Marco Paterni

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.

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.

Body Composition and Common Carotid Artery Remodeling in a Healthy Population

CONTEXT An independent association between obesity and preclinical carotid atherosclerosis has been demonstrated, however, the pathophysiological links were not clearly established. Body composition (BC) influences systemic hemodynamics and may participate in the remodeling of common carotid artery (CCA), independently of risk factors. OBJECTIVE This study evaluated the association between CCA structure and BC in a large population of healthy subjects. DESIGN This was a cross-sectional study. SETTINGS The study was conducted at 19 European centers. SUBJECTS The study included 627 healthy subjects (252 men, age 30-60 yr, body mass index 17-40 kg/m2). MAIN OUTCOME MEASURES CCA luminal diameter and intima-media thickness were measured on digitized ultrasound images. Acoustic properties of CCA wall were evaluated by digital densitometric analysis and described in terms of mean gray level. BC was assessed by electrical bioimpedance. Insulin sensitivity (euglycemic hyperinsulinemic clamp) and plasma adiponectin levels were measured. Associations between CCA structure, age, BC, and metabolic and atherosclerotic risk factors were analyzed by multivariate regression models. RESULTS Independent factors affecting CCA diameter were fat-free mass and waist girth (standardized r = 0.44 and 0.12; P < 0.01 and < 0.0001; R2 = 0.35); independent correlates of intima-media thickness were age, CCA diameter, systolic blood pressure, and low-density lipoprotein-cholesterol (standardized r = 0.39, 0.25, 0.10, and 0.14; P < 0.005-0.0001; R2 = 0.40). The mean gray level of carotid wall was independently associated with age and waist girth (standardized r = 0.23 and 0.12; P < 0.0001 and = 0.001; R2 = 0.30). CONCLUSIONS Findings of this cross-sectional study suggest that BC modulates CCA diameter, and may induce adaptive changes in carotid wall thickness, independently of metabolic and atherosclerotic factors. Central adiposity modifies the acoustic properties of carotid wall.

The First Absolute Central Moment in Low-Level Image Processing

The first absolute central moment is a statistical filter which measures the variability of the gray levels of an image with respect to the local mean. The analysis of the responses of the central and absolute central moments at noiseless isolated step discontinuities shows how the first absolute central moment can be usefull in enhancing these discontinuities. Moreover, experimental results show how a nonstandard form of the absolute central moment should be used to enhance other image key points. At noiseless step discontinuities, the first absolute central moment provides a ridge map similar to the one provided by the GoG magnitude. However, unlike the GoG magnitude, a nonstandard form of the first absolute central moment provides ridges at both edges and lines (pulse functions 1 pixel wide) and gives rise to local extrema of the ridges at line endings, corners, and intersections among different discontinuities. The analysis of the filter output in the presence of additive noise also shows that a generalized form of the first absolute central moment should be used to cope with noise properly. Both theoretical and experimental results show that, if right configurations of the generalized first absolute central moment are used, the filter retains most of its properties when real images are considered. Moreover, since the generalization of the original filter gives rise to a class of nonlinear filters, the recovered edge information can be also usefully combined; two examples are illustrated in this paper. The first one shows how to obtain the zero-crossing map of an equivalent DoG filter, whereas the second one shows how to obtain a local thresholding procedure.

Habitual Physical Activity and Vascular Aging in a Young to Middle-Age Population at Low Cardiovascular Risk

Background and Purpose— Regular endurance exercise has been shown to reduce the age-related increase in arterial stiffness that is thought to contribute to cardiovascular risk. The aim of this study was to evaluate the influence of age and habitual physical activity on carotid artery wall thickness and stiffness in a population of young to middle-age subjects at low cardiovascular risk. Methods— The study population consisted of 432 healthy subjects (166 men; mean±SD age, 43±8 years; range, 30 to 60 years) free of carotid atherosclerosis and with low coronary heart disease risk, as determined by the Framingham prediction score sheet. All subjects underwent B-mode ultrasonography of the extracranial carotid arteries and physical activity assessment by actigraph, an accelerometer capable of monitoring the intensity and duration of body movements. The intima-media thickness of the common carotid artery was measured on ultrasound images, along with systodiastolic changes in luminal diameter, and indices of carotid stiffness were calculated. Results— Intima-media thickness and carotid stiffness increased with age in both men and women (r=0.24 to 0.52, P<0.001). The magnitude of objectively assessed daily physical activity was negatively related to indices of carotid stiffness (r from −0.20 to −0.25, P<0.001) but not to intima-media thickness. In multivariate regression analyses that included several cardiovascular risk factors such as obesity, blood pressure, plasma lipids, and smoking habits, age and physical activity were independently related to carotid stiffness. Conclusions— This study provides cross-sectional evidence that habitual physical activity is inversely related to the age-dependent increase in carotid wall stiffness in a young to middle-age population at low risk.

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.

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.

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 111In-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 111In-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.

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease

BackgroundStress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities.MethodsIn a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy).ResultsWe expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios.ConclusionsThe study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.