Search Results (415)

Human adult cardiomyocytes (CMs) have limited regenerative capacity, posing a significant challenge in restoring cardiac function following substantial CM loss due to an acute ischemic event or chronic hemodynamic overload. Nearly half of patients show no improvement in left ventricular ejection fraction during recovery from acute myocardial infarction. At baseline, both humans and mice exhibit low but continuous cell turnover originating from the existing CMs. Moreover, myocardial infarction can induce endogenous CM cell cycling. Consequently, research has focused on identifying drivers of CM rejuvenation and proliferation from pre-existing CMs. High-throughput screening has facilitated the discovery of novel pro-proliferative targets through small molecules, microRNAs, and pathway-specific interventions. More recently, omics-based approaches such as single-nucleus RNA sequencing and spatial transcriptomics have expanded our understanding of cardiac cellular heterogeneity. The big-data strategies provide critical insights into why only a subset of CMs re-enter the cell cycle while most remain quiescent. In this review, we compare several high-throughput screening strategies used to identify novel targets for CM proliferation. We also summarize the benefits and limitations of various screening models—including zebrafish embryos, rodent CMs, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and cardiac organoids—underscoring the importance of integrating multiple systems to uncover new regenerative mechanisms. Further work is needed to identify translatable and safe targets capable of inducing functional CM expansion in clinical settings. By integrating high-throughput screening findings with insights into CM heterogeneity, this review provides a comprehensive framework for advancing cardiac regeneration research and guiding future therapeutic development. Full article

Background/Objectives: Conduction system pacing (CSP) is a potential alternative to biventricular pacing (BVP) in heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB) or non-LBBB. Available data also suggest that unlike BVP, CSP may improve clinical outcome in patients with right bundle branch block (RBBB), although its effects on cardiac mechanics and energetics are ill-defined. Herein, we report on echocardiographic and clinical outcomes of CSP in this patient cohort. Methods: CSP either with His bundle pacing or LBB area pacing was attempted as a primary strategy in patients with RBBB, QRS duration ≥ 130 ms, LVEF < 35% and NYHA II-IV symptoms after optimized medical therapy for 6 months. Data on functional status, NT-proBNP and echocardiographic parameters were collected at baseline and 6 months after CSP. Results: CSP performed in 16 patients reduced QRS duration from 155.3 ± 12.8 ms to 130 ± 16.5 ms (p < 0.001), increased LVEF from 27 ± 7% to 33 ± 9% (p = 0.01), improved LV global longitudinal strain from −7 ± 3% to −10 ± 4% (p = 0.004) and improved LV peak strain dispersion from 126 ± 28 ms to 96 ± 23 ms (p = 0.004). Global myocardial work index increased from 582 ± 277 mmHg% to 840 ± 306 mmHg% (p = 0.003), as did global constructive work (900 ± 374 mmHg% to 1203 ± 393 mmHg%; p = 0.006) and global work efficiency (from 71 ± 7% to 77 ± 8%; p = 0.004). NYHA class (12.5% with NYHA II, 87.5% with NYHA III before vs. 25% with NYHA I, 50% with NYHA II and 25% with NYHA III at 6 months; p = 0.002) and 6 min walk distance (from 354 ± 88 m to 411 ± 95 m; p = 0.003) improved, while NT-proBNP decreased (from 4093 ± 7215 ng/L to 2087 ± 2872 ng/L, p = 0.003). Conclusions: CSP improved functional capacity and echocardiographic parameters related to cardiac functions and myocardial work in HFrEF patients with RBBB. Nevertheless, these results await further confirmation by large-scale, multi-center randomized trials. Full article

Takotsubo syndrome (TTS) is an acute condition involving left ventricular dysfunction that may present clinically as acute coronary syndrome without obstructive coronary disease or congestive heart failure. Initially considered benign, TTS is now recognized as a complex neurocardiac disorder with hospital morbidity rates comparable to those of myocardial infarction, as well as similar long-term risks. Recent evidence establishes TTS as a multifactorial process involving catecholamine overload, coronary microvascular dysfunction, myocardial energetic abnormalities, and dysregulation of the brain and heart axes. Developments in echocardiography, cardiac magnetic resonance imaging, and improvements in diagnostic criteria have enhanced the recognition of syndromic phenotypes. Management of TTS continues to remain primarily supportive; however, recent studies have revealed improved functional outcomes with structured cardiac rehabilitation and cognitive behavioral therapies as the first long-term disease-altering approaches. Future studies should combine neurocardiology, imaging, and therapy-focused research. This review integrates the understanding of the epidemiology, pathophysiology, clinical features, diagnostic work-up, and management of TTS, with particular emphasis on developments emerging from the past decade. Full article

In this work, we report the development of a highly sensitive optical sensor for the detection of cardiac troponin I (cTnI), a key biomarker for early-stage myocardial infarction diagnosis. The sensor combines castor oil-derived biomimetic receptors, called GreenNanoMIPs and prepared via the molecular imprinting technology using as a template an epitope of cTnI (i.e., the NR10 peptide), with a portable multimode plastic optical fiber surface plasmon resonance (POF-SPR) transducer. For sensing, gold SPR chips were functionalized with GreenNanoMIPs as proven by refractive index changes and confirmed by means of XPS. Binding experiments demonstrated the cTnI_nanoMIP-SPR sensor’s ability to detect both the NR10 peptide epitope and the full-length cTnI protein within minutes (t = 10 min), with high sensitivity and selectivity in buffer and serum matrices. The cTnI_nanoMIP-SPR showed an LOD of 3.53 × 10⁻¹⁵ M, with a linearity range of 1 pM–100 pM, outperforming previously reported sensor platforms and making it a promising tool for early-stage myocardial infarction detection. Full article

Coronary artery bypass grafting (CABG) remains a cornerstone of treatment for patients with advanced or complex coronary artery disease, yet long-term success is influenced by graft patency, progression of native disease, and ventricular remodeling. Optimizing the follow-up of these patients requires a structured approach in which multimodality cardiovascular imaging plays a central role. Echocardiography remains the first-line modality, providing readily available assessment of ventricular function, valvular competence, and wall motion, while advanced techniques, such as strain imaging and myocardial work, enhance sensitivity for subclinical dysfunction. Coronary computed tomography angiography (CCTA) offers excellent diagnostic accuracy for graft patency and native coronary anatomy, with emerging applications of CT perfusion and fractional flow reserve derived from CT (FFR-CT) expanding its ability to assess lesion-specific ischemia. Cardiovascular magnetic resonance (CMR) provides comprehensive tissue characterization, quantifying scar burden, viability, and inducible ischemia, and stress CMR protocols have demonstrated both safety and independent prognostic value in post-CABG cohorts. Nuclear imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) remains essential for quantifying perfusion, viability, and absolute myocardial blood flow, with hybrid PET/CT approaches offering further refinement in patients with recurrent symptoms. In patients after CABG, multimodality imaging is tailored to the patient’s characteristics, symptoms, and pre-test probability of disease progression. In asymptomatic patients, imaging focuses on surveillance, risk stratification, and the early detection of subclinical abnormalities, whereas in symptomatic individuals, it focuses on establishing the diagnosis, defining prognosis, and guiding therapeutic interventions. Therefore, the aim of our review is to propose updated and comprehensive guidance on the crucial role of multimodality cardiovascular imaging in the evaluation and management of post-CABG patients and to provide a practical, evidence-based framework for optimizing outcomes. Full article

Background: Cardiovascular disease is one of the leading causes of death worldwide. The presence of atherosclerotic plaques in the arteries leads to continuous growth and obstruction of blood vessels, which ultimately leads to acute myocardial infarction and sudden cardiac death. Ultrasound-triggered GVs cavitation has great potential in plaque treatment due to its noninvasive nature and safety. Methods: In this work, we constructed a Hirudin–Gas Vesicle Recombinant Plasmid to achieve gene delivery using macrophage membrane/lipid membrane fusion bio-vesicles. Results: The bio-fusion vesicles retained the macrophage membrane protein integrin α4β1 to combine with vascular adhesion molecules highly expressed by inflammatory cells to achieve delivery; the Hirudin–Gas Vesicle Recombinant Plasmid could escape lysosomes and enter the nucleus to achieve highly efficient transfection; Hirudin and Gas Vesicles are exocytosed through cleavage peptide and exocytosis peptide, respectively; their pharmacological effects are linked and complementary. Gas vesicles can break up lesion plates with the assistance of in vitro ultrasound, and Hirudin achieves fragment ablation and anti-inflammatory and lipid regulation. Conclusions: GVs-HV@MM-Lipo exerts potent anti-atherosclerotic and anti-inflammatory effects with favorable safety. GVs-HV@Lipo reduces mice aortic arch plaque area by 17%, while GVs-HV@MM-Lipo+US achieves further plaque regression and improved hemodynamics. Our work opens up a new paradigm in the treatment of atherosclerosis with Chinese medicine. Full article

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated significant cardiovascular and renal benefits beyond glycemic control, yet their integrated mechanisms remain incompletely understood. Emerging evidence highlights the gut-kidney-heart axis as a pivotal pathological network, wherein gut dysbiosis, toxic metabolite accumulation, intestinal barrier disruption, and systemic inflammation synergistically drive cardiorenal injury. This review systematically elucidates how SGLT2i modulate this axis through multi-level interventions: reshaping gut microbiota composition, enriching short-chain fatty acid-producing bacteria, suppressing trimethylamine and other toxin-generating microbes, restoring tight junction integrity, and regulating bile acid metabolism. These upstream effects reduce systemic inflammatory and metabolic stress, interrupt kidney-derived toxin amplification, and mitigate myocardial remodeling. Unlike previous reviews focusing on single-organ pathways, this work integrates microecological regulation, metabolite reprogramming, and cross-organ protection into a unified “three-axis convergence to the heart” framework. We also highlight potential species-specific microbiota regulatory profiles among different SGLT2i and propose future directions, including fecal microbiota transplantation and microbiota-targeted co-therapies, to clarify causal relationships and optimize therapeutic strategies. By positioning the gut as a modifiable upstream driver, this framework provides novel mechanistic insight and translational potential for expanding SGLT2i applications in metabolic cardiovascular disease, including in non-diabetic populations. Full article

Excessive oxidative stress drives pathological ventricular remodeling after acute myocardial infarction (AMI), yet adaptive cardiomyocyte mechanisms are poorly understood. We analyzed 64,510 human cardiomyocytes from five integrated single-cell datasets to delineate oxidative stress heterogeneity. Using quartile thresholds of a composite oxidative stress score, cells were stratified into three distinct subpopulations: high oxidative stress (HOX, score > 2.608), dynamic transient oxidative stress (DTOX), and low oxidative stress (LOX, score < 2.061). Paradoxically, HOX cells exhibited severe oxidative stress alongside significantly higher cellular plasticity than DTOX and LOX cells (p < 0.001), as confirmed by CytoTRACE and pseudotime trajectory analyses. This subpopulation demonstrated a unique “metabolic activation–immune suppression” signature and served as a central communication hub. An integrative machine-learning framework incorporating six distinct algorithms and independent cohort validation identified five core marker genes (TRIM63, ETFDH, TXNIP, CKMT2, and PDK4). These genes demonstrated stable diagnostic capability for AMI in independent validation cohorts (AUCs 0.688–0.721, all p < 0.001) and were specifically enriched in HOX cells. Our work reveals a previously unrecognized adaptive state in post-infarction cardiomyocytes, offering promising new targets for precision diagnosis and intervention. Full article

Myocardial work (MW), derived from non-invasive pressure–strain loop (PSL) analysis, has recently emerged as a promising echocardiographic index for assessing left ventricular performance. It integrates speckle-tracking echocardiography with estimated left ventricular pressure, providing a load-adjusted measure of myocardial performance. This technique addresses the limitations of traditional parameters such as global longitudinal strain (GLS) and ejection fraction (EF), particularly in populations exposed to dynamic loading conditions, such as athletes. Athletic training induces a spectrum of cardiac adaptations, collectively referred to as the “athlete’s heart,” which may mimic or mask pathological conditions. In this context, MW represents a valuable tool to differentiate physiological remodeling from early myocardial dysfunction or underlying cardiovascular disease (e.g., cardiomyopathies, myocarditis). The aim of this review is to explore the physiological rationale for using MW in athletes, evaluate its relationship with performance metrics (e.g., VO₂max, lactate threshold), and discuss its potential, yet still emerging and not fully validated, role in informing training adaptation and detecting subclinical cardiac conditions. Additionally, we examine MW applications across different sport disciplines (strength, mixed-sport, and endurance), highlighting its role in individualized assessment and risk stratification. By synthesizing current evidence and outlining future research directions, this work emphasizes the potential of MW to become a standard component of cardiovascular evaluation in sports cardiology. Full article

Heart transplantation is severely limited by the shortage of suitable donor grafts, partly due to myocardial vulnerability to ischemia–reperfusion injury and the lack of standardized preservation strategies. Current solutions only partially maintain myocardial viability, compromising post-transplant function. To address this issue, we made further improvements to our preservation solution, LYPS (Lyon Preservation Solution), based on mitochondrial metabolic activation and the limitation of membrane depolarization. We first evaluated commonly used extracellular solutions (Celsior and St. Thomas (ST)) on cardiac cell lines (H9C2) exposed to 20 h of cold (4 °C) simulated ischemia followed by 2 h of simulated reperfusion. In parallel, the same three solutions were compared in isolated pig hearts subjected to 20 h of cold static storage followed by reperfusion, with a group directly reperfused with blood at 37 °C serving as the control. Heart function was assessed using a non-working heart preparation, while mitochondrial functions and electrophysiological analysis were evaluated via biopsies and isolated cardiomyocytes. LYPS provided superior protection against cell death and mitochondrial membrane potential loss in vitro, outperformed ST in preserving mitochondrial function, and limited troponin I release by the heart. During reperfusion, LYPS-treated hearts showed improved functional recovery and contractility and better rhythmicity with almost no defibrillation requirements. These effects may involve the modulation of the repolarizing IK₁ current. Overall, LYPS effectively preserves myocardial viability and function, representing a promising strategy to enhance graft quality during long-term cold preservation, even through using cold static storage. Full article

Background/Objectives: Moderate aortic stenosis (AS) with preserved ejection fraction (EF) is common, yet risk stratification remains challenging. Cardiopulmonary exercise testing (CPET) and myocardial mechanics analysis may identify subclinical dysfunction and impaired functional capacity. To evaluate the relationship between functional capacity (by % predicted peak VO₂), ventilatory efficiency (VE/VCO₂ slope), and myocardial mechanics (speckle tracking echocardiography—STE), and myocardial work (MW) indices) in moderate AS with preserved EF. Methods: We prospectively enrolled 107 patients with moderate AS (AVA 1.0–1.5 cm²; mean gradient 20–40 mmHg; EF ≥ 50%). Functional capacity was classified as preserved (≥83% predicted VO₂) or reduced (<83%). Ventilatory efficiency was defined as good (<30) or poor (≥30) VE/VCO₂ slope. STE assessed left ventricular (LV), left atrial (LA), and right ventricular (RV) strain, as well as myocardial work indices. Results: Patients with reduced % predicted VO₂ had higher LV end-systolic volume (p = 0.035), lower stroke volume index (p = 0.020), and smaller indexed aortic valve area (p = 0.025), with trends toward lower GLS and myocardial work. In contrast, patients with poor ventilatory efficiency (VE/VCO₂ ≥ 30) showed significant impairments in global longitudinal strain (GLS, p = 0.002), LA reservoir strain (PALS, p = 0.019) and LA conduit strain (LA Scd, p < 0.001), RV free wall strain (RW FWS, p = 0.029), and myocardial work indices (lower GWI and GCW, higher GWW, reduced GWE; all p < 0.05). LA Scd emerged as the strongest predictor of poor ventilatory efficiency. (receiver operating characteristic (ROC) area under the curve (AUC) 0.723, 95% confidence interval (CI) 0.623–0.823, p < 0.001). Conclusions: In moderate AS with preserved EF, impaired ventilatory efficiency is more strongly associated with subclinical LV, LA, and RV dysfunction than reduced % predicted VO₂, highlighting the key role of RV impairment. Integrating CPET and STE improves phenotyping, identifying high-risk patients who may benefit from closer surveillance or early intervention. These findings are exploratory and hypothesis-generating; longitudinal data are needed to confirm prognostic implications. Full article

Sirtuin 1 (SIRT1) is an NAD⁺-dependent deacetylase implicated in various physiological and pathological processes, including cardiovascular diseases. The lead compound for SIRT1, resveratrol (1), as well as natural-derived and synthetic SIRT1-activating compounds demonstrated to exert cardioprotective effects. In the present work, we evaluated a small series of diarylimidazoles, of which 4 emerged, in in vitro enzymatic assays, as an activator of SIRT1 endowed with a similar potency compared with that of 1. Therefore, 4 was subjected to pharmacological investigation, where it was proven to reduce myocardial damage induced by ischemia/reperfusion injury in isolated rat hearts, thus demonstrating its cardioprotective properties. An in silico study suggested the binding mode of this derivative within SIRT1 in the presence of the p53-AMC-peptide. These promising results could pave the way to further expand and optimize this chemical class of new SIRT1 activators as potential cardioprotective agents. Full article

Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, n = 10), post-test high cardiac remodeling group (AH, n = 10), pre-test low cardiac remodeling group (BL, n = 10), post-test low cardiac remodeling group (AL, n = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise. Full article

Growing age-related epidemiology, together with an increasing burden of cardiac co-pathology and comorbidities, has progressively subverted the clinical paradigm of Aortic Stenosis (AS) towards a multifaceted scenario. Timely surgical or transcatheter valve replacement is paramount to reduce morbidity and mortality in AS patients provided that the obstruction is hemodynamically important and responsible for the symptoms across a variety of clinical contexts. Despite its recognized role in AS assessment severity, transvalvular gradient (TVG) reflects complex interplay among anatomical, mechanical and fluid-dynamic factors, challenging the ultimate recognition of significant aortic valve obstruction. Careful phenotyping of TVG by assessing its underlying variables may enhance diagnostic work-up, risk stratification and management of AS. Emerging imaging modalities, such as three-dimensional echocardiography, automatic flow and myocardial function assessment, and advanced fluid dynamics analysis are promising for refining multifaceted TVG phenotypes. A deeper understanding of the substrate underlying TVG may add new insight into the trajectory of valve obstruction and its interaction with left ventricular function, thereby supporting the tailoring of TVG-guided clinical strategies of the evolving scenario of AS. Full article

Myocardial infarction (MI) remains one of the most critical causes of death worldwide, demanding predictive models that balance accuracy with clinical interpretability. This study introduces an explainable artificial intelligence (XAI) framework that integrates least absolute shrinkage and selection operator (LASSO) regression for feature selection, logistic regression for prediction, and Shapley additive explanations (SHAP) for interpretability. Using a dataset of 918 patients and 12 signal-derived clinical variables, the model achieved an accuracy of 87.7%, a recall of 0.87, and an F1 score of 0.89, confirming its robust performance. The key risk factors identified were age, fasting blood sugar, ST depression, flat ST slope, and exercise-induced angina, while the maximum heart rate and upward ST slope served as protective factors. Comparative analyses showed that the SHAP and p-value methods largely aligned, consistently highlighting ST_Slope_Flat and ExerciseAngina_Y, though discrepancies emerged for ST_Slope_Up, which showed limited statistical significance but high SHAP contribution. By combining predictive strength with transparent interpretation, this study addresses the black-box limitations of conventional models and offers actionable insights for clinicians. The findings highlight the potential of signal-driven XAI approaches to improve early detection and patient-centered prevention of MI. Future work should validate these models on larger and more diverse datasets to enhance generalizability and clinical adoption. Full article