Correspondence
Valvular Heart Disease and Systemic Lupus Erythematosus
N Engl J Med 1997; 336:1324-1325May 1, 1997
- Article
To the Editor:
The article by Roldan et al. on valvular heart disease associated with systemic lupus erythematosus (Nov. 7 issue)1 prompts two remarks. First, the authors did not give any data on antiphospholipid antibodies. There are at least five studies showing an association between the presence of antiphospholipid antibodies and valvular heart disease in patients with lupus.2 Furthermore, antiphospholipid antibodies have been detected in heart-valve lesions, suggesting a causative role of these antibodies.3 The close association of antiphospholipid antibodies with thrombotic events has shed light on the focal neurologic manifestations of lupus. Indeed, these manifestations, previously assumed to result from vasculitis, are usually due to thrombotic or cardioembolic events related to antiphospholipid antibodies, not to true vasculitis, which rarely affects large or medium-sized vessels in patients with lupus.4
The presence of antiphospholipid antibodies in patients with lupus and vascular events has major therapeutic implications, as shown by Khamashta et al.,5 making the missing data particularly important. Long-term treatment with warfarin has been shown to be much more effective than antiplatelet therapy for secondary prevention in patients with the antiphospholipid-antibody syndrome.5 Hence, data on new vascular events or changes in cardiac valvular abnormalities in relation both to the results of antiphospholipid-antibody tests and to the use or nonuse of anticoagulant agents are also obviously important.
Second, it should be noted that among the four patients requiring valve replacement, two declined surgery, and both died from refractory heart failure.1 In our series of patients with systemic lupus erythematosus, nine underwent heart-valve surgery because of hemodynamic intolerance. All but one of the patients had antiphospholipid antibodies. Extracardiac thrombotic events had occurred in seven. With a mean follow-up of four years after the surgery, all the patients survived and had functional improvement. Heart-valve surgery should be strongly recommended for patients with systemic lupus erythematosus and severe valvular heart disease.
5 ReferencesJean-Charles Piette, M.D.
Zahir Amoura, M.D.
Thomas Papo, M.D.
Groupe Hospitalier Pitié–Salpêtrière, 75013 Paris, France1
Roldan CA ,Shively BK ,Crawford MH . An echocardiographic study of valvular heart disease associated with systemic lupus erythematosus. N Engl J Med 1996;335:1424-1430
Full Text | Web of Science | Medline2
Cervera R, Font J, Ingelmo M. Cardiac manifestations in the antiphospholipid syndrome. In: Asherson RA, Cervera R, Piette JC, Shoenfeld Y, eds. The antiphospholipid syndrome. Boca Raton, Fla.: CRC Press, 1996:151-60.
3
Hojnik M ,George J ,Ziporen L ,Shoenfeld Y . Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation 1996;93:1579-1587
Web of Science | Medline4
Lie JT . Vasculopathy of the antiphospholipid syndromes revisited: thrombosis is the culprit and vasculitis the consort. Lupus 1996;5:368-371
Web of Science | Medline5
Khamashta MA ,Cuadrado MJ ,Mujic F ,Taub NA ,Hunt BJ ,Hughes GRV . The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995;332:993-997
Full Text | Web of Science | Medline
To the Editor:
Roldan et al. report the results of an echocardiographic study of valvular heart disease associated with systemic lupus erythematosus and conclude, “Neither the presence of valvular disease nor changes in valvular disease over time were temporally associated with the duration, activity or severity, or treatment of lupus.” All the patients in the study underwent a complete clinical evaluation at the time of each echocardiographic study, but the auscultatory findings on cardiac examination are not included in the report. It would be of great value to know the clinical correlates of the echocardiographic findings and whether these correlates were predictive of the prognosis.
As reported in the references cited by Roldan et al., an association between antiphospholipid antibodies and valvular injury in patients with lupus has been noted by other investigators. The initial echocardiographic findings in the patients described by Roldan et al. were reported in the context of the possible role of antiphospholipid antibodies, and the authors concluded that these antibodies are not associated with more frequent or more severe valvular disease.1 Their 10 patients with the antiphospholipid-antibody syndrome had no more valvular disease than the normal controls. It would be of interest to know whether this absence of an association persisted at follow-up.
1 ReferencesGeraldine M. McCarthy, M.D.
Daniel J. McCarty, M.D.
Medical College of Wisconsin, Milwaukee, WI 532261
Roldan CA ,Shively BK ,Lau CC ,Gurule FT ,Smith EA ,Crawford MH . Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies. J Am Coll Cardiol 1992;20:1127-1134
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: The role of antiphospholipid antibodies in the pathogenesis of valvular heart disease associated with systemic lupus erythematosus is controversial. We and others have found that the prevalence of valvular abnormalities in patients with antibodies is similar to the prevalence in those without antibodies, irrespective of their level.1,2 Other investigators3 have suggested an association between valvular abnormalities and antiphospholipid antibodies, but causality cannot be established for several reasons. First, 30 to 50 percent of patients with valvular abnormalities have low levels of antiphospholipid antibodies. Second, 25 to 40 percent of patients with normal valves have elevated levels of antiphospholipid antibodies. Third, at least 25 percent of patients without such antibodies have valvular abnormalities. Fourth, the reported prevalence rates for valvular abnormalities in patients with antibodies are similar to the rates for patients without antibodies, and the rates vary widely, from 14 to 77 percent and 11 to 72 percent, respectively. Fifth, the prevalence of valvular abnormalities in patients with lupus who do not have antibodies is similar to that in patients who have antibodies but not lupus. Sixth, there is pathological evidence of the deposition of immune complexes in valvular lesions.4 Finally, the predominance of valvulitis and Libman–Sacks vegetations, as compared with the rare occurrence of thrombotic vegetations without valvulitis, has been reported in the pathological literature.
Thrombogenesis is the proposed mechanism of valvular injury induced by antiphospholipid antibodies. Fifteen percent of our patients with valvular abnormalities on the initial echocardiogram were receiving anticoagulant therapy, but changes in these abnormalities over time were not related to the therapy. The majority of focal neurologic events in our patients were more likely to be related to cardioembolism or in situ thrombosis than to cerebritis or vasculitis. We concur that in patients with focal neurologic deficits, anticoagulant therapy should be considered without regard to the presence of antibodies. Currently, we have no follow-up data on antiphospholipid antibodies.
Within one month after the first echocardiographic study, all the patients with lupus and the normal controls underwent a complete cardiovascular physical examination by an experienced cardiologist who was unaware of the clinical data.5 Regurgitant murmurs were detected in all 10 patients with moderate or severe regurgitation, but the severity of regurgitation was frequently underestimated. The three patients with valvular stenosis received the correct diagnosis. The physical examination was less accurate in patients with mild regurgitation lesions and in those with valvular masses or thickening without regurgitation. However, most of the patients in whom valvular complications developed had clinically evident valvular heart disease. Thus, the cardiovascular physical examination has good diagnostic and prognostic value in the detection of valvular heart disease associated with systemic lupus erythematosus.
5 ReferencesCarlos A. Roldan, M.D.
Michael H. Crawford, M.D.
Veterans Affairs Medical Center, Albuquerque, NM 871081
Roldan CA ,Shively BK ,Lau CC ,Gurule FT ,Smith EA ,Crawford MH . Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies. J Am Coll Cardiol 1992;20:1127-1134
CrossRef | Web of Science | Medline2
Gleason CB ,Stoddard MF ,Wagner SG ,Longaker RA ,Pierangeli S ,Harris EN . A comparison of cardiac valvular involvement in the primary antiphospholipid syndrome versus anticardiolipin-negative systemic lupus erythematosus. Am Heart J 1993;125:1123-1129
CrossRef | Web of Science | Medline3
Hojnik M ,George J ,Ziporen L ,Shoenfeld Y . Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation 1996;93:1579-1587
Web of Science | Medline4
Shapiro RF ,Gamble CN ,Wiesner KB , et al. Immunopathogenesis of Libman-Sacks endocarditis: assessment by light and immunofluorescent microscopy in two patients. Ann Rheum Dis 1977;36:508-516
CrossRef | Web of Science | Medline5
Roldan CA ,Shively BK ,Crawford MH . Value of the cardiovascular physical examination for detecting valvular heart disease in asymptomatic subjects. Am J Cardiol 1996;77:1327-1331
CrossRef | Web of Science | Medline
