Cardiac Function Parameters Research Articles

Farrerol Alleviates Diabetic Cardiomyopathy by Regulating AMPK-Mediated Cardiac Lipid Metabolic Pathways in Type 2 Diabetic Rats.

Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats' body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.

Anchored PKA synchronizes adrenergic phosphoregulation of cardiac Cav1.2 channels

Adrenergic modulation of voltage gated Ca2+ currents is a context specific process. In the heart Cav1.2 channels initiate excitation-contraction coupling. This requires PKA phosphorylation of the small GTPase Rad (Ras associated with diabetes) and involves direct phosphorylation of the Cav1.2 α1 subunit at Ser1700. A contributing factor is the proximity of PKA to the channel through association with A-kinase anchoring proteins (AKAPs). Disruption of PKA anchoring by the disruptor peptide AKAP-IS prevents upregulation of Cav1.2 currents in tsA-201cells. Biochemical analyses demonstrate that Rad does not function as an AKAP. Electrophysiological recording shows that channel mutants lacking phosphorylation sites (Cav1.2 STAA) lose responsivity to the second messenger cAMP. Measurements in cardiomyocytes isolated from Rad-/- mice show that adrenergic activation of Cav1.2 is attenuated but not completely abolished. Whole animal electrocardiography studies reveal that cardiac selective Rad KO mice exhibited higher baseline left ventricular ejection fraction, greater fractional shortening, and increased heart rate as compared to control animals. Yet, each parameter of cardiac function was slightly elevated when Rad-/- mice were treated with the adrenergic agonist isoproterenol. Thus, phosphorylation of Cav1.2 and dissociation of phospho-Rad from the channel are local cAMP responsive events that act in concert to enhance L-type calcium currents. This convergence of local PKA regulatory events at the cardiac L-type calcium channel may permit maximal β-adrenergic influence on the fight-or-flight response.

Abstract Tu033: CXCL5: The Next Guardian of the Galaxy to challenge Atherosclerosis

Atherosclerosis is a persistent inflammatory disease characterized by the buildup of lipid-laden macrophages (foam cells) in arterial walls and has been linked to several cardiovascular ailments. Despite advances in understanding its pathogenesis, the underlying mechanisms of atherogenesis, particularly regarding chemokine influence, has yet to be investigated. Our laboratory has previously identified CXCL5, a chemokine known for its involvement in inflammatory responses, as a potential mediator of atherosclerosis. We found that patients with elevated CXCL5 levels were less likely to have experienced a previous heart attack or develop coronary artery disease, suggesting that CXCL5 may be atheroprotective. To further investigate the role of CXCL5 in atherosclerosis, we conducted a study using mice on an apolipoprotein E (apoE) knockout background, to promote the formation of plaque, with varying alleles (0, 1, or 2) of CXCL5. Mice were placed on a high-fat diet regimen starting at approximately 10 weeks of age and continued until 26 weeks of age. Aortas, echocardiograms, and blood plasma were obtained to assess the development of atherosclerosis and its impact on cardiac function and metabolic parameters. Our en face oil red o staining results showed that the aortas of mice lacking one (p=.0314) or both alleles (p=.0783) of CXCL5 exhibited elevated plaque formation compared to that of wild-type mice. Echocardiographic data revealed that left ventricular mass (corrected) was highest in CXCL5 knockout mice and increased significantly over time (p=.0170) in these animals. Additionally, a significant increase in heart rate (p=.0095) and glucose (p=.0274) levels was only observed in CXCL5 heterozygous mice over the 16-week period, while triglyceride levels increased in both CXCL5 heterozygous (p=.0010) and knockout (p=.0241) mice. Interestingly, high-density lipoprotein (HDL) levels, which is often considered as "good cholesterol," increased significantly only in wild-type (p=.0031) mice, where CXCL5 was present, over the 16-week period. These findings suggest that CXCL5 may play a protective role against atherosclerosis and its associated cardiac complications. In conclusion, our study provides novel insights into the complex interplay between inflammation, lipid metabolism, and cardiovascular disease, highlighting the potential therapeutic value of CXCL5 in the prevention and treatment of atherosclerosis.

Echocardiographic Functional Outcomes Following Regional Nodal Irradiation for Breast Cancer Using Volumetric Modulated Arc Therapy

Regional nodal irradiation (RNI) for breast cancer yields improvements in disease outcomes, yet comprehensive target coverage often increases cardiac radiation therapy (RT) dose. Volumetric modulated arc therapy (VMAT) may mitigate high-dose cardiac exposure, although it often increases the volume of low-dose exposure. The cardiac implications of this dosimetric configuration (in contrast to historic 3D conformal techniques) remain uncertain. Eligible patients receiving adjuvant RNI using VMAT for locoregional breast cancer were prospectively enrolled in an IRB-approved study. Echocardiograms were performed prior to RT, at the conclusion of RT, and 6 months following RT. Echocardiographic parameters were measured by a single reader and measures were compared pre- and post-RT via the signed-rank test. Changes in echocardiographic parameters over time were compared to mean and max heart doses via the Spearman correlation test. Among 19 evaluable patients (median age 38 years), 89% (n = 17) received doxorubicin and 37% (n = 7) received trastuzumab/pertuzumab combination therapy. All patients received VMAT-based whole-breast/chest wall and RNI. The average mean heart dose was 456 cGy (range, 187-697 cGy) and the average max heart dose was 3001 cGy (1560-4793 cGy). Among salient echocardiographic parameters, no significant decrement in cardiac function was observed when comparing pre-RT to 6 months post-RT: mean left ventricular ejection fraction (LVEF) was 61.8% (SD 4.4%) pre-RT and 62.7% (SD 3.8%) 6 months post-RT (P = .493); mean global longitudinal strain (GLS) was -19.3% (SD 2.2%) pre-RT and -19.6% (SD 1.8%) 6 months post-RT (P = .627). No individual patient exhibited reduced LVEF or sustained decrement in GLS. No correlations were observed for changes in LVEF or GLS when compared to mean or maximum heart doses (P > .1 for all). VMAT for left-sided RNI yielded no significant early decrement in echocardiographic parameters of cardiac function, including LVEF and GLS, within this limited cohort. No patient exhibited significant LVEF changes, and none exhibited sustained decrements in GLS. VMAT may be a reasonable approach to cardiac avoidance in patients requiring RNI, including those receiving anthracyclines and HER2-directed therapy. Larger cohorts with longer follow-ups will be needed to validate these findings.

Diastolic dysfunction in Alzheimer’s disease model mice is associated with Aβ-amyloid aggregate formation and mitochondrial dysfunction

Alzheimer's Disease (AD) is a progressive neurodegenerative disease caused by the deposition of Aβ aggregates or neurofibrillary tangles. AD patients are primarily diagnosed with the concurrent development of several cardiovascular dysfunctions. While few studies have indicated the presence of intramyocardial Aβ aggregates, none of the studies have performed detailed analyses for pathomechanism of cardiac dysfunction in AD patients. This manuscript used aged APPSWE/PS1 Tg and littermate age-matched wildtype (Wt) mice to characterize cardiac dysfunction and analyze associated pathophysiology. Detailed assessment of cardiac functional parameters demonstrated the development of diastolic dysfunction in APPSWE/PS1 Tg hearts compared to Wt hearts. Muscle function evaluation showed functional impairment (decreased exercise tolerance and muscle strength) in APPSWE/PS1 Tg mice. Biochemical and histochemical analysis revealed Aβ aggregate accumulation in APPSWE/PS1 Tg mice myocardium. APPSWE/PS1 Tg mice hearts also demonstrated histopathological remodeling (increased collagen deposition and myocyte cross-sectional area). Additionally, APPSWE/PS1 Tg hearts showed altered mitochondrial dynamics, reduced antioxidant protein levels, and impaired mitochondrial proteostasis compared to Wt mice. APPSWE/PS1 Tg hearts also developed mitochondrial dysfunction with decreased OXPHOS and PDH protein complex expressions, altered ETC complex dynamics, decreased complex activities, and reduced mitochondrial respiration. Our results indicated that Aβ aggregates in APPSWE/PS1 Tg hearts are associated with defects in mitochondrial respiration and complex activities, which may collectively lead to cardiac diastolic dysfunction and myocardial pathological remodeling.

Plasma Deoxycholic Acid Levels are Associated with Hemodynamic and Clinical Outcomes in Acute Pulmonary Embolism Patients.

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

Impact of volume indices in bioelectrical impedance measurement on the assessment of cardiac function indices by echocardiography in hemodialysis patients

Introduction Cardiovascular events resulting from volume overload are a primary cause of mortality in hemodialysis patients. Bioelectrical impedance analysis (BIA) is significantly valuable for assessing the volume status of hemodialysis (HD) patients. In this article, we explore the correlation between the volume index measured by BIA and the cardiac function index assessed by echocardiography (ECG) in HD patients. Methods Between April and November 2018, we conducted a cross-sectional study involving randomly selected 126 maintenance HD patients. Comprehensive data on medical history and laboratory test results were collected. Subsequently, we investigated the correlation between volume indices measured by BIA and cardiac function parameters by ECG. Results We discovered a significant correlation between the volume indices measured by BIA and various parameter of cardiac function. The Left Ventricular Hypertrophy (LVH) group exhibited higher levels of the percentage of Extracellular Water (ECW%) and the percentage of Total Body Water (TBW%) compared to the Non-LVH group. Extracellular Water (ECW) and Third Interstitial Fluid Volume (TSFV) were identified as independent risk factors for Left Ventricular Mass (LVM), and both demonstrated a high predictive value for LVM. ECW% emerged as an independent risk factor for the Left Ventricular Mass Index (LVMI), with a high predictive value for LVMI. Conclusion ECW and TSFV were found to be positively associated with cardiac function parameters in HD patients.

Impact of baseline ECG characteristics on changes in cardiac biomarkers and echocardiographic metrices after acute myocardial infarction treated with Empagliflozin

The EMMY trial was a multicentre, investigator-initiated, placebo-controlled, double-blind trial, which enrolled 476 patients immediately following AMI and the first study demonstrating a significant reduction in NT-proBNP-levels as well as significant improvements in cardiac structure and function in patients after acute myocardial infarction treated with empagliflozin vs. placebo. However, hardly any data are available investigating the prognostic role of baseline electrocardiogram metrics in SGLT2-inhibitor-treated patients. This post-hoc analysis investigated the association of baseline ECG metrics collected in one centre of the trial (181 patients) with changes in structural and functional cardiac parameters as well as cardiac biomarkers in response to Empagliflozin treatment. A total of 181 patients (146 men; mean age 58 ± 14 years) were included. Median PQ-interval was 156 (IQR 144–174) milliseconds (ms), QRS width 92 (84–98) ms, QTc interval 453 (428–478) ms, Q-wave duration 45 (40–60) ms, Q-wave amplitude 0.40 (0.30–0.70) millivolt (mV), and heart rate was 71 (64–85) bpm. For functional cardiac parameters (LVEF and E/eʹ) of the entire cohort, a greater decrease of E/eʹ from baseline to week 26 was observed in shorter QRS width (P = 0.005).Structural cardiac endpoints were only found to have a significant positive correlation between LVEDD and Q wave duration (P = 0.037). Higher heart rate was significantly correlated with better response in LVEF (P = 0.001), E/eʹ (P = 0.021), and NT-proBNP (P = 0.005). Empagliflozin-treatment showed no interaction with the results. Baseline ECG characteristics post AMI are neither predictive for beneficial NTproBNP effects of Empagliflozin post AMI, nor for functional or structural changes within 26 weeks post AMI.

Effects of Meditation and Breathing Therapy on Anxiety Improvement before and after Percutaneous Coronary Intervention in Patients with Coronary Artery Disease: A Prospective Cohort Study

Abstract Background: Coronary artery disease (CAD) is a leading cause of worldwide mortality, and percutaneous coronary intervention (PCI) has long been used to alleviate its symptoms. However, patient anxiety has been noted to exacerbate the negative symptoms of CAD, as well as reduce the effectiveness of PCI. Numerous techniques have been developed for alleviating patient stress, such as mindfulness and breathing exercises, though their efficacy with respect to improving PCI outcomes has still not been fully defined. In this study, we aimed to shed light by examining whether CAD patients who underwent such exercises demonstrated lowered anxiety and improved functional outcomes post-PCI compared to CAD patients who did not undergo these procedures. Methods: One hundred and sixty CAD patients were enrolled and randomly divided into two 80-member groups, one of which (intervention) was prescribed meditation therapies, in the form of 6-min mindfulness videos, breathing therapies carried out 12 times per cycle, for 3 times/day, as well as targeted psychological counseling. The other 80-patient group served as the untreated control (Con). Anxiety was monitored during that time period using the Zung’s Self-rating Anxiety Scale (SAS), while sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI); furthermore, various cardiac functioning parameters, such as heart rate, were measured. In addition, the occurrence of serious adverse events (SAEs) was monitored during the 3-month follow-up period post-PCI. Results: No significant differences were present between the intervention and Con groups for baseline patient characteristics, except for body mass index. However, the intervention group had lower stress levels, in the form of lower SAS, compared to baseline, while the opposite was true for the untreated Con group. Lower SAS also corresponded to lower PSQI pre-PCI in intervention, indicating that this group had improved sleep quality, while PSQI remained unchanged from baseline to PCI in Con. Along with lower stress levels, intervention had lower blood pressures, heart rate, and SAEs, compared to Con, both pre-PCI and during the 3-month follow-up period, illustrating that meditation and respiratory therapies are able to reduce stress pre-PCI, in turn improving PCI outcomes and reducing complications postprocedure. Conclusion: Meditation and respiratory therapies are able to effectively alleviate anxiety and improve sleep quality pre-PCI, in turn improving cardiac functional parameters and facilitating smooth PCI procedures. All of these improvements resulted in increased PCI success rates, lowered hospitalization time, and reduced postsurgical complications in the form of SAEs, enabling these strategies to be of great clinical utility for better preparing CAD patients for the procedure. Public Registration: ClinicalTrials.gov identifier is NCT05320848.

The Impact of Regorafenib on Cardiac Function in Metastatic Colorectal Cancer Patients a Retrospective Cohort Study

Introduction: Metastatic colorectal cancer (mCRC) poses significant clinical challenges, necessitating the exploration of novel treatment modalities. Regorafenib, a multi-kinase inhibitor, has emerged as a promising therapeutic option for refractory mCRC. However, concerns regarding its potential cardiotoxic effects warrant comprehensive evaluation of its impact on cardiac function parameters in this patient population. Methods: The purpose of this retrospective cohort research was to find out how regorafenib affected cardiac function measures in patients with metastatic colorectal cancer (mCRC) at the Pakistan Institute of Medical Sciences (PIMS) in Islamabad. 78 adult patients in all, having histologically proven mCRC, who were treated with regorafenib between January 2023 and March 2024 were included in the analysis. Baseline characteristics, treatment details, cardiac function parameters, and incidence of cardiac events were retrospectively analyzed. Statistical analyses were performed to assess changes in cardiac function parameters and identify predictors of cardiac toxicity associated with regorafenib therapy. Results: Following regorafenib therapy, there was a significant decrease in left ventricular ejection fraction (LVEF), alterations in diastolic function indices, and an incidence of clinically significant cardiac events (12%), including heart failure, arrhythmias, and myocardial infarction. Subgroup analyses identified older age, male sex, pre-existing hypertension, longer treatment duration, and higher cumulative doses of regorafenib as potential predictors of cardiac toxicity. Conclusion: This study underscores the potential cardiotoxic effects of regorafenib in mCRC patients and highlights the importance of personalized cardiac monitoring and risk management strategies during treatment. Further research is warranted to validate these findings and inform evidence-based approaches to optimize the cardiovascular safety of regorafenib in clinical practice.

Left ventricular geometry characteristics and clinical outcomes in hemodialysis patients with heart failure with preserved ejection fraction

BackgroundThe relationships among left heart remodeling, cardiac function, and cardiovascular events (CEs) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) undergoing maintenance hemodialysis (MHD) remain unclear. We evaluated the echocardiographic characteristics and clinical outcomes of such patients with diverse left ventricular geometric (LVG) configurations.MethodsOverall, 210 patients with HFpEF undergoing MHD (cases) and 60 healthy controls were enrolled. Cases were divided into four subgroups based on LVG and were followed up for three years. The primary outcomes were the first CEs and all-cause mortality.ResultsLeft ventricular ejection fraction (LVEF) and right ventricular systolic function did significantly differ between cases and controls, whereas echocardiographic parameters of cardiac structure, diastolic function, and left ventricular global longitudinal strain (LVGLS) differed significantly. The proportion of cases with left ventricular hypertrophy (LVH) was 67.1%. In addition, 2.38%, 21.90%, 12.86%, and 62.86% of cases presented with normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH), respectively. The left atrial diameter (LAD) was the largest and cardiac output index was the lowest in the EH subgroup. The score of Acute Dialysis Quality Initiative Workgroup (ADQI) HF class was worse in the EH subgroup than in other subgroups at baseline. The proportions of cases free of adverse CEs in the EH subgroup at 12, 24, and 36 months were 40.2%, 14.8%, and 0%, respectively, and the survival rates were 85.2%, 29.6%, 3.7%, respectively, which were significantly lower than those in other subgroups. Multivariate Cox regression revealed that age, TNI (Troponin I), EH, left ventricular mass index (LVMI), age and EH configuration were independent risk factors for adverse CEs and all-cause mortality in the cases.ConclusionMost patients with HFpEF receiving MHD have LVH and diastolic dysfunction. Among the four LVGs, patients with HFpEF undergoing MHD who exhibited EH had the highest risk of adverse CEs and all-cause mortality.

Pediatric dilated cardiomyopathy: a review of current clinical approaches and pathogenesis.

Pediatric dilated cardiomyopathy (DCM) is a rare, yet life-threatening cardiovascular condition characterized by systolic dysfunction with biventricular dilatation and reduced myocardial contractility. Therapeutic options are limited with nearly 40% of children undergoing heart transplant or death within 2 years of diagnosis. Pediatric patients are currently diagnosed based on correlating the clinical picture with echocardiographic findings. Patient age, etiology of disease, and parameters of cardiac function significantly impact prognosis. Treatments for pediatric DCM aim to ameliorate symptoms, reduce progression of disease, and prevent life-threatening arrhythmias. Many therapeutic agents with known efficacy in adults lack the same evidence in children. Unlike adult DCM, the pathogenesis of pediatric DCM is not well understood as approximately two thirds of cases are classified as idiopathic disease. Children experience unique gene expression changes and molecular pathway activation in response to DCM. Studies have pointed to a significant genetic component in pediatric DCM, with variants in genes related to sarcomere and cytoskeleton structure implicated. In this regard, pediatric DCM can be considered pediatric manifestations of inherited cardiomyopathy syndromes. Yet exciting recent studies in infantile DCM suggest that this subset has a distinct etiology involving defective postnatal cardiac maturation, such as the failure of programmed centrosome breakdown in cardiomyocytes. Improved knowledge of pathogenesis is central to developing child-specific treatment approaches. This review aims to discuss the established biological pathogenesis of pediatric DCM, current clinical guidelines, and promising therapeutic avenues, highlighting differences from adult disease. The overarching goal is to unravel the complexities surrounding this condition to facilitate the advancement of novel therapeutic interventions and improve prognosis and overall quality of life for pediatric patients affected by DCM.

Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism

BackgroundHeart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism.Methods In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated.ResultsIn both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism.ConclusionsXBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Echocardiography - a non-invasive alternative for assessing cardiac morphology and function in Atlantic salmon (Salmo salar L.)

Cardiac-related mortality is increasing in farmed salmon. Non-invasive tools for examining and screening for cardiac morphology and function are limited, and most common methodologies are lethal, time-consuming, and immobile. Echocardiography has previously been tested as a non-invasive, quick, and portable alternative, though its implementation is minimal. Improvements in echocardiographic techniques during the last decade have enabled more refined assessments of structure and function and hold potential for use in fish farms. Utilising a compact, transportable ultrasound system, we examined the applicability of echocardiography in Atlantic salmon (Salmo salar L.). Several protocols and projections were tested, and intra- and inter-variation for both operators (image acquisition) and observers (image analysis) were assessed. In addition, the accuracy of cardiac structure/function measurements was compared with standard methods. In general, high accuracy and reproducibility of cardiac dimensions and functional parameters were found within the same and between different observers analysing the same dataset (intra- and inter-observer). Measurements between recordings of the same operator (intra-operator) and between different operators (inter-operator) were less accurate and repeatable but comparable to observations in previous human and mammalian studies. Cardiac output was slightly higher when measured with echocardiography compared to transit time flow probe. Yet, a strong correlation exists between the two methods. Furthermore, morphology measured in excised hearts ex vivo was comparable to echocardiography measurements and strongly correlated. Thus, ultrasound presents a highly feasible, non-invasive, and swift alternative to current methods for detailed cardiac assessment of salmon hearts.

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis.

The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. https://inplasy.com, identifier (INPLASY202440114).

How automated techniques ease functional assessment of the fetal heart: Applicability of two-dimensional speckle-tracking echocardiography for comprehensive analysis of global and segmental cardiac deformation using fetalHQ®.

Prenatal echocardiographic assessment of fetal cardiac function has become increasingly important. Fetal two-dimensional speckle-tracking echocardiography (2D-STE) allows the determination of global and segmental functional cardiac parameters. Prenatal diagnostics is relying increasingly on artificial intelligence, whose algorithms transform the way clinicians use ultrasound in their daily workflow. The purpose of this study was to demonstrate the feasibility of whether less experienced operators can handle and might benefit from an automated tool of 2D-STE in the clinical routine. A total of 136 unselected, normal, singleton, second- and third-trimester fetuses with normofrequent heart rates were examined by targeted ultrasound. 2D-STE was performed separately by beginner and expert semiautomatically using a GE Voluson E10 (FetalHQ®, GE Healthcare, Chicago, IL). Several fetal cardiac parameters were calculated (end-diastolic diameter [ED], sphericity index [SI], global longitudinal strain [EndoGLS], fractional shortening [FS]) and assigned to gestational age (GA). Bland-Altman plots were used to test agreement between both operators. The mean maternal age was 33 years, and the mean maternal body mass index prior to pregnancy was 24.78kg/m2. The GA ranged from 16.4 to 32.0weeks (average 22.9weeks). Averaged endoGLS value of the beginner was -18.57%±6.59 percentage points (pp) for the right and -19.58%±5.63 pp for the left ventricle, that of the expert -14.33%±4.88 pp and -16.37%±5.42 pp. With increasing GA, right ventricular endoGLS decreased slightly while the left ventricular was almost constant. The statistical analysis for endoGLS showed a Bland-Altman-Bias of -4.24 pp±8.06 pp for the right and -3.21 pp±7.11 pp for the left ventricle. The Bland-Altman-Bias of the ED in both ventricles in all analyzed segments ranged from -.49mm±1.54mm to -.10mm±1.28mm, that for FS from -.33 pp±11.82 pp to 3.91 pp±15.56 pp and that for SI from -.38±.68 to -.15±.45. Between both operators, our data indicated that 2D-STE analysis showed excellent agreement for cardiac morphometry parameters (ED and SI), and good agreement for cardiac function parameters (EndoGLS and FS). Due to its complexity, the application of fetal 2D-STE remains the domain of scientific-academic perinatal ultrasound and should be placed preferably in the hands of skilled operators. At present, from our perspective, an implementation into clinical practice "on-the-fly" cannot be recommended.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation

BackgroundSepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PurposeThe present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. Study DesignThe palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. Methods/ResultsEchocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. ConclusionOur findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Structural and functional cardiac parameters across occupations: a cross-sectional study in differing work environments

Previous investigations have highlighted notable variations in cardiovascular risk indicators associated with various professional categories. However, only a few studies have examined structural and functional cardiac parameters using echocardiography within distinct occupational groups. Hence, this study endeavored to assess cardiac structural and functional parameters in three additional occupations: firefighters (FFs), police officers (POs), and office workers (OWs). This prospective study encompassed 197 male participants (97 FFs, 54 POs, and 46 OWs) from Germany. All participants underwent 2D and Doppler echocardiography in resting conditions; standard parasternal and apical axis views were employed to evaluate structural (diastolic and systolic) and functional (systolic and diastolic function, and strain) cardiac parameters. All three occupational groups exhibited a tendency towards septal hypertrophy. Notably, OWs exhibited the largest diastolic interventricular septum diameter (IVSd), at 1.33 ± 0.25 cm. IVSd significantly varied between POs and OWs (p = 0.000) and between POs and FFs (p = 0.025). Additionally, during diastole a substantially larger left ventricular posterior wall diameter (LVPWd) was observed in OWs compared to FFs (p = 0.001) and POs (p = 0.013). The left ventricular diastolic cavity diameter (LVIDd) and the left ventricular systolic cavity diameter (LVIDs) were significantly higher in POs than they were in FFs (LVIDd: p = 0.001; LVIDs: p = 0.009), and the LVIDd was notably higher in FFs (p = 0.015) and POs compared to OWs (p = 0.000). FFs exhibited significantly better diastolic function, indicated by higher diastolic peak velocity ratios (MV E/A ratio) and E/E’ ratios, compared to POs (E/A ratio: p = 0.025; E/E’ ratio: p = 0.014). No significant difference in diastolic performance was found between OWs and FFs. Significantly higher E’(lateral) values were noted in POs compared to FFs (p = 0.003) and OWs (p = 0.004). Ejection fraction did not significantly differ among FFs, POs, and OWs (p > 0.6). The left ventricular mass (LV Mass) was notably higher in POs than it was in FFs (p = 0.039) and OWs (p = 0.033). Strain parameter differences were notably improved in two- (p = 0.006) and four-chamber (p = 0.018) views for FFs compared to POs. Concentric remodeling was the predominant change observed in all three occupational groups. Significant differences in the presence of various forms of hypertrophy were observed in FFs, POs, and OWs (exact Fisher test p-values: FFs vs. OWs = 0.021, POs vs. OWs = 0.002). OWs demonstrated notably higher rates of concentric remodeling than FFs did (71.77% vs. 47.9%). This study underscores disparities in both functional and structural parameters in diverse occupational groups. Larger prospective studies are warranted to investigate and delineate differences in structural and functional cardiac parameters across occupational groups, and to discern their associated effects and risks on the cardiovascular health of these distinct professional cohorts.

Decreased heart rate variability in sympathetic dominant states in Parkinson's disease and isolated REM sleep behavior disorder

IntroductionParkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in parasympathetic dominant states. In this study, we aimed to examine whether HRV in sympathetic dominant states during the head-up tilt table test (HUT) serves as a marker of autonomic dysfunction in PD and isolated REM sleep behavior disorder (iRBD). MethodsWe retrospectively assessed 102 patients with PD, 10 patients with iRBD, and 43 healthy controls. We then measured the coefficient of variation of RR intervals as an HRV parameter in sympathetic dominant states (CVRR-S) and parasympathetic dominant states (CVRR-P). Furthermore, we evaluated parameters of cardiac autonomic function, including HUT and the heart-to-mediastinum (H/M) ratio of cardiac metaiodobenzylguanidine scintigraphy. ResultsPatients with iRBD and PD at Hoehn and Yahr stage I exhibited a significantly decreased CVRR-S compared to healthy controls (controls vs. iRBD vs. PD; 1.82 ± 0.64 % vs. 1.13 ± 0.41 % vs. 1.15 ± 0.51 %, p < 0.001), although no further deterioration was observed in PD at more severe Hoehn and Yahr stages. CVRR-S showed a significant correlation with the H/M ratio in PD (r = 0.51, p < 0.001). Additionally, receiver operating characteristic (ROC) analysis revealed a larger area under the ROC curve in CVRR-S compared to that in CVRR-P for discriminating PD or iRBD from healthy controls. ConclusionHRV in sympathetic dominant states shows the potential to be a marker of autonomic dysfunction in iRBD and early-stage PD, aiding in early diagnosis and patient stratification.

The Relationship Between Cardiac CT-based Left Atrial Structure and Epicardial Adipose Tissue and Postablation Atrial Fibrillation Recurrence Within 2 Years.

The aim of this study was to explore the association of cardiac CT-based left atrium (LA) structural and functional parameters and left atrial epicardial adipose tissue (LA-EAT) parameters with postablation atrial fibrillation (AF) recurrence within 2 years. Contrast-enhanced cardiac CT images of 286 consecutive AF patients (median age: 65 y; 97 females) who underwent initial ablation between June 2018 and June 2020 were retrospectively analyzed. Structural and functional parameters of LA, including maximum and minimum volume and ejection fraction of LA and left atrial appendage (LAA), and LA-EAT volume, were measured. The body surface area indexed maximum and minimum volume of LA (LAVImax, LAVImin) and LAA (LAAVImax, LAAVImin), and LA-EAT volume index (LA-EATVI) were calculated. Independent predictors of AF recurrence were determined using Cox regression analysis. The clinical predictors were added to the imaging predictors to build a combined model (clinical+imaging). The predictive performance of the clinical, imaging, and combined models was assessed using the area under the receiver operating characteristics curve (AUC). A total of 108 (37.8%) patients recurred AF within 2 years after ablation at a median follow-up of 24 months (IQR=11, 32). LA and LAA size and LA-EAT volume were significantly increased in patients with AF recurrence (P<0.05). After the multivariable regression analysis, LA-EATVI, LAAVImax, female sex, AF duration, and stroke history were independent predictors for AF recurrence. The combined model exhibited superior predictive performance compare to the clinical model (AUC=0.712 vs. 0.641, P=0.023) and the imaging model (AUC=0.712 vs. 0.663, P=0.018). Cardiac CT-based LA-EATVI and LAAVImax are independent predictors for postablation AF recurrence within 2 years and may provide a complementary value for AF recurrence risk assessment.