How should non‑infective (sterile) endocarditis be evaluated and managed?

Non-Infective Endocarditis: Evaluation and Management

Overview

Non-infective endocarditis (also called non-bacterial thrombotic endocarditis or marantic endocarditis) requires a fundamentally different approach than infective endocarditis—the cornerstone is treating the underlying disease and anticoagulation, NOT antibiotics. 1, 2

Diagnostic Evaluation

Initial Differentiation from Infective Endocarditis

• Obtain at least 3 sets of blood cultures from separate venipuncture sites before any antibiotics to distinguish true culture-negative infective endocarditis from sterile non-infective endocarditis 1, 3
• Blood cultures remain persistently negative in non-infective endocarditis, whereas culture-negative infective endocarditis may eventually grow fastidious organisms with specialized testing 1
• Perform both transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) as TEE achieves 90-100% sensitivity for detecting vegetations compared to TTE's 40-63% 3, 4

Identifying the Underlying Etiology

Non-infective endocarditis falls into four major categories 1:

Neoplasia-associated (most common cause):

• Marantic endocarditis in advanced malignancies (>75% of cases) 2, 5
• Atrial myxoma
• Carcinoid syndrome
• Direct neoplastic involvement 1

Autoimmune-associated:

• Systemic lupus erythematosus (Libman-Sacks endocarditis) is the second most common cause after malignancy 2, 4
• Antiphospholipid antibody syndrome (primary or secondary) 1
• Behçet disease 1, 2
• Rheumatoid arthritis, polyarteritis nodosa 1, 2
• Hypereosinophilic syndrome 2

Post-valvular surgery:

• Thrombus formation
• Suture material
• Other post-surgical changes 1

Miscellaneous:

• Eosinophilic heart disease
• Myxomatous degeneration
• Ruptured chordae 1

Key Clinical Features to Assess

• Search for evidence of hypercoagulable states including active malignancy, autoimmune disease markers (ANA, anti-dsDNA, anticardiolipin antibodies, lupus anticoagulant), and inflammatory markers 2, 5, 6
• Document embolic phenomena affecting brain, spleen, kidneys, skin, or extremities—these occur frequently due to friable vegetations 2, 5, 6
• Evaluate valve involvement patterns: mitral valve is most commonly affected in antiphospholipid syndrome, while both mitral and aortic valves are typically involved in malignancy-associated disease 1, 5
• Vegetations in non-infective endocarditis are typically small, friable, and sterile 2, 5

Advanced Imaging When Diagnosis Remains Uncertain

• Consider cardiac CT or PET/CT to differentiate from cardiac tumors, residual lesions from prior endocarditis, or to identify occult malignancy 7
• MRI may help exclude intracranial hemorrhage if neurological symptoms develop 8

Management

Primary Treatment Strategy

The fundamental treatment is aggressive management of the underlying disease, NOT antibiotics, as these are sterile vegetations. 2, 6, 7

Anticoagulation Therapy

• The American College of Chest Physicians recommends full-dose IV unfractionated heparin or subcutaneous low molecular weight heparin for patients with non-bacterial thrombotic endocarditis and systemic or pulmonary emboli (Grade 2C recommendation) 8, 7
• Anticoagulation should continue until vegetation resolution (median 11 months) or for at least 1-2 years to mitigate embolic risks 7
• This is the opposite recommendation from infective endocarditis, where routine anticoagulation is contraindicated 8

Critical Management Pitfall

Do not confuse non-infective endocarditis with infective endocarditis—they have opposite anticoagulation recommendations. In infective endocarditis, anticoagulation is generally avoided due to hemorrhagic risk, whereas in non-infective endocarditis, anticoagulation is the primary medical therapy 8, 5, 7

Surgical Intervention

• Indications for cardiac surgery are poorly defined compared to infective endocarditis 2
• Optimal control of the underlying disease before surgery is critical, as it dramatically reduces postoperative complications 2
• Surgery may be considered for severe valvular dysfunction, recurrent emboli despite anticoagulation, or hemodynamic compromise 2, 4
• Valve replacement was successful in isolated tricuspid Libman-Sacks endocarditis after medical stabilization 4

Disease-Specific Considerations

For systemic lupus erythematosus/Libman-Sacks endocarditis:

• Intensify immunosuppressive therapy with corticosteroids and disease-modifying agents 2, 4
• Echocardiography is the definitive modality for assessing valvular involvement, choosing therapy, and evaluating prognosis 4

For malignancy-associated marantic endocarditis:

• Prognosis is poor with high morbidity and mortality related to the underlying malignancy 5, 6
• Focus on treating the cancer while preventing embolic complications with anticoagulation 5, 6

For antiphospholipid syndrome:

• Long-term anticoagulation is essential 1
• Mitral regurgitation is the predominant functional abnormality 1

Monitoring and Follow-up

• Serial echocardiography to assess vegetation resolution and valve function 4, 7
• Vigilance for embolic events, particularly during the first weeks of treatment 5, 6
• Reassess for occult malignancy if no underlying cause is initially identified 2, 6

Common Diagnostic Pitfalls to Avoid

• Do not empirically treat with prolonged antibiotics when blood cultures remain negative and clinical features suggest non-infective etiology—this delays appropriate anticoagulation and treatment of underlying disease 2, 7
• Do not assume all culture-negative endocarditis is non-infective—fastidious organisms (Bartonella, Coxiella, Brucella) require specialized testing and serology 1
• Diagnosis is often made post-mortem due to subtle presentation, so maintain high clinical suspicion in patients with malignancy or autoimmune disease who develop embolic phenomena 5, 6