocardial involvement on echocardiogram

Minor Criteria

  • Fever

  • Predisposing heart condition or IV drug use

  • Vascular events (stroke, emboli, Janeway lesions)

  • Immunologic phenomena (Osler’s nodes, glomerulonephritis)

  • Positive blood cultures not meeting major criteria

A diagnosis is made when a certain combination of major and minor criteria is met.

Differential diagnosis

Doctors must rule out other conditions that mimic endocarditis symptoms, such as:

  • Autoimmune diseases like lupus or rheumatoid arthritis

  • Blood cancers like leukemia or lymphoma

  • Other infections (e.g., sepsis, tuberculosis, brucellosis)

  • Pulmonary embolism

This requires a comprehensive clinical approach and may involve consulting multiple specialists.

When surgery is needed

Sometimes diagnosis reveals complications that require surgical intervention, including:

  • Severe valve destruction causing heart failure

  • Large vegetations at risk of embolization

  • Abscess formation around the valve

  • Infections unresponsive to antibiotics

In these cases, imaging and lab results guide the urgency and type of surgery needed.

Monitoring during treatment

Diagnosis doesn't end once treatment begins. Repeat imaging, blood cultures, and inflammatory markers are used to:

  • Confirm infection is clearing

  • Monitor valve function

  • Detect early signs of complications

  • Plan post-treatment follow-ups

Continued vigilance helps ensure a full recovery and reduce the risk of recurrence.

Final thoughts

Diagnosing endocarditis involves a complex blend of clinical judgment, laboratory testing, and advanced imaging. No single test confirms it all—rather, it’s the combination of evidence that builds the case.

The earlier it’s caught, the better the outcomes. If you or someone you know has risk factors for endocarditis and presents with unexplained fever, fatigue, or heart-related symptoms, insist on a thorough diagnostic workup.