Work capacity and oxygen uptake abnormalities in hyperthyroidism.

AIM: The aim of our study was to evaluate the haemodynamic and the respiratory response to exercise in patients with hyperthyroidism before and 30 days after normalized thyroid hormones levels. These findings were compared with those of 10 control patients. METHODS: Thirty patients (23 women, aged 34.3 +/- 12 years) with untreated hyperthyroidism were studied. Twenty-four patients were treated with methimazole, 13 of which were also treated with propranolol. Six patients underwent surgery. A symptom-limited cardiopulmonary exercise test and an echocardiography were performed in all patients. RESULTS: At rest patients with hyperthyroidism showed at echocardiography an increased cardiac index (P = 0.006 vs euthyroid, P = 0.007 vs normal) and a higher ejection fraction (P = 0.008 vs euthyroid, P = 0.007 vs normal). The duration of the exercise was lower in hyperthyroid patients (P = 0.006 vs euthyroid; P = 0.0068 vs normal). Anaerobic threshold was reached at 49.6% of peak VO2 during hyperthyroidism, at 60.8% during euthyroidism (P = 0.01) and at 62% in normal (P = 0.01). Work rate was lower in patients with hyperthyroidism at anaerobic threshold (P = 0.01 vs euthyroid, P = 0.03 vs normal) and at maximal work (P = 0.001 vs euthyroid, P = 0.01 vs normal). Patients in hyperthyroidism showed a lower increment of heart rate between rest and anaerobic threshold (P = 0.021 vs euthyroid, P < 0.0001 vs normal) and a lower VO2 at anaerobic threshold (P = 0.03 vs euthyroid; P = 0.04 vs normal). Oxygen pulse at anaerobic threshold was significantly reduced in hyperthyroidism (P = 0.04 vs euthyroid, P = 0.005 vs normal). CONCLUSIONS: The mean result is that after only 30 days of appropriate antithyroid treatment there was an appreciable improvement of exertion capacity.

Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness.

Hypertension (HT) is frequently associated with diabetes mellitus (DM) and its prevalence doubles in diabetics compared to the general population. This high prevalence is associated with increased stiffness of large arteries, which often precedes macrovascular events. The aim of our study was to evaluate the influence of HT and type II DM on aortic stiffness in patients with one disease or the other compared to those with both HT and type II DM. We studied 220 patients, 50 with type II DM (Group A), 50 with HT (Group B), 85 with both diseases (Group C), and 35 healthy subjects (HS). Regional arterial stiffness was assessed by automatic measurement of the carotid-femoral pulse wave velocity (PWV). For each patient, we evaluated: age, sex, body mass index, smoking habit, heart rate, SBP/DBP, pulse pressure (PP), mean BP, fasting glucose, lipid profile, uric acid, and fibrinogen. Group C had significantly more women and non smokers and the highest PP (61+/-14 mmHg). Of biochemical parameters, only fibrinogen was higher in Group A and in Group C (P<0.01 and P<0.001, respectively). Group C had a significantly higher PWV than the other four groups (P<0.0001). Stepwise forward regression analysis showed that fasting glucose was the first independent determinant of PWV (P<0.0001). In conclusion, this study shows that patients with DM and HT have higher arterial stiffness compared to HS and those with one disease or the other. Fasting glucose is the major independent determinant of PWV, which may be used as a relevant tool to assess the influence of cardiovascular risk factors on arterial stiffness in high-risk patients.

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.

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.

Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1.

Vascular disease is an underestimated complication of neurofibromatosis type 1 (NF1). The few studies available on this disease are based on case reports. The purpose of this study was to evaluate the relationship between 24-h systolic blood pressure (SBP) and 24-h heart rate obtained by ambulatory blood pressure monitoring and the carotid femoral pulse wave velocity, a widely used index of arterial distensibility, evaluated with Complior. We studied 64 young NF1 patients and 30 healthy subjects. There was no difference in pulse wave velocity between NF1 patients and healthy subjects. Ten of the NF1 patients showed 24-h SBP or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into subgroups: NF1 patients with 24-h SBP and 24-h DBP < or = 95th percentile for age and sex (NF1A group) and NF1 patients with mean SBP or DBP >95th percentile for age and sex (NF1B group). The pulse wave velocity of NF1A and NF1B patients were 6.3 +/- 1 m/sec and 6.4 +/- 1 m/sec, respectively (P = not significant). A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups. Distensibility of the central arteries may be altered by various environmental or genetic factors. Thus, genetic determinants may play a role in the response of the large arteries to blood pressure. The recent discovery of neurofibromin in aortic smooth muscle may explain the vascular abnormalities present in NF1 patients. We emphasize the importance of a careful vascular evaluation using a noninvasive method, such as Complior and a periodic ambulatory blood pressure monitoring to detect NF1 patients at high risk of vascular complications.

Noninvasive evaluation of arterial abnormalities in young patients with neurofibromatosis type 1.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.

[TNF alpha and heart failure]. / TNF alpha e scompenso cardiaco.

Tumor necrosis factor alpha (TNF alpha) is a cytokine with proinflammatory properties which produces negative inotropic effects on the heart. It is produced in a variety of conditions such as septic shock, acute myocarditis, reperfusion injury, and congestive hear failure (CHF). This production is probably due to activation of immune elements localized in the heart or periphery, or both. TNF alpha acts by binding to two specific receptors: TNF-R1 and TNF-R2. These two proteins have different effects. TNF-R1 has cytotoxic and antiviral activity, induces fibroblast proliferation, and mediates apoptosis. TNF-R2 is involved in septic shock and in lymphocyte proliferation. They both have negative inotropic effect on the heart. It has been showed that these receptors are down-regulated in congestive heart failure, while their soluble forms (sTNF-R1 and sTNF-R2) increase with the severity of symptoms. However the significance of this increase is still unclear. The role of Fas, a receptor protein that induces apoptosis, is also examined. Fas and its ligand have homologies respectively with TNF alpha and TNF-R. Also the soluble form of Fas (sFas) increases in relation to heart failure and is related to soluble forms of the similar receptor family, therefore it is possible that the same stimuli lead the three receptors to act together. SFas, as well as sTNF receptors, may play an important role in CHF.

[Clinical value of multiplane transesophageal echocardiography in the diagnosis of lipomatous hypertrophy of the interatrial septum. Report of two clinical cases]. / Utilità clinica dell'ecocardiografia transesofagea multiplanare nella diagnosi di ipertrofia lipomatosa del setto interatriale. Descrizione di due casi clinici.

Lipomatous hypertrophy of interatrial septum is a very rare condition associated with supraventricular arrhythmias and sudden death. The authors describe two clinical cases of lipomatous hypertrophy and underline usefulness of multiplane transesophageal echocardiography in the diagnosis of this affection.

[Silent ischemia in patients on dialysis treatment]. / Ischemia silente in pazienti in trattamento dialitico.

The authors carried out a perspective study to determine the frequency of silent ischemia (SI), in 50 consecutive patients with end stage renal failure, during dialysis by Holter monitoring. Twenty patients had SI. The number of cardiovascular risk factors, principally diabetes, smoking and the underlying renal disease was related to ischemic events. Dialysis may predispose to and facilitate the detection of myocardial ischemia by the simultaneous presence of hypotension, hypovolemia, hypoxia and tachycardia. Holter monitoring may allow the detection of ischemic events and the identification of a subgroup of dialytic patients with a high cardiovascular risk.

[Diagnosis of delayed upper left ventricular activation: limits of electrocardiography and usefulness of vectorcardiography]. / La diagnosi di ritardo di attivazione ventricolare sinistra superiore: limiti dell'elettrocardiografia e utilità della vettorcardiografia.

The electrocardiographic (ECG) diagnosis of delayed ventricular left superior activation (DVLSA) is often difficult and uncertain, even when all the criteria proposed in clinical literature are fulfilled. The vectorcardiography (VCG) always permits an accurate diagnostic evaluation because the contour of the QRS loop describes successively the various phases of ventricular depolarization. Sensitivity and specificity of ECG in diagnosing DVLSA have been calculated referring to VCG analysis. The QRS loop initial forces orientation in the frontal plane, a VCG highly reliable criterion, was considered especially significant for this purpose. The sensitivity and specificity of ECG were, respectively, 75% and 95%. Moreover, this study has confirmed the low performance of frontal plane QRS axis criterion and the necessity of polyparametric method for a correct ECG-VCG diagnosis of DVLSA. However, the VCG is more reliable than ECG in such diagnosis because it allows thoroughly to analyze QRS-loop initial forces.