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- PATIENTS AND METHODS
Valvular thickening and valve vegetations are frequent in patients with systemic lupus erythematosus (SLE); they usually are associated with mild valvular regurgitation that is clinically irrelevant in a majority of patients (1–10). However, about 10% of SLE patients develop severe valvular regurgitation, with symptoms of heart failure, progressive left ventricular dysfunction, and need for surgery (1, 3, 10).
Attempts to identify patients at risk of developing severe valvular dysfunction have been unsuccessful so far. Some authors have found an association between valvular abnormalities detected by transthoracic echocardiography and the presence of antiphospholipid antibodies (aPL) (2–4, 7, 8). However, other authors (5, 6, 9), some using a more sensitive diagnostic tool such as transesophageal echocardiography (5), found no differences in the prevalence of valvular disease between patients with and without aPL.
The relationship between aPL and the incidence and outcome of valvular disease is difficult to assess because most reports had a short (2 years) followup (3, 8) or no followup at all (2, 4–6, 9). Only 2 series with a longer followup (5 years) focused on valvular heart disease in SLE patients have been published until now (1, 10), but neither contained data on aPL.
The aim of this prospective, clinical and echocardiographic study with a long followup (14 years) was to determine if the presence of aPL is related to the incidence of severe valvular dysfunction and the need for valve replacement in an unselected population of SLE patients.
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- PATIENTS AND METHODS
To our knowledge, this is the first report of a long-term followup study of SLE-associated valvular heart disease to include data on aPL. It is also the first study to focus specifically on severe, clinically significant valvular disease in patients with SLE. Previous reports have described an association between aPL and the presence of any valvular abnormality (2–9). In our series, the number of patients with any valvular abnormality increased from 40% to 70% over 10 years of followup, suggesting that over a long period, a substantial majority of patients will develop valvulopathy. A more sensitive diagnostic tool, such as transesophageal echocardiography, would probably have revealed that nearly all SLE patients (both with and without aPL) would have shown valvular abnormalities, basically valvular thickening with mild regurgitation.
However, not all valvular abnormalities have the same clinical significance. In our series, after 14 years of followup, only 12% of SLE patients had a severe valvular regurgitation causing left ventricular dysfunction and symptoms of heart failure. In this significant minority of patients, the valvular damage appears earlier, is more severe, and does not improve over time. These patients with SLE and severe valvular disease have a high incidence of thromboembolic events and often need valvular surgery. They should be identified early and followed closely by serial echocardiographic examinations.
The development of severe valvular regurgitation was associated with the presence of aPL and, more specifically, with the presence of high levels of IgG aCL. We found no association with the duration, activity, or treatment of lupus. Patients with severe regurgitation were slightly younger than patients with less severe valvular affectation, suggesting that degenerative valvular disease associated with aging does not explain the more severe valvular damage in this group of SLE patients. Our results suggest that high levels of IgG aCL are the most sensitive marker for the detection of SLE patients at high risk of developing severe valvular regurgitation.
A limitation of our study is the small number of patients with severe valvular disease. Nevertheless, this is a consequence of the low prevalence of severe valvular disease in SLE patients.
In our series, 5 of 7 patients who developed severe valvular regurgitation required valvular surgery. In all 5 cases, a valvular replacement was performed and a bivalve mechanical prosthesis was implanted. Reports of valvular surgery in SLE patients are scarce: only about 50 cases have been reported, mostly individual case reports (16–46). Our series of 5 patients is the same size as the largest previously published (41). Although mitral valve repair and mitral valve substitution by a biologic prosthesis or a homograft have been described, mitral valve replacement by a mechanical prosthesis accounts for the majority of surgical procedures in SLE patients.
We found that high levels of IgG aCL were strongly associated with the need for valvular surgery. This is clinically relevant because the risk of thromboembolic events may be significantly increased in patients with a mechanical prosthesis and circulating aPL (47, 48). In fact, 4 of our patients had thromboembolic events after surgery. The antithrombotic strategy in these cases should include the combination of warfarin and aspirin, according to the recommendations of the American Heart Association for patients with a high risk of thrombosis (49).
Lockshin et al have recently reviewed the treatment for valve disease in patients with antiphospholipid antibody syndrome (50). Undoubtedly, the best therapeutic approach for lupus valvulopathy would be to prevent the development of severe valvular damage. Our findings suggest that a local thrombotic mechanism might participate in the pathophysiology of valvular damage in those SLE patients who develop severe valvular regurgitation. However, we found no association between treatment with anticoagulants or antiplatelet drugs and the development of severe valvulopathy, probably due to the small number of patients who received warfarin or aspirin before the diagnosis of severe valvulopathy had been made.
In conclusion, we found that the development of severe valvular regurgitation in SLE patients over a long followup period is associated with the presence of high levels of IgG aCL and with a high incidence of need for valvular surgery and thromboembolic events. In this high-risk group of patients, close clinical and echocardiographic followup is recommended and a more aggressive anticoagulant or antiplatelet therapy aimed at preventing valvular damage may be beneficial.