Endocarditis and endocardial diseases

Article written and reviewed by Dr Luca Moretti

The endocardium lines the cardiac chambers and the structures projecting into them, including trabeculae, papillary muscles, chordae tendineae and valvular surfaces. It consists of an endothelium continuous with the vascular endothelium and underlying connective tissue, whose thickness and relationship with the myocardium vary by site. Its functions include maintaining an antithrombotic surface and participating in signalling exchanges between blood and the cardiac wall. An endocardial lesion can therefore produce very different consequences: it may become a site of microbial colonization, support sterile thrombosis, or alter the geometry and compliance of a cardiac chamber.

Endocarditis and endocardial diseases encompass three major areas: infections, non-infectious thrombotic or immune-mediated lesions, and endomyocardial diseases. This distinction is clinically decisive because similar imaging findings may require antibiotics and surgery, anticoagulation and control of a systemic disease, or treatment of an eosinophilic process or fibrotic deformity. The term vegetation describes a formation adherent to the endocardium, but by itself does not identify its nature. Similarly, negative blood cultures do not make a mass sterile, while endocardial thickening does not necessarily demonstrate active inflammation.

Infective endocarditis mainly involves native valves, prostheses and intracardiac material; non-infective endocarditis mainly includes nonbacterial thrombotic endocarditis and Libman-Sacks endocarditis; endomyocardial diseases include eosinophilic disorders, endomyocardial fibrosis and fibroelastosis. These categories do not encompass all cardiac masses: fibroelastomas, Lambl excrescences, calcifications and thrombi secondary to cardiomyopathy belong to the differential diagnosis. The initial classification serves to guide subsequent questions while keeping anatomical site, mechanism and functional consequences distinct.

There is no single prevalence for the group as a whole. Endocardial infection varies with age, valvular disease, use of prostheses and devices, vascular access and healthcare setting; sterile thrombotic forms depend on the prevalence of malignancy and autoimmune diseases and on how intensively embolic sources are sought. Endomyocardial fibrosis has geographical foci, whereas fibroelastosis is primarily a fetal and pediatric disorder. Autopsy, surgical and screening series observe different stages of disease and do not provide directly interchangeable estimates. For the individual patient, the main priority is to identify a treatable lesion before embolization or haemodynamic deterioration causes irreversible damage.

Etiology, pathogenesis and pathophysiology

Endothelial integrity limits platelet adhesion and activation of coagulation. High-velocity jets, mechanical stress, inflammation and systemic mediators can disrupt it, exposing the underlying matrix and promoting deposition of platelets and fibrin. This deposit provides a potential surface for adhesion of circulating microorganisms, but it may also remain sterile. Pre-existing damage is important but not mandatory: highly invasive pathogens, especially Staphylococcus aureus, can infect apparently normal valves. Risk therefore arises from the interaction between the surface, bloodstream exposure and the biological characteristics of the organism, rather than from the mere presence of valvular disease.

In infection, microbial adhesion and proliferation transform the deposit into a persistent focus. The high density of microorganisms, limited vascularization of the vegetation and presence of slowly metabolizing cells make eradication more difficult than in bacteremia without a deep-seated focus. On prostheses and devices, biofilm adds a matrix that promotes persistence and tolerance to treatment. This does not necessarily coincide with resistance detectable on susceptibility testing: a susceptible isolate can remain difficult to eradicate if it occupies a protected niche or infected material that is not removed.

In nonbacterial thrombotic endocarditis, platelet and fibrin deposition predominate in a setting of coagulation and endothelial activation, frequently associated with malignancy. Valvular damage may be modest relative to embolic risk because a friable vegetation can fragment without impairing leaflet coaptation. In lupus and antiphospholipid syndrome, inflammation, immune-mediated injury and thrombosis can combine and leave valvular scarring. Lupus, antibody positivity and clinically defined antiphospholipid syndrome are not equivalent: the significance of the lesion and the antithrombotic choice depend on the context actually documented.

In eosinophilic injury, degranulation products can damage cardiomyocytes and endothelium, promoting inflammation, mural thrombosis and fibrotic repair. Clonal myeloid proliferation, a cytokine-driven response, a drug reaction and vasculitis can produce a similar cardiac phenotype through different causes. The peripheral blood count does not directly measure tissue burden and may be blunted by treatment. The necrosis-thrombosis-fibrosis sequence is an evolutionary model, but the components can coexist and should not be treated as three mandatory, sharply separated phases.

Endomyocardial fibrosis in endemic areas shares part of the restrictive outcome without having been proven to be an eosinophilic disease in every case. Fibroelastosis, by contrast, is thickening rich in collagen and elastic fibers, often developing in the immature heart in association with abnormal flow, obstruction or cardiomyopathy. The final similarity between two scars does not prove identical pathogenesis. This distinction prevents a causal therapy that is effective in one subgroup from being extended to all diseases characterized by a thickened endocardium.

The site of the lesion determines a substantial proportion of its consequences. Leaflet perforation, chordal rupture or loss of annular support can cause acute regurgitation. In sudden mitral regurgitation, a non-adapted atrium receives a large volume during systole and rapidly transmits the pressure increase to the lungs; in acute aortic regurgitation, the ventricle may reach high diastolic pressures before it dilates. The absence of markedly enlarged chambers on echocardiography therefore does not exclude a haemodynamically critical lesion. Assessment of mechanism and pressures is more informative than cardiac size alone.

When mural involvement predominates, thickening and apical obliteration reduce usable chamber volume and increase stiffness. A normal ejection fraction may correspond to a low absolute stroke volume because the percentage ejected is calculated from a small cavity. Encasement of chordae and papillary muscles adds atrioventricular regurgitation. Congestion then results from the combination of impaired filling and reduced forward output, with systemic or pulmonary predominance according to the ventricle involved. These mechanisms explain why endocardial disease can be severe without marked depression of systolic function.

Embolization depends on the composition, mobility and stability of the lesion as well as its size. A left-sided source feeds the systemic circulation and a right-sided source the pulmonary circulation; any shunts may alter this distribution. An infected embolus can produce a secondary focus, whereas a sterile embolus mainly causes occlusion and ischemia. In both cases, a small residual mass does not quantify the lesion before detachment. Moreover, malignancy, antiphospholipid syndrome and hypereosinophilia may promote thrombosis away from the heart, making source verification necessary rather than automatically attributing every ischemic event to the valve.

Clinical manifestations

The presenting problem guides priorities: fever and bacteremia, heart failure, embolism or an incidental finding require different initial pathways. The medical history reconstructs chronology, changes in functional capacity, weight loss, sweating and organ-specific symptoms, together with previous valvular disease, prostheses, devices and vascular access. When infection is suspected, procedures and exposures help estimate probability, but the absence of an obvious portal of entry does not exclude disease. In older or immunocompromised patients, fever may be mild and delirium, anorexia or worsening renal function may predominate.

Haemodynamic manifestations include dyspnea, orthopnea, reduced exercise tolerance, edema and ascites. Rapid onset suggests acute regurgitation, sepsis or arrhythmia; a slow course may reflect restriction, scar-related valvular disease or progressive ventricular injury. Examination assesses venous pressure, perfusion, pulmonary congestion, the liver and murmurs, without assigning auscultation sufficient sensitivity to exclude important lesions. In infants, sweating and fatigue during feeding, tachypnea and poor weight gain may be more evident than peripheral edema.

Sudden neurological deficits, amaurosis, limb pain, abdominal pain or flank pain require investigation for an embolic event. Persistent low back pain, joint pain and fever may indicate secondary infectious foci; neuropathy, purpura and respiratory symptoms may instead point toward an immune-mediated or eosinophilic disease. The neurological examination and peripheral assessment should therefore accompany the cardiac evaluation from the outset. Classic signs of endocarditis, such as Osler nodes and Janeway lesions, are useful when present but too inconsistent to be required for diagnosis.

The systemic context includes malignancy, lupus, previous thrombosis, obstetric complications, asthma, eosinophilia and medication history. Antibiotics can reduce culture positivity, corticosteroids can attenuate fever and eosinophilia, and anticoagulants can modify a thrombotic mass. Reconstructing prior treatments is therefore part of disease interpretation, not merely an administrative list. A vegetation in a patient with cancer may be infected, while fever in a patient with lupus may have different causes: comorbidity changes probability without replacing proof.

Investigations and diagnosis

The diagnostic work-up must establish whether a real lesion exists, what its mechanism is and what consequences it has produced. Transthoracic echocardiography defines site, mobility, anatomical relationships, and valvular and ventricular function; transesophageal echocardiography provides further assessment of small masses, prostheses, perivalvular complications and persistent suspicion. A description limited to the word vegetation is insufficient: implantation site, dimensions, movement, regurgitation and comparison with previous studies should be documented. Calcifications, sutures and artifacts can mimic lesions, whereas a very small or already embolized vegetation may escape detection.

When infection is plausible, blood cultures are obtained before antimicrobials, usually three peripheral sets with an adequate blood volume. There is no need to wait for a fever peak; in unstable patients, sampling is organized rapidly without delaying treatment. The identity of the microorganism, number of positive sets, persistence and presence of intracardiac material alter the significance of the result. An isolate that may represent contamination can be relevant in a patient with a prosthesis, whereas a negative blood culture after antibiotics has a different meaning from a properly obtained sample collected before any dose.

When suspicion persists despite negative cultures, the pathway reconstructs antibiotic exposure and considers pathogens that are difficult to identify with routine methods. Serology and molecular tests are selected according to context, with particular relevance of Coxiella burnetii and Bartonella in appropriate situations. The Duke-ISCVID criteria and ESC criteria organize the evidence for infective endocarditis, but they should not be mixed into a hybrid system. A non-definitive classification may require further testing; it does not prove a sterile form and does not by itself justify anticoagulation or immunosuppression.

Cardiac CT is useful for perivalvular anatomy, abscesses, pseudoaneurysms and fistulas, especially when prostheses and calcifications limit echocardiography. Fluorodeoxyglucose PET/CT and, in selected settings, radiolabeled leukocyte imaging contribute to the evaluation of suspected prosthetic infection and the search for extracardiac foci. Uptake is an inflammatory signal, not a culture result: preparation, distribution, time since surgery and surgical materials influence interpretation. In small native-valve vegetations, a negative metabolic study does not exclude infection.

Cardiac magnetic resonance has a different role in endomyocardial diseases: cine imaging, edema-sensitive sequences and late enhancement help distinguish thrombus, fibrosis and myocardial injury. Thrombus is generally avascular, whereas fibrosis shows expansion of the extracellular space; age and organization may, however, modify signal characteristics. Persistent enhancement alone does not demonstrate active inflammation. CMR should answer a specific question, for example how much of the obliteration is due to thrombus and how much to scar, rather than being used as generic confirmation of every endocardial finding.

Systemic investigations are selected according to the clinical suspicion. Complete blood count with differential, renal and liver function, urinalysis, inflammatory markers and coagulation studies characterize severity and context; antiphospholipid antibodies and investigations for lupus require clinical interpretation and attention to interference. Persistent blood or tissue hypereosinophilia prompts evaluation for reactive, clonal and idiopathic causes. Cancer investigation should be guided by history and findings, while in a child with fibroelastosis structural and coronary abnormalities, genetics, metabolism and maternal autoantibodies are relevant. An indiscriminate panel does not replace this reasoned selection.

When tissue is available, histology and microbiology should be planned together. Part of the sample is kept suitable for culture and molecular methods, avoiding fixation of all material; histology assesses microorganisms, inflammation, thrombosis and organization. Molecular positivity must be correlated with the clinical picture because detection of genetic material does not always imply viable microorganisms. Endomyocardial biopsy is reserved for questions in which tissue characterization can change treatment, particularly in severe myocarditis; it is not mandatory for every typical, stable scar.

Treatment and prognosis

Treatment is built around the causal mechanism. Infection requires appropriate antimicrobials, source control and early assessment of surgical indications; disappearance of fever is not sufficient to demonstrate eradication. In sterile thrombosis, embolic prevention is combined with treatment of malignancy or autoimmune disease. In eosinophilic injury, the choice among corticosteroids, molecularly targeted therapy and other interventions depends on the cause; in established fibrosis, the problem may be predominantly mechanical. A treatment that is effective for one component may leave the others unchanged.

Anticoagulation illustrates these differences well. It may be central in sterile endocardial thrombosis or in the presence of an intracavitary thrombus, but it is not initiated solely to prevent emboli from infective endocarditis. In the latter, risk of intracranial hemorrhage, infectious aneurysms and procedures can make automatic application of the rules used for sterile thrombosis dangerous. A pre-existing indication, such as a mechanical prosthesis, remains a separate issue and requires individualized management. Drug choice and timing should reflect the embolic source, any neurological injury, renal function and surgical needs.

Haemodynamic stabilization accompanies causal treatment. Diuretics, respiratory support and circulatory support may be required, but a perforated valve or dehiscent prosthesis does not regain competence with medication alone. In endomyocardial restriction, volume removal should reduce congestion without compromising preload-dependent output. In children, anatomy and the intended circulation determine every intervention: standard adult heart-failure therapy cannot simply be transferred to obstructive heart disease or a borderline ventricle.

Surgery serves different objectives: removing infected tissue and material, correcting poorly tolerated regurgitation, preventing embolization in selected situations, or recovering volume and function in fibrosing disease. In infective endocarditis, heart failure, uncontrolled infection and embolic risk are the three principal axes of decision-making. In endomyocardial fibrosis, endocardiectomy and the valvular apparatus are assessed; in fibroelastosis, resection may be part of combined pediatric programs. Sharing the term intervention does not make indications, timing and potential for recovery equivalent.

Response must be assessed on distinct levels. Clearance of blood cultures documents control of bacteremia but does not exclude an abscess; reduction in vegetation size does not guarantee normalization of regurgitation; remission of eosinophilia does not remove a scar. Follow-up integrates symptoms, functional capacity, imaging, rhythm and markers of the systemic cause. A residual mass may be organized and inactive, whereas functional deterioration despite an unchanged mass may be due to the valve or an arrhythmia. Prognosis derives from the interaction among control of the cause, residual damage and comorbidities, not from the initial size of the lesion alone.

Prevention includes oral and skin health, proper management of vascular access, reduction of healthcare-associated bacteremia and prompt recognition of infections. Dental antibiotic prophylaxis follows specific risk categories and procedures, not the generic presence of endocardial disease. In systemic forms, continuity of treatment and planned interruptions reduce the risk of thrombotic or inflammatory recurrence. Education regarding warning symptoms and nutritional and functional recovery complete care, particularly after prolonged hospitalization or neurological injury.

Complications

Embolic complications can cause loss of independence, visceral or peripheral ischemia and, in infection, secondary abscesses. In the brain, ischemia, hemorrhagic transformation, primary hemorrhage and infectious aneurysm pose different problems for anticoagulation and surgical timing. The distribution of events helps in the search for the source but does not replace demonstration. An embolism occurring during treatment requires reassessment of disease activity, adequacy of exposure and possible alternative sources.

Perivalvular destruction is a particularly important complication of infection: abscess, pseudoaneurysm and fistula can compromise valvular support and structural continuity. A new conduction disturbance, especially with aortic involvement, suggests possible extension toward the conduction system and requires prompt reassessment. In prosthetic valves, dehiscence can cause paravalvular regurgitation and hemolysis. Treating bradycardia or congestion does not eliminate the anatomical focus that generated them.

Progressive heart failure may result from regurgitation, restriction or myocardial dysfunction, with renal and hepatic injury, malnutrition and reduced tolerance of treatment. An increase in creatinine may reflect hypoperfusion, congestion, emboli, glomerulonephritis or toxicity: distinguishing these mechanisms changes management. In chronic disease, advanced extracardiac dysfunction can narrow the options for corrective procedures or transplantation, making assessment important before the balance becomes irreversible.

Treatment introduces risks of its own, including bleeding, antimicrobial toxicity, infections during immunosuppression and complications of prostheses and devices. After an infection, recurrence with the same organism may suggest persistence of a focus, whereas a new infection requires investigation for a new bacteremia and the underlying predisposition. After a sterile or eosinophilic disease, recurrent thrombosis may indicate systemic reactivation. Surveillance should therefore retain the original causal diagnosis and treatment history so that a new event can be interpreted without starting over from the nonspecific finding of an endocardial mass.