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Biomedical subjects

R Belardinelli

Publications and source records attributed to R Belardinelli.

At least 19 recordsLinked to original sources
PubMed2002

Vasomotor reactivity evaluation in cardiac rehabilitation.

Endothelial dysfunction is a generalized phenomenon detectable at various levels in the vasculature, and is evident very early in the atherosclerotic process. These peculiarities have stimulated the introduction of new non-invasive techniques dedicated to evaluate the vasomotor response of arteries or districts in favourable position in the body (forearm, hand) that may reflect the response of inner arteries otherwise requiring invasive procedures (i.e. coronary arteries). Moreover, these techniques can be theoretically used to detect abnormalities of vasomotor response before a clinical adverse event may occur in subjects prone to vascular accidents with risk factors for atherosclerosis. Of physical stimuli inducing e-NOS activation and subsequent nitric oxide synthesis, the shear stress produced by pulsatile blood flow is the most important. This property is actually used in clinical practice to study the flow-mediated vasodilation (FMD) of the brachial artery. Any condition that reduces the ability of endothelial cells to produce nitric oxide causes endothelial dysfunction, which is directly reflected into a depressed FMD. There is evidence that brachial artery flow-mediated dilation is improved after local as well as systemic exercise, suggesting that the improvement in endothelial function is generalized and documentable in different arterial districts with similar results. Aerobic exercise induces e-NOS expression and improves the endothelial-dependent relaxation in normal as well as cardiac patients. The endothelium-independent vasorelaxation is generally unchanged after chronic conditioning, but this result is not evident in all studies. The improved endothelial vasoreactivity is correlated with enhanced functional capacity after moderate aerobic exercise, suggesting an important pathophysiological role of oxygen transport in exercise tolerance. These beneficial effects has been described in patients with stable heart failure in II and III NYHA functional class and in patients with coronary artery disease with programs different for frequency, duration and intensity. The evaluation of vasomotor reactivity gives promising results in explaining the effects of medications and exercise training. The demonstration that flow-mediated dilation may quantify endothelial dysfunction in subjects with a variety of conditions can be used in clinical practice not only to assess the effects of interventions, but also to provide a preliminary screening in apparently healthy subjects who have an underlying silent coronary artery disease. In cardiac rehabilitation, there are promising results from FMD evaluation in selecting patients who take major benefits in terms of functional capacity and endothelium-dependent vasodilation.

Endothelium, Vascular↗
PubMed2001

Exercise training intervention after coronary angioplasty: the ETICA trial.

OBJECTIVES: The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome. BACKGROUND: It is unknown whether ET induces beneficial effects after coronary angioplasty. METHODS: We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group. RESULTS: Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001). CONCLUSIONS: Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.

Angioplasty, Balloon, Coronary↗
PubMed2001

Cost-effectiveness analysis of long-term moderate exercise training in chronic heart failure.

The purpose of this study is to perform a cost-effectiveness analysis of long-term moderate exercise training (ET) in patients with stable chronic heart failure. In particular, the study focuses on the survival analysis and cost savings from the reduction in the hospitalization rate in the exercise group. In the past 10 years, ET has been shown to be beneficial for patients with stable class II and III heart failure in many randomized clinical trials. However, the cost-effectiveness of a long-term ET program has not been addressed for outcomes related to morbidity/mortality end points or health care utilization. We examined the cost-effectiveness of a 14-month long-term training in patients with stable chronic heart failure. The estimated increment cost for the training group, $3,227/patient, was calculated by subtracting the averted hospitalization cost, $1,336/patient, from the cost of ET and wage lost due to ET, estimated at $4,563/patient. For patients receiving ET, the estimated increment in life expectancy was 1.82 years/person in a time period of 15.5 years, compared with patients in the control group. The cost-effectiveness ratio for long-term ET in patients with stable heart failure was thus determined at $1,773/life-year saved, at a 3% discount rate. Long-term ET in patients with stable chronic heart failure is cost-effective and prolongs survival by an additional 1.82 years at a low cost of $1,773 per/life-year saved.

Cardiac Output, Low↗
PubMed2001

Effects of dipyridamole on coronary collateralization and myocardial perfusion in patients with ischaemic cardiomyopathy.

AIMS: There is evidence that oral dipyridamole, a nucleoside uptake blocker that increases myocardial adenosine levels, lessens myocardial ischaemia by inducing coronary collateral growth in animal models of ischaemic heart disease. However, whether dipyridamole can exert a similar effect in humans with coronary artery disease is controversial. METHODS AND RESULTS: We studied 30 male patients (mean age 55+/-9 years) with coronary artery disease and left ventricular systolic dysfunction (ejection fraction >40%). Patients were randomized into three matched groups. Group A patients (n=10) received dipyridamole alone at a dose of 75 mg t.i.d. orally for 8 weeks. Group B patients (n=10) underwent exercise training at 60% of peak .VO(2)three times a week for 8 weeks, and received dipyridamole. Group C patients (n=10) had neither exercise testing nor dipyridamole. On study entry and after 8 weeks all patients underwent an exercise test with gas exchange analysis, dobutamine stress echocardiography, 201-thallium planar myocardial scintigraphy, and coronary angiography. Peak .VO(2)increased significantly only in trained patients. Thallium uptake of the collateral-dependent myocardium, coronary collateral score and wall thickening score increased significantly only in groups receiving dipyridamole, the greatest improvement being in group B patients. Plasma adenosine levels were also the highest in group B (P<0.001 vs A and C). Correlations were found between changes in adenosine levels and increases of both thallium uptake (r=-0.70;P=0.001) and collateralization (r=0.72;P=0.001). CONCLUSION: Exercise training potentiates the effects of dipyridamole on coronary collateralization and myocardial perfusion in humans with ischaemic cardiomyopathy.

Adenosine↗
PubMed2001

Effects of trimetazidine on the contractile response of chronically dysfunctional myocardium to low-dose dobutamine in ischaemic cardiomyopathy.

BACKGROUND: There is evidence that trimetazidine, an anti-ischaemic agent with a direct cytoprotective effect on the myocardium, is effective in stable angina. However, it is not clear whether trimetazidine can improve the mechanical efficiency of chronically dysfunctional myocardium, and whether this potentially beneficial effect can translate into improvements in left ventricular function as well as functional capacity. METHODS: Thirty-eight patients (52.7 +/- 8 years) with post-necrotic left ventricular dysfunction (ejection fraction: 33 +/- 5%) and multivessel coronary artery disease were studied. Patients were randomized into two matched groups. Group A received trimetazidine (20 mg three times daily) for 2 months, while group B received a placebo during the same period. The usual antianginal medications were not altered during the study. At baseline and after 2 months, all patients underwent low-dose dobutamine echocardiography (5-20 microg x kg(-1) x min(-1)), and a symptom-limited cardiopulmonary exercise test. RESULTS: On initial evaluation, systolic wall thickening score index, heart rate, systolic blood pressure and rate pressure product were similar at rest and peak dobutamine in both groups. However, at 2 months, group A patients had significant improvements in the rest and peak systolic wall thickening score index (13% and 20.7%, P<0.001) and ejection fraction (19.7% and 14.1%, P<0.001) without concomitant changes in heart rate and blood pressure. Peak VO2 was also significantly increased in patients taking trimetazidine (15%, P=0.001 vs controls). CONCLUSIONS: In patients with ischaemic cardiomyopathy, trimetazidine improves the contractile response of chronically dysfunctional myocardium to dobutamine without haemodynamic changes. This effect was associated with improvements in left ventricular function and peak VO2.

Analysis of Variance↗
PubMed2001

Oxidative stress and homocysteine in coronary artery disease.

BACKGROUND: Oxidative stress is present in cardiovascular diseases (CVDs), and hyperhomocysteinemia, an independent risk factor for these diseases, may play a role by inducing production of oxygen free radicals. METHODS: To evaluate the possible role of homocysteine (Hcy) in inducing oxidative stress in coronary artery disease (CAD), plasma Hcy was measured in 68 consecutive cardiovascular patients, and plasma malondialdehyde (MDA), both free and total (free + bound), was measured in 40 patients with CAD (18 with chronic stable angina and 22 with unstable angina). As controls, we tested 70 healthy volunteers. Hcy was measured by an immunoenzymatic method and MDA, an index of lipid peroxidation, by gas chromatography-mass spectrometry. RESULTS: Plasma Hcy concentrations were significantly higher in cardiovascular patients than in controls (10.2 vs 8.9 micromol/L; P <0.0002), with no significant difference between values in the stable and unstable angina subgroups. Similarly, total MDA was significantly higher in the CAD group than in the controls (2.6 vs 1.3 micromol/L; P <0.00001), again with no significant difference between stable and unstable angina patients. By contrast, free MDA, which was significantly higher in the CAD patients than the controls (0.4 vs 0.2 micromol/L; P < 0.00001), was also significantly higher in the unstable than in the stable angina group (0.5 vs 0.3 micromol/L; P <0.03). However, no correlation was observed among Hcy and free and total MDA. CONCLUSIONS: Our findings show that a moderate increase of Hcy is associated with CVD but that Hcy at the detected values cannot be considered completely responsible for oxidative damage. That lipid peroxidation is involved in CAD is shown by our observation of significantly increased plasma free and total MDA concentrations compared with controls. Moreover, free MDA values discriminated between unstable and chronic stable angina, and could thus represent a new diagnostic tool.

Angina Pectoris↗
PubMed2000

Trimetazidine and the contractile response of dysfunctional myocardium in ischaemic cardiomyopathy.

BACKGROUND: The therapeutic effect of anti-ischemic compounds is related to their ability to improve the oxygen supply-demand balance of the ischemic myocardium by increasing myocardial blood flow (calcium-antagonists), by reducing regional myocardial oxygen consumption (verapamil, betablockers) and increasing peripheral pooling of blood (nitrates, nifedipine). All these actions are also accompanied by hemodynamic changes, as evidenced by a lower double product, reduced wall stress, lower pulmonary wedge pressure, and lower systemic arterial pressure. In general, it was found that the combination of a betablocker with nifedipine improved the antianginal effect by further reducing the number and duration of ischemic events. The combination of a nitrate with a beta-blocker is particularly useful because it reduces the risk of heart failure by lowering left ventricular end-diastolic pressure and volume and by attenuating the negative inotropic effect of the betablocker. Although a combination therapy demonstrated benefits in comparison with drug treatment alone, it is associated with a higher incidence of untoward events. Trimetazidine (2, 3, 4 trimethoxybenzyl-piperazine dihydrochloride) is a novel anti-ischemic compound with a peculiar mechanism of action. Its anti-ischemic properties are unrelated to changes in myocardial oxygen supply-to-demand ratio, as shown by no significant effects on heart rate, blood pressure or rate-pressure product both at rest and during dynamic exercise. There are several possible mechanisms of action by which trimetazidine promotes preservation of membrane structures and cellular function: limitation of intracellular acidosis, correction of disturbances of transmembrane ion exchange leading to calcium overload, prevention of an excessive production of free radicals, inhibition of the inflammatory reaction and an antiplatelet effect. These documented actions cooperate to increase the rate of resynthesis of high-energy phosphates within myocardial cells after episodes of ischemia. In several trials, trimetazidine has been tested as an antianginal agent, both as monotherapy and combined with "classical" anti-ischemic compounds. In comparison with nifedipine, trimetazidine had similar efficacy in reducing the number of weekly anginal attacks and in increasing the ischemic threshold in a group of 39 patients with stable angina. However, the incidence of side effects was significantly higher with nifedipine (5 vs 20), and affected 5 patients with trimetazidine and 13 patients with nifedipine (p = 0.03). In a relatively large European study involving 149 patients (Trimetazidine European Multicenter Study, TEMS), trimetazidine (20 mg t.i.d.) was compared with propranolol (40 mg t.i.d.) in patients with stable angina pectoris and documented significant coronary artery stenoses. The number of anginal attacks was reduced equally by both drugs and exercise duration was increased by both treatments. However, in contrast with propranolol trimetazidine did not alter the rate pressure product. In patients already treated with nifedipine or beta-blockers, the addition of trimetazidine (20 mg t.i.d.) was able to reduce the number and the duration of anginal attacks and improved also the exercise capacity. Trimetazidine is generally well tolerated and only minor side effects have been reported (drowsiness, sedation, diarrhea). The improvement in cardiac energy metabolism should theoretically translate into enhancement in mechanical efficiency. This hypothesis has been object of recent investigations in patients with ischemic heart disease with and without left ventricular dysfunction. Brottier, et al. demonstrated that patients with ischemic cardiomyopathy treated with trimetazidine had a higher ejection fraction (measured by radionuclide angiography) than control patients who received a placebo after 6 months of therapy (p < 0.018). The group of Chierchia demonstrated that trimetazidine improved ischemic regional myocardial dysfunction at rest and during stress-induced ischemia in 15 patients with chronic coronary artery disease without affecting the hemodynamic determinants of myocardial oxygen consumption. There is recent demonstration that trimetazidine improves the contractile response of left ventricular hibernating myocardium in patients with ischemic heart disease. Belardinelli et al. showed that trimetazidine improved the contractile response of dysfunctional myocardial to low-dose dobutamine in patients with ischemic heart disease and left ventricular function. Twenty-two patients with prior anterior myocardial infarction and injection fraction < 35% (33 +/- 7%) were randomized into 2 groups. A group (= 11) received trimetazidine (20 mg tid) for 2 months, while another group (= 11) received a placebo. The usual medications were not altered during the study. (ABSTRACT TRUNCATED)

Humans↗
PubMed1999

Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome.

BACKGROUND: It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF). METHODS AND RESULTS: To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165). CONCLUSIONS: Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome.

Aged↗
PubMed1999

Quantitative analysis of changes occurring in muscle vastus lateralis in patients with heart failure after low-intensity training.

OBJECTIVE: To quantitate the changes occurring in muscle vastus lateralis after exercise training of low intensity adopted for the rehabilitation of patients with chronic heart failure. STUDY DESIGN: Nine consecutive males with a clinical diagnosis of idiopathic dilated and ischemic cardiomyopathy underwent an eight-week period of training. The intensity of the work was calculated as 40% of peak VO2. The program consisted of 30 minutes of cycling three times per week. A cardiopulmonary exercise test, hemodynamic measurements and echocardiographic studies were carried out. Needle biopsies were taken from muscle vastus lateralis before starting and after completing training. Quantitative analysis was carried out on sections stained with ATPase at pH 9.5 for measurement of the lesser diameter of type 1 and 2 fibers (by using an image analyzer) and on UEA 1-stained sections for capillary density and capillary/fiber ratio (by using a frame in the eyepiece of the microscope). The Wilcoxon test was applied to identify significant differences before and after training. Spearman's rank correlation coefficient was also calculated to highlight any correlation between the morphologic data and results of clinical tests. RESULTS: After completing the training program, all the patients experienced an improvement in exercise tolerance and a significant increase (P < .004) in the VO2 and VCO2 peak. Skeletal muscle showed a significant (P < .02) increase in the capillary/fiber ratio. The changes were not significantly correlated with any of the clinical findings. CONCLUSION: Low-intensity training can improve the functional capacity of patients with heart failure while producing only mild morphologic changes in their muscles.

Adult↗
PubMed1998

A four-minute submaximal constant work rate exercise test to assess cardiovascular functional class in chronic heart failure.

To develop a submaximal constant work rate exercise test able to grade cardiovascular dysfunction in patients with chronic heart failure, 80 patients and 59 control subjects performed a symptom-limited incremental exercise test and a constant work rate exercise test at a fixed work rate (50 W for 4 minutes). The time constant of VO2 at the start of constant work rate exercise and time for gas exchange ratio (respiratory exchange ratio) to equal 1 were independent predictors of cardiovascular functional class and correctly classified the functional class in 89 +/- 9% and 83 +/- 11% of patients, respectively.

Cardiac Output, Low↗
PubMed1998

Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy.

BACKGROUND: There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans. However, the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium, 46 patients (42 men, 4 women; mean age, 57+/-9 years) with chronic coronary artery disease and impaired LV systolic function (ejection fraction < 40%) were randomly assigned to two groups. The exercise group (n = 26) underwent exercise training at 60% of peak oxygen uptake for 8 weeks. The control group (n = 20) was not exercised. At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine (5 to 10 microg/kg per minute) followed by thallium myocardial scintigraphy. Coronary angiography was performed in 23 patients at baseline and after 8 weeks. After 8 weeks, peak oxygen uptake increased significantly only in trained patients (24%). Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients (28% and 31%, respectively; trained versus control: P<.001 for both). In a subgroup of trained patients, both improvements were correlated with an increase in the coronary collateral score (P<.005 and P<.001, respectively). CONCLUSIONS: Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy. The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy.

Adaptation, Physiological↗
PubMed1998

Low dose dobutamine echocardiography predicts improvement in functional capacity after exercise training in patients with ischemic cardiomyopathy: prognostic implication.

OBJECTIVES: This study sought to investigate whether the identification of hibernating myocardium by low dose dobutamine stress echocardiography (LDSE) may predict an improvement in functional capacity after moderate exercise training in patients with ischemic cardiomyopathy. Another objective was to assess whether exercise training may affect the outcome. BACKGROUND: There is evidence that exercise training improves left ventricular (LV) function as well as functional capacity in patients with a previous myocardial infarction and LV dysfunction. We hypothesized that the magnitude of these improvements might be related to the extent of hibernating myocardium. METHODS: We studied 71 consecutive patients 56+/-9 years old (mean +/- SD) with chronic heart failure secondary to ischemic cardiomyopathy (LV ejection fraction [LVEF] <40%). All patients were in sinus rhythm and were clinically stable during the previous 3 months. Patients were randomized into two matched groups. Group T (n = 36) underwent exercise training at 60% of peak oxygen uptake (Vo2) three times a week for 10 weeks. Group C (n = 35) did not exercise. At study entry and end, all patients underwent an exercise test with gas exchange analysis and LDSE (5 to 20 microg/kg body weight per min). RESULTS: At baseline, a positive contractile response (CS+) to LDSE was observed in 317 of 576 segments in group T and 291 of 560 segments in group C. After 10 weeks, peak Vo2 and peak work rate increased only in trained patients (peak Vo2: from 16.2+/-3 to 20.8+/-4 ml/kg per min; work capacity: from 108+/-20 to 131+/-25 W, p < 0.001 vs. group C for both). The presence of CS+ at baseline was associated with a sensitivity of 70% and a specificity of 77% for predicting an increase in the functional capacity after exercise training. Positive and negative predictive values of LDSE were 84% and 59%, respectively. Independent predictors of cardiac events were a pre-to-posttraining difference in LVEF at peak dobutamine infusion and the presence of a viable response at baseline (p = 0.004 and 0.008, respectively). The log-rank test demonstrated that trained patients had a significantly lower probability of cardiac events during follow-up than sedentary control patients (p < 0.001). CONCLUSIONS: The presence of hibernating myocardium as assessed by LDSE predicts the magnitude of improvement in functional capacity after moderate exercise training in patients with chronic heart failure. A significant increase in functional capacity after exercise training is associated with a lower incidence of cardiac events during follow-up.

Adult↗