Diastolic Wall Thickness Research Articles

Abstract P2085: Growth Hormone Releasing Hormone Agonist Counteracts The Cardiometabolic Heart Failure With Preserved Ejection Fraction Phenotype In Vivo Via The Hypoxia Inducible Factor 1 Alpha

Heart failure (HF) with preserved ejection fraction (HFpEF) treatment is limited due in large part to a lack of understanding of the underlying mechanisms. Recently, we showed that growth hormone-releasing hormone-agonist (GHRH-agonist) has cardioprotective effects in a murine model of cardiometabolic HFpEF; however, the mechanism of these therapeutic effects is still unclear. Here, we hypothesize that the therapeutic effects of GHRH-agonist in HFpEF are mediated by GHRH-receptor activation of the hypoxia-induced factor (HIF)-1α pathway. Methods: Wild-type (WT) and HIF-1α cardiomyocyte knockout (HIF-1α CM KO) mice were fed a high-fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals received daily injections of placebo or the GHRH-agonist, MR-356, for the remaining 4-week period. Control animals received no HFD+L-NAME or MR-356 treatment. Echocardiography, blood pressure, glucose tolerance test, and hemodynamic measurements were evaluated. Results: The HFD+L-NAME diet produced a HFpEF phenotype, which was reversed in mice with intact HIF-1α treated with MR-356. In contrast, in mice with a cardiac-specific deletion of HIF-1α CM , MR-356 treatment failed to reverse the elevated relative wall thickness in diastole (RWTd), increased E/E’ ratio and reduced global longitudinal strain (GLS). The slope of end-diastolic pressure-volume relationship (EDPVR) was increased in the placebo group and restored by MR-356 in WT mice but not HIF-1α CM KO mice, while EF was preserved. Conclusion: Our findings suggest that HIF-1α is necessary for the cardioprotective and anti-HFpEF effects MR-356.

Cardiac Dimensions in Normal Pregnancy: A Prospective Study.

Pregnancy, a unique physiologic state, is associated with several changes in the various body systems. The cardiovascular system is one of the systems affected, with chronic volume overload being one of the characteristic changes experienced during pregnancy. Cardiovascular disease in pregnancy is the leading cause of non-obstetric maternal death worldwide. This study aims to determine and describe the changes in left and right ventricular and atrial sizes in systole and diastole in the course of normal pregnancy. A cohort study was conducted among healthy pregnant women between the age of 18 and 40 who attended the antenatal clinic of Federal Medical Centre (FMC), Yenagoa, Bayelsa State. Fifty women were recruited during the first trimester (T1) of pregnancy and followed up until six weeks postpartum. Ethical approval was obtained from the Research Ethics Committee of Federal Medical Centre, Yenagoa, with approval number FMCY/REC/ECC/2019/JAN/150. Clinical evaluation, hematologic, biochemical, and anthropometric assessments, and two-dimensionalM-mode and Doppler echocardiography were done for the participants in each trimester of pregnancy and at six weeks postpartum. The clinical and echocardiographic parameters were analyzed using Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM Corp., Armonk, NY, USA). The mean trend ofleft ventricular posterior wall thickness in diastole (LVPWd) and left ventricular posterior wall thickness in systole (LVPWs) increased progressively from the first to third trimester (T3) (not statistically significant) but dropped towardinitial values in postpartum to the level that was statistically significant for LVWPd alone when compared to baseline first trimester values. The left atrial diameter in systole (LADs) was largest in the third trimester, and the left atrial volume index (LAVI)and right ventricular basal diameter (RVD1) also showed a similar trend. The left ventricular internal diameter (LVID) in both systole and diastole increased progressively from the first to the third trimesters, but the increase was only statistically significant between the third trimester (T3) and the first trimester (T1). The right atrial diameter (RAD) and right atrial volume (RAV) alsoincreased progressively from the first to the third trimesters, but the increase was only statistically significant between the third trimester (T3) and the first trimester (T1). Changes were noticed in the cardiac chamber sizes during pregnancy. However, this reversed back to levels similar to the first trimester during the postpartum period. To aid in the early detection and treatment of cardiovascular disorders in pregnancy,screening of apparently healthy pregnant women who later developed complaints is advised as cardiovascular changes could be significant during pregnancy.

Indipendent predictors of akinetic segment recovery during dobutamine infusion assessed by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial viability assessment can guide myocardial revascularization in patients with coronary artery disease. Non-invasive imaging modalities are routinely used for detection of viable myocardium and the highest diagnostic performance is provided by Cardiac Magnetic Resonance (CMR): it combines high sensibility (95%) by delayed enhancement (DE) assessment and high specificity (91%) by evaluation of myocardial systolic thickening recovery at increasing dose of dobutamine (Db-systolic recovery). Purpose Identification of independent predictors for Db-systolic recovery of akinetic segments supplied by a chronic total occlusion (CTO) coronary artery. The second purpose was to develop a diagnostic tool as alternative to dobutamine stress imaging to provide an estimation of myocardial response to inotropic agents. Methods This single center prospective observational study enrolled 47 consecutive patients referred to CMR for evaluation of inducible ischemia and myocardial viability in the territory of one or more CTOs. All enrolled patients presented basal akinetic segments in the CTO territory. Cine-Steady State Free Precession (SSFP) sequences were acquired both in basal and at increasing dose of dobutamine to evaluate Db-systolic recovery. Stress perfusion imaging and DE were then acquired to detect inducible ischemia and necrotic areas. Post-processing CMR-Feature Tracking strain analysis provided both radial and circumferential strain on basal, mid and apical short axis planes. Results Table 1 lists clinical characteristics of the study population. A total of 189 akinetic segments supplied by a CTO were detected and divided into viable and non-viable groups according to their ability to recover or not at increasing dose of dobutamine, respectively. Parameters of each akinetic segment significantly (p value < 0.05) associated with viability at univariate analysis were included in the multivariable binary logistic regression to identify independent predictors of Db-systolic recovery (Table 2). These independent predictors have been then included in a logistic regression model as continuous variable except for Transmural Extent of DE which can be either 1 or 0 according to DE<75% or ≥75%, respectively: L= −5.459 + 0.033 * (Radial Peak Systolic Strain) + 0.067 * (Circumferential Endocardial Peak Systolic Strain) + 1.808 * (Transmural Extent of DE) + 0.358 * (Diastolic Wall Thickness). When L ≥ 0 the model predicts contractile recovery during dobutamine infusion with an accuracy of 83.1%. Conclusion This CMR prospective study identifies independent predictors of contractile recovery at increasing dose of dobutamine and provides a diagnostic tool which might substitute dobutamine assessment with a good accuracy, reducing acquisition time and adverse events in patients with CTOs. An external validation study is needed to assess the consistency of this model for clinical purposes.

Clinical and mathematical prediction of the physiotherapy results in adolescents with primary hypertension training on a stationary bike

Background. The aim of the research is to clarify the indications for physical rehabilitation of adolescents with primary hypertension based on the individual clinical and mathematical prediction of long-term treatment outcomes. Materials and methods. There were observed 82 adolescents, 44 boys and 38 girls, aged 17.10 ± 0.05 years with a newly diagnosed primary hypertension. Physical rehabilitation for 7 months in the form of exercises on a stationary bike was prescribed to 44 patients who formed the main group. The rest of 38 adolescents who did not complete the stationary bike course and adhered to the recommendations for a healthy lifestyle formed the control group. Results. According to the ROC analysis, predictors of an adverse outcome of an attempt at physical rehabilitation were as follows: the average systolic blood pressure above 130 mm Hg at the start of a program, pulse rate variability index pNN50 of more than 16.6 % and body mass index above 25 kg/m2. Also, for the development of stable hypertension and an increase in the left ventricular posterior wall thickness in diastole above 8.0 mm, the average heart rate at night more than 68 bpm according to the Holter monitoring and the daily pulse pressure for 24-h monitoring more than 57 mm Hg were unfavorable. Conclusions. Аdolescents with primary hypertension should train at stationary bike in conditions of waiting for an effect of treatment. If an unfavorable course of the disease is predicted, physical rehabilitation must be combined with drug treatment.

Echocardiographic reference intervals and cut-off values to diagnose dilated cardiomyopathy in guinea pigs (Cavia porcellus)

The objective of this study was to establish reference intervals in healthy guinea pigs and to calculate optimal cut-off values for several M-Mode parameters to diagnose dilated cardiomyopathy (DCM) phenotype. This prospective study included 146 guinea pigs. The apparently healthy group included 92 animals and was used to create reference intervals for left ventricular internal diameter in diastole (LVIDd), left ventricular internal diameter in systole (LVIDS), E-point-to-septal separation (EPSS), diastolic wall thickness and left atrium and aorta. Allometric scaling was used to normalize LVIDd(-n) and LVIDs(-n) to body weight with a scaling exponent (BWexp). The DCM phenotype group included 54 subjects and was used to calculate optimal cut-off values of several M-mode parameters. Guinea pigs with DCM phenotype had significantly larger measurements of LVIDd, LVIDs and EPSS, as well as lower FS and wall thicknesses compared to apparently healthy guinea pigs. Allometric scaling exponents to normalize LVIDd and LVIDs to BW (g) were 0.336 and 0.346, respectively. The highest area under the curve (AUC) to diagnose DCM were found for LVIDs-n (cut-off value >0.74 mm, AUC 0.996), FS (cut-off value <29%, AUC 0.995), LVIDd-n (cut-off value >1.07 mm, AUC 0.980) and EPSS (cut-off value >1.4 mm, AUC 0.944). M-mode and 2D reference intervals for guinea pigs are presented, including lower and upper limits. Diagnosis of DCM phenotype in guinea pigs can be established using parameters known to be useful in other species, namely LVIDs, LVIDs-n, FS, LVIDd, LVIDd-n and EPSS.

The prognostic value of morphological and functional parameters of cardiac magnetic resonance in patients with systemic light chain amyloidosis

Objective: To investigate the features of morphological and functional parameters of cardiac magnetic resonance (CMR) in patients with systemic light chain (AL) amyloidosis, and the prognostic values of these related parameters. Methods: The data of 97 patients (including 56 males and 41 females, aged 36 to 71 years) with AL amyloidosis from April 2016 to August 2019 in the General Hospital of Eastern Theater Command were retrospectively analyzed. All patients underwent CMR examination. Those patients were divided into survival (n=76) and death groups (n=21) according to the clinical outcomes, and the differences in clinical baseline and CMR parameters between the two groups were analyzed and compared. A smooth curve fitting was used to analyze the association between morphological and functional parameters and extracellular volume (ECV), and Cox regression models were conducted to explore the association between related parameters and mortality. Results: The left ventricular global function index (LVGFI), myocardial contraction fraction (MCF) and stroke volume index (SVI) decreased with increasing ECV [β (95%CI) was -0.566 (-0.685--0.446), -1.201 (-1.424--0.977), -0.149 (-0.293--0.004), respectively;all P<0.05]. Left ventricular mass index (LVMI), and diastolic left ventricular global peak wall thickness (LVGPWT) increased with increasing ECV [β(95%CI) was 1.440 (1.142-1.739), 0.190 (0.147-0.233), respectively;both P<0.001]. While left ventricular ejection fraction (LVEF) began to decrease only at higher amyloid burden (β=-0.460, 95%CI:-0.639--0.280, P<0.001). The median follow-up time was 39 months (range 2-64 months), and 21 patients died during the follow-up period. The estimated survival rates according to Kaplan-Meier curves at 1, 3, and 5 years were 92.8%, 78.7%, and 77.1%, respectively. MCF<39% (HR=10.266, 95%CI: 4.093-25.747) and LVGFI<26% (HR=9.267, 95%CI: 3.705-23.178) were independent risk factors for death in patients with AL amyloidosis after adjusting for other CMR parameters (P<0.001). Conclusion: Multiple morphologic and functional parameters of CMR vary with the increase of ECV. MCF<39% and LVGFI<26% were independent risk factors for death.

Evaluation of right ventricle echocardiographic variables in apparently healthy domestic shorthair cats.

Right ventricular structural and functional changes result from many cardiovascular disorders in cats. Accordingly, echocardiographic evaluation of the size and function of the right ventricle (RV) provides important prognostic information in many conditions affecting the right heart. Therefore, detection of these changes is clinically important and needs reference values to ease the diagnosis. The present study was designed to calculate structural and functional right ventricular variables in 10 apparently healthy cats (six males and four females, average age 1 year old and body weight 2.70 - 4.80 kg) with no sedation. For this purpose, The minimum, maximum, mean ± standard error of the mean of right ventricle internal dimension in systole and diastole (cm), right ventricle free wall thickness in systole and diastole (cm), fractional shortening (%), right ventricle volume in systole and diastole (mL), right ventricle area in systole and diastole (cm2), ejection fraction (%) and fractional area change (%) were measured and reported. Descriptive statistics were provided for all calculated variables. Statistical correlation of the collected variables with body weight, gender and heart rate were analyzed. Results showed that there is a significant correlation between heart rate with body weight and between systolic and diastolic RV volumes with gender. The results of the present study would help clinicians in the diagnosis of the right heart changes in DSH cats.

The Relationship Between Hypothyroidism and Cardiac Findings in Children With and Without Down Syndrome.

Down syndrome is a genetic syndrome characterized with various dysmorphisms and congenital malformations such as congenital heart diseases. We aimed to evaluate the relationship between Down syndrome, hypothyroidism, and cardiac ���ndings. Thyroid hormone pro���les and echocardiographic ���ndings were evaluated. Patients with hypothyroidism and Down syndrome were named group 1; patients with hypothyroidism without Down syndrome group 2 and group 3 was control. The echocardiographic parameters (interventricular septum and left ventricular systolic, diastolic posterior wall thickness, left ventricular end-diastolic diameter, ejection fraction) were indexed to body surface area. Left ventricular mass index and relative wall thickness were calculated. Patients with relative wall thickness equal to or below 0.42 were classi���ed as eccentric hypertrophy or normal geometry, while those over 0.42 as concentric remodeling or concentric hypertrophy. Thyroid stimulating hormone values of groups 1 and 2 were signi���cantly higher than those of group 3. There were no signi���cant di���erences for fT4 between the groups. Interventricular septum and left ventricular posterior wall end-diastolic and end-systolic thickness were signi���cantly higher in group 1 than groups 2 and 3. There was no statistically signi���cant di���erence in left ventricular mass index between groups 1 and 2. In terms of relative wall thickness, 16 out of 29 patients in group 1 were revealed as concentric remodeling, 12 as normal geometry, 1 patient as eccentric hypertrophy. In group 2, 6 patients were revealed as concentric remodeling, 14 as normal geometry. There was no statistically signi���cant di���erence of left ventricular end-diastolic thickness between 3 groups. Cardiac morphology and functions were signi���cantly a���ected by hypothyroidism in patients with Down syndrome. Hypertrophy in Down syndrome may be caused by the cellular changes in myocardium.

Subclinical Cardiovascular Disease Markers in Relation to Serum and Dietary Magnesium in Individuals from the General Population: The KORA-MRI Study.

Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study. We used cross-sectional data from the sub-study of the Cooperative Health Research in the Region of Augsburg (KORA-FF4). Markers of subclinical CVD, namely, left and right ventricular structure and function and carotid plaque and carotid wall thickness, were derived by magnetic resonance imaging (MRI). Multivariable-adjusted regression models were applied to assess the relationship between serum and dietary magnesium and MRI-derived subclinical CVD markers. Among 396 included participants (mean age: 56.3 ± 9.2 years; 57.8% male), 181 (45.7%) had low serum magnesium levels (<2.07 mg/dL). Among 311 subjects with complete dietary data (mean age: 56.3 ± 9.1 years; 56.3% male), 154 (49.5%) had low dietary magnesium intake (≤155.2 mg/1000 kcal/day). Serum and dietary magnesium were not correlated (p-value = 0.5). Serum magnesium was significantly associated with presence of carotid plaque (OR 1.62, p-value 0.033). Dietary magnesium was associated with higher left ventricular end-systolic and end-diastolic volume (0.04 mL/m2, 0.06 mL/m2; p-value 0.011, 0.013, respectively), and also with a decrease in left ventricular remodeling index and mean diastolic wall thickness (−0.001 g/mL/m2, −0.002 mm/m2; p-value 0.004, 0.029, respectively). In summary, there was no consistent association of serum and dietary magnesium with imaging markers of subclinical CVD.

Influence of Dorper lamb development from birth to 120 days of age on clinical and echocardiographic parameters

The expansion of the sheep model in research represents an attractive and economically beneficial academic reason for investigations in sheep echocardiography. The present study aimed to evaluate the clinical and echocardiographic parameters in Dorper lambs during the developmental period. Emphasis was placed on the use of the species in translational research for the echocardiographic diagnosis of congenital heart diseases, which can contribute to improvements in interventionist techniques. Ten Dorper lambs were evaluated at the following time points: 24 h after birth and 7, 14, 21, 30, 60, 90 and 120 days of age. Clinical parameters were compiled, and echocardiogram records were obtained without sedation. Rectal temperature was lower on the first day compared to the others. From 21 days of life, there was a reduction in HR, with differences between time points. Mean and systolic blood pressure differed, with the highest values at 90 and 120 days of age. The thickness of the interventricular septum in diastole (IVSd) increased as age progressed, with the highest value at 120 days of age, and the same occurred for LVIDd (left ventricle internal diameter in diastole), LVFWd (left ventricular free wall thickness in diastole), IVSs (interventricular septum thickness in systole), LVIDs (left ventricle internal diameter in systole) and LVFWs (left ventricular free wall thickness in systole). There were differences in the size of the LA, Ao and LA/Ao ratio, which were greater at 90 days and 120 days of age. Echocardiographic changes accompany the development of lambs, where changes in echocardiographic parameters are evident with advancing age. The echocardiographic measurements in lambs obtained in the present study are similar to those in newborns.

Abstract 13367: APOE ε4 Carriage Associates With Improved Myocardial Performance in Older Age

Introduction: Although APOE ε 4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy) . Hypothesis: Combining data from two British cohorts– the 1946 National Survey of Health and Development (NSHD) and Southall and Brent Revised (SABRE)–we explored whether APOE ε 4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional echocardiography parameters in older age. Methods: Based on the presence of APOE ε 4, genotypes were divided into: APOE ε 4 (ε2ε4, ε3ε4, ε 4 ε 4) and non- APOE ε 4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWT s/d , IVS s/d ), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). Generalized linear models explored associations between APOE ε 4 genotypes as exposures and echocardiographic biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted. Model 2 was adjusted for factors associated with the outcome (sex and socio-economic position) to yield more precise estimates; subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways. Random-effects meta-analyses were performed across the cohorts. Results: 2596 participants were included. Compared to non- APOE ε 4 carriers, APOE ε 4 carriers had similar cardiac phenotypes in terms of EF, E/e’, LVPWT s/d , IVS s/d and LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%, p =0.016) which persisted in Model 2 (95% CI 1–7%, p =0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6% all p &lt;0.070). Conclusions: APOE ε 4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to APOE ε4 carriage that might collectively explain its persistence in humans.

PSUN52 Patients with Left Ventricular Hypertrophy on Echocardiography are Frequently Evaluated with Renin and Aldosterone

Abstract Background Increased left ventricular (LV) mass is an independent predictor of cardiovascular morbidity and mortality. Primary aldosteronism (PA) is associated with increased LV mass regardless of concomitant essential hypertension. Therefore, we hypothesize that the findings of increased LV mass approximated by left-ventricular hypertrophy (LVH) on echocardiogram relate to renin-independent hyperaldosteronism. Methods We performed a retrospective review of patients who underwent echocardiography at our institution between April of 2013 and September of 2017 (n=98,007 individuals). Of this population, we identified patients who underwent transthoracic echocardiography who met criteria for LVH based on current American Society of Echocardiography guidelines using the interventricular septal thickness in diastole (IVSd) and left ventricular posterior wall thickness in diastole (LVPWd). We excluded patients who underwent isolated transesophageal imaging as well as those who had significant structural cardiac abnormalities other than LVH. This cohort was analyzed with an internal self-service data tool to determine if patients had undergone biochemical evaluation with serum aldosterone and renin, which defined the final analytical cohort. Results We identified 19,664 patients with LVH of whom 5.8% (n = 1132) underwent biochemical evaluation with serum aldosterone and corresponding plasma renin activity (PRA) or direct renin concentration (DRC). In all patients with LVH, the mean IVSd was 11.7 ± 1.2mm in those who underwent biochemical testing and 11.5 ± 1.2 mm in those who did not (p &amp;lt;0.001); the mean LVPWd was 11.4 ± 1.1 mm mm in those who underwent biochemical testing and 11.3 ± 1.1 mm in those who did not (p &amp;lt;0.001). Of African American patients with LVH, 9.8% underwent biochemical testing; 5.0% of Caucasian patients with LVH underwent testing. The median PRA was 0.9 ng/mL/h with a median aldosterone to renin activty ratio (ARR) of 8.9 ng/dL-ng/mL/h. . The majority (54.4%) of individuals who underwent testing with plasma renin activity had a PRA ≤ 1.0 ng/mL/h. Conclusion Patients with LVH are being evaluated with renin and aldosterone at a higher frequency than patients with resistant hypertension and other guideline based indications for PA screening. Individuals evaluated with renin and aldosterone had increased IVSD and LVPWd, suggestive of more extensive LVH, compared with other individuals with LVH. LVH may be a sensitive screening criterion for PA. Additional prospective studies are necessary. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Different mechanisms of mitral regurgitation in hypertrophic cardiomyopathy: A clinical case and literature review.

Abnormalities of the mitral valve (MV) apparatus are typical features of hypertrophic cardiomyopathy (HCM). These abnormalities include leaflet elongation, thick leaflets, displacement of papillary muscle, and systolic anterior motion (SAM) of the MV anterior leaflet. Mitral valve chordal rupture associated with HCM is a rare but serious issue capable of change the clinical apparence and the prognosis of the patient. A 57-year-old lady with a history of diabetes, dyslipidemia, and a previous single episode of atrial fibrillation (treated with pharmacological cardioversion), presented to the Emergency Department for worsening dyspnea (New York Heart Association Classification class IV). A trans-thoracic echocardiogram (TTE) showed a significant, septal, and asymmetric left ventricular hypertrophy (basal anteroseptal wall diastolic thickness of 19 mm) with normal left ventricle systolic function. A SAM of AML was evident together with a left ventricular outflow tract gradient of 56 mmHg at rest, rising to 136 mmHg during the Valsalva maneuver. In addition, there was evidence of moderate to severe mitral regurgitation (MR) with an anteriorly directed jet, not very typical of MR related to SAM. A 2D-3D trans-esophageal echocardiogram (2D-3D TEE) revealed a combined MR mechanism based on PML degenerative prolapse with P2-flail from ruptured chordae with related eccentric anteriorly directed regurgitant jet, together with a second regurgitant posteriorly directed jet, related to SAM of AML. The patient underwent MV repair together with septal myectomy, with a good final outcome. Pre-operative echocardiography (both TTE and 2D-3D TEE) is an essential tool in order to detect different MV abnormalities in patients with HCM. These types of patients should never be treated by septal reduction alone. Surgical MV repair or replacement, together with septal myectomy, may be the preferred approach.

Detection of soluble suppression of tumorigenicity 2 and N-terminal B-type natriuretic peptide in a rat model of aortic regurgitation: differential responses to omecamtiv mecarbil.

Both N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and soluble isoform of ST2 (sST2) have been identified as biomarkers of heart failure. We evaluated the plasma levels of NT-proBNP and sST2 in a rat model of severe aortic valve regurgitation (AR) and correlated these findings with echocardiographic measurements. We also examined the impact of omecamtiv mecarbil (OM) on these parameters. The plasma levels of NT-proBNP and sST2 were measured in 18 rats both before and 2months after surgical induction of AR, and at these same time points, in six rats assigned to a sham-procedure control group. Plasma biomarkers were then measured again after infusion of OM or placebo in rats with AR (n=8 and 10, respectively) and OM alone in the sham control rats (n=6). Echocardiographic measurements were collected before and 2months after induction of AR. Our results revealed increased levels of plasma NT-proBNP (219±34pg/mL vs. 429±374pg/mL; p<0.001) in rats with AR at day 7 after infusion of placebo, whereas plasma levels of sST2 were higher in this cohort after infusion of either OM or placebo. We identified a significant positive correlation between plasma sST2 with posterior wall thickness in diastole (r=0.34, p<0.05) and total body weight (r=0.45, p<0.01) in rats with surgically induced AR. Because sST2 increased markedly, whereas NT-proBNP remained unchanged, when OM was administered, we hypothesize that sST2 has a distinct capability to detect deleterious effects of passive muscle tension, not reliably assessed by NT-proBNP, in the setting of AR.

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

Role of endothelial CXCR4 in the development of aortic valve stenosis

BackgroundCXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS.Materials and methodsWe generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4fl/fl mice with Tie2-Cre mice to study the role of endothelial cell CXCR4 in AVS. CXCR4fl/fl mice were used as controls. Echocardiography was used to assess the aortic valve and cardiac function. Heart samples containing the aortic valve were stained using Alizarin Red for detection of calcification. Masson’s trichrome staining was used for the detection of fibrosis. The apex of the heart samples was stained with wheat germ agglutinin (WGA) to visualize ventricular hypertrophy.ResultsCompared with the control group, the deletion of CXCR4 in endothelial cells led to significantly increased aortic valve peak velocity and aortic valve peak pressure gradient, with decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy as evidenced by increased diastolic and systolic left ventricle posterior wall thickness (LVPW), cardiac myocyte size, and heart weight (HW) to body weight (BW) ratio. Our data also confirmed increased microcalcifications, interstitial fibrosis, and thickened valvular leaflets of the EC CXCR4 KO mice.ConclusionThe data collected throughout this study suggest the deletion of CXCR4 in endothelial cells is linked to the development of aortic valve stenosis and left ventricular hypertrophy. The statistically significant parameters measured indicate that endothelial cell CXCR4 plays an important role in aortic valve development and function. We have compiled compelling evidence that EC CXCR4 KO mice can be used as a novel model for AVS.

Do type 1 diabetic children have echocardiographic signs of subclinical cardiac dysfunction?

Background Diabetes mellitus is a major illness in which cardiac problems play a significant role in patient mortality. Objectives We aimed to evaluate whether children with diabetes mellitus type 1 have early echocardiographic signs of subclinical cardiac dysfunction and whether their sex, metabolic control, and duration of diabetes have an effect. Patients and methods A case–control study was performed from January 2022 to November 2022 that included 29 children and adolescents with type 1 diabetes aged from 4 to 15 years. A control group of 15 healthy children was also included. They were recruited from the pediatric endocrinology clinic, Al-Fayoum University Children’s Hospital, Al-Fayoum University, Egypt. Conventional echocardiographic study and tissue Doppler imaging measurements were done. Results With glycated hemoglobin levels less than 7%, the study group of diabetic children had inadequate glycemic control. There was a statistically significant low mean of fractional shortening and high mean of left ventricular septal wall thickness in diastole among diabetic children in comparison with controls, with P values of 0.04 and 0.038, respectively, but still within normal range. Conclusion Children with diabetes have poor glycemic control and scanty echocardiographic evidence of subclinical cardiac dysfunctions. According to the study, cardiac dysfunction in children with diabetes is uncommon. For the early identification of any potential cardiac dysfunctions, distant periodic cardiac examination using both conventional and tissue Doppler echocardiography is advised.

Abstract 068: Genetic Mechanisms Of Cardiac Hypertrophy And Fibrosis In Global Npr1 Gene-ablated Male And Female Mice

Genetic ablation of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) in mice triggers cardiac remodeling associated with hypertrophy, fibrosis, and heart failure. The objective of this study was to determine the mechanisms regulating the developments of cardiac hypertrophy and fibrosis in global Npr1 (encoding NPRA) gene-knockout (KO) mice and whether transforming growth factor-beta 1 (TGF-β1) plays a critical role in this process. Both male and female Npr1 KO ( Npr1 -/- , 0-copy), heterozygous ( Npr1 +/- , 1-copy), and wild-type (WT; Npr1 +/+ , 2-copy) mice were administered with TGF-β1 receptor antagonist GW788388 (2 mg/kg/day) by intraperitoneal (ip) injection for 28 days. The heart weight/body weight (HW/BW) and tibia length (TL) to BW (TL/BW) ratios were determined. Echocardiography was used to determine the cardiac structure and function. Quantitative polymerase chain reaction (qPCR) and Western blot were used to quantify the hypertrophic and fibrotic markers. HW/BW and TL/BW ratios were significantly higher in Npr1 KO mice and significantly greater in males than females. The Npr1 -/- mice showed significant induction of cardiac hypertrophic marker collagen-1α (3.5-fold) and fibrotic markers, monocyte chemoattractant protein (MCP, 4-fold), connective tissue growth factor (CTGF, 5-fold), alpha-smooth muscle actin (α-SMA, 4-fold) compared with WT mice. The expression of phosphorylated extracellular regulated kinase 1/2 (pERK1/2) was also upregulated in Npr1 -/- mice. Left ventricular end-systolic and diastolic dimensions (LVED-s, LEVD-d) and posterior wall thickness (PWT) were significantly increased in male KO mice than female KO mice compared with WT mice. The fractional shortening (FS) was compromised in male KO mice than female KO mice. The Treatment of Npr1 -/- mice with GW788388, prevented the development of cardiac hypertrophy and fibrosis compared to vehicle-treatment. The results suggest that the cardiac hypertrophy and fibrosis in Npr1 -/- mice is regulated through TGF-β1- SMAD-pathways.

Influence of sacubitril/valsartan on hibernating myocardium in patients with chronic heart failure with reduced ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial viability particularly hibernating myocardium is one of the critical parameters for the assessment of the long-term prognosis of patients with ischemic etiology heart disease. Purpose of the study was to evaluate the influence of angiotensin receptor neprilysin inhibitor - sacubitril/valsartan on hibernating myocardium in patients with ischemic etiology chronic heart failure with reduced ejection fraction. Material and Methods One hundred and twenty patients with chronic heart failure with reduced ejection fraction (EF&amp;lt;40%) were enrolled in the study (mean age 58.2±14.6 years, male=53%). Patients were divided into two groups by sixty. Group I patients were assigned sacubitril/valsartan while Group II were assigned valsartan in addition to the standard treatment. Hibernating myocardium were assessed with echocardiography with dopamine test. All statistical analysis were assessed using STATA software. Results Ejection fraction and the wall motion score has been improved in both groups from baseline (P&amp;lt;0.05), however when we compared two groups, sacubitril/valsartan group tended to have more positive effect on ejection fraction (from 32.2±8.2% to 43.6±12.4% vs. from 31.7±8.0% to 37.2±10.3%, P&amp;lt;0.05) and the wall motion score (from 2.34±0.5 to 1.92±0.4 vs. 2.36±0.6 to 2.15±0.45, P&amp;lt;0.05) compared to valsartan group. Diastolic and systolic wall thickness has been improved in both groups from baseline (P&amp;lt;0.05), however there were not statistically significant changes between groups (P&amp;gt;0.05). When we analyzed by gender there were not significant changes between male and female (P&amp;lt;0.05). Conclusion Sacubitril/valsartan improves myocardial viability in patients with ischemic etiology chronic heart failure with reduced ejection fraction. Further studies with large amount of patients are required to clarify exact mechanisms.

Weight status related early changes in blood pressure, cardiac structure and function in 4-year-old children

Objective: To explore the association between weight status and early changes in blood pressure, cardiac structure and function in children at 4 years of age. Methods: A cross-sectional study of the relationship between weight status and cardiovascular parameters was performed on the platform of "Shanghai Birth Cohort" in Shanghai Xinhua Hospital between 2017 and 2020. Height, weight, blood pressure and echocardiography were measured in 1 477 children at 4 years of age. According to body mass index (BMI), participants were classified into five groups: underweight, lean, normal weight, overweight and obese. Blood pressure, cardiac structure and function indexes were compared among different groups using one-way ANOVA. The associations between blood pressure, cardiac structure and function and weight status in children were analyzed by linear regression models. Multivariate logistic regression models were used to analyze whether weight status was an independent risk factor for elevated blood pressure or left ventricular hypertrophy (LVH) in children. Results: A total of 1 477 children including 772 boys and 705 girls were included in this study. There were 115 overweight and obese boys (14.9%) and 68 overweight and obese girls (9.6%). The majority of children had normal weight (916 cases, 62.0%), followed by underweight (303 cases, 20.5%), overweight (130 cases, 8.8%), lean (75 cases, 5.1%), and obese (53 cases, 3.6%). With the increase of BMI, systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness in systole, left ventricular posterior wall thickness in diastole, left ventricular diameter in end-systole, left ventricular diameter in end-diastole, interventricular septum thickness in systole and left ventricular ejection fraction showed significantly positive trend, and the differences among the groups were significant (F=31.73, 6.59, 14.22, 4.96, 3.01, 31.50, 39.79, 5.91, 3.09, all P<0.05). Multiple linear regression showed that overweight and obese were all positively associated with systolic blood pressure (β=5.2, 95%CI 3.6-6.8), LVMI (β=1.9, 95%CI 0.8-3.1), left ventricular diameter in end-systole (β=1.3, 95%CI 0.9-1.8), and left ventricular diameter in end-diastole (β=1.6, 95%CI 1.0-2.2). In the Logistic regression model, compared with normal weight children, overweight (OR=2.37, 95%CI 1.37-4.41) and obese children (OR=10.90, 95%CI 4.47-26.60) both had significantly increased risk of elevated blood pressure. However, the risk of LVH did not significantly increased. Conclusions: Overweight and obesity in 4-year-old children are associated with increased blood pressure, increased left ventricle diameter and LVMI. Overweight and obesity are independent risk factors for elevated blood pressure in children at 4 years of age.