Case Presentation

A 53-year-old woman presented to the hospital with a 6-month history of progressively worsening dyspnea on exertion, peripheral edema, and decreased exercise capacity. The patient’s medical history was notable for antiphospholipid syndrome (APS) diagnosed by positive anticardiolipin and β ₂ glycoprotein antibodies, multiple miscarriages, deep venous thromboses, and thrombocytopenia; an inferior vena caval filter had been placed 7 years earlier. On physical exam, her vital signs were within normal limits, the jugular venous pressure was 12 cm H ₂ O, and a loud P2 and soft diastolic and systolic murmurs were heard at the left lower sternal border. The lungs were clear, and there was moderate pitting edema to the midthighs. The results of 12-lead electrocardiography were normal. A chest x-ray revealed an enlarged cardiac silhouette and clear lung fields. The chest x-ray also confirmed that a peripherally inserted central catheter terminated in the superior vena cava. Laboratory studies revealed a platelet count of 37 × 10 ⁹ /L and elevated liver function test results.

Transthoracic echocardiography ( Figure 1 , Movie 1 ) showed right ventricular and right atrial enlargement, moderately thickened tricuspid valve leaflets and subvalvular tissues, and supra-annular thickening. Doppler revealed a moderate to severe central jet of tricuspid regurgitation, mild tricuspid stenosis, and severe pulmonary hypertension. Left ventricular size and function were normal. A real-time 3-dimensional transesophageal study revealed nodular echodensities on the tricuspid leaflets ( Figure 2 , Movies 2 and 3 ) and atrial endocardial thickening extending from the supravalvular region to the junction of the inferior vena cava and right atrium. The mitral, aortic, and pulmonary valves were normal. A patent foramen ovale with right-to-left shunting was demonstrated by color Doppler. The patient was diuresed and was discharged home on fondaparinux in good condition. An outpatient evaluation suggested a multifactorial etiology of her pulmonary hypertension.

Transthoracic echocardiogram. (A) Apical 4-chamber view with an enlarged right ventricle (RV) and right atrium (RA) and a calcified annulus with thickened tricuspid valve leaflets. (B) Basal short-axis view highlights the thickening and calcium along the supravalvular ridge, tricuspid annulus, and tricuspid leaflets.

Transesophageal echocardiogram (tilted 4-chamber view) shows the thickening of the tricuspid leaflets and annulus with echodensities extending into the atrial endocardial surface. RA , Right atrium; RV , right ventricle.

Discussion

The patient described herein presented with chronic right-heart failure and was found to have isolated tricuspid valve nonbacterial thrombotic endocarditis (NBTE) with resultant tricuspid stenosis and regurgitation. There have been a total of 6 patients reported in the literature with isolated tricuspid valve disease due to primary APS ; these cases are all notable for the presence of positive anticardiolipin antibodies occurring in women ranging from 23 to 62 years of age. Our case of NBTE associated with primary APS matches the demographics of these prior cases but, notably, involved not only the tricuspid valve but also the right atrial endocardium.

NBTE is characterized by noninfectious valvular vegetations and subsequent leaflet thickening and is associated with autoimmune and connective tissue disorders, malignancies, and mechanical trauma from vascular interventions. APS can be primary or secondary, the usual etiology being systemic lupus erythematosus (Libman-Sacks endocarditis). It has been proposed that the antiphospholipid antibodies are themselves pathogenetic; it has been documented that the presence of these antibodies corresponds to the likelihood of valvular disease in patients with systemic lupus erythematosus. Although most cases of APS-related NBTE involve the mitral and aortic valves, rare occasions of isolated tricuspid valve disease are reported. The lesions are sterile vegetations, but progression or recurrent healing is thought to lead to valvular thickening and scarring. The pathology of the lesions can be quite variable in terms of size and histology, but according to a pathologic series, they involve platelet-fibrin thrombi, fibroblastic changes, collections of macrophages, and calcification.

The diagnosis is typically made by echocardiography. The distinction between infective and noninfective endocarditis can be difficult to make by echocardiographic features alone, but diffuse valvular thickening suggesting a more chronic and recurring process supports the diagnosis of nonbacterial thrombotic vegetation.

Although the management of APS involves anticoagulation (usually with a vitamin K antagonist) and antiplatelet therapy, the management of NBTE in the setting of APS is less clear. Zavaleta et al evaluated the therapeutic role of anticoagulation in an observational transesophageal echocardiographic study involving 24 patients who underwent transesophageal echocardiography at entry, 12 of whom underwent follow-up transesophageal echocardiography at 5 years. They found that despite regular anticoagulation and antiplatelet therapy, NBTE lesions did not resolve during the follow-up period. Although steroids decrease inflammation, promote the resolution of vegetations, and accelerate the scarring of valves, no recent data support the role of steroids for NBTE. Thus, despite a suspected pathologic mechanism of immune reactivation and/or hypercoagulable thrombotic lesions, neither steroids nor anticoagulation seems to be an effective therapy. The role for surgery is not well defined, and no guidelines exist to specifically address the surgical management of NBTE.

In conclusion, our patient presented with symptomatic isolated tricuspid valve NBTE due to primary APS. She was managed successfully with diuretic therapy and anticoagulation. Clinicians should keep in mind that although they are rare, isolated tricuspid valve lesions can result from APS and/or lupus. There is a lack of clear evidence to guide any specific therapies for these patients given their relatively infrequent occurrence.