Noninfective endocarditis refers to formation of sterile platelet and fibrin thrombi on cardiac valves and adjacent endocardium in response to trauma, circulating immune complexes, vasculitis, or a hypercoagulable state. Symptoms are those of systemic arterial embolism. Diagnosis is by echocardiography and negative blood cultures. Treatment consists of anticoagulants.
Endocarditis usually refers to infection of the endocardium (ie, infective endocarditis). The term can also include noninfective endocarditis, in which sterile platelet and fibrin thrombi form on cardiac valves and adjacent endocardium. Noninfective endocarditis sometimes leads to infective endocarditis. Both can result in embolization and impaired cardiac function.
Noninfective endocarditis is rare and the diagnosis usually made at autopsy (1). Clinical diagnosis is based on a constellation of clinical findings rather than a single definitive test result.
General reference
1. Hurrell H, Roberts-Thomson R, Prendergast BD: Non-infective endocarditis. Heart 106(13):1023–1029, 2020. doi: 10.1136/heartjnl-2019-315204
Etiology of Noninfective Endocarditis
Vegetations are not caused by infection. They may be clinically undetectable or become a nidus for infection (leading to infective endocarditis), produce emboli, or cause valvular dysfunction. Valve destruction is uncommon.
Catheters passed through the right side of the heart may injure the tricuspid and pulmonic valves, resulting in platelet and fibrin attachment at the site of injury. In disorders such as systemic lupus erythematosus (SLE), circulating immune complexes may result in friable platelet and fibrin vegetations along a valve leaflet closure (Libman-Sacks lesions). These lesions do not usually cause significant valvular obstruction or regurgitation. Antiphospholipid syndrome (lupus anticoagulants, recurrent venous thrombosis, stroke, spontaneous abortions, livedo reticularis) also can lead to sterile endocardial vegetations and systemic emboli. Rarely, granulomatosis with polyangiitis, HIV infection, or COVID-19 leads to noninfective endocarditis.
Marantic endocarditis
In patients with chronic wasting diseases, disseminated intravascular coagulation, mucin-producing metastatic carcinomas (eg, of lung, stomach, or pancreas), or chronic infections (eg, tuberculosis, pneumonia, osteomyelitis), large thrombotic vegetations may form on valves and produce significant emboli to the brain, kidneys, spleen, mesentery, extremities, and coronary arteries. These vegetations tend to form on congenitally abnormal cardiac valves or those damaged by rheumatic fever. Half of patients with disseminated intravascular coagulation have noninfective endocarditis, suggesting a relationship between the conditions.
Symptoms and Signs of Noninfective Endocarditis
Vegetations themselves rarely cause symptoms unless their size and location cause valvular dysfunction, sometimes leading to dyspnea and/or palpitations. Symptoms result from embolization and depend on the organ affected (eg, brain, kidneys, spleen, digits). Fever and a heart murmur are sometimes present.
Diagnosis of Noninfective Endocarditis
Blood cultures
Echocardiography
Noninfective endocarditis should be suspected when patients who are chronically ill develop symptoms suggesting arterial embolism. Serial blood cultures and echocardiography should be done. Negative blood cultures and the presence of valvular vegetations (but not atrial myxoma) suggest the diagnosis. Examination of embolic fragments after embolectomy can help make the diagnosis.
Differentiation from culture-negative infective endocarditis may be difficult but is important. Anticoagulation is often needed in noninfective endocarditis but is avoided in infective endocarditis unless there is a pre-existing requirement such as a mechanical valve. Assays for hypercoagulability, antinuclear antibodies, and antiphospholipid syndrome should be done to evaluate for causes of true noninfective endocarditis.
Brain imaging is done to help guide treatment.
Treatment of Noninfective Endocarditis
Anticoagulation
Management of the underlying condition
Rarely surgery
Unless brain imaging finds a lesion prone to hemorrhagic transformation, treatment consists of indefinite anticoagulation12).
Predisposing disorders should be treated whenever possible.
Cardiac surgery (eg. vegetation excision, valve replacement) may be considered in cases where there is significant valvular dysfunction causing hemodynamic instability or recurrent embolic events despite optimal medical therapy.
Treatment references
1. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e576S-e600S. doi:10.1378/chest.11-2305
2. Zmaili M, Alzubi J, Lo Presti Vega S, Ababneh E, Xu B. Non-bacterial thrombotic endocarditis: A state-of-the-art contemporary review. Prog Cardiovasc Dis 2022;74:99-110. doi:10.1016/j.pcad.2022.10.009
Prognosis for Noninfective Endocarditis
Prognosis is generally poor, more because of the seriousness of predisposing disorders than the cardiac lesion.
Key Points
Noninfective endocarditis is much less common than infective endocarditis.
Sterile vegetations form on heart valves in response to factors such as trauma, circulating immune complexes, vasculitis, or a hypercoagulable state.
The sterile vegetations can embolize or become infected but rarely impair valvular or cardiac function.
Evaluation is with echocardiography and exclusion of infective endocarditis using blood cultures.
Prognosis depends mainly on the underlying disorder, which is often a serious illness.
Treatment is usually with anticoagulation.
