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Biomedical subjects

Michael Shechter

Publications and source records attributed to Michael Shechter.

At least 19 recordsLinked to original sources

The association between right coronary artery morphology and endothelial function.

BACKGROUND: Two distinct right coronary artery (RCA) morphologies have been previously described: sigma- and C-shaped RCAs. While the C-shaped RCA was significantly associated with atherosclerosis, the sigma-shaped was not. The association of RCA morphology and vascular endothelial function has not yet been assessed. METHODS: To evaluate the association between the RCA's morphology and flow-mediated endothelium-dependent dilation (FMD) in patients without evidence of atherosclerotic lesions, we prospectively assessed FMD in 49 consecutive patients with non-specific chest pain, who were referred to our laboratory 30+/-10 days after corroboration of normal coronary arteries on coronary angiography. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin-mediated vasodilation (NTG) were assessed using high resolution (15 MHz) linear array ultrasound. The patients were divided into 2 groups according to their RCA morphology on coronary angiograms (sigma and C) which were analyzed by 2 independent readers who were blinded to the patients' FMD results. RESULTS: The C-shaped group exhibited a significantly lower FMD compared to the sigma-shaped group (9.0+/-4.2% vs. 14.3+/-4.7%, p<0.04, respectively), while NTG was the same in both groups. There were no significant group differences in other variables. CONCLUSIONS: Endothelium-dependent FMD in the brachial artery is significantly greater in sigma- compared to C-shaped RCA in coronary arteries without overt atherosclerotic lesions, suggesting a potential mechanism whereby C-shaped RCA are predisposed to atherosclerosis.

Aged↗

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

AIM: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET). METHODS: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET. RESULTS: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all). CONCLUSIONS: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Exercise Therapy↗

Short-term sibutramine therapy is associated with weight loss and improved endothelial function in obese patients with coronary artery disease.

In obese patients with coronary artery disease (CAD), the vascular endothelium is usually impaired, and the modification or reversal of endothelial dysfunction may significantly enhance treatment. Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment, but its impact on endothelial function in obese patients with CAD has not yet been investigated. Eighty consecutive obese, nonhypertensive, stable patients with CAD (65 men; mean age 65 +/- 11 years, mean body mass index 32 +/- 3 kg/m2) were randomly assigned to either sibutramine 10 mg/day (n = 40) or routine treatment (n = 40; controls) for 4 months. The percentage improvement in endothelium-dependent brachial artery flow-mediated dilation (%FMD) and endothelium-independent nitroglycerin-mediated vasodilation were assessed at baseline and after 4 months using high-resolution ultrasound. At baseline, all patients had %FMD of 5.4 +/- 3.1% and percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation of 9.2 +/- 2.9%, showing no significant differences. After 4 months, however, initial body weight was reduced by 11.4 +/- 1.2% in the sibutramine group compared with only 2.2 +/- 1.3% in controls (p <0.001), demonstrating a significant improvement in postintervention %FMD (8.9 +/- 2.4%, p = 0.01, compared with baseline) in the sibutramine group compared with controls (5.2 +/- 3.6%, p = 0.68, compared with baseline). No significant therapeutic effect on the percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation was seen in either group (9.2 +/- 2.5% vs 9.1 +/- 3.0%, respectively, p = 0.792). In addition, sibutramine therapy was associated with significant C-reactive protein reduction compared with routine treatment (44% vs 9%, p = 0.035). Thus, short-term therapy with sibutramine, together with diet and lifestyle intervention, is associated with improved endothelial function assessed by brachial artery %FMD in nonhypertensive, stable patients with CAD.

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Atrial fibrillation in dobutamine stress echocardiography.

OBJECTIVES: To describe the incidence of atrial fibrillation induced by dobutamine stress echocardiography and characterize patients at risk of developing atrial fibrillation, by constructing a simple validated risk score index. DESIGN: An observational study using prospectively collected data. METHODS: 3800 consecutive patients in sinus rhythm undergoing dobutamine stress echocardiography were randomly divided to a case (2/3) and test group (1/3). Associations of predetermined demographic, clinical, electrocardiographic and echocardiographic variables were calculated in patients with and without atrial fibrillation induced by dobutamine stress echocardiography in the case group. Logistic regression analysis determined significant independent risk predictors, a scoring index was constructed and validated on the test group. RESULTS: There was a 2% incidence of dobutamine stress echocardiography-induced atrial fibrillation in the study population. Risk predictors of atrial fibrillation included: a history of atrial fibrillation (2 points), increased left atrial diameter, right bundle branch block, decreased rest heart rate and hypertension (1 point each). The case subgroup low-risk patients (score 0-2) had a 1% risk, moderate-risk patients (score 3) a 2.7% and high-risk patients (score 4-6) a 14.5% risk of developing atrial fibrillation during dobutamine stress echocardiography. The rates in the test subgroup were 1%, 3.8% and 15.3%, respectively. CONCLUSION: Atrial fibrillation during dobutamine stress echocardiography is not common, the risk of developing atrial fibrillation during dobutamine stress echocardiography can be predicted by using a simple risk score system comprised of clinical, electrocardiographic and rest echocardiographic variables, which may be of help when planning a dobutamine stress echocardiography test in selected cases.

Aged↗

Statin efficacy and safety for lipid modification in apparently healthy male military aircrew.

INTRODUCTION: Military aircrew men represent an elite group of relatively young, fit, and healthy people. The effectiveness of statin treatment in reducing low-density lipoprotein cholesterol (LDL-C) according to the current National Cholesterol Education Program (NCEP) guidelines, its safety, and compliance in this group of people has not yet been determined. METHODS: We prospectively evaluated 84 military aircrew men (mean age 43 +/- 7 yr) with LDL-C above the current NCEP guidelines. The patients were divided into two groups according to their coronary risk factors: Group 1, LDL-C goal < 160 mg x dL(-1); Group 2, LDL-C goal < 130 mg dL(-1). All patients received statins in addition to therapeutic lifestyle changes and were followed for a mean of 3 +/- 1 yr according to a simple flow chart. Lipoprotein levels, liver function tests, creatinine phosphokinase, and subjective adverse reactions were checked periodically. RESULTS: LDL-C significantly declined by 32% (p < 0.0001) within the first month of treatment and 99% of subjects achieved their LDL-C goal within 114 +/-35 d from statin therapy initiation. The Framingham estimated 10-yr coronary risk showed a reduction at an average of 12 mo after statin therapy initiation from a baseline value of 6.54% to 3.95% (p = 0.003). No subjects were grounded or disqualified from duty, there were no cardiovascular events during follow-up, and compliance to therapy was high [82/84 (98%)]. DISCUSSION: Statin treatment in this highly select, relatively young group of aircrew men significantly and safely lowered LDL-C cholesterol levels.

Adult↗

Magnesium and myocardial infarction.

The data on magnesium supplementation in patients with acute myocardial infarction (AMI) is conflicting. Although a number of relatively small randomized clinical trials have demonstrated a remarkable reduction in mortality when administered to relatively high risk AMI patients, two recently published large-scale randomized clinical trials (the Fourth International Study of Infarct Survival and Magnesium in Coronaries) failed to show any superiority of intravenous magnesium over placebo. Nevertheless, the theoretical potential benefits of magnesium supplementation as a cardioprotective agent in coronary artery disease (CAD) patients, in conjunction with previous promising results from work in animal and humans, its relatively low cost, easy administration, with no need for special expertise, and relatively free of adverse effects, gives magnesium a place in treating CAD patients, especially high-risk groups such as CAD patients with heart failure, the elderly and hospitalized patients with hypomagnesemia.

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The intensive statin therapy myth.

Statins play an important role in the treatment and prevention of coronary artery disease and atherosclerosis. Currently, however, despite its important qualities, the use of statin therapy in the treatment of CAD patients ranges only between 30 and 60% in Europe, the United States and Israel. A wide gap still exists between the numerous scientific publications demonstrating the beneficial effects of statins and the low rate of implementing the guidelines in practice. A Medline search up to June 2005 on all prospective, double-blind, randomized clinical trials evaluating the impact of intensive statin therapy (any statin dose >40 mg/daily) on clinical outcomes after a 1 year follow-up revealed only eight trials. In all the eight trials, with a follow-up period of 12-60 months, intensive statin therapy was significantly more effective than and at least as safe as placebo or other standard statin regimens. Thus, based on the current evidence-based medicine, intensive statin therapy enables more patients with CAD to achieve the current National Cholesterol Education Program goal for low density lipoprotein, while ensuring a relatively high safety profile.

Cholesterol, LDL↗

Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.

BACKGROUND: Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. METHODS AND RESULTS: The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment-elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103+/-8% of baseline), ADP-induced aggregation was reduced to 69+/-3%, 58+/-7%, and 33+/-12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (P=0.007). CONCLUSIONS: Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.

Adenosine Diphosphate↗

Impact of short-term intermittent intravenous dobutamine therapy on endothelial function in patients with severe chronic heart failure.

BACKGROUND: Intermittent intravenous dobutamine therapy is used to treat patients with decompensated end-stage chronic heart failure (CHF), in whom the vascular endothelium is usually impaired. Although it has been suggested that modification or reversal of endothelial dysfunction may be of significant therapeutic benefit, the impact of short-term intermittent intravenous dobutamine therapy on flow-mediated dilation (FMD) in patients with severe decompensated end-stage chronic CHF has not been assessed. METHODS: We prospectively assessed the impact of intermittent intravenous low-dose dobutamine therapy on endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation using high resolution ultrasound scanning in 20 consecutive male patients with severe CHF and ischemic cardiomyopathy (New York Heart Association functional class IV), at baseline and after 4 months, and compared them to 20 age- and sex-matched control subjects. The cardiac index (CI), stroke index (SI), and systemic vascular resistance (SVR) were assessed non-invasively with a thoracic electrical bioimpedance device before and after intravenous dobutamine therapy. RESULTS: Intermittent intravenous dobutamine therapy resulted in significant improvement in post-intervention FMD compared with baseline (7.7% +/- 2.4% vs 1.1% +/- 2.6%; P = .001), a finding not evident in control subjects (1.3% +/- 2.6% vs 1.2% +/- 2.1%; P = .78). There was no significant effect of dobutamine treatment compared with control subjects on NTG-induced vasodilation (7.6% +/- 5.5% vs 7.5% +/- 8.8%, P = .979). Short-term dobutamine therapy also significantly improved SVR (1797 +/- 926 dyne sec/cm5 vs 2172 +/- 1133 dyne sec/cm5, P = .05), CI (2. 4+/- 0.6 L/min/m2 vs 1.9 +/- 0.6 L/min/m2, P = .01), and SI (33.5 +/- 11.7 mL/m(2) vs 27.2 +/- 12.4 mL/m2, P = .02). CONCLUSIONS: Short-term intermittent intravenous low-dose dobutamine therapy significantly improved vascular endothelial function, perhaps demonstrating an additional mechanism for improved SVR, CI, and SI in patients with severe CHF.

Adrenergic beta-Agonists↗

Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature.

AIMS: To determine laboratory and clinical benefit of oral acetylcysteine, as an adjunct to saline hydration, in chronic renal insufficiency patients undergoing coronary angiography. METHODS AND RESULTS: We prospectively studied 80 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration 2.0+/-0.39mg/dl), who underwent coronary angiography with or without intervention. Patients were randomly assigned to receive either acetylcysteine (600mg orally t.i.d.) or placebo, in addition to intravenous 0.45% saline (1ml/kg of body weight per hour), 12h prior to and after coronary angiography. There was an increase of >/=0.5mg/dl in the serum creatinine concentration 48h after coronary angiography in seven of the 80 patients (9%): in four of the 41 patients (10%) in the acetylcysteine group and in three of the 39 patients (8%) in the placebo group (P=0.52). The incidence of in-hospital adverse clinical events (acetylcysteine, 5% vs placebo, 8%, P=0.47) and the length of hospital stay [acetylcysteine, median (interquartile range) 4 (2-4) days vs placebo, 2 (2-4) days, P=0.44] did not differ significantly between the two treatment groups. CONCLUSION: Our findings do not support routine prophylactic administration of oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy in chronic renal insufficiency patients undergoing coronary angiography.

Acetylcysteine↗

The assessment of infarct size in postmyocardial infarction patients undergoing thallium-201 tomographic imaging is improved using attenuation correction.

PURPOSE: Attenuation correction (ATC) has been shown to improve the accuracy of thallium-201 single photon emission computed tomography (SPECT) for the detection and evaluation of patients with coronary artery disease. The purpose of this study was to evaluate the value of ATC for the assessment of infarct size in patients after myocardial infarction (MI). MATERIALS AND METHODS: Tl-201 SPECT with ATC was performed on 39 patients with 49 previous MIs. This was followed by radionuclide ventriculography for the assessment of global and regional left ventricular function. Uncorrected and corrected 24-hour redistribution SPECT images were analyzed for regional perfusion using a 5-point segmental scoring scale from 0 (normal) to 4 (absent) thallium uptake. RESULTS: The mean number of segments with scores of >1 and 2 was significantly higher without ATC than with ATC (5.3 +/- 3.6 vs. 3.5 +/- 3.6, P = 0.0001 for scores >1; 3.8 +/- 3.6 vs. 2.5 +/- 3.0, P = 0.0001 for scores of >2, respectively). The mean total number of segments with scores of >1 assessed without ATC was significantly higher compared with that assessed with ATC (16.9 +/- 13.5 vs. 11.2 +/- 12.2, P = 0.0001). Evaluation without ATC demonstrated only a fair correlation between the SPECT parameters (number of segments with scores of >1 and >2, and total score of segments with scores of >1) and left ventricular regional and global function, whereas there was a clear improvement in all the parameters after ATC. With ATC, a decrease in infarct size was demonstrated in 27 of the 49 infarcts (55%). CONCLUSIONS: The improved correlation with left ventricular function indicates that SPECT imaging with ATC provides a more accurate assessment of infarct size in post-MI patients. The use of nonattenuation-corrected SPECT imaging overestimates infarct size in a majority of patients.

Adult↗

External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris.

OBJECTIVES: The goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD). BACKGROUND: In patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described. METHODS: We prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 +/- 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound. RESULTS: External counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 +/- 2.1%, p = 0.01), compared with controls (3.1 +/- 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 +/- 2.8% vs. 10.2 +/- 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 +/- 2.7 nitrate tablets vs. 0.4 +/- 0.5 nitrate tablets, p <0.001 and 4.5 +/- 2.3 nitrate tablets vs. 4.4 +/- 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 +/- 0.5 vs. 1.9 +/- 0.3, p <0.0001 and 3.3 +/- 0.6 vs. 3.5 +/- 0.5, p = 0.89, respectively). CONCLUSIONS: External counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism.

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Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease.

Previous studies have demonstrated that magnesium supplementation improves endothelial function in patients with coronary artery disease (CAD). However, the impact on clinical outcomes, such as exercise-induced chest pain, exercise tolerance, and quality of life, has not been established. In a multicenter, multinational, prospective, randomized, double-blind and placebo-controlled trial, 187 patients with CAD (151 men, 36 women; mean +/- SD age 63 +/- 10 years, range 42 to 83) were randomized to receive either oral magnesium 15 mmol twice daily (Magnosolv-Granulat, total magnesium 365 mg provided as magnesium citrate) (n = 94) or placebo (n = 93) for 6 months. Symptom-limited exercise testing (Bruce protocol) and responses given on quality-of-life questionnaires were the outcomes measured. Magnesium therapy significantly increased intracellular magnesium levels ([Mg]i) in a substudy of 106 patients at 6 months compared with placebo (35.5 +/- 3.7 vs 32.6 +/- 2.9 mEq/L, p = 0.0151). Magnesium treatment significantly increased exercise duration time compared with placebo (8.7 +/- 2.1 vs 7.8 +/- 2.9 minutes, p = 0.0075), and lessened exercise-induced chest pain (8% vs 21%, p = 0.0237). Quality-of-life parameters significantly improved in the magnesium group. These findings suggest that oral magnesium supplementation in patients with CAD for 6 months results in a significant improvement in exercise tolerance, exercise-induced chest pain, and quality of life, suggesting a potential mechanism whereby magnesium could beneficially alter outcomes in patients with CAD.

Administration, Oral↗

Long-term outcome of intravenous magnesium therapy in thrombolysis-ineligible acute myocardial infarction patients.

The aim of our study was to analyze the long-term survival and cardiac function in 194 consecutive, thrombolysis-ineligible acute myocardial infarction (AMI) patients receiving 48-hour intravenous magnesium sulfate (22 g) - 96 patients, compared with placebo - 98 patients. After a mean 4.8-year follow-up, all-cause mortality and cardiac mortality were significantly lower in the magnesium compared to the placebo group [(18 vs. 33 patients, p < 0.01) and (12 vs. 30 patients, p < 0.001), respectively]. Rest radionuclide ventriculography tests for left-ventricular ejection fraction (LVEF) were assessed in surviving patients up to completion of follow-up. Magnesium-treated patients had a significantly higher LVEF (0.51 +/- 0.10 vs. 0.44 +/- 0.14, p < 0.05) and a lower incidence of heart failure compared to placebo-treated patients (12 vs. 3 patients, p = 0.02). Beneficial effects of intravenous magnesium therapy in thrombolysis-ineligible AMI patients appeared to last for at least 4.8 years, concomitant with preserved LVEF, suggesting a favorable role for acute magnesium treatment in these patients.

Aged↗

Does magnesium have a role in the treatment of patients with coronary artery disease?

Hypomagnesemia is common in hospitalized patients, especially in elderly patients with coronary artery disease (CAD) and/or those with chronic heart failure. Hypomagnesemia is associated with increased all cause mortality and mortality from CAD. Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves endothelial function and inhibits platelet function, including platelet aggregation and adhesion, which potentially confers upon magnesium physiologic and natural effects similar to adenosine-diphosphate inhibitors such as clopidogrel. However, data regarding the use of magnesium in patients with acute myocardial infarction (AMI) are conflicting. Although some previous relatively small randomized clinical trials demonstrated a remarkable reduction in mortality when intravenous magnesium was administered to relatively high risk AMI patients, two recently published large-scale randomized clinical trials (the Fourth International Study of Infarct Survival [ISIS 4] and Magnesium in Coronaries [MAGIC]) were unable to demonstrate any advantage of intravenous magnesium over placebo. Nevertheless, the theoretical benefits of magnesium supplementation as a cardio-protective agent in CAD patients, promising results from animal and human studies, its relatively low-cost and ease of handling requiring no special expertise, together with its excellent tolerability, gives magnesium a place in treating CAD patients, especially in those at high risk, such as CAD patients with heart failure, the elderly and hospitalized patients with hypomagnesemia. Furthermore, magnesium therapy is indicated in life-threatening ventricular arrhythmias such as torsades de pointes and intractable ventricular tachycardia.

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