Gino Santoro

Heart rate variability and left ventricular diastolic function in anorexia nervosa

PURPOSE To investigate the cardiac effects of starvation in a group of adolescents with anorexia nervosa (AN). METHODS Twenty-five patients with AN (range 13-20 years), compared with 25 age-matched thin and 25 age-matched control women with body mass index > 20 Kg/m(2), underwent a complete clinical evaluation, including echocardiogram and 24-hour electrocardiogram monitoring to evaluate heart rate variability (HRV) indices. RESULTS Compared to both thin and control women, patients with AN had greater HRV time domain indices (SDNN: 246.5 +/- 32.4 vs. 170.4 +/- 24 ms and vs. 181 +/- 21.2 ms, p <.001), and in the frequency domain a lower LF/HF ratio (4.2 +/- 1.3 vs. 6.7 +/- 1.2 and vs. 6.8 +/- 1.3 ms, p <.001). AN patients showed reduced left ventricular mass with normal systolic function and typical diastolic patterns, characterized by a lower peak velocity transmitral flow in late diastole (peak A: 35.9 +/- 8.5 vs. 45.2 +/- 7.3 cm/sec and vs. 46.6 +/- 6.3 cm/sec, p <.01), a comparable peak velocity in early diastole (peak E: 92.7 +/- 12.1 vs. 83 +/- 6.2 and vs. 86.8 +/- 9.1 cm/sec, ns) and, subsequently, a greater E/A ratio (2.8 +/- 0.7 vs. 1.8 +/- 0.3 and vs. 1.9 +/- .5, p <.01) than thinness and control groups. Moreover, SDNN was also positively related to E/A ratio (r =.54, p <.01). CONCLUSIONS Our findings demonstrate a cardiovascular vagal hyperactivity in AN, which appears to influence the ventricular diastolic dynamics. HRV and diastolic function analysis may represent useful tools in monitoring anorexia-induced cardiac modifications.

Normal ultrasonic myocardial reflectivity in athletes with increased left ventricular mass. A tissue characterization study.

BackgroundUltrasonic integrated backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content. The integrated backscatter is also increased in hypertrophic cardiomyopathy, probably because of fiber disarray. The purpose of this study was to investigate myocardial tissue reflectivity in subjects with physiological hypertrophy caused by intense physical training and to assess the relation between the acoustic properties of myocardial tissue and left ventricular wall thickness assessed by conventional two-dimensional echocardiography. Methods and ResultsTwenty-four young male athletes (14 professional cyclists and 10 weight lifters, all in full agonistic activity) were studied together with 10 normal age-matched controls with sedentary life. By means of a commercially available two-dimensional echocardiograph, standard measurements were obtained according to the recommendations of the American Society of Echocardiography. With a prototype implemented in our Institute, an on-line radiofrequency analysis of ultrasound signals was also performed to obtain quantitative operator-independent measurements of the integrated backscatter of the myocardial walls. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent integrated backscatter (%IB). Compared with control subjects, athletes showed greater thickness values of septum (controls, 9±1; cyclists, 14±2; weight lifters, 15±1 mm, mean± SD; p < 0.01) and posterior wall (9±1, 12±2, and 12+1 mm, respectively; p < 0.01) but similar values of %IB for both septum (23±4%, 21±7%, and 23±8%, p = NS) and posterior wall (10±2%, 9±2%, and 11±2%, p = NS). In athletes, no correlation was found between septal and posterior wall thickness and the corresponding regional myocardial reflectivity (r = 0.23, p = NS and r = 0.01, p = NS, respectively). Furthermore, we compared the quantitative ultrasonic data between two subsets of 10 athletes and 10 patients with hypertrophic cardiomyopathy and similar degrees of septal thickness (16±1 versus 17±1 mm, respectively, p = NS). Septal and posterior wall %IB results were significantly higher in patients with hypertrophic cardiomyopathy (53±13% and 36±9%o, respectively) than in athletes (21±7% and 10±3%, respectively; p < 0.01 for both). ConclusionsWe conclude that 1) endurance athletes show a normal pattern of quantitatively assessed ultrasonic backscatter despite of a marked left ventricular hypertrophy and 2) athletes and patients with hypertrophic cardiomyopathy and similar degrees of myocardial wall thickness can be differentiated on the basis of quantitative analysis of backscattered signal.

Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism

Objectives To evaluate vascular wall structure and conduit artery stiffness in patients with primary aldosteronism. Methods This observational study, conducted in a University Hypertension Center, evaluated the carotid wall by 2-D ultrasonography and ultrasonic tissue characterization, and analyzed arterial stiffness by applanation tonometer. Twenty-three consecutive patients with primary aldosteronism, 24 matched patients with essential hypertension and 15 controls were studied. Intima-media thickness and corrected integrated backscatter signal of the carotid arteries were evaluated. Radial and femoral pulse wave velocity and aortic augmentation index were also investigated. Results Intima-media thickness in patients with essential hypertension (0.69 ± 0.03 mm) was higher (P < 0.04) than that in controls (0.59 ± 0.02 mm). This finding was more evident in primary aldosteronism patients (0.84 ± 0.03 mm), in whom intima-media thickness was greater than that in controls (P < 0.0001) or in patients with essential hypertension (P < 0.01). Similarly, corrected integrated backscatter signal in patients with essential hypertension (−23.6 ± 0.35 dB) was higher (P < 0.0001) than that in controls (−26.2 ± 0.44 dB), but it was even more elevated in patients with primary aldosteronism (−22.1 ± 0.46 dB), who showed greater corrected integrated backscatter signal than was the case in patients with essential hypertension (P < 0.009) or in controls (P < 0.0001). Femoral pulse wave velocity was higher in primary aldosteronism patients (10.8 ± 0.57 m/s) than in patients with essential hypertension (9.1 ± 0.34 m/s, P < 0.03) or in controls (7.1 ± 0.51 m/s, P < 0.0001). Femoral pulse wave velocity was lower in controls than in patients with essential hypertension (P < 0.0001). The same pattern was observed for radial pulse wave velocity. Aortic augmentation index was higher in primary aldosteronism patients (28.2 ± 2.1%) than in patients with essential hypertension (26.0 ± 1.8%) or in controls (16.8 ± 2.0%, P < 0.001). Patients with essential hypertension likewise exhibited higher aortic augmentation index than controls (P < 0.001). Conclusion Aldosterone excess is responsible per se for vascular morphological (wall thickening and carotid artery fibrosis) and functional (central stiffness) damage.

Left ventricular function during exercise in athletes and in sedentary men.

Aim of this study was to evaluate left ventricular function during exercise in 10 male elite runners and in 10 sedentary males. End-diastolic (EDV) and end-systolic volume (ESV), left ventricular ejection fraction (EF), early peak transmitral flow velocity (peak E), time-velocity integral of mitral inflow (m-TVI); mitral cross sectional area (m-CSA); mitral stroke volume (SV), and cardiac output (CO) were measured by echo-Doppler. We simultaneously analyzed: VO2max by spirometric method, mean arterial blood pressure (MAP) by sphygmomanometer, and heart rate (HR) by ECG. The parameters were measured under basal conditions (level 1), at 50% of maximal aerobic capacity (level 2), at peak of exercise (level 3) and during recovery. Ejection fraction in athletes increased significantly at peak of exercise through Frank-Starling mechanism. Stroke volume and cardiac output increased significantly in athletes at peak of exercise. Left ventricular diastolic function was superior in athletes versus controls: in fact, higher peak E in athletes enhanced early diastolic ventricular filling. Therefore, the athletes showed complex cardiovascular adjustments induced by training, which allowed an higher peak working power, a greater cardiac output, and VO2max when compared with an untrained control population.

Effects of age and physical fitness on microcirculatory function

Sedentary aging is associated with endothelial dysfunction and nitric oxide (NO) impairment. The aim of the present study was to assess the effects of regular physical exercise on nitrite/nitrate (NOx) concentrations and microcirculatory function in older men compared with young individuals. We measured NOx plasma concentrations and baseline and stimulated skin blood flow (SBF) by laser Doppler flowmetry in 39 male athletes [range, 22-72 years; maximal oxygen consumption (VO2max), 60.0 +/- 4.7 ml.min(-1).kg of body weight(-1) (mean +/- S.D.)] and 45 age- and sex-matched sedentary controls (VO2max, 38.0 +/- 7.1 ml.min(-1).kg of body weight(-1)). NOx concentrations were higher in athletes than in controls (50.4 +/- 16.3 compared with 39.0 +/- 15.4 micromol/l; P<0.005), whereas baseline SBF was comparable. Hand SBF after heating and ischaemia and foot SBF after heating were higher in athletes (P<0.0001) than in controls. By comparing the lowest and the highest tertile of age, sedentary young subjects had higher NOx concentrations than sedentary older subjects (43.3 +/- 13.4 compared with 31.8 +/- 12.2 micromol/l respectively; P<0.05). Exercise abolished this difference (49.1 +/- 9.6 micromol/l for young subjects and 52.1 +/- 11.5 micromol/l for older subjects; not significant). Resting SBF was similar in all the subgroups, but stimulated SBFs were lower in both subgroups of untrained compared with trained subjects. NOx concentrations were positively correlated with VO2max (r=0.46, P<0.001). Stimulated SBFs were correlated with NOx (r>0.30, P<0.05). These findings show that chronic exercise may improve endothelial function in older (and young) men, probably by increasing NO availability.

Microalbuminuria is a marker of left ventricular hypertrophy but not hyperinsulinemia in nondiabetic atherosclerotic patients.

Microalbuminuria predicts cardiovascular events in diabetic and nondiabetic patients. For a better understanding of the physiopathological importance of microalbuminuria in atherosclerotic disease, we evaluated the relation between urinary albumin excretion and arterial blood pressure, left ventricular mass, insulin, and lipid levels. The studies were conducted in patients with atherosclerotic peripheral vascular disease. Urinary albumin excretion (studied by nephelometry; an average of triplicate collections from 8 PM to 8 AM), causal blood pressure, echocardiographic left ventricular mass index and wall thickness, plasma immunoreactive insulin and C-peptide (both basally and after a 75-g oral glucose load), blood lipids, and fibrinogen were studied in eight normal subjects and 20 nonobese, nondiabetic male patients with angiographically documented atherosclerotic peripheral vascular disease and preserved renal function, 12 of whom were either hypertensive or on antihypertensive treatment. Eight patients were microalbuminuric (urinary albumin > 20 micrograms/min) and 12 were not. Ankle-arm index and calf and foot transcutaneous oxygen tension were reduced in comparison with normal control subjects but superimposable between the two patient groups to indicate a comparable clinical progression of the vascular disease. In the microalbuminuric subjects, left ventricular mass index was greater, interventricular septum was thicker, and cardiac hypertrophy was more frequent than in nonmicroalbuminuric patients. The prevalence of hypertension tended to be greater and systolic blood pressure values were higher in the presence of microalbuminuria. Overall, a highly significant relation existed between urinary albumin excretion and left ventricular mass. Systolic blood pressure was greater and a history of arterial hypertension was more frequent among microalbuminurics, whereas diastolic blood pressure values showed a statistically significant correlation with both variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation

Mitochondrial diseases are due to impairment of the mitochondrial respiratory chain. A plausible pathogenic mechanism leading to cellular dysfunction and phenotypic expression is oxidative stress, but there are surprisingly few clinical studies on this subject. Glutathione (GSH) deficiency has been reported in mitochondrial diseases, and the biosynthesis of glutathione depends on cysteine availability. We have examined oxidative stress biomarkers [advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP)] in blood samples from 27 patients and 42 controls. AOPP levels were greater in patients than in controls (P value <0.00001). Therefore, we performed a double-blind cross-over study to evaluate if 30-day supplementation with a whey-based cysteine donor could modify these markers, reduce lactate concentration during aerobic exercise, or enhance muscular strength and quality of life. Treatment did not modify lactate concentration, clinical scale (MRC) or quality of life (SF-36), but significantly reduced oxidative stress levels. Our findings reinforce the notions that in mitochondrial diseases oxidative stress is important and can be reduced by administration of a cysteine donor. Oxidative stress biomarkers may be useful to detect redox imbalance in mitochondrial diseases and to provide non-invasive tools to monitor disease status.

Skin vasomotion investigation: A useful tool for clinical evaluation of microvascular endothelial function?

Skin vasomotion is the rhythmic variation of skin microvessel diameter responsible for skin microcirculatory blood flow oscillation, the so called skin blood flowmotion. It can be easily investigated by means of the spectral analysis of skin laser Doppler flowmetry (LDF) signal. Experimental and clinical findings suggest that vasomotion is partially dependent on microvascular endothelial activity. Based on this, investigation of skin vasomotion, using spectral analysis of skin LDF signal has been recently proposed for the investigation of microvascular endothelial function in clinical setting. Clinical studies have demonstrated that the LDF technique coupled with spectral analysis of skin LDF tracing is a useful and accurate method for the measurement of skin microvascular endothelial-dependent vasomotion in patients with different pathological conditions. In these studies skin vasomotion investigation showed a higher sensitivity in the evaluation of skin microvascular endothelial function than tests based on the simple LDF measurement of skin blood flow response to different stimuli. Further studies are needed to evaluate whether the investigation of skin endothelial-dependent vasomotion can predict clinical and therapeutic outcomes of patients with vascular diseases.

Left ventricular function and calcium phosphate plasma levels in uraemic patients.

Background.  Recent investigations have focused on the pathogenetic role of disturbances of calcium phosphate metabolism in causing cardiovascular morbidity and mortality in haemodialysis patients. The aim of the present study was to assess left ventricular function and its relationship to phosphate and calcium plasma levels in stable uraemic patients on haemodialysis treatment.

Changes in heart rate variability and QT dispersion in patients with overt hypothyroidism

OBJECTIVE The aim of the present study was to evaluate the effect of clinical hypothyroidism on cardiovascular autonomic function and ventricular repolarization. DESIGN AND METHODS We studied 31 patients (22 females and 9 males; mean age 53.6+/-11.8 years) with overt hypothyroidism (TSH=56.2+/-14.7 microU/ml, low free thyroxine (T4), free tri-iodothyronine (T3)) and 31 euthyroid controls, to investigate the dispersion of the QT interval in electrocardiogram (ECG) (an index of inhomogeneity of repolarization) and heart rate variability (HRV; a measure of cardiac autonomic modulation). The hypothyroid patients and controls underwent a full medical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. The hypothyroid patients were re-examined after 6 months of treatment with L-T4. RESULTS Patients with hypothyroidism showed higher QT dispersion and lower HRV measures than controls (P<0.01 or P<0.001). In hypothyroid patients, standard deviation of all R-R intervals was inversely related (by simple regression) to serum (log)TSH levels (r=-0.47, P=0.008), while QT dispersion (r=0.50, P=0.004) and QTc dispersion (r=0.46, P=0.008) were directly related to (log)TSH. Parameters of HRV improved after 6 months of L-T4 treatment, with the correction of hypothyroidism, becoming comparable with those of the control subjects, whereas the QT and QTc dispersion results were found to be only partially restored, remaining higher than the controls. CONCLUSIONS The results of the study demonstrate that hypothyroidism is associated with a decreased sympatho-vagal modulation of the heart rate and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with overt hypothyroidism may represent a useful tool in monitoring the cardiovascular risks.