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Dive into the research topics where Edward Lakatos is active.

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Featured researches published by Edward Lakatos.


Circulation | 1991

Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function.

Robert O. Bonow; Edward Lakatos; Barry J. Maron; Stephen E. Epstein

BackgroundMany asymptomatic patients with aortic regurgitation and normal left ventricular systolic function remain clinically stable for many years, but others ultimately develop symptoms or left ventricular dysfunction and require operation. To identify indexes of left ventricular function predictive of symptomatic and functional deterioration during the long-term course of asymptomatic patients, we studied 104 asymptomatic patients with chronic severe aortic regurgitation and normal left ventricular ejection fraction at rest. Methods and ResultsSerial echocardiographic (average, 7.8 per patient) and radionuclide angiographic (average, 5.0 per patient) studies were obtained over a mean follow-up period of 8 years (range, 2–16 years). By Kaplan-Meier life table analysis, 58 ± 9% of patients remained asymptomatic with normal ejection fraction at 11 years, an average attrition rate of less than 5% per year; two patients died suddenly, four developed asymptomatic left ventricular dysfunction, and 19 underwent operation because symptoms developed. By univariate Cox regression analysis, many variables on initial study were associated with death, ventricular dysfunction, or symptoms, including age, left ventricular end-systolic dimension and enddiastolic dimension, fractional shortening, and both rest and exercise ejection fraction (all p < 0.001). The average rates of change of rest ejection fraction, fractional shortening, and end-systolic dimension were also associated with death or symptoms by univariate Cox analysis (all p < 0.01). However, when all variables were included in a multivariate Cox analysis, only age (p < 0.05), initial end-systolic dimension (p < 0.001), and rate of change in end-systolic dimension and rest ejection fraction during serial studies (both p < 0.05) predicted outcome. ConclusionsThus, in addition to indexes of left ventricular function determined on initial evaluation, serial long-term changes in systolic function identify patients likely to develop symptoms and require operation. Patients have a higher risk of symptomatic deterioration if there is progressive change in end-systolic dimension or resting ejection fraction during the course of serial studies.


Circulation | 1985

Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.

Robert O. Bonow; A L Picone; Charles L. McIntosh; Michael H. Jones; Douglas R. Rosing; Barry J. Maron; Edward Lakatos; Richard E. Clark; Stephen E. Epstein

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Circulation | 1992

Circadian variation in ischemic threshold. A mechanism underlying the circadian variation in ischemic events.

Arshed A. Quyyumi; Julio A. Panza; Jean G. Diodati; Edward Lakatos; Stephen E. Epstein

BackgroundThere is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. Methods and ResultsFifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p<0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8±2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p<0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p<0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. ConclusionsA lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time.


Controlled Clinical Trials | 1986

Sample size determination in clinical trials with time-dependent rates of losses and noncompliance

Edward Lakatos

Sample size determination is an important part of planning for clinical trials. During the course of a typical clinical trial, people are lost because of competing risks, noncompliance, and the like. Event rates available to the trial designers usually do not take these losses into consideration so that adjustment of these rates is necessary for sample size calculation. This article presents a method of adjusting such rates in the presence of time-dependent rates of losses, noncompliance, and the like. Lag in the effectiveness of medication is also considered.


Annals of Epidemiology | 1995

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure: Results from phase I of the Trials of Hypertension Prevention (TOHP)

Monica E. Yamamoto; William B. Applegate; Michael J. Klag; Nemat O. Borhani; Jerome D. Cohen; Kent A. Kirchner; Edward Lakatos; Frank M. Sacks; James Taylor; Charles H. Hennekens

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials.


The Journal of Pediatrics | 1994

Indexes of obesity and comparisons with previous national survey data in 9- and 10-year-old black and white girls: The National Heart, Lung, and Blood Institute Growth and Health Study

Barbara N. Campaigne; John A. Morrison; Barbara C. Schumann; Frank Falkner; Edward Lakatos; Dennis L. Sprecher; George B. Schreiber

OBJECTIVE To (1) describe anthropometric and body-size measurements in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) population at baseline and (2) examine potential secular trends in the prevalence of obesity in young black and white girls by comparing NGHS baseline data with those of the two National Health and Nutrition Examination Surveys (NHANES I and II) (measured before the NGHS). DESIGN Cross-sectional analysis of cohort baseline data. SETTING Recruitment in selected schools (Cincinnati and Berkeley) and among the membership of a group health association (Westat). PATIENTS Enrolled 2379 girls, 9 and 10 years of age, including 1213 black and 1166 white. MEASUREMENTS Anthropometric measures, including height, weight, and triceps and subscapular skin folds. Body mass index was used as a measure of body size. Nine- and ten-year-old black girls were taller, heavier, and had larger skin folds than white girls. Compared with age-similar girls in the 1970s, girls in the present study are taller and heavier and have thicker skin folds. The differences in body size were most notable among black girls. CONCLUSIONS Black girls have a greater body mass than white girls even as young as 9 and 10 years of age. The prevalence of obesity appears to be increasing among young girls, especially in black girls. This progression, if not altered, could lead to increased disease in the future for adult women, particularly black women.


Metabolism-clinical and Experimental | 1985

The association of LDL receptor activity, LDL cholesterol level, and clinical course in homozygous familial hypercholesterolemia

Dennis L. Sprecher; Jeffrey M. Hoeg; Ernst J. Schaefer; Loren A. Zech; Richard E. Gregg; Edward Lakatos; H. Bryan Brewer

Patients with homozygous familial hypercholesterolemia (FH), reveal a marked heterogeneity in plasma cholesterol levels, response to diet as well as drug treatment, and clinical course. Low-density lipoprotein (LDL) receptor activities were assessed by the rate of 14C-oleate cholesteryl ester biosynthesis in fibroblasts from 13 FH homozygotes in tissue culture. The receptor activity of the individual patients was highly correlated with initial pretreatment plasma cholesterol and LDL cholesterol levels (P less than .001, r = -0.89). In addition, the LDL receptor activity was positively correlated with the age of onset of angina based on the Cox model (P less than .035, likelihood ratio = 6.71). An association was also noted between LDL receptor activity and cholesterol reduction with drugs. These data provide direct evidence for the correlation between the heterogeneity of the LDL receptor and the expression of the clinical manifestations of homozygous FH. The determination of pretreatment plasma cholesterol level and LDL receptor activity in patients with homozygous FH provide useful parameters on which to base predictions of the clinical progression of cardiovascular disease. These parameters may also influence the selection of a program for diet and drug therapy. Patients with markedly elevated plasma cholesterol levels and very low LDL receptor activity should be considered to be candidates for multiple drug therapy, and portacaval shunt, and/or periodic plasma exchanges.


Journal of the American College of Cardiology | 1987

Three year anatomic, functional and clinical follow-up after successful percutaneous transluminal coronary angioplasty.

Douglas R. Rosing; Richard O. Cannon; Rita M. Watson; Robert O. Bonow; Rita Mincemoyer; Carolyn J. Ewels; Martin B. Leon; Edward Lakatos; Stephen E. Epstein; Kenneth M. Kent

Because the long-term anatomic effects of percutaneous transluminal coronary angioplasty are unknown, follow-up evaluations including coronary angiography, treadmill exercise testing and rest and bicycle exercise radionuclide angiography were performed in 46 patients 6.3 +/- 2.0 and 37.6 +/- 3.6 (mean +/- SD) months after they had undergone successful single lesion angioplasty. The severity of the coronary stenosis decreased significantly at each evaluation; the mean diameter stenosis was 66 +/- 13% before angioplasty, 30 +/- 13% immediately after and 26 +/- 16% and 19 +/- 13% at 6 months and 3 years, respectively. Exercise time increased from 9.8 +/- 4.4 minutes before angioplasty to 18.3 +/- 4.5 minutes immediately after the procedure and remained at that level at 6 months (20.3 +/- 4.6 minutes) and 3 years (18.2 +/- 4.5 minutes). Left ventricular ejection fraction during exercise decreased 4 +/- 6% compared with rest before angioplasty, but increased 7 +/- 7% immediately after angioplasty and this increase was maintained at 6 months (+/- 6 +/- 7%) and 3 years (+/- 4 +/- 6%). Before angioplasty, 1 patient was in Canadian Heart Association functional class 0, 15 were in class II, 24 in class III and 6 in class IV. Three years later, 25 were in class 0, 10 in class I, 7 in class II and 4 in class III. These results indicate that the short-term anatomic and functional success of coronary angioplasty is maintained for at least 3 years.


Journal of the American College of Cardiology | 1993

Angiogenic effects of low molecular weight heparin in patients with stable coronary artery disease: A pilot study

Arshed A. Quyyumi; Jean G. Diodati; Edward Lakatos; Robert O. Bonow; Stephen E. Epstein

OBJECTIVES The study was designed to assess the feasibility of conducting a trial to investigate whether exercise and low molecular weight heparin therapy with dalteparin sodium (Fragmin) would improve collateral function to the ischemic myocardium in patients with coronary artery disease. BACKGROUND The severity of myocardial ischemia in patients with coronary artery disease is at least partly dependent on the status of the collateral circulation. Therefore, improvement in collateral function would potentially provide a unique way of alleviating myocardial ischemia. Because the combination of ischemia and heparin has previously been demonstrated to enhance collateral growth, we studied the anti-ischemic effects of combined treatment with dalteparin sodium and exercise-induced ischemia in patients with coronary artery disease. METHODS Twenty-three patients with stable coronary artery disease were randomized to receive either subcutaneous dalteparin sodium or placebo for a 4-week period. Patients received either placebo or 10,000 IU of dalteparin sodium by subcutaneous injection once daily for weeks 1 and 2 and 5,000 IU daily for weeks 3 and 4. During the 1st 2 weeks, patients were exercised to ischemia three times a day. At baseline and 4 weeks after treatment, treadmill exercise testing, exercise radionuclide ventriculography and 48-h ambulatory ST segment monitoring were performed. RESULTS Eight (80%) of the 10 dalteparin sodium-treated patients compared with 4 (31%) of 13 placebo-treated patients (p < 0.02) had an increased rate-pressure product at the onset of 1 mm of ST segment depression. The duration of exercise to ischemia increased in all patients treated with low molecular weight heparin and in 62% of placebo-treated patients (p < 0.03). The number and duration of episodes of ST segment depression during ambulatory monitoring decreased by 30% and 35%, respectively (p < 0.05), in the dalteparin sodium group but were unchanged in the placebo group. The decrease in left ventricular ejection fraction with exercise was lower in 80% of dalteparin sodium-treated patients compared with 54% of placebo-treated patients (p = 0.06). When all five factors reflecting collateral function were considered together in a multivariate analysis of variance, there was a significant improvement in low molecular weight heparin-treated patients compared with placebo-treated patients (p = 0.014). CONCLUSIONS This study provides preliminary evidence suggesting that exercise and low molecular weight heparin therapy with dalteparin sodium lessen myocardial ischemia and that the improvement is likely to be mediated by enhanced collateral function.


American Journal of Cardiology | 1992

Degree of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy and chronic atrial fibrillation

Paolo Spirito; Edward Lakatos; Barry J. Maron

It has been generally assumed that most patients with hypertrophic cardiomyopathy (HC) who develop atrial fibrillation (AF) have marked left ventricular (LV) hypertrophy and subaortic obstruction. The morphologic and functional features of this subset of patients with HC have not been systematically investigated. The LV morphology and functional profile of 46 patients with HC and chronic AF were compared with those of 81 control patients with HC and normal sinus rhythm. Contrary to expectations, LV hypertrophy (assessed with 2-dimensional echocardiography) was substantially less marked in the patients with AF than in the control patients, and prevalence of subaortic obstruction was similar in the 2 groups. Maximal LV wall thickness and wall thickness index were lower in patients with AF (18 +/- 2 and 56 +/- 7 mm, respectively) than in control patients (22 +/- 6 and 67 +/- 16 mm, respectively; p less than 0.001). Furthermore, mild LV hypertrophy (maximal LV wall thickness less than or equal to 17 mm confined to 1 ventricular segment) was almost twice as frequent in patients with AF (63%) than in control patients (36%; p less than 0.005). Subaortic obstruction was present in 9 patients with AF (20%) and in 28 control patients (35%; p greater than 0.05). In a subgroup of 22 patients with AF who were followed for 4 to 10 years, 5 patients had marked LV wall thinning (greater than or equal to 5 mm, range 5 to 14). In conclusion, these results demonstrate that most patients with HC and chronic AF have the nonobstructive form of HC, and relatively mild LV hypertrophy.

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Barry R. Davis

University of Texas at Austin

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Jeffrey A. Cutler

National Institutes of Health

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Stephen E. Epstein

MedStar Washington Hospital Center

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Lot Page

National Institutes of Health

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