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Purpose: To research and evaluate the performance of broadband tailored kT‐point pulses (TP) and universal pulses (UP) for homogeneous excitation of the human heart at 7T. Methods: Relative 3D B1+$$ {\mathrm{B}}_1^{+} $$‐maps of the thorax were acquired from 29 healthy volunteers. TP and UP were designed using the small‐tip‐angle approximation for a different composition of up to seven resonance frequencies. TP were computed for each of the 29 B1+$$ {\mathrm{B}}_1^{+} $$‐maps, and UPs were calculated using 22 B1+$$ {\mathrm{B}}_1^{+} $$‐maps and tested in seven testcases. The performance of the pulses was analyzed using the coefficient of variation (CV) in the 3D heart volumes. The 3D gradient‐echo (GRE) scans were acquired for the seven testcases to qualitatively validate the B1+$$ {\mathrm{B}}_1^{+} $$‐predictions. Results: Single‐ and double‐frequency optimized pulses achieved homogeneity in flip angle (FA) for the frequencies they were optimized for, while the broadband pulses achieved uniformity in FA across a 1300 Hz frequency range. Conclusion: Broadband TP and UP can be used for homogeneous excitation of the heart volume across a 1300 Hz frequency range, including the water and the main six fat peaks, or with longer pulse durations and higher FAs for a smaller transmit bandwidth. Moreover, despite large inter‐volunteer variations, broadband UP can be used for calibration‐free 3D heart FA homogenization in time‐critical situations. [ABSTRACT FROM AUTHOR]

Purpose: Cushing's syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. Methods: This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. Results: Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. Conclusion: CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs. [ABSTRACT FROM AUTHOR]

The vagal regulation of cardiac function involves acetylcholine (ACh) receptor activation followed by negative chronotropic and negative as well as positive inotropic effects. The resulting signaling pathways may include Gi/o protein-coupled reduction in adenylyl cyclase (AC) activity, direct Gi/o protein-coupled activation of ACh-activated potassium current (IKACh), inhibition of L-type calcium ion channels, and/or the activation of protein phosphatases. Here, we studied the role of the protein phosphatases 1 (PP1) and 2A (PP2A) for muscarinic receptor signaling in isolated atrial preparations of transgenic mice with cardiomyocyte-specific overexpression of either the catalytic subunit of PP2A (PP2A-TG) or the inhibitor-2 (I2) of PP1 (I2-TG) or in double transgenic mice overexpressing both PP2A and I2 (DT). In mouse left atrial preparations, carbachol (CCh), cumulatively applied (1 nM–10 µM), exerted at low concentrations a negative inotropic effect followed by a positive inotropic effect at higher concentrations. This biphasic effect was noted with CCh alone as well as when CCh was added after β-adrenergic pre-stimulation with isoprenaline (1 µM). Whereas the response to stimulation of β-adrenoceptors or adenosine receptors (used as controls) was changed in PP2A-TG, the response to CCh was unaffected in atrial preparations from all transgenic models studied here. Therefore, the present data tentatively indicate that neither PP2A nor PP1, but possibly other protein phosphatases, is involved in the muscarinic receptor-induced inotropic and chronotropic effects in the mouse heart. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death in the world, with radiotherapy as one of the treatment options. Radiotherapy planning starts with delineating the affected area from healthy organs, called organs at risk (OAR). A new approach to automatic OAR segmentation in the chest cavity in Computed Tomography (CT) images is presented. The proposed approach is based on the modified U‐Net architecture with the ResNet‐34 encoder, which is the baseline adopted in this work. The new two‐branch CS‐SA U‐Net architecture is proposed, which consists of two parallel U‐Net models in which self‐attention blocks with cosine similarity as query‐key similarity function (CS‐SA) blocks are inserted between the encoder and decoder, which enabled the use of consistency regularisation. The proposed solution demonstrates state‐of‐the‐art performance for the problem of OAR segmentation in CT images on the publicly available SegTHOR benchmark dataset in terms of a Dice coefficient (oesophagus—0.8714, heart—0.9516, trachea—0.9286, aorta—0.9510) and Hausdorff distance (oesophagus—0.2541, heart—0.1514, trachea—0.1722, aorta—0.1114) and significantly outperforms the baseline. The current approach is demonstrated to be viable for improving the quality of OAR segmentation for radiotherapy planning. [ABSTRACT FROM AUTHOR]

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint. [ABSTRACT FROM AUTHOR]

Arrhythmias and depression are recognized as diseases of the heart and brain, respectively, and both are major health threats that often co-occur with a bidirectional causal relationship. The autonomic nervous system (ANS) serves as a crucial component of the heart–brain axis (HBA) and the pathway of interoception. Cardiac activity can influence emotional states through ascending interoceptive pathways, while psychological stress can precipitate arrhythmias via the ANS. However, the HBA and interoception frameworks are often considered overly broad, and the precise mechanisms underlying the bidirectional relationship between depression and arrhythmias remain unclear. This narrative review aims to synthesize the existing literature, focusing on the pathological mechanisms of the ANS in depression and arrhythmia while integrating other potential mechanisms to detail heart–brain interactions. In the bidirectional communication between the heart and brain, we emphasize considering various internal factors such as genes, personality traits, stress, the endocrine system, inflammation, 5-hydroxytryptamine, and behavioral factors. Current research employs multidisciplinary knowledge to elucidate heart–brain relationships, and a deeper understanding of these interactions can help optimize clinical treatment strategies. From a broader perspective, this study emphasizes the importance of considering the body as a complex, interconnected system rather than treating organs in isolation. Investigating heart–brain interactions enhance our understanding of disease pathogenesis and advances medical science, ultimately improving human quality of life. [ABSTRACT FROM AUTHOR]

To address the lack of clarity regarding contraceptive counselling and uptake of contraception among women with cardiovascular disease (CVD), this study aimed to conduct a systematic review and meta-analysis on contraceptive counselling and the subsequent uptake of contraception among women with CVD. A search across six databases identified 1228 articles, with 11 studies (2580 participants) included. The pooled prevalence of contraceptive counselling was 63%, varying from 36 to 94% in individual studies. Inconsistent delivery and documentation of counselling were noted, along with a lack of knowledge about pregnancy complications and misconceptions regarding CVD severity. For contraceptive uptake (n = 5), the pooled prevalence was 64% (95% confidence interval, 45 to 82%). Women with CVD were also found to use less effective methods as well as methods not recommended for their condition (e.g., combined hormonal methods among participants with absolute or relative contraindications). Improving contraceptive counselling and choices for women with CVD can not only enhance knowledge and decision-making for women with CVD in line with their reproductive goals and preferences but reduce high-risk unintended pregnancies and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

(1) The development and utilization of the vast saline–alkali land worldwide is an important way to solve the worsening food crisis. Eriocheir sinensis, due to its strong osmotic regulation capability and its characteristics of being suitable for culturing in alkaline water, has become a potential aquaculture species in saline–alkali water. The brain and heart are the key tissues for signal transduction and energy supply under environmental stress. (2) This study is the first to explore the synergistic regulatory molecular mechanism by integrated analysis on cerebral ganglion proteomics and heart metabolomics of Eriocheir sinensis under alkalinity stress. (3) The results indicate that the cerebral ganglion and heart of E. sinensis were closely related in response to acute alkalinity stress. The differential regulatory pathways mainly involved regulation of energy metabolism, amino acid metabolism, and homeostasis maintenance. Importantly, alkalinity stress induced the regulation of antioxidants and further adjusted longevity and rhythm in the cerebral ganglion and heart, reflecting that the cerebral ganglion and heart may be the key tissues for the survival of Eriocheir sinensis under an alkalinity environment. (4) This study provides a theoretical reference for research on the regulation mechanism of E. sinensis under alkalinity condition and contributes to the development of aquaculture in saline–alkali water. [ABSTRACT FROM AUTHOR]

BackgroundNitric oxide (NO) has been identified as a signaling molecule generated during β-adrenergic receptor stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca2+ release via S-nitrosylation of CaMKIIδ (Ca2+/calmodulin kinase II delta) is emerging. NO donors are routinely used clinically for their cardioprotective effects on the heart, but it is unknown how NO donors modulate the proarrhythmic CaMKII to alter cardiac arrhythmia incidence. We test the role of S-nitrosylation of CaMKIIδ at the Cysteine-273 inhibitory site and cysteine-290 activating site in cardiac Ca2+ handling and arrhythmogenesis before and during β-adrenergic receptor stimulation.MethodsWe measured Ca2+-handling in isolated cardiomyocytes from C57BL/6J wild-type (WT) mice and mice lacking CaMKIIδ expression (CaMKIIδ-KO) or with deletion of the S-nitrosylation site on CaMKIIδ at cysteine-273 or cysteine-290 (CaMKIIδ-C273S and -C290A knock-in mice). Cardiomyocytes were exposed to NO donors, S-nitrosoglutathione (GSNO; 150 μM), sodium nitroprusside (200 μM), and β-adrenergic agonist isoproterenol (100 nmol/L).ResultsBoth WT and CaMKIIδ-KO cardiomyocytes responded to isoproterenol with a full inotropic and lusitropic Ca2+ transient response as well as increased Ca2+ spark frequency. However, the increase in Ca2+ spark frequency was significantly attenuated in CaMKIIδ-KO cardiomyocytes. The protection from isoproterenol-induced Ca2+ sparks and waves was mimicked by GSNO pretreatment in WT cardiomyocytes but lost in CaMKIIδ-C273S cardiomyocytes. When GSNO was applied after isoproterenol, this protection was not observed in WT or CaMKIIδ-C273S but was apparent in CaMKIIδ-C290A. In Langendorff-perfused isolated hearts, GSNO pretreatment limited isoproterenol-induced arrhythmias in WT but not CaMKIIδ-C273S hearts, while GSNO exposure after isoproterenol sustained or exacerbated arrhythmic events.ConclusionsWe conclude that prior S-nitrosylation of CaMKIIδ at cysteine-273 can limit subsequent β-adrenergic receptor-induced arrhythmias, but that S-nitrosylation at cysteine-290 might worsen or sustain β-adrenergic receptor-induced arrhythmias. This has important implications for the administration of NO donors in the clinical setting.

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

ObjectiveFeline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.Animals43 client-owned cats with subclinical HCM.MethodsCats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.ResultsNo demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.Clinical relevanceResults demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n = 3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems-level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.

Abstract Objectives To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis. Methods In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge. Results In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p

Water temperature is one of the most important ecological environmental factors affecting fish survival and growth. When the water temperature is higher than the optimal temperature for fish survival, fish homeostasis may be disrupted. The heart plays a crucial role in maintaining vertebrate homeostasis. In this study, TMT and LC-MS/MS were performed to analyze differentially expressed protein (DEP) profiles in the hearts of turbot under high-temperature stress to explore the key proteins and metabolic pathways related to the high-temperature tolerance traits of turbot. Ninety turbot (mean weight 23.01±3.63 g, mean length 10.34±0.76 cm) were used in experiments. Three temperature points for heat stress experiments were designed: control=(14.0±0.5)℃, HT1=(20.0±0.5)℃, and HT2=(28.0±0.5)℃. Three parallel groups were established for each temperature group, with 10 turbots placed in each group. Fold Change≥1.2 or < 0.83, P < 0.05 was used as a criterion to screen for DEPs in turbot. Through mass spectrometry analysis of heart tissues from turbot, 85, 731 spectra were identified, with 35, 434 peptides, of which 31, 704 were unique, and 4, 765 proteins were identified. The HT1/control group in the heart of turbot had a total of 87 differentially expressed proteins, including 77 upregulated and 10 down-regulated proteins; the HT2/control group in the heart of turbot had 171 DEPs, including 149 upregulated and 22 down-regulated proteins; the HT2/HT1 group in the heart of turbot had a total of 188 DEPs, including 130 upregulated and 58 downregulated proteins. Through bioinformatics analysis, the DEPs between the 28℃ group and the 14℃ group, as well as the 28℃ group and the 20℃ group, were mainly enriched in KEGG pathways related to fatty acid metabolism, inflammation, and immune defense. Multiple proteins in the heat shock protein family (HSP90B, HSP70, etc.) were significantly upregulated in the 28℃ group compared to the 14℃ group. The protein interaction network revealed that HSP90B exhibited the highest correlation. A new discovery is that the expression levels of fibrinogen-related proteins (FGA, FGB, and FGG) increased, and their role in the thermal response requires further research. These results indicate that extremely high temperatures may cause fatty acid metabolic disorders in turbot, leading to inflammatory reactions. The upregulation of heat shock protein family proteins may have a positive effect on alleviating stress symptoms under heat stress. This study identified DEPs, such as HSP90B, HSPA5, and HYOU1, which were significantly upregulated under heat stress, as candidate proteins for high-temperature tolerance breeding in turbot and provided a theoretical basis for further elucidating the molecular mechanism of heat stress in turbot.

Polyomaviridae (PyV) are small, non-enveloped viruses leading after infection to mainly asymptomatic or oligosymptomatic disorders among different vertebrates. Currently 14 PyV are known to affect human health. This literature review aims to summarise accessible knowledge from both epidemiological and clinical studies conducted on healthy and PyV infected human populations, with a focus on studies containing transplantation and oncology issues. The search strategy involved screening four databases and finally 25 studies were selected for this article. The majority of the studies focused on the influence of BKPyV and JCPyV infections on renal graft recipients. Some research also described the prevalence of MCPyV and future oncological treatment. The results revealed that various types of patient fluids and tissues may be useful in PyV detection. Moreover, heterogeneity in available evidence on each PyV is observed. The studies implied possible future directions for PyV studies, including new biomarkers, the examination of risk factors or comparison of the course of the disease and treatment results in various age groups of patients.

Abstract Benign cardiac neoplasms are relatively uncommon. Cardiac leiomyomas are usually diagnosed as a benign metastasizing leiomyoma or as a part of intravenous leiomyomatosis spectrum. Primary cardiac leiomyomas are extremely rare and should be diagnosed after ruling out the involvement of systemic leiomyomas. Only nine cases were found in the literature that described De novo occurrence of primary intra-cardiac leiomyoma. In this study, we present a case of 60-year-old female patient with a large pedunculated mass located in the left ventricle. Histopathology examination and immunohistochemistry aid confirmed the diagnosis of benign leiomyoma. No evidence of extra cardiac lesions was detected in the patient. The patient remained healthy with no signs of recurrence four years after the surgical resection. Benign cardiac tumors are not often seen, but when they do occur, they can present a serious risk to life. This is particularly significant because these tumors can detach and cause embolization, leading to the development of strokes. Moreover, these individuals do not show any clinical symptoms, making their detection quite challenging. When there is a suspicion, it is advised to utilize echocardiography and other imaging techniques to verify the presence of a tumor. In this report, we present a rare case and provide differential diagnoses, along with a review of the literature.

Abstract Background Duchenne muscular dystrophy (DMD) is a rare disease that causes progressive muscle degeneration resulting in life-threatening cardiac complications. The objective of this systematic literature review was to describe and grade the published evidence of predictors of cardiac disease in DMD. Methods The review encompassed searches of Embase, MEDLINE ALL, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of cardiac disease in DMD. The certainty of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Results We included 33 publications encompassing 9,232 patients with DMD. We found moderate- to high-quality evidence that cardiac medication (i.e., ACE inhibitors [enalapril and perindopril], β-blockers [carvedilol], and mineralocorticoid receptor antagonists [eplerenone]) are significantly associated with preserved left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular circumferential strain (LVCS). DMD mutations in exons 51 and 52 were found to be significantly associated with lower risk of cardiomyopathy; deletions treatable by exon 53 skipping and mutations in the Dp116 coding region with improved LVEF and prolonged cardiac dysfunction-free survival; and exons 45–50 and 52 with early left ventricular systolic dysfunction (low/very low-quality evidence). We found high-quality evidence that glucocorticoids (deflazacort) are significantly associated with preserved LVEF and improved fractional shortening (FS), and low-quality evidence that glucocorticoids (deflazacort, prednisone, and/or prednisolone) are associated with improved ejection fraction (EF) and lower risk of cardiomyopathy, ventricular dysfunction, and heart failure-related mortality. Full-time mechanical ventilation was found to be significantly correlated with LVEF (low-quality evidence), muscle strength with FS (low-quality evidence), and genetic modifiers (i.e., LTBP4 rs10880 and ACTN3) with LVEF, lower risk of cardiomyopathy and left ventricular dilation (low-quality evidence). Conclusion Several sources of cardiac disease heterogeneity are well-studied in patients with DMD. Yet, the certainty of evidence is generally low, and little is known of the contribution of non-pharmacological interventions, as well as the impact of different criteria for initiation of specific treatments. Our findings help raise awareness of prevailing unmet needs, shape expectations of treatment outcomes, and inform the design of future research.

Abstract Background The incidence and mortality rates of cardiovascular disease worldwide are a major concern in the healthcare industry. Precise prediction of cardiovascular disease is essential, and the use of machine learning and deep learning can aid in decision-making and enhance predictive abilities. Objective The goal of this paper is to introduce a model for precise cardiovascular disease prediction by combining machine learning and deep learning. Method Two public heart disease classification datasets with 70,000 and 1190 records besides a locally collected dataset with 600 records were used in our experiments. Then, a model which makes use of both machine learning and deep learning was proposed in this paper. The proposed model employed CNN and LSTM, as the representatives of deep learning models, besides KNN and XGB, as the representatives of machine learning models. As each classifier defined the output classes, majority voting was then used as an ensemble learner to predict the final output class. Result The proposed model obtained the highest classification performance based on all evaluation metrics on all datasets, demonstrating its suitability and reliability in forecasting the probability of cardiovascular disease.

Abstract Objective To analyze the influencing factors of postoperative thrombocytopenia in critically ill patients with heart disease and construct a nomogram prediction model. Methods From October 2022 to October 2023, 319 critically ill patients with heart disease who visited our hospital were collected and separated into postoperative thrombocytopenia group (n = 142) and no postoperative thrombocytopenia group (n = 177) based on their postoperative thrombocytopenia, Logistic regression analysis was applied to screen risk factors for postoperative thrombocytopenia in critically ill patients with heart disease; R software was applied to construct a nomogram for predicting postoperative thrombocytopenia in critically ill patients with heart disease, and ROC curves, calibration curves, and Hosmer-Lemeshow goodness of fit tests were applied to evaluate nomogram. Results A total of 142 out of 319 critically ill patients had postoperative thrombocytopenia, accounting for 44.51%. Logistic regression analysis showed that gender (95% CI 1.607–4.402, P = 0.000), age ≥ 60 years (95% CI 1.380–3.697, P = 0.001), preoperative antiplatelet therapy (95% CI 1.254–3.420, P = 0.004), and extracorporeal circulation time > 120 min (95% CI 1.681–4.652, P = 0.000) were independent risk factors for postoperative thrombocytopenia in critically ill patients with heart disease. The area under the ROC curve was 0.719 (95% CI: 0.663–0.774). The slope of the calibration curve was close to 1, and the Hosmer-Lemeshow goodness of fit test was χ 2 = 6.422, P = 0.491. Conclusion Postoperative thrombocytopenia in critically ill patients with heart disease is influenced by gender, age ≥ 60 years, preoperative antiplatelet therapy, and extracorporeal circulation time > 120 min. A nomogram established based on above multiple independent risk factors provides a method for clinical prediction of the risk of postoperative thrombocytopenia in critically ill patients with heart disease.

Myocardial interstitial fibrosis (MIF) occurs in several ischemic and non-ischemic cardiomyopathies and is associated with left ventricular dysfunction and progression to heart failure (HF). MIF exists in two types – reparative and reactive with different origin and molecular mechanisms. Although MIF arises mainly because of alterations in collagen turnover leading to collagen fiber accumulation, there are also qualitative changes in collagen fibers in cardiac diseases. There are several studies for cellular and molecular mechanisms and his role in cardiac function, biomarkers and potential target therapies.

Purpose of the study. Studying the features of microcirculation, functional state and anatomy of the heart using the “Holiday Heart” syndrome model in rats we developed.Materials and methods. Experiments were carried out on white outbred male rats. The “Holiday Heart” syndrome was modeled as follows: animals received a 10 % aqueous ethanol solution as the only source of fluid for the first 10 days, then tap water for 10 days, and again a 10 % aqueous ethanol solution for the next 10 days. One day after the end of the repeated intake of alcohol, the animals were taken into the experiment. Animals that received free access to tap water served as control. Some rats in the experimental group (n = 10) had an echocardiogram recorded before the start of the experiment, and on the 31st day of the experiment, after which the level of microcirculation of blood and lymph in the brain and heart was measured using laser Doppler flowmetry. In the remaining animals (n = 10), microcirculation of blood and lymph in the brain and heart was assessed on the 3rd day of alcohol deprivation.Results. Analysis of the obtained data showed that in the conditions of the “Holiday Heart” syndrome model, significant changes occur in the anatomy, functional activity and geometry of the heart: there is a significant thinning of the anterior wall of the left ventricle heart (LV), an increase in systolic and diastolic volumes and sizes of the LV and a significant (p = 0.0018) decrease in its inotropic function. These changes occur against the background of a significant (p = 0.0081) decrease in the level of blood microcirculation in the myocardium, however, on the 3rd day of deprivation, blood flow in the microvessels of the heart increases statistically significantly (p = 0.0285).Conclusion. In model experiments reproducing the “Holiday Heart” syndrome, it was shown for the first time that ethanol causes significant changes in the microcirculation, anatomy, functional activity and geometry of the left ventricle of the heart, which, apparently, can play a key role in the formation of myocardial electrical instability pathognomonic for this syndrome.

Purpose of the study. Studying the blood microcirculation characteristics in the brain and heart of rats with ACM.Materials and methods. The study was carried out on white outbred male rats. The animals were randomized into 2 groups: 1st (n = 7) — control (intact) rats that received a normal diet and free access to water; 2nd (n = 6) — animals that received a normal diet and a 10 % ethanol solution as the only source of liquid. After 24 weeks of alcoholization in animals, the size and inotropic function of the heart were assessed using echocardiography. The next day, in anesthetized rats (urethane 1300 mg/kg i.p.), blood microcirculation in the heart and brain was recorded using a computerized laser analyzer “LAZMA-D” (manufactured by NPP “Lazma”, Russia) using the LDF 3.0.2.396 program. Using spectral wavelet analysis, the amplitudes of endothelial, neurogenic, myogenic, pulse and respiratory oscillations of microblood flow and the shunting index were determined.Results. According to echocardiography data, in rats that consumed a 10 % ethanol solution for 24 weeks, ACM is formed, which is accompanied by a decrease in blood microcirculation in the brain and myocardium. Thus, if in control animals the indicator of blood microcirculation in the myocardium was 36.60±2.19 perf. u., then in rats with ACM it was equal to 26.88±1.50 perf. u. units (p = 0.004). In the myocardium of rats with ACM, compared with control animals, the amplitude of both active and passive oscillations of microblood flow was significantly greater.Conclusion. In rats with ACM, the level of blood microcirculation in the heart muscle is significantly reduced, which, according to the results of spectral wavelet analysis, is prognostically unfavorable.

Abstract The diabetic heart is characterised by functional, morphological and metabolic alterations predisposing it to contractile failure. Chronic sympathetic activation is a feature of the pathogenesis of heart failure, however the type 1 diabetic heart shows desensitisation to β-adrenergic stimulation. Here, we sought to understand the impact of repeated isoprenaline-mediated β-stimulation upon cardiac mitochondrial respiratory capacity and substrate metabolism in the 90% pancreatectomy (Px) rat model of type 1 diabetes. We hypothesised these hearts would be relatively protected against the metabolic impact of stress-induced cardiomyopathy. We found that individually both Px and isoprenaline suppressed cardiac mitochondrial respiration, but that this was preserved in Px rats receiving isoprenaline. Px and isoprenaline had contrasting effects on cardiac substrate metabolism, with increased reliance upon cardiac fatty acid oxidation capacity and altered ketone metabolism in the hearts of Px rats, but enhanced capacity for glucose uptake and metabolism in isoprenaline-treated rats. Moreover, Px rats were protected against isoprenaline-induced mortality, whilst isoprenaline elevated cGMP and protected myocardial energetic status in Px rat hearts. Our work suggests that adrenergic stimulation may be protective in the type 1 diabetic heart, and underlines the importance of studying pathological features in combination when modeling complex disease in rodents.

Abstract Background Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive. Results We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown. Conclusions Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract

Introduction: Ketamine is a general anesthetic drug that acts by inhibiting the NMDA receptoran important component of excitatory neurotransmission. Existing of NMDA receptors all over the central nervous system and the special type of anesthesia induced by ketamine, called dissociative anesthesia has led to its use as an analgesic and also paved the way for abuse. Ketamine affects the cardiovascular system by increasing indices such as heart rate, blood pressure, and cardiac output. Methods: For further evaluation of ketamine effects on heart tissue, we used 15 male and 15 female Wistar rats and divided them into 6 groups, including male and female control groups (MC and FC), male and female short-term exposure (MS and FS), and male and female long-term exposure (ML and FL) to ketamine. Each group included 5 Wistar rats. The ML and FL groups received 75mg of ketamine once a week for 4 weeks in the posterior muscle of the thigh and the MS and FS groups received 25mg of ketamine 3 times a week for 4 weeks at the same site. Results: After preparation of histopathological slides, it was observed that only in the group of female mice receiving long-term ketamine, empty spaces and intercellular distances increased, and in the group of male mice receiving long-term ketamine, in addition to the increase of intercellular spaces, tissue accumulations were also observed in the heart tissue. Conclusion: This study showed that long-term ketamine injection in both sexes can cause some qualitative changes in heart tissue. Expanding the duration of long-term exposure to ketamine and more studies based on sexes can lead to more findings.

Abstract Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.

Abstract In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell–cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.

Abstract Background COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. Methods The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. Results Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. Conclusions In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

Quantum diamond magnetometers using lock-in detection have successfully detected weak bio-magnetic fields from neurons, a live mammalian muscle, and a live mouse heart. This opens up the possibility of quantum diamond magnetometers visualizing microscopic distributions of the bio-magnetic fields. Here, we demonstrate a lock-in-based widefield quantum diamond microscopy, achieving a mean volume-normalized per-pixel sensitivity of 43.9 nT μ m 1.5 / H z 0.5 . We optimize the sensitivity by implementing a double resonance with hyperfine driving and magnetic field alignment along the ⟨ 001 ⟩ orientation of the diamond. Additionally, we show that sub-ms temporal resolution (∼ 0.4 ms) can be achieved while keeping the per-pixel sensitivity at a few tens of nanotesla per second using quantum diamond microscopy. This lock-in-based diamond quantum microscopy could be a step forward in mapping functional activity in neuronal networks in micrometer spatial resolution. [ABSTRACT FROM AUTHOR]

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Background There is a paucity of large-scale epidemiological studies on the link between cardiac autonomic neuropathy (CAN) and the risk of silent myocardial infarction (SMI) in type 2 diabetes. We evaluated the association between CAN and the risk of SMI in a large sample of adults with type 2 diabetes. Methods and Results Participants with type 2 diabetes from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without atherosclerotic cardiovascular disease at baseline were included. CAN was ascertained using heart rate variability indices calculated from 10-s resting electrocardiograms. The heart rate variability indices included standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals. CAN was defined as both the standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals less than the fifth percentile of the general population. We used Cox proportional hazards regression to generate hazard ratios (HRs) for incident SMI in relation to CAN measures. Among 4842 participants (mean age, 62.5 years; 46.6% women; 60.2% White), there were 73 incident SMI cases over a median follow-up of 4.9 years (incidence rate 3.1 out of 1000 person-years [95% CI, 2.5-3.9]). After adjusting for confounders, low heart rate variability was associated with a higher risk of SMI (HR, 1.67 [95% CI, 1.02-2.72] and HR, 1.56 [95% CI, 0.94-2.58] for low standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals, respectively). Participants with CAN had a 1.9-fold greater risk of SMI (HR, 1.91 [95% CI, 1.14-3.20]). Conclusions In a large cohort of adults with type 2 diabetes, CAN was significantly associated with an increased risk of incident SMI.

Background Despite its high prevalence and clinical significance, clinical measurement of lipoprotein(a) is rare but has not been systematically quantified. We assessed the prevalence of lipoprotein(a) testing overall, in those with various cardiovascular disease (CVD) conditions and in those undergoing cardiac testing across 6 academic medical centers associated with the University of California, in total and by year from 2012 to 2021. Methods and Results In this observational study, data from the University of California Health Data Warehouse on the number of individuals with unique lipoprotein(a) testing, unique CVD diagnoses (using International Classification of Diseases, Tenth Revision [ICD-10], codes), and other unique cardiac testing were collected. The proportion of total individuals, the proportion of individuals with a given CVD diagnosis, and the proportion of individuals with a given cardiac test and lipoprotein(a) testing any time during the study period were calculated. From 2012 to 2021, there were 5 553 654 unique adults evaluated in the University of California health system, of whom 18 972 (0.3%) had lipoprotein(a) testing. In general, those with lipoprotein(a) testing were more likely to be older, men, and White race, with a greater burden of CVD. Lipoprotein(a) testing was performed in 6469 individuals with ischemic heart disease (2.9%), 836 with aortic stenosis (3.1%), 4623 with family history of CVD (3.3%), 1202 with stroke (1.7%), and 612 with coronary artery calcification (6.1%). For most conditions, the prevalence of testing in the same year as the diagnosis of CVD was relatively stable, with a small upward trend over time. Lipoprotein(a) testing was performed in 10 753 individuals (1.8%) who had lipid panels, with higher rates with more specialized testing, including coronary computed tomography angiography (6.8%) and apolipoprotein B (63.0%). Conclusions Lipoprotein(a) testing persists at low rates, even among those with diagnosed CVD, and remained relatively stable over the study period.

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1-/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3-6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the β-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease.

Physical activity engagement results in a variety of positive health outcomes, including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart. The purpose of this investigation was to determine if four replicate lines of High Runner mice that have been selectively bred for voluntary exercise on wheels have a cardiac phenotype that resembles the outcome of eccentric remodeling. Adult females (average age 55 days) from the 4 High Runner and 4 non-selected control lines were anaesthetized via vaporized isoflurane, then echocardiographic images were collected and analyzed for structural and functional differences. High Runner mice in general had lower ejection fractions compared to control mice lines (2-tailed p ​= ​0.023 6) and tended to have thicker walls of the anterior portion of the left ventricle (p ​= ​0.065). However, a subset of the High Runner individuals, termed mini-muscle mice, had greater ejection fraction (p ​= ​0.000 6), fractional shortening percentage (p ​

Recent studies have provided valuable insight into the key mechanisms contributing to the spatiotemporal regulation of intracellular Ca2+ release and Ca2+ signaling in the heart. In this research highlight, we focus on the latest findings published in Biophysical Journal examining the structural organization of Ca2+ handling proteins and assessing the functional aspects of intracellular Ca2+ regulation in health and the detrimental consequences of Ca2+ dysregulation in disease. These important studies pave the way for future mechanistic investigations and multiscale understanding of Ca2+ signaling in the heart.

PurposeCardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.MethodsData from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized.ResultsA harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain.ConclusionsAlthough our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging.

ABSTRACTCardiac tolerance to ischaemia can be increased by dietary interventions such as fasting, which is associated with significant changes in myocardial gene expression. Among the possible mechanisms of how gene expression may be altered are epigenetic modifications of RNA – epitranscriptomics. N6-methyladenosine (m6A) and N6,2’-O-dimethyladenosine (m6Am) are two of the most prevalent modifications in mRNA. These methylations are reversible and regulated by proteins called writers, erasers, readers, and m6A-repelled proteins. We analysed 33 of these epitranscriptomic regulators in rat hearts after cardioprotective 3-day fasting using RT-qPCR, Western blot, and targeted proteomic analysis. We found that the most of these regulators were changed on mRNA or protein levels in fasting hearts, including up-regulation of both demethylases – FTO and ALKBH5. In accordance, decreased methylation (m6A+m6Am) levels were detected in cardiac total RNA after fasting. We also identified altered methylation levels in Nox4 and Hdac1 transcripts, both of which play a role in the cytoprotective action of ketone bodies produced during fasting. Furthermore, we investigated the impact of inhibiting demethylases ALKBH5 and FTO in adult rat primary cardiomyocytes (AVCMs). Our findings indicate that inhibiting these demethylases reduced the hypoxic tolerance of AVCMs isolated from fasting rats. This study showed that the complex epitranscriptomic machinery around m6A and m6Am modifications is regulated in the fasting hearts and might play an important role in cardiac adaptation to fasting, a well-known cardioprotective intervention.

BACKGROUND: Acute myocardial infarction can cause cardiac remodeling and heart failure, as well as skeletal myopathy, affecting patients' quality of life. Exercise therapy is an important rehabilitation method for patients with heart failure; however, the optimal exercise prescription has not been clarified. OBJECTIVE: To compare the effects of different exercise modes (aerobic exercise, resistance exercise) on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism, so as to provide a basis for optimizing the exercise rehabilitation program. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into sham operation group, myocardial infarction group, aerobic exercise group and resistance exercise group. Coronary artery ligation was used to create model of heart failure. After 3 months, animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions, while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages. After the experiment, maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively, and heart structure and function were evaluated by echocardiography. The heart was isolated, and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling. For the gstrocnemius muscle, ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area, dihydroethidium method was used to evaluate reactive oxygen species levels, enzymelinked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity, western blot was used to determine the expression of ubiquitin-proteasome system proteins, and the number of activated satellite cells (Pax7+ /MyoD+ ) were detected by double immunofluorescence staining. RESULTS AND CONCLUSION: (1) Exercise performance: Compared with the sham operation group, maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased (P < 0.05); compared with the myocardial infarction group, the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased (P < 0.05). (2) Cardiac remodeling: Compared with the sham operation group, infarction area, myocardial cell cross-sectional area, and collagen content in the myocardial infarction group increased (P < 0.05), while left ventricular ejection fraction and shortening fraction decreased (P < 0.05); compared with the myocardial infarction group, there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups (P > 0.05). (3) Skeletal muscle remodeling: Compared with the sham operation group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, superoxide dismutase activity, glutathione peroxidase activity, and the number of activated satellite cells decreased in myocardial infarction group (P < 0.05), while reactive oxygen species content, malondialdehyde content, and the protein expression of ubiquitin, MuRF1 and MAFbx increased (P < 0.05); compared with the myocardial infarction group, gastrocnemius muscle mass index, superoxide dismutase activity, the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups (P < 0.05), while reactive oxygen species content and the protein expression of ubiquitin, MuRF1, and MAFbx decreased (P < 0.05); compared with the aerobic exercise group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, reactive oxygen species content, malondialdehyde content, the number of activated satellite cells increased in resistance exercise group (P < 0.05), while superoxide dismutase activity, glutathione peroxidase activity downregulated (P < 0.05). To conclude, aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure, and the mechanism is related to reducing oxidative stress, inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling. Aerobic exercise has a better effect on improving skeletal muscle oxidative stress, while resistance exercise has a more significant effect on promoting skeletal muscle regeneration. [ABSTRACT FROM AUTHOR]

The Canadian Association of Radiologists (CAR) Cardiovascular Expert Panel is made up of physicians from the disciplines of radiology, cardiology, and emergency medicine, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 30 clinical/diagnostic scenarios, a rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 48 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 125 recommendation statements across the 30 scenarios (27 unique scenarios as 2 scenarios point to the CAR Thoracic Diagnostic Imaging Referral Guideline and the acute pericarditis subscenario is included under 2 main scenarios). This guideline presents the methods of development and the referral recommendations for acute chest pain syndromes, chronic chest pain, cardiovascular screening and risk stratification, pericardial syndromes, intracardiac/pericardial mass, suspected valvular disease cardiomyopathy, aorta, venous thrombosis, and peripheral vascular disease. [ABSTRACT FROM AUTHOR]

In this study, by pooling the clinical data of patients who died with a history of long-term clozapine use and by examining their hearts, it was found that long-term clozapine use can lead to cardiomyopathy and that its presentation resembles arrhythmogenic cardiomyopathy (ACM), i.e., it exhibits a predominantly right ventricular fatty infiltration with mild left ventricular damage. The transcriptomic data of rat cardiomyocytes after clozapine intervention were analyzed by transcriptomic approach to explore the causes of clozapine cardiomyopathy. The cause of clozapine cardiomyopathy was then explored by a transcriptomic approach, which revealed that its clozapine action on cardiomyocytes enriched cardiomyocyte-related differential genes in biological processes such as muscle development and response to hypoxia, as well as pathways such as fatty acid metabolism and cellular autophagy. Transcriptomic analysis showed that Egr1, Egr2, ler2, Jun, Mapk9, Nr1d2, Atf3, Bhlhe40, Crem, Cry1, Cry2, Dbp were hub genes for clozapine injury to the myocardium, and that these genes may play an important role in the myocardial ACM-like changes caused by clozapine. Combined with the results of pathological examination and transcriptomic analysis, it can be concluded that the long-term action of clozapine on cardiomyocytes leads to cellular autophagy and subsequent structural remodeling of the heart, and in the remodeling affects fatty acid metabolism, which eventually leads to ACM-like changes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of reduced k‐space sampling on B1+$$ {\mathrm{B}}_1^{+} $$ mapping and the resulting impact on phase shimming and dynamic/universal parallel transmit (pTx) RF pulse design. Methods: Channel‐wise 3D B1+$$ {\mathrm{B}}_1^{+} $$ maps were measured at 7 T in 35 and 23 healthy subjects for the heart and prostate region, respectively. With these B1+$$ {\mathrm{B}}_1^{+} $$ maps, universal phase shims optimizing homogeneity and B1+$$ {\mathrm{B}}_1^{+} $$ efficiency were designed for heart and prostate imaging. In addition, universal 4kT‐point pulses were designed for the heart. Subsequently, individual phase shims and individual 4kT‐pulses were designed based on B1+$$ {\mathrm{B}}_1^{+} $$ maps with different acceleration factors and tested on the original maps. The performance of the pulses was compared by evaluating their coefficients of variation (CoV), B1+$$ {\mathrm{B}}_1^{+} $$ efficiencies and specific energy doses (SED). Furthermore, validation measurements were carried out for one heart and one prostate subject. Results: For both organs, the universal phase shims showed significantly higher B1+$$ {\mathrm{B}}_1^{+} $$ efficiencies and lower CoVs compared to the vendor provided default shim, but could still be improved with individual phase shims based on accelerated B1+$$ {\mathrm{B}}_1^{+} $$ maps (acquisition time = 30 s). In the heart, the universal 4kT‐pulse achieved significantly lower CoVs than tailored phase shims. Tailored 4kT‐pulses based on accelerated B1+$$ {\mathrm{B}}_1^{+} $$ maps resulted in even further reduced CoVs or a 2.5‐fold reduction in SED at the same CoVs as the universal 4kT‐pulse. Conclusion: Accelerated B1+$$ {\mathrm{B}}_1^{+} $$ maps can be used for the design of tailored pTx pulses for prostate and cardiac imaging at 7 T, which further improve homogeneity, B1+$$ {\mathrm{B}}_1^{+} $$ efficiency, or SED compared to universal pulses. [ABSTRACT FROM AUTHOR]

Clinical data: A nine-month-old female infant diagnosed with transposition of the great arteries with symptoms of heart failure associated with cyanosis and difficulty in gaining weight was referred to our center with late diagnosis (at nine months of age). Chest radiography: Cardiomegaly; attenuated peripheral vascular markings. Electrocardiography: Sinus rhythm with biventricular overload and aberrantly conducted supraventricular extra systoles. Echocardiography: Wide atrial septal defect, ventricular axis torsion with concordant atrioventricular connection and discordant ventriculoarterial connection. Computed tomography angiography: Concordant atrioventricular connection, right ventricle positioned superiorly and left ventricle positioned inferiorly; discordant ventriculoarterial connection with right ventricle connected to the aorta and left ventricle connected to pulmonary artery. Diagnosis: Crisscross heart is a rare congenital heart defect, accounting for 0.1% of congenital heart diseases. It consists of the 90° rotation of ventricles' axis in relation to their normal position; therefore, ventricles are positioned in the superior-inferior direction rather than anterior-posterior. Most cases have associated cardiac anomalies, and in this case, it is associated with transposition of the great arteries. The complexity and rarity of its occurrence make diagnosis and surgical treatment challenging. Operation: Modified Senning procedure using the pericardial sac in the construction of a tunnel from pulmonary veins to the right atrium. Cardiopulmonary bypass time of 147 minutes with nine minutes of total circulatory arrest. [ABSTRACT FROM AUTHOR]