Left Ventricular Diastolic Posterior Wall Research Articles

Association between the atherogenic index of plasma and left ventricular hypertrophy in patients with obstructive sleep apnea: a retrospective cross-sectional study

BackgroundThe atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients.MethodsThis retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C).ResultsCompared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P < 0.05). Furthermore, AIP was independently associated with LVMIh2.7 according to multivariate linear regression model (β = 0.125, P = 0.001). Notably, AIP remained independently associated with an elevated risk of LVH [odds ratio (OR) = 1.317 per 1 standard deviation (SD) increment, 95% confidence interval (CI): 1.058 - 1.639, P = 0.014) and concentric LVH (OR = 1.545 per 1 SD increment, 95% CI: 1.173 - 2.035, P = 0.002) after fully adjusting for all confounding risk factors by multivariate logistic regression analyses.ConclusionsAIP was independently associated with an increased risk of LVH and concentric LVH in OSA patients. Therefore, AIP, as a practical and cost-effective test, might be useful in monitoring hypertrophic remodeling of the heart and improving CVDs risk stratification in clinical management of OSA.

Evaluation of cardiac function in paediatric Wilson's disease patients with advanced echocardiographic modalities (strain and strain rate echocardiography).

In Wilson's disease (WD), copper accumulation in the organs and/or damage caused by oxygen free radicals occurs due to disturbances in copper excretion. In our study, we aimed to evaluate cardiac involvement with advanced echocardiographic modalities (tissue Doppler echocardiography, strain and strain-rate echocardiography). Twenty WD patients and 20 healthy children from the Pediatric Gastroenterology Department of Diyarbakır Children's Hospital were included in the study between 2022 and 2023. The mean age of the WD patients was 12.89 ± 3.79 years. Left ventricular wall thicknesses and diameters (diastolic interventricular septum thickness, diastolic left ventricular posterior wall thickness, left ventricular end-diastolic diameter), left ventricular diastolic function parameters (E, A, E/A, deceleration time) and left ventricular ejection fraction and tricuspid annular plane systolic excursion were similar and not statistically significantly different in the WD and control groups. Mitral lateral e', mitral septal e' and tricuspid lateral e' velocities were lower in the WD patients and statistically significantly different from the controls (p = 0.02, 0.04 and 0.005, respectively), as assessed by tissue Doppler echocardiography. Global longitudinal systolic strain was similar in the WD and control groups and no statistically significant difference was detected. Longitudinal early diastolic strain rate was lower in the WD patients and statistically significantly different (p = 0.002). Subclinical early diastolic dysfunction and segmental systolic dysfunction were detected in WD patients with advanced echocardiographic modalities, in addition to normal cardiac function as assessed by conventional echocardiography. Advanced echocardiographic modalities can be used in the follow up of WD patients.

Natural history of cardiac findings in mucopolysaccharidosis type I: report from an international registry.

Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler-Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry. Interrogation of echocardiography data (presence of cardiac valve regurgitation and/or stenosis; measurements of left ventricular chamber dimensions in diastole and systole, diastolic left ventricular posterior wall and interventricular septal thicknesses and ventricular systolic function (shortening fraction)) showed that mitral regurgitation was the most common and earliest finding for individuals with both severe (58.3%, median age 1.2 years) and attenuated (74.2%, median age 8.0 years) disease. Left-sided valve stenosis was also common in individuals with attenuated disease (mitral 30.3%; aortic 25%). Abnormal ventricular wall and septal thickness (Z-scores ≥2) were observed early in both phenotypes. Z-scores for diastolic left ventricular posterior wall and interventricular septal thicknesses increased with age in the severe phenotype (annualised slopes of 0.2777 [p = 0.037] and 0.3831 [p = 0.001], respectively); a similar correlation was not observed in the attenuated phenotype (annualised slopes of -0.0401 [p = 0.069] and -0.0029 [p = 0.875], respectively). Decreased cardiac ventricular systolic function (defined as shortening fraction <28%) was uncommon but, when noted, was more frequent in infants with the severe phenotype. While cardiac abnormalities occur early in both severe and attenuated mucopolysaccharidosis type I, the pattern of valve dysfunction and progression of ventricular abnormalities vary by phenotype.

Mechanism of Kaixin Powder prescriptions Buxin Decoction regulating PI3K/AKT signaling pathway to protect cardiovascular system: based on network pharmacology and experimental verification

This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 μg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.

Heterozygous APOE ε4 carriage associates with improved myocardial efficiency in older age

Abstract Background Carriage of the ancestral APOE ε4 allele confers a risk of developing Alzheimer's and coronary artery disease, but its persistence in human populations also suggests some potential survival advantages. To date it remains unclear whether APOE ε4 carriage independently associates with a better or worse long-term cardiac phenotype. Purpose Using data from the 1946 National Survey of Health and Development (NSHD) birth cohort, we investigated whether APOE ε4 carriage associates with adverse or beneficial left ventricular (LV) size and function parameters by echocardiography in older age. Methods Based on the presence or absence of APOE ε4, genotypes were divided into: non-APOE ε4 (ε2ε2, ε2ε3, ε3ε3), heterozygous-APOE ε4 (ε2ε4 and ε3ε4) and homozygous-APOE ε4 (ε4ε4). Echocardiographic data at 60–64 years included: left ventricular ejection fraction (LV EF), E/e', systolic and diastolic LV posterior wall and interventricular septal thickness (LVPWTs/d, IVSs/d), and body-surface area indexed LV mass (LVmassi) and myocardial contraction fraction (MCFi). Generalized linear models explored associations between APOE ε4 genotypes as exposures and echocardiographic biomarkers as outcomes. As a combination of gene variants, APOE ε genotype is expected to be an instrumental variable and therefore unconfounded. Thus, Model 1 was unadjusted. To obtain more precise regression estimates, Model 2 was adjusted for factors associated with the outcome, namely sex and socio-economic position (SEP). To explore the mechanistic pathway downstream of APOE ε genotype but upstream of the echocardiographic outcomes, subsequent models were adjusted for mediators as follows: Model 3 for body mass index, Model 4 for the presence of cardiovascular disease (CVD), Model 5 for diabetes, Model 6 for high cholesterol and Model 7 for hypertension. Results 1464 participants were included. Compared to non-APOE ε4 and homozygous groups, heterozygous-APOE ε4 individuals had similar cardiac phenotypes in terms of EF, E/e', LVPWTs/d, IVSs/d and LVmassi but had a 7% higher MCFi 95% confidence interval [CI]: 1%-13%, p=0.017) which persisted even after adjustment for sex and SEP (95% CI 1%-12%, p=0.026) that was attenuated to 6% after adjustment for CVD (95% CI 0–13% p=0.050) and hypertension (95% CI 1–13% p=0.022). Conclusion The heterozygous-APOE ε4 state associates with improved myocardial shortening in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. As we found no association between APOE ε4 carriage and LVPWTs/d, IVSs/d or LVmassi, MCFi enhancement may be mediated by improved myocardial energetics and contractility, with calcium and androgens potentially implicated, rather than through pathological ventricular thickening. Although a dose relationship is normally expected with ε4 carriage, any benefit from increased energetics and contractility is likely to be counterbalances by the higher risk of CVD and cardiovascular risk factors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Medical Research Council British Heart Foundation

MicroRNA-195-5p Downregulation Inhibits Endothelial Mesenchymal Transition and Myocardial Fibrosis in Diabetic Cardiomyopathy by Targeting Smad7 and Inhibiting Transforming Growth Factor Beta 1-Smads-Snail Pathway.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus, which is associated with fibrosis and microRNAs (miRs). This study estimated the mechanism of miR-195-5p in endothelial mesenchymal transition (EndMT) and myocardial fibrosis in DCM. After the establishment of DCM rat models, miR-195-5p was silenced by miR-195-5p antagomir. The cardiac function-related indexes diastolic left ventricular anterior wall (LVAW, d), systolic LVAW (d), diastolic left ventricular posterior wall (LVPW, d), systolic LVPW (d), left ventricular ejection fraction (LVEF), and fractional shortening (FS) were measured and miR-195-5p expression in myocardial tissue was detected. Myocardial fibrosis, collagen deposition, and levels of fibrosis markers were detected. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (HG) and miR-195-5p was silenced. The levels of fibrosis proteins, endothelial markers, fibrosis markers, EndMT markers, and transforming growth factor beta 1 (TGF-β1)/Smads pathway-related proteins were measured in HUVECs. The interaction between miR-195-5p and Smad7 was verified. In vivo, miR-195-5p was highly expressed in the myocardium of DCM rats. Diastolic and systolic LVAW, diastolic and systolic LVPW were increased and LVEF and FS were decreased. Inhibition of miR-195-5p reduced cardiac dysfunction, myocardial fibrosis, collagen deposition, and EndMT, promoted CD31 and VE-cadehrin expressions, and inhibited α-SMA and vimentin expressions. In vitro, HG-induced high expression of miR-195-5p and the expression changes of endothelial markers CD31, VE-cadehrin and fibrosis markers α-SMA and vimentin were consistent with those in vivo after silencing miR-195-5p. In mechanism, miR-195-5p downregulation blocked EndMT by inhibiting TGF-β1-smads pathway. Smad7 was the direct target of miR-195-5p and silencing miR-195-5p inhibited EndMT by promoting Smad7 expression. Collectively, silencing miR-195-5p inhibits TGF-β1-smads-snail pathway by targeting Smad7, thus inhibiting EndMT and alleviating myocardial fibrosis in DCM.

Abnormalities in lysine degradation are involved in early cardiomyocyte hypertrophy development in pressure-overloaded rats

BackgroundCardiomyocyte metabolism changes before cardiac remodeling, but its role in early cardiac hypertrophy detection remains unclear. This study investigated early changes in plasma metabolomics in a pressure-overload cardiac hypertrophy model induced by transverse aortic constriction (TAC).MethodsThe TAC model was constructed by partly ligating the aortic arch. Twelve Sprague–Dawley rats were randomly divided into the TAC group (n = 6) and sham group (n = 6). Three weeks after surgery, cardiac echocardiography was performed to assess cardiac remodeling and function. Hematoxylin/eosin (HE), Masson, and wheat germ agglutinin (WGA) stains were used to observe pathological changes. Plasma metabolites were detected by UPLC-QTOFMS and Q-TOFMS. Specific metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). Metabolic pathways were characterized by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the predictive value of the screened metabolites was analyzed by receiver operating characteristic (ROC) curve analysis.ResultsThree weeks after surgery, the TAC and sham groups had similar left heart function and interventricular septum and diastolic left ventricular posterior wall thicknesses. However, on pathological examination, the cross-sectional area of cardiomyocytes and myocardial fibrosis severity were significantly elevated in TAC rats. OPLS-DA showed different metabolic patterns between the TAC and sham groups. Based on the criteria VIP > 1 and P < 0.05, 13 metabolites were screened out. KEGG analysis identified disrupted lysine degradation through the related metabolites 5-aminopentanoic acid, N6-acetyl-l-lysine, and l-lysine, with areas under the ROC curve (AUCs) of 0.917, 0.889, and 0.806, respectively, for predicting compensated cardiomyocyte hypertrophy.ConclusionDisruption of lysine degradation might be involved in early cardiac hypertrophy development, and related metabolites might be potential predictive and interventional targets for subclinical cardiomyocyte hypertrophy.

A Study of Echocardiographic Changes in Patients with Newly Diagnosed Primary Hypothyroidism: A Cross-sectional Study

Background: Hypothyroidism is known to cause reversible cardiac dysfunction in humans. Thyroid hormone alters the cardiovascular hemodynamics. This study was performed to assess echocardiographic changes in untreated newly diagnosed primary hypothyroid states as such studies are scarce in our setting.Methods: This hospital based cross-sectional study was conducted among 71 patients with newly diagnosed primary hypothyroidism who presented to the medicine outpatient department, at Universal College of Medical Sciences and Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from December 2018 to June 2020 after taking ethical clearance from institutional review committee (UCMS/IRC/212/18). Thyroid function test and echocardiography were carried out in patients under study. The data was analyzed with SPSS Version 16.Results: A total of 71 patients (52 females and 19 males) with primary hypothyroidism were enrolled for the study. Among these 58 cases were overt/clinical hypothyroidism, and 13 cases were subclinical hypothyroidism. Echocardiography was abnormal in 63.4% of cases with 43.7% showing diastolic dysfunction, 18.3% diastolic interventricular septal thickness abnormality, 8.5% diastolic left ventricular posterior wall thickness abnormality, and 8.4% pericardial effusion. Conclusion: Our study found diastolic dysfunction, diastolic interventricular septal thickness abnormality, diastolic left ventricular posterior wall thickness abnormality, and pericardial effusion as the common echocardiographic change in patients with newly diagnosed primary hypothyroidism. Therefore, our study highlights the need for cardiac evaluation of patients with primary hypothyroidism so that early intervention can be performed to improve the clinical outcome.

Ultrasonography to detect cardiovascular damage in children with essential hypertension

BackgroundEssential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography.MethodsAll patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography.ResultsThe cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups.ConclusionChildren and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Gender features of structural and functional changes of the heart and levels of copeptin and NTproBNP in patients with acute Q-myocardial infarction in the presence of pulmonary hypertension

The aim. To evaluate the gender features of structural and functional changes in the heart and levels of copeptin and NTproBNP in patients with acute myocardial infarction (AMI) with concomitant pulmonary hypertension (PH). Materials and methods. 74 patients with AMI and concomitant PH who were treated in the intensive care unit and emergency cardiology for patients with myocardial infarction of the Municipal Non-Profit Enterprise “City Hospital of Emergency and Ambulance” of Zaporizhzhia City Council were examined. The patients were divided into two groups: the first group consisted of 42 male patients (mean age 71.06 ± 2.21 years) and 32 female patients (mean age 76.41 ± 2.32 years). All the patients were examined in the first three days by two-dimensional echocardiography on a device MyLab50 (“Esaote”, Italy). The serum levels of kopeptin and NTproBNP were determined by enzyme-linked immunosorbent assay using a set of reagents Elabscience (USA). Results. There was a trend towards a predominantly anterior AMI in the group of men and lower AMI – in the group of women. Individuals with functional class III and IV heart failure predominated (76.1 %) among the men with AMI and PH. At the same time, there were significantly more persons with III and IV functional class in the group of men than in the group of women (P &lt; 0.05). There was a significant diastolic left ventricular posterior wall thickening in women compared to men (8.4 %; P &lt; 0.05) and a tendency to diastolic interventricular septal thickening in females. There was an upward trend in end-systolic and end-diastolic sizes in the group of men compared to women; however, the differences did not reach the required level of significance. Evaluation of serum copeptin and NTproBNP in patients with AMI and PH revealed significantly higher levels of these indicators in the group of men compared to women (P &lt; 0.05). Conclusions. Men with AMI and PH had more severe heart failure compared to women due to the predominance of patients with functional classes III and IV. Women with AMI and PH demonstrated predominantly concentric type of remodeling in the form of significantly thickened LV posterior wall and the tendency to increase interventricular septum wall thickness, and eccentric hypertrophy in the form of LV dilatation prevailed in men. Men with AMI and PH had significantly higher serum copeptin and NTproBNP levels compared to women.

Protective effect of sinomenine on isoproterenol-induced cardiac hypertrophy in mice.

To study the effect of sinomenine (Sin) on isoproterenol (Iso, β-agonist)-induced cardiac hypertrophy (CH), we set up four mouse groups: control, Iso model, Iso+metoprolol (Met, β blocker) 60 mg/kg and Iso+Sin 120 mg/kg. CH was induced by Iso (s.c. for 28 days) in mice, and Sin or Met were orally administered by gavage for 28 days in total. Left ventricular diastolic anterior wall thickness (LVAWd), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular ejection fraction (LVEF), and short axis shortening (FS) were measured by echocardiography. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were measured by commercial kits. Lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were measured by ELISA kits. Histological changes were observed using hematoxylin-eosin (HE) and Masson staining. Protein level of nuclear transcription factor-kappa B (NF-κB) was detected by immunohistochemistry. Compared with the control group, LVAWd, Left ventricular weight index (LVWI) and myocardial fibrosis of the Iso model group significantly increased, as well as NF-κB, LDH, MDA, TNF-α, and IL-1β levels. However, the activity of T-SOD decreased. Compared with the Iso model group, LVWI of Iso model+Sin or Iso model+Met group was improved, LVAWd, LVPWd and myocardial fibrosis decreased, and NF-κB, LDH, MDA, TNF-α and IL-1β levels decreased. T-SOD activity also increased. This study reveals that Sin inhibits the activation of NF-κB, lowers the levels of TNF-α and IL-1β, has anti-oxidative stress effect and inhibits myocardial inflammation in mouse heart, thereby demonstrating its efficacy in preventing Iso induced CH.

RARE-59. CARDIAC REMODELING IN PATIENTS WITH CHILDHOOD-ONSET CRANIOPHARYNGIOMA – RESULTS OF HIT-ENDO AND KRANIOPHARYNGEOM 2000/2007

BACKGROUNDHypothalamic obesity caused by childhood–onset craniopharyngioma results in long–term cardiovascular morbidity. Knowledge about clinical markers and risk factors is rare.PATIENTS AND METHODSA cross–sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 patients with childhood-onset adamantinomatous craniopharyngioma.RESULTSBody mass index (BMI) correlated with the thickness of interventricular septum in diastole (IVSd) (r=0.604, p<0.001) and left ventricular diastolic posterior wall in diastole (LVPWd) (r=0.460, p=0.011). Due to wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥18 years), BMI correlated with IVSd (r=0.707, p=0.003), LVPWd (r=0.592, p=0.020) and left ventricular internal diameter in diastole (LVIDd) (r=0.571, p=0.026). In the pediatric subgroup (age at study <18 years), no correlation between cardiac parameters and BMI was observed. Only LVIDd correlated with disease duration (r=0.645, p<0.001). All cardiac functions were within the normal range, indicating no association with severe functional impairments.CONCLUSIONSCardiac remodeling in patients with childhood-onset craniopharyngioma correlates with the degree of hypothalamic obesity and disease duration. However, echocardiography has limited sensitivity in craniopharyngioma patients with obesity, so cardiac magnetic resonance imaging (MRI) should be considered as an alternative diagnostic approach for patients with craniopharyngioma and hypothalamic obesity.

Influence of Vigorous Physical Activity on Structure and Function of the Cardiovascular System in Young Athletes-The MuCAYA-Study.

Objective: Moderate physical activity (PA) is associated with a reduced risk to develop cardiovascular disease. However, junior athletes exercise between 10 and 20 h a week with intensities exceeding moderate levels by far. In this regard, the cardiovascular system has to increase its work five to six times compared to moderate intensities. This may result in potentially pathological adaptations of the cardiovascular system. The underlying process of vascular adaptations to exercise is yet not fully understood and hardly investigated in junior athletes. An increased blood pressure and pulse wave velocity, ventricular hypertrophy, arrhythmia, and even sudden cardiac death (SCD) has been reported in adult athletes. Studies, examining the cardiovascular system in children, its association to intensity and type of exercise, are rare. Therefore, we present the study protocol of a prospective cross-sectional study that investigates the influence of PA on the cardiovascular system in young athletes.Methods and Design: Children and adolescents, 7–18 years, presenting for their annual pre-participation screening at the Institute of Preventive Pediatrics, Faculty of Sports and Health Sciences, Technical University of Munich (TUM), are examined in this prospective cross-sectional study. Vascular parameters measured by ultrasound are carotid intima-media thickness (cIMT), vascular stiffness (AC, Ep, β, PWV β), and the vascular diameter (D) to calculate the IMT:Diameter-Ratio (IDR). Cardiac function is evaluated by a 12-lead ECG, and echocardiographic parameters (end-diastolic left ventricular diameter, left ventricular diastolic posterior wall thickness, diastolic septal thickness, left ventricular mass and relative wall thickness, ejection fraction, and shortening fraction). A cardiopulmonary exercise test is performed on a bicycle ergometer, muscular strength is assessed with the handgrip test, and physical activity with the MoMo questionnaire.Discussion: It is essential to follow young athletes over the course of their career in order to detect pathophysiological changes in the myocardium as soon as possible. If these changes are preceded or followed by changes in vascular structure and function is not known yet. Therefore, we present the study protocol of the Munich Cardiovascular adaptations in young athletes study (MuCAYA-Study) which investigates the association between vascular and cardiac adaptation to intensive exercise in junior athletes.

Effects of uncoupling protein 2 overexpression on myocardial mitochondrial dynamics in sepsis rats

To investigate the effects of uncoupling protein 2 (UCP2) overexpression on mitochondrial dynamics (mitochondrial division and fusion) of sepsis myocardial injury in rats. Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group (Sham group) using normal saline instead of transfection and simulating cecal ligation and perforation (CLP); CLP group using normal saline instead of transfection, performing CLP to induce sepsis; adeno-associated virus (AAV) group using CLP after myocardial transfection with empty virus; UCP2 overexpression group (UCP2 group) CLP was performed 3 weeks after AAV-UCP2 (1×1015 vg/L, a total of 60 μL) myocardial transfection. The rats in each group were examined by echocardiography at 24 hours after the CLP, and then the rats were sacrificed immediately to harvest myocardial tissue. Myocardial ultrastructural changes were observed under the electron microscope, the expression of regulatory proteins related to myocardial mitochondrial dynamics [optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1)] were detected by Western Blot, and the level of mitochondrial adenosine triphosphate (ATP) production was detected by chemiluminescence. (1) The echocardiographic results showed that there was no significant difference in left ventricular mass (LVM) and stroke volume (SV). Compared with Sham group, left ventricular diastolic anterior wall thickness (LVAWd), left ventricular systolic anterior wall thickness (LVAWs), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (LVFS) were significantly increased in CLP group and AAV group, while left ventricular systolic diameter (LVEDs), left ventricular diastolic diameter (LVEDd), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased. Compared with CLP group and AAV group, LVAWs, LVEF, LVFS were significantly decreased in UCP2 group, and LVEDs, LVEDV and LVESV were significantly increased [LVAWs (mm): 3.82±0.42 vs. 4.34±0.30, 4.44±0.12; LVEF: 0.921±0.038 vs. 0.979±0.019, 0.991±0.010; LVFS: (65.33±6.56)% vs. (80.11±8.23)%, (85.31±6.11)%; LVEDs (mm): 1.81±0.36 vs. 0.89±0.54, 0.60±0.17; LVEDV (μL): 137.09±50.05 vs. 89.72±53.04, 85.42±40.99; LVESV (μL): 10.48±4.59 vs. 2.48±3.52, 2.58±2.50, all P < 0.05]. (2) Electron microscope showed that the structure of myocardial fibers in the Sham group was clear and aligned with complete intervertebral disc and mitochondrial structure, no damage to mitochondrial membranes, and tight arrangement of cristae. In CLP group and AAV group, muscle fiber breakage, sarcoplasmic reticulum expansion, severe mitochondrial swelling and even cristage structure disorder were observed. In the UCP2 group, only myocardial fiber edema was observed, and the muscle fiber structure was more complete than that of Sham group and AAV group. The mitochondria were slightly swollen and the cristae were intact. (3) Western Blot showed that there was no significant difference in the expression of Opa1 and Fis1 in the four groups. The expression of Drp1 in CLP group and AAV group were significantly higher than that in Sham group. The expression of Drp1 in UCP2 group was significantly lower than that in CLP group and AAV group (Drp1/β-actin: 1.01±0.03 vs. 1.39±0.03, 1.49±0.03, both P < 0.05). (4) The results of immunofluorescence showed that the ATP content of CLP group and AAV group were significantly lower than that of Sham group; the ATP content of UCP2 group was significantly higher than that of CLP group and AAV group (μmol/L: 1.99±0.15 vs. 1.10±0.17, 1.13±0.19, both P < 0.05). UCP2 overexpression can significantly improve the systemic systolic function of myocardium in sepsis rats, protect myocardial mitochondrial ultrastructure, inhibit mitochondrial division, and improve mitochondrial ATP synthesis.

P2508Physical exercise improves diastolic function and attenuates type III collagen myocardial accumulation in aged rats

Abstract Background Interstitial collagen matrix increase and left ventricular (LV) diastolic dysfunction are the most frequent cardiac alterations during aging. Whether changes are part of the aging process or induced by a sedentary life style is not clear. Purpose To evaluate the effects of aerobic exercise on functional capacity, cardiac and myocardial function, and interstitial collagen matrix of aging rats. Methods Male Wistar rats were assigned into three groups: 1) sedentary six-month-old rats (W6, n=24); 2) sedentary 21-month-old rats (W21-Sed, n=25); and 3) exercised 21-month-old rats (W21-Ex, n=20). Physical exercise was by treadmill for 12 weeks. In vivo cardiac evaluation was performed by Doppler echocardiography. Myocardial function was assessed in LV papillary muscle preparation. Total and soluble myocardial collagen concentrations were evaluated by spectrophotometry. Protein expression was analyzed by Western blot. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn. Results Body weight was greater in W21-Sed and W21-Ex than W6. Before exercise, functional capacity did not differ between aged groups. After training, W21-Ex group ran farther and longer in treadmill than W21-Sed e W6, and W21-Sed presented worse physical capacity than W6. LV diastolic posterior wall, interventricular septum, and relative wall thicknesses were greater in W21-Sed and W21-Ex than W6, and did not differ between aged groups. E wave was lower in both aged groups than W6. E/E' ratio was lower in W21-Ex than W21-Sed. Isolated papillary muscle developed tension was higher in W21-Sed than W6; W21-Ex values did not differ from both W6 and W21-Sed groups. Time to peak tension was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. The same results were observed after positive inotropic stimulation. Total collagen concentration was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. Soluble collagen did not differ between groups. Type III collagen expression was higher in W21-Sed than W6; the W21-Ex group presented intermediary values that did not differ from W21-Sed or W6 groups. Type I collagen was similar between groups. Conclusion Regular physical aerobic training improves functional capacity and left ventricular diastolic function and attenuates type III collagen myocardial accumulation in aged rats. Acknowledgement/Funding Fapesp, CNPq, Capes, and UNESP

QT interval, general mortality and the role of echocardiographic parameters of left ventricular hypertrophy: Results from the prospective, population-based CARLA study.

There is convincing evidence of an association between the QT interval on electrocardiograms and general mortality. However, results are inconclusive regarding the extent to which this association depends on ventricular mass and size. Data were obtained from the prospective, population-based CARLA study, with a mean follow-up of 8.8 years, after exclusion of subjects with atrial fibrillation (919 men, 797 women aged 45-83 years remained eligible). Echocardiographic parameters were left ventricular mass index, left ventricular diastolic dimension index, diastolic interventricular septum thickness, diastolic left ventricular posterior wall and the relative left ventricular wall thickness. Heart rate-corrected QT interval (QTc) was measured with standard 12-lead electrocardiograms using the MEANS algorithm. The association between QTc and survival was modelled using Cox-regression models (crude- and covariate-adjusted). Values were standardized by dividing the QTc by the standard deviation. The association between QTc and survival was assessed in terms of tertiles of echocardiographic parameters. In covariate-adjusted models, QTc was associated with general mortality (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03, 1.38). Compared with higher tertiles, subjects in the lowest tertile of left ventricular mass index (HR=1.73, 95% CI: 1.26, 2.36) showed the strongest association with general mortality, which was also true for the lowest tertile of diastolic left ventricular posterior wall thickness (HR=1.49, 95% CI: 1.10, 2.02). In the general population, the association between QTc and general mortality is strongest in subjects with low left ventricular mass index and diastolic thickness of the left ventricular posterior wall, thus the prognostic value of QTc needs to be interpreted with regard to these echocardiographic parameters.

Model of the Distribution of Diastolic Left Ventricular Posterior Wall Thickness in Healthy Adults and Its Impact on the Behavior of a String of Virtual Cardiomyocytes

Correlation of the thickness of the left ventricular posterior wall (LVPWd) with various parameters, including age, gender, weight and height, was investigated in this study using regression models. Multicenter derived database comprised over 4,000 healthy individuals. The developed models were further utilized in the in vitro–in vivo (IVIV) translation of the drug cardiac safety data with use of the mathematical model of human cardiomyocytes operating at the virtual healthy population level. LVPWd was assumed to be equivalent to the length of one-dimensional string of virtual cardiomyocyte cells which was presented, as other physiological factors, to be a parameter influencing the simulated pseudo-ECG (pseudoelectrocardiogram), QTcF and ∆QTcF, both native and modified by exemplar drug (disopyramide) after I Kr current disruption. Simulation results support positive correlation between the LVPWd and QTcF/∆QTc. Developed models allow more detailed description of the virtual population and thus inter-individual variability influence on the drug cardiac safety.Electronic supplementary materialThe online version of this article (doi:10.1007/s12265-014-9558-4) contains supplementary material, which is available to authorized users.

The Diagnostic Significance of the Plasma N-Terminal Pro-B-Type Natriuretic Peptide Concentration in Asymptomatic Cats with Cardiac Enlargement

We evaluated the diagnostic significance of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in asymptomatic cats with cardiac enlargement. The plasma NT-proBNP concentration was measured in 21 clinically healthy control cats, and 67 asymptomatic cats with cardiac enlargement defined as end-diastolic interventricular septum thickness (IVSd) and/or diastolic left ventricular posterior wall thickness (LVPWd) >0.6 cm, vertebla heart scale (VHS) >7.8, and/or left atria/aorta ratio (LA/Ao) >1.5. The plasma NT-proBNP concentration in the asymptomatic cats with cardiac enlargement (median: 662.0, range: 24.0-2,449.0 pmol/l) was significantly higher than that in the controls (24.0, 24.0-95.0 pmol/l, P<0.001). The plasma NT-proBNP concentration was significantly correlated with the VHS, LA/Ao, IVSd and LVPWd (r=0.578, P<0.001; r=0.462, P<0.001; r=0.563, P<0.001; and r=0.764, P<0.001, respectively). Receiver operating characteristic analysis showed a cut-off value of 95.0 pmol/l for the detection of asymptomatic cats with cardiac enlargement, sensitivity and specificity of 88.1 and 100%, respectively, and an area under the curve of 0.971. These results suggest that the determination of the plasma NT-proBNP concentration can be a useful screening test for asymptomatic cats with cardiac enlargement.

Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction

BackgroundThe beta-1 adrenergic receptor (β1AR) plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly), which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH). Diabetes mellitus (DM), on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI) survivors.MethodsThe study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay.ResultsThe Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI) when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes) [62.7 vs. 58.4, respectively (p = 0.023)]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd) measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004)]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd) values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001) and LVPWd = 14.2 vs. 12.3 mm (p < 0.001), respectively]. Furthermore, among the euglycemic patients, the Arg389 homozygotes displayed increased LVMI and IVSd values compared to the Gly389 carriers [LVMI = 60.6 vs. 56.3, respectively (p = 0.028) and IVSd = 13.1 vs. 12.0 mm, respectively (p = 0.001)]. There was no difference in the LVMI and IVSd values between the diabetic Arg389 homozygotes and Gly389 carriers.ConclusionsThe data suggest an association between the β1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

Mitral Valve Prolapse In Atrial Septal Defect

Mitral valve prolapse is encountered at a rate of 25-95 % in patients with atrial septal defect. In this study, we aimed at obtaining physiopathological patterns causing mitral valve prolapse in patients with atrial septal defect by comparing the patients with atrial septal defect but no mitral valve prolapse (Group 1) to those with atrial septal defect and mitral valve prolapse (Group 2) in accordance with the following echocardiographic parameters: diastolic interventricular septum thickness, diastolic left ventricular posterior wall thickness, left ventricular ejection fraction, left ventricle end-diastolic diameter, left ventricle end-systolic diameter, right ventricular out-flow tract diameter, right ventricular in-flow tract diameter and mitral valve area calculated with pressure half-time. There were significant differences between the two groups in terms of diastolic interventricular septum thickness and left ventricular posterior wall thickness (10±2.16 to 8.7±0.38 and 9.27±l.56 to 8.1±l.18, p<0.0035 and p<0.0006 respectively). The left ventricular ejection fraction was found to be significantly high in patients with atrial septal defect and mitral valve prolapse (72.26±5.48 to 69.06±6.23, p<0.011).