Exaggerated chronotropic and energetic response to dobutamine after orthotopic cardiac transplantation.

BACKGROUND: After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic response to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when challenged with dobutamine. METHODS AND RESULTS: A total of 18 heart transplant recipients and 14 normal volunteers underwent measurements of myocardial oxygen consumption (MVO2), external work (EW), and pressure-volume area (PVA), at rest and during infusion of dobutamine. At rest, calculated myocardial (PVA/MVO2) and mechanical (EW/MVO2) efficiencies were similar among transplant recipients and normal volunteers. During low-dose dobutamine infusion (8 microg/kg/min), transplant recipients exhibited a larger increase in heart rate (to 126 +/- 14 vs 87 +/- 26 beats/min, p < 0.001) and MVO2 (to 269 +/- 43 vs 233 +/- 19 J/min/100g, p < 0.05) and a smaller increase in EW (64 +/- 18 vs 72 +/- 13 J/min/100g, p < 0.05) and PVA (70 +/- 16 vs 81 +/- 13 J/min/100g, p < 0.05) than did normal volunteers. As a result, both myocardial (26 +/- 4 vs 35 +/- 4%, p < 0.05) and mechanical (23 +/- 4 vs 30 +/- 4%, p < 0.001) efficiencies were lower during dobutamine infusion in transplant recipients than in normal volunteers. During the infusion of a higher dose of dobutamine (19 microg/kg/min), the chronotropic and inotropic responses of heart transplant recipients were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate (r = -0.58) and could be reproduced in normal volunteers by coadministration of atropine. CONCLUSIONS: Transplant recipients exhibit a larger fall in contractile efficiency and a larger oxygen-wasting effect during dobutamine infusion than do normal volunteers. Because normal volunteers pre-medicated with atropine presented with a similar increase in heart rate and a similar fall in efficiency, the exaggerated energetic response of transplanted hearts to dobutamine likely resulted from the same mechanisms as their chronotropic supersensitivity, i.e., the loss of inhibitory parasympathetic innervation.

Early short-term intensive cardiac rehabilitation induces positive results as long as one year after the acute coronary event: a prospective one-year controlled study.

AIMS: The one-year effects of early and short-term intensive cardiac rehabilitation programmes in patients after acute myocardial infarction or coronary artery bypass surgery (CABG) are not well established. METHODS AND RESULTS: One to four weeks after hospital discharge for acute myocardial infarction (n=55) or CABG (n=54), 109 patients were included in a multidisciplinary ambulatory cardiac rehabilitation programme, lasting 2 to 3 months and including a mean of 33 daily sessions. A complete cardiological assessment of the classical coronary risk factors was performed at entry into the study and again 12 months later, that is 9 to 10 months after the end of the rehabilitation programme. Major effects at one-year follow-up were a high rate of aspirin intake, a low rate of smoking (14% of the patients), a 15% increase in physical capacity, a 7 beats/min decrease in resting heart and a 4 mg/dl increase in the HDL-cholesterol. Body weight increased by 4.9 kg in the patients who stopped smoking; the modest increase in body weight in the other patients reflected a partial weight recovery in the CABG patients. Blood pressure levels also increased at the end of the study but our data in CABG patients and their extrapolation to the post MI patients strongly suggest a progressive return of blood pressure to the pre-acute event levels. In a control group matched for age, sex and type of coronary event, no significant modifications were observed after one year, except for an increase in body weight of 1.7 kg (P < 0.000). CONCLUSIONS: Cardiac rehabilitation which started early after an acute coronary event and regularly followed during 2 to 3 months induced beneficial effects which were still present 9 to 10 months later. Weight gain after smoking cessation was prevalent. The lack of changes in the control group reinforced the benefit of cardiac rehabilitation.

Contribution of left ventricular diastolic function to exercise capacity in normal subjects.

Previous studies have established that most of the heterogeneity in exercise capacity seen with sedentariness, aging, or physical training can be accounted for by individual differences in the maximal rate of total body oxygen consumption (VO2 max) during dynamic exercise. However, the factors that limit VO2 max in normal subjects remain disputed. To test the hypothesis that differences in left ventricular diastolic performance contribute to the heterogeneity of VO2 max seen in healthy subjects, 57 normal sedentary volunteers (36 +/- 13 yr, range 20-76 yr) and 9 endurance athletes (37 +/- 8 yr, range 26-51 yr) were studied. Aerobic capacity was estimated as VO2 max during a multistage dynamic cycle exercise protocol, whereas resting left ventricular systolic and diastolic function was assessed by two-dimensional and Doppler echocardiography. The relationship of the left ventricular functional indexes with VO2 max was investigated by stepwise multiple regression analysis. VO2 max ranged from 25 to 58 ml.kg-1 x min-1 in sedentary subjects and from 44 to 60 ml.kg-1 x min-1 in athletes. With univariate analysis, significant correlations were observed between VO2 max and age (r = -0.60), maximal heart rate (r = 0.48), maximal work load (r = 0.80), left ventricular volumes at both end diastole (r = 0.51) and end systole (r = 0.62), peak early transmitral filling velocities (r = 0.80), and the ratio of early to late transmitral filling velocities (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Regional oxidative metabolism in patients after recovery from reperfused anterior myocardial infarction. Relation to regional blood flow and glucose uptake.

BACKGROUND: Enhanced uptake of the glucose analogue 18F-fluorodeoxyglucose (FDG) in relation to flow has been proposed as an accurate method of identifying viable myocardium. The evaluation of myocardial oxidative metabolism could be an alternate way to identify reversible injury. The aim of the present study was to investigate in patients with reperfused anterior infarction whether differences in regional oxidative metabolism exist among regions with and without flow-metabolism mismatch. METHODS AND RESULTS: Fifteen patients with reperfused anterior myocardial infarction were studied between 2 weeks and 3 months after the acute event. Regional myocardial blood flow (13N-ammonia; three-compartment model), oxidative metabolism (11C-acetate; monoexponential clearance), and glucose uptake (FDG, linear graphic analysis) were evaluated with dynamic positron emission tomography. Flow-metabolism patterns were used to differentiate reversibly (FDG/flow greater than 1.2) from irreversibly injured myocardium (FDG/flow less than 1.2) using circumferential profile technique. Relative 13N-ammonia uptake was reduced in 71 of 90 anterior and/or septal segments, including 24 with (seven patients) and 38 without (eight patients) flow-metabolism mismatch. Acetate clearance (k), reflecting oxidative metabolism, was reduced by 51% in the center of the infarct area versus remote segments (27 +/- 12 versus 55 +/- 13 min-1.10(-3), p less than 0.001). Compared with infarct segments without flow-metabolism mismatch, segments exhibiting increased glucose uptake relative to flow had faster acetate clearance (35 +/- 14 versus 23 +/- 9 min-1.10(-3), p less than 0.01). Similarly, myocardial blood flow was better preserved in segments with flow-metabolism mismatch (54 +/- 13 versus 45 +/- 8 ml/min/100 g, p less than 0.01) compared with segments without mismatch. However, at similar levels of hypoperfusion, there was no significant difference in acetate clearance among segments with and those without flow-metabolism mismatch: 37 +/- 14 versus 41 +/- 15 min-1.10(-3), respectively. A positive correlation (r = 0.89, p less than 0.001) was found between absolute myocardial blood flow and acetate clearance, regardless of the flow-metabolism pattern. CONCLUSIONS: In patients with reperfused myocardial infarction studied between 2 weeks and 3 months after the acute event, regional oxidative metabolism is reduced in proportion to residual myocardial blood flow and does not differ significantly among similarly hypoperfused segments with and without flow-metabolism mismatch.

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.

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)

To test or not to test--to treat or not to treat: the decision-threshold approach to patient management.

The inability to consider explicitly factors that should enter into clinical judgment compromises physician efforts to make cost-effective decisions regarding diagnostic testing and treatment. The authors describe the decision-threshold approach, a decision-analysis strategy that helps physicians identify an optimal test-treatment decision based upon the prior probability of disease, the characteristics of the test (sensitivity, specificity, risk), and the benefits/costs of treatment. They also present a microcomputer graphics program that makes the decision-threshold approach readily available to physicians.

Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and efficiency of probability analysis.

Alternative strategies using conditional probability analysis for the diagnosis of coronary artery disease (CAD) were examined in 93 infarct-free women presenting with chest pain. Another group of 42 consecutive female patients was prospectively analyzed. For this latter group, the physician had access to the pretest and posttest probability of CAD before coronary angiography. These 135 women all underwent stress electrocardiographic, thallium scintigraphic, and coronary angiographic examination. The pretest and posttest probabilities of coronary disease were derived from a computerized Bayesian algorithm. Probability estimates were calculated by the four following hypothetical strategies: SO, in which history, including risk factors, was considered; S1, in which history and stress electrocardiographic results were considered; S2, in which history and stress electrocardiographic and stress thallium scintigraphic results were considered; and S3, in which history and stress electrocardiographic results were used, but in which stress scintigraphic results were considered only if the poststress probability of CAD was between 10% and 90%, i.e., if a sufficient level of diagnostic certainty could not be obtained with the electrocardiographic results alone. The strategies were compared with respect to accuracy with the coronary angiogram as the standard. For both groups of women, S2 and S3 were found to be the most accurate in predicting the presence or absence of coronary disease (p less than .05). However, it was found with use of S3 that more than one-third of the thallium scintigrams could have been avoided without loss of accuracy. It was also found that diagnostic catheterization performed to exclude CAD as a diagnosis could have been avoided in half of the patients without loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and long-term effects of nitrendipine on resting and exercise hemodynamics in essential hypertension.

The hemodynamic effects of nitrendipine have been studied at rest and during exercise in eight patients with mild to moderate essential hypertension. Acutely, nitrendipine (20 mg) induced at rest a decrease in arterial blood pressure (from 194/100 to 151/78 mm Hg) and an increase in heart rate (from 81 to 101 beats/min); the cardiac output was unchanged and the systemic vascular resistances fell by 30%. Similar changes were observed during exercise, i.e., a decrease in arterial blood pressure (from 245/106 to 204/87 mm Hg) and in systemic vascular resistances (-25%) with an increase in heart rate (from 133 to 142 beats/min). After chronic treatment during 55 days (average daily dose was 46 mg), the hypotensive effects of nitrendipine were similar, although less marked, both at rest and during exercise; the tachycardia noted after acute intake disappeared after chronic therapy. The addition of atenolol (100 mg) at the end of the chronic study in six patients further reduced arterial blood pressure at rest (138/80 mm Hg) and during exercise (180/91 mm Hg); the heart rate decreased to 60 beats/min at rest and 94 beats/min during exercise. These data show that nitrendipine is a potent antihypertensive agent that induces an important fall in the systemic vascular resistances both at rest and during exercise; during chronic therapy, these antihypertensive effects were maintained while the reflex tachycardia disappeared. The addition of atenolol during chronic therapy contributed to the normalization of the resting and exercise arterial blood pressures in nearly all patients.

Bayesian analysis of stress thallium scintigraphy for the detection of multivessel coronary disease.

This study was performed in 224 men to determine the respective contribution of history and thallium-201 stress myocardial scintigraphic imaging in the non-invasive prediction of the severity of coronary disease. Myocardial scintigraphic imaging had the better diagnostic accuracy (80%) for the detection of multivessel disease but the results emphasize the importance of the history in predicting the extent of coronary artery disease. In patients with myocardial infarction, the diagnostic accuracy of the history (80%) was similar to the diagnostic accuracy of myocardial scintigraphic imaging (79%); in the subgroup of patients with residual angina pectoris after infarction, the accuracy of the history was even greater (87%) than that of myocardial scintigraphic imaging (78%). Thus, after myocardial infarction, scintigraphy was useful only in the small subgroup of patients without residual angina pectoris when it had a diagnostic accuracy of 79%, slightly but insignificantly superior to that of the history (62%). In patients without previous myocardial infarction, but with typical angina, myocardial scintigraphy was clearly superior to the simple history (diagnostic accuracy of 78% versus 53%; P less than 0.001). In patients without myocardial infarction and with atypical angina the prevalence of multivessel disease was low (17%) and the diagnostic accuracy of history (83%) was barely different from the diagnostic accuracy of myocardial scintigraphic imaging (90%). Thus, when the likelihood of multivessel disease is very high (angina pectoris post myocardial infarction), or very low (atypical angina), the contribution of exercise testing is very limited. Important additional information is provided by maximal exercise testing and myocardial scintigraphic imaging only in the groups with an intermediate prevalence of multivessel disease, namely in the asymptomatic patients after myocardial infarction and in the patients with typical angina but no previous myocardial infarction.