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This research examines glucose's effect on heart development and congenital heart defects. Chicken embryos and D-glucose and L-glucose were used together to model hyperglycemia. Each egg was windowed, glucose was applied, and data was collected in the form of images and videos using stereo microscopes. Each chicken embryo's heart length, rate, and outflow tract diameter were analyzed using two image/video segmentation software: MATLAB and ImageJ. In MATLAB, two different algorithms were developed to segment and analyze the chicken embryos. The delineation algorithm outputted the diameter of the heart outflow tract during heart diastole and the heart length in mm. The M-mode analysis algorithm outputted the contrast values of a cardiac cycle of a user-specified segment. In ImageJ, a linear measurement algorithm was used to quantify embryo characteristics. The results of our study show that adding glucose caused the heart rate of the embryo to increase, the length of the heart to decrease, and the outflow tract distance during heart diastole to increase, all-in-all demonstrating that adding any concentration/type of glucose induces hyperglycemia in chicken embryos and alters the development of their heart which can be projected to humans. [ABSTRACT FROM AUTHOR]

Aims A shorter cardiac rest period within a cardiac cycle is usually thought to be a result of a fast heart rate, and its clinical relevance has long been ignored. The aim of the present study was to test the hypothesis that the length of cardiac rest periods is altered in postcapillary pulmonary hypertension (PH). Methods and results Twenty-six patients with postcapillary PH and 20 healthy controls were recruited for cardiac magnetic resonance imaging (MRI) scans. All participants had a heart rate no higher than 80 beats/minute. Cine magnetic resonance imaging (MRI, acquired at a four-chamber view) was analyzed to determine the length of cardiac rest periods at end-systole and mid-to-late diastole. PH patients had a shorter rest period at mid-to-late diastole than controls (17.5 ± 8.7% vs. 24.2 ± 4.2%, P = 0.003). Receiver operating characteristic (ROC) curves showed that the proportion of the rest period in diastole (defined as the length of diastasis/diastole) can discriminate PH patients from controls [area under the curve (AUC) = 0.83, 95% confidence interval (CI): 0.71–0.96]. The existence of postcapillary PH was a significant contributor (β = −5.537, P = 0.023) to shorter cardiac rest periods at mid-to-late diastole after adjusting for potential confounders, including age, sex, heart rate, and blood pressure. Conclusions Postcapillary PH is independently associated with shorter cardiac rest periods at mid-to-late diastole. The length of cardiac rest periods has the potential to become a novel quantitative imaging biomarker for indicating cardiovascular health. [ABSTRACT FROM AUTHOR]

Introduction: Hypertrophic cardiomyopathy (HCM) is a cardiovascular genetic disease caused largely by sarcomere protein mutations. Gaps in our understanding exist as to how maladaptive sarcomeric biophysical signals are transduced to intra- and extracellular compartments leading to HCM progression. To investigate early HCM progression, we focused on the onset of myofilament dysfunction during neonatal development and examined cardiac dynamics, coronary vascular structure and function, and mechano-transduction signaling in mice harboring a thin-filament HCM mutation. Methods: We studied postnatal days 7-28 (P7-P28) in transgenic (TG) TG-cTnTR92Q and non-transgenic (NTG) mice using skinned fiber mechanics, echocardiography, biochemistry, histology, and immunohistochemistry. Results: At P7, skinned myofiber bundles exhibited an increased Ca2+-sensitivity (pCa50 TG: 5.97 ± 0.04, NTG: 5.84 ± 0.01) resulting from cTnT-R92Q expression on a background of slow skeletal (fetal) troponin I and a/ß myosin heavy chain isoform expression. Despite the transition to adult isoform expressions between P7-P14, the increased Ca2+- sensitivity persisted through P28 with no apparent differences in gross morphology among TG and NTG hearts. At P7 significant diastolic dysfunction was accompanied by coronary flow perturbation (mean diastolic velocity, TG: 222.5 ± 18.81 mm/s, NTG: 338.7 ± 28.07 mm/s) along with localized fibrosis (TG: 4.36% ± 0.44%, NTG: 2.53% ± 0.47%). Increased phosphorylation of phospholamban (PLN) was also evident indicating abnormalities in Ca2+ homeostasis. By P14 there was a decline in arteriolar cross-sectional area along with an expansion of fibrosis (TG: 9.72% ± 0.73%, NTG: 2.72% ± 0.2%). In comparing mechano-transduction signaling in the coronary arteries, we uncovered an increase in endothelial YAP expression with a decrease in its nuclear to cytosolic ratio at P14 in TG hearts, which was reversed by P28. Conclusion: We conclude that those early mechanisms that presage hypertrophic remodeling in HCM include defective biophysical signals within the sarcomere that drive diastolic dysfunction, impacting coronary flow dynamics, defective arteriogenesis and fibrosis. Changes in mechano-transduction signaling between the different cellular compartments contribute to the pathogenesis of HCM. [ABSTRACT FROM AUTHOR]

The multicellular organization of diverse systems, including embryos, intestines, and tumors relies on coordinated cell migration in curved environments. In these settings, cells establish supracellular patterns of motion, including collective rotation and invasion. While such collective modes have been studied extensively in flat systems, the consequences of geometrical and topological constraints on collective migration in curved systems are largely unknown. Here, we discover a collective mode of cell migration in rotating spherical tissues manifesting as a propagating single-wavelength velocity wave. This wave is accompanied by an apparently incompressible supracellular flow pattern featuring topological defects as dictated by the spherical topology. Using a minimal active particle model, we reveal that this collective mode arises from the effect of curvature on the active flocking behavior of a cell layer confined to a spherical surface. Our results thus identify curvature-induced velocity waves as a mode of collective cell migration, impacting the dynamical organization of 3D curved tissues. The existence of multicellular systems relies on coordinated cell motion in three dimensions. Here, cell migration in rotating spherical tissues is shown to exhibit a collective mode with a single-wavelength velocity wave, which arises from the effect of curvature on the flocking behavior of cells on a spherical surface. [ABSTRACT FROM AUTHOR]

Aim of this study was to compare right ventricular echocardiography parameters in urbanized hypertensive patients of the Shor and non-indigenous ethnic groups in the Mountain Shoria region. The study included patients with arterial hypertension: 58 Shors and 50 non-indigenous urbanized residents, comparable in age, and divided by ethnicity and gender into 4 groups: Shors men (n = 20), Shors women (n = 38) , non-indigenous men (n = 15) and non-indigenous women (n = 35). All underwent echocardiographic examination, and the right heart parameters were studied. Shor men with arterial hypertension had the lowest values ​​of the pulmonary artery index (p = 0.05), the right atrium dimensions (p = 0.04), and the highest values ​​of the blood flow velocity in the right ventricle, et' (p = 0.05) and st' (p = 0.05) in comparison with non-indigenous men. Shor women have the lowest values Et/At ratios (p = 0.05). RV diastolic dysfunction was detected mainly in women compared with men (23.1% and 1.9%, p = 0.0014), somewhat more often in Shors. Ethnicity was one of the factors associated with the right ventricular diastolic dysfunction presence (p = 0.002). Among the factors associated with the RV diastolic dysfunction were risk factors (smoking, obesity), blood pressure, gender, ethnicity, and left ventricular parameters (diastolic dysfunction and the myocardial mass increase). Thus, our study established the influence of ethnic differences on the right heart echocardiographic parameters in Shors and Caucasians with arterial hypertension. The effect of sex on RV diastolic dysfunction was a lot bigger compared to the effect of ethnicity. The revealed differences should improve the assessment of the right heart structure and function in patients with arterial hypertension from small ethnic groups, which will help to improve the diagnosis and treatment of such patients. [ABSTRACT FROM AUTHOR]

Background: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson's correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson's trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1β, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats. [ABSTRACT FROM AUTHOR]

Diastolic dysfunction persists despite coronary artery bypass graft surgery (CABG) in patients with hibernating myocardium (HIB). We studied whether the adjunctive use of a mesenchymal stem cells (MSCs) patch during CABG improves diastolic function by reducing inflammation and fibrosis. HIB was induced in juvenile swine by placing a constrictor on the left anterior descending (LAD) artery, causing myocardial ischemia without infarction. At 12 weeks, CABG was performed using the left-internal-mammary-artery (LIMA)-to-LAD graft with or without placement of an epicardial vicryl patch embedded with MSCs, followed by four weeks of recovery. The animals underwent cardiac magnetic resonance imaging (MRI) prior to sacrifice, and tissue from septal and LAD regions were collected to assess for fibrosis and analyze mitochondrial and nuclear isolates. During low-dose dobutamine infusion, diastolic function was significantly reduced in HIB compared to the control, with significant improvement after CABG + MSC treatment. In HIB, we observed increased inflammation and fibrosis without transmural scarring, along with decreased peroxisome proliferator-activated receptor-gamma coactivator (PGC1α), which could be a possible mechanism underlying diastolic dysfunction. Improvement in PGC1α and diastolic function was noted with revascularization and MSCs, along with decreased inflammatory signaling and fibrosis. These findings suggest that adjuvant cell-based therapy during CABG may recover diastolic function by reducing oxidant stress–inflammatory signaling and myofibroblast presence in the myocardial tissue. [ABSTRACT FROM AUTHOR]

The lifetime effects of space irradiation (IR) on left ventricular (LV) function are unknown. The cardiac effects induced by space-type IR, specifically 5-ion simplified galactic cosmic ray simulation (simGCRsim), are yet to be discovered. Three-month-old, age-matched, male C57BL/6J mice were irradiated with 137Cs gamma (γ; 100, 200 cGy) and simGCRsim (50 and 100 cGy). LV function was assessed via transthoracic echocardiography at 14 and 28 days (early), and at 365, 440, and 660 (late) days post IR. We measured the endothelial function marker brain natriuretic peptide in plasma at three late timepoints. We assessed the mRNA expression of the genes involved in cardiac remodeling, fibrosis, inflammation, and calcium handling in LVs harvested at 660 days post IR. All IR groups had impaired global LV systolic function at 14, 28, and 365 days. At 660 days, 50 cGy simGCRsim-IR mice exhibited preserved LV systolic function with altered LV size and mass. At this timepoint, the simGCRsim-IR mice had elevated levels of cardiac fibrosis, inflammation, and hypertrophy markers Tgfβ1, Mcp1, Mmp9, and βmhc, suggesting that space-type IR may induce the cardiac remodeling processes that are commonly associated with diastolic dysfunction. IR groups showing statistical significance were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). The observed dose-response shape did not indicate a lower threshold at these IR doses. A single full-body IR at doses of 100–200 cGy for γ-IR, and 50–100 cGy for simGCRsim-IR decreases the global LV systolic function in WT mice as early as 14 and 28 days after exposure, and at 660 days post IR. Interestingly, there is an intermediate time point (365 days) where the impairment in LV function is observed. These findings do not exclude the possibility of increased acute or degenerative cardiovascular disease risks at lower doses of space-type IR, and/or when combined with other space travel-associated stressors such as microgravity. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) leads to acute cardiac injury and dysfunction in cardiorenal syndrome Type 3 (CRS3) through oxidative stress (OS). The stress-inducible Sestrin2 (Sesn2) protein reduces reactive oxygen species (ROS) accumulation and activates AMP-dependent protein kinase (AMPK) to regulate cellular metabolism and energetics during OS. Sesn2 levels and its protective effects decline in the aged heart. Antidiabetic drug metformin upregulates Sesn2 levels in response to ischemia–reperfusion (IR) stress. However, the role of metformin in CRS3 remains unknown. This study seeks to explore how the age-related decrease in cardiac Sesn2 levels contributes to cardiac intolerance to AKI-induced insults, and how metformin ameliorates CRS3 through Sesn2. Young (3–5 months) and aged (21–23 months) C57BL/6J wild-type mice along with cardiomyocyte-specific knockout (cSesn2−/−) and their wild type of littermate (Sesn2f/f) C57BL/6J mice were subjected to AKI for 15 min followed by 24 h of reperfusion. Cardiac and mitochondrial functions were evaluated through echocardiograms and seahorse mitochondria respirational analysis. Renal and cardiac tissue was collected for histological analysis and immunoblotting. The results indicate that metformin could significantly rescue AKI-induced cardiac dysfunction and injury via Sesn2 through an improvement in systolic and diastolic function, fibrotic and cellular damage, and mitochondrial function in young, Sesn2f/f, and especially aged mice. Metformin significantly increased Sesn2 expression under AKI stress in the aged left-ventricular tissue. Thus, this study suggests that Sesn2 mediates the cardioprotective effects of metformin during post-AKI. [ABSTRACT FROM AUTHOR]

Background: Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality. Methods: Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations. Results: One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 [0.24–0.80], p = 0.007) and total arrhythmia (OR 0.56 [0.37–0.92], p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality. Conclusions: Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia. [ABSTRACT FROM AUTHOR]

Myocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1β or the IL-1 receptor. In contrast, the potential role of IL-1α in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1α may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1α deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1α deficiency (IL-1α KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1α therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation. [ABSTRACT FROM AUTHOR]

To date, the ventricular myocardial band is the anatomical‐functional model that best explains cardiac mechanics during systolic‐diastolic phenomena in the cardiac cycle. The implications of the model fundamentally affect the anatomical interpretation of the ventricular myocardium, giving meaning to the direction that muscle fibers take, turning them into an object of study with potential clinical, imaging, and surgical applications. Re‐interpreting the anatomy of the ventricular muscle justifies changes in the physiological interpretation, from its functional focus as a fiber unraveling the mechanical phenomena carried out during systole and diastole. We identify the functioning of the heart from the electrical and hemodynamic point of view, but it is necessary to delve into the mechanics that originate the hemodynamic changes observed flowmetrically, and that manifested during the pathology. In this review, the mechanical phenomena that the myocardium performs in each phase of the cardiac cycle are broken down in detail, emphasizing the physical displacements that each of the muscle segments presents, as well as a vision of their alteration and in which pathologies they are mainly identified. Visually, an anatomical correlation to the echocardiogram is provided, pointing out the direction of the segmental myocardial displacement by the strain velocity vector technique. [ABSTRACT FROM AUTHOR]

Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40–160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias. [ABSTRACT FROM AUTHOR]

Patients with Type 2 diabetes mellitus (T2DM) frequently exhibit a distinctive cardiac phenotype known as diabetic cardiomyopathy. Cardiac complications associated with T2DM include cardiac inflammation, hypertrophy, fibrosis, and diastolic dysfunction in the early stages of the disease, which can progress to systolic dysfunction and heart failure. Effective therapeutic options for diabetic cardiomyopathy are limited and often have conflicting results. The lack of effective treatments for diabetic cardiomyopathy is due in part, to our poor understanding of the disease development and progression, as well as a lack of robust and valid preclinical human models that can accurately recapitulate the pathophysiology of the human heart. In addition to cardiomyocytes, the heart contains a heterogeneous population of non-myocytes including fibroblasts, vascular cells, autonomic neurons, and immune cells. These cardiac non-myocytes play important roles in cardiac homeostasis and disease, yet the effect of hyperglycaemia and hyperlipidaemia on these cell types is often overlooked in preclinical models of diabetic cardiomyopathy. The advent of human-induced pluripotent stem cells provides a new paradigm in which to model diabetic cardiomyopathy as they can be differentiated into all cell types in the human heart. This review will discuss the roles of cardiac non-myocytes and their dynamic intercellular interactions in the pathogenesis of diabetic cardiomyopathy. We will also discuss the use of sodium-glucose cotransporter 2 inhibitors as a therapy for diabetic cardiomyopathy and their known impacts on non-myocytes. These developments will no doubt facilitate the discovery of novel treatment targets for preventing the onset and progression of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Formalin preservation affects the stable isotope composition of zooplankton samples, thus limiting the analysis of valuable collections covering large time intervals. Here, we compare different procedures for correcting the bias caused by formalin in δ13C and δ15N of zooplankton community samples. Zooplankton samples representative of seasonal variations in the period 2000–2009 were collected off A Coruña (NW Spain). Part of the sample was immediately dried and analysed for δ13C, δ15N, and elemental composition within 3 years of collection. These values were used as the unpreserved reference. The remaining sample was preserved in 4% formaldehyde and aliquots obtained after a period ranging from 3 years to more than 10 years of storage were analysed as the originally dried samples. Additionally, the copepod fraction of total biomass was determined in the preserved samples. Corrections of formalin effects based on ordinary least squares regression had large uncertainties, while mass balance corrections based on the change in C:N ratio (only possible for δ13C) overestimated reference values. However, either simple corrections based on the mean difference between values in dry and preserved samples or more complex generalised additive models considering seasonality, copepod biomass, and time of sample storage, produced estimations with relatively low uncertainty. Our results highlight the importance of determining specific correction solutions for each preserved collection before reconstructing stable isotope time series. Furthermore, the uncertainties associated with the estimates can be used in sensitivity analysis to assess their potential impact on the interpretation of the series. [ABSTRACT FROM AUTHOR]

Background: Smoking is a preventable cause of human death. While the chronic effects of smoking on cardiovascular health are well known, its acute effects remain obscure. Objectives: This study aimed to assess the acute effects of smoking on left ventricle (LV) diastolic and systolic cardiac function and right ventricle (RV) systolic function in healthy smokers. Methods: In this before-after (quasi-experimental) study conducted at Modarres and Shohada-e-Tajrish hospitals in Tehran, Iran, healthy smokers were asked to discontinue smoking and caffeine for half an hour. Then, they underwent echocardiography by the same echo-cardiologist at baseline and 10 minutes after smoking a single cigarette with 10 mg of nicotine. The 2D speckle tracking mode illustrated the diastolic and systolic ventricular functions. Results: Among 80 participants were 54 males (67.5%) and 26 females (32.5%). The mean age was 36.8 ± 13.6 years. The mean smoking history was 7.3 ± 7.5 pack years. Significant changes occurred after smoking in the global longitudinal strain (GLS), E/A ratio, and pulmonary artery systolic pressure (P = 0.001). No changes occurred in other factors including ejection fraction (EF), S wave velocity of septum, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic function (SRV) (P > 0.05). Conclusions: This study was carried out as a pilot for larger clinical studies to demonstrate the acute effects of smoking on heart function and cardiovascular health. Our findings indicate that smoking acutely affects both right and left ventricular parameters on echocardiography. [ABSTRACT FROM AUTHOR]

It is estimated that 30 to 50% of heart failure patients have heart failure with preserved ejection fraction (HFpEF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of heart failure patients with reduced ejection fraction (HFrEF). The management of patients with HFpEF is essentially empirical, limited, and disappointing. HFpEF is characterized by diastolic dysfunction leading to increased left ventricular (LV) filling pressures. We have previously described how mechanical energy transfer from the systole phase to the diastole phase of the cardiac cycle can potentially reduce filling pressures during the diastolic phase which may improve clinical symptoms of HFpEF. The CORolla device is a novel device anatomically designed for positioning in the left ventricle (LV) and mechanically designed to apply an outward radial force on the LV endocardium thus transferring energy from the systolic phase, in which the device contracts, gaining potential energy, to the diastolic phase from its recoil. Here we summarize the present knowledge concerning the energy transfer therapeutic approach for HFpEF, describe the CORolla device, and depict its potential future clinical indications. [ABSTRACT FROM AUTHOR]

Simple Summary: Cardiac fibrosis is a vital pathophysiologic change in heart disease, which eventually leads to heart failure. Several molecular mechanisms positively or negatively regulate myocardial fibrosis, among which long noncoding RNAs have gained increased attention. We summarize the contributions of lncRNAs to miRNA expression, TGF-β signaling, and ECMs synthesis, with a particular attention on the exosome-derived lncRNAs in the regulation of adverse fibrosis as well as the mode of action of lncRNAs secreted into exosomes. We also discuss how the current knowledge on lncRNAs can be applied to develop novel therapeutic strategies. This study may provide clues for the prevention and therapy of cardiac fibrosis. Cardiac fibrosis remains an unresolved problem in cardiovascular diseases. Fibrosis of the myocardium plays a key role in the clinical outcomes of patients with heart injuries. Moderate fibrosis is favorable for cardiac structure maintaining and contractile force transmission, whereas adverse fibrosis generally progresses to ventricular remodeling and cardiac systolic or diastolic dysfunction. The molecular mechanisms involved in these processes are multifactorial and complex. Several molecular mechanisms, such as TGF-β signaling pathway, extracellular matrix (ECM) synthesis and degradation, and non-coding RNAs, positively or negatively regulate myocardial fibrosis. Long noncoding RNAs (lncRNAs) have emerged as significant mediators in gene regulation in cardiovascular diseases. Recent studies have demonstrated that lncRNAs are crucial in genetic programming and gene expression during myocardial fibrosis. We summarize the function of lncRNAs in cardiac fibrosis and their contributions to miRNA expression, TGF-β signaling, and ECMs synthesis, with a particular attention on the exosome-derived lncRNAs in the regulation of adverse fibrosis as well as the mode of action of lncRNAs secreted into exosomes. We also discuss how the current knowledge on lncRNAs can be applied to develop novel therapeutic strategies to prevent or reverse cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: ivabraddine is a pure heart rate lowering medication that its usage is beneficial in SIRS and MODS as it can reduce heart rate and decrease oxygen consumption especially at low ejection fraction where other medications cannot undergo their potential cardioprotective effect. Aim of work: The aim of this case study was to report the use of Ivabradine in patients who developed SIRS and compare this group with patients who developed SIRS without Ivabradine use for incidence of changes in systolic and diastolic indices, ejection fraction EF and cardiac index CI and effects on hemodynamics, organ perfusion parameters, and outcome of SIRS and MODS. Patients and methods: Patients who presented to emergency department with SIRS and admitted to ICU. The study population will include 40 patients who developed SIRS and admitted to ICU. A total of 40 patients were divided into two groups: Group I: SIRS patients with ivabradine treatment. Group II: SIRS patients without Ivabradine treatment. Results; Comparative study between the 2 groups revealed, highly significant increase in follow up SvO2, EF and CI, at end of Ivabradine treatment, compared to control group without Ivabradine treatment (p < 0.05 respectively). Conclusion: By comparative study between two groups of sepsis there was a significant improvement in cardiac indices in Ivabradine group at the end of the study (high cardiac index and ejection fraction), In addition to improvement of petfusion parameters. [ABSTRACT FROM AUTHOR]

The mineralocorticoid receptor (MR) plays an important role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option, but their use in patients with CKD is limited due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA associated with an improved benefit-risk profile in comparison to steroidal MRAs. In this study, we decided to test whether finerenone improves renal and cardiac function in male hypertensive and diabetic ZSF1 rats as an established preclinical HFpEF model. Finerenone was administered at 10 mg/kg/day for 12 weeks. Cardiac function/hemodynamics were assessed in vivo. ZSF1 rats showed classical signs of CKD with increased BUN, UACR, hypertrophy, and fibrosis of the kidney together with characteristic signs of HFpEF including cardiac fibrosis, diastolic dysfunction, and decreased cardiac perfusion. Finerenone treatment did not impact kidney function but reduced renal hypertrophy and cardiac fibrosis. Interestingly, finerenone ameliorated diastolic dysfunction and cardiac perfusion in ZSF1 rats. In summary, we show for the first time that non-steroidal MR antagonism by finerenone attenuates cardiac diastolic dysfunction and improves cardiac perfusion in a preclinical HFpEF model. These cardiac benefits were found to be largely independent of renal benefits. [ABSTRACT FROM AUTHOR]

Inappropriate mineralocorticoid receptor (MR) activation in different cardiovascular cell types has deleterious effects on cardiac remodeling and function. Therefore, MR inhibition is a crucial pharmacological strategy to overcome cardiovascular dysfunction. Despite efficient blockade of MR with steroidal MR antagonists (MRAs), their clinical application is unsatisfactory due to the adverse effects. Newer non-steroidal MRAs with greater potency could be suitable for clinical application, especially in patients with type 2 diabetes mellitus and chronic kidney disease. Although clinical evidence has shown the beneficial effects of non-steroidal MRAs on cardiovascular outcomes in patients with heart failure with reduced ejection fraction, clinical trials are ongoing to evaluate the efficacy of heart failure with preserved ejection fraction. Therefore, comparative pharmacological characterization of non-steroidal MRAs over classic steroidal MRAs is crucial. Here, we summarize the pre-clinical evidence of non-steroidal MRAs, which suggests an improvement in cardiac dysfunction, as well as the underlying molecular mechanisms in animal models mimicking different clinical conditions. In addition, we discuss up-to-date information from clinical trials regarding the beneficial effects of non-steroidal MRAs on meaningful cardiovascular outcomes. Both pre-clinical and clinical evidence support treatment with non-steroidal MRAs in patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. Methods: 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. Results: BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = − 83.2 and c = − 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = − 253.1, p < 0.001) and diastolic (c = − 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). Conclusion: 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies. [ABSTRACT FROM AUTHOR]

The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the development and functional role of CM crests during the postnatal period. We found in rodents that CM crest maturation occurs late between postnatal day 20 (P20) and P60 through both SSM biogenesis, swelling and crest-crest lateral interactions between adjacent CM, promoting tissue compaction. At the functional level, we showed that the P20-P60 period is dedicated to the improvement of relaxation. Interestingly, crest maturation specifically contributes to an atypical CM hypertrophy of its short axis, without myofibril addition, but relying on CM lateral stretching. Mechanistically, using constitutive and conditional CM-specific knock-out mice, we identified ephrin-B1, a lateral membrane stabilizer, as a molecular determinant of P20-P60 crest maturation, governing both the CM lateral stretch and the diastolic function, thus highly suggesting a link between crest maturity and diastole. Remarkably, while young adult CM-specific Efnb1 KO mice essentially exhibit an impairment of the ventricular diastole with preserved ejection fraction and exercise intolerance, they progressively switch toward systolic heart failure with 100% KO mice dying after 13 months, indicative of a critical role of CM-ephrin- B1 in the adult heart function. This study highlights the molecular determinants and the biological implication of a new late P20-P60 postnatal developmental stage of the heart in rodents during which, in part, ephrin-B1 specifically regulates the maturation of the CM surface crests and of the diastolic function. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 infection is associated with multiple cardiac manifestations. Left atrial strain (LA-S) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and diastolic dysfunction, which could lead to early recognition of cardiac injury in severe COVID-19 patients with possible implications on clinical management, organ dysfunction, and mortality. Cardiac injury may occur by direct viral cytopathic effects or virus-driven immune activation, resulting in heart infiltration by inflammatory cells, despite limited and conflicting data are available on myocardial histology. Purpose: We aimed to explore LA-S and immune profiles in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: We enrolled 30 patients > 18 years with positive SARS-CoV-2 RT-PCR, admitted to ICU. Acute myocardial infarction and pulmonary embolism were exclusion criteria. On days D1, D3, and D7 after ICU admission, patients performed TTE, hemogram, cardiac (pro-BNP; troponin) and inflammatory biomarkers (ESR; ferritin; IL1β; IL6; CRP; d-dimer; fibrinogen; PCT; adrenomedullin, ADM), and immunophenotyping by flow cytometry. Results: Patient's mean age was 60.7 y, with 63% males. Hypertension was the most common risk factor (73%; with 50% of patients under ACEi or ARA), followed by obesity (40%, mean BMI = 31 kg/m2). Cardiac dysfunction was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. Mortality, hospitalization days, remdesivir use, organ dysfunction, cardiac and serum biomarkers were not different between patients with (DYS) and without cardiac dysfunction (nDYS), except for ADM (increased in nDYS group at D7). From the 77 TTE, there was a striking difference between diastolic dysfunction evaluation by classic criteria compared to STE (28.6% vs. 57.1%, p = 0.0006). Lower reservoir (Ɛ) and contraction (ƐCT) LA-S correlated with IL-6 (Ɛ, p = 0.009, r = − 0.47; ƐCT, p = 0.0002, r = − 0.63) and central memory CD4 T-cells (ƐCT, p = 0.049, r = − 0.24). Along all timepoints, DYS patients showed persistent low lymphocyte counts that recovered at D7 in nDYS patients. DYS patients had lower platelets at D3 and showed a slower recovery in platelet counts and CRP levels; the latter significantly decreased at D7 in nDYS patients (p = 0.009). Overall, patients recovered with an increasing P/F ratio, though to a lesser extent in DYS patients. Discussion: Our study shows that LA-S may be a more sensitive marker for diastolic dysfunction in severe COVID-19, which could identify patients at risk for a protracted inflammatory state. A differential immune trait in DYS patients at ICU admission, with persistent lymphopenia, enriched CM T-cells, and higher IL-6 may suggest distinct inflammatory states or migration patterns in patients that develop cardiac injury. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism can predispose systolic and diastolic cardiac dysfunction, increased peripheral vascular resistance, endothelial dysfunction, altered coagulopathy, and dyslipidemia resulting in atherosclerosis. Thyroid hormones can influence homocysteine metabolism by regulating the methylenetetrahydrofolate reductase (MTHR). So, this study aimed to compare the markers homocysteine, high sensitive C-reactive protein (hs-CRP), and Athero - genic Indices (AI) between newly diagnosed hypothyroid and euthyroid premenopausal women. Methods: 80 Female patients between 20 and 45 years were enrolled in this study and were equally divided into cases and controls group. Laboratory tests included: i) Serum T3, T4, TSH was measured using electrochemiluminescence, ii) lipid profile, homocysteine, and hs-CRP were measured for all the participants. Atherogenic indices: Castelli risk indices I&II, Atherogenic coefficient (AEC), and Atherogenic Index of Plasma (AIP) were calculated using formulas. A comparison between the study groups was made by using the Independent t-test and Mann-Whitney U test. p-value <0.05 was considered significant. Results: The hypothyroid group had significantly higher levels of homocysteine (p=0.014), and hs-CRP (hs-CRP >3.0 mg/L, 70% of participants have intermediate to high risk for a cardiovascular event) and elevated BMI compared to participants in the euthyroid group. Atherogenic indices (p<0.001) was significantly increased in the hypothyroid participants’ group. TC, TG, and LDL were significantly elevated in the hypothyroid group but did not show any association with systolic and diastolic blood pressure. Conclusions: Premenopausal women with hypothyroidism have a greater predisposition for cardiovascular disease compared to euthyroid. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (PKD) is a hereditary kidney disorder which can affect cardiovascular system. Cardiac hypertrophy and cardiomyopathy in PKD have been reported by echocardiography analyses, but histopathology analyses of human PKD hearts have never been examined. The current studies evaluated human heart tissues from five subjects without PKD (non-PKD) and five subjects with PKD. Our histopathology data of human PKD hearts showed an increased extracellular matrix associated with cardiac hypertrophy and fibrosis. Hypertrophy- and fibrosis-associated pathways involving abnormal cardiac structure were next analyzed. We found that human PKD myocardium was infiltrated by inflammatory macrophage M1 and M2; expression of transforming growth factor (TGF-β1) and its receptor were upregulated with overexpression of pSmad3 and β-catenin. Because patients with PKD have an abnormal kidney function that could potentially affect heart structure, we used a heart-specific PKD mouse model to validate that cardiac hypertrophy and fibrosis were independent from polycystic kidney. In summary, our data show that hearts from human PKD were characterized by hypertrophy, interstitial fibrosis, perivascular fibrosis, and conduction system fibrosis with upregulated TGF-β1 and its receptor. We suggest that such structural abnormalities may predispose to systolic and diastolic cardiac dysfunction in the PKD myocardium. [ABSTRACT FROM AUTHOR]

Smoothelin-like 1 (SMTNL1) modulates the contractile performance of smooth muscle and thus has a key role in vascular homeostasis. Elevated vascular tone, recognized as a contributor to the development of progressive cardiac dysfunction, was previously found with SMTNL1 deletion. In this study, we assessed cardiac morphology and function of male and female, wild-type (Smtnl1+/+) and global SMTNL1 knockout (Smtnl1−/−) mice at 10 weeks of age. Gross dissection revealed distinct cardiac morphology only in males; Smtnl1−/− hearts were significantly smaller than Smtnl1+/+, but the left ventricle (LV) proportion of heart mass was greater. Male Smtnl1−/− mice also displayed increased ejection fraction and fractional shortening, as well as elevated aortic and pulmonary flow velocities. The impact of cardiac stress with pressure overload by transverse aortic constriction (TAC) was examined in male mice. With TAC banding, systolic function was preserved, but the LV filling pressure was selectively elevated due to relaxation impairment. Smtnl1−/− mice displayed higher early/passive filling velocity of LV/early mitral annulus velocity ratio (E/E′ ratio) and myocardial performance index along with a prolonged isovolumetric relaxation time. Taken together, the findings support a novel, sex-dimorphic role for SMTNL1 in modulating cardiac structure and function of mice. [ABSTRACT FROM AUTHOR]

The impact of a dilated left ventricular (LV) on right ventricular (RV) diastolic function has not been investigated. We hypothesized that in patients with a patent ductus arteriosus (PDA), LV dilation causes elevation of the RV end-diastolic pressure (RVEDP) through ventricular-ventricular interaction. We identified patients' ages 6 months to 18 years who underwent transcatheter PDA closure at our center from 2010 to 2019. One hundred and thirteen patients were included with a median age of 3 years (0.5-18). The median LV end-diastolic dimension (LVEDD) Z-score was 1.6 (-1.4-6.3). RVEDP was positively associated with RV systolic pressure (0.38, P < 0.01), ratio of pulmonary artery/aortic systolic pressure (0.4, P < 0.01), and pulmonary capillary wedge pressure (0.71, P < 0.01). RVEDP was not associated with LVEDD Z-score (0.03, P = 0.74). In children with a PDA, RVEDP was not associated with LV dilation, but was positively associated with RV systolic pressure. [ABSTRACT FROM AUTHOR]

BACKGROUND: The function of left atrium (LA) is difficult to assess because of its ventricledependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. METHODS: Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. RESULTS: The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). CONCLUSIONS: The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size. [ABSTRACT FROM AUTHOR]

In the wake of studies targeting atherosclerotic plaques and searching for quantifiable variables that contribute additional information to therapeutic decision-making, plaque assessment using Shear Wave Elastography (SWE) is emerging as a reproducible and promising alternative. We used a single Logiq S8 device (General Electric, Boston, Massachusetts, United States) with an 8.5-11MHz multifrequency linear transducer at 10MHz in longitudinal section. We considered relevant criteria for image acquisition: adequate longitudinal insonation, differentiation of the intima-media complex, delineation of proximal and distal tunica adventitia and the vascular lumen, good visualization of the atherosclerotic plaque, cardiac cycle in ventricular diastole, and absence of incongruous changes. SWE is an emerging and extremely promising method for assessment of carotid plaques that may contribute to therapeutic decision-making based on characteristics related to the atherosclerotic plaque, with inter-device and inter-examiner reproducibility. [ABSTRACT FROM AUTHOR]

Purpose: To explore the mechanism of action of crocin in rat chronic heart failure (CHF). Methods: One hundred male Sprague Dawley (SD) rats were used to establish CHF rat model by the abdominal aorta constriction method. They were equally randomized into either the model control group (injected with distilled water), crocin low, medium, and high dose groups (daily administered 0.05, 0.1, and 0.75 g/kg of crocin, respectively), or positive control group (daily administration of benazepril hydrochloride), and normal control (without treatment). Parameters evaluated include heart function, inflammatory index changes, and oxidative stress damage. Results: The crocin low, medium, and high dose groups and the positive control group had significantly better cardiac function indices versus the model control group (p < 0.05). High-dose crocin resulted in significantly lower levels of inflammatory factors than a low or medium dose (p < 0.05). Rats that received a medium or high dose of crocin showed significantly increased activity of myocardial antioxidant enzymes, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) content when compared to those given low doses of crocin (p < 0.05). Protein expressions of Bax-activated caspase-3, and NF-kB decreased significantly with increase in crocin dosage. A high dose of crocin produced a significantly lower apoptotic rate of cardiomyocytes, sodium--calcium exchanger (NCX) level and higher content of sarcoplasmic reticulum calcium pump 2a (SERCA2a) compared with low- and medium-doses. Conclusion: Crocin protects myocardial tissue and enhances ventricular diastolic function of CHF rats through down-regulation of NCX expression and up-regulation of SERCA2a expression. Further studies using clinical CHF models to categorize and analyze crocin-related cellular pathways will be required. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to analyze the concurrent validation between the resistance index (RI) obtained by Spectral Doppler (SD) and the vascular resistance (VR) calculated by quantifying pixel color intensity of the power Doppler (PD) signal. Methods. The brachial artery of 30 healthy participants (24.8 yrs; SD = 6.44 yrs) were evaluated with SD to automatically obtain RI and with PD to estimate de VR with de Pourcelot's formula from systolic and diastolic peaks. Three assessments were performed on each participant, obtaining a total of 90 ultrasound assessments of the brachial artery with their respective RI. Processing and analysis were performed ImageJ software were manually selected and extracted from the brachial artery PD images with the highest and lowest signal corresponding to peak systolic and end diastole for each patient. The mean pixel color of the image with the highest signal was considered as the peak systolic velocity and of the image with the lowest signal as the end-diastolic velocity. Results. A high correlation was found between RI and VR (r = 0.92; 95%CI = 0.88 to 0.95; p ≤ 0.001) so there is a very strong concurrent validity between the two measures, and they can be considered equivalents (common variability of 84%). Conclusions. This new method of analyzing DS by quantifying the color intensity of the PD signal pixel is a good predictor of RI and could be useful for VR analysis in musculoskeletal tissues where measurement of RI is complicated such in neovascularization in tendinopathies with multiple Doppler signals. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of selected echocardiographic variables used to predict fluid responsiveness in hospitalized dogs with compromised hemodynamics and tissue hypoperfusion. Design: Diagnostic test study in a prospective cohort of hospitalized dogs. Setting: Veterinary referral clinics. Animals: Forty‐four hospitalized dogs with compromised hemodynamics and tissue hypoperfusion were utilized in this study. Interventions: Echocardiographic examination before and after fluid replacement with 30 ml/kg of lactated Ringer's solution. Measurements and Main Results: Pre‐fluid replacement measurements of velocity of transmitral E wave (E‐peak), the left ventricular end‐diastolic internal diameter normalized to body weight (LVIDdN), and the left ventricular end‐systolic internal diameter normalized to body weight (LVIDsN) were significantly lower in fluid‐responsive patients compared with nonresponders (P < 0.001). The area under the receiver operating characteristic curve (AUROC) with its 95% confidence interval (CI) for each significant predictor was as follows: E‐peak 0.907 (0.776–1.000, P < 0.001) and LVIDdN 0.919 (0.801–1.000, P < 0.001). The predictive capacity of LVIDsN was not significantly better than chance (AUROC, 0.753; 95% CI, 0.472–1.000, P = 0.078). A significant negative linear correlation was observed between the percentage of increase in velocity–time integral after expansion and the echocardiographic variables LVIDdN (rs = –0.452, P = 0.023) and E‐peak (rs = –0.396, P = 0.008) pre‐fluid replacement. The intraobserver and interobserver variability was very low (<5 %) for all measurements. Conclusions: In this study using critically ill dogs with compromised hemodynamics and tissue hypoperfusion, pre‐fluid replacement measurements of LVIDdN and E‐peak adequately predict fluid responsiveness. Because a small number of fluid nonresponders were involved in the present study (11.4%), further studies that include larger numbers of fluid‐nonresponsive animals are required. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) dysfunction is a potent predictor of mortality and morbidity after acute myocardial infarction (MI). Even though elective percutaneous coronary intervention (PCI) has significantly decreased myocardial damage of the left ventricle; in literature, there has been a lack of information regarding the effect of PCI on RV function. Objective: The objective of this study is to examine the effect of the right coronary artery (RCA) revascularization on systolic and diastolic functions of the right ventricle following acute inferior wall MI (IWMI). Subjects and Methods: Fifty-nine patients diagnosed with acute IWMI following RCA revascularization were prospectively investigated between April 2018 and January 2020. Patients were subjected to two-dimensional echocardiography. RV systolic and diastolic functions were reported before and after the PCI procedure and compared using different echocardiographic RV systolic and diastolic parameters. Results: After PCI, echocardiographic RV systolic and diastolic functions were significantly improved in proximal and mid RCA in terms of tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), and early RV filling velocity/late RV filling velocity (E/A). Significant improvement was found in mid RCA in terms of peak systolic (S') velocity (P = 0.008) and proximal RCA in terms of early RV filling velocity/early diastolic tricuspid annulus velocity (E/e') (P = 0.021). Overall echocardiographic systolic and diastolic parameters in patients with RV dysfunction following PCI were improved (TAPSE [37.29% vs. 81.82%], S' velocity [37.29% vs. 68.18%], RVFAC [33.90% vs. 90.00%], and E/A [33.90% vs. 75.00%]). Conclusions: Patients with RV dysfunction were remarkably improved after RCA revascularization. Hence, RCA revascularization can become an appropriate treatment alternative for the recovery of patients who suffer from RV dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to compare levels of NT-proBNP in various grades of hypertension, correlate with electrocardiographic criteria of LVH and with diastolic function on echocardiography.. Materials and Methods: This study was conducted on 100 patients attending the cardiology outpatient department of Nizam's Institute of Medical Sciences, patients satisfying the inclusion criteria were enrolled in this study after taking informed consent. Results: This study includes the patient population with a mean of 54.32 ± 6 years of age. ECG criteria of LVH are more common in patients with Grade 1 (60%) and Grade 2 (89%) hypertension. Conclusion: Patients with higher grades of hypertension have more LV mass which is corresponding to ECG criteria satisfying LVH and more diastolic dysfunction as well as higher NT pro-BNP values. [ABSTRACT FROM AUTHOR]

Aims Exercise echocardiography (ExE) may evaluate left ventricular (LV) systolic and diastolic function. We aimed to assess the value of diastolic parameters at exercise [early LV inflow velocity to early tissue Doppler annulus velocity (E / e ′)] in patients with normal or abnormal resting diastolic function (DF) referred for a clinically indicated ExE. Methods and results LV systolic and DF according to ASE/EACVI guidelines and mitral regurgitation (MR) were evaluated at rest in 772 patients (age 67 ± 12 years) with preserved LV ejection fraction (LVEF ≥ 50%). We assessed regional/global LV systolic function at peak exercise, while MR and E / e ′ where evaluated in the immediate post-exercise period. Abnormal ExE was defined as ischaemia or fixed wall motion abnormalities, and raised E / e ′ values as >15 at rest and at exercise (e ′ at the septal level). Patients were grouped as complaining or not of dyspnoea. Events were overall mortality, myocardial infarction, admission for unstable angina or cardiac failure, and coronary revascularization. DF was abnormal at rest in 221 patients (29%) and indeterminate in 77 (10%), with similar percentages in patients with and without dyspnoea. Exercise E / e ′ >15 was found in 37% of patients with abnormal DF, 21% with indeterminate DF, and 6% with normal DF (P < 0.001). Patients with abnormal ExE had more often abnormal resting DF (39% vs. 25%, P = 0.001) and exercise E / e ′ >15 (25% vs. 13%, P < 0.001) than those with normal ExE. During a median follow-up of 1.68 years, there were 132 events. Independent predictors included peak exercise LVEF [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.91–0.94, P < 0.001], and exercise E / e ′ (HR= 1.04, 95% CI = 1.01–1.07, P = 0.01). Neither resting E / e ′ values nor resting abnormal DF by ASE/EACVI guidelines, were independent predictors. Annualized event-rates were 43.2% in patients with (+) ExE plus (+) exercise E / e ′, 23.8% in those with (+) ExE and (−) exercise E / e ′, 7.9% in (−) ExE and (+) exercise E / e ′, and 3.6% with both variables normal. Conclusions The results of diastolic dysfunction at rest and at exercise were similar between patients with or without dyspnoea referred for ExE, but they were associated with abnormal ExE. Exercise E / e ′ reclassified 21% of patients with indeterminate DF and further predicted outcome on top of ExE results. [ABSTRACT FROM AUTHOR]

The article titled "Subclinical systolic dysfunction in genotype‐positive phenotype‐negative relatives of dilated cardiomyopathy patients: A systematic review and meta‐analysis" by Faggiano and colleagues explores the use of speckle‐tracking echocardiography to detect early myocardial dysfunction in individuals who are genetically predisposed to dilated cardiomyopathy (DCM) but do not yet show symptoms. The study adheres to PRISMA guidelines and highlights the potential of left ventricular global longitudinal strain (GLS) as a prognostic tool beyond traditional measures like left ventricular ejection fraction (LVEF). However, the article raises questions about the variability and standardization of GLS measurement, the genotype-specific influences on GLS and LVEF, the integration of GLS monitoring into routine clinical practice, and the generalizability of the findings to diverse populations. Addressing these queries could enhance the clinical utility of GLS and lead to earlier interventions for asymptomatic carriers of DCM. [Extracted from the article]

Level of Evidence: 5 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Boiling histotripsy (BH) is a mechanical tissue liquefaction method that uses sequences of millisecond-long high intensity focused ultrasound (HIFU) pulses with shock fronts. The BH treatment generates bubbles that move within the sonicated volume due to acoustic radiation force. Since the velocity of the bubbles and tissue debris is expected to depend on the lesion size and liquefaction completeness, it could provide a quantitative metric of the treatment progression. In this study, the motion of bubble remnants and tissue debris immediately following BH pulses was investigated using high-pulse repetition frequency (PRF) plane-wave color Doppler ultrasound in ex vivo myocardium tissue. A 256-element 1.5 MHz spiral HIFU array with a coaxially integrated ultrasound imaging probe (ATL P4-2) produced 10 ms BH pulses to form volumetric lesions with electronic beam steering. Prior to performing volumetric BH treatments, the motion of intact myocardium tissue and anticoagulated bovine blood following isolated BH pulses was assessed as two limiting cases. In the liquid blood the velocity of BH-induced streaming at the focus reached over 200 cm/s, whereas the intact tissue was observed to move toward the HIFU array consistent with elastic rebound of tissue. Over the course of volumetric BH treatments tissue motion at the focus locations was dependent on the axial size of the forming lesion relative to the corresponding size of the HIFU focal area. For axially small lesions, the maximum velocity after the BH pulse was directed toward the HIFU transducer and monotonically increased over time from about 20–100 cm/s as liquefaction progressed, then saturated when tissue was fully liquefied. For larger lesions obtained by merging multiple smaller lesions in the axial direction, the high-speed streaming away from the HIFU transducer was observed at the point of full liquefaction. Based on these observations, the maximum directional velocity and its location along the HIFU propagation axis were proposed and evaluated as candidate metrics of BH treatment completeness. [ABSTRACT FROM AUTHOR]

Background: As a noninvasive tool, myocardial deformation imaging may facilitate the early detection of cardiac dysfunction. However, normal reference ranges of myocardial strain and strain rate (SR) based on large-scale East Asian populations are still lacking. This study aimed to provide reference values of left ventricular (LV) and right ventricular (RV) strain and SR based on a large cohort of healthy Chinese adults using cardiovascular magnetic resonance (CMR) feature tracking (FT). Methods: Five hundred and sixty-six healthy Chinese adults (55.1% men) free of hypertension, diabetes, and obesity were included. On cine CMR, biventricular global radial, circumferential, and longitudinal strain (GRS, GCS, and GLS), and the peak radial, circumferential, and longitudinal systolic, and diastolic SRs (PSSRR, PSSRC, PSSRL, PDSRR, PDSRC, and PDSRL), and regional radial and circumferential strain at the basal, mid-cavity, and apical levels were measured. Associations of global and regional biventricular deformation indices with age and sex were investigated. Results: Women demonstrated greater magnitudes of LV GRS (37.6 ± 6.1% vs. 32.1 ± 5.3%), GCS (− 20.7 ± 1.9% vs. − 18.8 ± 1.9%), GLS (− 17.8 ± 1.8% vs. − 15.6 ± 1.8%), RV GRS (25.1 ± 7.8% vs. 22.1 ± 6.7%), GCS (− 14.4 ± 3.6% vs. − 13.2 ± 3.2%), GLS (− 22.4 ± 5.2% vs. − 20.2 ± 4.6%), and biventricular peak systolic and diastolic SR in all three coordinate directions (all P < 0.05). For the LV, aging was associated with increasing amplitudes of GRS, GCS, and decreasing amplitudes of PDSRR, PDSRC, PDSRL (all P < 0.05). For the RV, aging was associated with an increase in the magnitudes of GRS, GCS, GLS, PSSRR, PSSRC, PSSRL, and a decrease in the magnitude of PDSRR, PDSRC (all P < 0.05). Biventricular radial and circumferential strain measurements at the basal, mid-cavity, and apical levels were all significantly related to age and sex in both sexes (all P < 0.05). Conclusions: We provide age- and sex-specific normal values of biventricular strain and SR based on a large sample of healthy Chinese adults with a broad age range. These results may be served as a reference standard for cardiac function assessment, especially for the Chinese population. [ABSTRACT FROM AUTHOR]

Electric interventions are used to terminate arrhythmia. However, myocardial injury from the electrical intervention can follow unique pathways and it is unknown how this affects regional ventricular function. This study investigated the impact of transthoracic electrical shocks on systolic and diastolic myocardial deformation. Ten healthy anaesthetized female swine received five transthoracic shocks (5 × 200 J) and six controls underwent a cardiovascular magnetic resonance exam prior to and 5 h after the intervention. Serial transthoracic shocks led to a global reduction in both left (LV, − 15.6 ± 3.3% to − 13.0 ± 3.6%, p < 0.01) and right ventricular (RV, − 16.1 ± 2.3% to − 12.8 ± 4.2%, p = 0.03) peak circumferential strain as a marker of systolic function and to a decrease in LV early diastolic strain rate (1.19 ± 0.35/s to 0.95 ± 0.37/s, p = 0.02), assessed by feature tracking analysis. The extent of myocardial edema (ΔT1) was related to an aggravation of regional LV and RV diastolic dysfunction, whereas only RV systolic function was regionally associated with an increase in T1. In conclusion, serial transthoracic shocks in a healthy swine model attenuate biventricular systolic function, but it is the acute development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema. [ABSTRACT FROM AUTHOR]

Ventricular diastolic mechanical properties are important determinants of cardiac function and are optimized by changes in cardiac structure and physical properties. Oncorhynchus masou masou is an anadromous migratory fish of the Salmonidae family, and several ecological studies on it have been conducted; however, the cardiac functions of the fish are not well known. Therefore, we investigated ventricular diastolic function in landlocked (masu salmon) and sea-run (cherry salmon) types at 29–30 months post fertilization. Pulsed-wave Doppler echocardiography showed that the atrioventricular inflow waveforms of cherry salmon were biphasic with early diastolic filling and atrial contraction, whereas those of masu salmon were monophasic with atrial contraction. In addition, end-diastolic pressure–volume relationship analysis revealed that the dilatability per unit myocardial mass of the ventricle in cherry salmon was significantly suppressed compared to that in masu salmon, suggesting that the ventricle of the cherry salmon was relatively stiffer (relative ventricular stiffness index; p = 0.0263). Contrastingly, the extensibility of cardiomyocytes, characterized by the expression pattern of Connectin isoforms in their ventricles, was similar in both types. Histological analysis showed that the percentage of the collagen accumulation area in the compact layer of cherry salmon increased compared with that of the masu salmon, which may contribute to ventricle stiffness. Although the heart mass of cherry salmon was about 11-fold greater than that of masu salmon, there was no difference in the morphology of the isolated cardiomyocytes, suggesting that the heart of the cherry salmon grows by cardiomyocyte proliferation, but not cell hypertrophy. The cardiac physiological function of the teleosts varies with differences in their developmental processes and life history. Our multidimensional analysis of the O. masou heart may provide a clue to the process by which the heart acquires a biphasic blood-filling pattern, i.e., a ventricular diastolic suction. [ABSTRACT FROM AUTHOR]

Background/aim: Vitamin D insufficiency is a common public health problem that is often unrecognized in children with congenital heart disease, and is not generally evaluated at congenital heart disease (CHD) follow-up. Recent studies have suggested that inadequate vitamin D status may have an adverse effect on cardiovascular health. This study investigates the relationship between vitamin D levels and hemodynamic parameters in children with CHD. Methods: Included in the study 40 patients (25 females, 15 males) with CHD, who were evaluated for Ross heart failure score, vitamin D, parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase (ALP), whole blood count (WBC) and echocardiographic measurements, and all measurements were repeated in the third month of the therapy. Results: The mean vitamin D level was 16.4 ± 6.6 ug/L before and 27.5 ± 9.9 μg/L in the third month of therapy, while the mean PTH level was 53.3 ± 34.9 pg/mL before and 43.8 ± 21.4 pg/mL in the third month of therapy. The mean WBC was 8084 ± 2324/µL before and 7378±1893/µL in the third month of the therapy, and the mean platelet (PLT) count was 280,897 ± 80,119/µL before and 307,179 ± 60,202/µL in the third month of the therapy. The mean ejection fraction (EF) was 64% ± 7.2% before and 66.7% ± 6.2% in the third month of therapy, while the right ventricle (RV) myocardial performance index (MPI) was 32.1% ± 6.7% before and 28.9% ± 6.5% in the third month of the therapy. IL10 level was increased in four patients in the third month of therapy. A statistically significant decrease in PTH level and WBC, and an increase in PLT number and IL-10 level were detected by the therapy. Furthermore, echocardiographic findings revealed a statistically significant increase in EF and a decrease in RVMPI attributable to the therapy. Conclusion: The decreased levels of PTH, which is a proinflammatory marker, the increases in IL-10, which is an antiinflammatory cytokine, and the decreases in the number of WBC resulting from vitamin D treatment demonstrate the antiinflammatory effects of vitamin D. An improvement in EF means improvement in left ventricular contractility, while a decrease in RV MPI has been shown to improve the systolic and diastolic function of the right ventricle. These results suggest that vitamin D therapy has a positive effect on the heart, and so vitamin D levels should be evaluated during the routine follow-up of congenital heart disease. [ABSTRACT FROM AUTHOR]

Shear wave elastography (SWE) is a promising technique used to assess cardiac function through the evaluation of cardiac stiffness non-invasively. However, in the literature, SWE varies in terms of tissue motion data (displacement, velocity or acceleration); method used to characterize mechanical wave propagation (time domain [TD] vs. frequency domain [FD]); and the metric reported (wave speed [WS], shear or Young's modulus). This variety of reported methodologies complicates comparison of reported findings and sheds doubt on which methodology better approximates the true myocardial properties. We therefore conducted a simulation study to investigate the accuracy of various SWE data analysis approaches while varying cardiac geometry and stiffness. Lower WS values were obtained by the TD method compared with the FD method. Acceleration-based WS estimates in the TD were systematically larger than those based on velocity (∼10% difference). These observations were confirmed by TD analysis of 32 in vivo SWE mechanical wave measurements. In vivo data quality is typically too low for accurate FD analysis. Therefore, our study suggests using acceleration-based TD analysis for in vivo SWE to minimize underestimation of the true WS and, thus, to maximize the sensitivity of SWE to detect stiffness changes resulting from pathology. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the main cause of death worldwide. Recent studies have revealed the influence of histone-modifying enzymes in cardiac remodeling and heart dysfunction. The Set7 methyltransferase regulates the expression of several genes through the methylation of histones and modulates the activity of non-histone proteins. However, the role of Set7 in cardiac remodeling and heart dysfunction remains unknown. To address this question, wild-type (WT) and Set7 knockout (KO) male mice were injected with isoproterenol or saline. WT mice injected with isoproterenol displayed a decrease in Set7 activity in the heart. In addition, WT and Set7 KO mice injected with isoproterenol exhibited cardiac hypertrophy. Interestingly, Set7 deletion exacerbated cardiac hypertrophy in response to isoproterenol but attenuated myocardial fibrosis. Echocardiograms revealed that WT mice injected with isoproterenol had lowered ejection fractions and fractional shortening, and increased E′-wave deceleration time and E/A ratio compared with their controls. Conversely, Set7 KO mice did not show alteration in these parameters in response to isoproterenol. However, prolonged exposure to isoproterenol induced cardiac dysfunction both in WT and Set7 KO mice. Both isoproterenol and Set7 deletion changed the transcriptional profile of the heart. Moreover, Set7 deletion increased the expression of Pgc1α and mitochondrial DNA content in the heart, and reduced the expression of cellular senescence and inflammation markers in response to isoproterenol. Taken together, our data suggest that Set7 deletion attenuates isoproterenol-induced myocardial fibrosis and delays heart dysfunction, suggesting that Set7 plays an important role in cardiac remodeling and dysfunction in response to stress. [ABSTRACT FROM AUTHOR]

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy. [ABSTRACT FROM AUTHOR]

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia–reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia–reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGF β 1–Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling. Cardiac fibroblast HSP47 inspired TGF β 1–Smad4 pathway by USP10 dependent deubiquitination in fibrogenesis under hypoxia. HSP47 suppression by chemicals with Col003 may have therapeutic potential for alleviating ischemic cardiac fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]