Myocardial Structure Research Articles

So close, yet so far away: the relationship between MAM and cardiac disease.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Effect of Intradialytic Exercise on Cardiovascular Outcomes in Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Cardiovascular disease is the leading cause of death among people with kidney failure on hemodialysis, for whom improving cardiovascular health is a research priority. Intradialytic myocardial stunning is common and associated with adverse cardiovascular events. Intradialytic exercise may mitigate intradialytic myocardial stunning and improve cardiovascular structure and function. This systematic review investigated the effect of intradialytic exercise on cardiovascular outcomes in adults undergoing maintenance hemodialysis (PROSPERO #CRD42018103118). Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, SportDiscus, and PEDro databases from 1960 until June 2022, for randomized and non-randomized studies investigating the effect of intradialytic exercise programs on objective cardiovascular outcomes, pre-specified as primary or secondary outcomes. The primary outcome was arterial resistance. Of 10837 references identified, 32 met eligibility criteria. These studies investigated the effect of intradialytic exercise on arterial resistance (8 studies), blood pressure (20 studies), myocardial structure and function (7 studies), endothelial function (2 studies), sympathetic overactivity (9 studies), biomarkers of cardiac injury (3 studies), cardiovascular hospitalization and mortality (2 studies). Most studies used aerobic exercise as the intervention and usual care (no exercise) controls. Meta-analysis of intradialytic exercise versus usual care resulted in a statistically significant reduction in arterial resistance measured by pulse wave velocity (PWV) with mean difference -1.63 m/sec (95% CI -2.51, -0.75). Meta-analyses for diastolic blood pressure, left ventricular ejection fraction (LVEF), and low-frequency/high-frequency (LF/HF ratio) measure of heart rate variability also showed statistically significant improvements with exercise. There was no significant difference in change in systolic blood pressure, augmentation index, and left ventricular mass index between groups. Intradialytic exercise programming resulted in a clinically meaningful improvement to PWV, a component of arterial resistance. Sseveral physiologic measures of cardiovascular health, including diastolic blood pressure, LVEF and heart rate variability measured by the LF/HF ratio were also observed. The effects of intradialytic exercise on major adverse cardiovascular events remains uncertain.

Left ventricle function and post-transcriptional events with exercise training in pigs.

Standardized exercise protocols have been shown to improve overall cardiovascular fitness, but direct effects on left ventricular (LV) function, particularly diastolic function and relation to post-transcriptional molecular pathways (microRNAs (miRs)) are poorly understood. This project tested the central hypothesis that adaptive LV remodeling resulting from a large animal exercise training protocol, would be directly associated with specific miRs responsible for regulating pathways relevant to LV myocardial stiffness and geometry. Pigs (n = 9; 25 Kg) underwent a 4 week exercise training protocol (10 degrees elevation, 2.5 mph, 10 min, 5 days/week) whereby LV chamber stiffness (KC) and regional myocardial stiffness (rKm) were measured by Doppler/speckle tracking echocardiography. Age and weight matched non-exercise pigs (n = 6) served as controls. LV KC fell by approximately 50% and rKm by 30% following exercise (both p < 0.05). Using an 84 miR array, 34 (40%) miRs changed with exercise, whereby 8 of the changed miRs (miR-19a, miR-22, miR-30e, miR-99a, miR-142, miR-144, miR-199a, and miR-497) were correlated to the change in KC (r ≥ 0.5 p < 0.05) and mapped to matrix and calcium handling processes. Additionally, miR-22 and miR-30e decreased with exercise and mapped to a localized inflammatory process, the inflammasome (NLRP-3, whereby a 2-fold decrease in NLRP-3 mRNA occurred with exercise (p < 0.05). Chronic exercise reduced LV chamber and myocardial stiffness and was correlated to miRs that map to myocardial relaxation processes as well as local inflammatory pathways. These unique findings set the stage for utilization of myocardial miR profiling to identify underlying mechanisms by which exercise causes changes in LV myocardial structure and function.

Co-treatment with bone marrow-derived mesenchymal stem cells and curcumin improved angiogenesis in myocardium in a rat model of MI.

The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI). Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group. Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.

Precision medicine enhances personalized medicine in cardiology

Personalized medicine and precision medicine, frequently used synonymously, shall be clearly differentiated. Accordingly, personalization in cardiac medicine is based on the clinical presentation of apatient, as well as his/her cardiovascular risk factors and comorbidities, electrocardiography, imaging, and biomarkers for myocardial load and ischemia. Personalization is based on large clinical trials with detailed subgroup analyses and is practiced on the basis of guidelines. Further in depth personalization is achieved by precision medicine, which is based on innovative imaging for myocardial structure, coronary morphology, and electrophysiology. From the clinical perspective, genome analyses are relevant for comparatively rare monogenetic cardiovascular diseases. While these as well as transcriptome and metabolome analyses play asignificant role in cardiovascular research with great translation potential, they have not yet been broadly introduced in the diagnosis, prevention, and treatment of complex cardiovascular diseases. Furthermore, digital technologies have considerable potential in cardiovascular precision medicine. On the one hand, this is based on the frequency of the diseases with the availability of Big Data and, on the other hand, on the availability of bio-signals and sensors of those signals in cardiovascular diseases.

Shared and Reciprocal Mechanisms Between Heart Failure and Cancer - An Emerging Concept of Heart-Cancer Axis.

Epidemiological evidence of increased risks of cancer in heart failure (HF) patients and HF in cancer patients has suggested close relationships between the pathogenesis of both diseases. Indeed, HF and cancer share common risk factors, including aging and unhealthy lifestyles, and underlying mechanisms, including activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, chronic inflammation, and clonal hematopoiesis of indeterminate potential. Mechanistically, HF accelerates cancer development and progression via secreted factors, so-called cardiokines, and epigenetic remodeling of bone marrow cells into an immunosuppressive phenotype. Reciprocally, cancer promotes HF via cachexia-related wasting and metabolic remodeling in the heart, and possibly via cancer-derived extracellular vesicles influencing myocardial structure and function. The novel concept of the "heart-cancer axis" will help in our understanding of the shared and reciprocal relationships between HF and cancer, and provide innovative diagnostic and therapeutic approaches for both diseases.

Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Myocardial Injury in Type 2 Diabetic Rats by Regulating Autophagy

Background Diabetes mellitus (DM) is a persistent metabolic condition resulting from insufficient insulin or insulin resistance, which gives rise to diverse complications endangering human well-being. Ramulus Mori (Sangzhi) alkaloids ­(SZ-A) have various pharmacological effects, potentially benefiting clinical comprehensive kidney and cardiovascular protection. Nevertheless, the potential protective effect of SZ-A on myocardial injury in individuals with type 2 diabetes mellitus (T2DM) remains unexplored. Materials and Methods Sprague-Dawley (SD) rats were divided into four groups, including control, model, metformin, and SZ-A. The establishment of the type 2 diabetes model was initiated by injecting streptozotocin (STZ) along with a diet of high glucose and fat. Following a 12-week period of treatment, measurements were taken for heart mass index (HMI), fasting blood glucose (FBG), and 2-h postprandial blood glucose (2hPG). Additionally, serum glycated hemoglobin (HbA1c), indicators of myocardial injury, and oxidative stress were assessed. The expressions of mammalian target of rapamycin (mTOR), p-mTOR, beclin-1, and LC3 in myocardial tissue were detected by Western blot. Results The administration of SZ-A effectively reduced the levels of HMI, FBG, 2hPG, HbA1c, malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine kinase isoenzymes (CK-MB) in rats with type 2 diabetes while enhancing the activity of superoxide dismutase (SOD). Additionally, SZ-A could improve myocardial tissue arrangement structure and fibrosis degree. Additional analysis revealed that SZ-A suppressed the activation of p-mTOR while enhancing the levels of Beclin-1 and LC3, suggesting that the potential therapeutic impact of SZ-A on myocardial damage could be attributed to its ability to regulate autophagy, thereby mitigating oxidative stress. Conclusion In summary, the results indicate that SZ-A might possess inhibitory properties against myocardial damage in rats with type 2 diabetes, presenting a potential therapeutic approach in the clinic.

Dual-specificity phosphatase 1 interacts with prohibitin 2 to improve mitochondrial quality control against type-3 cardiorenal syndrome.

Type-3 cardiorenal syndrome (CRS-3) is acute kidney injury followed by cardiac injury/dysfunction. Mitochondrial injury may impair myocardial function during CRS-3. Since dual-specificity phosphatase 1 (DUSP1) and prohibitin 2 (PHB2) both promote cardiac mitochondrial quality control, we assessed whether these proteins were dysregulated during CRS-3-related cardiac depression. We found that DUSP1 was downregulated in heart tissues from a mouse model of CRS-3. DUSP1 transgenic (DUSP1Tg) mice were protected from CRS-3-induced myocardial damage, as evidenced by their improved heart function and myocardial structure. CRS-3 induced the inflammatory response, oxidative stress and mitochondrial dysfunction in wild-type hearts, but not in DUSP1Tg hearts. DUSP1 overexpression normalized cardiac mitochondrial quality control during CRS-3 by suppressing mitochondrial fission, restoring mitochondrial fusion, re-activating mitophagy and augmenting mitochondrial biogenesis. We found that DUSP1 sustained cardiac mitochondrial quality control by binding directly to PHB2 and maintaining PHB2 phosphorylation, while CRS-3 disrupted this physiological interaction. Transgenic knock-in mice carrying the Phb2S91D variant were less susceptible to cardiac depression upon CRS-3, due to a reduced inflammatory response, suppressed oxidative stress and improved mitochondrial quality control in their heart tissues. Thus, CRS-3-induced myocardial dysfunction can be attributed to reduced DUSP1 expression and disrupted DUSP1/PHB2 binding, leading to defective cardiac mitochondrial quality control.

Porcine Model of Hypertrophy-Independent Left Ventricular Stiffening via Repetitive Pressure Overload.

Diastolic dysfunction arising from alterations in myocardial structure and/or function is a central component of several cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF). Basic research aimed at understanding underlying mechanisms contributing to the development of diastolic dysfunction has generally centered upon models of left ventricular (LV) hypertrophy arising from persistent and severe elevations in myocardial afterload (e.g., aortic banding). Mechanisms of hypertrophy-independent diastolic dysfunction, on the other hand, have received less attention, even though overt anatomic LV hypertrophy is absent in many HFpEF patients. Here, we describe the development of a novel porcine model of repetitive pressure overload (RPO) in which chronic, intermittent exposure to transient episodes of hypertension produces an increase in LV stiffness, interstitial fibrosis, cardiomyocyte hypertrophy, and capillary rarefaction without significant changes in LV mass. This model offers important insight into how diastolic dysfunction and HFpEF may develop in the absence of comorbidities, sustained hypertension, or LV hypertrophy, while also providing a useful translational research tool for investigation of novel therapeutic approaches to restore myocardial compliance and improve diastolic function.

Warming Yang Promoting Blood Circulation and Diuresis Alleviates Myocardial Damage by Inhibiting Collagen Fiber and Myocardial Fibrosis and Attenuating Mitochondria Signaling Pathway Mediated Apoptosis in Chronic Heart Failure Rats.

Warming Yang promoting blood circulation and diuresis (WYPBD) has been proven effective in treating some diseases. This study aimed to evaluate therapeutic effect of WYPBD in treating chronic heart failure (CHF). CHF rats were established by intraperitoneally injecting doxorubicin (DOX). Therapeutic effects of WYPBD on cardiac function and hemodynamic parameters of myocardial tissues were analyzed. Collagen fiber production and myocardial fibrosis were evaluated. Transcriptions of COL1A1 gene, COL3A1 gene, and TGFB1 gene were evaluated with RT-PCR. Expression of BNP, AVP, PARP, caspase-3, and Bcl-2 in myocardial tissues were evaluated. TUNEL assay was used to identify apoptosis of cardiomyocytes. WYPBD alleviated degree of myocardial hypertrophy in CHF rats compared to the rats in CHF model group (P < 0.05). WYPBD significantly improved cardiac hemodynamics (increased LVEF and LVSF) of CHF rats compared to rats in the CHF model group (P < 0.05). WYPBD protected myocardial structure and inhibited collagen fiber production in myocardial tissues of CHF rats. WYPBD markedly decreased myocardial fibrosis mediators (Col1α, Col3α, TGF-β1) transcription in myocardial tissues of CHF rats compared to rats in CHF model group (P < 0.05). WYPBD significantly reduced BNP and AVP expression in myocardial tissues of CHF rats compared to rats in the CHF model group (P < 0.05). WYPBD markedly reduced the expression of PRAP and caspase-3, and increased Bcl-2 expression in myocardial tissues of CHF rats compared to rats in the CHF model group (P < 0.05). In conclusion, WYPBD alleviated CHF myocardial damage by inhibiting collagen fiber and myocardial fibrosis, attenuating apoptosis associated with the mitochondria signaling pathway of cardiomyocytes.

Toward Accurate Cardiac MRI Segmentation With Variational Autoencoder-Based Unsupervised Domain Adaptation.

Accurate myocardial segmentation is crucial in the diagnosis and treatment of myocardial infarction (MI), especially in Late Gadolinium Enhancement (LGE) cardiac magnetic resonance (CMR) images, where the infarcted myocardium exhibits a greater brightness. However, segmentation annotations for LGE images are usually not available. Although knowledge gained from CMR images of other modalities with ample annotations, such as balanced-Steady State Free Precession (bSSFP), can be transferred to the LGE images, the difference in image distribution between the two modalities (i.e., domain shift) usually results in a significant degradation in model performance. To alleviate this, an end-to-end Variational autoencoder based feature Alignment Module Combining Explicit and Implicit features (VAMCEI) is proposed. We first re-derive the Kullback-Leibler (KL) divergence between the posterior distributions of the two domains as a measure of the global distribution distance. Second, we calculate the prototype contrastive loss between the two domains, bringing closer the prototypes of the same category across domains and pushing away the prototypes of different categories within or across domains. Finally, a domain discriminator is added to the output space, which indirectly aligns the feature distribution and forces the extracted features to be more favorable for segmentation. In addition, by combining CycleGAN and VAMCEI, we propose a more refined multi-stage unsupervised domain adaptation (UDA) framework for myocardial structure segmentation. We conduct extensive experiments on the MSCMRSeg 2019, MyoPS 2020 and MM-WHS 2017 datasets. The experimental results demonstrate that our framework achieves superior performances than state-of-the-art methods.

Cardiac MR Fingerprinting: Overview, Technical Developments, and Applications.

Cardiovascular magnetic resonance (CMR) is an established imaging modality with proven utility in assessing cardiovascular diseases. The ability of CMR to characterize myocardial tissue using T1- and T2-weighted imaging, parametric mapping, and late gadolinium enhancement has allowed for the non-invasive identification of specific pathologies not previously possible with modalities like echocardiography. However, CMR examinations are lengthy and technically complex, requiring multiple pulse sequences and different anatomical planes to comprehensively assess myocardial structure, function, and tissue composition. To increase the overall impact of this modality, there is a need to simplify and shorten CMR exams to improve access and efficiency, while also providing reproducible quantitative measurements. Multiparametric MRI techniques that measure multiple tissue properties offer one potential solution to this problem. This review provides an in-depth look at one such multiparametric approach, cardiac magnetic resonance fingerprinting (MRF). The article is structured as follows. First, a brief review of single-parametric and (non-Fingerprinting) multiparametric CMR mapping techniques is presented. Second, a general overview of cardiac MRF is provided covering pulse sequence implementation, dictionary generation, fast k-space sampling methods, and pattern recognition. Third, recent technical advances in cardiac MRF are covered spanning a variety of topics, including simultaneous multislice and 3D sampling, motion correction algorithms, cine MRF, synthetic multicontrast imaging, extensions to measure additional clinically important tissue properties (proton density fat fraction, T2*, and T1ρ), and deep learning methods for image reconstruction and parameter estimation. The last section will discuss potential clinical applications, concluding with a perspective on how multiparametric techniques like MRF may enable streamlined CMR protocols. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

MOTS-c Peptide Attenuated Diabetic Cardiomyopathy in STZ-Induced Type 1 Diabetic Mouse Model.

Diabetic cardiomyopathy (DCM) pathogenesis is a common complication of diabetes, but effective treatments remain limited. Mitochondrial-derived peptide MOTS-c has shown therapeutic promise in animal models of various heart diseases, but its efficacy in DCM is unknown. This study investigates the effects of MOTS-c treatment in a mouse model of type 1 diabetes-induced DCM. Type 1 diabetes (T1DM) was induced in mice by streptozotocin (STZ) injection. After diabetes establishment, the mice were randomly dividend into two groups treated with or without MOTS-c peptide, which was administered subcutaneously by osmotic pump for 12 weeks. At the end of the experiment, cardiac function, histology, and molecular changes were determined. The results showed that diabetic mice exhibited significant cardiac dysfunction, dilatation, and adverse cardiac remodeling. MOTS-c treatment markedly ameliorated these diabetes-associated myocardial function and structure abnormalities. Additionally, MOTS-c reversed AMPK signaling deactivation and inhibited inflammation in the diabetic heart. Our data demonstrated a protective effect of MOTS-c against diabetic cardiomyopathy potentially by activating the AMPK pathway and inhibiting inflammation. These findings demonstrate the therapeutic efficacy of MOTS-c for diabetic cardiomyopathy and warrant further investigation into its clinical potential.

Songorine ameliorates LPS-induced sepsis cardiomyopathy by Wnt/β-catenin signaling pathway-mediated mitochondrial biosynthesis.

Septic cardiomyopathy (SCM) is manifested by impairment of cardiac contractile function with myocardial mitochondrial dysregulation. Natural product, songorine (SGR), a diterpenoid alkaloid derived from the lateral root of Aconitum carmichaeli, has been reported for the treatment of heart failure. Here, the protective role of SGR in heart injury of SCM was investigated and its underlying action of mechanism was explored. Firstly, the mouse and cardiomyocytes (H9C2 cell) SCM model induced by LPS were established to evaluate the therapeutic effect of SGR. The in vivo results exhibited that SGR rescued the survival rate of SCM mice, restored the loss of ejection fraction (EF) and fractional shortening (FS), and reduced left ventricular systolic diameter and left ventricular diastole diameter (LVIDs, LVIDd) by echocardiography. SGR improved the mitochondrial biosynthesis and myocardial fiber structure and arranged them neatly by transmission electron microscope (TEM). Further, SGR inhibited inflammatory targets myeloperoxidase (MPO) and tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1). And SGR activated the mitochondrial biosynthesis-related peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), β-catenin, and matrix metallopeptidase 2 (MMP2) proteins. Meanwhile, the in vitro results showed that SGR promoted the increased the myocardial H9C2 cell viability, and mitochondrial biosynthesis and structure. SGR also blocked the inflammatory factors and reversed PGC-1α, β-catenin, and MMP2 in vitro, while SGR alleviated the myocardial cell apoptosis via flow cytometry. The findings indicate that SGR mitigates sepsis-caused myocardial damage by Wnt/β-catenin signaling pathway-mediated mitochondrial biosynthesis. SGR may be a promising candidate for treatment of SCM.

The role of c-Jun for beating cardiomycyte formation in prepared embryonic body

BackgroundMorbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation.MethodsThe c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses.ResultsCompared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group.ConclusionsKnocking out c-Jun directs ESCs toward a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.

Dexmedetomidine post-treatment exacerbates metabolic disturbances in septic cardiomyopathy via α2A-adrenoceptor

Cardiomyopathy is a common complication and significantly increases the risk of death in septic patients. Our previous study demonstrated that post-treatment with dexmedetomidine (DEX) aggravates septic cardiomyopathy. However, the mechanisms for the side effect of DEX post-treatment on septic cardiomyopathy are not well-defined. Here we employed a cecal ligation and puncture (CLP) model and α2A-adrenoceptor deficient (Adra2a-/-) mice to observe the effects of DEX post-treatment on myocardial metabolic disturbances in sepsis. CLP mice displayed significant cardiac dysfunction, altered mitochondrial dynamics, reduced cardiac lipid and glucose uptake, impaired fatty acid and glucose oxidation, enhanced glycolysis and decreased ATP production in the myocardium, almost all of which were dramatically enhanced by DEX post-treatment in septic mice. In Adra2a-/- mice, DEX post-treatment did not affect cardiac dysfunction and metabolic disruptions in CLP-induced sepsis. Additionally, Adra2a-/- mice exhibited impaired cardiac function, damaged myocardial mitochondrial structures, and disturbed fatty acid metabolism and glucose oxidation. In sum, DEX post-treatment exacerbates metabolic disturbances in septic cardiomyopathy in a α2A-adrenoceptor dependent manner.

Imaging for the assessment of the arrhythmogenic potential of mitral valve prolapse.

Mitral valve prolapse (MVP) is the most common valve disease in the western world and recently emerged as a possible substrate for sudden cardiac death (SCD). It is estimated an annual risk of sudden cardiac death of 0.2 to 1.9% mostly caused by complex ventricular arrhythmias (VA). Several mechanisms have been recognized as potentially responsible for arrhythmia onset in MVP, resulting from the combination of morpho-functional abnormality of the mitral valve, structural substrates (regional myocardial hypertrophy, fibrosis, Purkinje fibers activity, inflammation), and mechanical stretch. Echocardiography plays a central role in MVP diagnosis and assessment of severity of regurgitation. Several abnormalities detectable by echocardiography can be prognostic for the occurrence of VA, from morphological alteration including leaflet redundancy and thickness, mitral annular dilatation, and mitral annulus disjunction (MAD), to motion abnormalities detectable with "Pickelhaube" sign. Additionally, speckle-tracking echocardiography may identify MVP patients at higher risk for VA by detection of increased mechanical dispersion. On the other hand, cardiac magnetic resonance (CMR) has the capability to provide a comprehensive risk stratification combining the identification of morphological and motion alteration with the detection of myocardial replacement and interstitial fibrosis, making CMR an ideal method for arrhythmia risk stratification in patients with MVP. Finally, recent studies have suggested a potential role in risk stratification of new techniques such as hybrid PET-MR and late contrast enhancement CT. The purpose of this review is to provide an overview of the mitral valve prolapse syndrome with a focus on the role of imaging in arrhythmic risk stratification. CLINICAL RELEVANCE STATEMENT: Mitral valve prolapse is the most frequent valve condition potentially associated with arrhythmias. Imaging has a central role in the identification of anatomical, functional, mechanical, and structural alterations potentially associated with a higher risk of developing complex ventricular arrhythmia and sudden cardiac death. KEY POINTS: • Mitral valve prolapse is a common valve disease potentially associated with complex ventricular arrhythmia and sudden cardiac death. • The mechanism of arrhythmogenesis in mitral valve prolapse is complex and multifactorial, due to the interplay among multiple conditions including valve morphological alteration, mechanical stretch, myocardial structure remodeling with fibrosis, and inflammation. • Cardiac imaging, especially echocardiography and cardiac magnetic resonance, is crucial in the identification of several features associated with the potential risk of serious cardiac events. In particular, cardiac magnetic resonance has the advantage of being able to detect myocardial fibrosis which is currently the strongest prognosticator.

Uncertainty Quantification of Fiber Orientation and Epicardial Activation.

Predictive models and simulations of cardiac function require accurate representations of anatomy, often to the scale of local myocardial fiber structure. However, acquiring this information in a patient-specific manner is challenging. Moreover, the impact of physiological variability in fiber orientation on simulations of cardiac activation is poorly understood. To explore these effects, we implemented bi-ventricular activation simulations using rule-based fiber algorithms and robust uncertainty quantification techniques to generate detailed maps of model variability. Specifically, we utilized polynomial chaos expansion, enabling efficient exploration with reduced computational demand through an emulator function approximating the underlying forward model. Our study focused on examining the epicardial activation sequences of the heart in response to six stimuli locations and five metrics of activation. Our findings revealed that physiological variability in fiber orientation does not significantly affect the location of activation features, but it does impact the overall spread of activation. We observed low variability near the earliest activation sites, but high variability across the rest of the epicardial surface. We conclude that the level of accuracy of myocardial fiber orientation required for simulation depends on the specific goals of the model and the related research or clinical goals.

Impact of Hypertension on Left Ventricular Geometry and Diastolic Function in Africa: Results from the Population-Based TAnve Health (TAHES) Cohort Study

High blood pressure leads to morphologic changes and functional alterations of the myocardial structure. Transthoracic echocardiography is of great clinical interest to evaluate these alterations, using reference values proposed by the American Society of Echocardiography/European Association of Cardiovascular Imaging, largely based on studies in Caucasian Whites. We aimed to assess the impact of hypertension on echocardiographic parameters in a sub-Saharan African community, using ethnic-specific reference values. This study is part of the TAnve HEalth Study, a population-based prospective cohort study initiated in 2015 in the district of Tanve, Republic of Benin. Hypertension was defined as systolic blood pressure ≥140mm Hg and/or diastolic blood pressure ≥90mm Hg and/or currently taking antihypertensive medications. All participants had a transthoracic echocardiography. The patterns of diastolic dysfunction and left ventricular (LV) geometry were defined from 486 subjects in the cohort, free from cardiovascular disease, diabetes, and hypertension. Of all participants, 318 (65% women, median age 48years) had hypertension. Systolic blood pressure correlated significantly (p <0.0001) with LV mass (r = 0.28), wall thickness (r = 0.25), isovolumic relaxation time (r = 0.27), E/A ratio (r = -0.35), lateral e' velocity (r= -0.41), and E/E' ratio (r = 0.39). Ventricular geometry was normal in only 22% of participants with hypertension when using the American Society of Echocardiography/European Association of Cardiovascular Imaging reference values, versus 69% with ethnic-specific reference ranges. The severity of hypertension was associated with ventricular geometry abnormalities. The prevalence of diastolic dysfunction was 14.5% (confidence interval 10.6% to 18.4%), including relaxation impairment (9%) and pseudonormal pattern (6%). Thus, correct assessment of the repercussions of hypertension on LV geometry in Black Africans requires ethnic-specific reference values.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.