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Biomedical subjects

J M Detry

Publications and source records attributed to J M Detry.

At least 19 recordsLinked to original sources

Effect of dexfenfluramine treatment on body weight, blood pressure and noradrenergic activity in obese hypertensive patients.

The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients given Pl completed the entire experimental protocol, including monthly visits for metabolic and hormonal measurements, as well as a bicycle exercise test with arterial catheterisation for haemodynamic and catecholamine measurements performed before and after 3 months of treatment. A progressive significant decrease in body weight, averaging 6.0 kg after 3 months was observed in the dF-treated group, whereas loss of weight in the placebo group (1.4 kg) was not significant. While blood pressure and noradrenergic activity, assessed as changes in the plasma levels and urinary excretion of norepinephrine, remained unaffected in the Pl group, a significant drop in the supine systolic and diastolic blood pressures, as well as in the resting venous norepinephrine level and in urinary norepinephrine excretion was found after the first month of dF administration. In addition, the exercise-induced rise in systolic and diastolic blood pressure, as well as in arterial plasma norepinephrine and epinephrine concentrations, was significantly reduced after 3 months of dF administration; there were no such changes in the Pl-treated group. The results of the present study indicate that, in addition to the weight-reducing effect of dexfenfluramine, its hypotensive effect may be mediated by a decrease in noradrenergic activity.

Adult

Hemodynamic and volume correlates of left ventricular diastolic relaxation and filling in patients with aortic stenosis.

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic and volume correlates of early diastolic filling and isovolumetric relaxation in patients with aortic stenosis. BACKGROUND: Left ventricular diastolic relaxation and filling have been found to be heterogeneous in patients with aortic stenosis. Potential mechanisms underlying this heterogeneity include individual differences in the severity of muscle hypertrophy or systolic dysfunction, or both, in the presence and severity of mitral regurgitation and in the level of left atrial pressure. METHODS: Right (fluid-filled) and left (high fidelity micromanometer) ventricular pressures, left ventricular volumes (contrast angiography) and transmitral inflow dynamics (Doppler echocardiography) were measured in 17 patients with isolated severe aortic stenosis (valve area less than 0.75 cm2). Measurements included left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction, peak positive and negative first derivative of left ventricular pressure (dP/dt), the time constant of isovolumetric relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass, left ventricular end-systolic stress, mean capillary wedge pressure and peak early (E) and late (A) transmitral filling velocities. Patients were subclassified according to left ventricular ejection performance at rest and mean capillary wedge pressure. RESULTS: Patients with normal ejection performance and normal mean capillary wedge pressure had a normal rate of isovolumetric left ventricular pressure decay and an abnormal diastolic filling pattern, with diastolic filling occurring primarily during atrial systole. In contrast, in patients with systolic dysfunction and elevated mean capillary wedge pressure, isovolumetric pressure decay was prolonged and diastolic filling occurred essentially during the rapid filling period, with reduced atrial contribution to left ventricular filling and a short isovolumetric relaxation period. Stepwise multiple linear regression analysis identified two variables as independent predictors of transmitral velocity profile and three variables independently predictive of the rate of left ventricular pressure decay. The single most important predictor of transmitral filling pattern was the pulmonary capillary wedge pressure (p less than 0.0001), followed by the left ventricular peak negative dP/dt (p = 0.002). The single most powerful predictor of the rate of reduction in left ventricular pressure was left ventricular mass index (p less than 0.0001), followed by end-systolic volume index (p = 0.0002) and left ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS: In patients with aortic stenosis, left ventricular filling is essentially determined by left atrial pressure, whereas isovolumetric relaxation more closely depends on the severity of muscle hypertrophy and chamber dilation.

Aged

Prognostic significance of silent exertional myocardial ischaemia in symptomatic men without previous myocardial infarction.

A total of 360 consecutive male patients with complaints of chest pain and documented coronary artery disease underwent a maximal exercise test combined with thallium myocardial scintigraphy. Patients with a history of previous myocardial infarction were excluded. During follow-up (46 months; from 12 to 96) 27 patients died and 26 had a first non-fatal myocardial infarction. The 6-year survival rate and the 6-year event-free rate were 81 and 71%. Four variables contributed independently to the prognosis (Cox Model): the number of diseased vessels, the angiographic ejection fraction, the age and a multivariate score of the exercise test. From these patients, 227 had an abnormal response to exercise (ST-segment depression greater than or equal to 0.1 mV); in 138 patients, angina pectoris was induced during exercise while 89 patients had no pain during exercise (silent ischaemia). These 89 patients with silent exertional ischaemia were matched to 89 patients with exertional angina pectoris, according to the above-mentioned four prognostic predictors. The two groups of patients had similar signs of ischaemia during exercise (ST-segment depression and thallium perfusion score). The 6-year survival rates (81 and 81.5%) and the 6-year event-free rates (71 and 70.5%) were similar in the two groups. Thus, in men without previous myocardial infarction, silent exertional ischaemia bears the same prognosis as exertional ischaemia attended by angina pectoris.

Adult

Circadian rhythms in cardiovascular disease: the crucial hours.

Major cardiovascular events, i.e. myocardial infarction and sudden death, have a circadian variation with a peak incidence during the morning hours. The factors possibly triggering those events, namely myocardial ischaemia, sympathetic tone and blood coagulability, have a similar circadian variation which could explain the circadian distribution of the major cardiovascular events.

Cardiovascular Diseases

Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem.

Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic properties attributed to a modulation of myocardial metabolism. Its antianginal action was assessed in 104 patients recruited in a double-blind, crossover, randomized study comparing placebo with a single dose of ranolazine (10, 60, 120, and 240 mg). All patients had chronic stable angina pectoris and remained symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy exercise testing) despite treatment with a beta-blocker or with diltiazem. No significant effects of ranolazine on exercise duration or time to angina were observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however, significant improvement in exercise duration (+13.1% in the combined group, two-tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time to 1 mm ST-segment depression was observed. The cumulative proportion of patients who improved their time to angina by at least 30 s above placebo were 25, 42, 50, and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven percent of the patients with ranolazine plasma levels above 500 ng/ml improved their time to angina against 40% at plasma levels below 500 ng/ml and summed ST-segment depression during exercise and recovery was also significantly reduced at these plasma concentrations. Both heart rate and arterial pressure at rest and at peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetanilides

Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function.

Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Prolonged exercise induces left ventricular dysfunction in healthy subjects.

To determine the effects of a moderately prolonged exercise on left ventricular systolic performance, 23 healthy male subjects, aged 18 to 51 yr (mean 37 yr) were studied. The subjects exercised first on a treadmill (brief exercise) and completed, on a separate day, a 20-km run. M-mode, two-dimensional, and Doppler echocardiography, as well as calibrated carotid pulse tracings, were obtained at rest and immediately on completion of both brief and prolonged exercise. Left ventricular systolic function was assessed by end-systolic stress-shortening relationships. Heart rate increased similarly after brief and prolonged exercise (+30%). Mean arterial pressure decreased from 99 +/- 7 to 92 +/- 8 mmHg (P less than 0.001) after prolonged exercise, but it remained unchanged after brief exercise. Left ventricular end-diastolic volume was decreased after prolonged exercise (130 +/- 23 vs. 147 +/- 18 ml at rest, P less than 0.01). Both ejection fraction and rate-adjusted mean velocity of fiber shortening decreased after prolonged exercise [from 67 +/- 5 to 60 +/- 6% (P less than 0.001) and from 1.12 +/- 0.2 to 0.91 +/- 0.2 cm/s (P less than 0.001), respectively] despite a lower circumferential end-systolic wall stress (133 +/- 23 vs. 152 +/- 20 g/cm2). The relationship between ejection fraction (or mean velocity of fiber shortening adjusted for heart rate) and end-systolic wall stress was displaced downward on race finish (P less than 0.05). These changes were independent of the changes in left ventricular end-diastolic volume and hence those in preload. The data suggest that moderately prolonged exercise may result in depressed left ventricular performance in healthy normal subjects.

Adult

Logistic discriminant analysis improves diagnostic accuracy of exercise testing for coronary artery disease in women.

BACKGROUND: Diagnostic accuracy of the exercise electrocardiogram in women has been shown to be limited for the detection of coronary artery disease. New diagnostic methods based on computer analysis of the exercise electrocardiogram and multivariate analysis have improved the diagnostic value of exercise testing in male subjects. The aim of the present study was to assess whether the diagnostic value of exercise testing can be enhanced in women by using multivariate analysis of exercise data. METHODS AND RESULTS: Between 1978 and 1984, 135 infarct-free women underwent exercise testing and coronary angiography. Significant coronary artery disease was present in 41% of the patients. In this first group, maximal exercise variables were submitted to a stepwise logistic analysis. Work load, heart rate, and ST60X were selected to build a diagnostic model. The model was tested in a second group of 115 catheterized women (significant coronary artery disease in 47%) and of 76 volunteers. We compared the present model with conventional analysis of the exercise electrocardiogram, with ST changes adjusted for heart rate, and with a previously described analysis. In both groups, sensitivity was better with the present model (66% and 70%) than by conventional (68% and 59%) and by the previously described analysis (57% and 44%) without a loss of specificity (85% and 93%). Receiver-operator characteristic curves showed also a better diagnostic accuracy with the present model. CONCLUSIONS: In women, logistic analysis of exercise variables improves the diagnostic value of exercise testing. It yields a significantly better sensitivity without a loss of specificity.

Coronary Disease

A new semiautomated algorithm to quantify Holter-detected myocardial ischemia: preliminary experience in the Trimetazidine European Multicenter trial (TEMS).

Holter-detected myocardial ischemia, either painful or painless, is an important issue in the functional and prognostic evaluation of coronary patients. This paper describes one of the first attempts to reliably quantify the duration and severity of the ischemic ST-segment changes over a given period of time; the algorithm described here provides physicians with a global index of ischemia that is the total ischemic area, namely, the integral of ST-segment depression or elevation over time (expressed in mm x min). The diagnostic and prognostic power of this new index remains to be established and to be compared with the actually used simple measurements, i.e., the number and duration of ischemic events.

Algorithms

Additional prognostic value of exercise testing and thallium-201 scintigraphy in catheterized patients without previous myocardial infarction.

To determine whether exercise testing and thallium scintigraphy provide additional prognostic information in symptomatic patients undergoing catheterization, we studied 432 consecutive male patients without a previous myocardial infarction by means of an exercise test, thallium scintigraphy and catheterization. The follow-up period was 46 +/- 24 months (from 12 to 96). Events were defined as death (27 patients), nonfatal myocardial infarction (occurring in 27 patients) or late (greater than 60 days after test) surgery or dilatation (needed in 45 patients). The 5 year survival rate was 89% and the event-free rate was 72%. History, noninvasive and invasive variables were submitted to a stepwise Cox regression analysis. By multivariate analysis, the significant variables related to death were the number of diseased vessels and exercise workload; the selected variables for all cardiac events were the number of diseased vessels; the score at thallium exercise testing and exercise workload. Among the subgroups of 337 coronary patients, the predictive variables for death were exercise workload and the number of diseased vessels. For all cardiac events, the selected variables were the number of diseased vessels, the score of defects during thallium exercise and exercise workload. Thus, in patients without a previous myocardial infarction, noninvasive variables do provide prognostic information which is not available either from the history or from catheterization.

Cardiac Catheterization

Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables.

A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris

Influence of age and sex on left ventricular volumes and ejection fraction during upright exercise in normal subjects.

To determine the effects of age and sex on exercise left ventricular volume indexes and ejection fraction, a cross-sectional study was performed in 18 young volunteers (nine men and nine women) and in 17 older volunteers (nine men and eight women) without evidence of coronary artery disease by exercise electrocardiographic and thallium-201 criteria. All subjects performed a multistage maximal upright exercise with measurements of maximal oxygen consumption and heart rate; left ventricular ejection fraction and absolute volume indexes were measured at rest and during submaximal and maximal exercise using equilibrium radionuclide ventriculography. At rest, no effect of age or sex on any parameter was observed. At peak exercise, an age-related increase in mean blood pressure, end-diastolic and end-systolic volume indexes, and decrease in ejection fraction, cardiac index, heart rate and oxygen consumption were noticed. Sex had a significant effect on maximal workload, maximal oxygen consumption and ejection fraction.

Adolescent

The spouse as a possible anginal warning system in silent myocardial ischaemia.

It has been previously shown that undercomplaining behaviour is involved in the 'silence' of Silent Myocardial Ischaemia (SMI). By means of symptom checklists completed blindly by both the patient and his spouse we found that: (1a) at an individual level, even in non-cardiac related symptoms areas (everyday illnesses), SMI patients have a lower propensity to complain than symptomatic patients; yet (1b) they describe the same level of worrying about symptoms as painful patients. (2) At a second level, when looking at patient-spouse discrepancies it appears that the spouse of the SMI patient describes the patient as having not only more symptoms but also as being less worried than he reports. On the contrary, the spouse of the symptomatic patient generally describes the patient as having fewer symptoms than he does and as being more worried by the symptom's appearance than he reports. These data support the denial hypothesis in SMI and allow us to consider the spouse not only as a good anamnestic collaborator in order to avoid information biases in SMI but also as a potential warning system that could be used in prevention and treatment strategies related to SMI.

Angina Pectoris

Non-invasive data provide independent prognostic information in patients with chest pain without previous myocardial infarction: findings in male patients who have had cardiac catheterization.

From 1978 to 1985, 470 consecutive male patients with complaints of chest pain underwent a maximal exercise test with a thallium scan and coronary angiography (CA). Patients with a history of myocardial infarction (MI) were excluded. During the follow-up (from 12 to 96 months), 32 patients died and 30 had a non-fatal MI. Survival (SR) and event-free rates (EFR) were estimated by actuarial methods; the influence of non-invasive and invasive variables were examined in univariate and multivariate models using Cox analysis. The five-year SR was 89% and EFR was 81%. Among historical data, age (less than 0.001), type of complaints (less than 0.01) and pretest likelihood of CAD (less than 0.01) were univariate predictors of EFR; by multivariate analysis, age was the only significant predictor (less than 0.001). Most of the maximal-exercise (MEX) test data were good univariate predictors; by multivariate analysis, workload (less than 0.001) and the maximal-exercise test score (less than 0.001) were the significant predictors. From history and maximal-exercise test data, multivariate analysis indicated that the prognostic information was given by age (less than 0.05) and maximal-exercise test score (less than 0.001). Among the invasive data, the number of diseased vessels (less than 0.001) and ejection fraction were the predictors. The combination of invasive and non-invasive data indicated that age, MEX score, number of diseased vessels and ejection fraction contributed significantly and independently to the estimation of prognosis. Among 242 patients with two or three diseased vessels, the prognosis was determined by the maximal workload (less than 0.01); ejection fraction (less than 0.07) was no longer significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ejection fraction response to upright exercise in hypertension: relation to loading conditions and to contractility.

The respective roles of peripheral and myocardial determinants of exercise ventricular performance were studied in 10 normal volunteers and in 9 mildly hypertensive patients without evidence of coronary disease. Hemodynamic measurements and equilibrium blood pool scintigraphy were simultaneously performed at rest and during maximal upright exercise. In hypertensive patients, mean systolic and diastolic blood pressure were, respectively, 199 +/- 23 and 102 +/- 12 mm Hg at rest, and 271 +/- 28 and 113 +/- 8 mm Hg at peak exercise. Ejection fraction response to exercise was normal (increase by more than 5%) in 4 hypertensive patients (normal hypertensive group: 63 +/- 4 to 77 +/- 6%) and in volunteers (65 +/- 3 to 78 +/- 4%) and abnormal in 5 hypertensive patients (abnormal hypertensive group: 66 +/- 6 to 58 +/- 10% at peak exercise). The abnormal response in the abnormal hypertensive group was not due to an inadequate decrease in systemic vascular resistance during exercise. By contrast, the ratio systolic blood pressure/end-systolic volume, an index of contractility, decreased by 2.3 +/- 4.9 in the abnormal hypertensive group, whereas it increased by 9.8 +/- 9.1 in the normal hypertensive group and by 7.3 +/- 2 in volunteers. Thus, abnormal exercise ejection fraction response in mild hypertension was not related to increased afterload but rather to intrinsic myocardial factors.

Adult

Implementation of the Louvain program for exercise ECG analysis on a microprocessor system.

Several years ago we developed a computer system for the processing of exercise ECGs: the Louvain program for exercise ECG analysis which runs on a minicomputer "Modcomp Classic" and processes XYZ data remotely collected on digital cartridge at the exercise room. This off-line batch procedure is time consuming for the technician (reading of cartridge), but theoretically could be fast. Our experience shows that the results of the exercise test are provided to the referring physician from one day to one week after the procedure because of delays at different levels. The implementation of the programs in a stand-alone unit can produce the results one minute after the end of the test. This solution obviously is more satisfactory for routine clinical testing.

Computers