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FEATURE ARTICLE

Ernest 6. Luce, DDS, Charles F. Presti, MD, Irma Montemayor, MD, Michael H. Crawford, MD

Detecting cardiac valvular pathology in patients with systemic lupus erythematosus Systemic lupus erythematosus (SLE) is associated with multiple cardiac complications, including valvular damage and an increased risk of bacterial endocarditis. The purpose of this study was to evaluate prospectively a group of patients with SLE for the presence of valvular abnormalities in order to assess their candidacy for antibiotic prophylaxis pdor to invasive dental procedures. Of the 43 participants, 19 (44%)had echocardiographic evidence of valvular pathology; however, only seven (16%)had a physical exam consistent with pathologic valve anatomy or function. Because of the high percentage of SLE patients with valvular abnormalities, and the poor sensitivity of the physical exam, referral to a cardiologist for echocardiography is suggested prior to invasive dental care for patients with SLE. If cardiac valvular pathology is detected, antibiotic prophytaxis should be considered.

S

ystemic lupus erythematosus (SLE) is an auto-immune disorder affecting multiple organ systems.‘ his progressiie disease process is known to damage multiple tissue and organ systems, such as muscle, skin, brain, kidney, and heart, with much of the damage believed to be secondary to the deposition of immune complexes in tissue.’ The disease often presents with vague symptoms-such as unexplained low-grade fevers, rashes, and arthralgias-and can take several years to be diagnosed definitively. Diagnosis is complicated, since there is no single test upon which to base the diagnosis of SLE. In 1982, the American Rheumatism Association published revised criteria for the diagnosis of SLE.2 A patient must manifest four or more of these criteria, either serially or simultaneously, in order for the diagnosis to be verified.2 (See Table 1.) Management of the disease is multivariate, depending on the severity and type of organ involvement. Nonsteroidal antiinflammatory agents, corticosteroids, antimalarial and immunosuppressive drug regimens are all used? Cardiac involvement includes conditions such as pericarditis4l5, verrucous endocarditisq aortic7and mitral*insufficiency, myocardial infarction9,and acute myocarditislO. In 1924, Libman and Sacks described four cases of ”atypical verrucous endocarditis” in patients later recognized as having SLE.6 Multiple terms-such as ”atypical verrucous endocarditis”, ”verrucous endocarditis”, “non-bacterial thrombotic endocarditis” (NBTE), and ”Libman-Sacksendocarditis”-are all

used to identify the cardiac valvular lesions seen in patients with SLE. Hereafter in this paper, the term “Libman-Sacks” will be used to identify these endocardia1lesions. Formation of these lesions begins with the deposition of circulating immune complexes on cardiac endothelium. Inflammatory mediators are released which increase tissue permeTable 1. Diagnostic criteria for SLE.’

Butterfly rash 2. Discoid lupus 3. Photosensitivity 4. Oral ulcers 5 . Arthritis 6. Serositis a. pleuritis b. pericarditis 7. Renal disorder a. persistent proteinuria greater than 0.5 g/day or greater than 3+ b. cellular casts 8. Neurologic disorder 9. Hematologic disorder a. hemolytic anemia b. leukopenia c. lymphopenia d. thrombocytopenia 10. Immunologic disorder a. positive LE cell preparation b. anti-DNA antibody c. anti-Sm d. false-positiveSTS (serologictest for syphilis) 11. Antinuclear antibody 1.

Special Care In Dentidry, Val 12 No I 1992 193

ability and edema. Capillaries and fibroblasts then invade the area." The Libman-Sacks lesions which form are typically 1.0-10.0 mm in diameter, round, raised, fibrinous projections adhering to the valve leaflet, annulus, or papillary muscles, and may appear as solitary or clustered growths. Libman-Sacks lesions are most often seen on the mitral valve leaflets.6J2 Prior to the widespread use of corticosteroids, however, these lesions were commonly seen on other valves, valve rings, and papillary muscles? The original description of these endocardia1lesions by Libman and Sacks noted that, in all patients examined, the valvular vegetations were free of bacteria.6 Histologically, Libman-Sacks lesions can be divided into three zones. The outermost area, or zone of exudation, is characterized by the presence of fibrin and proteinaceous material. The middle layer, or zone of organization, is populated by proliferating capillaries and fibroblasts. The innermost layer, or zone of neovascularization,contains maturing fibrous connective tissue with fibroblasts." The prevalence of these lesions in patients with SLE is approximately 50% at post mortem examination? In 1940, a review at autopsy of 23 cases of SLE showed a link between SLE and Libman-Sacks lesions. The author went on to differentiate these lesions from the valvular abnormalities seen in conjunction with rheumatic heart disease.12 (See Table 2.) While usually of little significance hemodynamically, Libman-Sacks lesions can act as a potential nidus for infection during transient ba~teremias'~,~~, thus putting the host at risk for developing bacterial end~carditis.'~ Multiple reports have appeared in the literature describing infective endocarditis complicating

SLE.46,12J618 The incidence of bacterial endocarditis in this patient group was reported at 4.9% before steroids came into common usage in the 1940's. Since that time period, glucocorticoids have been commonly used to treat SLE, and the incidence of bacterial endocarditis in this patient population is now at approximately 1.3%.15,19,20 The importance of this statistic is magnified upon comparison with other patient populations. The incidence of bacterial endocarditis in patients with rheumatic heart disease is 0.3%, and in patients with prosthetic heart valves it is 1.1%.15 Detection of Libman-Sacks lesions prior to autopsy has proven problematic. Previous studies have shown that there is no correlation between the presence of a murmur clinically and the finding of valvular pathology with echocardiography or at autopsy.21-23 Echocardiography has proven to be the most sensitive means of detecting valvular abnormalities. This noninvasive technique involves placing a sound-emitting transducer over the chest wall, or in the esophagus. Sound of a very high frequency (2-5 MHz) is transmitted into the chest cavity, reflects off structures within the chest, and returns to the transducer. Different types of echocardiography are available. Mmode utilizes sound in a single direction and gives detailed information regarding the motion patterns of individual cardiac structures, but the image does not lend itself well to the study of anatomical relationships between structures. Two-dimensional echocardiography passes sound in a sweeping motion back and forth over approximately a 75-degree angle. In this manner, a more anatomical picture of cardiac structures can be created, and abnormalities as small as 2-3 mm can be identified. Color

Doppler echocardiography takes advantage of the Doppler effect, which explains the change in pitch perceived from a sound-emitting object coming toward or moving away from the observer. With this technique, cardiologists are able to visualize blood flow within the heart and determine its direction at any given moment at a particular place. For example, when color Doppler echocardiography is utilized, regurgitant blood flow can be detected by virtue of color changes seen on a monitor.24 Studies utilizing echocardiography to evaluate SLE patients for the presence of valvular pathology have reported a 12-21%prevalence of valvular abnormalities."z,26Abnormalities reported to be seen on echocardiographic study include valvular vegetations (Libman-Sacks lesions), valvular thickening (predominantly mitral valve thickening), rigid valves, regurgitation, stenosis, and annular calcification, all of which are factors associated with an increased risk of bacterial endocarditi~.~~g Long-term follow-up data to determine the evolution of valvular disease in this patient population is lacking. The purpose of this study was to evaluate prospectively a group of SLE patients, by physical exam and echocardiography in comparison with each other, for the presence of valvular disease in order to assess their candidacy for antibiotic prophylaxis prior to invasive dental procedures. Techniques to complete the study include a careful physical examination, including dynamic auscultation, and echocardiography, specifically two-dimensional and color Doppler.

Materials and methods Forty-six patients with a reported

Table 2. Differences between valvular leslons seen in SLE and rheumatic heart disease (RHD).=

Factor 1. Aschoff bodies (smallnodules composed of cells and leukocytes found in the interstitial tissues of the heart) 2. Location of lesions 3. Valvular necrosis 4. Lesions present in places other than valves

194 Speclai Care in Dentlstry, Vol12 No 5 1992

RHD present

absent

one side of valve only absent

both sides of valves present

no

Yes

SLE

.

diagnosis of SLE participated in this study. Patients were recruited from the county teaching hospital in San Antonio, Texas, as well as from the private community. Study results for a particular patient were accepted only if there was documented medical evidence of at least four of the 11 diagnostic criteria as set forth by the American Rheumatism Association for the diagnosis of SLE.2 Three patients did not meet these criteria and were excluded from the study. Of the 43 patients included in the study, 38 were female and five were male. Ages ranged from 14-86, with the average age being 39.2 years. The average time since diagnosis of SLE was 9.1 years. The informed consent of all human subjects who participated in the experimental investigation reported or described in this manuscript was obtained after the nature of the procedure and possible discomforts and risks had been fully explained. One of two cardiologists completed a cardiovascular physical exam on each patient using a technique called dynamic auscultation. Physical maneuvers-such as stand, squat, hand grip, and Valsalva’s-were utilized with this technique in an attempt to detect and differentiate pathologic from non-pathologic cardiac murmurs. Findings were recorded, and a clinical diagnosis was made. Following the physical examination, a third physician completed a two-dimensional and color Doppler echocardiographicsurvey of each patient. The echocardiograms were interpreted by each of the cardiologists performing the physical examinations, but at a later date in a blinded fashion. It was not until after each part of the study (physical examination and echocardiogram)was interpreted independently that results were compared by patient.

ResuIts Of the 43 participants, 23 (53%)had heart murmurs on physical examination, and of those, seven (16%)were judged to be pathologic (regurgitation or stenosis) on the basis of the dynamic auscultation alone. Of the 43 patients who completed

the echocardiographic study, 19 (44%) were found to have anatomic valvular abnormalities on two-dimensional echocardiography. The results of the color Doppler echocardiograms showed that 15 (35%)had some degree of valvular dysfunction, ranging from trace to moderate regurgitation and stenosis. Three patients had mitral valve prolapse. Of those three patients, two also had valvular thickening with mitral regurgitation. When the results of the echocardiographic studies were combined, 20 (47%)of 43 tested patients had evidence of valvular abnormalities or dysfunction on either two-dimensional or color Doppler echocardiography. Only one patient had evidence of dysfunction on color Doppler without also having changes on the two-dimensional examination. After evaluation of each portion of the study, the results were compared. Of the seven patients with a clinical diagnosis of valvular disease, all had echocardiographic studies consistent with the clinical diagnosis. However, 13 had echocardiographic evidence of valvular disease which was not detected on physical examination. The average age of patients with abnormal echocardiographic studies was 38.9 years, with an average time since diagnosis of SLE of 9.4 years. There was no correlation among patient age, duration of SLE, and the presence or absence of valvular pathology as determined by echocardiography. There was also no correlation between the simple presence of a murmur on physical examination and the presence of echocardiographic abnormalities.

Discussion The results of this study corroborate the results of previous works which document an increased prevalence of valvular pathology in patients with SLE22,25,26, and that the clinical exam alone is not an adequate technique for the detection of the presence of such abnormalities in this patient population.21-uThere are, however, several limitations to this study. Probably the most notable is the lack of an age-matched control group of subjects without SLE, which pre-

vented direct comparisons between SLE and non-SLE patients by the examiners and limits our ability to make definitive comments with regard to the true incidence of valvular pathology in patients with SLE. It also would have been preferable to have only one physician performing the clinical examinations, rather than two. An attempt was not made to correlate severity of SLE to the presence of valvular disease, since there is no widely accepted scale of disease severity for SLE. This study reports a 44% prevalence of pathologic valvular abnormalities in patients with SLE. This is greater than results from other studies in the literature. Several factors may account for this difference. In the article by Galve et aLZ6,patients with abnormal valves revealed by imaging echocardiography but without significant stenosis or regurgitation revealed by Doppler echocardiography were not believed to have clinically important valvular disease, whereas in the present study, subjects with thickened valves who did not necessarily have significant regurgitation were included in the group of patients with valvular abnormalities. Likewise, in the JAMA study by Klinkhoff et a1.Y subjects with SLE and mitral valve prolapse ( M v p )were not included in the patients with valvular abnormalities, whereas in the present study, these patients were included. If patients with MVP had been included by Klinkhoff et al., the incidence of patients with valvular abnormalities would have risen from 21% to 34%. Finally, improvement in echocardiographic equipment over the past several years has enhanced the diagnostician’s ability to detect abnormally thickened valves along with smaller anatomical abnormalities and functional inadequacies. A recent study reports valvular abnormalities in 82% of patients studied with SLE by means of transesophageal echocardi~graphy.~~ Through the use of the multiple forms of echocardiography (M-mode, two-dimensional, Doppler, and color Doppler), diagnosis of cardiac abnormalities has dramatically improved.

Special Care In Dentistry, Vol12 No I 1992 195

It is, however, important that results appeared in the literat~re.4"~~,~~,'~ be interpreted as a whole, since While the prevalence of Libman-Sacks different types of echocardiography lesions has decreased dramatically are effective in detecting different since the use of steroids in the treataspects of cardiac form or function. ment of SLE, infection of these lesions There has been significant discussion is still a significant risk for this patient within the medical literature concernpopulation. Bacterial endocarditis ing the presence of trace or mild occurs in this group approximately as valvular regurgitation (as detected by often as it does in patients with Doppler or color Doppler exam) in the prosthetic heart valve^.^^^^^ normal, healthy population (as Summary defined by a normal two-dimensional echocardiographic This study utilized Several studies have noted that from echocardiography and the physical 15-88%of the general population may exam to evaluate prospectively a exhibit some valvular regurgitation group of patients with SLE for valvuwithout evidence of abnormalities on lar disease and to assess their candithe two-dimensional e~amination.~O-~~ dacy for antibiotic prophylaxis prior Color Doppler techniques have to undergoing invasive dental procedramatically improved the physician's dures. Of the 43 participants, seven ability to detect flow disturbances (16%)had physical exams indicative within the heart; however, one of the of valvular disease; however, 19 (44%) conclusions of these works was that had echocardiograms which showed the mere presence of trace or mild pathologic valvular changes. Because regurgitation in and of itself did not of the high prevalence of valvular automatically justify a diagnosis of disease in patients with SLE, and the organic valvular disease, and could be poor sensitivy of the physical exam to construed as a normal variation. The detect valvular pathology, practitioresults of any one form of ners should consider referral of echocardiography must be interpreted patients with SLE to a cardiologist for in conjunction with other modes of echocardiographic evaluation prior to echocardiography utilized. With invasive dental care. Antibiotic regard to this investigation, the prophylaxis should be considered for authors wish to emphasize that, of the those patients with documented 20 patients with abnormal pathologic valvular disorders. echocardiograms, 19 had changes on two-dimensional echocardiography. Only one patient had flow abnormaliDr.Luce is Assistant Professor, Department of ties on color Doppler without supGeneral Practice, University of Texas Health Science Center, 7703 Floyd Curl Drive, San portive, concomitant, anatomical Antonio, TX 78284-7914. When this paper was findings on two-dimensional written, Dr. Presti was an Assistant Professor of echocardiography. If a conservative Medicine, Division of Cardiology, Department attitude is taken, and the single of Medicine, University of Texas Health Science patient with color Doppler changes Center at San Antonio. He is currently in private practice, Fort Wayne Cardiology, Fort with a normal two-dimensional exam is not considered as having pathologic Wayne, IN. Dr. Montemayor is Research Associate, Division of Cardiology, Department valvular abnormalities, 19 of 43 (44%) of Medicine, University of Texas Health Science of the study patients had evidence of Center at San Antonio. Dr. Crawford is Robert S. Flinn Professor and Chief, Division of valvular pathosis, still a high percentCardiology, Department of Medicine, Univerage. It is the opinion of the authors sity of New Mexico School of Medicine. that these patients are at an increased Address correspondence to Dr. Luce. risk of bacterial endocarditis and should be considered candidates for antibiotic prophylaxis prior to under1. Schur PH, editor. The clinical management of systemic lupus erythematosus. going invasive dental procedures, New York Grune & Stratton, 945,1983. according to current American Heart 2. Tan EM, Cohen AS, Fries JF, Masi AT, Association g~idelines.3~ McShane DJ, Rothfield NF, Schaller JG, Multiple reports of bacterial Talal N, Winchester RJ. The 1982 revised endocarditis complicating SLE have criteria for the classification of systemic

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Special Care In Dentistry, Vol12 No 5 1992 197

Detecting cardiac valvular pathology in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with multiple cardiac complications, including valvular damage and an increased risk of bacterial end...
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