Effect of prolonged administration of transdermal estradiol on flow-mediated endothelium-dependent and endothelium-independent vasodilation in healthy postmenopausal women.

In 15 postmenopausal women with no cardiovascular risk factors, hormone replacement with transdermal estradiol (50 microg/day for 2 months) did not enhance flow-mediated endothelium-dependent vasodilation, reduce endothelium-independent vasodilation, and did not modify the pulsatility index and blood flow of the brachial artery. The present data do not support a positive effect of replacement with transdermal estradiol on vessel vasodilation in healthy, postmenopausal women.

Short atrioventricular delay reduces the degree of mitral regurgitation in patients with a sequential dual-chamber pacemaker.

This study was performed in a population of sequential dual-chamber pacemaker-patients with isolated mitral regurgitation (MR) to identify the "ideal atrioventricular (AV) delay" and to determine the effect of sequential pacing with the ideal AV delay on MR degree. Twenty consecutive patients (age 69 +/- 7 years; 45% men) hospitalized at our institution for symptomatic III degree AV block and isolated MR were studied. All received a dual-chamber pacemaker programmed in DDD at a rate of 70 pulses/minute. The ideal AV delay was selected using echo-color Doppler parameters; it was defined as that resulting in a lower degree of MR and in the highest cardiac output. The mean "optimal short" AV delay resulted in 98 +/- 7 ms. At short AV delay we observed a significant reduction in MR severity (regurgitant fraction from 48 +/- 12% to 25 +/- 10% and jet area from 15 +/- 2 to 9 +/- 2 cm2; p <0.0001) together with an increase in stroke volume (68 +/- 16 vs 88 +/- 15 ml; p = 0.007) and mitral early-to-late peak velocity ratio (0.79 +/- 0.33 vs 1.38 +/- 0.37; p <0.0001). In conclusion, a short AV delay may be used to improve cardiac output in sequential paced patients with pure, isolated MR.

Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women.

We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of the cardiovascular risk profile in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 200 postmenopausal women with mild to moderate hypertension. Patients received 17beta-estradiol (50 microg/day, transdermal) and norethisterone acetate (2.5 mg/ day, orally) or placebo. At baseline serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and fibrinogen plasma levels were measured and all subjects underwent complete M-mode and 2-D echocardiograms, which were repeated after 6, 12, and 18 months of hormonal replacement therapy. Compared with placebo, all values decreased significantly except for HDL cholesterol. In both groups, no modifications were observed in echocardiographic parameters, except for left ventricular mean diastolic and systolic wall thickness and left ventricular mass index, which showed a significant decrease in both groups. The reduction was greater in the treated group; the percentage of patients with left ventricular hypertrophy was 46% before randomization and 17.2% after 18 months of treatment (P < .0001), whereas in group II the percentage was 48% at baseline and 31.5% after 18 months (P < .05). In conclusion, transdermal 17beta-estradiol, associated with antihypertensive therapy, may contribute to the reduction of cardiovascular risk profile in hypertensive postmenopausal women.

Relationship between atrial function, left ventricular isovolumic relation time, and early filling in dual chamber-paced patients.

This investigation was performed to study atrial systolic function is response to modification of atrioventricular delay in a sample of 36 patients with a DDD pacemaker implanted for complete atrioventricular block. The relation between atrial systolic performance and diastolic-related parameters was also evaluated. Isovolumic relaxation time, early diastolic peak velocity, late (atrial) diastolic peak velocity, atrial filing fraction, and atrial ejection force were recorded at a pacing rate of 70 impulses/min and at atrioventricular delay of 200, 150, and 100 msec. Our data showed that the progressive shortening of atrioventricular delay induced a gradual increase in early peak velocity (median value 46 to 53 to 61.5 cm/sec, respectively, at 200, 150, and 100 msec intervals) and a gradual decrease in isovolumic relaxation time (median 92.6 to 81.5 to 69.7 msec at 200, 150, and 100 msec, respectively), atrial peak velocity (59 to 52 to 44.5 cm/sec at 200, 150, and 100 msec, respectively), atrial filling fraction (50.5% to 40% to 23.5% at 200, 150, and 100 msec, respectively), and atrial ejection force (17.2 to 14.7 to 8.5 kilodynes at 200, 150, and 100 msec, respectively). For every atrioventricular delay value detected, we found a significant correlation between isovolumic relaxation time and early peak velocity with atrial filling fraction and atrial ejection force. In addition, atrial ejection force was related directly to atrial filling fraction at studied atrioventricular delays. The two indexes of atrial systolic performance showed a parallel decrease by shortening the atrioventricular delay, and they can quantify atrial systolic performance equally in sequentially paced patients. Furthermore, our results are in accordance with the hypothesis that the interaction between the effectiveness of active left atrial emptying and isovolumetric relaxation time may play an important role in maintaining an ideal ventricular filling despite changes in atrial systolic function.

Early predictors of late dilation and remodeling after thrombolized anterior transmural myocardial infarction.

BACKGROUND AND HYPOTHESIS: Dilation of the left ventricle after myocardial infarction is associated with an adverse prognosis. There are no clinical studies on the role viable myocardium in the infarcted area assumes in relation to the development of late ventricular remodeling. The hypothesis of this study was to define the relation between remodeling and the presence of viable but akinetic myocardium in the infarct area and to identify early predictors of left ventricular (LV) dilation at 1 year. METHODS: In all, 92 consecutive patients with myocardial infarction were divided into two groups according to their ventricular volumes. Group I included 57 patients with normal volumes at discharge (9 +/- 3 days after acute infarction) and after 12 months or with LV dilation at discharge who had a normalization of their volumes over a 12-month period. Group II included 35 patients who, independent of their initial volumes, developed LV dilation during follow-up. Low-dose dobutamine infusion was utilized at discharge for echocardiographic evaluation of contractile recovery of viable myocardial segments. RESULTS: At the first control, patients in Group I presented an end-diastolic volume index (EDVI) of 100 +/- 7 ml/m2 which decreased to 68.8 +/- 6.5 ml/m2 12 months later (p < 0.0001), and an end-systolic volume index (ESVI) of 47.6 +/- 6.7 ml/m2 at the first control and 30.5 +/- 8.8 ml/m2 after 12 months (p < 0.001). Patients in Group II presented a mean EDVI of 116.2 +/- 8.1 ml/m2 at the first control and 138.8 +/- 8 ml/m2 12 months later (p < 0.001), and a mean ESVI of 68.8 +/- 6.5 ml/m2 at the first control and 79.5 +/- 5.4 after 12 months (p < 0.01). Ventricular mass index (VMI) in Group I increased from 106.4 +/- 11 to 122.3 +/- 15 g/m2 (p < 0.01), while in Group II it decreased from 101.1 +/- 10 to 98.7 +/- 8 g/m2 (p = NS). In Group I, mass-to-volume ratio was 1.15 +/- 0.1 g/ml at the first control and 1.67 +/- 0.1 g/ml 12 months later (p < 0.001), while in Group II it declined from 0.88 +/- 0.1 to 0.69 +/- 0.1 g/ml (p < 0.01). The multivariate analysis revealed that ejection fraction < or = 40%, restrictive filling pattern, wall motion score index > 2.5 in response to dobutamine infusion, and mass-to-volume ratio < or = 1 g/ml, all at discharge, as well as an occluded left anterior descending artery discriminate in favor of late LV dilation and remodeling. CONCLUSIONS: Correct use of noninvasive strategies should result in early identification of postinfarct patients who are at risk of developing LV remodeling.

Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study.

HYPOTHESIS: This study was undertaken to determine whether echo-derived left atrial dimension and other echocardiographic, clinical, and hemodynamic parameters detected at the time of entry into the study may influence prognosis in patients with dilated cardiomyopathy during a long-term follow-up. METHODS: This was a prospective cohort analysis of 123 patients with dilated cardiomyopathy. Clinical evaluation, chest x-ray, M-mode and two-dimensional echocardiogram, exercise test, 72-h ambulatory electrocardiogram monitoring, and cardiac catheterization study were performed in all patients. The study was divided into two phases: in the first phase, patients were divided into two groups according to the left atrial size (> or = 45 mm; < 45 mm), with cardiac death as the end point. In the second phase, all patients were further divided into two groups according to their clinical course. A multivariate analysis was performed to determine independent correlated parameters of cardiac mortality and overall clinical outcome. RESULTS: Cardiac mortality rate was 47.9%: 29% in the group without left atrial dilation and 54.3% in the group with dilated left atrium. Multivariate analysis revealed that left atrium > or = 45 mm, New York Heart Association functional classes III/IV, and the presence of one or more episodes of ventricular tachycardia at Holter monitoring were independent predictors of cardiac mortality, while left atrium > or = 45 mm, left ventricular end-diastolic pressure > 17 mmHg, and exercise tolerance < or = 15 min were independent predictors of poor clinical outcome. CONCLUSIONS: Our results revealed that left atrial size is the principal independent predictor of prognosis in patients with dilated cardiomyopathy in that patients with left atrial dilation had an increase in mortality and a worse clinical outcome compared with those without left atrial dilation.

Short-term results of transdermal estrogen replacement therapy in cardiovascular disease-free postmenopausal females with and without hypertension.

BACKGROUND: Many studies have shown that estrogen replacement with oral micronized 17 beta-estradiol reduces the risk of cardiovascular disease. The aim of the present study was to evaluate the efficacy of transdermal estrogen replacement therapy in improving the risk profile of cardiovascular disease in postmenopausal women. METHODS: Two hundred and fifty postmenopausal women were enrolled from the "Bene Essere Donna" Center and grouped according to the absence (Group I, n = 175; mean age 54.6 +/- 3.5) or presence of mild to moderate hypertension (Group II, n = 75; mean age 54.1 +/- 4.5). Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose and fibrinogen levels were tested in all women. The total study population was treated with estrogen replacement therapy for 12 months: hysterectomized women received 17 beta-estradiol (0.05 mg/die), while non-hysterectomized women received 17 beta-estradiol 0.05 mg/die plus 5 mg/die of medroxyprogesterone acetate for 12 days during every 28-day cycle. After 12 months, blood pressure and blood chemistry were measured as baseline. RESULTS: Total cholesterol, LDL cholesterol and glucose levels decreased in both groups. HDL cholesterol levels increased significantly only in the sub-group of Group II treated with estrogen plus progesterone. Triglycerides glucose and fibrinogen blood levels decreased in both groups. No cardiovascular events were recorded during the first year of follow-up. CONCLUSION: Transdermal estrogen replacement therapy should be considered as a therapeutic support in order to contrast the elevated cardiovascular risk in postmenopausal women.

Effects of transdermal 17beta-estradiol on left ventricular anatomy and performance in hypertensive women.

To reduce cardiovascular complications, antihypertensive therapy should not only normalize blood pressure but also induce a regression of structural abnormalities, which are the expression of end-organ damage. We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of left ventricular anatomy and systolic performance in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 169 postmenopausal women with mild or moderate hypertension. Eighty-six patients (group 1) received transdermal 17beta-estradiol (50 microg/d) and norethisterone acetate (2.5 mg/d, orally), and 83 patients (group 2) received placebo. At baseline, all women underwent M-mode and 2-D echocardiogram, which was repeated after 6, 12, and 18 months of follow-up. After 18 months of treatment, we observed a significant decrease in left ventricular diastolic septal and posterior wall thickness and mass in both groups. Furthermore, after 18 months, left ventricular mass was significantly less than in the estrogen-treated group. No significant modifications were observed in left ventricular systolic and diastolic dimensions or in systolic performance, as expressed by left ventricular fractional shortening. In conclusion, transdermal 17beta-estradiol, which is associated with antihypertensive therapy, may contribute in the reduction of left ventricular mass in hypertensive postmenopausal women.

[Cine magnetic resonance with dobutamine following a myocardial infarct]. / Cine Risonanza Magnetica con dobutamina dopo infarto del miocardio.

PURPOSE: Dobutamine cine MRI is a new diagnostic imaging technique in the pretreatment (revascularization) assessment of myocardial infarction patients. We report the results of a comparative study of the diagnostic yield of dobutamine cine MRI with that of stress echocardiography in the assessment of viable myocardium. We also propose a new method for analysis of cine MR images, employing digital subtraction, aimed at decreasing subjectivity in the quantitative assessment of myocardial wall thickening. MATERIAL AND METHODS: Twenty-six patients (21 men and 5 women) with a history of myocardial infarction who were scheduled for revascularization were submitted to stress echocardiography and dobutamine cine MRI to evaluate contractile recovery of the segments considered akinetic or hypokinetic at baseline echocardiography. Dobutamine was administered in growing doses (5, 10, 15 gamma/kg/min). We considered 16 segments of the left ventricle in each patient. We performed a quantitative analysis of systolic wall thickening on individual cine MR frames both by manual measurements and by digital subtraction. RESULTS: In the 416 segments studied, we found 307 normokinetic, 64 scarred and 45 viable segments with stress echocardiography, versus 302 normokinetic, 83 scarred and 31 viable segments with dobutamine MRI. Wall thickening analysis on Cine MR images showed 268 normal, 68 scarred and 80 viable segments, versus 274 normal, 58 scarred and 84 viable segments with digital subtraction. Three months after revascularization 15 patients were examined to check contractile recovery of the segments considered as viable. Echocardiography had 79% sensitivity and 97% specificity, while cine MRI had 96% and 86%, respectively. Quantitative assessment of systolic wall thickening by cine MRI and digital subtraction had 96% sensitivity and 91% specificity, with no statistically significant differences between the two techniques. In patients with anteroseptal wall myocardial infarction stress echocardiography had 75% sensitivity and 97% specificity. In the subgroup of 13 patients with diaphragmatic or inferior wall infarction echocardiography sensitivity dropped to 68%, versus 96% of cine MRI, but its specificity was higher, namely 97 versus 86%. CONCLUSIONS: In anteroseptal infarction, echocardiography permits to distinguish viable myocardium and scarred myocardial tissue with good sensitivity and specificity, but cine MRI performs better. In inferolateral or diaphragmatic infarction, cine MRI has much higher sensitivity than stress echocardiography and thus makes the technique of choice to evaluate viable myocardium in these sites. The digital subtraction technique is as accurate as manual measurements, but reduces the error rate and permits quicker evaluation, particularly in subendocardial thickening.

[Changes in serum levels of N-terminal procollagen type III propeptide as an index of postinfarction ventricular remodeling]. / Le modificazioni del livello sierico del propeptide N-terminale del procollageno di tipo III quale indice di rimodellamento ventricolare postinfartuale.

The levels of aminoterminal propeptide of type III procollagen (PIIINP) can be used as an index of collagen breakdown. The aim of our study was to evaluate modifications in serum concentration of PIIINP (PIIINPs) in patients with a first episode of myocardial infarction. We examined 70 patients admitted at our Institution for acute myocardial infarction and 10 normal subjects. PIIINPs dosage was obtained by radioimmunoassay method utilizing a commercial available kit. All patients underwent three PIIINPs dosages: within 24 hours after admission, at 6 and 12 months after myocardial infarction. Control values were 0.4 +/- 0.1 U/ml. In 38 patients (Group I) PIIINPs levels increased at 6 and 12 months after infarction: 0.53 +/- 0.2, 0.75 +/- 0.2 and finally 0.76 +/- 0.1 U/ml. In the remaining 32 patients (Group II) PIIINPs values increased at 6 months and then returned to baseline at 12 months: 0.56 +/- 0.2, 0.75 +/- 0.1 and then 0.46 +/- 0.1 U/ml. The end-diastolic volume index did not change significantly in Group I (from 93.7 +/- 21 to 79.7 +/- 20 ml/m2) while it decreased after 12 months in Group II (from 88.9 +/- 13 to 58.6 +/- 11 ml/m2; confidence interval 95% from 2 to 55 ml/m2; p = 0.03). Similarly, there was no significant variation in end-systolic volume index (ESVI, from 39.7 +/- 11 to 36.9 +/- 11 ml/m2) and ejection fraction (from 60 +/- 10 to 59 +/- 15%) in Group I; while in Group II ESVI decreased significantly (from 33.6 +/- 13 to 20 +/- 5 ml/m2, confidence interval 95% from 3 to 24 ml/m2; p = 0.02) and ejection fraction improved (from 62 +/- 11 to 72 +/- 15%; confidence interval 95% from -20 to -1%; p = 0.04). In conclusion, patients with elevated levels of PIIINPs at 12 months did not improve ventricular function while patients with PIIINPs returning to baseline at 12 months had an improvement. Our results suggest an active participation of newly formed collagen in post-infarct ventricular remodeling. Therefore PIIINPs may be a marker of this process.

Modification in serum concentrations of aminoterminal propeptide of type III procollagen in patients with previous transmural myocardial infarction.

The aim of our study was to evaluate the modification of serum concentration of aminoterminal propeptide of type III procollagen (PIIINP) in 70 patients with previous transmural myocardial infarction. In 38 patients (group 1 ) PIIINP levels increased at 6 and 12 months after infarction; in 32 patients (group 2) PIIINP increased at 6 months, returning to baseline at 12 months. At the same time we observed a significant left ventricular enlargement and worsening of the performance in group 1, whereas in group 2 an improvement was seen in left ventricular volumes and performance. In conclusion, rearrangement of collagen myocardial matrix plays an important role in left ventricular postinfarction modification. This process can be easily followed over time in a noninvasive manner by dosing serum PIIINP concentrations.

Clinical and electrophysiological characteristics in patients with atrioventricular reentrant and atrioventricular nodal reentrant tachycardia.

AIM: To compare clinical, electrophysiological characteristics and transcatheter ablation results between two groups of patients, one with atrioventricular reentrant tachycardia (AVRT) and the other with atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: The study population consisted of 94 consecutive patients who underwent endocavitary electrophysiological study and radiofrequency (RF) ablation: 46 patients had AVRT due to an accessory pathway with only retrograde conduction while 48 patients had AVNRT. RESULTS: In relation to general and clinical characteristics, differences between the two groups emerged regarding the age of symptom onset (25+/-16 vs 37+/-17 years, p=0.001), the prevalence of heart disease (8 vs 31%, p=0.001) and the correct diagnosis on surface ECG (50 vs 79%, p=0.001). Clinical presentation was quite similar apart from a higher prevalence of fatigue and sweating in the AVNRT group. Transcatheter RF ablation therapy results were similar. CONCLUSIONS: Patients with AVRT have a lower mean age at arrhythmia symptom onset compared with those with AVNRT and have fewer associated cardiac abnormalities. Clinical presentation is quite similar as well as their outcome after ablation. A correct diagnosis by standard ECG is more frequent in AVNRT.