D Giorgi

Excess Aldosterone Is Associated With Alterations of Myocardial Texture in Primary Aldosteronism

Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P ≤0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7±1.8 versus 45.5±2.0 g/m2.7;P =0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVIs; −12.02±5.84% versus 6.06±3.08%;P =0.012) and posterior wall (−11.13±6.42% versus 8.63±9.62%;P =0.012). A regression analysis showed that CVIs was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for ≈36% of CVIs variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.

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.

Ultrasonic Videodensitometric Analysis of Two Different Models of Left Ventricular Hypertrophy Athlete’s Heart and Hypertension

Absolute or relative increases in intramyocardial fibrosis accompany hypertrophy development in human hypertension. Myocardial texture analysis of two-dimensional echocardiographic gray-level distribution has been shown to identify alterations attributed to abnormal collagen content in several conditions. Therefore, this echocardiographic tool might help to identify those hypertensive individuals with abnormal interstitial collagen deposition, a condition that may promote and/or aggravate morbidity in this group of people who are at high risk for cardiovascular events. We compared male essential hypertensive subjects who had marked cardiac hypertrophy (left ventricular mass index adjusted for height > 2 SD of mean of control group) (group 1) with normotensive elite veteran athletes who had comparable cardiac hypertrophy (group 2) and sedentary normotensive subjects as controls (group 3). The groups (n = 14 each) were matched for age (+/- 2 years) and sex. We analyzed echocardiographic digitized data quantitatively by means of a calibrated 256 gray level digitization system to calculate midseptal and midposterior end-diastolic and end-systolic mean gray levels and to derive the so-called cyclic variation index, ie, the percent mean gray level variation during the cardiac cycle. Echocardiographic parietal and septal thicknesses and masses were evaluated according to the Penn convention. Left ventricular mass index (adjusted for height) overlapped between groups 1 and 2 (187.1 +/- 17.5 and 181.3 +/- 19.3 g/m, respectively; P = NS), whereas it was obviously smaller in control subjects (93.1 +/- 18.6 g/m; P < .001 for both). According to inclusion criteria, both septal and posterior wall thicknesses were comparable in athletes and hypertensive subjects, and they were higher than in the control group (P < .0001). The hypertensive subjects showed a significantly lower cyclic variation index than the control and athlete groups for both the septum (P < .001) and posterior wall (P < .001); no statistical difference was found between athletes and control subjects for this parameter. In conclusion, abnormalities of two-dimensional echocardiographic gray-level distribution are present in hypertensive hypertrophied individuals but seem unrelated to the degree of echocardiographic hypertrophy as such. An altered collagen network distribution or a decrease in capillary distribution in severe myocardial hypertrophy, secondary to pressure-volume overload in hypertension with other yet unknown mechanisms, could help to explain our findings. Further work is needed to establish the prognostic, clinical, and therapeutic implications of these findings.

Microalbuminuria and Transcapillary Albumin Leakage in Essential Hypertension

Microalbuminuria (an increased urinary albumin excretion that is not detectable by the usual dipstick methods for macroproteinuria) predicts cardiovascular events in essential hypertensive patients. A possible reason for this behavior is that albumin leaks through exaggeratedly permeant glomeruli exposed to the damaging impact of subclinical atherogenesis. To evaluate this possibility, the transcapillary escape rate of albumin (TER(alb), the 1-hour decline rate of intravenous (125)I-albumin), a parameter that estimates the integrity of systemic capillary permeability, albuminuria, blood pressure, echocardiographic left ventricular mass, lipids, and body mass index were measured in 73 uncomplicated, glucose-tolerant men with essential hypertension and normal renal function; 53 were normoalbuminuric, and 20 were microalbuminuric. Twenty-one normotensive age-matched male subjects were the controls. TER(alb) was higher in hypertensives, a behavior explained in part by a positive correlation with blood pressure values, although body mass index, lipids, and left ventricular mass showed no association. Transcapillary albumin leakage values did not differ between normoalbuminuric and microalbuminuric patients and were unrelated to albuminuria. Blood pressure, particularly systolic, and cardiac mass were higher in microalbuminuric patients in whom albuminuria correlated with both cardiovascular variables and indicated the influence of the hemodynamic load on urinary albumin levels. Thus, TER(alb), a parameter influenced by the permeability surface area product for macromolecules and the filtration power across the vascular wall, is altered in essential hypertensives. However, this abnormality is dissociated from the amount of albuminuria, which is contrary to the hypothesis that a higher albumin excretion reflects a greater degree of systemic microvascular damage in essential hypertension.

Severe Aortic Stenosis and Myocardial Function Diagnostic and Prognostic Usefulness of Ultrasonic Integrated Backscatter Analysis

Background—The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. Methods and Results—Thirty-five subjects (AS: valve orifice ≤1 cm2; 12 female; mean age, 71.8±6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). Conclusions—One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation.

Effects of anabolic-androgenic steroids on weight-lifters' myocardium : an ultrasonic videodensitometric study

BACKGROUND Recent bioptical data have shown that in weight-lifters (WL) under the pharmacological effects of anabolic-androgenic steroids (AAS), a focal increase in myocardial collagen content might occur as a reparative mechanism against a myocardial damage. OBJECTIVE The aim of this study was to investigate whether by using videodensitometry an early identification of the changes in myocardial texture is possible or a potential sign of myocardial damage, which can potentially occur in WL who have used AAS. METHODS Ten males WL (mean age: 32+/-6 yr) who had regularly used AAS (users), were compared with 10 male WL at same training level (nonusers), who had not used any drugs and with 10 healthy sedentary controls (controls). The three groups were age and sex-matched. Echocardiographic parietal, septal thickness, and left ventricular mass (LVMbs) were evaluated. Left ventricular systolic and diastolic functions were evaluated with Doppler examination. Quantitative analysis of echocardiographic digitized data was carried out with a calibrated 256 gray level digitization system, in order to calculate the mid-septum and the mid-posterior mean gray level (MGL) and to derive the cyclic variation index (CVI), i.e., the percent MGL variation during cardiac cycle. RESULTS The weight and relative body mass index were significantly higher in WL (P<0.001); also the diastolic blood pressure was slightly but significantly higher in users in comparison both with nonusers and controls (P<0.01). Systolic and diastolic functional parameters overlapped in the three groups. LVMbs was significantly higher in users (145+/-17) and in nonusers (122+/-27) vs. C (104+/-18 g x m(-2)) (p<0.001). CVI at septum level showed significant differences: users: (2.3+/-31%) vs nonusers: (23+/-8) and controls (29+/-5) (P<0.005); although no significant difference was found between nonusers and controls. CVI at posterior wall level followed a similar pattern. No relationship was found between CVI and LVMbs or wall thickness. DISCUSSION As brought out by videodensitometry, despite an increase in septal and parietal thickness and consequently in LVMbs, the physiological pressure overload that happens in WL during sport activities, in absence of any drugs, does not modify the myocardial ultrasonic texture. The abuse of AAS in WL, on the other hand, determines some alterations of the myocardial textural parameters. The real significance of these changes of myocardial texture detected with videodensitometry in WL who use anabolic-androgenic steroids, present also in the absence of other systolic and diastolic left ventricular functional indexes alterations, needs to be further explored with a larger population through the comparison with endobioptical data and with a follow-up study approach.

Heart involvement in systemic sclerosis: an ultrasonic tissue characterisation study

BACKGROUND Clinicoepidemiological findings indicate that symptomatic heart involvement in patients with systemic sclerosis (SSc) predicts a very poor prognosis. At necropsy studies, SSc heart involvement without significant coronary lesions is characterised by patchy myocyte necrosis and contraction band necrosis with collagen replacement leading to myocardial fibrosis. There is a discrepancy between the frequency of clinically evident myocardial disease (25%) and autoptical myocardial fibrosis (81%). OBJECTIVE The aim of this study was to detect preclinical myocardial alterations in SSc patients by ultrasonic videodensitometric analysis. METHODS Thirty five SSc patients (three male, aged 48.6 (11) SD years, range 22–65) with normal ventricular function and 25 age and sex matched healthy controls were studied. All patients had a negative maximal exercise stress; in all cases arterial hypertension, renal involvement, and diabetes were excluded. Echocardiographic images were digitised by a real time videodigitiser (Tomtec Imaging Systems). Quantitative texture analysis was performed on data from the septum and the posterior wall, obtaining mean gray level histogram (MGL) at both end-diastole (d) and end-systole (s). The cyclic variation index (CVI), was calculated according to the formula ((MGLd−MGLs)/MGLd) × 100. Left ventricular mass (LVM), body surface corrected, was calculated according to Penn convention. RESULTS Comparable systolic and diastolic blood pressure, LVM, diastolic and systolic function were recorded in both SSc patients and controls. In contrast, in SSc patients the CVI, which is the expression of the intrinsic myocardial structural function, was significantly lower than in controls (septum: −18 (28)%v 35 (10)%, p<0.0001; and posterior wall: −13 (32)%v 50 (20)%, p<0.0001). Changes in cyclic echo amplitude, probably related to myocardial fibrosis, were detected in the large majority of SSc patients (88%). CONCLUSIONS Ultrasonic videodensitometric analysis represents a non-invasive, feasible method that can detect early myocardial changes in SSc patients, which could be related to both fibrosis and microcirculatory abnormalities. Their potential evolution towards ventricular dysfunction and their link with cardiac sudden death, because of severe conduction system or rhythm disturbancies, should be further investigated.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease

BackgroundThe incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves.Methods and ResultsForty-five consecutive patients (33 men and 12 women; 53±6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis >50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamonds algorithm) was low (45.6%±12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3%±10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4%±4.3% (p<0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3%±5.5% (p<0.003), a level that appeared significantly higher than that of model 2 (p<0.016).ConclusionBoth noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

Transvascular and Urinary Leakage of Albumin in Atherosclerotic and Hypertensive Men

Increased urine albumin is associated with atherosclerotic disease and predicts cardiovascular morbidity and mortality in nondiabetic populations. This finding is frequently postulated to reflect the impact of atherosclerotic damage on glomerular and systemic capillary permeability, an interesting but as yet untested hypothesis. The transcapillary escape rate of albumin (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of capillary macromolecular permeability), albuminuria, lipid levels, echocardiographic wall thickness, and insulin responses to oral glucose were measured in 30 untreated dipstick-negative lean men and clinically stable atherosclerotic peripheral vascular disease; tolerance to oral glucose was a requirement for inclusion in the study. Because hypertension per se might influence TERalb, the sample included either normotensive (n=18, 118+/-6/72+/-7 mm Hg) or hypertensive (n=12, 141+/-7/84+/-6 mmHg by 24-hour blood pressure monitoring) arteriopathic patients; 11 normal age- and gender-matched subjects (121+/-7/76+/-5 mmHg) were used as control subjects. TERalb was higher in patients (10.7+/-3.2 versus 7.4+/-1.7%/h, P<0.013), a difference that persisted after postload glucose, insulin, and lipid levels were accounted for by covariance analysis; atherosclerosis and hypertension together did not further impair vascular permeation to albumin. In contrast with TERalb, albuminuria was elevated only in the hypertensive subgroup; the 2 variables showed no relationship, even when the data were analyzed separately in normotensive and hypertensive subgroups. Urine albumin correlated positively with 24-hour blood pressure and wall thickness. Thus, systemic capillary permeability is altered in nondiabetic atherosclerotic patients independently from blood pressure levels, but this abnormality is not reflected by proportionate changes in albuminuria.

Ultrasonic myocardial texture in hypertensive mild-to-moderate left ventricular hypertrophy a videodensitometric study

Myocardial texture analysis of two-dimensional echocardiographic gray level distribution is abnormal in hypertensive patients with severe increase of left ventricular mass. The aim of this study was to investigate the behavior of this parameter in hypertensive patients with absent-to-moderate left ventricular hypertrophy, more representative of the overall hypertensive population. We compared male essential hypertensive patients, with absent or mild-to-moderate left ventricular hypertrophy, with normotensive sedentary healthy subjects as controls. The groups (n = 18 each) were age- (+/- 2 years) and sex-matched. All subjects performed ambulatory blood pressure measurements for the evaluation of 24 h mean systolic and diastolic blood pressure. Quantitative analysis of echocardiographic digitized imaging was performed through a calibrated 256 gray level digitization system to calculate midseptum and midposterior end-diastolic and end-systolic first and second order textural analysis. In particular were observed the mean gray level cyclic variations to deriving the cyclic variation index (CVI). The hypertensives showed a significantly lower CVI compared with controls both for septum (P < .001) and for posterior wall (P < .0001). No significant relationships were found between CVI and relative diastolic thickness both of septum and posterior wall. Conversely, a significant inverse relationship was found between systolic arterial pressure values and CVI both of septum and posterior wall. Abnormalities of two dimensional echocardiographic gray level distribution are present also in hypertensive patients with absent or with mild-to-moderate levels of left ventricular hypertrophy, but seem unrelated to the degree of echocardiographic hypertrophy as such. Changes in collagen network distribution or microcirculatory alterations, secondary to pressure-volume overload per se or to other complex humoral factors, could explain these abnormalities. Further work is needed to establish the clinical, therapeutic, and prognostic implications of these findings.