Search Results (3,359)

Mitochondria, as the metabolic hubs of cells, play a pivotal role in maintaining cardiovascular homeostasis through dynamic regulation of energy metabolism, redox balance, and calcium signaling. Cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, cardiomyopathies, and myocardial infarction, remain the leading cause of global mortality, with mitochondrial dysfunction emerging as a unifying pathological mechanism across these conditions. Emerging evidence suggests that impaired mitochondrial transport systems—critical gatekeepers of metabolite flux, ion exchange, and organelle communication—drive disease progression by disrupting bioenergetic efficiency and exacerbating oxidative stress. This review synthesizes current knowledge on mitochondrial transport proteins, such as the voltage-dependent anion channels, transient receptor potential channels, mitochondrial calcium uniporter, and adenine nucleotide translocator, focusing on their structural–functional relationships and dysregulation in CVD pathogenesis. We highlight how aberrant activity of these transporters contributes to hallmark features of cardiac pathology, including metabolic inflexibility, mitochondrial permeability transition pore destabilization, and programmed cell death. Furthermore, we critically evaluate preclinical advances in targeting mitochondrial transport systems through pharmacological modulation, gene editing, and nanoparticle-based delivery strategies. By elucidating the mechanistic interplay between transport protein dysfunction and cardiac metabolic reprogramming, we address a critical knowledge gap in cardiovascular biology and provide a roadmap for developing precision therapies. Our insights underscore the translational potential of mitochondrial transport machinery as both diagnostic biomarkers and therapeutic targets, offering new avenues to combat the growing burden of CVDs in aging populations. Full article

Background/Objectives: Systemic toxicities to key organs like the heart, liver, and kidneys impair the efficacy of chemotherapy in cancer treatment. These toxicities are caused by oxidative stress, inflammation, mitochondrial malfunction and ferroptosis, causing clinical morbidity and possibly impaired adherence to treatment. This review, also, examines how magnesium, selenium, zinc and vitamin D protect against chemotherapy-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. Methodology: A complete literature search of PubMed (MEDLINE), Scopus, Cochrane Library and Embase was used to synthesize data till 29 June 2025. Studies included randomized and non-randomized trials, cohort studies, case series (≥3 patients), and relevant systematic reviews. To contextualize pathways, preclinical in vivo and in vitro studies were studied independently. Patients undergoing systemic chemotherapy and magnesium, selenium, zinc or vitamin D therapies were eligible. Supplementation’s safety and organ-specific toxicity were investigated. Results: Magnesium protected against cisplatin-induced nephrotoxicity via modulating renal transporters and oxidative defenses across chemotherapy regimens. Selenium supplementation has strong antioxidant and anti-inflammatory characteristics, especially in avoiding cardiac and hepatic injury, although its nephroprotective potential was formulation-dependent. Zinc’s activity was connected to metallothionein-mediated redox stabilization, inflammatory regulation, and cardiac and hepatic resilience. Vitamin D and its analogs reduced cardiotoxicity and nephrotoxicity through mitochondrial preservation and immunomodulatory signaling. Conclusions: To date, magnesium, selenium, zinc, and vitamin D have been shown to reduce chemotherapy-related organ toxicities. Preclinical studies are promising, but randomized clinical trials are needed to prove therapeutic effectiveness and oncologic safety. Full article

Background: Acute kidney injury (AKI) following cardiac surgery can lead to chronic kidney disease, increased hospitalization costs, and higher mortality risk. Our retrospective study identified risk factors of severe AKI (AKI 3) in patients undergoing on-pump surgical aortic valve replacement (SAVR). Additionally, we analyzed the significance of inflammatory indexes and risk scores in predicting AKI 3, focusing on sex differences. These findings could provide cost-efficient tools for clinical practice to identify patients at risk, improve preoperative risk stratification, and personalize monitoring. Methods: We reviewed the on-pump SAVR patients from our tertiary center between 2022 and 2024. Results: Out of 422 patients, 121 (28.67%) experienced AKI, including 27 (6.39%) AKI 3 patients. The multivariable binary logistic regression identified AKI 3 independent risk factors: hemostasis reintervention (OR9.76, CI95%:3.565–26.716, p = 0.001), early postoperative vasoactive-inotropic score (VIS) (OR1.049, CI95%:1.013–1.086, p = 0.007), postoperative lymphocyte (OR2.252, CI95%:1.224–4.144, p = 0.009). Preoperative systemic inflammatory response index (AUC0.700, p = 0.019), preoperative aggregate index of systemic inflammation (AUC0.712, p = 0.011), postoperative platelet-to-lymphocyte ratio (PLR) (AUC 0.759, p = 0.001), and the delta value of preoperative-to-postoperative PLR (AUC0.752, p = 0.001) were better predictors of AKI 3 occurrence in female SAVR patients than the additive EuroSCORE (AUC0.692, p = 0.011), but were less accurate compared to EuroSCORE II (AUC0.841, p = 0.001). None of the studied inflammatory indexes or additive EuroSCORE predicted our endpoint in male SAVR patients, while Thakar score was able to predict it exclusively in males. Conclusions: Early postoperative VIS, lymphocyte count, and hemostasis reintervention were independent risk factors for severe AKI in SAVR patients. There is a differentiation between males and females from the AKI prediction perspective. Full article

Thallium (Tl) is a non-essential and highly toxic heavy metal capable of replacing potassium (K⁺) in biological systems, leading to mitochondrial dysfunction, oxidative stress, and inhibition of protein synthesis. In humans, the estimated oral lethal dose ranges from 10 to 15 mg/kg, with acute mortality rates of 6–15% and chronic neurological sequelae in up to 55% of survivors. Environmental releases of thallium of up to 5000 metric tons annually from industrial and mining activities, combined with its high oral bioavailability and nonspecific multisystemic symptoms, underscore the urgent need for more effective therapeutic strategies. This review summarizes current evidence on Tl toxicity, including its mechanisms of action, clinical manifestations, and available treatments. It emphasizes the strategic selection of biological models: simple organisms such as Caenorhabditis elegans and Drosophila melanogaster enable high-throughput screening and early biomarker detection; zebrafish (Danio rerio) provide vertebrate-level evaluation of multi-organ effects; and rodent models offer systemic toxicokinetic and therapeutic validation. Human-derived organoids and induced pluripotent stem cell (iPSC) systems recreate tissue-specific microenvironments, allowing translational assessment of mitochondrial, neuronal, and cardiac toxicity. Integrating these models within a tiered and complementary framework, alongside environmental and clinical surveillance, can accelerate the development of targeted treatments and strengthen public health responses to Tl exposure. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

Background: Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative to conventional pacing, offering improved ventricular synchrony and clinical outcomes. However, extraction of deeply implanted LBBAP leads remains challenging, particularly in the context of device-related infections. Case Summary: We report two cases of successful extraction of chronically implanted LBBAP leads using a novel technique based on femoral countertraction with pigtail catheters. In the first case, a deep septal implanted 3830 lead was extracted in a patient with persistent bacteremia and suspected device-related endocarditis. Continuous traction was applied to the mid-portion of the lead using a pigtail catheter introduced via femoral access, facilitating safe removal without the use of powered sheaths proximal to the distal tip of the lead. In the second case, three leads (RA, RV, LBBAP) from a cardiac resynchronization therapy with deffibrilation support (CRT-D) system were completely removed in a patient with device extrusion and pocket erosion, using a dual pigtail approach anchored to the atrial and septal leads. Results: In both cases, the technique enabled successful extraction without complications. Procedural times were approximately 70 and 65 min, respectively. In vitro testing suggested that the pigtail catheter applied a sustained moderate traction force (~0.06 kgf), translating to an estimated pressure of 0.85–1.91 kgf/cm² at the septal lead interface. Conclusions: This case series demonstrates that LBBAP lead extraction is feasible using a novel femoral countertraction technique with pigtail catheters. Steady, moderate traction over time may provide a safer alternative to forceful subclavicular extraction, especially in chronically implanted deep septal leads. Further studies are warranted to evaluate the reproducibility, safety, and clinical applicability of this approach. Full article

Background/Objectives: Heart rate variability (HRV) is a reliable, non-invasive marker of autonomic nervous system function and is often impaired in individuals with metabolic syndrome (MetS). Physical exercise has emerged as an effective strategy to improve autonomic modulation; however, the comparative effects of different training modalities on HRV in individuals with MetS remain unclear. This systematic review and meta-analysis aimed to evaluate the impact of various exercise interventions on HRV and to identify which training types yield the most significant improvements. Methods: A systematic search was conducted in PubMed and Scopus up to April 2025. Eligible studies (n = 16) included adults with obesity and MetS (n = 752) who underwent structured exercise interventions with HRV assessments pre- and post-intervention. Standardized mean differences were calculated using random effects models. Subgroup analyses were performed based on training modality (endurance training [ET], resistance training [RT], high-intensity interval training [HIIT], and concurrent training [CT]). Results: Sixteen studies of moderate to high quality were included, with eleven studies eligible for meta-analysis. ET and HIIT significantly improved time-domain indices (Root mean square of differences of successive R-R intervals —rMSSD—, Standard deviation of the R-R interval series —SDNN—) and frequency-domain parameters (high-frequency —HF—), suggesting enhanced parasympathetic activity. RT showed inconsistent effects, while CT improved long-term HF and total power (TP). Non-linear indices were the least reported due to insufficient data. Conclusions: Physical exercise—particularly ET and HIIT—appears to enhance cardiac autonomic modulation in individuals with obesity and MetS. These findings support incorporating targeted training strategies into clinical practice to optimize cardiovascular health in these populations. Full article

Background/Objectives: Cancer immunotherapy has revolutionized the field of oncology by harnessing the immune system to attack cancer cells, increasing survival in a broad spectrum of malignancies. However, despite its positive therapeutic benefit, immunotherapy is also associated with a spectrum of adverse events affecting various vital organs, including the cardiovascular system. Methods: We conducted a comprehensive review of the available literature on the epidemiology, pathophysiological mechanisms, and current management approaches for cardiovascular adverse events associated with cancer immunotherapy. In addition, we evaluated emerging personalized strategies and interventions aimed at mitigating these risks and improving patient outcomes. Results: Immunotherapy is associated with a broad spectrum of potentially serious cardiovascular adverse events, including immune-mediated myocarditis, heart failure, arrhythmias, pericarditis, and accelerated atherosclerosis. Among these, immune checkpoint inhibitor-associated myocarditis is the most well characterized and potentially fatal form of cardiotoxicity, with reported mortality rates approaching 50%. Similarly, chimeric antigen receptor T-cell therapy, despite its powerful antitumor efficacy, is frequently associated with cytokine release syndrome—a profound immune activation that can lead to significant systemic and cardiovascular complications. In response to these challenges, several personalized strategies are currently under development, including artificial intelligence and machine learning approaches, genetic and transcriptomic profiling, novel biomarker discovery, and integrated risk scoring systems, all aimed at enhancing risk stratification and improving patient care. Conclusions: Cancer immunotherapy has been associated with a range of immune-related cardiac adverse events, both non-severe and severe. As such, it is critically important to adopt a personalized approach to patient management before, during, and after the administration of immunotherapy. Early recognition through heightened clinical vigilance, along with the implementation of individualized risk assessment tools, is essential for identifying patients at high risk of immunotherapy-induced cardiotoxicity. These strategies are imperative for optimizing patient outcomes and ensuring safe and effective cancer treatment. Full article

Background: Recently, a new type of full-face snorkeling mask (FFSM), called “Easy-breath” masks, has become extremely popular both in adults and children due to their effective marketing and relative comfort. However, these masks are complex engineering systems that, in case of malfunctioning or if used by young children, may readily cause CO₂ rebreathing, especially in young children. Case Presentation: We present three cases of children under six years of age admitted to the emergency department, with two of them due to non-fatal drowning incidents and one following a cardiac arrest induced by drowning. All incidents occurred during brief submersions while using full-face snorkeling masks. Conclusions: When inappropriately used by younger children, full-face snorkeling masks may have a mechanical dead space larger than tidal volume, with a significant increased risk of rebreathing of CO₂ and consequent risk for hypercapnic hypoxia. The hypercapnia may cause dizziness and respiratory distress, while hypoxia may cause confusion. Both may lead to loss of consciousness, which could be a potential cause of drowning, particularly in younger children. Full article

Background/Objectives: Heart failure (HF) remains a major global cause of morbidity and mortality, exerting substantial health and economic burdens. Increasing evidence suggests that systemic inflammation plays a pivotal role in HF pathophysiology, with key cytokines; interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) contributing to disease progression and worsening cardiac function. This study aimed to evaluate serum levels of IL-1, IL-6, and TNF-α in patients with HF compared to control subjects, to assess differences in these inflammatory mediators between groups, and to explore their relationship with left ventricular ejection fraction (LVEF). Methods: A case–control study was conducted at the Madinah Cardiac Center between October 2024 and April 2025, including 61 patients diagnosed with HF and 65 age- and sex-matched controls without HF. Serum concentrations of IL-1, IL-6, and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). Clinical parameters, including LVEF and echocardiographic data, were recorded and analyzed. Results: Patients with HF demonstrated significantly elevated levels of IL-1 (6.77 ± 1.17 vs. 1.27 ± 0.42 pg/mL, p < 0.001), IL-6 (54.12 ± 4.64 vs. 9.29 ± 1.72 pg/mL, p < 0.001), and TNF-α (235.56 ± 18.88 vs. 67.37 ± 6.28 pg/mL, p < 0.001) compared to controls. Higher inflammatory marker levels were associated with reduced LVEF and more advanced New York Heart Association (NYHA) functional class, indicating a clear link between systemic inflammation and HF severity. Conclusions: The significant elevation of IL-1, IL-6, and TNF-α in HF patients highlights the pivotal role of inflammation in disease progression and severity, offering valuable insights into the underlying mechanisms that may inform future therapeutic strategies. By providing a comprehensive evaluation of these key pro-inflammatory cytokines in relation to LVEF, this study presents an integrated perspective on the inflammatory profile associated with HF. Full article

Regular physical activity has a beneficial impact on the cardiovascular system. However, the intense and prolonged exertion typical of professional athletes and amateur marathon runners can lead to adaptive changes in the heart. These changes encompass both structural and functional modifications, which may have positive or negative effects on cardiac function and contribute to the development of so-called “athlete’s heart.” Prolonged exercise induces adaptations at the molecular and cellular levels, including altered gene expression and remodeling of myocardial proteins. It may also cause transient elevations in biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin. Some athletes experience cardiac arrhythmias, including atrial fibrillation. Morphological changes, such as myocardial hypertrophy or chamber dilation, can be assessed using echocardiography. Studies have reported potentially benign valvular abnormalities, as well as cases of myocardial fibrosis and arrhythmias. Early diagnosis of cardiac conditions in marathon runners is essential for effective prevention and health monitoring. This article reviews the current data on cardiac changes in endurance athletes, based on the literature from the past decade. Full article

Galectin-3 (Gal-3), a multifunctional protein, plays a pivotal role in a wide range of physiological and pathological processes in the human body. Substantial evidence has linked its overexpression and secretion to the pathogenesis of various conditions, including diabetes mellitus, heart failure, fibrosis, atherosclerosis, and chronic kidney disease. Diabetes mellitus, a persistent metabolic disorder, exerts profound effects on both renal and cardiovascular systems. Contemporary research has investigated a range of various biomarkers aimed at predicting the early onset of renal and cardiac dysfunction in diabetic patients. An early decline in glomerular filtration rate (GFR) may occur even with normal urinary albumin excretion. Given that NT-proBNP concentrations are influenced by GFR, there is a critical need to identify biomarkers capable of detecting early cardio–renal injury in individuals with diabetes. Elevated Gal-3 levels in diabetic patients have been associated with an increased risk of all-cause mortality, cardiovascular disease, and progressive kidney failure and may serve as an indicator of subclinical cardiac and renal dysfunction. Incorporating Gal-3 assessment into clinical practice has the potential to improve diagnostic precision and support personalized management for cardiovascular, renal, and metabolic disorders. This review aims to elucidate the role of Gal-3 as a pivotal biomarker for diagnosis, prognosis, and therapeutic guidance in general in different types of diseases which involve cardio–renal complications. Full article

β-blockers have found wide application in cardiology, neurology, psychiatry, anaesthesiology, and endocrinology. Due to the reduction in excessive reactivity of the peripheral sympathetic nervous system, they have been used in the treatment of symptoms of hyperthyroidism. Significant efficacy in alleviating neuro-psychiatric symptoms associated with hyperthyroidism is attributed to propranolol, while cardiac symptoms are alleviated by both non-selective and cardioselective β-blockers. The aim of our study is to collect and summarise the existing knowledge on the role of β-blockers in patients with hyperthyroidism, with particular emphasis on pregnant patients, the group with iatrogenic hyperthyroidism, and patients after amiodarone. Due to their favourable safety profile, they appear to be a beneficial supplementary therapy to the treatment of hyperthyroidism in pregnant patients. β-blockers are also used in the treatment of complications of hyperthyroidism after amiodarone administration. They may influence the therapeutic process of amiodarone-induced hyperthyroidism itself, as well as being a therapeutic alternative to amiodarone in a cardiovascular context. By alleviating the symptoms associated with high doses of L-thyroxine, which are used, e.g., in. patients with thyroid cancer, β-blockers may make it possible to maintain low TSH values. Full article

Background/Objectives: Cardiac amyloidosis (CA) and cardiac sarcoidosis (CS) are two distinct infiltrative cardiomyopathies that can present with overlapping clinical features, including heart failure and arrhythmias. However, they arise from fundamentally different pathophysiological mechanisms: amyloid protein deposition in CA versus granulomatous inflammation in CS. These differing pathophysiologies result in divergent imaging patterns, clinical trajectories, and treatment strategies. This study aims to compare the clinical presentations, imaging characteristics, and outcomes of patients with CA and CS to identify key differentiating factors that can improve diagnostic precision and guide therapy. Methods: This single-center, retrospective, cross-sectional study analyzed electronic medical records of patients diagnosed with CA (limited to transthyretin CA) or CS at Mount Sinai Morningside system from January 2017 until October 2023. Patients were identified using diagnostic codes and confirmed by histology or disease-specific imaging criteria. Clinical data, transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR) imaging, pyrophosphate scintigraphy (PYP), and fluorodeoxyglucose positron emission tomography (FDG-PET) findings were collected. Statistical comparisons between groups were performed using chi-square tests and independent t-tests, with p < 0.05 considered statistically significant. Results: A total of 16,834 patients were screened and 216 patients were included in the analysis (125 CA, 92 CS). CA patients were older (78.2 vs. 62.0 years, p = 0.01), had greater interventricular septal thickness (1.57 vs. 1.10 cm, p = 0.01), and exhibited diffuse late gadolinium enhancement (LGE) and elevated extracellular volume (ECV) on CMR. CS patients had higher rates of ventricular tachycardia (53.3% vs. 10.7%, p = 0.01), increased myocardial fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) (90%), and more frequent implantable cardioverter-defibrillator (ICD) placement (66.3% vs. 13.0%, p = 0.01). Conclusions: CA and CS demonstrate distinct imaging profiles, arrhythmic risks, and treatment patterns. Early differentiation using advanced imaging is crucial for implementing disease-modifying therapies in CA and for immunosuppression and ICD implantation in CS, thereby improving patient outcomes. Full article

Background: Chronic heart failure (CHF) continues to present significant prognostic challenges despite advances in diagnosis and therapy. While the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is widely recognized as a key marker of cardiac stress, and serum albumin reflects systemic inflammation and nutritional status, their integration into a single parameter—the NT-proBNP-to-albumin ratio (NTAR)—may improve risk stratification. This study aimed to evaluate the NTAR as a novel biomarker for predicting in-hospital mortality in patients with CHF. Methods: We performed an exploratory, retrospective, observational, single-center study involving 542 patients (306 males) admitted for CHF between January 2022 and August 2024. NTAR was calculated as log₁₀(NT-proBNP/albumin). Statistical analyses included ROC curves, univariate and multivariable Cox regression, and Kaplan–Meier survival analysis. Sex-specific performance of NTAR was compared against NT-proBNP and serum albumin alone. Results: Females had significantly lower serum albumin levels than males, while NT-proBNP levels were similar across sexes. NTAR increased with NYHA functional class and was highest in patients with heart failure with reduced ejection fraction (HFrEF). NTAR showed very good discriminatory performance for predicting in-hospital mortality (AUC = 0.840, 95% CI: 0.794–0.879, p < 0.001), marginally but statistically outperforming NT-proBNP in the male subgroup. In univariate Cox regression analyses, higher serum albumin was significantly associated with reduced in-hospital mortality risk in males (HR = 0.352; 95% CI: 0.154–0.803; p = 0.010) and females (HR = 0.169; 95% CI: 0.072–0.399; p < 0.001). Elevated NT-proBNP levels were associated with increased mortality risk in males (HR = 8.627; 95% CI: 1.956–38.042; p < 0.001) and females (HR = 6.060; 95% CI: 1.498–24.521; p = 0.002) with similar findings in NTAR (HR_males = 10.318, 95% CI: 2.452–43.417, p < 0.001 and HR_females = 7.542, 95% CI: 1.874–30.358, p < 0.001). Multivariable analysis identified NTAR as the strongest independent predictor for in-hospital mortality among males. Conclusions: These findings suggest that NTAR effectively integrates cardiac and systemic dysfunction to improve mortality risk stratification in CHF, particularly in male patients. Its ease of calculation from routinely available biomarkers supports its clinical applicability. Full article