Low prevalence of valvular heart disease in 226 phentermine-fenfluramine protocol subjects prospectively followed for up to 30 months.

OBJECTIVES: This investigation sought to determine the effect of phentermine-fenfluramine (phen-fen) on the prevalence of valvular heart disease in 226 obese subjects enrolled in a prospective, strict weight loss, research protocol. BACKGROUND: Early reports have suggested that the use of phen-fen for weight loss may be associated with increased valvular heart disease. Such reports were based on small numbers of patients, limited data on dose and duration of phen-fen therapy, and no correlation with matched controls. METHODS: All subjects underwent transthoracic echocardiography for significant valvular lesions within a mean of 97 days from the manufacturer's announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine. All echocardiograms were interpreted by two independent readers. RESULTS: The study population included 183 women and 43 men with a mean age of 46.9 +/- 8.9 years and mean starting body mass index of 39.8 +/- 7.7 kg/m2. Using the Food and Drug Administration criteria, significant aortic regurgitation was detected in 15 subjects (6.6%) and mitral regurgitation in 3 subjects (1.3%). Only one patient had significant regurgitation of both aortic and mitral valves. No valves had severe regurgitation. Significant valvular disease did not correlate with the dose or duration of phen-fen therapy. Furthermore, the prevalence of valvular regurgitation is comparable to the normal offspring in the Framingham Heart Study, who are similar in age, gender, and geographical location. CONCLUSIONS: Phen-fen therapy is associated with a low prevalence of significant valvular regurgitation. Valvular regurgitation in our subjects may reflect age-related degenerative changes.

Short- and long-term reproducibility of heart rate variability in patients with long-standing type I diabetes mellitus.

Heart rate variability (HRV) has been used to assess cardiac autonomic function noninvasively, understand the pathophysiologic mechanisms of heart disease, evaluate therapy, and assess long-term prognosis. We examined both the short- and long-term reproducibility of the time and frequency domain HRV parameters in 23 type I diabetics over a 12-month interval. Entry criteria included juvenile onset diabetes before age 35 years, >24-year duration of diabetes, diabetes difficult to control, and albuminuria. Standardized noninvasive autonomic testing and 24-hour ambulatory electrocardiographic recordings were obtained. Fifteen men and 8 women (mean age 36.7 years) were enrolled. Fifty-three percent of the men and 75% of the women were smokers, and women had higher cholesterol than men. All HRV parameters were markedly decreased when compared with normal persons. Using Pearson correlation, the time domain indicators of parasympathetic activity demonstrated very strong correlations at 3 and 6 months compared with baseline, with good correlations at 1 year. The average SD of all 5-minute RR intervals maintained a very strong correlation for the entire year (r >0.94). In the frequency domain, the measures of parasympathetic and sympathetic activity maintained a solid correlation for the entire study period. Reproducibility of HRV was also examined using repeated-measures analysis of variance. The time and frequency domain parameters demonstrated very little variation over the study period of 12 months. Thus, our investigation demonstrated that HRV in long-term diabetics using 24-hour ambulatory recordings is abnormal and reproducible over a 12-month interval; very little variation in all HRV parameters, especially in parameters of parasympathetic activity, occurred during the study period.

Circadian patterns of heart rate variability in normals, chronic stable angina and diabetes mellitus.

The purpose of our investigation was to compare circadian patterns of heart rate variability as assessed by 24-h ambulatory electrocardiographic (ECG) recordings in normal subjects, chronic stable angina, and Type 1 diabetes mellitus. The study population consisted of three groups: 12 normal subjects, 23 chronic angina patients, and 23 Type 1 diabetics. For purposes of analyzing circadian variation, the ECG recordings were divided into daytime (08:00-00.00 h) and night-time (00:00-08:00 h) periods. Analysis was performed for all time and frequency domain measures of heart rate variability, attempting to identify differences in day-to-night variability among these three groups. All time domain parameters except standard deviation of all 5-min mean RR intervals, and all frequency domain indices maintain significant circadian variations (P<0.0001), with the greatest day to night variation seen in normals, the least in diabetics, and intermediate values in chronic angina. These changes in heart rate variability circadian rhythms reflect significant reductions in cardiac parasympathetic activity with the most marked reduction in nocturnal vagal activity. Given the circadian pattern of myocardial ischemia and infarction, these data suggest that quantification of the magnitude of circadian variation in heart rate variability may have the potential to further risk stratify chronic angina and diabetes for future cardiac events.

Low risk of significant echocardiographic valvulopathy in patients treated with anorectic drugs.

BACKGROUND: Phentermine--fenfluramine and dexfenfluramine use for weight loss has been previously associated with increased prevalence of valvular heart disease. This association was initially based on small numbers of patients, limited data on dose and duration of drug therapy, and no correlation with matched controls. METHODS: Our investigation involved 343 obese subjects enrolled in a prospective, strict weight loss, research protocol from September 1994 to September 1997. All subjects underwent transthoracic echocardiography for significant valvular lesions within a mean of 121 days from the manufacturer's announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine from the market. All echocardiograms were interpreted by 2 independent readers. RESULTS: The study population included 281 females and 62 males with a mean age of 46.7+/-9.1 years and mean initial body mass index of 40.1+/-8.1 kg/m(2). Using the Food and Drug Administration's criteria, only 21 subjects (6.1%) had significant valvular lesions. Aortic regurgitation was detected in 18 subjects, mitral regurgitation in 3 subjects, and both aortic and mitral regurgitation in 1 subject; no one had severe regurgitation. Significant valvular disease did not correlate with age, gender, initial/ending body mass index, the drug dose, duration of drug therapy, or serotonin reuptake inhibitors. CONCLUSIONS: Anorexigen therapy is associated with a low prevalence of significant valvular regurgitation. Late valvular abnormalities from drug treatment await long term prospective studies.

Low incidence of embolic strokes with atrial septal aneurysms: A prospective, long-term study.

BACKGROUND: Previous retrospective studies have suggested that atrial septal aneurysms (ASA) are associated with embolic strokes. The purpose of this study was to evaluate prospectively the embolic potential of ASA. METHODS: Of 846 consecutive patients undergoing cardiac surgery from December 1990 to March 1993, we identified 42 patients who had ASA as an incidental finding on intraoperative transesophageal echocardiography. Patency was determined by color and/or contrast echocardiography. The majority of patients were given aspirin postoperatively. Patients were monitored by personal and/or telephone interviews, and their clinical conditions were confirmed by their personal physicians. Any patient with any question of a neurologic event had a detailed neurologic history, examination, and computed tomographic or magnetic resonance imaging scan. RESULTS: The incidence of ASA in our population was 4.9%; there were 22 men and 20 women with a mean age of 72 years. Oscillating ASA were present in 28 patients and fixed aneurysm in 10. The mean diameter of the ASA was 21 +/- 4 mm. Eighteen (56%) of 32 patients had a patent ASA. Patients were monitored for a mean period of 69.5 months (56 to 85 months). No patient had a cerebrovascular event or systemic embolization. CONCLUSION: The risk of cerebrovascular events or embolic strokes in our patient population with incidental ASA was low. If treatment is needed for this condition, aspirin appears to be effective therapy.