**4. Clinical presentation**

NBTE is characterized as an asymptomatic disease in early stages, whose most frequent initial manifestation is the presence of systemic embolisms. Although it can occur at any age, it is believed that young patients are less likely to suffer from embolic phenomena at a distance.

The clinic of valvular dysfunction (in the form of heart failure, syncope, etc.) usually appears in more advanced stages of the disease, and although it is recognizable by echocardiographic studies, they usually have little hemodynamic repercussion, except in advanced cases or the presence of large masses. The development of heart failure is present in less than half of patients with underlying valvular dysfunction.

#### **4.1 Characteristics of embolisms**

Given the rarity of this entity, the incidence of embolisms at the systemic level is not known. It is believed that it can appear from 14 to 91% of the NBTE. The embolisms, some with hemorrhagic transformation, are more frequent in cases associated with malignancy [12]. In these patients, embolisms are evident in up to 50% of the cases, the most frequent clinical form being the central nervous system involvement.

Patients with NBTE usually debut in the form of multiple embolisms, especially distributed throughout the brain territory in the form of multiple infarcts (sometimes casual diagnosis after performing brain imaging tests). This contrasts with IE, where typically infarcts are usually focal and/or localized.

#### **4.2 Signs and symptoms**

Most patients are asymptomatic during the early stages of the disease. In fact, the appearance of fever, weight loss, and night sweats is uncommon, and its presence should guide us in the search for an underlying neoplastic process. On the other hand,

#### **Figure 2.**

*ETT-IM: Four-chamber color view showing a jet of severe mitral regurgitation in a 48-year-old man with catastrophic antiphospholipid syndrome.* 

 the association of arthritis, photosensitive skin lesions, and arterial and/or venous thromboses requires screening for systemic autoimmune diseases (SLE or APS).

The typical form of presentation (in more than half of the cases) derives from the symptoms and signs that occur as a result of the presence of systemic embolisms. Although they can be produced in different organs (CNS, kidney, spleen, skin, etc. ), in 50% of cases, embolisms are observed at the pulmonary level, sometimes in the absence of valvular lesions in right cardiac cavities [13].

Sometimes the symptoms may be mild or nonspecific, such as hematuria, lumbar pain, and rash, in the context of renal, splenic, or cutaneous embolisms, respectively. However, the presence of coronary and CNS lesions is more specific and helps the diagnosis more early (chest pain, psychomotor agitation, delirium, stroke, etc.). The debut in the form of valvular insufficiency or decompensated heart failure is very infrequent [14] (**Figure 2**).

#### **5. Diagnosis**

The diagnosis of NBTE is a challenge for the clinician (which is why it is often diagnosed after carrying out necropsies) and not only due to the lack of specificity of the clinic but also because it occurs in advanced stages of the disease.

 The diagnosis of NBTE is made through a high clinical suspicion after observing systemic manifestations derived from systemic embolisms and after performing complementary imaging tests (echocardiogram and transesophageal echocardiography mainly) that confirm the presence of valvular vegetations. However, the definitive diagnosis can be obtained after histologically demonstrating the presence of platelet thrombi at the level of the cardiac valves. It is a rare phenomenon, since valvular biopsies are not performed routinely. For this, it is essential to rule out the presence of a systemic infection and to identify the underlying etiology (mainly autoimmune neoplasms and diseases).

 It is necessary to make a correct differential diagnosis that includes IE, degenerative valvular disease, rheumatic valvular disease, and normal anatomic variants. Applying the modified Duke's criteria can help establish the IE diagnosis [15].

#### *Infective Endocarditis*

 Therefore, we should suspect an NBTE in those patients with active neoplasia, SLE or, APS who present coronary or CNS ischemia or, in the absence of said predisposing pathologies, in those cases in which we suspect an IE (without microbiological findings) that does not respond adequately directed empirical antibiotic treatment and that evolves torpidly with a greater number of systemic embolisms.
