**5.3 Echocardiography**

In those patients with suspected NBTE, a two-dimensional transthoracic echocardiography (TTE) should be performed to demonstrate the presence of vegetations or valvular thickening (**Figure 3**). Vegetations in the NBTE usually appear in left valves, with the mitral valve most frequently affected (up to 75% of cases) followed by the aortic valve. Several valves can be affected simultaneously, although it is usually an uncommon finding (**Figure 4**).

#### **Figure 4.**

*ETE-2C: Mid-esophageal two-chamber color view. A vegetation in the mitral valve can be visualized. A severe mitral regurgitation jet is shown in this figure.* 

 However, TTE has several limitations. Small vegetations (below 5 mm) may go unnoticed, so if the clinical suspicion is still high, there is an indication to perform a transesophageal echocardiography (TEE), since it is more sensitive and specific than the TTE in detecting smaller vegetations. Do not forget that very small vegetations (<3 mm) cannot be detected by both types of echocardiogram, being able to obtain "false negatives." If the clinical suspicion persists, echocardiographic study should be repeated after a prudential time. Although TTE is less sensitive and specific than TEE, it should always be performed not only to confirm the presence of endocarditis but also to evaluate other fundamental parameters such as function and cardiac volumes.

 Although the echocardiogram is essential in the diagnosis of valvular vegetations, it will not be useful for the differential diagnosis of the type of endocarditis (thrombotic infection vs. aggregations of platelets and fibrin).

#### **5.4 Histology**

 Although the definitive diagnosis is histological, most of the anatomopathological tests of valvular vegetations are obtained from necropsies or after valve replacement after the finding of a severe dysfunction or insufficiency, being very rare the biopsies of tendinous, valvular cords, or endocardial.

#### **6. Treatment and management**

There is no specific treatment for NBTE. The two basic pillars are systemic anticoagulation and targeted specific treatment of the associated disease (chemotherapy, corticosteroids, etc.). In general, surgery by means of intervention, debridement, or valve replacement is usually not necessary and is rarely indicated.

#### **6.1 Anticoagulation**

Anticoagulant treatment is essential in the management of NBTE since it aims to prevent the production of systemic embolisms. In fact, unlike EI, these patients have an indication for anticoagulation for long periods of time or even indefinitely (unless absolutely contraindicated), regardless of whether embolic phenomena are observed or not. This fact is based on the fragility of the vegetations and the recurrent tendency to systemic embolization, especially in the absence of antithrombotic therapy. It should always be anticoagulated with a double objective: preventive and therapeutic. There are no published randomized clinical trials or prospective studies, so the recommendations are based on case series and retrospective studies and are supported by the American College of Chest Physician's antithrombotic therapy for valvular heart disease guidelines [16].

 Anticoagulation will be carried out by subcutaneous low molecular weight heparin or intravenous unfractionated heparin at anticoagulant doses. All the evidence published to date supports the use of this pharmacological family and does not recommend the use of warfarin, direct thrombin, nor factor Xa inhibitor (direct oral anticoagulants like apixaban, rivaroxaban, dabigatran, or edoxaban) especially in patients with active neoplastic disease since they seem to have less efficacy in the reduction of systemic embolisms. There is no data to support the use of the new anticoagulants. Recently the first case of cancer-associated non-bacterial thrombotic endocarditis in the era of direct oral anticoagulants was published where a patient with a previous history of thromboembolic disease developed a NBTE with vegetations and multiple cerebral embolisms in the context of a pancreatic adenocarcinoma despite being under treatment with rivaroxaban at optimal doses [17]. This case supports the

#### *Non-bacterial Thrombotic Endocarditis DOI: http://dx.doi.org/10.5772/intechopen.84398*

need to carry out more studies that help to elucidate the physiopathogenic mechanisms of the NBTE with the aim of achieving an optimal anticoagulant regimen.

The most frequent complications are life-threatening bleeding and thrombocytopenia. The development of any of these complications will force clinicians to raise the risk-benefit of their use and therefore to value discontinuing their use.

#### **6.2 Surgery**

In general, indications for valve replacement or vegetation excision are very limited in the NBTE. The main objective of surgery in the NBTE is to reduce or prevent the production of systemic embolisms. Because there are no prospective clinical trials, the same recommendations should be followed as in patients with IE [18].

However, unlike IE, we will try to preserve the valve as much as possible and focus all the objectives in controlling the state of hypercoagulability by treating predisposing disease.

When deciding whether a patient is going to benefit from surgery, it is essential to assess the risk-benefit individually. The surgical repair of heart valve is preferable (it is less aggressive, has less mortality, and in general decreases the need for postoperative anticoagulation), with respect to valve replacement. The latter will be considered depending on the complications and the degree of destruction or valvular insufficiency. We must take into account the prognosis of life and morbidity and mortality, especially in patients with advanced neoplastic diseases. Although there is little evidence, it is believed that anticoagulation should be maintained after surgery, especially in patients with systemic autoimmune diseases (mainly in APS).

#### **6.3 Treatment for underlying disease**

 The treatment of neoplasia or systemic autoimmune disease is a fundamental pillar in the management of NBTE. It is very probable that at the time of diagnosis of the neoplasm, distant metastases are already observed, which will considerably reduce the probability of therapeutic success. The same is not true in patients with SLE, where NBTE can be diagnosed at any time and whose presence does not correlate with the activity index. The treatment of patients with lupus valve disease includes prophylaxis of endocarditis, antiplatelet or anticoagulant treatment in selected cases, and valvular replacement when valvular involvement is severe; the role of corticosteroid treatment in the evolution of valvular disease is still undetermined. Regarding the type of surgical intervention, there are controversies. Some authors suggest the superiority of mechanical prostheses in this type of condition over bioprostheses, including cryopreserved homografts, as these can contract lupus valvulitis on the new valve. However, other authors have advocated reconstructive surgery to avoid the disadvantages of a mechanical prosthesis in young patients who usually require high doses of steroids and anticoagulant therapy [19].

It is unknown whether NBTE improves with antineoplastic therapy, and therefore it is believed that anticoagulation should be maintained independently of the response to treatment of the underlying disease.

### **7. Evolution and prognosis**

#### **7.1 Follow-up**

The follow-up should be individualized depending on the characteristics and morbidities of each patient. It will be necessary to take into account possible

#### *Infective Endocarditis*

complications of the disease or treatment: systemic embolization, bleeding, or thrombocytopenia. It will be necessary to periodically perform echocardiograms to monitor valve function, control the development of new vegetations (or check their resolution), as well as monitor the appearance of an IE concomitantly.
