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PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Background/Objectives: Recent advances in artificial intelligence, particularly in cardiac imaging, can potentially enhance patients' diagnosis and prognosis and identify novel imaging markers. We propose an automated, computer-aided algorithm utilizing native cardiac computed tomography (CT) imaging to identify myocardial fibrosis. This study aims to evaluate its performance compared to CMR markers of fibrosis in a cohort of patients diagnosed with breast cancer. Methods: The study included patients diagnosed with early HER2+ breast cancer, who presented LV dysfunction (LVEF < 50%) and myocardial fibrosis detected on CMR at the time of diagnosis. The patients were also evaluated by cardiac CT, and the extracted images were processed for the implementation of the automatic, computer-assisted algorithm, which marked as fibrosis every pixel that fell within the range of 60–90 HU. The percentage of pixels with fibrosis was subsequently compared with CMR parameters. Results: A total of eight patients (n = 8) were included in the study. High positive correlations between the algorithm's result and the ECV fraction (r = 0.59, p = 0.126) and native T1 (r = 0.6, p = 0.112) were observed, and a very high positive correlation with LGE of the LV(g) and the LV-LGE/LV mass percentage (r = 0.77, p = 0.025; r = 0.81, p = 0.015). A very high negative correlation was found with GLS (r = −0.77, p = 0.026). The algorithm presented an intraclass correlation coefficient of 1 (95% CI 0.99–1), p < 0.001. Conclusions: The present pilot study proposes a novel promising imaging marker for myocardial fibrosis, generated by an automatic algorithm based on native cardiac CT images. [ABSTRACT FROM AUTHOR]

Objective To investigate the inhibitory effects of astaxanthin (AST) on pressure overload-induced left ventricular hypertrophy in mice and to explore its molecular mechanism. Methods Twenty-four C57BL/6 wild-type male mice were randomly divided into the following four groups： sham group, sham +AST group, cardiac hypertrophy group, and cardiac hypertrophy +AST group, with 6 in each group. The model of left ventricular myocardial hypertrophy was established by thoracic aorta coarctation (TAC) in the cardiac hypertrophy group and cardiac hypertrophy +AST group. The thoracic aortas of mice in both the sham group and sham +AST group were not ligated. AST ［150 mg/ (kg·d) ］ was intragastrically administered daily from the next day after surgery for 4 weeks in sham +AST group and cardiac hypertrophy +AST group. The mice in sham group and cardiac hypertrophy group were given the same volume of normal saline. After sacrifice, the ratios of heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) of mice were measured. The hypertrophy and fibrosis degree of myocardium in mice were observed by HE staining and Picro Sirius Red (PSR) staining, and the cardiomyocyte cross-sectional area and collagen volume fraction were calculated. The mRNA expression levels of atrial natriuretic peptide (ANP), myocardial β isoform (β-MHC), fibrosis-related molecules collagen fiber type Ⅰ (Collα1), and connective tissue growth factor (CTGF) were detected by real-time PCR (RT-PCR). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in myocardium were estimated by hydroxylamine method and thiobarbituric acid method, respectively. The protein expression levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) and Heme oxygenase 1 (HO-1) were detected by Western blotting. Results The myocardial structures in the sham group and sham +AST group were neatly arranged without fibrosis. In contrast, the heart volume and fibrosis significantly increased in the cardiac hypertrophy group and cardiac hypertrophy +AST group, and the changes in the cardiac hypertrophy group were more obvious. Compared with the sham group and sham +AST group, the HW/BW, HW/TL, cardiomyocyte cross-sectional area and collagen volume fraction increased in the cardiac hypertrophy group and cardiac hypertrophy +AST group, the mRNA expression levels of ANP,β-MHC, Collα1 and CTGF, and myocardial MDA expression increased, while the protein expression levels of Nrf2 and HO-1, and SOD activity decreased, and the changes in the cardiac hypertrophy group were more significant (all P<0. 05) . Conclusion AST effectively attenuates pressure overload-induced induced left ventricular hypertrophy in mice and its mechanism may be related to reducing the oxidative stress of myocardial tissues by activating Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell (ADMSC) exosomes (Exo) on adverse ventricular remodeling after myocardial infarction (MI). Methods The changes of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed. MI rats were injected with an equal volume of normal saline, adipose derived mesenchymal stem cell exosomes (MSC-Exo) or fibroblast exosomes (MEF-Exo) via a tail vein. The expression of autophagy related 16 like protein 1 (ATG16L1), autophagy related protein 7 (ATG7) and NOD-like receptor protein 3 (NLRP3), inflammatory response, the degree of myocardial fibrosis, and the cardiac function were observed in different groups. Results After treatment with H2O2 on cardiac fibroblasts, the expressions of ATG16L1 and ATG7 were significantly decreased (P<0. 001), NLRP3 was significantly increased ( P < 0. 001 ), and the levels of inflammatory cytokines interleukin-1β ( IL-1β) and IL-18 were significantly elevated (P < 0. 001 ). After MI rats were intervened with MSC-Exo, the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated (P<0. 001), NLRP3 was significantly down-regulated (P<0. 001), serum IL-1β and IL-18 levels were significantly decreased (P<0. 001), fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced (P<0. 001), myocardial fibrosis was significantly relieved (P<0. 001), and cardiac function was significantly improved (P<0. 001). Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes. [ABSTRACT FROM AUTHOR]

Background: Exercise is associated with several cardiac adaptations that can enhance one's cardiac output and allow one to sustain a higher level of oxygen demand for prolonged periods. However, adverse cardiac remodelling, such as myocardial fibrosis, has been identified in athletes engaging in long-term endurance exercise. Cardiac magnetic resonance (CMR) imaging is considered the noninvasive gold standard for its detection and quantification. This review seeks to highlight factors that contribute to the development of myocardial fibrosis in athletes and provide insights into the assessment and interpretation of myocardial fibrosis in athletes. Methods: A literature search was performed using the PubMed/Medline database and Google Scholar for publications that assessed myocardial fibrosis in athletes using CMR. Results: A total of 21 studies involving 1642 endurance athletes were included in the analysis, and myocardial fibrosis was found in 378 of 1595 athletes. A higher prevalence was seen in athletes with cardiac remodelling compared to control subjects (23.7 vs. 3.3%, p < 0.001). Similarly, we found that young endurance athletes had a significantly higher prevalence than veteran athletes (27.7 vs. 19.9%, p < 0.001), while male and female athletes were similar (19.7 vs. 16.4%, p = 0.207). Major myocardial fibrosis (nonischaemic and ischaemic patterns) was predominately observed in veteran athletes, particularly in males and infrequently in young athletes. The right ventricular insertion point was the most common fibrosis location, occurring in the majority of female (96%) and young athletes (84%). Myocardial native T1 values were significantly lower in athletes at 1.5 T (p < 0.001) and 3 T (p = 0.004), although they had similar extracellular volume values to those of control groups. Conclusions: The development of myocardial fibrosis in athletes appears to be a multifactorial process, with genetics, hormones, the exercise dose, and an adverse cardiovascular risk profile playing key roles. Major myocardial fibrosis is not a benign finding and warrants a comprehensive evaluation and follow-up regarding potential cardiac disease. [ABSTRACT FROM AUTHOR]

Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01); the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01); serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01); serum IL-1β and cTn levels were increased (P < 0.01); myocardial collagen volume fraction were increased (P < 0.01); and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01); the expression of SMAD7 mRNA was decreased (P < 0.01); the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01); the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group; the collagen volume fraction and deposition of type I/III collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix. [ABSTRACT FROM AUTHOR]

Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Lamin A/C gene (LMNA) mutations cause myocardial fibrosis manifesting as arrhythmogenic, non-compaction, or dilated cardiomyopathies. Fibro-fatty replacement largely involves the conduction system and conduction disease commonly occurs prior to contractile dysfunction. Case summary Two young, unrelated Caucasian males, aged 34 and 25, were referred to our centre for treatment of advanced heart failure. Both patients had a family history of heart failure and sudden cardiac death among their first-degree relatives and were diagnosed with Lamin A/C mutations, but they had not been screened prior to disease onset. Although the initial phenotypes were dilated cardiomyopathy and left ventricular non-compaction cardiomyopathy, both patients' disease progressed rapidly to include ventricular arrhythmias, severe global left ventricular hypokinesis, and dependence on outpatient milrinone to complete activities of daily living. Both patients received heart transplantation within 2 years of initial disease onset. The surgical pathology of the explanted hearts revealed characteristic findings of fibro-fatty degeneration of the conduction system, and using light microscopy, they were found to have nuclear membrane thinning, bubbling, and convolution throughout all areas sampled. Discussion Lamin A/C–related cardiomyopathy is associated with sudden cardiac death early in the disease course, warranting early consideration of implantable cardioverter defibrillator implantation, and rapid progression to end-stage cardiomyopathy refractory to standard medical therapies, necessitating early referral to an advanced heart failure centre. We report a newly observed and recorded finding of morphologic nuclear alterations in late-stage disease using high-power light microscopy. These alterations underscore the pathophysiology of Lamin A/C–related cardiomyopathy and provide a basis for future research into disease-specific therapies. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. Methods and results CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8--–84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24–68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000 ± 22 ms in males and 1022 ± 23 ms in females [mean difference (MD) = 22 ms, 95% confidence interval (CI) (17, 27)]. Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 [β=10 ms, 95% CI (3.4, 15.8)]. There was no significant interaction between sex and age (P = 0.27). Further, age was not associated with native T1 [β=0.1 ms, 95% CI (−0.02, 0.2)], and native T1 did not change during a 1-year period [MD −4 ms, 95% CI (−11, 3)]. Conclusion Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition. [ABSTRACT FROM AUTHOR]

BACKGROUND: N6-methyladenosine (m6A) is a hot research topic in the mechanism of pathological cardiac remodeling and plays an important role in the development of cardiovascular diseases. OBJECTIVE: To summarize the possible mechanism by which m6A modification in non-coding RNAs regulates the main processes of pathological cardiac remodeling, such as pathological cardiac hypertrophy, cardiomyocyte death, myocardial fibrosis and vascular remodeling. METHODS: “m6A, non-coding RNA, pathological cardiac hypertrophy, cardiomyocyte apoptosis, cardiomyocyte pyroptosis, cardiomyocyte ferroptosis, myocardial fibrosis, vascular remodeling” were used as search terms in Chinese and English. Relevant literature from CNKI, PubMed and Web of Science databases published from January 1974 to April 2023 was retrieved, and finally 86 eligible articles were reviewed. RESULTS AND CONCLUSION: m6A modification is a highly dynamic and reversible modification. Pathological cardiac remodeling mainly involves pathological cardiac hypertrophy, cardiomyocyte apoptosis, cardiomyocyte pyroptosis, cardiomyocyte ferroptosis, myocardial fibrosis and vascular remodeling. m6A-related enzymes can regulate pathological cardiac remodeling processes through various non-coding RNAs and different signaling pathways, which can be used as a new potential intervention for cardiovascular diseases. In pathological cardiac remodeling, research on the regulatory relationship between m6A modification and non-coding RNAs is still in its infancy. With the development of epigenetics, m6A modification in non-coding RNAs is expected to have a new development in the regulation of pathological cardiac remodeling. [ABSTRACT FROM AUTHOR]

Health care is currently showing a fall in heart failure (HF) incidence and prevalence, particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF remain unidentified, which would help in choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique which is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated the clinical application and accuracy of STE in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption. Furthermore, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS), which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. However, STE is known for its limitations; despite these, it has been shown to explain symptoms and signs and also to be an accurate prognosticator. The aim of this review is to examine the advantages of STE in the early evaluation of myocardial dysfunction and its correlation with right heart catheterization (RHC) parameters, which should have significant clinical relevance in the management of HF patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes in the myocardial fibrosis indexes of myocardial infarction mice with transient receptor potential channel C1(TRPC1） knockout. Methods Twenty wild type mice and 20 TRPC1-/- mice were divided into four groups: the wild control group, wild experimental group, TRPC1-/-control group, and TRPC1-/- experimental group, with 10 mice in each. In the wild experimental group and TRPC1-/- experimental group, the left anterior descending coronary artery was lapped and sutured to establish the myocardial infarction models. In the the wild control group and TRPC1-/- control group, mice were only threaded without ligature. Twenty-four hours later, the mice were sacrificed to obtain the hearts. Normal tissues from the left ventricle were taken from the mice in the two control groups, and infarcted tissues from the anterior wall of the left ventricle were taken from the mice in the two experimental groups. RT-PCR was used to detect the expression of TRPC1 mRNA, and Western blotting was used to detect the TRPC1 protein and Collagen Ⅰ(Col-Ⅰ） and α-smooth muscle actin(α-SMA). ResultsThe mRNA expression of TRPC1 in the wild experimental group was higher than that in the TRPC1-/- experimental group, and that in the wild control group was higher than that in the TRPC1-/- control group（ both P<0. 05). The expression of TRPC1 protein in the wild experimental group was higher than that in the wild control group and the TRPC1-/- experimental group, and the expression of TRPC1 protein in the TRPC1-/-experimental group was higher than that in the TRPC1-/- control group(all P<0. 05). Col-Ⅰ and α -SMA protein expression levels in the wild experimental group were higher than those in the wild control group and TRPC1-/- experimental group, and Col-Ⅰ and α-SMA protein expression levels in the wild control group were higher than those in the TRPC1-/- control group； the expression levels of Col-Ⅰ and α-SMA in the TRPC1-/- experimental group were higher than those in the TRPC1-/- control group（all P<0. 05). Conclusion Knocking down TRPC1 gene expression can down-regulate the expression of myocardial fibrosis indexes of myocardial infarction mice. [ABSTRACT FROM AUTHOR]

Aim: To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI). Methods: The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5−/−). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H2O2, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV‐Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T‐SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT‐qPCR. Results: Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFβ1‐TGFβR2‐Smad2/3 pathway, activated AMPK‐Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK‐Sirt1 pathway and inactivated the TGFβ1‐Smad2/3 pathway, and promoted apoptosis in H2O2‐treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFβR2 expression, were attenuated by LV‐Sirt1 shRNA. Conclusion: Resistance exercise upregulates Fndc5 expression, activates AMPK‐Sirt1 pathway, inhibits the activation of TGFβ1‐Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI. [ABSTRACT FROM AUTHOR]

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Background: Exercise‐induced cardiac remodeling (CR) and myocardial fibrosis (MF) can increase cardiovascular risk in athletes. Early detection of pulmonary arterial hemodynamics parameters among athletes may be beneficial in optimizing the frequency of clinical follow‐ups. Purpose: To analyze the hemodynamics of pulmonary arteries and its relationship with CR and MF in athletes using four‐dimensional (4D) flow MRI. Study Type: Prospective. Population: One hundred twenty‐one athletes (median age, 24 years; mean exercise per week 10 hours, for mean of 5 years) and twenty‐one sedentary healthy controls (median age, 25 years; exercise per week <3 hours, irregular pattern). Field Strength/Sequence: True fast imaging with steady state free precession, time‐resolved 3D Cartesian phase‐contrast, and phase sensitive inversion recovery late gadolinium enhancement sequences at 3.0 T. Assessment: CR was defined as any cardiac parameters exceeding the 99th percentile upper reference limits, encompassing ventricular function, bi‐atrium and bi‐ventricle diameters, and ventricular wall thickness. MF was visually evaluated by three independent radiologists. 4D flow parameters were assessed in the main, right, and left pulmonary arteries (MPA, RPA, and LPA, respectively) and compared between different groups. Four machine learning (ML) models were developed to differentiate between athletes with and without CR and/or MF. Statistical Tests: Univariate analysis was used to compare groups. Area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML models. Results: Athletes had significantly higher WSSmax in the MPA, RPA, and LPA than controls. Athletes with CR and/or MF (N = 30) had significantly lower RPmax from MPA to RPA than those without (N = 91). Among the ML models, the gradient boosting machine model had the highest performance, with an AUC of 0.90. Conclusion: The pulmonary arterial hemodynamics parameters could differentiate CR and/or MF in athletes, which may be potential to assist in optimizing frequency of follow‐up. Evidence Level: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. Methods: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. Results: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. Conclusion: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice. [ABSTRACT FROM AUTHOR]

Aims Hypertensive patients of African ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodelling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. Methods and results 63 Afr-a and 47 Eu-a hypertensives underwent multi-parametric cardiovascular magnetic resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M / V) ratios, T2 and pre-/post-contrast T1 relaxation times, synthetic extracellular volume, and myocardial fibrosis (MF) were measured. 3D shape modelling was implemented to delineate ventricular geometry. LV and RV mass (indexed to body-surface-area) and M/V ratio were significantly greater in Afr-a than Eu-a hypertensives (67.1 ± 21.7 vs. 58.3 ± 16.7 g/m2, 12.6 ± 3.48 vs. 10.7 ± 2.71 g/m2, 0.79 ± 0.21 vs. 0.70 ± 0.14 g/mL, and 0.16 ± 0.04 vs. 0.13 ± 0.03 g/mL, respectively; P < 0.03). Afr-a patients showed greater basal interventricular septum thickness than Eu-a patients, influencing LV hypertrophy and RV cavity changes. This biventricular remodelling was associated with prolonged T2 relaxation time (47.0 ± 2.2 vs. 45.7 ± 2.2 ms, P = 0.005) and higher prevalence (23% vs. 4%, P = 0.001) and extent of MF [2.3 (0.6–14.3) vs. 1.6 (0.9–2.5) % LV mass, P = 0.008] in Afr-a patients. Multivariable linear regression showed that modifiable cardiovascular risk factors and greater end-diastolic volume, but not ethnicity, were independently associated with greater LV mass. Conclusion Afr-a hypertensives had distinctive biventricular remodelling, including increased RV mass, septal thickening and myocardial tissue abnormalities compared with Eu-a hypertensives. From this study, modifiable cardiovascular risk factors and ventricular geometry, but not ethnicity, were independently associated with greater LV myocardial mass. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review offers an evidence-based analysis of established and emerging cardiovascular magnetic resonance (CMR) techniques used to assess the severity of primary mitral regurgitation (MR), identify adverse cardiac remodeling and its prognostic effect. The aim is to provide different insights regarding clinical decision-making and enhance the clinical outcomes of patients with MR. Recent Findings: Cardiac remodeling and myocardial replacement fibrosis are observed frequently in the presence of substantial LV volume overload, particularly in cases with severe primary MR. CMR serves as a useful diagnostic imaging modality in assessing mitral regurgitation severity, early detection of cardiac remodeling, myocardial dysfunction, and myocardial fibrosis, enabling timely intervention before irreversible damage ensues. Summary: Incorporating myocardial remodeling in terms of left ventricular (LV) dilatation and myocardial fibrosis with quantitative MR severity assessment by CMR may assist in defining optimal timing of intervention. [ABSTRACT FROM AUTHOR]

Na Yang,1,2,&ast; Yong-Bo Hou,2,3,&ast; Tian-Hao Cui,2 Jun-Ma Yu,2 Shu-Fang He,4,5 Hai-Juan Zhu1 1Department of Anesthesiology, Maternal and Child Medical Center of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, People’s Republic of China; 3Department of Anesthesiology, Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Fang He; Hai-Juan Zhu, Email sfhe@ahmu.edu.cn; 35880762@qq.comBackground: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism.Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI.Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-β (TGF-β) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-β 1in MI rats.Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-β pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair. Keywords: ischemic preconditioning, myocardial infarction, Exosomes, MicroRNAs, cardiac function, myocardial fibrosis

The most common causes of death in acromegaly are cardiovascular diseases (about 60%). Heart arrhythmias and conduction disorders lead to sudden cardiac death (SCD). In this article, we described a clinical case about preventing SCD in a patient with acromegaly. We identified in this patient predictors of SCD: severe left ventricular hypertrophy, the signs of myocardial fibrosis, decreased systolic function of the left ventricular myocardium, ventricular rhythm disturbances, and heart failure. Patients with acromegaly have higher risk of heart arrhythmias due to development acromegalic cardiomyopathy with includes: left ventricular hypertrophy, diastolic and systolic dysfunction, myocardial fibrosis and electrical disturbances of the myocardium. The main limitation is the lack of special clinical recommendations for the management of this group of patients. Current recommendations based on a standard algorithm and do not consider specificity of acromegalic cardiomyopathy.

Increased myocardial T1 values on cardiovascular MRI (CMRI) have been shown to be a surrogate marker for myocardial fibrosis. The use of CMRI in patients on hemodialysis (HD) remains limited. This research aimed to explore the characteristics of native T1 values in HD patients and identify factors related to T1 values. A total of thirty-two patients on HD and fourteen healthy controls were included in this study. All participants underwent CMRI. Using modified Look-Locker inversion recovery (MOLLI) sequence, native T1 mapping was achieved. Native CMRI T1 values were compared between the two groups. In order to analyze the relationship between T1 values and clinical parameters, correlation analysis was performed in patients on HD. Patients on HD exhibited elevated global native T1 values compared to control subjects. In the HD group, the global native T1 value correlated positively with intact parathyroid hormone (iPTH) (r = 0.418, p = 0.017) and negatively with triglycerides (r= −0.366, p = 0.039). Moreover, the global native T1 value exhibited a positive correlation with the left ventricular end-diastolic volume indexed to body surface area (BSA; r = 0.528, p = 0.014), left ventricular end-systolic volume indexed to BSA (r = 0.506, p = 0.019), and left ventricular mass indexed to BSA (r = 0.600, p = 0.005). A negative correlation was observed between the global native T1 value and ejection fraction (r = 0.-0.551, p = 0.010). The global native T1 value was prolonged in HD patients compared with controls. In the HD group, the global T1 value correlated strongly with iPTH, triglycerides, and cardiac structural and functional parameters. [ABSTRACT FROM AUTHOR]

Abstract Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.

Abstract Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. Case presentation A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. Conclusion Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

Abstract Background Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. Methods The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. Results We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. Conclusions Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease. Graphical abstract Hyperglycemia aggravates mitochondrial injury through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA in DCM mice. Fibroblasts then engulf these mtDNA-enriched vesicles, activating TLR9 signaling and the cGAS-STING pathway to initiate profibrotic process and adverse remodeling. However, both exogenous and endogenous IL-37 ameliorate mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, and reducing the release of mtDNA-enriched vesicles, which attenuates the progression of DCM

Xin Chen,1– 3,&ast; Xing Zhong,1,4,&ast; Dan Luo,1– 3,&ast; Yuhua Lei,1– 3 Rui Huang1– 3 1Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshii, Hubei Province, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshii, Hubei Province, People’s Republic of China; 4Department of Medicine, Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei; Rui Huang, Email yuhualei0319@163.com; henry0923@whu.edu.cnBackground: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF.Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software.Results: The study included 188 patients, and the average follow-up time was 489.5± 88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012– 1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up.Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.Keywords: SMOC2, heart failure, ischemic cardiomyopathy, readmission rate, myocardial fibrosis

Abstract Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-β1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1β and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1β and SIRT1 in ISO treated mice and TGF-β1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway.

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of astragaloside IV (AS-IV) on myocardial fibrosis and Th17 cell differentiation in rats with adriamycin induced dilated cardiomyopathy (DCM). Methods: The model of DCM rats were established by intraperitoneal injection of adriamycin at the dose of 2.5 mg/kg, and the DCM rats were divided into model group, low AS-IV group, medium AS-IV group and high AS-IV group, with 10 rats in each group. In addition, 10 healthy SD rats were set as control group. The rats in low AS-IV group, medium AS-IV group and high AS-IV group were given AS-IV at doses of 20 mg/kg, 40 mg/kg and 80 mg/kg once a day for a total of 6 weeks. Rats in control group and model group were simultaneously given equal volume normal saline intragastric administration. After administration, the cardiac function index included left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were detected by ultrasound. The pathological changes of myocardial tis- sue were detected by Hematoxylin-eosin (HE) and Masson staining. The level of Th17 cells in spleen tissue of rats were detected by flow cytometry. The levels of IL-17, IL-21 and TNF-α in serum were detected by ELISA. The mRNA expression levels of RORyt and FoxP3 in rat myocardial tissue were detected by qRT-PCR, and the protein expressions of α-SMA, collagen I, TGF-β1, RORyt and FoxP3 in rat myocardial tissue were detected by Western blot. Results: The results of HE and Masson staining showed that inflammatory cell infiltration and cell hypertrophy occurred in the myocardium of the model group, and blue-stained collagen deposition increased in the interstitial tissue. Compared with model group, inflammatory cell infiltration and cell hypertrophy in myocardium of rats in low AS-IV group, medium AS-IV group and high AS-IV group were gradually relieved, and the amount of collagen deposition was reduced. Compared with control group, LVESD and LVEDD indexes of model group were increased (P<0.05), while LVEF indexes were decreased (P<0.05). The levels of α-SMA, collagen I, TGF-β1 and RORyt in myocardial tissue were increased (P<0.05), while FoxP3 level was decreased (P<0.05). The proportion of Th17 cells in spleen tissue was increased (P<0.05). The levels of IL-17, IL-21 and TNF-α in serum were in- creased (P<0.05). Compared with control group, LVESD and LVEDD indexes of model group were decreased (P<0.05), while LVEF indexes were increased (P<0.05). The levels of α-SMA, collagen I, TGF-β1 and RORyt in myocardial tissue were decreased (P<0.05), while FoxP3 level was increased (P<0.05). The proportion of Th17 cells in spleen tissue was decreased (P<0.05). The levels of IL-17, IL-21 and TNF-α in serum were decreased (P<0.05). Conclusion: AS-IV showed good therapeutic effect on DCM rats induced by adriamycin, the mechanism of which may be related to anti-myocardial fibrosis and inhibition of Th17 cell differentiation. [ABSTRACT FROM AUTHOR]

The article focuses on the role of multiple gene mutations in worsening hypertrophic cardiomyopathy (HCM). Topics include the correlation of sarcomere gene mutations with severe outcomes, the impact of calcium-channel gene mutations on heart failure progression, and the identification of genetic predictors through advanced Deoxyribonucleic Acid (DNA) sequencing techniques.

BACKGROUND: Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart, but its action mechanism needs further study. OBJECTIVE: To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats. METHODS: Totally 48 male Sprague-Dawley rats were randomly divided into four groups, with 12 rats in each group. Rats in the blank control group were fedconventionally. After one week of adaptive training, rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming (5% body mass lead block fixed in the tail, 70%-80% maximal oxygen uptake intensity), 6 days a week, 60 minutes a day. Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol (50 mg/kg per day) by gavage one hour after exercise intervention. Blank control group and exercise-related fatigue group were given the same volume of 2% dimethyl sulfoxide, 6 days a week, once a day for 6 weeks. The body mass and heart mass of the rats were measured 24 hours after the last intervention. Plasma creatine kinase isoenzyme, cardiac troponin 1, pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA. The mRNA expression levels of ventricular remodeling-related factor Foxp1, transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION: Compared with the blank control group, the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group (P < 0.05). Compared with the exercise-related fatigue group, the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group (P < 0.05). Compared with the blank control group, the levels of creatine kinase isoenzyme, cardiac troponin 1 and uncoupling protein 1 increased (P < 0.01), and the level of pyruvate dehydrogenase decreased (P < 0.01) in the exercise-related fatigue group. Compared with the exercise-related fatigue group, the levels of creatine kinase isoenzyme, myocardial troponin 1 and uncoupling protein 1 decreased (P < 0.05), and the level of pyruvate dehydrogenase increased (P < 0.05) in the exercise-related fatigue with resveratrol supplement group. Compared with the blank control group, the expression of the Foxp1 gene decreased (P < 0.01), and the expression of transforming growth factor β1 and endothelin 1 gene increased (P < 0.01) in the myocardium of the exercise-related fatigue group. Compared with the exercise-related fatigue group, the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased (P < 0.01), while the expression of the transforming growth factor β1 and endothelin 1 gene decreased (P < 0.05). It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy. Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats. This effect may be related to the regulation of Foxp1/ transforming growth factor β1/endothelin 1 signaling pathway. [ABSTRACT FROM AUTHOR]

Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration. [ABSTRACT FROM AUTHOR]

Sudden death due to unknown cardiac disease in children is an unusual occurrence. An apparently healthy 12-year-old boy without any physical restrictions collapsed suddenly and died despite cardiopulmonary resuscitation. The main autopsy finding was extensive scarring of the myocardium, especially the interventricular septum. This extensive scarring was exceptional for the young age. Histologically, replacement-type fibrosis with patchy lymphomonocytic infiltrate and infiltration by macrophages were observed. The case was diagnosed as chronic myocarditis, which may have progressed to dilated cardiomyopathy with inflammation or inflammatory cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aim Previous studies have indicated that H2 S can attenuate myocardial fibrosis. However, it is unclear whether mitochondria-targeted H2 S can attenuate myocardial fibrosis after myocardial infarction and whether its mechanism is associated with the regulation of mitochondrial fusion and fission. To investigate this relationship, this study was conducted. Methods Isoproterenol (ISO, 50 mg / (kg·d)) was injected intraperitoneally to induce myocardial infarction in SD rats. Electrocardiograms were performed on each group of rats, and the rats were treated with AP39 (36 μg / (kg·d), intraperitoneal) for 4 weeks. Masson's staining was used to assess the extent of myocardial fibrosis. Western blot was used to measure the expression of relevant proteins. In vitro experiments were performed to induce hypoxic injury in H9c2 cardiomyocytes with CoCl 2(800 μmol / L), H9c2 cells were treated with AP39 (100 nmol / L), and the endogenous hydrogen sulfide synthase cystathionine-γ-lyase ( CSE) was inhibited using DL-propargylglycine ( PAG, 2 mmol / L), and fluorescence probe was used to measure the level of reactive oxygen species(ROS) in myocardial cells. Results Myocardial fibrosis was evident in infarcted rat hearts, with a significant accumulation of collagen fibers. Additionally, the expression of CSE and mitofusin 2 (MFN2) proteins was downregulated, while dynamin-related protein 1 (DRP1) protein expression was increased. Intervention with AP39 significantly improved the above changes, and the addition of CSE inhibitor PAG reversed the effects of AP39. In in vitro experiments, when H9c2 myocardial cells were subjected to hypoxic injury induced by CoCl 2, intracellular ROS levels increased, MFN2 expression was downregulated, and DRP1 expression was upregulated. AP39 upregulated MFN2 protein expression, inhibited DRP1 protein expression, and reduced ROS levels in myocardial cells. The addition of PAG reversed these changes. Conclusion The mitochondria-targeted H2 S donor, AP39, can improve myocardial fibrosis in rats with myocardial infarction and promote mitochondrial fusion and inhibit excessive mitochondrial division. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea (OSA) is an independent risk factor for cardiovascular diseases. We aimed to investigate the role of nuclear factor‐kappa B (NF‐κB) in the changes of cardiac structures in OSA rabbits treated by mandibular advancement device (MAD). Methods: Eighteen male New Zealand white rabbits aged 6 months were randomly divided into three groups: control group, group OSA and group MAD. Hyaluronate gel was injected into the soft palate of the rabbits in group OSA and group MAD to induce OSA. The cone beam computer tomography (CBCT) of the upper airway and polysomnography (PSG) was performed to ensure successful modelling. CBCT and PSG were applied again to detect the effects of MAD treatment. All animals were induced to sleep in a supine position for 4–6 h a day for 8 weeks. Then the levels of NF‐κB, Interleukin 6 (IL‐6), Interleukin 10 (IL‐10) and the proportion of myocardial fibrosis (MF) were detected. Results: The higher activation of NF‐κB, IL‐6 and IL‐10 were found in the OSA group than in the control group, leading to the increase of collagen fibres compared with the control group. Furthermore, the apnoea‐hypopnea index (AHI) was positively correlated with the above factors. There were no significant differences between group MAD and the control group. Conclusion: The NF‐κB pathway was activated in the myocardium of OSA rabbits, which accelerated the development of MF. Early application of MAD could reduce the activation of NF‐κB in the myocardium and prevent the development of MF. [ABSTRACT FROM AUTHOR]

Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), even though often underdiagnosed. SSc-pHI has been recently defined as cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications. SSc-pHI represents a major determinant of mortality in SSc, accounting alone for about 12% of disease-related deaths; its early recognition and promptly therapeutic interventions are therefore crucial. Both perfusion defects and myocardial inflammation contribute to the occurrence of myocardial fibrosis that precipitates myocardial remodeling, potentially leading to heart failure and arrhythmic complications. To date, clear evidence and guidelines for effectively managing SSc pHI are not established yet, resulting in a lack of a defined therapeutic algorithm. In this review we summarize the most recent scientific literature on the prevailing therapeutic strategies and interventions to manage SSc-pHI, with particular focus on therapeutic strategies to counteract the 3 major pathogenic events of the disease, i.e. microvascular damage, myocardial inflammation and myocardial fibrosis. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation's role in cardiac fibrosis and evaluates emerging anti-diabetic medications' effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF. [ABSTRACT FROM AUTHOR]

Aims Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). Methods and results One-hundred fifty-eight patients [73 (68–77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0–9.7)]. Native T1 was above normal [1053 ms (1024–1071)] and T2 within the normal range [39.3 ms (37.3–42.0)]. Median MF was 11.9% (6.54–19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125). Conclusion Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting. [ABSTRACT FROM AUTHOR]