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Background: Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage., Methods: We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them., Results: In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters., Conclusions: Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population., Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period., Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk., Competing Interests: Declaration of interests M.G.I. has received research support, paid to Northwestern University, from AiCuris, GlaxoSmithKline Janssen, and Shire. M.G.I. is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins. M.G.I. is a paid member of the data and safety monitoring boards (DSMBs) of CSL Berhring, Janssen, Merck, SAB Biotherapeutics, Sequiris, and Takeda. J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences and is a paid consultant for Merck., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aim: A certain degree of impaired kidney function is related to an increased cardiovascular risk. The cardiovascular protection exerted in the postmenopausal state by the hormone replacement therapy (HRT) is debated. No studies have so far explored the relationship between menopause, renal function and cardiovascular risk profile in healthy menopausal women in relation with HRT., Subjects and Methods: A total of 362 postmenopausal healthy women with normal albumin excretion rate were recruited and divided into two groups (HRT+ and HRT-) according to the presence or absence of HRT. All participants underwent a complete routine biochemical analyses and an echocardiogram., Results: Clinical characteristics of the two groups were similar, but HRT+ showed a significantly higher estimated glomerular filtration rate (GFR; by CKD-EPI formula). Regarding the heart ultrasonography, HRT+ had a significantly lower size of the aortic root and left atrium diameter (p = 0.038 and p = 0.012, respectively); no differences were found in the ejection fraction and Left Ventricular Mass Index (LVMI). In the whole study group, eGFR correlated inversely with LVMI and with the size of the aortic root (both p < 0.0001), being GFR the only determinant of the former by a stepwise regression. Dividing the study population according to an eGFR cut-off (> 80 and < 80 ml/min/1.73 m(2)); > 80 women, in comparison with < 80, showed a significantly lower LVMI and lower size of aortic bulb, further reduced in the HRT+., Conclusion: In a cohort of healthy, drug-naïve, postmenopausal women, HRT seems to positively affect glomerular filtration and is associated with lower values of left ventricular mass and aortic root size, thus offering a further mechanism through female hormones exert cardioprotection., (© 2014 John Wiley & Sons Ltd.)

Microalbuminuria (UAE) may be considered a marker of systemic vascular dysfunction, while pulse pressure (PP) is an indicator of the stiffness of vascular conduits. Both these parameters, together with left ventricular hypertrophy (LVH), are linked to cardiovascular morbidity in hypertensive patients. The aim of this study was the analysis of the possible relationships among UAE, PP, and LVH with ultrasonic myocardial textural parameters, which are altered in hypertensives patients. A group of male (n = 70) essential hypertensive patients (mean age: 58 +/- 7 yr) was analyzed with a group of age-comparable normotensive healthy subjects as controls (n = 32). Ambulatory blood pressure monitoring (ABPM) was performed with an oscillometric monitor; UAE was measured by nephelometry. A conventional 2D-Doppler echocardiography (to analyze left ventricular mass: LVM) and a quantitative analysis of the echocardiographic digitized imaging with the use of a calibrated digitization system (to calculate the septum and the posterior wall textural parameters) were performed on all subjects. The myocardial mean gray level was calculated to derive the cyclic variation index (CVI). The CVI was significantly lower in hypertensives both for the septum (- 16.3 +/- 22.8 vs 34.7 +/- 15.3%; p < 0.001) and for the posterior wall (- 15.2 +/- 23.6 vs 38.2 +/- 15.4%; p < 0.001). A significant negative correlation was found between logUAE and the CVI of the septum (r = -0.42; p < 0.001), between the PP and the CVI of the septum (r = -0.40; p < 0.002) and between the CVI and the LVM (r = -0.38; p < 0.001). Multiple regression analysis having as dependent variable the CVI at septum level showed as significantly related independent variables: PP (p < 0.01), logUAE (p < 0.001), and LVM (p < 0.05) (multiple R: 0.76, squared multiple R: 0.57; p < 0.001). It was found that LVM, logUAE, and PP are all correlated with textural parameters, and the CVI can be considered a sensitive parameter in the identification of an abnormal myocardial texture in hypertension. A high level of arterial stiffness and the presence of vascular dysfunction in essential hypertension could participate in the determination of myocardial alterations and permit the identification of patients with the worst prognosis in terms of morbidity or mortality due to cardiovascular events.

Background: Left ventricular hypertrophy which realizes in athlete's heart could create some problems of acoustic reflection related to the increase of myocytic and not-myocytic elements of the heart. The aim of the present study was to analyze the ultrasonic backscatter myocardial indexes both as peak end-diastolic signal intensity and as its cardiac-cyclic variation in athlete's heart, compared to healthy sedentary controls., Methods: Two groups of ten subjects each, all males of mean age (31.6+/-3.5), and of comparable weight and height were analyzed: group (A) comprised ten cyclists of good professional level and group (C) included ten healthy subjects acting as controls. A 2D-color Doppler echocardiography with a digital echograph Agilent Technologies (AT) Sonos 5500 was carried out on all subjects in the study for the conventional analysis of the left ventricular mass and function. The ultrasonic myocardial integrated backscatter signal (IBS) was analyzed with an "Acoustic Densitometry" module implemented on an AT echograph. The signal was also sampled with a R.O.I. placed at interventricular septum and at posterior left ventricular wall level. The systo-diastolic variation of the backscatter was also considered as Cyclic Variation Index (CVIibs)., Results: The left ventricular mass was significantly higher in athletes in comparison with controls (LVMbs: A: 154.5+/-18.7; C: 101.4+/-12.4; p<0.001). The end diastolic IBS signal did not show significant statistical differences between the two groups. The CVIibs both at septum (A: 30.5+/-5.3; C: 27.2+/-7.3; p<0.002) and posterior wall level (A: 43.7+/-9.1; C: 40.7+/-9.1; p<0.001) though was comparable in both groups., Conclusion: The conclusions reached in the present study confirmed the physiology of the left ventricular hypertrophy of the athlete's heart evaluated with an ultrasonic integrated backscatter tissue characterization, in particular through the cyclic variation of integrated backscatter myocardial signal. This finding is probably the expression of a preserved intramural myocardial function in the athlete's heart despite the increase of left ventricular mass induced by physical training.

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.

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.

Objective: To test the hypothesis that quantitative analysis of two-dimensional echocardiographic gray-level distributions could allow one to detect the early changes in acoustic properties of human diabetes myocardium differentiating it from normal myocardium., Methods: We evaluated, by two-dimensional echocardiography, 28 asymptomatic type 1 insulin-dependent diabetic patients with normal ventricular function (group A) and 15 age- and sex-matched healthy controls (group B). By selection, all of the diabetics were normotensive and had a negative maximal exercise stress. Echocardiographic images were digitized by using a calibrated digitization system. Quantitative texture analysis was accomplished on data from the septum and posterior wall both at end-diastole and at end-systole. The following parameters were obtained: the mean gray level of the regions of interest, and its absolute SD, skewness, kurtosis, and cyclic variation index., Results: The main result of this study was that the cyclic variation indices of the echo amplitudes of the septum and posterior wall in the diabetic group were significantly lower than those in controls (P < 0.001 and P < 0.002, respectively). Furthermore, the diabetic group had a significantly higher mean gray level of the septum [group A 54.3 +/- 22.5 (mean +/- SD) versus group B 39.7 +/- 9.8, P < 0.03] at end-diastole. The mean gray-level of the posterior wall was similar in the two groups, both at end-diastole and at end-systole., Conclusion: Alterations of cyclic echo amplitude (possibly related to collagen deposition) can be detected in asymptomatic diabetic patients with normal resting function. Theoretically, this finding might be considered an early preclinical alteration, potentially related to subsequent development of "diabetic cardiomyopathy'.

Aim of this work was to study in a group of elite cyclists, undergoing laboratory testing, the trend of the left ventricular systolic and diastolic function, echocardiographically and Doppler derived, simultaneously with the evaluation of ergospirometric parameters during maximal exercise. We studied a group of male subjects, consisting of 10 professional elite bicyclists (mean age: 25.1 +/- 3.2 years) during competitive activity (VO2/kg max: 78.5 +/- 7.7 ml.kg.min-1). The maximal exercise test, conducted with Wind Loaded Simulator for optimisation of ergometric capacity, showed, at the end of exercise, at a speed of 49.2 +/- 2.4 km/h, a VO2max of 5365 +/- 543.4 ml/min, with a calculated Cardiac Output (CO) of 19.3 +/- 3.7 l/min. A linear regression relationship was found between VO2max and CO (r = 0.84; p < 0.0001) as well as between VO2max and maximal reached speed (r = 0.97; p < 0.0001). During the aerobic period a slight but significant increase in End Diastolic Volume (EDV) was observed due to the greater venous return from exercising muscles. At stop, in anaerobic period, the EDV remained substantially constant. Ejection Fraction (EF) also increased during exercise through the Frank-Starling mechanism activation. The slight, but not significant, increase in EF at stop level may be explained by an activation of homeometric control of contractility with a sympathetic modulation on myocardial fibres. The early diastolic mitral flow velocity (Peak E) increased significantly during exercise, in comparison with basal upright values. The left ventricular diastolic compliance observed in athletes permits a good left ventricular filling, particularly in early diastolic phase; this allows an excellent left ventricular systolic performance. Based on echocardiography and pulsed Doppler measurements, calculated cardiac output is underestimated by approximately 20%.

Young elite athletes often show left ventricular hypertrophy, but normal values of quantitatively evaluated myocardial wall reflectivity. The aim of this study is to assess the acoustic pattern of ventricular wall reflectivity, as well as of systolic and diastolic function, in older endurance runners with increased left ventricular mass. For this purpose, 12 elite, senior isotonic athletes in full training and 11 normal, age-matched controls with sedentary life styles were studied. The following parameters were measured with a commercially available 2D echo-Doppler machine: end-diastolic diameter, diastolic septum thickness, left ventricular mass index, ejection fraction (by Teicholtz rule); peak E, peak A, E/A ratio, acceleration and deceleration time of mitral inflow velocity and isovolumic relaxation time. On-line radio frequency analysis was also performed to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signals were normalized for the pericardial interface and expressed in percent (% 2D-IB). In spite of the greater left ventricular mass in athletes versus normal controls (319 +/- 81 vs 225 +/- 63 g.m-2, P < 0.0005), there were no significant intergroup differences as regards end-diastolic diameter (50.7 +/- 5.1 vs 48.1 +/- 5.2 mm, P = ns), ejection fraction (75.5 +/- 9.3 vs 71.8 +/- 9.1%, P = ns), and 2D-IB of septum (22.2 +/- 6.9 vs 22.4 +/- 7.0, P = ns) and posterior wall (12.5 +/- 5.6 vs 13.1 +/- 2.8, P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Ultrasonic 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 Results: Twenty-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 less than 0.01) and posterior wall (9 +/- 1, 12 +/- 2, and 12 +/- 1 mm, respectively; p less than 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%, respectively) than in athletes (21 +/- 7% and 10 +/- 3%, respectively; p less than 0.01 for both)., Conclusions: We 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.

Fractional shortening/end-systolic stress (FS/ESS) correlation by echocardiography is a reliable index of left ventricular function. Acetate infusion or preload reduction due to water compartment re-equilibrium may induce ventricular derangements during dialytic treatment. In 13 patients on lactate haemofiltration (LHF) (mean age 56.8 +/- 11.9 years on regular dialytic treatment (RDT) for 75.3 +/- 56.5 months) and in seven patients on acetate haemodialysis (AHD) (mean age 48 +/- 10.7 years; on RDT for 43.9 +/- 49.2 months) fractional shortening/end-systolic stress was evaluated before and after single dialytic session. The following biochemical parameters were also studied: haematocrit (Htc), plasmatic osmolarity, ionised Ca, Na, K, and blood gases. In both groups the mean fractional shortening/end-systolic stress correlation maintained the same correlation coefficient before and after treatment (r = -0.68, P less than 0.001). Lactate haemofiltration and acetate haemodialysis by reducing the volume expansion and preload (mean interdialytic body-weight increase 2.5 +/- 0.8 kg in our patients), may decrease left ventricular contractility (Starling's law). Furthermore, acetate was postulated as a myocardial depressant. Dialysis-induced myocardial contractility variations plotted against fractional shortening/end-systolic stress correlation allowed the division of our patients into four different groups: (1) patients with increased fractional shortening and reduced end-systolic stress; (2) patients with unchanged fractional shortening and reduced end-systolic stress; (3) patients with reduced fractional shortening and increased end-systolic stress; and (4) patients with reduced fractional shortening and unchanged or reduced end-systolic stress. These groups include patients treated with either lactate haemofiltration or acetate haemodialysis. Our data cannot confirm the postulated acetate myocardial depressant activity.(ABSTRACT TRUNCATED AT 250 WORDS)