Impact of excess weight and estrogen receptor gene polymorphisms on clinical course of homozygous beta thalassemia.

In homozygous beta thalassemic patients we examined the role played by the interaction of ER gene polymorphisms with adverse environmental factors. A total of 108 homozygous beta thalassemic patients, 60 prepubertal mean age 9,5 +/- 3,7 years (27 M, 33 F) and 48 pubertal mean age 22,2 +/- 5,4 years (21 M, 27 F), regularly treated with red cell transfusion and iron chelation therapy were segregated on the basis of their XbaI and PvuII ER gene polymorphisms. Body mass index (BMI), lipidic pattern and blood pressure values were evaluated in each group. No significant differences were observed between patients segregated by their PvuII ER genotypes. Prepubertal and pubertal patients of both sexes lacking XbaI site showed BMI, HDL, LDL cholesterol significantly different than the other patients. In addition, triglyceride levels and blood pressure values were significantly higher in pubertal patients of both sexes lacking XbaI site than in other patients. ER XbaI polymorphism appear to influence nutritional factors, metabolic status and blood pressure and could be considered additional risk factors for later cardiac involvement in beta thalassemic patients.

Streptococcus bovis endocarditis and its association with chronic liver disease: an underestimated risk factor.

Clinical and epidemiological characteristics of Streptococcus bovis endocarditis were prospectively studied among 199 patients with definite endocarditis. Thirty patients (15.1%) had S. bovis endocarditis. Compared with patients with non-S. bovis endocarditis, these 30 patients were older (mean age, 58.6+/-12.4 years vs. 46.0+/-17.0 years; P<.001) and had higher rates of bivalvular involvement (43.3% vs. 7.7%; P<.001), embolism (73.3% vs. 40.2%; P=.002), and diskitis (23.3% vs. 0.6% P<.001). In patients with S. bovis biotype I (S. bovis I) endocarditis, advanced liver disease was present in 56.7%, compared with 15.3% of patients with non-S. bovis endocarditis (P<.001), and colonic adenoma was present in 46.7%. The in-hospital mortality rate (16.7%) was correlated with delayed diagnosis and advanced liver diseases. In our city, S. bovis I endocarditis is frequently correlated with liver diseases; diskitis may be the first sign of the disease.

Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood.

BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.

Educational level and hypertension: how socioeconomic differences condition health care.

This is the first European study that has evaluated educational level in a large sample of hypertensive outpatients. We established the educational level of the hypertensive outpatients in our unit, and determined whether the awareness of hypertension and its organ damage was education-related. We analysed data from 812 consecutive outpatients (378 men, mean age 50 +/- 10 years) with essential stage I-II hypertension. Subjects were subdivided into two categories: group A subjects were highly educated; group B subjects had a little education. Data were compared with educational level from the 1991 population census for the Campania region (ISTAT data) and with 200 type 2 diabetes patients (96 men, mean age 51 +/- 9 years) from the nearest diabetes unit. For each hypertensive patient we considered clinical, echocardiographic and biochemical parameters. Data from the last census showed a high percentage (80%) of subjects with low education. The percentage of type 2 diabetic patients with little education was high (190 patients, 95%). Conversely, it is somewhat surprising that most hypertensive patients reached high standards of education and worked at sedentary jobs (group A: 736 patients, 91%; P < 0.0001). Multivariate analysis showed that only diastolic blood pressure (P = 0.03) was independently associated with low educational level. Compared to diabetes, hypertension and its risk factors are relatively unknown to people with little education. Education is associated with greater health care and awareness that may overcome the risk related to low physical activity. Thus, we stress the importance of a sound health policy able to reach out to the uneducated and make them aware of hypertension and the health care services available to them.

Recent advances in the prevention of anthracycline cardiotoxicity in childhood.

The prevention of anthracycline cardiotoxicity is particularly important in children who can be expected to survive for decades after cancer chemotherapy with these agents. The rapid increase in clinical toxicity at doses greater than 550 mg/m(2) of doxorubicin (DOX) has made this dose the limiting one in order to avoid DOX-induced cardiac failure. However, arbitrary dose limitation is inadequate because of variability of individual tolerance. Decreasing myocardial concentrations of anthracyclines (ANT) and their metabolites and schedule modification of administration can reduce anthracycline cardiotoxicity. Anthracycline structural analogues such as epirubicin, idarubicin and mitoxantrone have been used in clinical practice. In addition, the liposomal ANT, which can be incorporated into a variety of liposomal preparations, are a new class of agents that may permit more specific organ targeting of ANT, thereby producing less cardiac toxicity. Much interest has focused on the administration of ANT in conjunction with another agent that will selectively attenuate the cardiotoxicity. As is known, the ANT chelate iron and the DOX-iron complex catalyzes the formation of extremely reactive hydroxyl radicals. Many agents, such as dexrazoxane (DEX), able to remove iron from DOX, have been investigated as anthracycline cardioprotectors. Clinical trials of DEX have been conducted in children and significant short-term cardioprotection with no evidence of interference with antitumor activity has been demonstrated. Whether long-term cardiac toxicity will also be avoided in surviving patients has not yet been determined.

Left atrial size in 164 hypertensive patients: an echocardiographic and ambulatory blood pressure study.

BACKGROUND: Left atrial enlargement (LAE) is associated with an increased risk of death and cardiovascular (CV) hospitalization. Whether or not LAE reflects early structural change from hypertension is unclear. HYPOTHESIS: The aim of this study was to evaluate the relationship between LA size, 24-h blood pressure measurements, age, body mass index (BMI), and left ventricular mass index (LVMI) in hypertensive patients. METHODS: We studied 164 outpatients (age range 30-76 years, 73 men and 91 women) with mild to moderate hypertension. Physical examination, electrocardiogram, noninvasive blood pressure monitoring (ABPM), Doppler echocardiogram were performed. Left ventricular mass index and LA dimensions were calculated. The sample was divided by age (< 60 and > or = 60 years). RESULTS: Left ventricular hypertrophy (LVH) was present in 45% of patients aged < 60 years and in 70% of patients aged > or = 60 years (p = 0.002). Left atrial enlargement (> 4 cm) was present in 35% of elderly and in 24% of young patients (p = 0.31), and in 36% of patients with and 21% of patients without LVH (p = 0.0057). There was no significant difference in the younger patients with and without LVH. The incidence of obesity was low (31%) in the whole sample. The percentage of overweight in the elderly patients with LVH and higher LA size was equally low. Multivariate analysis showed age (p = 0.044) and LVMI (p = 0.002) as the only significant predictors of LA enlargement. CONCLUSION: Since LAE is associated with a high risk of death and CV hospitalization, we emphasize the importance of development and use of drugs that inhibit LVH.

Association of left ventricular hypertrophy and aortic dilation in patients with acute thoracic aortic dissection.

This study was designed to evaluate the impact of left ventricular mass on aortic diameters in patients who presented with acute thoracic aortic dissection where aortic dilation is common. Retrospective review of transthoracic and transesophageal echocardiograms was conducted for 63 patients treated for acute thoracic aortic dissection and for 16 normal subjects who were comparable for gender prevalence, age, heart rate, and blood pressure. The diameter of the aortic root was measured by transthoracic echocardiography. Diameters of the ascending aorta, and of the aorta at locations of 25, 30, and 35 cm from the dental arch were measured by transesophageal echocardiography. The findings indicated that all aortic diameters were significantly larger in patients with aortic dissection. Patients with aortic dissection also presented with greater left ventricular mass indices (p<0.00001) than normal subjects. Fractional shortening and left atrial diameter measurements obtained in patients with aortic dissection were similar to those obtained in the control group. Overall, the left ventricular mass index exhibited univariate relationships with aortic root diameter (r=0.27, p<0.02) and aortic diameters at 25 cm (r=0.51, p<0.00001), 30 cm (r=0.58, p<0.00001), and 35 cm (r=0.55, p<0.00001) distal to the arch but not with the diameter of the ascending aorta. After adjusting for gender, body mass index, history of hypertension and aortic dissection extent (Stanford types) by separate multivariate models, the authors found that the left ventricular mass index was independently associated with aortic diameters at 25 cm (beta=0.32, p<0.001), 30 cm (beta=0.38, p<0.0001), and 35 cm (beta=0.34, p < 0.0005) distal to the arch. They conclude that left ventricular mass is independently associated with aortic arch and descending aorta diameters in patients with acute thoracic aortic dissection. Left ventricular hypertrophy may be considered a risk factor for aortic enlargement and subsequent dissection.

Aortic dissection with fistula to right atrium after heart transplantation: diagnosis by transthoracic and transesophageal echocardiography.

Aortic dissection with rupture into the right atrium is an extremely rare and rapidly fatal condition that may occur after cardiac surgery. We report the case of a 59-year-old woman with a 6-year history of heart transplantation who presented with subacute illness characterized by chest pain and severe cardiac decompensation accompanied by a continuous murmur in the precordium. The diagnosis of aortic dissection complicated by right atrial fistula was made by the combination of transthoracic and transesophageal echocardiographic examination.

Aortic dissection with fistula to left atrium: diagnosis by transesophageal echocardiography with successful repair.

The aorta-atria fistula is an infrequent complication of aortic dissection, and it is rarely diagnosed before death. A 41-year-old man who 8 years previously had undergone prosthetic aortic valve replacement had an aortic dissection complicated by aorta-left atrial fistula. This patient had acute left heart failure associated with a systolic and diastolic murmur at the lower left sternal border suggesting an aortic prosthetic malfunction. The cardiac diagnosis was made with transesophageal echocardiography and Doppler color flow imaging; it was notable that the cardiac lesions were not detected by transthoracic echocardiography. On the basis of the echocardiographic findings, the patient underwent successful emergency replacement of the dissecting ascending aorta with closure of the aorta-left atrial fistula. Transesophageal echocardiography is the procedure of choice for defining this abnormality. In this case a prompt surgical repair consisting of replacement of the affected segment of the aorta with the prosthesis and closure of the fistula provided optimum resolution of the clinical situation.

Cardiac toxicity after anthracycline chemotherapy in childhood.

The clinical use of anthracyclines, a family of chemotherapeutic agents with efficacy against many solid tumors and leukemias is limited by unique cumulative dose-limiting cardiotoxicity. Overt heart failure occurs in 4.5% to 7% of patients treated with anthracyclines and the incidence of cardiac function abnormalities increases with the time. Anthracycline-induced congestive heart failure is usually due to permanent changes in the myocardium, changes most consistent with the contractile failure of cardiomyopathy. Although the causes of anthracycline-induced cardiotoxicity are probably many, a large body of evidence points to free-radical-mediated myocyte damage. The risk of developing cardiac heart failure is modified by the presence of certain risk factors that reduce cardiac tolerance to anthracyclines. Age and female gender seem to have an important role in the anthracycline cardiotoxicity. This cardiotoxicity can be divided, on the base of when it started, into acute, subacute and progressive late, chronic form. Various invasive and non-invasive methods have been used to measure the extent of cardiac damage done. Depending on the sensitivity of the method employed, the proportion of hearts found to be damaged has varied widely. Attempts to ameliorate anthracycline cardiotoxicity have been directed toward: 1. decreasing myocardial concentrations of anthracyclines and their metabolites, 2. developing less cardiotoxic analogous, and 3. concurrently administering cardioprotectants to attenuate the effects of anthracyclines on the heart. Much progress has been made in terms of monitoring of clinical and subclinical anthracycline cardiotoxicity, finding alternative schedules, introducing special carriers of anthracyclines and using cardioprotecting agents. It is hoped that with all these effects and with results of ongoing and future trials, we will be able to reduce further or even eliminate anthracycline cardiotoxicity.

Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients.

We examined long-term changes in cognitive function and quality of life (QL) in hypertensive patients by comparing the antihypertensive effect of hydrochlorothiazide (HCTZ) and losartan. We studied 69 patients (age range, 30 to 73 years) with mild-to-moderate hypertension. All patients, in a double-blind study, were randomly allocated to either treatment with 50 mg losartan once daily or 25 mg HCTZ once daily. The sample in each treatment group was divided by age (younger than 60 years or 60 years or older). At baseline and after 26 months, a QL questionnaire appropriate for the hypertensive patients was given. Cognitive function was evaluated, at baseline and after 26 months, by psychometric tests consisting of items from the Mini-Mental State Examination (MMSE) and the Sandoz Clinical Assessment Geriatric (SCAG). A score of less than 24 on the MMSE and more than 40 on the SCAG was predictive of cognitive impairment. The losartan group had a significant improvement in SCAG (P<.001) and MMSE (P<.001). No significant changes were observed in the HCTZ group (SCAG, P = .1; MMSE, P = .2). Sixty-five percent of the elderly had a MMSE score less than 24 and 70% had a SCAG score greater than 40, v. 35% and 48%, respectively, in younger patients. The health state index of QL improved significantly in both groups (losartan group, P<.01; HCTZ group, P<.02); the improvement in QL scores in patients using HCTZ was significant only in subjects aged 60 years and older (P<.04). These results suggest that losartan can have a positive effect not only on blood pressure but also on impaired cognitive function, reversing even minimal cognitive deficits induced by hypertension. The elderly patients in our sample had worse scores and cognitive performance was lower than in younger patients, even if in the losartan group the score improvement was the same at all ages. The same could not be said for HCTZ.

Effects of losartan on hypertension and left ventricular mass: a long-term study.

This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients, mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients, mean age 56+/-7 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group: 11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients

Left ventricular function and exercise tolerance in patients with type II diabetes mellitus.

BACKGROUND: Left ventricular (LV) preload changes may alter exercise tolerance (ET), probably lessening activation of the Maestrini-Starling mechanism. Reduced LV filling (pre-load) during the diastolic phase, usually impaired in diabetic patients, could affect ventricular function. HYPOTHESIS: To evaluate the relationship between some echocardiographic LV function indices and ET, 24 patients (age 43-75 years, mean 54 +/- 13 years, Group A) with type II diabetes mellitus (DM), not suffering from other pathologies, and for whom the ergometric stress test (EST) resulted in an early interruption because of muscular fatigue and/or dyspnea, and 14 patients (age 38-70 years, mean 53 +/- 12 years, Group B) with type II DM and maximal ergometric stress test, used as control group, were studied. METHODS: The EST was performed by increasing the load by 25 W every 2 min; its duration was used as an ET index and correlated with clinical parameters of LV function obtained with M-mode, two-dimensional, and Doppler echocardiography. RESULTS: No patients in either Group A or Group B showed a high systolic blood pressure value at rest and/or an LV hypertrophy and/or an alteration of systolic functional indices. In neither group was there significant correlation between ET and duration of DM, basal heart rate, basal and max systolic blood pressure, and EF values. Linear regression analysis showed a significant correlation between Doppler parameters of the diastolic function and ET index in Group A, while there was no significant correlation in Group B. CONCLUSION: From these data we can deduce that in absence of left systolic ventricular dysfunction the impairment of LV relaxation in DM can influence exercise tolerance, probably by limiting activation of the contractile reserve.

[The effectiveness and tolerability of losartan and effect on left ventricular mass in patients with essential hypertension]. / Efficacia e tollerabilità del losartan ed effetto sulla massa ventricolare sinistra in pazienti con ipertensione essenziale.

The purpose of our study was to evaluate the antihypertensive efficacy, tolerability and effects on left ventricular mass of losartan over 10 months in patients with essential hypertension. Losartan is a selective angiotensin II receptor-antagonist. The whole study comprised 89 hypertensive patients who were randomized, at baseline, to 10 months of double-blind once daily treatment with losartan 50 mg (L Group, n = 49, mean age 55 +/- 13 years) or hydrochlorothiazide 25 mg (HCTZ Group, n = 40, mean age 56 +/- 10 years). Routine hematology, blood chemistry and urinalysis were performed before and after 5 and 10 months; standard electrocardiography, ambulatory non invasive 24-hours blood pressure monitoring, M-mode echocardiography, psychometric test and quality of life evaluation were obtained from all the patients before and after 10 months. In patients non responding after 4 weeks, hydrochlorothiazide 25 mg or losartan 50 mg was added in the L Group and in the HCTZ Group, respectively (L-HCTZ Group). The results showed good tolerability and a significant mean systolic and diastolic blood pressure reduction in all groups (L Group from 157/96 +/- 9/7 to 137/85 +/- 9/5 mmHg, p < 0.001; HCTZ Group from 158/97 +/- 11/8 to 150/91 +/- 9/7 mmHg, p < 0.003; L-HCTZ Group from 159/98 +/- 9/5 to 141/88 +/- 6/4 mmHg, p < 0.001), although L and L-HCTZ treatment were more effective during 24 hours than HCTZ. Moreover, a remarkable reduction in left ventricular mass index was obtained after 10 months only in the L Group (from 138.4 +/- 26.2 to 127.2 +/- 23.1 g/m2, p < 0.04) and in the L-HCTZ Group (from 140 +/- 20.3 to 125.5 +/- 20.1 g/m2, p = 0.126). Finally, in patients treated with losartan the results of psychometric test significantly improved (L Group: p < 0.05; L-HCTZ Group: p < 0.05) and a positive remarkable change in the quality of life was observed (L Group: p < 0.05; L-HCTZ Group: p = 0.083). In conclusion, losartan in monotherapy or in association with hydrochlorothiazide, was well tolerated, respected the quality of life, and produced a significant and remarkable reduction in blood pressure and left ventricular mass in hypertensive patients.

Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus.

Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD); negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.

[Current cardiologic diagnosis of infective endocarditis]. / La diagnostica cardiologica attuale dell'endocardite infettiva.

This report shows the importance of non-invasive techniques in infective endocarditis (IE) diagnosis. ECG is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Our casuistry (76 patients with IE) confirms the literature data about the great importance and the utility of transthoracic and transesophageal echocardiography to detect vegetation presence or complications as abscesses or valvular leaflet perforations. Therefore, these techniques are widely applied to predict major clinical events as embolism and death or to suggest a surgical therapy. Nuclear medicine studies play a minimal role. Magnetic resonance imaging appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined.