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Background: Alcohol‐associated cardiomyopathy (ACM) is a cardiac muscle disease characterized by inflammation and oxidative stress. Thromboxane‐prostanoid receptor (TP‐R) plays an important role in the pathogenesis of cardiovascular disease. Herein, we hypothesize that TP‐R mediates alcohol‐induced early cardiac injury. Methods: Eight‐week‐old male C57BL/6 wild‐type mice were fed a chronic ethanol (ET) or control diet (CON) for 10 days followed by a single binge of ethanol or maltose‐dextrin through oral gavage. A cohort of ethanol‐fed mice received SQ 29,548 (SQ), a TP‐R antagonist. RNA sequencing, real‐time PCR, and western blot analysis were performed on left ventricle to investigate alterations in genes and/or proteins mediating oxidative stress, inflammation, and cardiac remodeling. Sirius Red staining was performed to measure myocardial fibrosis. Results: RNA‐sequencing analysis of myocardium from CON and ET groups identified 142 genes that were significantly altered between the two groups. In particular, the gene expression of thioredoxin‐interacting protein (TXNIP), a component of NLR family pyrin domain containing 3 (NLRP3) signaling, which mediates oxidative stress and inflammatory response, was upregulated in response to ethanol exposure. The myocardial protein levels of TP‐R and thromboxane A2 synthase were increased upon alcohol exposure. Ethanol increased the levels of 4‐hydroxynonenal, a marker of oxidative stress, with a concomitant increase in the protein levels of TXNIP and NLRP3, and administration of SQ attenuated these effects. Additionally, ethanol increased the protein levels of pro‐inflammatory mediators, including tumor necrosis factor alpha and the NLRP3 downstream product, secretory interleukin 1 beta, and SQ blunted these effects. Finally, the Sirius red staining of the myocardium revealed an increase in collagen deposition in ethanol‐fed mice which was attenuated by TP‐R antagonism. Conclusion: This study demonstrates that ethanol promotes the NLRP3 signaling pathway within the myocardium, leading to a pro‐inflammatory milieu that potentially initiates early myocardial remodeling, and TP‐R antagonism attenuates this effect. [ABSTRACT FROM AUTHOR]

Huanglian Jiedu Decoction (HLJDD) is a quintessential prescription renowned for its heat-clearing and detoxifying properties. It is primarily prescribed to counteract the syndrome characterized by the excessive heat of the Sanjiao fire. Notably, the hyperactivity of liver fire is frequently linked with hypertension, where wind fire and wind toxicity emerge as pivotal pathogenic factors. This study aimed to investigate the impact of HLJDD on the endoplasmic reticulum in spontaneously hypertensive rats (SHR), further delving into the interplay between endoplasmic reticulum stress (ERS) and myocardial remodeling and damage. Fifty SHR rats were stratified randomly into five cohorts: model, low-dose HLJDD, medium-dose HLJDD, high-dose HLJDD, and captopril groups. For comparison, a set of Wistar-Kyoto (WKY ) rats served as the baseline control group, with each group comprising 10 rats. While the model and control groups received equivalent volumes of normal saline via gavage, the other groups were administered the respective drug dosages through the same route daily for a span of 6 weeks. Upon the experiment's conclusion, metrics such as the heart mass index (HWI) and left ventricular mass index (LVWI) were assessed. Cardiac tissue anomalies were identified using H&E staining, while ERS-related protein and mRNA expression levels were ascertained via Western blotting analysis and qPCR. Moreover, TUNEL staining was employed to detect cardiomyocyte apoptosis. The findings indicated that increasing HLJDD concentrations corresponded with escalated HWI and LVWI in rat hearts (P < 0.05). There was a marked enhancement in myocardial structural integrity, accompanied by a notable reduction in collagen fibers. The mRNA and protein expressions of myocardial inositol-dependent enzyme 1α (IRE1α), X-box binding protein 1 (XBP1), glycoregulatory protein 78 (GRP78), and CCAAT enhancer binding protein homologous protein (CHOP) in the medium and high-dose groups saw significant declines (P < 0.05). These effects mirrored those observed in the captopril group. The study underscored HLJDD's efficacy in mitigating myocardial tissue damage in SHR. This therapeutic effect was potentially attributed to the downregulation of IRE1α, XBP1, GRP78, and CHOP, curbing excessive ERS, diminishing cardiomyocyte apoptosis, and thereby conferring cardioprotection. [ABSTRACT FROM AUTHOR]

Myocardial infarction is the most common cause of heart failure, and myocardial remodeling can occur after infarction, thus contributing to the progression of heart failure. The occurrence of post-infarction ventricular remodeling is closely related to m6 A methylation. m6 A methylation is a reversible and highly dynamic process. This process is mainly mediated by m6 A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-infarction myocardial remodeling through mechanisms such as cellular autophagy. This article mainly reviews relevant literature in recent years. Firstly, a brief introduction is given to m6 A methylation, followed by an introduction to the role of m6 A methylase in regulating myocardial remodeling. Finally, a summary analysis is conducted on the mechanism of m6 A methylation in regulating myocardial remodeling from the perspectives of autophagy, inflammation, cell apoptosis, calcium ion homeostasis, extracellular matrix remodeling, and ferroptosis. The feasibility of using m6 A methylation serological detection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed, in order to provide reference for related research. [ABSTRACT FROM AUTHOR]

Objectives: Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice. Methods: We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed. Key findings: Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation. Conclusions: Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area. [ABSTRACT FROM AUTHOR]

Myocardial remodeling is developed by increased stress in acute or chronic pathophysiologies. Stressed heart morphology (SHM) is a new description representing basal septal hypertrophy (BSH) caused by emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension could be together in clinical practice. Therefore, there are some geometric and functional aspects regarding this specific location, septal base under acute and chronic stress stimuli. The findings by our and the other research groups support that hypertension-mediated myocardial involvement could be pre-existed in ASC cases. Beyond a frequently seen predominant base, hyperkinetic tissue response is detected in both hypertension and ASC. Furthermore, hypertension is the responsible factor in recurrent ASC. The most supportive prospective finding is BSH in which a hypercontractile base takes a longer time to exist morphologically than an acutely developed syndrome under both physiologic exercise and pressure overload by transaortic binding in small animals using microimaging. However, cardiac decompensation with apical ballooning could mask the possible underlying hypertensive disease. In fact, enough time for the assessment of previous hypertension history or segmental analysis could not be provided in an emergency unit, since ASC is accepted as an acute coronary syndrome during an acute episode. Additional supportive findings for SHM are increased stress scores in hypertensive BSH and the existence of similar tissue aspects in excessive sympathetic overdrive like pheochromocytoma which could result in both hypertensive disease and ASC. Exercise hypertension as the typical form of blood pressure variability is the sum of physiologic exercise and pathologic increased blood pressure and results in increased mortality. Hypertension is not rare in patients with a high stress score and leads to repetitive attacks in ASC supporting the important role of an emotional component as well as the potential danger due to multiple stressors at the same time. In the current review, the impact of multiple stressors on segmental or global myocardial remodeling and the hazardous potential of multiple stressors at the same time are discussed. As a result, incidentally determined segmental remodeling could be recalled in patients with multiple stressors and contribute to the early and combined management of both hypertension and chronic stress in the prevention of global remodeling and heart failure. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac magnetic resonance (CMR) is emerging as a valuable imaging modality for the assessment of aortic regurgitation (AR). In this review, we discuss the assessment of AR severity, left ventricular (LV) remodeling, and tissue characterization by CMR while highlighting the latest studies and addressing future research needs. Recent Findings: Recent studies have further established CMR-based thresholds of AR severity and LV remodeling that are associated with adverse clinical outcomes, and lower than current guideline criteria. In addition, tissue profiling with late gadolinium enhancement (LGE) and extracellular volume (ECV) quantification can reliably assess adverse myocardial tissue remodeling which is also associated with adverse outcomes. Summary: The strengths and reproducibility of CMR in evaluating ventricular volumes, tissue characteristics, and regurgitation severity position it as an excellent modality in evaluating and following AR patients. Advanced CMR techniques for the detection of tissue remodeling have shown significant potential and merit further investigation. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All patients had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24 h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 involved a 76-year-old man with hypertension and diabetes, and Case 3 involved a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. The LP, TWA, HRV, and HRT were positive in all three cases with no significant structural cardiac disease at the initial phase of admission. The further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed. Depending on the accumulation of data, the LP, TWA, HRV, and HRT could be identified as potential risk factors for COVID-19 pneumonia in the early phase of admission. [ABSTRACT FROM AUTHOR]

Abstract Background/objectives Myocardial infarction (MI) frequently leads to cardiac remodeling and failure with impaired life quality, playing an important role in cardiovascular deaths. Although physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases, the effects of strength training (ST) on the structural and functional aspects of cardiac remodeling need to be further documented. In this study, we aimed to investigate the role of a linear block ST protocol in the rat model of MI. Methods and results After 6 weeks of MI induction or sham surgery, male adult rats performed ST for the following 12 weeks. The ladder-based ST program was organized in three mesocycles of 4 weeks, with one load increment for each block according to the maximal carrying load test. After 12 weeks, the infarcted-trained rats exhibited an increase in performance, associated with reduced cardiac hypertrophy and pulmonary congestion compared with the untrained group. Despite not changing MI size, the ST program partially prevented cardiac dilatation and ventricular dysfunction assessed by echocardiography and hemodynamics, and interstitial fibrosis evaluated by histology. In addition, isolated cardiac muscles from infarcted-trained rats had improved contractility parameters in a steady state, and in response to calcium or stimuli pauses. Conclusions The ST in infarcted rats increased the capacity to carry mass, associated with attenuation of cardiac remodeling and pulmonary congestion with improving cardiac function that could be attributed, at least in part, to the improvement of myocardial contractility.

Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1 （TEM1）. Methods Sixty-four mice were equally randomized into four groups: sham operation, myocardial infarction （MI）, MI+sh-NC and MI+ sh-TEM1. On the 7th day after MI, the changes of EndMT in the infarct border area were detected by immunofluorescence staining, and the cardiac function of mice was evaluated by echocardiography on the 28th day. Mouse aortic endothelial cells （MAECs） were divided into three groups: control, Vector and rTEM1. In addition, MAECs were pretreated with MAPK inhibitor SB203580, and the cells were treated with rTEM1 for 48 h. The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot. Results In the myocardium at the border of infarction, the level of TEM1-1 increased slightly on the 1st day after MI, reached the peak on the 7th day, and then decreased on the 28th day. Compared with Vector group, the expression of VECadherin protein in the rTEM1 group decreased significantly （P < 0.05）, and the levels of α-SMA and vimentin, relative migration distance, the number of invading cells, and the number of branching formation increased significantly （P < 0.05）. SB203580 reversed these changes of MAECs induced by rTEM1. Compared with the MI group, the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly （P < 0.01）. On the 28th day, the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group （P < 0.05）. Compared with the MI group, the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh- TEM1 group decreased. Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI, which may be mechanically related to the activation of MAPKs signaling pathway. [ABSTRACT FROM AUTHOR]

Forkhead box O3a (FOXO3a)-mediated mitochondrial dysfunction plays a pivotal effect on cardiac hypertrophy and heart failure (HF). However, the role and underlying mechanisms of FOXO3a, regulated by breviscapine (BRE), on mitochondrial function in HF therapy remain unclear. This study reveals that BRE-induced nuclear translocation of FOXO3a facilitates mitofusin-1 (MFN-1)-dependent mitochondrial fusion in cardiac hypertrophy and HF. BRE effectively promotes cardiac function and ameliorates cardiac remodeling in pressure overload-induced mice. In addition, BRE mitigates phenylephrine (PE)-induced cardiac hypertrophy in cardiomyocytes and fibrosis remodeling in fibroblasts by inhibiting ROS production and promoting mitochondrial fusion, respectively. Transcriptomics analysis underscores the close association between the FOXO pathway and the protective effect of BRE against HF, with FOXO3a emerging as a potential target of BRE. BRE potentiates the nuclear translocation of FOXO3a by attenuating its phosphorylation, other than its acetylation in cardiac hypertrophy. Mechanistically, over-expression of FOXO3a significantly inhibits cardiac hypertrophy and mitochondrial injury by promoting MFN-1-mediated mitochondrial fusion. Furthermore, BRE demonstrates its ability to substantially curb cardiac hypertrophy, reduce mitochondrial ROS production, and enhance MFN-1-mediated mitochondrial fusion through a FOXO3a-dependent mechanism. In conclusion, nuclear FOXO3a translocation induced by BRE presents a successful therapeutic avenue for addressing cardiac hypertrophy and HF through promoting MFN-1-dependent mitochondrial fusion. [Display omitted] • Breviscapine protects against pathological cardiac hypertrophy and heart failure. • The FOXO3a/MFN-1 signaling is partly involved in the mitochondrial dysfunction in cardiac hypertrophy. • Nuclear FOXO3a translocation by breviscapine promotes MFN-1 mediated mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Background/objectives: Myocardial infarction (MI) frequently leads to cardiac remodeling and failure with impaired life quality, playing an important role in cardiovascular deaths. Although physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases, the effects of strength training (ST) on the structural and functional aspects of cardiac remodeling need to be further documented. In this study, we aimed to investigate the role of a linear block ST protocol in the rat model of MI. Methods and results: After 6 weeks of MI induction or sham surgery, male adult rats performed ST for the following 12 weeks. The ladder-based ST program was organized in three mesocycles of 4 weeks, with one load increment for each block according to the maximal carrying load test. After 12 weeks, the infarcted-trained rats exhibited an increase in performance, associated with reduced cardiac hypertrophy and pulmonary congestion compared with the untrained group. Despite not changing MI size, the ST program partially prevented cardiac dilatation and ventricular dysfunction assessed by echocardiography and hemodynamics, and interstitial fibrosis evaluated by histology. In addition, isolated cardiac muscles from infarcted-trained rats had improved contractility parameters in a steady state, and in response to calcium or stimuli pauses. Conclusions: The ST in infarcted rats increased the capacity to carry mass, associated with attenuation of cardiac remodeling and pulmonary congestion with improving cardiac function that could be attributed, at least in part, to the improvement of myocardial contractility. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of sodium creatine phosphate (SCP) in pediatric viral myocarditis, and cellular immune functions. Methods: Clinical data of 83 children with viral myocarditis admitted to Dezhou Traditional Chinese Medicine Hospital, China between May 2019 and June 2021 were collected and randomly assigned to control (n = 41) and study groups (n = 42). Control group (CNG) received conventional treatment for 14 days, including intravenous drip of sodium fructose diphosphate, vitamin C, and ribavirin, with the addition of prednisone if necessary. Study group (SG) received SCP in addition to conventional treatment for 14 days. Clinical efficacy, cardiac function, inflammatory and immune markers, myocardial injury, and adverse effects at the end of treatment were determined. Results: Results indicated a significantly higher total effective rate in study group (95.24 %) compared to control group (78.05 %) (p < 0.05). Study group demonstrated significantly lower heart rates and improved cardiac output, stroke volume, and left ventricular ejection fraction after 14 days of treatment compared to control group (p < 0.05). Furthermore, study group exhibited significant reduction in levels of inflammatory markers (p < 0.05), enhanced cellular immune markers (p < 0.05), and reduced myocardial injury and remodeling markers (p < 0.05). Both groups showed similar incidence of adverse reactions. Conclusion: Sodium creatine phosphate (SCP) is effective in treating pediatric viral myocarditis, enhances cardiac function, restores cellular immune function, reduces inflammation, and minimizes myocardial damage and remodeling. There will be need to evaluate the long-term efficacy and prognosis of SCP in treating pediatric viral myocarditis in the future. [ABSTRACT FROM AUTHOR]

Background and Objectives: Biochemical and molecular regulation of both adaptive and pathological responses of heart tissue to ischemic injury is widely investigated. However, it is still not fully understood. Several biomarkers are tested as predictors of left ventricle (LV) remodeling after myocardial infarction (MI). The aim of this study was to assess the relationship between selected microRNAs (miRNAs) and LV function and morphology in patients after MI. Materials and Methods: Selected miRNAs related to heart failure were assessed in the acute phase of MI: miR-150-3p, miR-21-5p, miR-19b-3p, miR-155-5p, miR-22-5p. Echocardiography with 3D imaging was performed at baseline and after 6 months. Remodeling was defined as >20% increase in LV end-diastolic volume, whereas reverse remodeling was defined as >10% reduction in LV end-systolic volume. Results: Eighty patients entered the registry. Remodeling occurred in 26% and reverse remodeling was reported in 51% of patients. In the presented study, none of the analyzed miRNAs were found to be a significant LV remodeling predictor. The observed correlations between miRNAs and other circulating biomarkers of myocardial remodeling were relatively weak. Conclusions: Our analysis does not demonstrate an association between the analyzed miRNAs and LV remodeling in patients with MI. [ABSTRACT FROM AUTHOR]

Aim to reveal specific features of the left ventricle (LV) structural and functional state and the pro-inflammatory status indicators in women of perimenopausal age. Material and methods. The cross-sectional study included 80 women (age 45 to 55 years) who were divided into 2 groups: a menopausal transition group and an early postmenopausal group according to the STRAW + 10 classification. Anthropometric measurements were taken; blood tests for homocysteine C, interleukin-6 (IL6), C-reactive protein (CRP), and echocardiography were performed according to the standard technique. Results. The study findings were as follows: 1. women in early postmenopause had higher levels of CRP when compared with women in the menopausal transition (4.5 (1.5; 8.0) mg/l versus 2.5 (0.6; 7.4) mg/l), in obese women, the level of IL6 was higher than in normal-weight women regardless of menopausal status (1.8 (0.6; 2.8) pg/ml versus 0.6 (0.2; 1.3) pg/ml); 2. the distribution of participants according to the type of myocardial remodeling did not differ in the comparison groups; 3. the presence of arterial hypertension and menopause was associated with myocardial hypertrophy; 4. significant differences were found in the distribution of myocardial geometry in women with obesity and overweight when compared to women with a normal body mass index (BMI) regardless of menopausal status; 5. significant direct correlation was registered between the structural and volume parameters of the LV and age, blood pressure, BMI, waist to hips circumference ratio. A positive correlation was found between the level of pro-inflammatory biomarkers and structural parameters of LV. Conclusion. In women of perimenopausal age, a myocardial remodeling was revealed that could not be explained by traditional risk factors. The activation of the systemic inflammatory response in menopause and obesity was accompanied by the pathological LV remodeling and myocardial hypertrophy.

Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes.

Objective: MicroRNA-30a-5p (miR-30a-5p) has been identified as a marker of heart failure; however, its functional mechanisms in chronic heart failure (CHF) remain unknown. We aim to investigate the role of miR-30a-5p targeting sirtuin-1 (SIRT1) in myocardial remodeling in CHF via the nuclear factor-κB/NOD-like receptor 3 (NF-κB/NLRP3) signaling pathway. Methods: CHF rat models were established using aortic coarctation. The expression of miR-30a-5p, SIRT1, and the NF-κB/NLRP3 signaling pathway-related factors in CHF rats was determined. The CHF rats were then respectively treated with altered miR-30a-5p or SIRT1 to explore their roles in cardiac function, myocardial function, inflammatory response, pathological changes, and cardiomyocyte apoptosis. The binding relation between miR-30a-5p and SIRT1 was confirmed. Results: MiR-30a-5p was upregulated whereas SIRT1 was downregulated in myocardial tissues of CHF rats. MiR-30a-5p inhibition or SIRT1 overexpression improved cardiac and myocardial function, and suppressed the inflammatory response, alleviated pathological changes and inhibited cardiomyocyte apoptosis in CHF rats. MiR-30a-5p targeted SIRT1 to regulate the NF-κB/NLRP3 signaling pathway. In CHF rats, downregulated miR-30a-5p and silenced SIRT1 could reverse the beneficial effects of downregulated miR-30a-5p. Conclusion: Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR) δ is a major transcriptional regulator of cardiac energy metabolism with pleiotropic properties, including anti-inflammatory, anti-oxidative and cardioprotective action. In this study, we sought to investigate whether pharmacological activation of PPARδ via intraperitoneal administration of the selective ligand GW0742 could ameliorate heart failure and mitochondrial dysfunction that have been previously reported in a characterized genetic model of heart failure , the desmin null mice (Des −/−). Our studies demonstrate that treatment of Des −/− mice with the PPARδ agonist attenuated cardiac inflammation, fibrosis and cardiac remodeling. In addition, PPARδ activation alleviated oxidative stress in the failing myocardium as evidenced by decreased ROS levels. Importantly, PPARδ activation stimulated mitochondrial biogenesis, prevented mitochondrial and sarcoplasmic reticulum vacuolar degeneration and improved the mitochondrial intracellular distribution. Finally, PPARδ activation alleviated the mitochondrial respiratory dysfunction, prevented energy depletion and alleviated excessive autophagy and mitophagy in Des −/− hearts. Nevertheless, improvement of all these parameters did not suffice to overcome the significant structural deficiencies that desmin deletion incurs in cardiomyocytes and cardiac function did not improve significantly. In conclusion, pharmacological PPARδ activation in Des −/− hearts exerts protective effects during myocardial degeneration and heart failure by preserving the function and quality of the mitochondrial network. These findings implicate PPARδ agonists as a supplemental constituent of heart failure medications. [Display omitted] • PPARδ activation alleviates mitochondrial respiratory dysfunction in Des −/− heart. • PPARδ activation stimulates mitochondrial biogenesis and improves mitochondrial network quality in the Des −/− failing heart. • PPARδ activation attenuates oxidative stress in Des −/− hearts. • PPARδ activation alleviates Des −/− induced cardiac remodeling and tissue damage. [ABSTRACT FROM AUTHOR]

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF

Cardiovascular diseases have been identified as vital factors in global morbidity and mortality in recent years. The available evidence suggests that various cytokines and pathological proteins participate in these complicated and changeable diseases. The thrombospondin (TSP) family is a series of conserved, multidomain calcium-binding glycoproteins that cause cell-matrix and cell-cell effects via interactions with other extracellular matrix components and cell surface receptors. The TSP family has five members that can be divided into two groups (Group A and Group B) based on their different structures. TSP-1, TSP-2, and TSP-4 are the most studied proteins. Among recent studies and findings, we investigated the functions of several family members, especially TSP-5. We review the basic concepts of TSPs and summarize the relevant molecular mechanisms and cell interactions in the cardiovascular system. Targeting TSPs in CVD and other diseases has a remarkable therapeutic benefit.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and β receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Yuan Tian,1,&ast; Zilin Wang,2,&ast; Feng Liang,3,&ast; Yi Wang1 1Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 2Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Heart Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wang, Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, NO. 100 Haining Road, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 021 63241377, Email wangyi2016@sjtu.edu.cnPurpose: Myocardial remodeling after myocardial infarction (MI) is a complex repair process following myocardial injury, characterized by the infiltration of multiple types of immune cells. However, the underlying molecular mechanism of myocardial remodeling after MI remains obscure. This study aimed to identify the hub differential expression genes (DEGs) of myocardial remodeling after MI and determine the distribution of immune cells infiltrating the pathology.Methods: We downloaded GSE132143, GSE151834, and GSE176092 data from the GEO database. The GSE132143 dataset was used to identify DEGs, perform functional annotation, and screen hub genes based on protein-protein interaction (PPI) analysis. The GSE151834 dataset was used to validate the expression of hub genes. CIBERSORTx analysis was performed to explore the immune microenvironment in myocardial remodeling after MI. After conducting a literature review, we selected P3H3 to confirm the expression by utilizing immunohistochemistry and qRT-PCR. Finally, the snRNA-seq data in dataset GSE176092 was used for clarifying the expression of these hub genes in various cell clusters.Results: We found 975 DEGs in myocardial remodeling after MI. Four hub genes (P3H3, COL15A1, COL16A1, COL27A1) were identified and were verified in the GSE151834 dataset. According to immune infiltration analysis, CD4+ naive T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils were involved in the pathological process of myocardial remodeling after MI. Additionally, in vitro experiments verified that P3h3 expression was significantly elevated in myocardial remodeling after MI. The snRNA-seq data analyzed that P3h3, Col15a1, Col16a1, and Col27a1 were highly expressed in fibroblasts of post-MI.Conclusion: This study identified four hub genes P3H3, COL15A1, COL16A1, and COL27A1, particularly P3H3, as potential targets for targeted therapy in MI patients.Keywords: myocardial infarction, myocardial remodeling, hub genes, immune infiltration, bioinformatic analysis

BackgroundClinical management of boys with Duchenne muscular dystrophy (DMD) relies on in-depth understanding of cardiac involvement, but right ventricular (RV) structural and functional remodeling remains understudied.PurposeTo evaluate several analysis methods and identify the most reliable one to measure RV pre- and postcontrast T1 (RV-T1) and to characterize myocardial remodeling in the RV of boys with DMD.Study typeProspective.PopulationBoys with DMD (N = 27) and age-/sex-matched healthy controls (N = 17) from two sites.Field strength/sequence3.0 T using balanced steady state free precession, motion-corrected phase sensitive inversion recovery and modified Look-Locker inversion recovery sequences.AssessmentBiventricular mass (Mi), end-diastolic volume (EDVi) and ejection fraction (EF) assessment, tricuspid annular excursion (TAE), late gadolinium enhancement (LGE), pre- and postcontrast myocardial T1 maps. The RV-T1 reliability was assessed by three observers in four different RV regions of interest (ROI) using intraclass correlation (ICC).Statistical testsThe Wilcoxon rank sum test was used to compare RV-T1 differences between DMD boys with negative LGE(-) or positive LGE(+) and healthy controls. Additionally, correlation of precontrast RV-T1 with functional measures was performed. A P-value  0.91) for assessing RV-T1. Precontrast RV-T1 was significantly higher in boys with DMD compared to controls. Both LGE(-) and LGE(+) boys had significantly elevated precontrast RV-T1 compared to controls (1543 [1489-1597] msec and 1550 [1402-1699] msec vs. 1436 [1399-1473] msec, respectively). Compared to healthy controls, boys with DMD had preserved RVEF (51.8 [9.9]% vs. 54.2 [7.2]%, P = 0.31) and significantly reduced RVMi (29.8 [9.7] g vs. 48.0 [15.7] g), RVEDVi (69.8 [29.7] mL/m2 vs. 89.1 [21.9] mL/m2 ), and TAE (22.0 [3.2] cm vs. 26.0 [4.7] cm). Significant correlations were found between precontrast RV-T1 and RVEF (β = -0.48%/msec) and between LV-T1 and LVEF (β = -0.51%/msec).Data conclusionPrecontrast RV-T1 is elevated in boys with DMD compared to healthy controls and is negatively correlated with RVEF.Level of evidence1 TECHNICAL EFFICACY: Stage 2.

Myocardial remodeling is developed by increased stress in acute or chronic pathophysiologies. Stressed heart morphology (SHM) is a new description representing basal septal hypertrophy (BSH) caused by emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension could be together in clinical practice. Therefore, there are some geometric and functional aspects regarding this specific location, septal base under acute and chronic stress stimuli. The findings by our and the other research groups support that hypertension-mediated myocardial involvement could be pre-existed in ASC cases. Beyond a frequently seen predominant base, hyperkinetic tissue response is detected in both hypertension and ASC. Furthermore, hypertension is the responsible factor in recurrent ASC. The most supportive prospective finding is BSH in which a hypercontractile base takes a longer time to exist morphologically than an acutely developed syndrome under both physiologic exercise and pressure overload by transaortic binding in small animals using microimaging. However, cardiac decompensation with apical ballooning could mask the possible underlying hypertensive disease. In fact, enough time for the assessment of previous hypertension history or segmental analysis could not be provided in an emergency unit, since ASC is accepted as an acute coronary syndrome during an acute episode. Additional supportive findings for SHM are increased stress scores in hypertensive BSH and the existence of similar tissue aspects in excessive sympathetic overdrive like pheochromocytoma which could result in both hypertensive disease and ASC. Exercise hypertension as the typical form of blood pressure variability is the sum of physiologic exercise and pathologic increased blood pressure and results in increased mortality. Hypertension is not rare in patients with a high stress score and leads to repetitive attacks in ASC supporting the important role of an emotional component as well as the potential danger due to multiple stressors at the same time. In the current review, the impact of multiple stressors on segmental or global myocardial remodeling and the hazardous potential of multiple stressors at the same time are discussed. As a result, incidentally determined segmental remodeling could be recalled in patients with multiple stressors and contribute to the early and combined management of both hypertension and chronic stress in the prevention of global remodeling and heart failure.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All patients had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24 h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 involved a 76-year-old man with hypertension and diabetes, and Case 3 involved a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. The LP, TWA, HRV, and HRT were positive in all three cases with no significant structural cardiac disease at the initial phase of admission. The further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed. Depending on the accumulation of data, the LP, TWA, HRV, and HRT could be identified as potential risk factors for COVID-19 pneumonia in the early phase of admission.

Intermittent hypoxia has been studied for many years as a promising non-pharmacological method of cardiovascular disease prevention. Hypoxic effects are accompanied by structural and functional changes in the myocardium. There is a direct link between the duration of hypoxic exposures and the severity of left ventricular myocardial remodeling. A range of histochemical markers of myocardial remodeling (cardiotrophin-1, titin, collagen type 1, annexin V) characterizing parenchymal-stromal relationships in the myocardium has shown high informativeness and prognostic value. The aim of the study was to examine cardiotrophin-1, titin, collagen type 1, annexin V and the morphofunctional state of the left ventricle of the heart in experimental rats exposed to intermittent 15-day (IH15) and 60-day hypoxia (IH60). Materials and methods. Intermittent hypoxia was modeled using 30 normotensive male Wistar rats, 7–8 months old, which were randomly assigned to 3 experimental groups of 10 animals each: 1) INT – a control group – intact animals (196.3 ± 6.8 g); 2) IH15 – 15-day hypoxia (205.6 ± 4.1 g); 3) IH60 – 60-day hypoxia (201.1 ± 5.5 g). The study compared the effects of intermittent hypoxia of varying duration: 15-day and 60-day hypoxia. Experimental modeling of intermittent hypoxia of 2 terms revealed a number of differences between the effects dependent on this factor duration through functional (blood pressure measurement, echocardiography) and immunofluorescent studies. Results. Blood pressure in rats of both groups was in the normotensive range, but an increase in systolic by 10 % and diastolic by 19 % was found in IH60 group compared to IH15 group (p < 0.05). In IH15 group, there was a significant decrease in end-diastolic dimension by 20 %, end-systolic dimension by 22 %, an increase in the thickness of left ventricular posterior wall by 44 % and interventricular septum by 33 % as well as left ventricular mass by 12 %, indicating concentric remodeling of the left ventricle, the development of which was confirmed by a 76 % increase in relative wall thickness compared to that in the control group (p < 0.05). Along with these changes, a decrease in end-diastolic volume by 47 %, end-systolic volume by 48 %, stroke volume by 49 % and cardiac output by 50 % with preserved ejection fraction was revealed (p < 0.05). While the parameters of IH60 rats were characterized by an increase in the thickness of interventricular septum by 33 % and left ventricular posterior wall by 17 %, as well as left ventricle mass by 23 %, relative left ventricular wall thickness was 15 % higher than the control value (p < 0.05). At the same time, diastolic volume was 9 % decreased and systolic volume was 24 % increased (p < 0.05). Also, cardiac output was increased by 58 % compared to that in 15-day hypoxic rats with an 8 % decrease in ejection fraction (p < 0.05). The concentrations of markers in IH60 group exceeded those in IH15, namely: cardiotrophin-1 by 39 %, titin by 70 %, collagen type 1 by 60 % and annexin V by 130 % (p < 0.05). Conclusions. 15-day hypoxia forms concentric left ventricular hypertrophy according to echocardiography findings; the study of marker profile of myocardial remodeling has revealed the development of moderate hypertrophy with increased resilient-elastic properties and decreased intensity of cardiomyocyte death. Remodeling caused by 60-day hypoxia is characterized by the eccentric pattern of changes with severe hypertrophy, significant fibrosis associated with apoptosis of cardiomyocytes. Such morphofunctional state of the myocardium may indicate the initial stages of maladaptation, increasing the risk of heart failure development.

Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure and a significant public health concern for which limited effective therapies exist. Inflammation triggered by comorbidity burden is a critical element of HFpEF pathophysiology. Here, we discuss evidence for comorbidity-driven systemic and myocardial inflammation and the mechanistic role of inflammation in pathological myocardial remodeling in HFpEF. [ABSTRACT FROM AUTHOR]

Understanding the macroscopic biventricular changes induced by pulmonary artery banding (PAB) in children with dilated cardiomyopathy (DCM) represents the first step to unraveling the regenerative potential of the myocardium. We herein investigated the phases of left ventricular (LV) rehabilitation in PAB responders, using a systematic echocardiographic and cardiac magnetic imaging (CMRI) surveillance protocol. We prospectively enrolled all patients with DCM treated with PAB from September-2015 at our institution. Among 9 patients, 7 positively responded to PAB and were selected. Transthoracic 2D echocardiography was performed before PAB; and 30, 60, 90, and 120 days after PAB; and at the last available follow-up. CMRI was performed before PAB (whenever possible) and one year after PAB. In PAB responders, LV ejection fraction showed a modest 10% increase 30–60 days after PAB, followed by its almost complete normalization after 120 days (median of 20[10–26]% vs 56[44.5–63.5]%, at baseline and 120 days after PAB, respectively). Parallelly, the LV end-diastolic volume decreased from a median of 146(87–204)ml/m2 to 48(40–50)ml/m2. At the last available follow-up (median of 1.5 years from PAB), both echocardiography and CMRI showed a sustained positive LV response, although myocardial fibrosis was detected in all patients. Echocardiography and CMRI show that PAB can promote a LV remodeling process, which starts slowly and can culminate in the normalization of LV contractility and dimensions 4 months later. These results are maintained up to 1.5 years. However, CMRI showed residual fibrosis as evidence of a past inflammatory injury whose prognostic significance is still uncertain. • PAB has been reinvented as an alternative surgical option for DCM in children. • We examined 7 PAB responders using a structured echocardiographic and CMRI protocol. • Left ventricular remodeling process starts early (30–60 days) after PAB, and ventricular function normalize at about 4-6 months. • 1.5-year follow-up CMRI shows sustained favorable left ventricular remodeling. • Areas of myocardial fibrosis were detected by CMRI in all patients. [ABSTRACT FROM AUTHOR]

Herbal-based medications have been used as therapeutic agents for thousands of years, particularly in Asian cultures. It is now well established that these herbal medications contain potent bioactive phytochemicals which exert a plethora of beneficial effects such as those seen on the cardiovascular system. Among the most widely studied of these herbal agents is ginseng, a member of the genus Panax, which has been shown to produce beneficial effects in terms of reducing cardiac pathology, at least in experimental studies. The beneficial effects of ginseng observed in such studies are likely attributable to their constituent ginsenosides, which are steroid-like saponins of which there are at least 100 and which vary according to ginseng species. Many ginseng species such as Panax ginseng (also known as Asian ginseng) and P quinquefolius (North American ginseng) as well as specific ginsenosides have been shown to attenuate hypertrophy as well as other indices of myocardial remodeling in a wide variety of experimental models. Ginkgo biloba on the other hand has been much less studied although the leaf extract of the ancient ginkgo tree has similarly consistently been shown to produce anti-remodeling effects. Ginkgo's primary bioactive constituents are thought to be terpene trilactones called ginkgolides, of which there are currently seven known types. Ginkgo and ginkgolides have also been shown to produce anti-remodeling effects as have been shown for ginseng in a variety of experimental models, in some cases via similar mechanisms. Although a common single mechanism for the salutary effects of these compounds is unlikely, there are a number of examples of shared effects including antioxidant and antiapoptotic effects as well as inhibition of pro-hypertrophic intracellular signaling such as that involving the calcineurin pathway which results in the upregulation of pro-hypertrophic genes. Robust clinical evidence represented by large scale phase 3 trials is lacking although there is limited supporting evidence from small trials at least with respect to ginseng. Taken together, both ginseng and ginkgo as well as their bioactive components offer potential as adjuvant therapy for the treatment of myocardial remodeling and heart failure. [ABSTRACT FROM AUTHOR]

Background Clinical treatment of target organ damage in hypertension is mainly based on systemic hypotension supplemented by topical medication, but the treatment is unsatisfactory due to different or even mutually exclusive responses of tissues to the drugs. The relationship between calcium-sensing receptors (CaSR) and hypertension has been investigated, however, studies on their role and mechanisms in hypertensive retinal disease are still lacking. Objective To investigate the expression level of CaSR in hypertensive retina and its relationship with myocardial remodeling and retinal vascular changes in hypertension. Methods Ten 8-week-old healthy wistar-kyoto rats (WKY) were selected as the WKY group, and 20 homologous spontaneous hypertensive rats (SHR) of the same age were randomly divided into SHR group and inhibitor (SHR+NPS2143) group from May to December 2021. During a 16-week intervention, the SHR+NPS2143 group received intraperitoneal injection of CaSR inhibitor NPS2143, while WKY and SHR groups were intraperitoneally injected with the equal volume of normal saline. At baseline and the end of intervention, blood pressure was measured by non-invasive blood pressure monitor in all rats, and from each group, five rats were selected and executed, and myocardial and retinal tissues were taken out for testing. Masson's Trichrome staining was used to measure the collagen deposition in the myocardium. H & E staining was used to detect the pathological changes in retinal tissues. The distribution and expression of CaSR and vascular endothelial growth factor A (VEGFA) in retinal tissues were detected using immunohistochemical staining and qRT-PCR. Results SHR group had significantly higher levels of systolic blood pressure (SBP) , diastolic blood pressure (DBP) and mean arterial pressure (MAP) than WKY group either at baseline or the end of intervention (P

Abstract Background We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. Methods This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. Results ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant (p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (− 76.9% vs. −9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant (p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m2 to 71.4 ± 8.8 mL/m2, p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 103 dynes/cm2 to 279.7 ± 34.1 × 103 dynes/cm2, p = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction (p = 0.080). In the ARNI-continue group, no differences in echocardiographic parameters were observed from the baseline to week 24. Conclusion Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels.

BackgroundCardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)-a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T1 and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T1 measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T1 differences between healthy controls and LGE + and LGE- boys with DMD; and (2) to report global and regional myocardial post-contrast T1 values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T1-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.MethodsBoys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T1 mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T1 and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T1 and ECV maps. ROI measurements were compared for pre-contrast myocardial T1 between boys with DMD and healthy controls, and for post-contrast myocardial T1 and ECV between LGE + and LGE- boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values

Background and Objectives: Biochemical and molecular regulation of both adaptive and pathological responses of heart tissue to ischemic injury is widely investigated. However, it is still not fully understood. Several biomarkers are tested as predictors of left ventricle (LV) remodeling after myocardial infarction (MI). The aim of this study was to assess the relationship between selected microRNAs (miRNAs) and LV function and morphology in patients after MI. Materials and Methods: Selected miRNAs related to heart failure were assessed in the acute phase of MI: miR-150-3p, miR-21-5p, miR-19b-3p, miR-155-5p, miR-22-5p. Echocardiography with 3D imaging was performed at baseline and after 6 months. Remodeling was defined as >20% increase in LV end-diastolic volume, whereas reverse remodeling was defined as >10% reduction in LV end-systolic volume. Results: Eighty patients entered the registry. Remodeling occurred in 26% and reverse remodeling was reported in 51% of patients. In the presented study, none of the analyzed miRNAs were found to be a significant LV remodeling predictor. The observed correlations between miRNAs and other circulating biomarkers of myocardial remodeling were relatively weak. Conclusions: Our analysis does not demonstrate an association between the analyzed miRNAs and LV remodeling in patients with MI.

Excessive salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Given the cardioprotective effect of soy proteins in chronic kidney disease, the question arose of the possibility of leveling dietary interventions, in particular soy proteins, the damaging effect of a high-salt diet on the cardiovascular system. The aim of this work is to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling and skin histomorphology in monkeys. The study was performed on male Javan macaques (Macaca fascicularis). The control group received a standard diet (2 g NaCl/kg feed). The second was a high-salt diet (8 g NaCl/kg feed), the third was a high-salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography, registration of BP and heart rate were performed at baseline, after 4 and 12 months. After 12 months, a histological examination of the musculocutaneous flap was performed. In all animals, BP and heart rate did not change significantly during 12 months. In macaques on a high-salt diet, by the end of the study, deterioration in systolic and diastolic functions of the left ventricle (LV) was noted. In animals receiving additional soy protein, these changes leveled out. After 12 months, macaques fed soy protein had LV myocardial mass smaller and higher LV contractility than animals fed excess salt without soy protein. In monkeys on a high-salt diet, accumulation of collagen fibers in the hypodermis, hyalinization of the cytoplasm of capillary smooth muscle cells, perivascular and perineural edema of the reticular dermis were revealed. In animals treated with soy protein, skin capillary remodeling was less pronounced. Thus, high salt intake leads to adverse structural and functional disorders of the heart and blood vessels in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system. [ABSTRACT FROM AUTHOR]

Sustained hypertension causes structural, functional, and neurohumoral abnormalities in the heart, a disease commonly termed hypertensive heart disease (HHD). Modern concepts of HHD, including processes of remodeling leading to the development of various LVH patterns, HF patterns accompanied by micro- and macrovasculopathies, and heart rhythm and conduction disturbances, are missing in the available definitions, despite copious studies being devoted to the roles of myocardial and vascular fibrosis, and neurohumoral and sympathetic regulation, in HHD development and progression. No comprehensive and generally accepted universal definition and classification of HHD is available to date, implementing diagnostic criteria that incorporate all the possible changes and adaptions to the heart. The aim of this review series is to summarize the relevant literature and data, leading to a proposal of a definition and classification of HHD. This first article reviews the processes of initial myocardial remodeling, and myocardial and vascular fibrosis, occurring in HHD. We discuss important pathophysiological and microstructural changes, the different patterns of fibrosis, and the biomarkers and imaging used to detect fibrosis in HHD. Furthermore, we review the possible methods of targeting myocardial fibrosis in HHD, and highlight areas for further research. [ABSTRACT FROM AUTHOR]

Abstract Background Since cardiovascular magnetic resonance (CMR) imaging allows comprehensive quantification of both myocardial function and structure we aimed to assess myocardial remodeling processes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods CMR imaging was performed in 40 patients with severe AS before and 1 year after TAVR. Image analyses comprised assessments of myocardial volumes, CMR-feature-tracking based atrial and ventricular strain, myocardial T1 mapping, extracellular volume fraction-based calculation of left ventricular (LV) cellular and matrix volumes, as well as ischemic and non-ischemic late gadolinium enhancement analyses. Moreover, biomarkers including NT-proBNP as well as functional and clinical status were documented. Results Myocardial function improved 1 year after TAVR: LV ejection fraction (57.9 ± 16.9% to 65.4 ± 14.5%, p = 0.002); LV global longitudinal (− 21.4 ± 8.0% to -25.0 ± 6.4%, p

Cardiovascular diseases, the leading global cause of death, are usually associated with cardiac hypertrophy (CH). CH is an adaptive response of the heart against cardiac overloading, but continuous CH accelerates cardiac remodeling and results in heart failure. Available CH therapies delay the progress of heart failure, but they often fail to control symptoms or restore quality of life. Although flaxseed lignans have been shown to have significant anti-oxidant, anti-hypertensive, anti-inflammatory, and anti-fibrotic effects in various cardiovascular diseases, little is known about their effect on CH. Thus, this study evaluated the therapeutic effect of flaxseed lignans on CH, which was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Flaxseed lignans (200 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological, and ultrastructural analyses were performed. Flaxseed lignans significantly ameliorated CH structural and functional alterations as shown by echocardiography. Lignans also reduced the relative heart weight, significantly decreased the elevated CK-MB and the lipid peroxidation marker malondialdehyde, augmented the myocardial total antioxidant capacity, and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The results demonstrate promising anti-hypertrophic effect of flaxseed lignans against isoproterenol-induced cardiac hypertrophy, via regulating myocardial remodeling and oxidative stress. Therefore, lignans could be used as potential pharmacological intervention in the management of CH. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is observed in arterial hypertension, heart failure, ischemic heart disease, and pulmonary pathology, particularly, chronic obstructive pulmonary disease (COPD). COPD in turn is a risk factor for developing these cardiovascular diseases and various arrhythmias. In the coronavirus disease (COVID) situation, such comorbid patients are the most vulnerable group with a high risk of adverse outcomes. The relevance of the relationship between COPD and coronavirus infection is explained by the similarity of clinical and pathophysiological manifestations, creating more difficulties in diagnosing and determining rational treatment. The aim of the current study is to explore the role COPD plays in the onset and progression of AF, especially in the situation of COVID-19. Methods: We searched PubMed databases and included studies with information on comorbid patients suffering from COPD and AF, as well as similar patients in the context of COVID-19. Results: A modern view on the problem of comorbidity of COPD and AF is presented. In the presence of cardiorespiratory comorbidity, symptoms of mutual worsening of the clinical course are observed, due to the commonality of some links of pathogenesis, including hypoxia, hemodynamic disturbances, activation of the sympathoadrenal system, systemic inflammation, and development of fibrosis, leading to myocardial remodeling, a decrease in the effectiveness of the therapy, and a worsening prognosis, especially in the context of COVID-19. Conclusions: The results of a study of the features of the pathogenesis and course of AF in COPD are presented, as well as the formation and progression of this comorbid pathology in the context of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. Methods: This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. Results: ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant (p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (− 76.9% vs. −9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant (p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m2 to 71.4 ± 8.8 mL/m2, p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 103 dynes/cm2 to 279.7 ± 34.1 × 103 dynes/cm2, p = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction (p = 0.080). In the ARNI-continue group, no differences in echocardiographic parameters were observed from the baseline to week 24. Conclusion: Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels. [ABSTRACT FROM AUTHOR]

Cardiovascular disease has become the primary disease that threatens human health and is considered the leading cause of death. Cardiac remodeling, which is associated with cardiovascular disease, mainly manifests as cardiac hypertrophy, fibrosis, inflammation, and oxidative stress. Farrerol plays an important role in treating conditions such as inflammation, endothelial injury and tumors, and we speculated that Farrerol may also play an important role in mitigating cardiac hypertrophy and remodeling. We established a model of myocardial remodeling using Angiotensin II (Ang II) with concurrent intraperitoneal injection of Farrerol as an intervention. We used cardiac ultrasound, immunohistochemistry, Immunofluorescence, Wheat Germ Agglutinin, Dihydroethidium, Western Blot, qPCR and other methods to detect the role of Farrerol in cardiac remodeling. The results showed that Farrerol inhibited Ang II-induced cardiac hypertrophy; decreased the ratio of heart weight to tibia length in mice; reduced inflammation, fibrosis, and oxidative stress; and reduced the size of cardiomyocytes in vivo. Farrerol inhibited Ang II-induced cardiomyocyte hypertrophy, levels of oxidative stress, and the proliferation and migration of fibroblast in vitro. Our results revealed that Farrerol could inhibit Ang II-induced cardiac remodeling. Farrerol may therefore be a candidate drug for the treatment of myocardial remodeling. [ABSTRACT FROM AUTHOR]

The impact of long-term sleep deprivation on the heart and its underlying mechanisms are poorly understood. The present study aimed to investigate the impact of chronic sleep deprivation (CSD) on the heart and mitochondrial function and explore an effective drug for treating CSD-induced heart dysfunction. We used a modified method to induce CSD in mice; lipoic acid (LA) and N-acetylcysteine (NAC) were used to treat CSD mice. Echocardiography, hematoxylin-eosin (H&E) staining, Sirius red staining, and immunohistochemistry were used to determine heart function and cardiac fibrosis. The serum levels of brain natriuretic peptide (BNP), superoxide Dismutase (SOD), micro malondialdehyde (MDA), and glutathione (GSH) were measured to determine cardiovascular and oxidative stress-related damage. Transmission electron microscopy was used to investigate mitochondrial damage. RNA-seq and Western blotting were used to explore related pathways. We found that the left ventricular ejection fraction (LVEF) and fraction shortening (LVFS) values were significantly decreased and myocardial hypertrophy was induced, accompanied by damaged mitochondria, elevated reactive oxygen species (ROS), and reduced SOD levels. RNA-sequence analysis of the heart tissue showed that various differentially expressed genes in the metabolic pathway were enriched. Sirtuin 1 (Sirt1) and Glutathione S-transferase A3 (Gsta3) may be responsible for CSD-induced heart and mitochondrial dysfunction. Pharmacological inhibition of ROS by treating CSD mice with LA and NAC effectively reduced heart damage and mitochondrial dysfunction by regulating Sirt1 and Gsta3 expression. Our data contribute to understanding the pathways of CSD-induced heart dysfunction, and pharmacological targeting to ROS may represent a strategy to prevent CSD-induced heart damage. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI. [ABSTRACT FROM AUTHOR]

Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF. Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry. Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31−0.39; p < 0.05); negative correlation (r = −0.31−0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31−0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = −0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease. Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels.

BackgroundSea-level residents experience altitude sickness when they hike or visit altitudes above ~2,500 m due to the hypobaric hypoxia (HH) conditions at such places. HH has been shown to drive cardiac inflammation in both ventricles by inducing maladaptive metabolic reprogramming of macrophages, which evokes aggravated proinflammatory responses, promoting myocarditis, fibrotic remodeling, arrhythmias, heart failure, and sudden deaths. The use of salidroside or altitude preconditioning (AP) before visiting high altitudes has been extensively shown to exert cardioprotective effects. Even so, both therapeutic interventions have geographical limitations and/or are inaccessible/unavailable to the majority of the population as drawbacks. Meanwhile, occlusion preconditioning (OP) has been extensively demonstrated to prevent hypoxia-induced cardiomyocyte damage by triggering endogenous cardioprotective cascades to mitigate myocardial damage. Herein, with the notion that OP can be conveniently applied anywhere, we sought to explore it as an alternative therapeutic intervention for preventing HH-induced myocarditis, remodeling, and arrhythmias.MethodsOP intervention (6 cycles of 5 min occlusion with 200 mmHg for 5 min and 5 min reperfusion at 0 mmHg – applying to alternate hindlimb daily for 7 consecutive days) was performed, and its impact on cardiac electric activity, immunoregulation, myocardial remodeling, metabolic homeostasis, oxidative stress responses, and behavioral outcomes were assessed before and after exposure to HH in mice. In humans, before and after the application of OP intervention (6 cycles of 5 min occlusion with 130% of systolic pressure and 5 min reperfusion at 0 mmHg – applying to alternate upper limb daily for 6 consecutive days), all subjects were assessed by cardiopulmonary exercise testing (CPET).ResultsComparing the outcomes of OP to AP intervention, we observed that similar to the latter, OP preserved cardiac electric activity, mitigated maladaptive myocardial remodeling, induced adaptive immunomodulation and metabolic homeostasis in the heart, enhanced antioxidant defenses, and conferred resistance against HH-induce anxiety-related behavior. Additionally, OP enhanced respiratory and oxygen-carrying capacity, metabolic homeostasis, and endurance in humans.ConclusionsOverall, these findings demonstrate that OP is a potent alternative therapeutic intervention for preventing hypoxia-induced myocarditis, cardiac remodeling, arrhythmias, and cardiometabolic disorders and could potentially ameliorate the progression of other inflammatory, metabolic, and oxidative stress-related diseases.

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM.Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules.Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications.Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.

Myocardial remodeling refers to structural and functional disorders of the heart caused by molecular biological changes in the cardiac myocytes in response to neurological and humoral factors. A variety of heart diseases, such as hypertension, coronary artery disease, arrhythmia, and valvular heart disease, can cause myocardial remodeling and eventually lead to heart failure. Therefore, counteracting myocardial remodeling is essential for the prevention and treatment of heart failure. Sirt1 is a nicotinamide adenine dinucleotide+-dependent deacetylase that plays a wide range of roles in transcriptional regulation, energy metabolism regulation, cell survival, DNA repair, inflammation, and circadian regulation. It positively or negatively regulates myocardial remodeling by participating in oxidative stress, apoptosis, autophagy, inflammation, and other processes. Taking into account the close relationship between myocardial remodeling and heart failure and the involvement of SIRT1 in the development of the former, the role of SIRT1 in the prevention of heart failure via inhibition of myocardial remodeling has received considerable attention. Recently, multiple studies have been conducted to provide a better understanding of how SIRT1 regulates these phenomena. This review presents the progress of research involving SIRT1 pathway involvement in the pathophysiological mechanisms of myocardial remodeling and heart failure.

Myocarditis (MC) is an inflammatory disease of the myocardium that can cause sudden death in the acute phase, and dilated cardiomyopathy (DCM) with chronic heart failure as its major long-term outcome. However, the molecular mechanisms beyond the acute MC phase remain poorly understood. The ankyrin repeat domain 1 (ANKRD1) is a functionally pleiotropic stress/stretch-inducible protein, which can modulate cardiac stress response during various forms of pathological stimuli; however, its involvement in post-MC cardiac remodeling leading to DCM is not known. To address this, we induced experimental autoimmune myocarditis (EAM) in ANKRD1-deficient mice, and evaluated post-MC consequences at the DCM stage mice hearts. We demonstrated that ANKRD1 does not significantly modulate heart failure; nevertheless, the genetic ablation of Ankrd1 blunted the cardiac damage/remodeling and preserved heart function during post-MC DCM. [ABSTRACT FROM AUTHOR]

Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. One of the key mechanisms determining myocardial dysfunction in heart failure is oxidative stress. MicroRNAs (miRNAs, miRs) are short, endogenous, conserved, single-stranded non-coding RNAs of around 21–25 nucleotides in length that act as regulators of multiple processes. A systematic review following the PRISMA guidelines was performed on the evidence on the interplay between microRNA and oxidative stress in heart failure. A search of Pubmed, Embase, Scopus, and Scopus direct databases using the following search terms: 'heart failure' AND 'oxidative stress' AND 'microRNA' or 'heart failure' AND 'oxidative stress' AND 'miRNA' was conducted and resulted in 464 articles. Out of them, 15 full text articles were eligible for inclusion in the qualitative analysis. Multiple microRNAs are involved in the processes associated with oxidative stress leading to heart failure development including mitochondrial integrity and function, antioxidant defense, iron overload, ferroptosis, and survival pathways. [ABSTRACT FROM AUTHOR]

Objective: We propose a deep learning-based fully automatic right ventricle (RV) segmentation technique that targets radially reconstructed long-axis (RLA) images of the center of the RV region in routine short axis (SA) cardiovascular magnetic resonance (CMR) images. Accordingly, the purpose of this study is to compare the accuracy of deep learning-based fully automatic segmentation of RLA images with the accuracy of conventional deep learning-based segmentation in SA orientation in terms of the measurements of RV strain parameters. Materials and methods: We compared the accuracies of the above-mentioned methods in RV segmentations and in measuring RV strain parameters by Dice similarity coefficients (DSCs) and correlation coefficients. Results: DSC of RV segmentation of the RLA method exhibited a higher value than those of the conventional SA methods (0.84 vs. 0.61). Correlation coefficient with respect to manual RV strain measurements in the fully automatic RLA were superior to those in SA measurements (0.5–0.7 vs. 0.1–0.2). Discussion: Our proposed RLA realizes accurate fully automatic extraction of the entire RV region from an available CMR cine image without any additional imaging. Our findings overcome the complexity of image analysis in CMR without the limitations of the RV visualization in echocardiography. [ABSTRACT FROM AUTHOR]