Patients with infective endocarditis can present with symptoms such as fevers, chills, chest pain, shortness of breath and new heart murmurs.

When blood cultures are taken, the most common bacteria that are isolated include Staph aureus, streptococcus bovis, viridians strept and enterococci. Depending on the definition and laboratory sampling used, anywhere between 2.5% to approximately 30% of endocarditis cases will be blood-culture negative.1

One common definition of blood-culture negative endocarditis is when three or more aerobic and anaerobic blood cultures collected during 48 hours remain negative after more than 1 week of incubation in the setting of definite or probable endocarditis.1 One potential cause of noninfectious, blood-culture negative endocarditis is an underlying malignancy.

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Noninfectious, blood-culture negative endocarditis has several names including nonbacterial thrombotic endocarditis (NBTE) as well as verrucous, marantic or Libmann-Sacks endocarditis1. These patients will have sterile depositions of thrombi consisting of platelets and fibrin on their heart valves (typically aortic and mitral valves).2

The exact pathophysiology behind NBTE is not entirely understood, however a pro-inflammatory state that is supported by elevated levels of cytokines such as tumor necrosis factor-alpha (TNF-α) or interleukins 1 and 2 (IL-1, IL-2) may predispose these patients to thrombi formation. It has been well established that malignancy places patients in a relatively hypercoaguable state, which could also contribute to valvular damage and subsequent clot formation.

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The most common condition associated with NBTE is malignancy with other associations including systemic lupus erythematosus (SLE), sepsis, and rheumatoid arthritis (RA). NBTE is a relatively rare condition, and is typically identified on autopsy in approximately 1% to 1.6% of patients.3,4

NBTE was more common in those patients with SLE as well as malignancy especially those with adenocarcinomas of the pancreas, ovaries, lung, stomach, prostate, and colon.2,3,4

Patients with NBTE may present clinically differently than patients with infective endocarditis. The general symptoms of fevers, chills, and malaise may be present, however patients with NBTE are more likely to have symptoms associated with distant emboli of their valvular lesions.

The thrombi found on the valves of patients with NBTE are less likely to cause direct valvular dysfunction and more likely to cause symptoms by embolizing to the coronary arteries, extremities, kidney, or brain.2