What are the causes of marantic (non‑bacterial thrombotic) endocarditis?

Causes of Marantic Endocarditis

Marantic endocarditis (non-bacterial thrombotic endocarditis) is primarily caused by advanced malignancy, followed by autoimmune disorders with hypercoagulable states, particularly antiphospholipid antibody syndrome and systemic lupus erythematosus. 1

Primary Etiologic Categories

The European Society of Cardiology classifies marantic endocarditis into four major groups based on underlying pathology 1:

1. Malignancy-Associated (Most Common)

• Advanced adenocarcinomas account for >75% of all cases 2, 3
• Pancreatic, lung, gastric, and ovarian cancers are the most frequently implicated malignancies 4, 3
• Atrial myxoma can directly cause valvular vegetations 2
• Carcinoid syndrome produces characteristic valvular lesions 2
• Direct tumor invasion of cardiac structures may occur 2

2. Autoimmune and Connective Tissue Disorders

• Systemic lupus erythematosus with antiphospholipid antibodies (Libman-Sacks endocarditis) 1
• Primary or secondary antiphospholipid antibody syndrome 1, 2
• Behçet disease 2
• Rheumatoid arthritis 2
• Polyarteritis nodosa 2

3. Hypercoagulable States

• Disseminated intravascular coagulation 1
• Trousseau syndrome (migratory thrombophlebitis with malignancy) 1
• Inherited thrombophilias in the appropriate clinical context 5

4. Chronic Debilitating Conditions

• Septicemia (without direct valve infection) 1
• Severe burns 1
• Tuberculosis 1
• Uremia 1
• AIDS 1

5. Post-Cardiac Surgery

• Vegetations on suture material following valve replacement 2
• Other postoperative valvular changes 2

6. Valvular Degenerative Changes

• Myxomatous degeneration of valve tissue 2
• Ruptured chordae tendineae 2

Pathophysiologic Mechanism

The underlying mechanism involves endothelial damage from turbulent blood flow, leading to platelet and fibrin deposition that forms sterile vegetations in the setting of a hypercoagulable state 1, 6. Unlike infective endocarditis, these vegetations contain no bacteria and cause no destructive changes to the underlying valve 1.

Key Distinguishing Features from Infective Endocarditis

• Persistently negative blood cultures despite adequate sampling 1, 2
• No response to antibiotic therapy 1
• Vegetations are typically small (<3mm), broad-based, and irregularly shaped 1
• More friable and prone to embolization than infectious vegetations 1
• Bilateral valve involvement is more common than in infective endocarditis 1
• Mitral valve affected more frequently than aortic 1

Clinical Pitfalls to Avoid

• Do not confuse culture-negative infective endocarditis (due to prior antibiotics or fastidious organisms) with true marantic endocarditis 1, 2
• Always obtain comprehensive hematologic and coagulation studies to identify the underlying hypercoagulable state 1
• In patients with recurrent systemic emboli, test for antiphospholipid syndrome with lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies on two occasions 12 weeks apart 1
• Consider occult malignancy screening in any patient presenting with unexplained valvular vegetations and systemic emboli 4, 3
• Perform transesophageal echocardiography when clinical suspicion is high, as transthoracic echo may miss small vegetations 1, 2