Increase In Left Ventricular Mass Research Articles

Baicalin alleviates angiotensin II-induced cardiomyocyte apoptosis and autophagy and modulates the AMPK/mTOR pathway.

As a main extraction compound from Scutellaria baicalensis Georgi, Baicalin exhibits various biological activities. However, the underlying mechanism of Baicalin on hypertension-induced heart injury remains unclear. Invivo, mice were infused with angiotensin II (Ang II; 500 ng/kg/min) or saline using osmotic pumps, followed by intragastrically administrated with Baicalin (5 mg/kg/day) for 4 weeks. Invitro, H9C2 cells were stimulated with Ang II (1 μM) and treated with Baicalin (12.5, 25 and 50 μM). Baicalin treatment significantly attenuated the decrease in left ventricular ejection fraction and left ventricular fractional shortening, increase in left ventricular mass, left ventricular systolic volume and left ventricular diastolic volume of Ang II infused mice. Moreover, Baicalin treatment reversed 314 differentially expressed transcripts in the cardiac tissues of Ang II infused mice, and enriched multiple enriched signalling pathways (including apoptosis, autophagy, AMPK/mTOR signalling pathway). Consistently, Baicalin treatment significantly alleviated Ang II-induced cell apoptosis invivo and invitro. Baicalin treatment reversed the up-regulation of Bax, cleaved-caspase 3, cleaved-caspase 9, and the down-regulation of Bcl-2. Meanwhile, Baicalin treatment alleviated Ang II-induced increase of autophagosomes, restored autophagic flux, and down-regulated LC3II, Beclin 1, as well as up-regulated SQSTM1/p62 expression. Furthermore, autophagy inhibitor 3-methyladenine treatment alleviated the increase of autophagosomes and the up-regulation of Beclin 1, LC3II, Bax, cleaved-caspase 3, cleaved-caspase 9, down-regulation of SQSTM1/p62 and Bcl-2 expression after Ang II treated, which similar to co-treatment with Baicalin. Baicalin treatment reduced the ratio of p-AMPK/AMPK, while increased the ratio of p-mTOR/mTOR. Baicalin alleviated Ang II-induced cardiomyocyte apoptosis and autophagy, which might be related to the inhibition of the AMPK/mTOR pathway.

HYPERTENSION-SPECIFIC ASSOCIATION OF CARDIO-ANKLE VASCULAR INDEX WITH SUBCLINICAL LEFT VENTRICULAR FUNCTION IN A CHINESE POPULATION: DANYANG STUDY

Objective: The association of arterial stiffness, as measured by cardio-ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. Our study aims to examine their relationship in hypertensive patients compared with that in normotensive subjects. Design and method: Our study included 1887 subjects who were enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS-1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e’), and speckle tracking to estimate left ventricular (LV) global longitudinal strain (GLS). Results: Increased LV mass index (76.3, 80.0, and 84.0 g/m2), decreased GLS (21.1, 21.0, and 20.4%), lower E/A (1.2, 1.0, and 0.8) and e’ velocity (11.2, 9.4, and 8.2 cm/s), and higher E/e’ (7.6, 8.2, and 8.8) were significantly associated with higher CAVI on unadjusted analyses (P < 0.001). After adjustment for covariates, GLS, E/A, and e’ were still significantly decreased from tertiles 1 to 3 of CAVI (P < 0.04). Further sensitive analyses revealed similar association pattern for diastolic function. However, the relationship of higher CAVI to worse GLS was stronger in hypertensives (P = 0.008) but not normotensives (P = 0.167) (Figure 1). Compared with lowest tertile, subjects with top tertile of CAVI were at higher risk of subclinical LV systolic dysfunction in hypertensive patients (OR = 2.61; P = 0.005). Conclusions: Increased CAVI is associated with worse subclinical diastolic function. However, this relationship of CAVI to subclinical systolic function was more prominent in hypertensive patients.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study.

We investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study. The study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e' ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis. In unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1g/m2 [71.8,104.9] vs. 69,0g/m2 [57.9,80.8]) and E/e' ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e' ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy. Glomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.

Association of Changes in Vector Length with Changes in Left Ventricular Mass Among Patients on Maintenance Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial.

Hypervolemia is thought to be a major contributor to higher left ventricular mass (LVM), a potent predictor for cardiovascular mortality among patients on maintenance hemodialysis. We hypothesized that a decrease in vector length (a bioimpedance proxy of hypervolemia) would be associated with an increase in LVM. Using data from the Frequent Hemodialysis Network Daily Trial (n=160) we used linear regression to assess the association of changes in vector length from baseline to month 12 with changes in magnetic resonance imaging (MRI) measures of LVM and other cardiac parameters. We adjusted models for the randomized group, baseline vector length, age, sex, race, body mass index, vascular access, dialysis vintage, history of hypertension, heart failure, and diabetes, residual kidney function, pre-dialysis systolic blood pressure (BP), ultrafiltration rate, serum-dialysate sodium gradient, hemoglobin, phosphate, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, erythropoietin dose, and equilibrated Kt/V. The mean age was 50 ±13 years; 35% were female. In the fully adjusted models, a decline in vector length (per 50 Ω/m; i.e., increase in volume) was associated with a 6.8 g (95%CI -0.1, 13.7) and 2.6 g/m2 (95%CI -1.2, 6.3) increase in LVM and LVM index, respectively; and an increase of 15.0 mL (95%CI 7.5, 22.4), 7.3 mL (95%CI 3.0, 12.7), 7.8 mL (95%CI 3.0, 12.7), and -0.9 % (95%CI -3.1, 1.3) in left ventricular (LV) end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF), respectively. The lowest tertile of change in vector length (i.e., greater increase in volume) was associated with greater increases in LVEDV and LVSV, versus the highest tertile. There was no evidence of heterogeneity by randomized group. Change in vector length, a bioimpedance-derived proxy of volume status, was inversely associated with indices of left ventricular mass and volume measured by cardiac MRI in patients randomized to conventional or frequent hemodialysis over 12 months.

Abstract P437: Cumulative Effect of Early-Onset Type 2 Diabetes on Left Ventricular Geometry - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Type 2 diabetes (T2D) is increasingly common in young adults. Increases in left ventricular (LV) mass and wall thickness are early manifestations of myocardial involvement in T2D. The association between the cumulative burden of risk factors (RFs) and LV structural abnormalities in patients with early-onset T2D has not been well characterized. Objective: Investigate how metabolic RFs accumulated in a 25-year period among patients with early-onset T2D relate to LV mass index (LVMI) and relative wall thickness (RWT). Methods: We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA, baseline to year 25). We defined early-onset T2D by self-reported T2D or anti-diabetic medication use, fasting glucose (FG) ≥126 mg/dL, or oral glucose ≥200 mg/dL at or before follow-up year 10 (age&lt;40). LV outcomes were measured by Doppler echocardiography (LVMI by Devereux formula indexed to body surface area; RWT = LV posterior wall thickness at end diastole x 2/LV internal dimension at end-diastole). Hypertrophy was defined by LVMI ≥115 g/m 2 in men or ≥95 g/m 2 in women. We used the area under the growth curve (AUC) that was derived from quadratic random-effects models of ≥4 repeated measures of RFs (BMI, SBP, DBP, LDL-c, HDL-c, triglycerides, fasting glucose, and fasting insulin) to estimate the cumulative burden of T2D through adulthood. We performed linear regressions to examine the associations of the total AUC of each RF with LVMI or RWT, accounting for sex, race, mid-life age, education, smoking, and control for hypertension, lipids, and diabetes. We assessed the associations by sex and race. Results: Among 227 patients with early-onset T2D, 39% had hypertrophy, and 13% had RWT&gt;0.42 at midlife. Each standard deviation (SD) increase in total AUCs of BMI, SBP, DBP, triglycerides, FG, and fasting insulin was significantly associated with increased LVMI (β coefficients =5.9, 11.5, 10, 7, 4.1, and 6.7, respectively), while high total AUC of HDL-c was inversely associated with LVMI (β = -5.1). Increased total AUC of triglycerides was associated with increased RWT (β = 0.2). Significant sex and race differences were shown in the cumulative effect of RFs on outcomes. The positive associations between AUC of RFs and LVMI were significant in both sexes, but the associations were stronger in male patients than in women. The inverse association between AUC of HDL-c and LVMI was only significant in male patients (P-interaction &lt;0.05). Women with early-onset T2D but not men exhibited significantly increased RWT related to the increase in AUCs of SBP, DBP, triglycerides, FG, and insulin (P-interaction &lt;0.05). The positive association between AUC of BMI and LVMI was significant in Whites but not Blacks (P-interaction &lt;0.05). Conclusion: Cumulative RFs alter mid-adulthood LV geometry in patients with early-onset T2D. This cumulative impact of early-onset T2D on LV geometry varies by sex and race.

Estimating Left Ventricular Mass from the Electrocardiogram across the Spectrum of LV Mass from Normal to Increased LV Mass in an Older Age Group.

To examine the relationship of QRS voltages and left ventricular (LV) mass across the spectrum of individuals with different LV mass. Twenty QRS voltage measurements or combinations were determined in a consecutive series of 159 adults with an ECG and echocardiogram without previous myocardial infarction, left or right bundle branch block, pre-excitation, or electronic pacemaker. The four strongest and significant correlations between QRS and LV mass were S in V4, deepest S wave in any precordial lead plus S in V4, S in V3, and S in V3 plus R in AVL times QRS duration. For men, the strength of the relationships were S in V3 (F = 33.8), deepest S wave in any precordial lead plus S V4 (F = 33.7), S in V3 plus R aVL (F = 29.9), S in V4 (F = 29.79), and deepest S in precordial leads (F = 17.9). The R wave in AVL alone did not correlate with LV mass. Criteria using the R wave in lateral precordial leads did not correlate as strongly with LV mass. For women, only S in V4 significantly correlated with LV mass. Overall, the R wave voltage in limb leads (AVL I or II) did not correlate with precordial S wave amplitudes. Univariate and multivariate analysis showed that some but not all QRS voltages correlated with each other. In multivariate analysis, using only single variables and not combination of QRS variables, the only significant relationship between QRS voltage and left ventricular mass was for men the S in V3 (p = 0.04) and for women S in V4 (p = 0.016) and R in V6 (p = 0.04). The S wave in V3 and V4 correlate most strongly with LV mass while the R wave in limb leads, including AVL, do not correlate.

Echocardiographic Comparison of Left Ventricular Systolic Function and Aortic Blood Flow Velocimetry in Children with Ventricular Septal Defect.

The assessments of left ventricular (LV) longitudinal systolic dynamics in children with ventricular septal defect (VSD) have achieved a major milestone in the evaluation of LV systolic function. This study aims to evaluate the LV function, LV mass (LVM), and the descending aorta blood flow in children with VSD compared to that obtained in age and sex-matched controls. The mean LVM of the control, 113.5 ± 123.9 was higher than that of those who had VSD, 75.8 ± 83.9, and the difference in mean was found to be statistically significant (Mann-Whitney U = 2.322, P = 0.022). The mean EF of the control, 67.9 ± 10.3 was comparable to that of those with VSD, 65.6 ± 13.9, (Student's t = 1.223, P = 0.223). Similarly, the mean descending aorta blood flow of control, 1.6 ± 2.2 was comparable to that of those with VSD, 3.9 ± 16.1, (Mann-Whitney U = 1.002, P = 0.321). There was a very weak positive correlation between LVM and descending aorta blood flow among the subjects (n = 85, r = 0.117, P = 0.425). There was a very weak negative correlation between LVM and descending aorta blood flow among control. (n = 85, r = -0.065, P = 0.609). The LVM among children with VSD is lower than controls but there is no difference between LV function in subjects and controls. There is a linear increase of LVM with descending aorta blood flow.

Acute and chronic effects of levosimendan in the ZSF1 obese rat model of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by impaired cardiovascular reserve in which therapeutic options are scarce. Our aim was to evaluate the inodilator levosimendan in the ZSF1 obese rat model of HFpEF. Twenty-week-old male Wistar-Kyoto (WKY), ZSF1 lean (ZSF1 Ln) and ZSF1 obese rats chronically treated for 6-weeks with either levosimendan (1 mg/kg/day, ZSF1 Ob + Levo) or vehicle (ZSF1 Ob + Veh) underwent peak-effort testing, pressure-volume (PV) haemodynamic evaluation and echocardiography (n = 7 each). Samples were collected for histology and western blotting. In obese rats, skinned and intact left ventricular (LV) cardiomyocytes underwent in vitro functional evaluation. Seven additional ZSF1 obese rats underwent PV evaluation to assess acute levosimendan effects (10 μg/kg + 0.1 μg/kg/min). ZSF1 Ob + Veh presented all hallmarks of HFpEF, namely effort intolerance, elevated end-diastolic pressures and reduced diastolic compliance as well as increased LV mass and left atrial area, cardiomyocyte hypertrophy and increased interstitial fibrosis. Levosimendan decreased systemic arterial pressures, raised cardiac index, and enhanced LV relaxation and diastolic compliance in both acute and chronic experiments. ZSF1 Ob + Levo showed pronounced attenuation of hypertrophy and interstitial fibrosis alongside increased effort tolerance (endured workload raised 38 %) and maximum O2 consumption. Skinned cardiomyocytes from ZSF 1 Ob + Levo showed a downward shift in sarcomere length-passive tension relationship and intact cardiomyocytes showed decreased diastolic Ca2+ levels and enhanced Ca2+ sensitivity. On molecular grounds, levosimendan enhanced phosphorylation of phospholamban and mammalian target of rapamycin. The observed effects encourage future clinical trials with levosimendan in a broad population of HFpEF patients.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI

BackgroundSarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition.MethodsA total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model.ResultsPatients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (β = -0.25; P < 0.001), rather than body mass index (β = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4–52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92–0.99; P = 0.01).ConclusionsWith respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

Measurement of Turbulent Kinetic Energy in Hypertrophic Cardiomyopathy Using Triple-velocity Encoding 4D Flow MR Imaging.

The turbulent kinetic energy (TKE) estimation based on 4D flow MRI has been currently developed and can be used to estimate the pressure gradient. The objective of this study was to validate the clinical value of 4D flow-based TKE measurement in patients with hypertrophic cardiomyopathy (HCM). From April 2018 to March 2019, we recruited 28 patients with HCM. Based on echocardiography, they were divided into obstructed HCM (HOCM) and non-obstructed HCM (HNCM). Triple-velocity encoding 4D flow MRI was performed. The volume-of-interest from the left ventricle to the aortic arch was drawn semi-automatically. We defined peak turbulent kinetic energy (TKEpeak) as the highest TKE phase in all cardiac phases. TKEpeak was significantly higher in HOCM than in HNCM (14.83 ± 3.91 vs. 7.11 ± 3.60 mJ, P < 0.001). TKEpeak was significantly higher in patients with systolic anterior movement (SAM) than in those without SAM (15.60 ± 3.96 vs. 7.44 ± 3.29 mJ, P < 0.001). Left ventricular (LV) mass increased proportionally with TKEpeak (P = 0.012, r = 0.466). When only the asymptomatic patients were extracted, a stronger correlation was observed (P = 0.001, r = 0.842). TKE measurement based on 4D flow MRI can detect the flow alteration induced by systolic flow jet and LV outflow tract geometry, such as SAM in patients with HOCM. The elevated TKE is correlated with increasing LV mass. This indicates that increasing cardiac load, by pressure loss due to turbulence, induces progression of LV hypertrophy, which leads to a worse prognosis.

Cardiovascular Involvement in Patients with Autosomal Dominant Polycystic Kidney Disease: A Review.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease with a prevalence of 1:400 to 1:1,000 in Caucasians. It is caused by mutations in the PKD1 gene located on chromosome 16p13.3 (in about 85% cases) as well as in the PKD2 gene on chromosome 4q13-23. In the Polish population, the disease is associated with PKD1 mutations in 84% of the ADPKD-affected families. PKD1 and PKD2 genes encode the proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The presence of kidney cysts is a characteristic feature in the ADPKD patients. But in the ADPKD patients, cardiovascular abnormalities, such as hypertension (HT) with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, higher left ventricular mass (LVM), intracranial (ICAN) and extracranial aneurysms, and cardiac valve defects, are significantly more common than in the general population. According to the literature data, both higher LVM and vascular dysfunction already occur in children and young adults with normal renal function and without HT. Moreover, biventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima-media thickness, and impaired coronary flow velocity reserve are present even in young patients with ADPKD who have normal HT and well-preserved renal function. In patients with ADPKD, hypertension has some specific features; in the youngest age group of children, the prevalence of hypertension is greater if their parents suffer from hypertension; in normotensive young ADPKD-diagnosed individuals, ambulant SBP and DBP values were significantly higher than in age- and gender-matched controls; hypertension appears at least 10 years earlier than spontaneous HT in general population. In adults, HT is often diagnosed before any substantial reduction in the GFR, and a lower nocturnal dip in BP in comparison to hypertensives in the general population. PKD1 and PKD2 gene products (PC1 and PC2 proteins) have been shown to assemble at the plasma membrane and to regulate calcium (Ca2+) entry. A defect in Ca2+ binding mediated by mutations in polycystin proteins is a hypothetical factor contributing to left ventricular mass increase. Altered intracellular Ca2+ handling contributes importantly to impaired contractility associated with heart failure. Impairment of intracellular Ca2+ homeostasis and mitochondrial function has been implicated in the development of LVH. It can be assumed that the cause of LVH in ADPKD patients is the natural course of this disease with developing HT and deteriorating kidney function, which may be influenced by the presence of PKD1- and PKD2-mutated gene products: PC1 and PC2 proteins.

Cardiac Evaluation and its Correlation with Volume Status in Maintenance Hemodialysis Patients

Introduction: Fluid overload (FO) in hemodialysis (HD) patients can result in increase in left atrial volume (LAV) and left ventricular mass (LVM). Here, we correlated volume status with cardiac outcome in these patients over a period of 6 months. Methodology: Consecutive clinically euvolumic end stage renal disease (ESRD) patients on thrice weekly maintenance hemodialysis (MHD) for at least 6 months were included. Inferior vena cava (IVC) Collapsibility Index of ≤40% by IVC or B-Line score of ≥15 by lung ultrasound (LUS) or over hydration/extracellular water (OH/ECW) by bioimpedence spectroscopy (BIS) ≥15% were defined as FO. A cut-off of left ventricular mass index (LVMI) ≥115 gm/m2 and LAV index (LAVI) ≥34 mL/m2 on echocardiography were used for defining left ventricular hypertrophy (LVH) and left atrial dilatation (LAD), respectively. The diagnostic value of LUS for OH, considering BIS as the gold standard and correlation between LVMI and LAVI with OH/ECW and LUS score was studied. Results: Among 100 MHD patients, 29% had OH at baseline. Baseline FO was significantly associated with LAD but not LVH. The specificity of LUS in diagnosing FO at 3rd and 6th months was 98% and 95.1%, respectively. OH/ECW on BIS showed a correlation with both LAVI at baseline ( p-value of .03, R2 0.71). B line score determined by LUS did not show a correlation with LAVI at baseline ( p-value of .07, R2 0.49). Conclusion: Routine ultrasound use in HD unit for determining OH and echocardiography screening for LAD would assess and reduce early cardiovascular events.

Ultrasound-Induced Microbubble Cavitation for Targeted Delivery of MiR-29b Mimic to Treat Cardiac Fibrosis.

Cardiac fibrosis contributes to adverse ventricular remodeling and is associated with loss of miR-29b. Overexpression of miR-29b via plasmid or intravenous injection of microRNA mimic has blunted fibrosis, but these are inefficient and non-targeted delivery strategies. In this study, we tested the hypothesis that delivery of microRNA-29b (miR-29b) using ultrasound-targeted microbubble cavitation (UTMC) of miR-29b-loaded microbubbles would attenuate cardiac fibrosis and preserve left ventricular (LV) function. Lipid microbubbles were loaded with miR-29b mimic (miR-29b-MB) or negative control (NC) mimic (NC-MB), placed with cardiac fibroblasts (CFs) and treated with pulsed ultrasound. Cells were harvested to measure downstream fibrotic mediators. Mice received angiotensin II (ANG II) infusion causing afterload increase and direct ANG II-induced cardiac fibrosis. UTMC of miRNA-loaded microbubbles was administered to the heart at days 0, 3 and 7. Serial echocardiography was performed, and hearts were harvested on day 10. UTMC treatment of CFs with miR-29b-MB increased miR-29b and decreased fibrotic transcripts compared with NC-MB treatment. In vivo UTMC+NC-MB led to increased LV mass, reduction in cardiac function and increase in fibrotic markers, demonstrating ANGI II-induced adverse cardiac remodeling. Mice treated with UTMC+miR-29b-MB had preservation of cardiac function, downregulation of cardiac fibrillin and trends of lower COL1A1, COL1A2 and COL3 mRNA and decreased cardiac α-smooth muscle protein. UTMC-mediated delivery of miR-29b mimic blunts expression of fibrosis markers and preserves LV function in ANG II-induced cardiac fibrosis.

Apohemoglobin-Haptoglobin Complex Improves Cardiac and Pulmonary Function in Homozygous Townes (HbSS Townes) Mice

The constant ischemia-reperfusion injury and the release of hemoglobin and heme in patients with sickle cell disease (SCD) can affect the heart, lungs, and vasculature. While treatments have improved survival, cardiovascular complications are becoming more prevalent, including pulmonary hypertension and left ventricular diastolic dysfunction. Pulmonary hypertension is associated with increased mortality risk and linked to intravascular hemolysis, leg ulcers, renal insufficiency, iron overload, and liver dysfunction. Chronic anemia leads to heart chamber dilation and left ventricular mass increase, often accompanied by left ventricular diastolic dysfunction, both impacting exercise capacity. Additionally, it can cause Acute Chest Syndrome (ACS), which is characterized by inflammation and blockage of small blood vessels in the lungs. In some cases, the heart may enlarge (cardiomegaly) due to the increased workload it faces in pumping blood through narrowed or obstructed blood vessels. Sudden death is also emerging as a concern, necessitating further cardiac investigations and risk assessment for effective management. These issues are speculated to result from the high amount of hemoglobin and heme released into circulation. In this study, a synthetic protein scavenger for heme and Hb, the apohemoglobin (apoHb) was stabilized with haptoglobin (Hp) to create the apoHb-Hp complex, was used to study the cardiac and pulmonary changes in SCD mice resulting from heme and Hb. Homozygous Townes (HbSS Townes) mice (B6; 129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB)Tow/Hbbtm3(HBG1,HBB)Tow/J) were used as the murine model of SCD, and HbAA Townes mice (homozygous for Hbatm1(HBA)Tow and Hbbtm3(HBG1,HBB)Tow) were used as the phenotypically controls. The results conclusively illustrate the benefits of using apohb-Hb, as it improves cardiac output, decreases pulmonary hypertension, and alleviates the immune response that is expected. In conclusion, our study provides strong evidence supporting the significant cardiovascular implication of heme and hemoglobin. We have demonstrated that apoHb-Hp complex effectively neutralizes these harmful activities, rendering these heme and free Hb nonreactive, leading to a marked reduction in hemolysis induced endothelial activation. These findings have important implications, suggesting that apoHb-Hp complex plays a protective role for cardiac and pulmonary cells exposed to elevated levels of heme and free Hb, a condition commonly seen in SCD. Furthermore, our study's consistency with prior research reinforces the role of apoHb-Hp complex in preventing P-selectin expression. Our SCD mouse model experiments reveal that apoHb-Hp complex effectively ameliorates vaso-occlusion, regardless of whether the vaso-occlusion was triggered by Hb or heme-independent factors like hypoxia-reoxygenation. Notably, the apoHb-Hp complex also demonstrated some efficacy, indicating that the protective effect extends beyond simple heme clearance and TLR4 signaling inhibition. While our results are promising, further experiments are required to gain a deeper understanding of the apoHb-Hp complex activity in both clearance-dependent and independent mechanisms of resolving vaso-occlusion. Overall, our research highlights the potential therapeutic value of the apoHb-Hp complex in combating the detrimental effects of Hb and heme, and offers valuable insights into its protective role in managing vaso-occlusive events associated with conditions like SCD.

Eccentric remodeling in patients undergoing mitral valve repair due to severe degenerative mitral regurgitation: impact of relative wall thickness on clinical outcomes

Abstract Background Left ventricular (LV) volume overload in mitral regurgitation (MR) leads to a progressive increase in LV mass. Eccentric hypertrophy is defined as the relative wall thickness (RWT) &amp;lt;0.43, and LV hypertrophy is a frequently observed LV remodeling phenotype in patients with severe MR. However, the prognostic impacts of RWT in these patient groups are not well known. We tested the relationship between RWT and clinical outcomes in severe MR patients undergoing MV repair (MVR). Methods A total of 979 consecutive adult patients with severe degenerative MR and eccentric hypertrophy (55 ± 13 years, 616 males) who underwent MVR were retrospectively analyzed. The study population was stratified by the median RWT value (RWT=0.34) on baseline echocardiography [the lesser RWT group (RWT&amp;lt; 0.34 (n=651)) and the greater RWT group (RWT ≥0.34 (n = 328)). Results The patients in the lesser RWT group were younger (54±13 vs. 57±13, p&amp;lt;0.001) and had a significantly higher prevalence of hypertension and diabetic mellitus than those in the greater RWT group. The greater RWT group had significantly lower indexed LV systolic dimension, thicker ventricular walls, and higher LV ejection fraction as compared with those in the lesser RWT group. In Kaplan-Meier analysis, the greater RWT group had a significantly higher incidence of all-cause death (6.4% vs. 2.3%; log-rank p&amp;lt;0.001) and cardiac death (3.0% vs. 0.9%; log-rank p = 0.01) at five years after MVR than in the low RWT group. RWT≥0.34 was independently associated with higher all-cause and cardiac mortality in the multivariate Cox regression analysis. In subgroup analysis, RWT≥0.34 was associated with worse outcomes in men (P &amp;lt;0.001) but not in women (P = 0.23). Moreover, hypertensive patients in the greater RWT group showed the worst outcomes as compared with the three other groups. Conclusions We concluded that excessive ventricular hypertrophy, manifested as an increased relative wall thickness, is associated with a significantly increased risk of postoperative mortalities after mitral valve repair in patients with severe degenerative MR and eccentric hypertrophy. We also found that eccentric remodeling patterns and clinical outcomes differ according to sex and the presence of hypertension.

Dysbiotic microbiome induce cardiac impairment by attenuating brain-derived neurotrophic factor in inflammatory bowel diseases

Abstract Background &amp; Aims Mounting evidence suggests that inflammatory bowel disease (IBD) is associated with increased incidences of cardiovascular diseases (CVD), including myocardial infarction and heart failure. However, the molecular mechanisms by which IBD predisposes patients to CVD are poorly understood. This study aimed to identify the role of dysbiosis in gut-heart crosstalk. Methods Chronic colitis-induced cardiac impairment was assessed in mice subjected to dextran sodium sulfate (DSS), rats treated with trinitrobenzenesulfonic acid, and IL10-/-mice which develop spontaneous colitis after weaning. Fecal microbiota of wild type or IL10-/- mice were transplanted to C57BL/6J mice treated with microbiome-depleting antibiotic cocktail and germ-free mice to determine if dysbiosis afflicts the heart. Heart function was evaluated by echocardiography. Heart transcriptomes were profiled by RNA-sequencing. Gut microbiota profiling was performed by 16S rRNA sequencing. Adverse effect of brain-derived neutrophic factor (BDNF) deficiency on the heart was evaluated in cardiac-specific BDNF knockout mice (BdnfΔheart). Results Impairment of heart function, evidenced by decreased left ventricle ejection fraction (LVEF), increased LV mass, and elevated serum B-type natriuretic peptide, was observed in all 3 models of colitis, providing direct evidence that chronic colitis deteriorates the heart (Figure 1). RNA-sequencing revealed loss of Bdnf and alterations of multiple genes critical to heart homeostasis in the myocardium. Many of the changes, including Bdnf reduction, were found in microbiota-depleted C57BL/6J mice and germ-free mice received dysbiotic fecal microbiome, compared to controls, suggesting that dysbiosis impaired the heart by suppressing Bdnf. BdnfΔheart mice had impaired heart function, including decreased contractility and EF, increased fibrosis, and impaired coronary microcirculation (lower CD31), compared to Bdnf[2lox] mice. Mechanistically, miR-155 in the heart and exosomal miR-29b in the plasma were significantly elevated by chronic colitis. miR-155 and miR-29b mimics suppressed BDNF in cardiomyocytes both in vitro and in vivo. Administration of miR-155 inhibitors or exosomes packaged with miR-29b antagonists ameliorated BDNF reduction in the heart of IL10-/- mice. BDNF supplementation markedly improved heart function in DSS mice. Conclusions Chronic colitis impairs the heart through dysbiosis/miR-29b/miR-155/BDNF signaling axis. Targeting this pathway is a promising strategy to overcome gut dysbiosis harmful for the heart in IBD.

Exercise-induced cardiac remodelling in elite athletes is characterized by a stronger ventricular mass-volume association in females as compared with males: MRI results from the ELITE cohort

Abstract Background Differentiation between exercise-induced cardiac remodelling (EICR) and cardiac pathology constitutes a central challenge in sports cardiology. To assist clinicians, theoretical frameworks have been developed: i.e. dynamic sports are associated with ventricular dilatation, static sports with hypertrophy, and sports containing both components with both dilatation and hypertrophy. However, EICR frameworks have been almost exclusively based on findings in male athletes, and whether these associations are found in female athletes is to date unclear. Purpose We aimed to investigate intersex differences in left ventricular (LV) remodelling in the extreme phenotypes of elite athletes. Methods We included 227 healthy, elite athletes from the ELITE cohort who underwent cardiac magnetic resonance imaging (CMR). Our outcomes of interest were absolute and body surface area (BSA) indexed LV end-diastolic volume, LV end-diastolic wall mass, LV end-diastolic mass-volume ratio to express cardiac remodelling (LV end-diastolic wall mass / LV end-diastolic volume) and correlations of BSA-indexed LV mass with LV end-diastolic volume to compare LV remodelling between sexes. Results A total of 122 male and 105 female elite athletes (age 26±6 years) were included. The age and division in sports categories according to the ESC classification were similar between the sexes. Male athletes showed larger indexed LV end-diastolic volumes (127±19 versus 108±14 ml, p &amp;lt;0.001) and indexed LV wall mass (66±12 versus 50±11 grams, p &amp;lt;0.001) compared to female athletes. Male athletes had a proportionally larger LV mass-volume ratio than women (0.53±0.12 versus 0.46±0.09 g/ml, p &amp;lt;0.001). Female elite athletes showed a moderate association between indexed LV mass increase with indexed LV end-diastolic volume increase (Spearman’s rho 0.45, p &amp;lt;0.001), whereas male athletes showed a weak association (Spearman’s rho 0.25, p =0.006). Conclusions Elite male athletes have larger left ventricular volumes and wall mass, with a greater mass-volume ratio, than their female counterparts. However, female athletes demonstrate a stronger mass-volume association than males. Our findings suggest the presence of distinct sex-dependent features of EICR.

Sex-Related Differences of Left Atrial Strain in Patients With Hypertension Using Cardiac Magnetic Resonance Feature Tracking.

Previous studies demonstrated the impact of sex on left ventricular (LV) strain in patients with essential hypertension. However, little is known about the effect of sex on left atrial (LA) strain in patients with hypertension. This study aimed to explore the sex-related differences of LA strain by using cardiac magnetic resonance feature tracking in patients with hypertension and preserved LV ejection fraction. One hundred and fifty hypertensive patients (100 men and 50 women) and 105 age-matched and sex-matched normotensive controls (70 men and 35 women) were retrospectively enrolled and underwent cardiac magnetic resonance examination. LA strain parameters included LA reservoir strain (εs), conduit strain (εe), pump strain (εa), and their corresponding strain rate (SRs, SRe, and SRa). Men had significantly higher LV mass index, lower εs and εe than women in both patients and controls (all P <0.05). LA strain and strain rate were significantly reduced in hypertensive patients compared with controls, both in men and women (all P <0.05). In men, hypertension and its interaction were associated with increased LV mass index and decreased εs and εe. In multivariable analysis, men, LV ejection fraction, and LA minimum volume index remained independent determinants of εs and εe in all hypertensive patients (all P <0.05). LA strain was significantly impaired in hypertensive patients, and men had more impaired LA strain than women. These findings further emphasize the sex-related differences in the response of LA strain to hypertension in the early stage.

Characterization of Cardiac Fat in Atrial Fibrillation Patients Prior to Ablation Treatment

Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) contribute to the development of left atrial fibrillation (AF). The purpose of this study is to determine the factors influencing cardiac fat, evaluate its impact on heart function, and evaluate its role in the recurrence of AF. Cardiac MRI exams of n = 198 patients with paroxysmal AF were retrospectively analyzed to quantify EAT and PAT. Body mass index (BMI) showed significant associations with increased EAT, PAT, and total cardiac fat, particularly with the total end-systolic area (p &lt; 0.001). Males were associated with increased PAT (r = −0.331, p &lt; 0.001) and EAT (r = −0.168, p = 0.019). Increased PAT end-diastolic volume was also associated with an increase in LV mass (r = 0.249, p &lt; 0.01). An inverse relationship between EAT end-systolic area and cardiac index (r = −0.220, p &lt; 0.01) was observed. Although BMI did not significantly affect AF recurrence, overweight patients (36%) experienced slightly more AF recurrence than obese patients (33%). Obesity is substantially associated with an increase in EAT and PAT, while sex appears to play a greater role in PAT than EAT and decreased cardiac function.

LBBB and heart failure-Relationships among QRS amplitude, duration, height, LV mass, and sex.

Height, left ventricular (LV) size, and sex were proposed as additional criteria for patient selection for cardiac resynchronization therapy (CRT) but their connections with the QRS complex in left bundle branch block (LBBB) are little investigated. We evaluated these. Among patients with "true" LBBB, QRS duration (QRSd) and amplitude, and LV hypertrophy indices, were correlated with patient's height and LV mass, and compared between sexes. In this study cohort (n = 220; 60 ± 12 years; left ventricular ejection fraction [LVEF] 21 ± 7%; mostly New York Heart Association II-III, QRSd 165 ± 19 ms; 57% female; 70% responders [LVEF increased ≥5%]), LV mass was increased in all patients. QRS amplitude did not correlate with LV mass or height in any individual lead or with Sokolow-Lyon or Cornell-Lyon indices. QRSd did not correlate with height. In contrast, QRSd correlated strongly with LV mass (r = .51). CRT response rate was greater in women versus men (84% vs. 58%, p < .001) despite shorter QRSd [7% shorter (p < .0001)]. QRSd normalized for height resulted in a 2.7% and for LV mass 24% greater index in women. True LBBB criteria do not exclude HF patients with increased LV mass. QRS amplitudes do not correlate with height or LV mass. Height does not affect QRSd. However, QRSd correlates with LV size. QRSd normalized for LV mass results in 24% greater value in women in the direction of sex-specific responses. LV mass may be a significant nonelectrical modifier of QRSd for CRT.