Combined functional magnetic resonance imaging and skin conductance to detect localized neural response to psychological stress: a pilot study.

OBJECTIVE: This preliminary study aims at investigating the neural correlates of the stress response, intended as an emotional and cognitive response, through the description of the activation of the autonomic nervous system in a problem-solving task and central functional data; in particular, we recorded skin conductance level (SCL) and response (SCR) and observed the correlation with fMRI data. MATERIALS AND METHODS: The results obtained from 6 healthy subjects, 3 males and 3 females, aged between 18 and 45 (average = 27, SD = 7.08) who voluntarily offered to participate in the study were examined. They were previously subjected to a brief clinical psychological assessment (MMPI-2) and then to a psychophysiological evaluation. The real experiment consisted in subjecting the participants to an adapted version of the Raven's Coloured Progressive Matrices 47 (CPM 47) test to evaluate some consequences on brain activity of attention, orientation, reflex and response to stress during fMRI data acquisition and SCL-SCR recording. RESULTS: SCR changes were found to be related to the activity of different brain regions such as bilateral precentral gyrus, right inferior frontal gyrus, right medial frontal gyrus, bilateral superior frontal gyri and left anterior cingulate suggesting a specific relationship between attentive processing and autonomic arousal. CONCLUSION: The association of SC measurement with neuroimaging allows to highlight the interaction between emotional and cognitive processes: although preliminary, these results partially confirm what previously found in literature on the neural correlates of psychological stress and underline the interaction between cognitive function and autonomic arousal system during a stressful problem-solving task.

Long-term remodeling of rat pial microcirculation after transient middle cerebral artery occlusion and reperfusion.

OBJECTIVE: The aim of this study was to assess the in vivo structural and functional remodeling of pial arteriolar networks in the ischemic area of rats submitted to transient middle cerebral artery occlusion (MCAO) and different time intervals of reperfusion. METHODS AND RESULTS: Two closed cranial windows were implanted above the left and right parietal cortex to observe pial microcirculation by fluorescence microscopy. The geometric characteristics of pial arteriolar networks, permeability increase, leukocyte adhesion and capillary density were analyzed after 1 h or 1, 7, 14 or 28 days of reperfusion. MCAO and 1-hour reperfusion caused marked microvascular changes in pial networks. The necrotic core was devoid of vessels, while the penumbra area presented a few arterioles, capillaries and venules with severe neuronal damage. Penumbra microvascular permeability and leukocyte adhesion were pronounced. At 7 days of reperfusion, new pial arterioles were organized in anastomotic vessels, overlapping the ischemic core and in penetrating pial arterioles. Vascular remodeling caused different arteriolar rearrangement up to 28 days of reperfusion and animals gradually regained their motor and sensory functions. CONCLUSIONS: Transient MCAO-induced pial-network remodeling is characterized by arteriolar anastomotic arcades. Remodeling mechanisms appear to be accompanied by an increased expression of nitric oxide synthases.

Dobutamine stress: effects on regional myocardial blood flow and wall motion.

OBJECTIVES: This investigation studied the relation between regional myocardial blood flow and left ventricular function during dobutamine stress in patients with coronary artery disease. BACKGROUND: Dobutamine stress is becoming more frequently used as an alternative to dynamic exercise in patients with ischemic heart disease. METHODS: We studied 12 patients with coronary artery disease. Dobutamine was infused from 5 micrograms/kg body weight per min up to 40 micrograms/kg per min or until chest pain or other intolerable side effects. Regional myocardial blood flow was measured with positron emission tomography and oxygen-15-labeled water. Regional wall motion was assessed in three short-axis slices by magnetic resonance imaging. Each slice was subdivided into four regions: septal, anterior, lateral and inferior. A total of 140 regions were suitable for comparison. RESULTS: During stress, new wall motion abnormalities developed in 27 regions. Myocardial blood flow (mean +/- SD) increased in 113 regions that did not develop wall motion abnormalities (0.98 +/- 0.26 [baseline] vs. 1.98 +/- 0.87 [dobutamine] ml/min per g, p < 0.001), whereas it did not change significantly in regions with stress-induced wall motion abnormalities (1.00 +/- 0.28 [baseline] vs. 1.30 +/- 0.62 [dobutamine] ml/min per g, p = NS). An absolute decrease in myocardial blood flow below the value at rest was observed in seven segments that developed wall motion abnormalities during stress. CONCLUSIONS: The normal functional response to dobutamine stress is paralleled by an increase in coronary flow, whereas mechanical dysfunction is accompanied by a blunted increase, or even a paradoxic decrease, in regional coronary flow.

Increased echodensity of myocardial wall in the diabetic heart: an ultrasound tissue characterization study.

OBJECTIVES: We sought to characterize myocardial echodensity in asymptomatic patients with insulin-dependent diabetes and normal conventional two-dimensional echocardiographic findings to determine whether ultrasound tissue characterization can detect ultrastructural changes in myocardium, such as an increase in collagen content. BACKGROUND: Fibrosis alters the acoustic properties of the heart in animals and humans, and these changes are detectable by cardiac tissue characterization with ultrasound. Early changes detected in the diabetic heart include increased interstitial collagen deposition. METHODS: Using two-dimensional echocardiography, we evaluated 26 asymptomatic patients with insulin-dependent diabetes with normal regional and global rest function, and 17 age- and gender-matched control subjects. By selection, all diabetic patients were normotensive and had negative maximal exercise stress test results to avoid the confounding effects of hypertension and coronary artery disease. Using an echocardiographic instrument implemented at the Institute of Clinical Physiology, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated back-scatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal from the myocardial wall were normalized for those from the pericardial interface and were expressed as percentages (integrated backscatter index). RESULTS: Diabetic patients showed a significant increase in myocardial echodensity both in the septum ([mean +/- SD] 36.6 +/- 8.1 vs. 23.6 +/- 4.4, p < 0.0001) and posterior wall (21.2 +/- 5.3 vs. 18.4 +/- 3.7, p < 0.001). By individual patient analysis, 17 patients exceeded the 95% confidence limits for normal myocardial echocardiographic reflectivity found in normal subjects, and only 3 had a relatively abnormal transmitral Doppler filling pattern (E/A ratio), mainly consisting of an abnormally increased late peak flow velocity (65% vs. 11%, p < 0.001). The increased myocardial intensity was similar in patients with (n = 16) and without (n = 10) noncardiac complications, such as retinopathy or nephropathy (37.5 +/- 7.9% vs. 35.0 +/- 8.3%, p = 0.35). CONCLUSIONS: Abnormally increased myocardial echodensity, possibly related to collagen deposition, can be detected in asymptomatic diabetic patients with normal rest function. Theoretically, this finding might be considered a very early preclinical alteration potentially related to subsequent development of diabetic cardiomyopathy.

Increased echodensity of transiently asynergic myocardium in humans: a novel echocardiographic sign of myocardial ischemia.

OBJECTIVES: This study was conducted to establish whether changes in myocardial texture can be observed in humans by transthoracic echocardiography during ischemic episodes of different severity and duration induced by various pathogenetic mechanisms. BACKGROUND: Increased echo-reflectivity of ischemic myocardium has been detected in experimental animals by epicardial echocardiography and by backscatter evaluation. METHODS: Transthoracic two-dimensional echocardiographic monitoring with a commercially available electronic sector scanner (2.25- or 3.5-MHz transducer) was performed during 35 episodes of transient myocardial ischemia induced by ergonovine in patients with vasospastic angina (n = 9), by dipyridamole in patients with angiographically assessed coronary artery disease (n = 11) and by balloon occlusion during coronary angioplasty (n = 15). Quantitative texture analysis of gray levels was performed off-line on digitized images during rest conditions, ischemia and the recovery phase in regions showing normal contraction at rest, obvious dyssynergy during ischemia and normal contraction in the recovery phase. In each condition, a control region with normal contraction throughout the study was also evaluated. RESULTS: Chest pain occurred in 23 of the 35 episodes; electrocardiographic (ECG) changes were present in 26 episodes, and consisted of ST segment elevation in 13, ST segment depression in 10 and pseudonormalization of a basally negative T wave in 3. The duration of ischemic episodes was 67 +/- 53 s by symptomatic criteria and 91 +/- 52 s by ECG criteria. The risk region showed an increased end-diastolic mean gray level amplitude in a.u. (arbitrary units) during ischemia (57 +/- 19) compared with rest (38 +/- 15) and recovery (38 +/- 18, p < 0.01). No significant changes were detected in the control region (rest 36 +/- 16 vs. ischemia 34 +/- 18 vs. recovery 31 +/- 13, p = NS). The percent increase in mean gray level was similar in the various types of stress employed (ergonovine, dipyridamole or angioplasty) and was not significantly correlated with either the duration of ST segment shift (r = 0.05, p = NS) or the severity of dyssynergy evaluated semiquantitatively by means of the wall motion score (r = 0.28, p = NS). In the 15 balloon occlusions performed in six patients during coronary angioplasty, the increased echoreflectivity of the risk zone was already evident during echocardiographic sampling performed after 10 +/- 4 s of occlusion (rest 35 +/- 9 vs. 53 +/- 10 a.u., p < 0.01) when no dyssynergy could be detected by quantitative wall motion analysis (percent area change by fixed center of mass reference system 31 +/- 10% at rest vs. 32 +/- 11% after 10 s of occlusion, p = NS). CONCLUSIONS: Transient short-lasting myocardial ischemia is associated with an abrupt increase in myocardial echodensity detectable by videodensitometric analysis applied to standard transthoracic echocardiographic images and is largely independent of the underlying pathogenetic mechanism (reduced blood supply or flow maldistribution with coronary stenosis). During controlled coronary occlusion, increased echodensity precedes the onset of regional dyssynergy.

111In platelet scintigraphy for the noninvasive detection of carotid plaque thrombosis.

BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. METHODS: We compared the performance of (111)In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at (111)In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Ultrasonic myocardial texture versus Doppler analysis in hypertensive heart: a preliminary study.

-Doppler-derived parameters of transmitral flow are useful indices of diastolic dysfunction in the hypertensive heart. Different degrees of myocardial involvement in hypertensive heart can be detected by videodensitometric myocardial textural analysis. The aim of this study was to compare Doppler-derived and ultrasonic videodensitometric parameters in the differentiation of healthy hearts from hypertensive hearts. We compared a group of age-matched (59+/-9 years) male essential hypertensive patients (n=53) with normotensive healthy subjects as controls (n=32). All subjects provided ambulatory blood pressure measurements for the evaluation of 24-hour mean systolic and diastolic blood pressure. A transmitral flow Doppler analysis was performed on all subjects. A quantitative analysis of the echocardiographic digitized imaging was performed with the help of a calibrated digitization system to calculate the septum and the posterior wall textural parameters. The myocardial mean gray level (MGL) was calculated to derive the cyclic variation index (CVI): (MGLend-diastolic-MGLend-systolic)/MGLend-diastolic x100. When compared with controls, the hypertensive patients showed a significantly lower CVI for both septum (-11.1+/-26.8% versus 34. 7+/-16.3%; P<0.001) and posterior wall (-11.2+/-27.6% versus 38. 2+/-15.4%; P<0.001). Individual analyses for the ratio of peak transmitral flow velocity in early diastole to the peak transmitral flow velocity in late diastole showed that only 24% of the patients (13/53) were discriminated from normal subjects by this parameter. Individual analyses for CVI, however, at both septum and posterior wall levels, showed that 74% of the patients (39/53) were discriminated from normal subjects by this second parameter. In comparison with Doppler-derived indices of diastolic filling, the videodensitometric parameters showed a significantly higher ability to discriminate between hypertensive subjects and normal controls.

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.

A videodensitometric study of transmural heterogeneity of cyclic echo amplitude variation in human myocardium.

The aims of this study were: (1) to assess whether variations in cyclic echo amplitude might be detected across the human myocardium by videodensitometric analysis of images obtained with epicardial echocardiography; and (2) to explore the possible relation between cyclic gray level variation and left ventricular (LV) hypertrophy and function. Experimental studies show that transmural differences in contractile performance across the normal myocardium are paralleled by differences in the cyclic (diastolic-to-systolic) variation of myocardial echo amplitude. Thirty-three patients (aged 60 +/- 11 years) undergoing cardiac surgery were studied by intraoperative epicardial echocardiography. LV mass index as normal (<110 g/m2 in women, <131 g/m2 in men) in 10 patients and increased in 22. Two-dimensional echocardiographic images were obtained with a 5 MHz transducer and digitized off-line. Videodensitometric analysis was performed at end-diastole and end-systole with regions of interest across the septal and posterior wall. The cyclic variation was more pronounced in the left than in the right septal subendocardium (31% +/- 14% vs 16% +/- 14% <0.01) and higher in the subendocardial than in the subepicardial layer of the posterior wall (30% +/- 21% vs 23 +/- 18%, p <0.01). Cyclic variation of the left septal subendocardium was higher in 11 patients with nonhypertrophic ventricles than in 22 with hypertrophic left ventricles (42% +/- 15% vs 27% +/- 12%; p <0.01). The percent cyclic variation of the left septal subendocardium appeared to be much more tightly related to percent systolic thickening in patients with eccentric LV hypertrophy (r=0.80 p <0.01) than in patients with concentric LV hypertrophy (r=0.27, p=0.9) or normal LV mass (r=0.43, p=0.2). A cyclic gray level variation can be consistently detected in different human myocardial regions and layers. It is more obvious in the subendocardial than in the subepicardial layer, and in nonhypertrophic than hypertrophic ventricles. The cyclic subendocardial variation is tightly related to regional systolic thickening in patients with eccentric LV hypertrophy.

Increased myocardial ultrasonic reflectivity is associated with extreme hypertensive left ventricular hypertrophy: a tissue characterization study in humans.

We assessed myocardial reflectivity pattern in a large spectrum of left ventricular mass values, covering the extremes from absent to severe myocardial hypertensive hypertrophy. Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to the morphometrically evaluated collagen content in humans. We enrolled 88 essential hypertensives. With an echo prototype implemented in our Institute, integrated values of the radiofrequency signal of myocardial walls were obtained and normalized for those of the pericardium (Integrated Backscatter Index, IBI, %). Left ventricular mass index (LVMI) was measured by Devereux formula. There was a weak correlation between septal IBI and LVMI (r = 0.35; P < .001). On the basis of LVMI values, three groups of hypertensives were identified, with absent (Group I, n = 23; LVMI < 125 g/m2), mild to moderate (Group II, n = 44; LVMI from 125 to 174 g/m2), or severe (Group III, n = 21; LVMI > 175 g/m2) left ventricular hypertrophy. The Integrated Backscatter Index in the septum was lower in patients of Group I (IBI = 23.3% +/- 3.6%) and II (IBI = 26.5 +/- 7.6; P = NS v Group I), in comparison with patients of Group III (IBI = 31.1 +/- 5.9; P < .02 v II; P < .0001 v I). An increased myocardial wall reflectivity is detectable only in the presence of extreme forms of hypertensive left ventricular hypertrophy.

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.

Can insulin action induce myocardial texture alterations in essential hypertension?

The prevalence of hyperinsulinemia/insulin resistance in hypertensive individuals, as well as the effects of insulin on myocytic and fibroblastic growth, are well known in both epidemiologic and animal models. To check whether there are any links between ultrasonic myocardial texture parameters and insulin level in essential hypertensives, we compared 18 essential hypertensive men (Group 1, H) with 18 age- and gender-matched healthy controls (Group 2, C) (age, 57 +/- 10 years). For all study subjects we performed ambulatory blood pressure monitoring (ABPM); conventional 2-D Doppler echocardiography for the assessment of the left ventricular mass index (LVMi) and function; quantitative analysis of digitized echocardiographic images for evaluation of cyclic variation (CVI) of mean gray level (MGL) at the septum and posterior wall levels; and 75-g 3-h oral glucose tolerance test (OGTT) for analysis of area under glycemic curve (AUGC, g/min/dL) and insulinemic curve (AUIC, mU/min/mL), as well as serum glucose and insulin peaks. Both the daily mean blood pressure (H: 109 +/- 4.6 v C: 94.6 +/- 4.6, P < .0001) and LVMi (adjusted for body surface) (H: 133 +/- 24 v C: 97 +/- 21 g/m2, P < .0001) were significantly higher in hypertensives. Values for AUIC were significantly higher in hypertensives (10.37 +/- 5.53 v 6.33 +/- 5.28), P < .032); CVI was also significantly higher in group C, for both septum (C: 40.2 +/- 16.9 v H: 15.9 +/- 18.1, P < .0001) and posterior wall (C: 44.5 +/- 19.6 v H: 20 +/- 17.5; P < .0001). There was a significant inverse correlation between AUIC and CVI for both septum (r: -0.57, P < .001) and posterior wall (r: -0.50, P < .002). The significantly higher impairment of myocardial ultrasonic texture and the higher level of the AUIC insulinemia in hypertensives, as well as the significant inverse relationship between CVI and hyperinsulinemia, are our major findings. Hyperinsulinemia/insulin resistance could cause an altered collagen/muscular ratio, which could potentially explain, at least in part, the CVI alterations detected in hypertensive patients.

Cardiac cycle-dependent gray-level variation is not distorted by abnormal septal motion after cardiac surgery: a transesophageal videodensitometric study in humans.

Variation in cyclic (systolic-to-diastolic) echodensity has been demonstrated to be a reliable index of preserved myocardial function. Paradoxic septal motion can be observed frequently after cardiac surgery in the absence of any functional impairment. The aim of the study was to evaluate whether regional cycle-dependent gray-level variation in the septum is affected by abnormal septal motion after cardiac surgery. Ten patients undergoing cardiac surgery for coronary artery bypass grafting were evaluated by continuous transesophageal echocardiographic monitoring from the transgastric approach, both before and after surgery. In each patient septal motion was assessed qualitatively as normal or paradoxic. Images were digitized off-line and cyclic gray-level variation was measured in each patient by means of dedicated software. By selection, all patients exhibited normal septal motion and thickening at baseline. After surgery, five patients showed a paradoxic septal motion (group I), whereas in the remaining five patients (group II) septal motion remained normal. Percent area change, measured with the floating center-of-mass reference system, was similar in the two groups both before (I = 42% +/- 7% versus II = 44% +/- 13%; difference not significant) and after surgery (I = 39% +/- 8% versus II = 40% +/- 1%; difference not significant). Cyclic gray-level variation was also similar in the two groups, both at baseline (group I = 61% +/- 16% versus group II = 68% +/- 18%; difference not significant) and after surgery (50% +/- 13% versus 57% +/- 16%; difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased myocardial echo density in left ventricular pressure and volume overload in human aortic valvular disease: an ultrasonic tissue characterization study.

Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to morphometrically evaluated collagen in human beings. Our objective was to assess myocardial reflectivity pattern of patients with severe left ventricular hypertrophy caused by either aortic stenosis (AS) or aortic regurgitation (AR). Ten patients with AS, 10 patients with AR, and 10 closely age- and gender-matched healthy controls were studied by two-dimensional Doppler echocardiography. By using an echocardiographic prototype, we performed a radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall (integrated backscatter index: IBI, expressed in percentage). All patients with stenosis or aortic insufficiency showed a normal regional and global resting systolic function (fractional shortening: AS = 36.0 +/- 6.6 versus AR = 40.3 +/- 6.2 versus control = 40.2 +/- 8.7; p = not significant [NS]) Left ventricular mass index (Devereux's formula) was markedly increased in patients with stenosis or aortic insufficiency (AS = 199.3 +/- 18 versus AR = 208.8 +/- 60 versus control = 97.3 +/- 11 g/m2; p < 0.0001). Myocardial echo density was increased in patients with stenosis or aortic insufficiency in comparison with controls, both in the septum (IBI%: AR = 40.7 +/- 7.9 versus AS = 33.4 +/- 4.2 versus control = 23.0 +/- 6.2; p < 0.0001) and in the posterior wall (IBI%: AR = 27.1 +/- 4.3 versus AS = 23.0 +/- 2.6 versus control = 15.0 +/- 4.2; p < 0.0001). No significant correlations were found between septal and posterior wall IBI and their thickness. Abnormally increased myocardial echo density--possibly related to disproportionate collagen deposition--can be detected in patients with pressure or volume overload caused by aortic valve disease and without overt systolic dysfunction.

The clinical value of blunting of cyclic gray level variation for the detection of acute cardiac rejection: a two-dimensional, Doppler, and videodensitometric ultrasound study.

Aims of this study were to assess (1) whether videodensitometric analysis of myocardial gray-level variation can distinguish normal from rejecting transplanted hearts in a clinical setting and (2) whether this sign, used in combination with the other conventional two-dimensional and Doppler echocardiographic findings, might improve the accuracy of ultrasound techniques. Thirty heart transplant recipients (23 men; mean age 40 years; range 20 to 54 years) were studied in 87 different situations by endomyocardial biopsy and echocardiographic evaluation. Of the 87 situations, 37 ("rejectors") showed histologic evidence of rejection of mild (n = 17) or moderate (n = 10) severity and 50 ("nonrejectors") did not show rejection processes. Cyclic variation was decreased significantly in rejectors compared with nonrejectors in both the septum (15% +/- 10% versus 25% +/- 11%; p < 0.0001) and the posterior wall (19% +/- 10% versus 25% +/- 12%; p < 0.01). When a cutoff of 20% or greater of cyclic variation in the septal wall was taken as a positivity criterion, it yielded a 70% sensitivity and 70% specificity for identifying rejection. Sensitivity of conventional two-dimensional and Doppler echocardiographic signs was 51% and increased to 89%, increased by the videodensitometric criteria (p < 0.001). Specificity was 92% and decreased to 62% with videodensitometric criteria (p < 0.001). Overall diagnostic accuracy was 75% for conventional two-dimensional echocardiographic Doppler criteria alone and remained unchanged by the addition of videodensitometric criteria. In conclusion, blunting of cyclic gray-level variation induced by rejection is detectable with videodensitometric analysis. The clinical impact of this sign appears to be limited, because the resulting increase in sensitivity is counter-balanced by a reduced specificity compared with the currently available conventional ultrasound techniques.

Ultrasonic myocardial textural analysis in subclinical hypothyroidism.

BACKGROUND: In subclinical hypothyroidism (sHT), a condition in which impaired hormone synthesis is compensated by thyroid-stimulating hormone (TSH) hypersecretion, previous studies have suggested the presence of disturbances in left ventricular (LV) function. OBJECTIVES: Our goal was to investigate LV structure and function through the combined use of conventional Doppler echocardiography and ultrasonic videodensitometry. METHODS: We studied 16 patients with sHT (aged 32+/-12 [mean +/- SD] years) who had raised TSH levels (> 3.6 mIU/L) but normal levels of free thyroid hormones (free thyroxine [FT(4)] and free triiodothyro-nine [FT(3)]), and 16 carefully age- and sex-matched euthyroid subjects. Transmitral flow Doppler analysis and quantitative analysis of the echocardiographic digitized images were performed in all study subjects. Textural parameters of the septum and posterior wall were obtained as mean gray levels, which were then used to calculate the cyclic variation index (CVI), that is, the percent change in mean gray levels between diastole and systole. RESULTS: Patients with sHT had a significantly higher LV mass index (92 +/- 16 versus 76 +/- 16 g.m(2), P<.01) and isovolumic relaxation time corrected for heart rate (IVRTc) (2.9 +/- 0.6 versus 2.5 +/- 0.6, P<.04) than did controls. On videodensitometry, patients had lower CVIs both for the septum (-5% +/- 22% versus 33% +/- 9%, P<.0001) and the posterior wall (10% +/- 26% versus 49% +/- 18%, P<.0001). IVRTc discriminated only 25% of the patients from the controls, whereas CVI analysis correctly identified 85% of the patients with sHT (P<.002). Furthermore, CVI values were found to be significantly related to serum FT(4) and FT(3) concentrations in a direct fashion, and to serum TSH levels in an inverse fashion. CONCLUSIONS: Subclinical hypothyroidism is associated with changes in videodensitometric myocardial structure. These changes, which are not accurately detected by conventional or Doppler echocardiography, are quantitatively related to loss of thyroid function and could represent an early sign of myocardial damage in hypothyroidism.

Detection of perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis by intravenous administration of the echo-enhancing agent BR1.

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.

Coronary microcirculation into different models of left ventricular hypertrophy-hypertensive and athlete's heart: a contrast echocardiographic study.

The study was carried out in two different models of left ventricular hypertrophy: athlete's heart and essential arterial hypertension. Three groups of strictly age-matched males were studied: one group of 10 young adult untreated essential hypertensive patients (H), a second group of 10 athletes (A), and a group of 10 healthy individuals as controls (C). A Sonos 5500 echograph with S4 harmonic transducer was used with Levovist (ultrasonic tracer) before and after dipyridamole injection; digitised images of quantitative myocardial contrast echocardiography were collected with Power Harmonic Doppler. Angio images were analysed using dedicated PC software by placing a region-of-interest on the septum. Peak intensity, half-time (HT), the area under the curve of appearance and disappearance of microbubbles at 2/3 of PI, both in absolute and indexed values (/LVMi), were sampled. The per cent increase of PI after dipyridamole was significantly higher in C (+73%, P < 0.01) than in H (+31%) and in A (+33%) (P < 0.05). The area of appearance was significantly lower in H in comparison with C and A, both at rest and after vasodilatation. The disappearance area after dipyridamole was significantly higher in C and in A (+124%) than in H (+104%) (P < 0.05). Some hypothesis could be made: an impairment in the coronary microcirculatory function in hypertensive patients could be because of an in-crease in the arteriolar resistance. Angiogenesis and several different functional adaptations are the mechanisms that allow an optimal distribution of oxygen and of substrates to the hypertrophied myocardium of the athletes.

Ultrasonic myocardial textural parameters and midwall left ventricular mechanics in essential arterial hypertension.

BACKGROUND: The evaluation of the systolic left ventricular performance in hypertensive patients presents some problems related to left ventricular hypertrophy (LVH) which alters the ventricular geometry. The videodensitometric textural ultrasonic analysis of hypertensive myocardium has provided evidence of impairment in the cyclic variation of the mean gray level. This might be considered as an index of intrinsic myocardial function. OBJECTIVES: The aim of the present study was to analyse the connection between the midwall fractional shortening and end-systolic stress. The ultrasonic textural parameters in hypertensive patients, arranged in different groups according to the level of LVH and relative wall thickness, were also evaluated. METHODS: A group of age-matched (58 +/- 7 years) male essential hypertensive patients (n = 70) were compared to a group of normotensive and healthy subjects used as controls (n = 32). All subjects performed a conventional 2D-Doppler echocardiography to analyse the left ventricular performance. A quantitative analysis of the echocardiographic digitised imaging was also carried out with the help of a calibrated digitization system in order to calculate the septum and the posterior wall textural parameters. The myocardial mean gray level was calculated to derive the cyclic variation index (CVI). RESULTS: When subjected to a higher meridional end-systolic stress, the hypertensive patients showed a significantly lower midwall fractional shortening than the control patients. The CVI was also significantly lower in the hypertensives group, both for the septum wall (-16.3 +/- 22.8 vs34.7 +/- 15.3%; P < 0.001) and the posterior wall (-5.2 +/- 23.6 vs 38.2 +/- 15.4%; P < 0.001). A significant correlation was found between the midwall fractional shortening (MFS) and the textural parameters, and between these two variables and the end-systolic stress. CONCLUSION: The CVI was found to be a highly sensitive parameter in the identification of abnormal echodensity in essential hypertension. The CVI was significantly lower in patients with concentric hypertrophy in comparison with other left ventricular geometric models. This parameter could be considered as an index of the intrinsic myocardial function, being related, in essential hypertension, to midwall fractional shortening and to end-systolic stress. Journal of Human Hypertension (2000) 14, 9-16.

The potential prognostic value of ultrasonic characterization (videodensitometry) of myocardial tissue in essential arterial hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) and the geometric shape of the left ventricle are well-established important risk factors for cardiovascular morbidity and mortality in the hypertensive population. Videodensitometry is an alternate echocardiographic approach to the study of myocardial structural and functional alterations in essential hypertension. OBJECTIVES: To analyze the behavior of the ultrasonic videodensitometric parameter for various subgroups of a hypertensive population; first according to the severity of LVH (group A, without LVH; group B, with mild-to-moderate LVH; and group C, with severe LVH) and second according to geometric adaptation of left ventricle to pressure-volume overload of essential hypertension (group NG, normal geometry; group CR, concentric remodeling; group CH, concentric hypertrophy; and group EH, eccentric hypertrophy). METHODS: For 70 male, essential hypertensive patients and 32 normotensive healthy subjects matched for age (58 +/- 7 years) and sex as controls (group N) we performed ambulatory blood pressure measurements for the evaluation of 24 h mean systolic and diastolic blood pressures, conventional two-dimensional Doppler echocardiography to evaluate left ventricular performance and left ventricular mass index, and digitization of left ventricular parasternal long-axis echocardiographic images. For regions of interest selected within the septum and the posterior wall, the mean gray levels were calculated at end-systole and end-diastole. The resulting values were used to estimate the percentage cyclic variation index (CVI). RESULTS: The results according to left ventricular mass index were CVI for septum group N 34.7 + 16.3%; group A - 0.18 +/- 16%, group B - 13 +/- 19%, and group C - 22 +/- 12% (P < 0.001); and CVI of posterior wall, group N 38.2 +/- 15.4%, group A -0.75 +/- 16%, group B -16 +/- 16% and group C -16 +/- 13% (P< 0.001). According to left ventricular geometry CVI for septum were group NG 0.6 +/- 24%, group CR 1.9 +/- 17%; group CH - 25.4 +/- 18%, and group EH -17.1 +/- 20% (P < 0.01). CVI of posterior wall were group NH -5.8 + 24%, group CR 6.4 +/- 23%, group CH -29 +/- 20%, group EH -20 +/- 21 (P < 0.01). CONCLUSIONS: Our results demonstrate that subjects with high left ventricular masses and those with concentric hypertrophy, which have the worst prognostic impacts, have the most significant changes in CVI. Furthermore, videodensitometric findings are quite different even among the subgroups with mild-to-moderate left ventricular hypertrophy and eccentric hypertrophy. Therefore this videodensitometric approach could provide some useful information for better definition of cardiovascular risk in hypertension.