Search Results (63)

(1) Background: Electrical cardioversion (ECV) is effective in restoring sinus rhythm (SR) in atrial fibrillation (AF), but the extent of atrioventricular remodeling and determinants of short-term rhythm maintenance remain unclear. This study evaluated echocardiographic changes following ECV and explored parameters associated with SR persistence. (2) Methods: We prospectively enrolled 94 patients undergoing elective ECV and performed comprehensive echocardiography before, 24 h after, and 30 days after the procedure. Rhythm status was assessed at scheduled follow-up visits. Due to the limited sample size, failure to meet the assumptions required for regression analyses, and non-normal data distributions, the analyses were primarily non-parametric and exploratory. (3) Results: Among 94 patients (mean age 65.9 +/− 9.3 years; 69% male), SR was maintained in 76 patients at 24 h and 49 patients at 30 days. Patients with sustained SR showed progressive improvement in LA reservoir strain, LA emptying fraction, and LA stiffness index, consistent with reverse atrial remodeling. Left ventricular (LV) function also improved, including LV ejection fraction, global longitudinal strain, and myocardial work indices. Between-group analyses identified several baseline LV parameters (including global wasted work, global work efficiency, LV end-systolic volume, LV end-systolic diameter, and global work index) with moderate effect sizes and possible association with short-term SR maintenance. (4) Conclusions: Successful ECV is associated with significant short-term atrioventricular functional improvement. In this exploratory single-center cohort, selected LV mechanical parameters were associated with short-term SR maintenance, while LA functional parameters mainly reflected reverse remodeling after rhythm restoration. Larger studies with longer follow-up and adjusted analyses are needed. Full article

There is a substantial correlation between cardiac dysfunction and elevated mortality in sepsis. Impaired myocardial perfusion, direct myocardial injury, and mitochondrial dysfunction are all part of the complex pathophysiology of sepsis-induced myocardial dysfunction. Recent evidence has shown the critical role mitochondrial dysfunction plays in the development of sepsis-induced myocardial dysfunction. In order to prevent and treat sepsis-induced myocardial dysfunction, a variety of drugs have been proposed. However, patient outcomes have not been appreciably enhanced by this therapy. This underscores the need for novel treatment approaches that target the specific pathways underlying cardiac dysfunction in sepsis. The prognosis is greatly impacted by sepsis-induced cardiac dysfunction, monitoring it is crucial. Clinicians employ a mix of clinical evaluations, hemodynamic monitoring, echocardiography, and bSICiomarkers to efficiently monitor this illness. The combined application of these techniques provides a comprehensive evaluation of cardiac function, thereby supporting timely optimization of treatment strategies. Treatments for septic shock and established sepsis will be beneficial for patients with this condition. However, there is little information and evidence about more targeted therapy, except than general management with vasopressors, inotropes, and fluid resuscitation. This study provides an outline of current knowledge on the pathophysiological mechanisms underlying sepsis-induced cardiac dysfunction, as well as the effects of monitoring and current treatments on sepsis-induced myocardial dysfunction. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy. Full article

Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency and shifts substrate utilization toward greater oxidation of fatty acids and ketones, effects that correlate with long-term reverse remodeling on cardiac magnetic resonance imaging. Earlier metabolomic profiling demonstrated that CRT normalizes circulating energy metabolites, improving Krebs cycle intermediates and substrate balance between glucose and lipids, while baseline metabolite patterns may differentiate responders from non-responders. These metabolic adaptations accompany favorable changes in diastolic performance, right ventricular function, and ventriculo-arterial coupling. In parallel, improved splanchnic perfusion and reduced congestion may ameliorate gut dysbiosis and endotoxemia, mitigating systemic inflammation. Collectively, these findings position CRT as a therapy capable of both mechanical and metabolic restoration in advanced HF. In this review, we discuss the emerging data on how CRT reconditions myocardial energy metabolism, influences ventricular–arterial interactions, and modulates peripheral and gut-derived metabolic pathways. Full article

Cardiovascular disease is the leading cause of mortality in insulin-resistant individuals, with metabolic cardiomyopathy preceding overt heart failure in a substantial proportion of patients with diabetes. Skeletal muscle accounts for approximately 40% of body mass and nearly 80% of insulin-stimulated glucose disposal, positioning it as a major determinant of systemic lipid flux. Dysregulation of lipid droplet dynamics, lipolysis, and fatty acid trafficking in skeletal muscle alters circulating lipid availability and promotes ectopic lipid deposition and mitochondrial stress in the myocardium. Intramyocellular lipid handling is governed by coordinated actions of lipid droplets, perilipin proteins (PLIN2 and PLIN3), adipose triglyceride lipase (ATGL), and diacylglycerol acyltransferases (DGAT1/2), which together regulate the rate and composition of fatty acid release into the circulation. Impaired coupling between intramyocellular lipid droplet turnover and mitochondrial oxidation in insulin-resistant muscle increases circulating free fatty acids, reducing cardiac oxidative capacity. In response, the myocardium undergoes mitochondrial lipid remodeling, including alterations in cardiolipin composition that impair cristae structure and electron transport chain efficiency. Excess lipid exposure activates apoptosis signal-regulating kinase-1 (ASK-1), promoting cardiomyocyte apoptosis and inflammatory signaling, while peroxisome proliferator-activated receptor gamma (PPARγ) modulates lipid uptake, storage, and mitochondrial oxidation in a context-dependent manner. This review integrates skeletal muscle–cardiac lipid crosstalk with ASK-1 and PPARγ signaling to define mechanisms linking peripheral insulin resistance to early myocardial dysfunction and to identify targets for intervention before irreversible cardiac remodeling develops. Full article

The natural polypeptide drug hirudin, a direct thrombin inhibitor, exhibits potent anticoagulant, anti-myocardial fibrotic, and anti-inflammatory effects in the treatment of cardiovascular diseases (CVD), but its clinical application remains limited by its low bioavailability, insufficient targeting capability, and bleeding risk. In recent years, the development of nanotechnology has enabled peptide drug delivery systems to demonstrate substantial promise in medical practice. Significant progress has been made in overcoming limitations and enhancing therapeutic efficacy against CVD through the use of Hirudin-based drug delivery systems by addressing drug stability in vivo, improving targeting ability, and ultimately achieving responsive release. This paper systematically reviews the mechanisms of action, clinical applications, and novel delivery strategies of the peptide drug hirudin in the treatment of CVD, with a particular focus on recent advances in hirudin-based drug delivery systems, and it also looks forward to future research directions for hirudin delivery systems, including the development of scalable intelligent carriers, the construction of real-time feedback systems, and the establishment of standardized in vitro and in vivo evaluation systems, aiming to present novel strategies for safe and efficient treatment of CVD. Full article

Microfluidic technologies have ushered in a new era in cardiac tissue engineering, providing more predictive in vitro models compared to two-dimensional culture studies. This review examines Organ-on-a-Chip (OoC) and Lab-on-a-Chip (LoC) platforms, with a specific focus on cardiovascular applications. OoCs, and particularly Heart-on-a-Chip systems, have advanced biomimicry to a higher level by recreating complex 3D cardiac microenvironments in vitro and dynamic fluid flow. These platforms employ induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), engineered extracellular matrices, and dynamic mechanical and electrical stimulation to reproduce the structural and functional features of myocardial tissue. LoCs have introduced miniaturization and integration of analytical functions into compact devices, enabling high-throughput screening, advanced diagnostics, and efficient pharmacological testing. They enable the investigation of pathophysiological mechanisms, the assessment of cardiotoxicity, and the development of precision medicine approaches. Furthermore, progress in multi-organ systems expands the potential of microfluidic technologies to simulate heart–liver, heart–kidney, and heart–tumor interactions, providing more comprehensive predictive models. However, challenges remain, including the immaturity of iPSC-derived cells, the lack of standardization, and scalability issues. In general, microfluidic platforms represent strategic tools for advancing cardiovascular research in translation and accelerating therapeutic innovation within precision medicine. 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

Ischemic heart disease (IHD), the leading causes of cardiovascular morbidity and mortality worldwide, is currently treated though revascularization strategies such as pharmacological thrombolysis, coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI). However, the restoration of blood flow often induces cardiac dysfunction, known as myocardial ischemia–reperfusion injury (MIRI). The pathogenesis of MIRI involves a complex, multifactorial process characterized by the interplay of diverse pathophysiological mechanisms, including oxidative stress, intracellular calcium overload, inflammatory cascade activation, apoptosis, autophagy, and microvascular endothelial dysfunction. In recent years, modified RNA (modRNA) technology has emerged as a novel therapeutic strategy for MIRI due to its enhanced molecular stability, reduced immunogenicity, and controllable transient protein expression. Studies have demonstrated that optimized modRNA delivery systems enable efficient, localized expression of therapeutic genes (e.g., antioxidant, anti-apoptotic, and pro-angiogenic factors) at injury sites, significantly mitigating MIRI-associated pathological damage. Nevertheless, significant challenges remain in clinical translation, such as delivery system targeting, transfection efficiency and cytotoxicity. This review focuses on recent advances in the development and application of modRNA-based delivery systems for MIRI treatment. Understanding the molecular mechanisms of MIRI and the structural characteristics and application of modRNA may encourage researchers to explore promising therapeutic modalities for addressing reperfusion-related cardiac injury. Full article

Heart failure (HF) is increasing in prevalence in many countries around the world. HF is a complex clinical syndrome characterized by the heart’s inability to pump blood effectively, resulting in significant morbidity and mortality. After an initial cardiac event (e.g., myocardial infarction, valve dysfunction, hypertension, etc.), adaptive mechanisms are activated to preserve cardiac function. Sustained activation of these mechanisms leads to cellular and structural changes involving cardiac remodeling and hypertrophy. This ultimately leads to impaired cardiac contractility and reduced cardiac output, with a 5-year HF-associated mortality rate up to 75%. The current treatment strategies for HF are not sufficient to cover all the underlying complex mechanisms. It has been demonstrated that molecular hydrogen (H₂) exerts cardioprotective effects via its antioxidant, anti-inflammatory, and anti-apoptotic action. The number of studies exploring beneficial effects of H₂ in different HF models is increasing. This is the first review summarizing the knowledge in this field. The available literature indicates that H₂ may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H₂ treatment in different HF types need further investigation. Full article

Background: Left ventricular (LV) mechanics assessed by speckle-tracking echocardiography provides sensitive markers of cardiac adaptation to exercise. Different training modalities—endurance, high-intensity interval training (HIIT), and acute exercise tests—impose distinct hemodynamic loads, yet their comparative effects on LV deformation remain unclear. Importantly, acute and chronic endurance exposures may elicit divergent myocardial responses that must be interpreted separately. Methods: A systematic search of PubMed, Scopus, and EMBASE (through September 2025) identified studies evaluating LV mechanics in response to endurance, HIIT, or acute exercise among healthy or recreationally active individuals. Echocardiographic parameters of strain and torsion were extracted, and methodological quality was appraised using the NIH Quality Assessment Tool. Results: Twenty-three studies (859 participants) met inclusion criteria. Acute prolonged endurance exercise—particularly marathon and ultra-endurance events—was associated with transient, fully reversible reductions in global longitudinal, circumferential, and radial strain and torsion, despite preserved ejection fraction, reflecting short-term myocardial fatigue rather than maladaptive remodeling. In contrast, chronic endurance training maintained or improved LV mechanics without evidence of dysfunction, while HIIT interventions consistently enhanced LV systolic strain and rotational indices across diverse age groups and sexes, reflecting improved contractile efficiency and physiological remodeling. Acute exercise produced heterogeneous, load-dependent strain responses, with isometric stress increasing regional strain and maximal exertion inducing temporary global reductions. Between-study heterogeneity was moderate, methodological quality generally good, and small-study effects varied by modality, being most evident in endurance studies, borderline for HIIT, and limited for acute tests due to sample size. Conclusions: Acute endurance exercise produces transient, reversible LV deformation changes, whereas chronic endurance training preserves mechanical efficiency. HIIT reliably enhances systolic strain and torsional mechanics, and acute exercise elicits variable but physiologically meaningful responses. These findings clarify that transient post-race strain reductions reflect physiological fatigue, not chronic maladaptation, and underscore the modality-specific nature of myocardial adaptation to exercise. 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

Left ventricular hypertrophy (LVH) refers to the pathological thickening of the myocardial wall and is strongly associated with several adverse cardiac outcomes and sudden cardiac death. While the biomechanical drivers of LVH are well established, growing evidence points to a critical role for cardiac and systemic metabolism in modulating hypertrophic remodeling and disease pathogenesis. Despite the efficiency of fatty acid oxidation (FAO), LVH hearts preferentially increase glucose uptake and catabolism to drive glycolysis and oxidative phosphorylation (OXPHOS). The development of therapies to increase and enhance LFCA FAO is underway, with promising results. However, the mechanisms of systemic metabolic states and LCFA dynamics in the context of cardiac hypertrophy remain incompletely understood. Further, it is unknown to what extent cardiac metabolism is influenced by whole-body energy balance and lipid profiles, despite the common occurrence of lipotoxicity in LVH. In this study, we measured whole-body and cellular respiration along with analysis of lipid and glycogen stores in a mouse model of LVH. We found that loss of the cardiac-specific gene, myosin-binding protein C3 (Mybpc3), resulted in depletion of adipose tissue, decreased mitochondrial function in skeletal muscle, increased lipid accumulation in both the heart and liver, and loss of whole-body metabolic flux. We found that supplementation of exogenous LCFAs boosted LVH mitochondrial function and reversed cardiac lipid accumulation but did not fully reverse the hypertrophied heart nor systemic metabolic phenotypes. This study indicates that the LVH phenotype caused systemic metabolic rewiring in Mybpc3^−/− mice and that exogenous LCFA supplementation boosted mitochondrial function in both cardiac and skeletal muscle. Full article

PLIN2 is involved in the lipid metabolism of macrophages resident in atherosclerotic plaques, and its upregulation leads to lipid droplets (LDs) accumulation. LDs enlargement results in the macrophage transformation into foam cells, a key step for the onset of atherosclerosis. In the present study, we investigated the role of PLIN2 and its regulation mechanisms in atherosclerosis and plaque instability in patients with a diagnosis of ST-elevation myocardial infarction (STEMI) and chronic coronary syndrome (CCS). We enrolled STEMI (n = 122) and CCS patients (n = 45). Peripheral blood mononuclear cells were isolated from whole blood samples. The PLIN2 protein level was analyzed in CD14+ monocytes by flow cytometry. Lipidomic panel and proteasome activity were evaluated. PLIN2 protein expression was significantly correlated with the age of CAD patients. We found no significant difference in monocyte lipid content between the two patient groups. The PLIN2 increased in STEMI as compared to CCS patients (p < 0.001). The proteasome activity being higher in STEMI as compared to CCS patients (p < 0.001), significant inverse correlations were evident between PLIN2 levels and proteasome activity in the CCS groups (p = 0.02). PLIN2 expression was higher in STEMI as compared to CCS patients, suggesting an involvement in plaque instability. Despite the proteasome activity being higher in STEMI patients, probably due to the elevated inflammatory burden, PLIN2 could escape proteasome degradation in a more efficient manner in STEMI as compared to CCS patients. Full article

Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies is primarily attributable to the complex and heterogeneous pathophysiology underlying HFpEF. The hallmark of HFpEF is systemic inflammation, mostly originating from extracardiac comorbidities, which initiates and sustains the process of myocardial fibrosis, resulting in diastolic dysfunction. Recent evidence has identified specific micro ribonucleic acids (miRNAs) as key regulatory molecules in this inflammation–fibrosis cascade. Particularly, miR-21 and miR-29 play a central role in modulating these pathological processes by regulating the post-transcriptional expression of genes involved in inflammation, cardiac fibrosis, and remodeling. The inflammation-fibrosis axis in HFpEF offers multiple therapeutic opportunities ranging from direct anti-fibrotic strategies to the modulation of inflammation and fibrosis-related miRNA signatures. Such targeted approaches, especially miRNA modulation, hold potential to disrupt fundamental molecular mechanisms driving disease progression, moving beyond conventional HFpEF management. This narrative review explores the roles of miRNAs in modulating inflammation and fibrosis in HFpEF, critically assesses their potential as diagnostic and prognostic biomarkers, and evaluates their therapeutic application. Given the urgent clinical need for efficient HFpEF treatment strategies, understanding miRNA-mediated regulation of the inflammation–fibrosis axis is essential for developing personalized, mechanism-based therapies for HFpEF that could fundamentally change the HFpEF management paradigm. Full article