Diana Iarussi

Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography. A Prospective Multicenter Study

Background—The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. Methods and Results—In a multicenter prospective European study, including 384 consecutive patients (aged 57±17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). Conclusions—In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

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.

Endocarditis in the elderly: clinical, echocardiographic, and prognostic features

Aims Infective endocarditis (IE) is more and more frequent in elderly persons and it has been associated with various clinical, bacteriological, and prognostic features. The aim of the study was to define the clinical, echographic, and prognostic characteristics of IE in a large population of elderly patients from four European centres (three French, one Italian). Methods and results Three hundred and fifteen consecutive patients with definite IE underwent clinical evaluation, echocardiography, blood cultures, and follow-up. Patients were separated into three groups: group A: 117 patients aged 50 and 70 years. Elderly patients (group C) presented more frequently than other groups with digestive or urinary portal of entry, pacemaker endocarditis, and anaemia. S bovis endocarditis was less frequent and S aureus endocarditis more frequent in younger (group A) patients than in other groups. No difference was observed among groups concerning echocardiographic data as well as the incidence and localization of embolic events. Elderly patients were operated on as frequently as younger patients and their operative risk was similar than in other groups (11%, 3%, and 5% in groups C, B, and A, respectively, P =ns). Overall mortality in elderly patients was low (17%) but significantly higher than in younger patients (10% in group A, 7% in group B, P =0.02). By multivariate analysis, the only risk factors for in-hospital mortality were age ( P =0.003), prosthetic valve ( P =0.002), and cerebral embolism ( P =0.006). Conversely, surgical management was associated with a lower in hospital mortality ( P =0.03). Conclusions In this largest series of elderly patients with IE, IE in elderly carries specific features when compared with younger patients, although the echographic characteristics and embolic risk are similar. The overall mortality rate in elderly patients is higher than in younger, but the mortality in operated patients is low and similar than that of younger patients

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: Δ = –11 g/m2, P <0.02; hctz group: δ = –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

Anthracycline-induced cardiotoxicity in children with cancer: strategies for prevention and management.

The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure (CHF) and dilated cardiomyopathy in adults and in children. The prevention of anthracycline-induced cardiotoxicity is particularly important in children who can be expected to survive for decades after being cured of their malignancy. Attempts to reduce anthracycline cardiotoxicity have been directed towards: (i) decreasing myocardial concentrations of anthracyclines and their metabolites by dose limitation and schedule modification; (ii) developing less cardiotoxic analogs; and (iii) concurrently administering cardioprotective agents to attenuate the effects of anthracyclines on the heart. As regards schedule modification, avoidance of anthracycline peak levels may reduce the pathologic and clinical cardiotoxicity, although this has not always been observed. The analogs of doxorubicin, such as idarubicin and epirubicin, have similar cardiotoxicity to that of doxorubicin when given in amounts of equivalent myelotoxicity. Liposomal anthracyclines are a new class of agents that may permit more specific organ targeting, thereby producing less systemic and cardiac toxicity, but more studies are required to assess the advantages, if any, of these preparations over classical anthracyclines. The cardioprotective agent, dexrazoxane, an iron chelator, is highly effective and provides short-term cardioprotection to most patients receiving even the most intensive doxorubicin-containing regimens. Its long-term benefits remain to be determined. In addition, data remain insufficient to make specific recommendations regarding current use of dexrazoxane in children.It is thought that subtle abnormalities, related to anthracycline treatment in childhood, can develop into more permanent myocardial disease resulting in cardiomyopathy, which may progress to CHF. As regards the therapy of patients with anthracycline cardiotoxicity, two different situations have, therefore, to be considered: (i) if the patient presents with cardiac abnormalities, such as a reduction in fractional shortening at echocardiogram, without cardiac symptoms; and (ii) if the patient has CHF.In the presence of CHF, recovery with digitalis-diuretic therapy alone seldom occurs, and in patients who have refractory hemodynamic decompensation, heart transplantation is indicated. In patients with CHF, therapy with ACE inhibitors induces improvement in left ventricular structure and function, but this improvement is transient. Randomized clinical trials are, therefore, necessary to determine the effects of ACE inhibitors in mild-to-moderate left ventricular dysfunction.The beneficial effects of β-adrenoceptor antagonists (β-blockers) on cardiac function in heart failure due to anthracyclines seem comparable with those observed in other forms of heart failure with systolic dysfunction. Many drugs are available to treat children with CHF due to anthracycline treatment, but they are only palliative.

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.

Pulsed Doppler tissue imaging and myocardial function in thalassemia major

Abstract. Few studies are available on left ventricular diastolic function in β-thalassemia major, and these have conflicting results. Our aim in this study was to analyze myocardial systolic and diastolic functions in patients with β-thalassemia major using, for the first time, pulsed Doppler tissue imaging (DTI), and compare data with standard Doppler echocardiography. We studies 30 young patients with β-thalassemia major (age ≤16 years) with normal left ventricular systolic function and in 30 age and sex-matched controls using pulsed DTI, and compared the data with standard data obtained with Doppler echocardiography. In the β-thalassemia major group before transfusion, early (E) and late (A) peak diastolic flow velocities were increased when compared with controls (P = 0.0032 and P = 0.0039, respectively). The E/A ratio did not differ between the groups. All DTI parameters in the patients were similar to those of controls, except for lateral annulus ejection time adjusted for heart rate, that was significantly reduced when compared with healthy subjects (P < 0.01). Multivariate analysis showed that ejection time adjusted for heart rate, has a significant relation with only E peak velocity (P < 0.01) and left atrial size (P < 0.01), two volume-dependent parameters. Our study shows that pulsed DTI parameters and standard Doppler left ventricular filling pattern in young β-thalassemia major patients with normal left ventricular systolic function are similar to those seen in conditions of increased preload.

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.

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 cardiotoxocity 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. currently 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.ZusammenfassungIn der Klinik ist die Anwendung von Anthrazyklinen, eine Gruppe von chemotherapeutischen Substanzen mit guter Wirkung gegen solide Tumoren und bei Leukämie, limitiert, da bei steigender Dosierung eine kardiotoxische Wirkung auftritt. Eine manifeste Herzinsuffizienz wird bei 4,5 bis 7% der Patienten beobachtet, wenn sie mit Anthrazyklinen behandelt werden. Die Inzidenz von Herzerkrankungen steigt mit der Zeit der Verlaufsbeobachtung. Die Anthrazyklin-induzierte Herzinsuffizienz wird gewöhnlich durch reversible Veränderungen des Myokards hervorgerufen, die im Wesentlichen in einem Versagen der kardialen Leistungsfähigkeit des Herzens besteht. Derzeit wird als Hauptmechanismus eine Myozytenzerstörung durch freie Radikale diskutiert. Das Risiko der Herzinsuffizienz wird durch verschiedene Faktoren verändert, die die kardiale Toleranz in Bezug auf Anthrazykline verändern können. Das Alter und auch das Geschlecht haben eine besondere Bedeutung bei der Entwicklung der Anthrazyklin-Kardiotoxizität.Die Kardiotoxizität nach Anthrazyklin wird unterschieden in eine akute, subakute und eine progressiv latente chronische Form. Verschiedene invasive und nicht-invasive Methoden sind eingesetzt worden, um die sich entwickelnde Funktionsstörung aufzudecken, allerdings ohne bisher eine Methode der Wahl gefunden zu haben.Verschiedene Ansätze wurden gewählt, um die Anthrazyklin-induzierte Kardiotoxizität zu reduzieren: 1. Reduktion der Myokardkonzentration von Anthrazyklin und Metaboliten, 2. Entwicklung von weniger kardiotoxischen Analoga, 3. Gabe von protektiven Medikamenten gegen die Wirkung von Anthrazyklin.Wesentlich war die Entwicklung von speziellen Trägersubstanzen für Anthrazykline und der Einsatz von kardioprotektiven Substanzen. Es bleibt zu hoffen, dass eine weitere Reduktion der Anthrazyklin-Kardiotoxizität in Zukunft gelingt.

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.