Carlos A. Roldan

AN ECHOCARDIOGRAPHIC STUDY OF VALVULAR HEART DISEASE ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BACKGROUND Valvular heart disease is the most important cardiac manifestation of systemic lupus erythematosus. We performed a study to determine the relation of valvular disease to other clinical features of lupus, whether or not the valve disease progresses, and the associated morbidity and mortality. METHODS We performed transesophageal echocardiography and rheumatologic evaluations in 69 patients with systemic lupus erythematosus. The echocardiographic findings were compared with those in 56 healthy volunteers. Fifty-eight patients (84 percent) had second evaluations a mean (+/-SD) period of 29 +/- 13 months later. The patients and controls were followed for 57 months. RESULTS Valvular abnormalities were common on the initial and the follow-up echocardiograms (in 61 and 53 percent of the patients, respectively). Valvular thickening was the predominant finding initially and on follow-up (in 51 and 52 percent of the patients, respectively), followed by vegetations (in 43 and 34 percent), valvular regurgitation (in 25 and 28 percent), and stenosis (in 4 and 3 percent). Valvular abnormalities frequently resolved, appeared for the first time, or persisted but changed in appearance or size between the two studies. Mild or moderate valvular regurgitation did not progress to become severe, and new stenoses did not develop. Neither the presence of valvular disease nor changes in the echocardiographic findings were temporally related to the duration, activity, or severity of lupus or to its treatment. The combined incidence of stroke, peripheral embolism, heart failure, infective endocarditis, and the need for valve replacement was 22 percent in the patients with valvular disease, but only 8 percent in those without it. A total of seven patients died during follow-up, in most cases as a result of valvular disease. Valvular abnormalities and complications were uncommon in the controls (occurring in 9 and 2 percent, respectively). CONCLUSIONS Valvular heart disease is common in patients with systemic lupus erythematosus, frequently changes over time, appears to be temporally unrelated to other clinical features of lupus, and is associated with substantial morbidity and mortality.

Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies

OBJECTIVES The aims of this study were to better characterize valve disease in systemic lupus erythematosus and to determine its association with antiphospholipid antibodies. BACKGROUND Estimates of the prevalence of valve disease in systemic lupus erythematosus have been higher in autopsy series than in clinical studies using transthoracic echocardiography. Antiphospholipid antibodies have been suggested to be a primary pathogenetic factor. METHODS Transesophageal echocardiography was performed on 1) 54 patients with lupus erythematosus, 22 of them with (group I) and 32 without (group II) antiphospholipid antibody; 2) on 10 patients with antiphospholipid syndrome (group III); and 3) on 35 normal subjects (group IV). RESULTS Patients in groups I and III had similar types and concentrations of antibodies. Leaflet thickening was found in 50% of group I, 47% of group II, 10% of group III and 9% of group IV patients (group I or II vs. group III or IV, p < 0.03). Leaflet thickening in patients with lupus erythematosus was diffuse; it usually involved the mitral and aortic valves and was associated with valve regurgitation (73%) or valve masses (50%). Valve masses were observed in 41% of group I, 25% of group II, 10% of group III and in none of group IV patients (group I or II vs. group IV, p < 0.002). Most valve masses in patients with lupus erythematosus were located near the base on the atrial side of the mitral valve or on the vessel side of the aortic valve, had variable size (0.2 to 0.85 cm2), shape and echodensity. Valve regurgitation was observed in 64% of group I, 59% of group II, 10% of group III and 20% of group IV patients (group I or II vs. group III or IV, p < 0.006). Moderate or severe regurgitant lesions were noted in 27% of group I and 25% of group II patients. CONCLUSIONS Lupus erythematosus valve disease is frequent (74%) regardless of the presence or absence of antiphospholipid antibodies. Therefore antiphospholipid antibodies may not be a primary pathogenetic factor. The characteristic appearance of leaflet thickening and masses in patients with lupus erythematosus may be unique.

Aortic root disease and valve disease associated with ankylosing spondylitis

OBJECTIVES This study sought to determine the prevalence, characteristics, relation to clinical features and evolution of aortic root disease and valve disease associated with ankylosing spondylitis (AKS). BACKGROUND Aortic root disease and valve disease are common in patients with AKS, but their clinical and prognostic implications have not been well defined. METHODS Forty-four outpatients with AKS and 30 age- and gender-matched healthy volunteers underwent initial transesophageal echocardiography and rheumatologic evaluations. Twenty-five patients underwent clinical and echocardiographic follow-up 39+/-10 months later. RESULTS Aortic root disease and valve disease were common in patients (82%) as compared with controls (27%; p < 0.001). Aortic root thickening, increased stiffness and dilatation were seen in 61%, 61% and 25% of patients, respectively. Valve thickening (41% for the aortic and 34% for the mitral valve) manifested predominantly (74%) as nodularities of the aortic cusps and basal thickening of the anterior mitral leaflet, forming the characteristic subaortic bump. Valve regurgitation was seen in almost half of patients, and 40% had moderate lesions. Except for the duration of AKS, aortic root disease and valve disease were unrelated to the activity, severity or therapy of AKS. During follow-up of 25 patients, in up to 24% new aortic root or valve abnormalities developed, in 12% existing valve regurgitation worsened significantly and in 20% abnormalities resolved. Twenty percent of patients developed heart failure, underwent valve replacement, had a stroke or died, as compared with 3% of control subjects. CONCLUSIONS Aortic root disease and valve disease are common in patients with AKS, are unrelated to clinical features of AKS, can resolve or progress over time and are associated with clinically important cardiovascular morbidity.

Value of the cardiovascular physical examination for detecting valvular heart disease in asymptomatic subjects.

To determine the accuracy of the cardiovascular physical examination for the diagnosis of asymptomatic valvular heart disease (VHD), we prospectively studied 143 subjects, 68 apparent normal subjects and 75 patients with diseases known to produce VHD. All subjects underwent a complete physical examination with dynamic cardiac auscultation by a physician blinded to clinical data and compared with the results of transesophageal color Doppler echocardiography (TEE). By TEE, 33 subjects (23%), and by physical examination, 25 subjects (17%) had at least 1 form of VHD. Despite a high frequency of mild valve abnormalities and a 31% prevalence of functional murmurs, the physical examination showed a sensitivity of 70%, a specificity of 98% (confidence interval = 0.51 to 0.84, and 0.94 to 0.99, respectively), and a positive and negative predictive value of 92% for the diagnosis of VHD. Only 2 of the 10 patients with VHD by TEE, but not by physical examination, had clinically important VHD. We conclude that the physical examination is a sensitive and highly specific method of screening for VHD in subjects without cardiac symptoms. Therefore, its use should be encouraged rather than the routine application of echocardiography.

Magnetic Resonance Imaging And Brain Histopathology In Neuropsychiatric Systemic Lupus Erythematosus

OBJECTIVE Magnetic resonance imaging (MRI) often demonstrates brain lesions in neuropsychiatric systemic lupus erythematosus (NPSLE). The present study compared postmortem histopathology with premortem MRI in NPSLE. METHODS Two hundred subjects with NPSLE were studied prospectively with MRI over a 10-year period during which 22 subjects died. In 14 subjects, a brain autopsy with histopathology, that permitted direct comparison with premortem MRI, was successfully obtained. Surface anatomy was used to determine the approximate location of individual lesions. RESULTS Premortem MRI findings in fatal NPSLE were small focal white matter lesions (100%), cortical atrophy (64%), ventricular dilation (57%), cerebral edema (50%), diffuse white matter abnormalities (43%), focal atrophy (36%), cerebral infarction (29%), acute leukoencephalopathy (25%), intracranial hemorrhage (21%), and calcifications (7%). Microscopic findings in fatal NPSLE included global ischemic changes (57%), parenchymal edema (50%), microhemorrhages (43%), glial hyperplasia (43%), diffuse neuronal/axonal loss (36%), resolved cerebral infarction (33%), microthomboemboli (29%), blood vessel remodeling (29%), acute cerebral infarction (14%), acute macrohemorrhages (14%), and resolved intracranial hemorrhages (7%). Cortical atrophy and ventricular dilation seen by MRI accurately predicted brain mass at autopsy (r = -0.72, P = 0.01, and r = -0.77, P = 0.01, respectively). Cerebral autopsy findings, including infarction, cerebral edema, intracranial hemorrhage, calcifications, cysts, and focal atrophy, were also predicted accurately by premortem MRI. CONCLUSION Brain lesions in NPSLE detected by MRI accurately represent serious underlying cerebrovascular and parenchymal brain injury on pathology.

Prevalence and Determinants of Valvulopathy in Patients Treated With Dexfenfluramine

BACKGROUND Valve regurgitation has been associated with dexfenfluramine, but its prevalence and severity are uncertain. Additional factors that may contribute to valve regurgitation in patients exposed to this drug are poorly understood. METHODS AND RESULTS Echocardiography was performed on subjects recruited from 26 prescribing sites in 15 states. The total sample of 412 subjects included 172 dexfenfluramine patients and 172 unexposed controls matched for age, sex, and body mass index and 68 unmatched subjects meeting the same entry criteria (51 dexfenfluramine patients and 17 controls). Mean treatment duration was 6.9 months; mean interval from treatment discontinuation to echocardiogram was 8.5 months. Each echocardiogram was interpreted independently by 3 echocardiographers. FDA-grade regurgitation (at least mild aortic regurgitation or at least moderate mitral regurgitation) was significantly more frequent in dexfenfluramine patients (7.6% versus 2.1% for controls; P=0.01; odds ratio, 3.82). This difference was primarily due to more frequent mild aortic regurgitation in dexfenfluramine patients (6.3% versus 1.6% in controls; P<0.02; odds ratio, 4.15). No differences were found in sclerosis or mobility for either the aortic or mitral valve. Factors independently related to FDA-grade regurgitation or any grade of aortic regurgitation were older age, higher diastolic blood pressure at the time of echocardiography, and shorter time from drug discontinuation to echocardiogram. CONCLUSIONS Dexfenfluramine use is associated with an increase in the prevalence of abnormal valve regurgitation. Age and blood pressure may also affect the prevalence of regurgitation. Dexfenfluramine-related valve regurgitation may regress after drug discontinuation.

Aortic valve sclerosis, mitral annular calcium, and aortic root sclerosis as markers of atherosclerosis in men

Aortic valve sclerosis (AVS) and mitral annular calcium (MAC) as detected by transthoracic echocardiography have been associated with atherosclerosis. Aortic root sclerosis (ARS) may have a similar association, but has not been studied. This study evaluates, by transesophageal echocardiography, the association of AVS, MAC, and ARS with aortic atheromatous disease and cardiovascular disease. Multiplane transesophageal echocardiography with evaluation of AVS, MAC, ARS, and aortic atheromatous disease by 2 experienced observers unaware of clinical data was performed in 157 male patients > or =50 years old. The presence of cardiovascular disease, defined as coronary, carotid, or peripheral artery disease, was determined by specific criteria. The prevalence of AVS, MAC, ARS, and aortic atheromatous disease was 42%, 30%, 48%, and 71%, respectively. The presence of AVS, MAC, or ARS was highly associated with aortic atheromatous disease (odds ratio 4.9 to 12.0, confidence interval 1.4 to 35.8, p <0.001). ARS was also associated with cardiovascular disease (odds ratio 2.2, confidence interval 1.0 to 4.5, p = 0.038). The presence of AVS, MAC, or ARS had a sensitivity of 77%, specificity of 72%, a positive predictive value of 88%, and a negative predictive value of 55% for aortic atheromatous disease. We concluded that the prevalence of AVS, MAC, or ARS by transesophageal echocardiography in men is common, and their presence is highly associated with aortic atheromatous disease and coronary, carotid, or peripheral artery disease.

Valve Excrescences: Prevalence, Evolution and Risk for Cardioembolism

OBJECTIVES We sought to determine prospectively the prevalence, evolution and embolic risk of valve excrescences in normal subjects and patients with and without suspected cardioembolism. BACKGROUND Valve excrescences detected by transesophageal echocardiography (TEE) have been considered a cardioembolic substrate in selected patients. METHODS Ninety healthy volunteers (Group I) and 88 patients without suspected cardioembolism and a normal TEE (Group II) were studied and followed up clinically for 58 +/- 21 and 48 +/- 20 months, respectively. To assess the evolution of valve excrescences, 45 of these subjects underwent repeat TEE at 31 +/- 13 months. The findings in Groups I and II were compared with those of Group III--49 patients referred for TEE for suspected cardioembolism. RESULTS Valve excrescences were detected in 34 subjects (38%) in Group I and in 41 patients (47%) in Group II. In Group III, 20 patients (41%) had excrescences, but 85% of them had other potential cardiac or vascular sources of embolism. In all groups, mitral valve excrescences were predominant (68% to 76%), followed by aortic (38% to 50%) and right-sided valves (<10%). Excrescences were equally frequent in men and women and between all age groups studied. During follow-up in Groups I and II, excrescences persisted unchanged, and 1 (1.4%) of 74 patients with and 2 (2%) of 99 subjects without excrescences had cerebral ischemic events (80% power to detect a clinically meaningful difference of 4%). CONCLUSIONS Valve excrescences are common on the left-sided heart valves of normal subjects and patients regardless of gender and age; they persist unchanged over time and do not appear to be a primary source of cardioembolism.

Cortical Thickness and Subcortical Gray Matter Reductions in Neuropsychiatric Systemic Lupus Erythematosus

Within systemic lupus erythematosus (SLE) patients can be divided into groups with and without central nervous system involvement, the latter being subcategorized as neuropsychiatric systemic lupus erythematosus (NPSLE). While a number of research groups have investigated NPSLE, there remains a lack of consistent application of this diagnostic criteria within neuroimaging studies. Previous neuroimaging research suggests that SLE patients have reduced subcortical and regional gray matter volumes when compared to controls, and that these group differences may be driven by SLE patients with neuropsychiatric symptoms. The current study sought to compare measures of cortical thickness and subcortical structure volume between NPSLE, SLE, and healthy controls. We hypothesized that patients with NPSLE (N = 21) would have thinner cortex and reduced subcortical gray matter volumes when compared to SLE (N = 16) and control subjects (N = 21). All subjects underwent MRI examinations on a 1.5 Tesla Siemens Sonata scanner. Anatomical reconstruction and segmentation were performed using the FreeSurfer image analysis suite. Cortical and subcortical volumes were extracted from FreeSurfer and analyzed for group differences, controlling for age. The NPSLE group exhibited decreased cortical thickness in clusters of the left frontal and parietal lobes as well as in the right parietal and occipital lobes compared to control subjects. Compared to the SLE group, the NPSLE group exhibited comparable thinning in clusters of the frontal and temporal lobes. Controlling for age, we found that between group effects for subcortical gray matter structures were significant for the thalamus (F = 3.06, p = .04), caudate nucleus (F = 3.19, p = .03), and putamen (F = 4.82, p = .005). These results clarify previous imaging work identifying cortical atrophy in a mixed SLE and NPSLE group, and suggest that neuroanatomical abnormalities are specific to SLE patients diagnosed with neuropsychiatric symptoms. Future work should help elucidate the underlying mechanisms underlying the emerging neurobiological profile seen in NPSLE, as well as clarify the apparent lack of overlap between cortical thinning and functional activation results and other findings pointing to increased functional activation during cognitive tasks.

Diffusion tensor imaging in neuropsychiatric systemic lupus erythematosus

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) is associated with increased morbidity and mortality.MethodsWe used Diffusion Tensor Imaging (DTI) to assess white matter abnormalities in seventeen NPSLE patients, sixteen SLE patients without NPSLE, and twenty age- and gender-matched controls.ResultsNPSLE patients differed significantly from SLE and control patients in white matter integrity of the body of the corpus callosum, the left arm of the forceps major and the left anterior corona radiata.ConclusionsSeveral possible mechanisms of white matter injury are explored, including vascular injury, medication effects, and platelet or fibrin macro- or microembolism from Libman-Sacks endocarditis.