Search Results (327)

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development in cardio-oncology. This review highlights the importance of sex-specific surveillance, prevention, and multi-omic risk stratification to advance precision cardio-oncology and support better outcomes for patients across the cancer care continuum. Full article

Cardiovascular toxicity has emerged as a major determinant of long-term outcomes in cancer survivors as advances in oncologic therapies continue to improve survival. Conventional cardiac surveillance strategies predominantly rely on functional and structural changes, often identifying myocardial injury after clinically significant damage has occurred. The aim of this narrative review is to critically evaluate the role of nuclear imaging in advancing precision cardio-oncology by enabling earlier, mechanism-based detection and characterization of cancer therapy-related cardiotoxicity. We summarize current clinical applications of PET- and SPECT-based imaging, examine molecular and tracer-level innovations, and discuss emerging hybrid imaging and analytic approaches relevant to individualized cardiovascular risk stratification. Current literature indicates that nuclear imaging provides unique insights into myocardial perfusion, metabolism, inflammation, and microvascular dysfunction, facilitating detection of subclinical injury across diverse anticancer therapies, including anthracyclines, targeted agents, and immune checkpoint inhibitors. By integrating molecular imaging with conventional modalities, nuclear techniques support more personalized surveillance and management strategies. This narrative review highlights nuclear imaging as an emerging complementary modality within precision cardio-oncology supporting earlier detection and risk stratification, and outlines future directions required to optimize its clinical integration and impact on cardiovascular outcomes across the cancer care continuum. Full article

Since the first approval of CTLA-4 blockade for melanoma, immune checkpoint inhibitors (ICIs) have expanded into a major class of cancer therapy, with more than 100 FDA-approved oncological indications across metastatic and earlier-stage disease settings, including use as monotherapy and in combination regimens. Preclinical research has largely focused on myocarditis and atherosclerosis, but a wider set of phenotypes, such as non-inflammatory left ventricular dysfunction (NILVD), arrhythmias, and vasculitis, can be observed, and they are rarely connected within a single mechanistic model. We aim to build a systems-oriented, mechanistic framework of the most widely studied biological processes; it will link the main checkpoint pathways to relevant cardiac and vascular cell types, molecular pathways, immune synapses, and candidate biomarkers. We searched PubMed, Scopus, and Web of Science using combinations of terms for immune checkpoint inhibition and cardiovascular-immune-related adverse events that provide mechanistic insight into cardiac-immune-related adverse reactions (irAEs). An AI-assisted semantic clustering approach was used only to organize the included literature. The integrated framework identifies PD-1/PD-L1 as the dominant mechanistic hub linking T-cell activation, endothelial recruitment, myocardial injury, and vascular inflammation. Across phenotypes, a shared immune core involving checkpoint pathways, cytokine signaling, and leukocyte trafficking coexists with phenotype-restricted mediators that may bias injury toward myocarditis, vascular inflammation, conduction-system disease, or NILVD. KEGG analyses support the enrichment of T-cell receptor signaling, Th17 differentiation, JAK-STAT signaling, cytokine–cytokine receptor interaction, and lipid and atherosclerosis pathways. Candidate biomarkers emerging from the reviewed literature include troponin, IL-6, CXCL9/CXCL10/CXCL13, S100A family proteins, ROCK2, HLA-linked susceptibility signals, and T-cell receptor clonality markers. The AI-assisted clustering broadly recapitulated the expert-defined thematic structure while identifying finer semantic neighborhoods within the literature. This framework provides a support map for further hypotheses about toxicity patterns with current and next-generation checkpoint strategies on the cardiac system, while AI-assisted clustering provides a complementary method for organizing the literature rather than an independent source of biological inference. Full article

Background: Kounis syndrome is an acute coronary syndrome triggered by hypersensitivity reactions, which may result in coronary vasospasm, thrombosis, or stent-related complications. Case Summary: A 64-year-old male smoker with dyslipidemia and recently diagnosed urothelial carcinoma presented with exertional angina and underwent coronary angiography. Percutaneous coronary intervention was performed for a critical proximal–mid left anterior descending artery lesion using a drug-eluting stent. Immediately after stent deployment, the patient developed diffuse multivessel coronary vasospasm involving the left main stem, left anterior descending, and left circumflex arteries, accompanied by slow-flow/no-reflow phenomena and subsequent acute in-stent thrombosis. The clinical course rapidly progressed to ventricular arrhythmias and cardiogenic collapse. Despite transient return of spontaneous circulation after cardiopulmonary resuscitation, the patient developed fatal asystole during a repeat angiographic attempt. No cutaneous or respiratory allergic manifestations were observed. The abrupt onset of diffuse coronary dysfunction immediately following contrast exposure was suggestive of suspected Kounis syndrome, although mechanical causes and chemotherapy-related vasospasm could not be entirely excluded. Conclusions: Diffuse coronary vasospasm with multivessel dysfunction occurring abruptly after contrast exposure should raise suspicion for Kounis syndrome, even in the absence of overt allergic manifestations. Early recognition is essential to avoid misattribution to procedural complications and may be particularly important in patients with malignancy undergoing invasive coronary procedures. Full article

Background: Cancer is common among patients with acute myocardial infarction (AMI) and may influence management and outcomes. The prognostic impact of cancer status (active vs. past) and its anatomical site remains insufficiently defined. We evaluated the association between cancer and short- and long-term outcomes after AMI in a large population cohort. Methods: Using linked administrative databases from Lombardy, Italy, we identified adults with a first AMI hospitalization from 2014 to 2022 (N = 124,403). Patients were categorized by cancer history, cancer status (active vs. past), and cancer site. The primary endpoint was in-hospital mortality; secondary endpoints were 1-year all-cause mortality and 1-year rehospitalization for AMI or acute heart failure (AHF). Multivariable log-binomial, Cox, and Fine&Gray models were applied. Results: Overall, 18,463 (14.8%) had a history of cancer. They were older and had higher comorbidity burden. Cancer history was associated with higher in-hospital mortality (adjusted risk ratio [RR] 1.06, 95% CI 0.99–1.13) and one-year mortality (adjusted hazard ratio [HR] 1.46, 95% CI 1.40–1.52). Active cancer carried the greatest risk (in-hospital RR 1.07, 95% CI 1.00–1.15; 1-year HR 1.60, 95% CI 1.53–1.68), whereas past cancer showed no excess mortality. Site-specific analyses identified lung (one-year HR 2.69, 95% CI 2.15–3.37) and hematological cancers (one-year HR 2.19, 95% CI 1.88–2.56) as highest-risk. Elevated mortality with cancer was consistent in STEMI and NSTEMI. Competing-risk analyses showed a similar risk of rehospitalization among cancer and non-cancer patients. Conclusions: In a real-world, unselected AMI population, cancer worsens short- and long-term survival, especially when active and involving the lungs or the hematopoietic tissues. Incorporating cancer status into AMI risk stratification and strengthening cardio-oncology pathways in acute care are warranted to improve patient outcomes. Full article

Background/Objectives: Bradyarrhythmias are an under-recognized component of cancer therapy-related cardiovascular toxicity. As survivorship improves and exposure to targeted and immune therapies increases, clinicians increasingly face clinically relevant sinus node dysfunction and atrioventricular (AV) conduction disease that may interrupt otherwise effective oncologic treatment. We aimed to synthesize evidence on the incidence, phenotype, mechanisms, and management of bradyarrhythmias across major anticancer drug classes. Methods: We performed a narrative review of PubMed and major clinical guidelines, prioritizing prospective trials and large observational cohorts for incidence estimates, and case reports/series for phenotype and management details. Regulatory prescribing information and pharmacovigilance datasets were consulted to complement trial data. Evidence was organized by drug class and prototypical agents. Results: Bradyarrhythmias ranged from transient sinus bradycardia to high-grade atrioventricular block requiring pacing. The most severe phenotype was associated with immune checkpoint inhibitor-related myocarditis, whereas ALK inhibitors, thalidomide, antimetabolites—particularly 5-fluorouracil—and taxanes showed more reproducible signals for sinus bradycardia. Bradyarrhythmic events were also described with proteasome inhibitors, BTK (Bruton tyrosine kinase) inhibitors, anthracyclines, platinum compounds, high-dose cyclophosphamide, corticosteroids, and other agents, but the strength of evidence varied from regulatory or cohort-based data to isolated case reports. Conclusions: Bradyarrhythmias during cancer therapy are heterogeneous but clinically consequential. Recognition of class-specific patterns, proactive ECG/electrolyte monitoring, and context-specific management (e.g., drug interruption/dose modification, pacing when indicated, risk-factor control) can minimize therapy interruption while maintaining oncologic efficacy. Full article

Background/Objectives: Clinical application of Doxorubicin (Doxo) is limited by cardiotoxicity, a process strongly associated with an interplay between oxidative stress and inflammatory signaling, particularly Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and Nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome engagement. Identifying strategies capable of mitigating these interconnected pathways is of critical importance in cardio-oncology. Simvastatin (SIM) is a promising option since it modulates oxidative stress, inflammation, and cell death through its pleiotropic effects, so this study aimed to evaluate whether SIM attenuates Doxo-induced inflammatory responses. Methods: Human Cardiomyocyte (HCM) cells were pre-treated with SIM (10 µM) for 4 h and then co-exposed to SIM and Doxo (1 µM) for 20 h. Cytofluorimetric analysis was used to evaluate inducible nitric oxide synthase (iNOS), Connexin 43 (Cx43), and Cx43 phosphorylated at Serine 368 (p^S368Cx43) levels. Real-time qPCR was performed to evaluate iNOS gene expression, while Nitric oxide (NO) release was evaluated by spectrophotometric analysis. Interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor alpha (TNF-α) production, and NLRP3 levels were evaluated by means of ELISA assay. Expression levels of inhibitor of nuclear factor kappa B alpha (IκB-α), Caspase-1, and Gasdermin D (GSDMD) were evaluated by Western Blot analysis. Nuclear translocation of NF-κB was evaluated by immunofluorescence assay. Results: In our experimental model, SIM significantly (p < 0.01) reduced Doxo-induced nitrite release, as well as iNOS gene expression (p < 0.05) and protein levels (p < 0.01). SIM also markedly attenuated Doxo-induced NF-κB signaling, pro-inflammatory cytokines production (TNF-α and IL-6, p < 0.01), and inflammosome-related responses (cleaved caspase-1, IL-1β, N-terminal domain of GSDMD), and NLRP3 expression p < 0.05). Additionally, SIM significantly attenuated the overexpression of Cx43 and its phosphorylated form (p^S368Cx43), which are responsible for impairing intercellular communication and electrical coupling in cardiomyocytes and contribute to arrhythmias and conduction abnormalities characteristic of acute Doxo-induced cardiotoxicity. Conclusions: Overall, these findings demonstrate that SIM exerts a multifaceted cardioprotective effect against Doxo-induced injury, thereby targeting interconnected inflammatory and pro-arrhythmic pathways implicated in Doxo cardiotoxicity. Full article

Although breast cancer has been associated with subclinical left ventricular dysfunction in humans, the cardiac effects of CMTs remain poorly defined. This pilot, exploratory (communication) study compared clinical and echocardiographic parameters between dogs with CMTs and healthy controls and assessed the feasibility of combining myocardial deformation imaging with exploratory data-driven analysis for preoperative cardiac assessment. All dogs underwent a standardized clinical and echocardiographic assessment, including two-dimensional speckle-tracking echocardiography (2D-STE). Given the limited sample size, analyses were designed to generate hypotheses rather than to provide definitive predictive conclusions. Exploratory machine learning modeling (XGBoost), receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis were performed as proof-of-concept approaches without external validation. Despite normal conventional systolic indices, dogs with CMTs exhibited reduced global longitudinal strain (GLS) and mitral annular plane systolic excursion (MAPSE) (p < 0.01), suggesting subclinical systolic dysfunction. Deformation-derived parameters appeared more sensitive for detecting subtle myocardial alterations within this cohort. The exploratory machine learning model demonstrated moderate discrimination (AUC-ROC = 0.75); however, these findings are preliminary and should not be interpreted as evidence of clinical predictive performance. Overall, these results suggest that conventional systolic indices may underestimate early myocardial changes in dogs with CMTs. This communication highlights the feasibility of integrating deformation imaging with exploratory analytical approaches and provides a basis for future large-scale, validated studies in veterinary cardio-oncology. Full article

Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods: We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty. Eligibility assessment, data extraction, and qualitative synthesis followed key PRISMA 2020 principles, and findings were organized into three prespecified domains: surgical complexity, cardiovascular vulnerability (including patients with heart failure where reported), and frailty. Results: Nineteen studies (retrospective cohorts, registry-based analyses, and large database studies, primarily ACS NSQIP) met inclusion criteria, encompassing diverse breast surgery populations, including elderly, metastatic, and reconstructive cohorts. Across datasets, escalation from breast-conserving surgery to mastectomy and then to increasingly complex reconstruction was associated with a stepwise increase in perioperative complications, reoperations, bleeding, and, in selected series, catastrophic events. Preexisting cardiovascular disease and systemic vascular pathology significantly amplified postoperative morbidity even in procedures considered low or intermediate cardiac risk, with signals that patients with underlying heart failure carry particularly heightened vulnerability, although HF-specific events were infrequently reported as separate endpoints. Frailty, mainly assessed using modified frailty indices, consistently emerged as a strong, age-independent predictor of 30-day complications, mortality, and readmissions across surgical types, including both breast-conserving and reconstructive procedures. Conclusions: Early postoperative outcomes after breast cancer surgery are associated with the interaction between surgical complexity, cardiovascular comorbidity (with limited HF-specific reporting), and frailty rather than by operative technique alone. In this context, our synthesis primarily reflects overall cardiovascular vulnerability in comorbid and frail patients, with heart failure risk inferred indirectly from the available data. These findings support a patient-centered, risk-adapted surgical strategy in which the extent and timing of surgery and reconstruction are tailored to each patient’s cardiovascular profile and frailty status, with preferential use of breast-conserving or less complex procedures in vulnerable individuals. Integrating standardized frailty assessment and cardio-oncologic evaluation into preoperative workflows, and prospectively validating this tri-axial framework in dedicated cohorts, may improve perioperative risk stratification and reduce the burden of postoperative medical complications in an aging breast cancer population. Full article

Background: Ponatinib (PON), an effective tyrosine kinase inhibitor for leukemias harboring the T315I mutation, is limited by severe cardiotoxicity, including myocardial infarction and heart failure. Here, we investigated the therapeutic potential of Bone Morphogenetic Protein-7 (BMP-7), an anti-inflammatory growth factor, in a murine model of PON-induced cardiotoxicity. Methods: C57BL/6J mice were distributed into experimental groups receiving PON (25 mg/kg cumulative dose) either alone or with BMP-7 (600 μg/kg cumulative dose), along with a corresponding control group. Cardiac analyses included molecular and histological assessments. Results: PON administration induced a marked increase in monocyte infiltration and M1 macrophage polarization. These inflammatory events led to the upregulation of the pyroptotic cascade, leading to activation of the TGF-β1/SMAD2/3 signaling axis. In contrast, BMP-7 significantly attenuated these pathological responses by suppressing inflammation-induced pyroptosis and the TGF-β1/SMAD2/3 signaling axis. Conclusions: These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7’s capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance. Full article

Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack cancer-specific variables. We evaluated whether these models, even after statistical optimization, could predict cardiovascular mortality in cancer survivors. Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2001–2018, linked with National Death Index (NDI) mortality data, we conducted a retrospective analysis of 634 and 429 cancer survivors, respectively, across model-specific cohorts free of baseline cardiovascular disease. Discrimination was assessed for ASCVD, Framingham Score, and PREVENT using standardized thresholds of 7.5% and 20%, as well as Youden-optimized cutoffs. Area under the curve (AUC) comparisons were performed using the DeLong non-parametric method. Results: Standard thresholds showed suboptimal discrimination across all models (AUCs: ASCVD 0.56, Framingham 0.53, PREVENT 0.64). In contrast, Youden-optimized AUCs (ASCVD: 0.68; PREVENT: 0.71; all p < 0.001, DeLong test). Optimization increased the “low-risk” group’s mortality rate from 2.8% to 4.1% (RR = 1.47), suggesting improved statistical fit came at the cost of overestimating the risk. Optimized thresholds outperformed conventional cutoffs, underscoring the necessity for recalibrated, cohort-specific risk stratification in cancer survivors. Conclusions: Standard risk scores have inadequate discrimination for cardiovascular mortality prediction in cancer survivors. Threshold recalibration improves statistical metrics but does not resolve the structural failure of these models to account for cardiotoxic exposure. Development of cardio-oncology-specific risk models incorporating oncologic exposures is therefore warranted. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Background/Objectives: While doxorubicin (DOX) and trastuzumab (TRZ) improve overall survival in women with breast cancer, these two anti-cancer drugs increase the risk of developing heart failure. As a novel and largely unexplored approach, our aim was to evaluate whether the prophylactic use of the sodium-glucose co-transporter 2 inhibitor empagliflozin (EMPA), with and without the angiotensin converting enzyme inhibitor perindopril (PER), is cardioprotective in preventing DOX + TRZ-mediated cardiotoxicity. Methods: In a chronic in vivo murine model, female mice received prophylactic treatment with PER (3 mg/kg), EMPA (10 mg/kg), or EMPA + PER via oral gavage for a total of 3 weeks as a run-in period prior to weekly administration of DOX + TRZ (8 mg/kg and 3 mg/kg, respectively) intraperitoneally for an additional 3 weeks (total of 6 weeks). Results: In mice treated with DOX + TRZ, the left ventricular ejection fraction (LVEF) decreased from 75 ± 2% at baseline to 40 ± 4% at week 6. Prophylactic treatment with either PER, EMPA, or EMPA+PER improved LVEF to 58 ± 3%, 66 ± 3%, and 67 ± 4% at week 6, respectively (p < 0.05). Histological analyses confirmed significant disruption of myofibrils, vacuolization, and loss of sarcomere integrity in the DOX + TRZ-treated mice. Prophylactic administration with PER, EMPA, or EMPA + PER, however, improved myofibril integrity at week 6 in mice receiving DOX + TRZ. Finally, although the Bax/Bcl-xL ratio was significantly elevated by 1.5-fold in mice treated with DOX + TRZ, this marker of apoptosis was attenuated by prophylactic treatment with either PER, EMPA, or EMPA + PER. Conclusions: Prophylactic administration of EMPA mitigated adverse cardiovascular remodeling in a chronic in vivo model of DOX + TRZ-mediated cardiotoxicity. Full article

Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context. Full article

Doxorubicin (DOX) is a widely used anthracycline, but its clinical use is limited by dose-dependent cardiotoxicity. This experimental study evaluated the cardioprotective potential of empagliflozin (EMPA) against DOX-induced cardiotoxicity. Thirty healthy adult rats were randomized into five groups (n = 6): control (group I), EMPA (group II), EMPA + DOX (group III), DOX (group IV), and EMPA-preconditioning + DOX (group V). EMPA was administered orally at 10 mg/kg/day, either concomitantly with DOX or as a 14-day preconditioning course. Cumulative DOX exposure reached 15 mg/kg to establish a reproducible cardiotoxicity model. Serial electrocardiograms (ECGs) were recorded, blood samples were collected, and hearts were harvested for detailed histopathological analysis. Compared with the control group, group IV demonstrated significant QT/QTc prolongation and repolarization abnormalities, marked troponin elevation, and characteristic histological lesions, including cardiomyocyte vacuolization, loss of striations, diffuse inflammation, myocyte atrophy, and increased fibrosis. In groups receiving EMPA with DOX exposure (groups III and V), ECG changes were attenuated, troponin elevation was lower, and structural myocardial damage was substantially reduced, with better preservation of cardiomyocyte architecture and less fibrosis. These results suggest that EMPA provides significant cardioprotection against DOX-induced cardiotoxicity in rats, supporting further investigation of SGLT2 inhibitors in cardio-oncology. Full article