Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/fenfluramine.

CONTEXT: Use of anorexigen therapy is associated with valvular abnormalities, although there is limited information on long-term changes in valvular regurgitation following discontinuation of these agents. OBJECTIVE: To evaluate changes in valvular regurgitation, valve morphology, and clinical parameters 1 year after an initial echocardiogram in patients previously treated with dexfenfluramine or phentermine/fenfluramine and in untreated controls. DESIGN AND SETTING: A reader-blinded, multicenter, echocardiographic and clinical 1-year follow-up study at 25 outpatient clinical sites. PATIENTS: A total of 1142 obese patients (1466 participated in the initial study) who had follow-up echocardiogram; all but 4 had a follow-up medical history and physical examination. Follow-up time from discontinuation of drug to follow-up echocardiogram for 371 dexfenfluramine patients was 17.5 months (range, 13-26 months) and for 340 phentermine/fenfluramine patients was 18.7 months (range, 13-26 months) after discontinuation of drug therapy. MAIN OUTCOME MEASURE: Change in grade of valvular regurgitation and valve morphology and mobility. RESULTS: Echocardiographic changes in aortic regurgitation were observed in 8 controls (7 [1.7%] had decreases; 1 [0.2%] had an increase); 29 dexfenfluramine patients (23 [6.4%] had decreases; 6 [1.7%] had increases; P<.001 vs controls); and 15 phentermine/fenfluramine patients (4.5% all decreases; P =.03 vs controls). No statistically significant differences were observed when treated patients were compared with controls for changes in medical history, physical findings, mitral regurgitation, aortic or mitral leaflet mobility or thickness, pulmonary artery systolic pressure, ejection fraction, valve surgery, or cardiovascular events. CONCLUSION: Progression of valvular abnormalities is unlikely in patients 1 year after an initial echocardiogram and 13 to 26 months after discontinuation of dexfenfluramine and phentermine/fenfluramine.

Smoking and obesity are associated with the progression of aortic stenosis.

OBJECTIVE: The purpose of the study was to identify clinical predictors of progression of aortic stenosis. BACKGROUND: The natural history of valvular aortic stenosis includes a latency period followed by an unpredictable progression. Recent investigations have shown an association between risk factors for atherosclerosis and the presence of aortic stenosis. The authors hypothesized that atherosclerosis risk factors are also associated with the progression of aortic stenosis. METHODS: In a retrospective study, patients with a diagnosis of aortic stenosis were identified by continuous wave Doppler and a follow-up study of at least 6 months. Clinical data at the time of the index echocardiogram were obtained from review of patients' medical records. Independent risk factors for the progression of aortic stenosis were identified by stepwise logistic regression analysis. RESULTS: One hundred twenty-three patients were identified, and complete data were obtained for 87 patients (mean age, 70.7 +/- 10 years; men, 81%; mean follow-up, 2.54 +/- 1.6 years). The initial gradient was mild in 61% of patients and moderate in 31%. The mean rate of progression was 6.3 +/- 13 mm Hg/year. Mild aortic stenosis in 36% of patients at the time of the index echocardiogram progressed to moderate or severe over an average of 2.9 +/- 2.0 years. Independent clinical factors associated with a progression of 5 mm Hg/year or greater included a history of smoking (relative risk [RR] = 3.06; 95% confidence interval [CI] = 1.09-8.61; p = 0.034) and body mass index (RR = 1.16; 95% CI = 1.03-1.30; p = 0.013). Hypertension, diabetes, cholesterol, age, gender, and coronary artery disease were not independently associated with progression. CONCLUSIONS: Body mass index and a history of smoking are independent predictors of significant progression of aortic stenosis, defined as > 5 mm Hg/year. The rate of progression of aortic stenosis is variable. However, a substantial number of patients have progression of even initially mild aortic stenosis within a relatively short period of time. The effect of controlling atherosclerosis risk factors on the rate of progression of aortic stenosis remains to be determined.

Accelerated dobutamine stress testing: safety and feasibility in patients with known or suspected coronary artery disease.

BACKGROUND: Dobutamine pharmodynamics require approximately 10 min to reach steady state. Despite this, standard dobutamine stress echo typically uses 3-min stages of advancing dobutamine doses because of safety concerns. HYPOTHESIS: In patients with a high pretest probability of coronary artery disease (CAD), a continuous infusion of high-dose dobutamine is a feasible and safe method for performing a dobutamine stress test. METHODS: Forty-seven consecutive patients (mean age 64 +/- 11 years) with 3.0 +/- 1.4 cardiac risk factors underwent dobutamine stress testing utilizing a single, high-dose (40 mcg/kg/min), continuous dobutamine infusion. The 40 mcg/kg/min infusion was continued for up to 10 min or until a test endpoint had been reached. If a test endpoint was not achieved, atropine (up to 1.0 mg) was added. RESULTS: Heart rate rose from 71 +/- 12 to 137 +/- 18 beats/min at peak (p<0.0001) with a concomitant change in systolic blood pressure (143 +/- 35 vs. 167 +/- 38 mmHg; p = 0.001) but no change in diastolic blood pressure (74 +/- 19 vs. 75 +/- 18 mmHg; p = NS). Target heart rate was achieved in 20 of 47 (43%) patients with accelerated dobutamine alone and in 34 of 47 (72%) with the addition of atropine. An average of 11.6 +/- 3.7 min was required to obtain target heart rate. Subjective sensations from the dobutamine occurred in 49% of patients (palpitations 21%, nausea 6%, chest pain 6%, headache 6%, dizziness 13%), mild arrhythmia in 48% of patients (ventricular premature beats 38%, supraventricular tachycardia 10%), and one patient had nonsustained ventricular tachycardia. CONCLUSION: A single, high-dose (40 mcg/kg/min) dobutamine-atropine protocol provides an efficient means of performing dobutamine stress echocardiography with a similar symptom profile as conventional dobutamine infusion protocols in patients with a high pretest probability of CAD. Randomized, controlled studies will be necessary to assess the sensitivity and specificity of this accelerated dobutamine echo protocol.

Frequency of ring abscess and cuspal infection in active infective endocarditis involving bioprosthetic valves.

When active infective endocarditis (IE) involves a bioprosthetic valve, the infective process may involve only the cusps or sewing ring or both. We studied 34 patients with infected bioprostheses to determine whether the infection involved the cusps or ring, or both, because these locations could affect prognosis. In the 5 patients in whom active IE began < 60 days after operation, the infection involved the cusps only in 2, the ring only in 2, and both in 1. The 29 patients in whom signs and symptoms of active IE appeared > 60 days after valve replacement were subdivided into 3 categories based on the valve or valves replaced. In the 16 patients with isolated aortic valve replacement, the infection involved the cusps only in 6, the ring only in 4, and both in 6. In the 6 patients with isolated mitral valve replacement, the infection involved the cusps only in 2, the ring only in 1, and both in 3. In the remaining 7 patients, 15 native valves were replaced with bioprostheses, and 10 of them were infected. The infection involved the cusps only in 7, and both the cusps and ring in 3. Of all 34 patients, 13 had operative excision of the infected bioprosthesis: 1 died within 60 days of the bioprosthetic excision, and 1 was lost to follow-up; of the remaining 11 patients, 4 died late (1.5, 3, 5 and 14 years), and the other 7 are alive 5 to 10 years after bioprosthetic excision (all in New York Heart Association functional class I or II). Thus, although infection limited to the bioprosthetic cusps may reasonably allow a better outlook, reoperation with infection involving the annular ring (8 of 13 reoperation patients) does not prevent successful outcome.

Comparison of active infective endocarditis involving a previously stenotic versus a previously nonstenotic aortic valve.

No previous studies, either clinical or morphologic, have compared findings in patients with active infective endocarditis (IE) involving a previously stenotic versus a previously nonstenotic aortic valve. Clinical and cardiac necropsy findings were analyzed in 96 patients with active IE involving the aortic valve. Of the 96 patients, 25 (26%) had active IE superimposed on a previously stenotic aortic valve and 71 (74%) on a previously nonstenotic aortic valve. The patients with stenotic aortic valves compared with those with nonstenotic aortic valves had significantly higher mean ages (61 vs 47 years), a higher percentage > 60 years of age (52 vs 24%), a higher percentage of men (92 vs 73%), a higher frequency of an absent or unknown predisposing factor to infection (68 vs 38%), a lower frequency of a precordial murmur of aortic regurgitation (44 vs 79%), a lower percent with a long duration (> 60 days) of signs and symptoms of active IE (4 vs 23%), a larger mean heart weight (594 vs 514 g), a higher percentage with aortic valve calcific deposits (100 vs 24%), and a higher frequency of associated ring abscess (84 vs 52%). Thus, active IE superimposed on a stenotic aortic valve differs in some features compared with active IE on a nonstenotic aortic valve. Because ring abscess is so common when active IE involves a stenotic aortic valve in adults, operative intervention at an early stage may be warranted.

Clinicopathologic features of active infective endocarditis isolated to the native mitral valve.

Although a number of clinicopathologic studies in patients with active infective endocarditis (IE) have been reported, none have focused on patients studied at necropsy with active IE isolated to the mitral valve. We studied at necropsy 63 patients (aged 12 to 88 years [mean 50], 44 males [70%]) with active IE limited to the native mitral valve: 21 (33%) had preexisting mitral valve disease (rheumatic in 8, prolapse in 3, hypertrophic cardiomyopathy in 1, and mitral annular calcium in 9), and the other 42 patients (67%) had previously normal mitral valves. Of the latter 42 patients, 22 (52%) had recognized predisposing factors to IE: opiate addiction in 14, habitual alcoholism in 6 and/or chronic hemodialysis in 4. Staphylococcus aureus or epidermidis was the responsible organism in 32 patients (51%), and the active IE was associated with an infection elsewhere in the body in 31 patients (50%). The active IE caused rupture of mitral chordae tendineae in 11 patients (18%), perforation of the anterior mitral leaflet in 7 patients (11%), and mitral ring abscess in 10 patients (16%). Grossly visible systemic emboli were found in 44 patients (70%) and 33 (52%) had infarcts in 1 or more body organs. Thus, active IE isolated to the mitral valve in necropsied patients appears to be more common in males than females (2 to 1); the infection more commonly than not involves a preexisting anatomically normal valve rather than a preexisting abnormal one (2 to 1); the vegetations often do not cause or worsen valvular dysfunction; a predisposing factor is commonly present (2 of 3 patients), and the IE commonly is part of a generalized or systemic infection (1 of 2 patients).

Composition of atherosclerotic plaques in coronary arteries in women less than 40 years of age with fatal coronary artery disease and implications for plaque reversibility.

This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women less than 40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults greater than 45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed greater than 75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD.