Bruce K. Shively

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.

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.

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.

Regional left atrial stasis during fibrillation and flutter determinants and relation to stroke

Objectives. This study sought to 1) determine the location of left atrial stasis during atrial arrhythmia; 2) define the degree of stasis associated with significant risk of stroke; and 3) identify clinical or transthoracic echocardiographic data useful for predicting left atrial stasis. Background. Prior studies suggest that stroke during atrial arrhythmia is related to stasis in either the body of the left atrium or the appendage. Recent data indicate that appendage stasis is associated with appendage thrombus formation, but stroke during atrial arrhythmia occurs frequently in the absence of appendage stasis. Methods. Blood flow velocity was measured in multiple sites in the body of the left atrium and in the appendage by transesophageal pulsed wave Doppler echocardiography in 89 patients with atrial fibrillation or flutter. Regional velocities were related to the frequency of probable embolic stroke and to clinical and transthoracic echocardiographic variables. Results. The lowest velocity region was either the posterior left strium or the appendage. Stroke frequency increases progressively and steeply with velocity <15 cm/s is either region; this cutoff value had an 87% sensitivity and 40% specificity for stroke. Factors related to stasis were low left atrial ejection fraction, mitral regurgitation <3+, fibrillation (vs. type 1 flutter), left ventricular dilation and mitral valve area <2.0 cm2. Conclusions. Posterior left atrial stasis appears to the as important as appendage statis for the risk of stroke, which increases sleeply with lower blood flow velocity in either region. Patients likely to have severe stasis during atrial arrhythmia are those with left ventricular dilation and low atrial ejection fraction accompanying left atrial dilation. Direct measurement of atrial velocity by transesophageal echocardiography appears to be useful for the identification of patients at risk for stroke during atrial arrhythmia.

Osteogenesis Imperfecta and Cardiovascular Diseases

Aortic and mitral valvular insufficiency in patients with osteogenesis imperfecta result from an underlying defect in connective tissue formation. The surgical cases reported in the literature have included mechanical and bioprosthetic valve replacement as well as attempts at repair and reconstruction. Despite complications related to bleeding and tissue friability, acceptable results have been obtained. In this report, we describe aortic regurgitation secondary to osteogenesis imperfecta treated with homograft replacement. The unique cardiovascular complications of osteogenesis imperfecta and the available therapeutic options are discussed in light of the literature review.

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.

Flow dependence of valve area in aortic stenosis : Relation to valve morphology

OBJECTIVES We sought to develop an index of flow dependence of valve area in aortic valve (AoV) stenosis and to determine whether this index is related to structural characteristics of the diseased valve. BACKGROUND Many studies of AoV stenosis using Gorlin or continuity equation methods have demonstrated flow dependence (an increase in valve area with increased flow). Variation in flow dependence between patients despite similar flow rates remains unexplained. METHODS Dobutamine Doppler echocardiography was used to calculate flow rate and valve area by the continuity equation in 27 patients with aortic stenosis. For each patient the slope of the regression line of valve area to flow rate was determined (slope of flow dependence). Transesophageal echocardiography was used to evaluate features of valve morphology potentially related to the etiology of AoV stenosis and the mechanism of flow dependence. RESULTS Mean slope of flow dependence was 0.28 cm2/100 ml per s (range -0.06 to 0.53); flow dependence was significantly >0 in 21 patients and was lower for bicuspid valves (slope 0.21 cm2/100 ml per s) than for tricuspid valves with <10% commissural fusion (slope 0.35, p < 0.01). Off-center/ovoid orifices demonstrated the least flow dependence (slope 0.19), whereas star-shaped orifices showed the most (slope 0.36, p < 0.01). Greater flow dependence was related to a lower percentage of commissural fusion (r = -0.46, p = 0.02) as well as diffuse sclerosis, primarily involving the cusp bodies, rather than localized sclerosis, with involvement of cusp margins. CONCLUSIONS The slope of flow dependence of valve area in AoV stenosis differs markedly between patients. More flow dependence was associated with tricuspid valves and the morphologic features characteristic of calcific AoV stenosis, whereas less flow dependence was associated with bicuspid valves and the features of rheumatic disease.

Echocardiographic Predictors of Survival in Low Gradient Aortic Stenosis

Echocardiographic predictors of long-term survival for patients with low gradient aortic stenosis who undergo aortic valve replacement have not been previously reported. This study shows that patients with larger pre- and postoperative left ventricular volumes, a lower mean preoperative aortic pressure gradient, and failure of volumes to decrease and ejection fraction to increase postoperatively may have a poor prognosis.

Transesophageal echocardiography in the diagnosis of aortic disease

Transesophageal echocardiography (TEE) has recently become a major diagnostic tool in aortic disease. By far the most important role of TEE is in the rapid diagnosis of acute aortic dissection. In this disease the sensitivity and specificity of TEE are both well more than 90%, patient risk is minimal, and the test can (and should) be done in the emergency department. Limitations of TEE include, in some cases, difficulty delineating involvement of the proximal arch, major branch vessels, and abdominal aorta. Another emergency department application of TEE is the assessment of patients suspected of traumatic aortic rupture. TEE also is being applied to the diagnosis of aortic protruding atheromas, thought to have significant embolic potential.