Filippo Leonardo

Acute Anti-Ischemic Effect of Testosterone in Men With Coronary Artery Disease

BACKGROUND The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men. METHODS AND RESULTS After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05). CONCLUSIONS Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

Cyclical variation in paroxysmal supraventricular tachycardia in women

BACKGROUND Paroxysmal supraventricular tachycardia (SVT) in premenopausal women is often judged to be related to anxiety, and may be associated with the menstrual cycle. The aim of this study was to determine whether a cyclical variation of episodes of SVT exists and to correlate such variation with cyclical variation in plasma ovarian hormones. METHODS 26 women (mean age 36 [SD 8] years; with paroxysmal SVT were screened; those with regular menses who experienced at least three episodes of paroxysmal SVT in two consecutive 48-hour ambulatory ECG recordings were included. 13 patients (aged 32 [6] years) met these criteria. Patients underwent 48-hour ambulatory ECG monitoring and determination of plasma concentrations of oestradiol-17 beta and progesterone on day 7, 14, 21, and 28 of their menstrual cycle. FINDINGS An increase in the number and duration of episodes of paroxysmal SVT was observed on day 28 as compared to day 7 of the menstrual cycle. A significant positive correlation was found between plasma progesterone and number of episodes and duration of SVT (5.6 [2.2] ng/mL; r=0.83, p=0.0004; and r=0.82, p=0.0005), while a significant inverse correlation was found between plasma oestradiol-17 beta and number of episodes and duration of SVT (155 [22] pg/mL; r=0.89, p<0.0001; and r=0.81, p=0.0007). INTERPRETATION Women with paroxysmal SVT and normal menses exhibit a cyclical variation in the occurrence of the arrhythmia with their menstrual cycle. There is a close correlation between the episodes of paroxysmal SVT and the plasma concentrations of ovarian hormones. These data suggest that changes in plasma levels of ovarian hormones (and their interaction) may be of importance in determining episodes of arrhythmia in such patients. The mechanisms of these effects are unknown.

Direct coronary stenting without predilation

OBJECTIVES Coronary stenting is the primary therapeutic option for percutaneous treatment of many coronary lesions, after the risk of subacute stent thrombosis and bleeding complications has been reduced by improved antithrombotic regimens and high pressure stent expansion. BACKGROUND Direct stent implantation (without predilation) has been considered a promising new technique that may reduce the procedure time, radiation exposure time and cost. METHODS After having reviewed all cases of stent implantation from February to June 1998 (n = 585), 185 (32%) of these patients were retrospectively considered candidates for direct stent implantation without predilation, according to prespecified criteria (i.e., absence of severe coronary calcifications and/or tortuosity of the lesion or the segment proximal to the lesion). By operator preference, direct coronary stent implantation was actually attempted in 123 (21%) of the 585 patients (100 men, 60 +/- 10 years old) on 123 lesions. The impact of direct stenting in terms of cost, procedure time, radiation exposure time and amount of contrast dye used was assessed by comparing the two groups of patients who underwent single-vessel stenting without (n = 69) and with (n = 46) predilation. RESULTS Direct stenting was successful in 118 patients (96%). No acute or subacute complications occurred in these patients. Procedure time, radiation exposure time and cost were significantly lower in the group of patients who had single-vessel direct versus conventional stenting (45 +/- 31 vs. 64 +/- 46 min, 12 +/- 9 vs. 16 +/- 10 min and 1,305 +/- 363 vs. 2,210 +/- 803 Euro, respectively; p < 0.05 for all). CONCLUSIONS Direct stenting without predilation in selected lesions seems to be a safe and successful procedure that provides a way to contain cost and to shorten radiation exposure time.

Short-term Anti-Ischemic Effect of 17β-Estradiol in Postmenopausal Women With Coronary Artery Disease

BACKGROUND Short-term administration of 17beta-estradiol improves effort-induced myocardial ischemia in female patients with coronary artery disease. 17Beta-estradiol also has direct and indirect coronary vascular smooth muscle relaxing properties. The aim of the present study was to evaluate the effect of short-term administration of 17beta-estradiol on pacing-induced myocardial ischemia by means of continuous monitoring of coronary sinus pH in 16 postmenopausal female patients with coronary artery disease. METHODS AND RESULTS Patients underwent incremental atrial pacing starting at a rate of 100 bpm and increments of 20 bpm every 2 minutes up to 160 bpm before and 20 minutes after either 17beta-estradiol (1 mg sublingual, 9 patients) or placebo (sublingual, 7 patients). The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol (mean+/-SD, 254+/-36 versus 298+/-23 seconds; P<.02) but not by placebo (262+/-45 versus 256+/-34 seconds; P=NS) The pH shift was significantly reduced by 17beta-estradiol but not by placebo at every step of the pacing protocol. The maximum pH shift at peak pacing was significantly reduced by the administration of 17beta-estradiol by 0.022 pH units (95% CI, 0.001, 0.043; P<.04) but not by sublingual placebo (-0.002 pH units; 95% CI, -0.0073, 0.0021; P=NS). The maximum pH shift at maximum comparable pacing was also reduced by 17beta-estradiol by 0.015 pH units (95% CI, 0.012, 0.017; P<.001) but not by placebo (-0.0022 pH units; 95% CI, -0.006, 0.0015; P=NS). CONCLUSIONS 17Beta-estradiol reduces the degree of pacing-induced myocardial ischemia in postmenopausal patients with coronary artery disease. The reduction of pacing-induced coronary sinus pH shift is consistent with an anti-ischemic effect of the hormone and is not due to preconditioning, as evidenced by the absence of improvement after placebo.

Effect of atenolol on QT interval and dispersion in patients with syndrome X

Atenolol reduces QT dispersion and corrected QT interval in patients with syndrome X. This suggests that symptomatic improvement induced by atenolol in syndrome X patients may be partly related to reduction in abnormally augmented sympathetic tone.

Acute electrophysiologic effect of estradiol 17β in menopausal women

Sixteen postmenopausal women underwent electrophysiologic study before and 20 minutes after the administration of sublingual estradiol 17beta or placebo. Estradiol 17beta significantly affected electrophysiologic parameters, thereby suggesting its role in the development of palpitations in women.

Lipid profiles and endothelial function with low-dose hormone replacement therapy in postmenopausal women at risk for coronary artery disease: a randomized trial

AIMS To compare the effect of low (0.3 mg) and commonly prescribed (0.625 mg) doses of conjugated equine estrogens (CEE) on brachial artery flow-mediated dilation and lipid profiles. METHODS AND RESULTS Twenty-five postmenopausal women (mean age, 65+/-6 years) at risk for coronary artery disease (CAD) (> or =2 established risk factors) entered a double-blind crossover study. Brachial artery endothelial function was evaluated by means of high-resolution vascular echography. Both CEE doses significantly decreased total cholesterol (-13%, 0.3 mg; -15%, 0.625 mg), low-density lipoprotein-cholesterol (LDL-C) (-15%, 0.3 mg; -16%, 0.625 mg), and lipoprotein(a) (-28%, 0.3 mg; -39%, 0.625 mg) values from baseline levels. Both treatments increased high-density lipoprotein-cholesterol (HDL-C) (5%, 0.3 mg; 7%, 0.625 mg) and triglycerides (3%, 0.3 mg; 8%, 0.625 mg). There was no dose effect for changes in the LDL-C/HDL-C ratio (-21%, 0.3 mg; -23%, 0.625 mg). Both doses improved brachial artery dilation during reactive hyperemia by 63% over baseline. CONCLUSION In women at risk for CAD, low-dose hormone replacement treatment (HRT) improves lipid profiles and brachial artery endothelial function comparably to the most commonly prescribed dose. The benefit:risk ratio of low-dose HRT provides an attractive option for postmenopausal women at risk for CAD.

Effect of estradiol valerate alone or in association with cyproterone acetate upon vascular function of postmenopausal women at increased risk for cardiovascular disease

OBJECTIVES a large body of evidence has been accumulated suggesting that impairment of vascular endothelial function is an initial step in the development of atherosclerosis. Recent studies have shown that estrogen replacement therapy in postmenopausal women (PMW) improves endothelium-dependent, flow-mediated dilatation (FMD) while the cyclical adjunct of a progestin may reverse this effect. METHODS the purpose of this study was to evaluate endothelium-dependent, FMD in the brachial artery and the plasma levels of Endothelin-1 in menopausal females treated with estradiol valerate with and without cyclical cyproterone acetate in 20 PMW (mean age 64+/-6 years) with more than one risk factor for coronary artery disease. After a baseline evaluation, PMW entered a double-blinded, placebo controlled single cross-over study and were randomized to receive either estradiol valerate (2 mg) for 21 days or estradiol valerate (2 mg) for 11 days and estradiol valerate (2 mg) and cyproterone acetate (1 mg) for 10 days. Patients were crossed-over the complementary treatment 7 days after completing the first treatment phase. The study of forearm blood flow was repeated at the end of each treatment period. RESULTS estradiol valerate significantly increased FMD as compared with baseline (12+/-3 vs. 7+/-4%, P<0.01) the adjunct of cyproterone acetate did not affect the effect of estradiol valerate upon FMD (12+/-3 vs. 11+/-4%, P=NS). Similarly reactive hyperemic flow increased after estradiol valerate alone (24%) or in association with cyproterone acetate (24%) compared with baseline. Plasma levels of Endothelin-1 were significantly reduced by estradiol valerate alone or in association with cyproterone acetate. CONCLUSIONS in conclusion hormone replacement therapy with estradiol valerate and cyproterone acetate improves endothelial function and reduces plasma levels of Endothelin-1 in PMW at risk of coronary artery disease. These effects may be relevant for cardioprotection.

Effect of Acute Administration of Estradiol 17 Beta on Aortic Blood Flow in Menopausal Women

Acute administration of estradiol 17beta increases aortic blood flow velocity in menopausal women. This suggests that the effect of the ovarian hormone on cardiac dynamics is mainly dependent on a reduction in peripheral vascular resistances.

Subclavian artery stenting: Immediate and mid term clinical follow-up results

BACKGROUND: Intravascular stents are increasingly being used to treat subclavian artery obstructive disease. This study aimed to assess the immediate and midterm clinical outcome of subclavian artery stenting. METHODS AND RESULTS: Total occlusion of the subclavian artery was seen in 7 (28%) out of the 25 consecutive patients treated for subclavican artery stenosis. Mean lesion length was 14 - 4.3 mm. The mean preprocedure diameter stenosis was reduced from 83.2 - 14.9% to 9.6 - 5.4% postprocedure. success was achieved in all patients. Clinical follow-up was obtained in all patients. The initial success was maintained at follow-up (mean = 12 - 4 months) in 24 (96%) patients. Recurrence of symptoms occurred in 1 (4%) patient who had an angiographically documented restenosis four months after the procedure. It was successfully redilated. CONCLUSION: Stenting for subclavian artery obstructive disease is safe, technically feasible and has favorable clinical outcomes. It may be considered as the therapy of choice for subclavian artery Procedural obstructive disease. (Int J Cardiovasc Intervent 2000; 3: 231-235)