Sepsis-induced cardiomyopathy (SICM) constitutes a critical myocardial impairment that substantially elevates mortality risk in septic patients. The structural and functional changes of SICM are accompanied by metabolic disturbances, including mitochondrial dysfunction and altered myocardial metabolism. Diagnostic advancements feature biomarkers, circulating microRNAs, and imaging tools, such as speckle-tracking echocardiography. Therapies extend from vasopressors to immunomodulators, mitochondrial-targeted antioxidants, and mesenchymal stem cell-based approaches. Despite progress, challenges related to heterogeneity and the need for long-term data persist. Thus, integrated approaches leveraging machine learning and omics are essential for optimizing personalized care and reducing the global burden of SICM.

Takayasu's arteritis (TAK) is a rare chronic arteritis that can lead to serious consequences. Understanding of the pathogenesis of TAK remains limited, and effective therapeutic strategies for this condition are lacking. Previous studies have suggested that there may be an association between TAK and the interaction between Mycobacterium tuberculosis infection and genetic susceptibility. Emerging data indicate that the nucleotide-binding and oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 receptor (NLRP3) inflammasome may be involved in the pathogenesis of TAK, potentially contributing to the initiation of the disease. This review summarizes the current epidemiological data, possible mechanisms, and targeting strategies of TAK, focusing on the involvement of the NLRP3 inflammasome in the pathogenesis of TAK, and provides new insights into the prevention and treatment of this condition.

Heart failure (HF) is a major contributor to morbidity and mortality in the US and worldwide. HF is a complex condition characterized by the disruption of normal physiology and the activation of neurohumoral pathways, including the renin–angiotensin–aldosterone system, the sympathetic system, and inflammatory pathways. These have adverse effects on renal handling of salt and water balance, leading to salt and water retention and a vicious cycle of worsening congestive changes with progressive volume overload. Meanwhile, diuretics are pharmacologic agents that are essential in the management of HF. Indeed, diuretics induce natriuresis to disrupt this vicious cycle of progressive volume overload, thereby reducing congestive changes and alleviating the symptoms of HF. In this review, we discuss the different classes of diuretics and their sites and mechanisms of action across the nephron. We highlight differences in the potency and usefulness of these diuretics. Moreover, we examine their application in the management of various stages of HF, focusing on their optimal and effective use in clinical practice. In this review, we also cover several aspects of the pathophysiology of HF. We address the milder forms of HF that are treated in outpatient clinics, as well as the more advanced states of HF, including acute decompensated HF (ADHF), which are usually managed in a hospital setting. We discuss management strategies in the outpatient setting, with a specific focus on maintaining sufficient decongestion of patients to prevent hospitalization. We stress the importance of closely monitoring congestive symptoms and weight trends, as well as electrolyte and renal parameters. We recommend setting a “target weight goal” for the patient between clinic visits, which helps with outpatient diuretic therapy adjustments and avoids drifts in volume status. We also examine the usefulness of diuretics in hospitalized patients with ADHF. For these more challenging conditions, we discuss the use of combination diuretics to overcome diuretic resistance and highlight current recommendations for achieving the desired goals and speed of diuresis. Patients with HF commonly have chronic kidney disease (CKD), which frequently complicates overall management strategies. CKD also leads to diuretic resistance, necessitating escalation of diuretic dosing and more frequent changes in diuretic prescription. Hence, this review also discusses management strategies for CKD patients and highlights the importance of close monitoring of kidney function in both inpatient and outpatient settings when using diuretics in patients with HF. We briefly discuss the benefits of monitoring central venous filling pressures in patients with ADHF as a tool to guide the optimization of diuresis. Finally, we allude to new advanced technologies such as remote monitoring of outpatients with HF. These can be used to detect early signs of impending HF decompensation that earlier adjustments to the diuretic dose could then address.

Percutaneous coronary intervention (PCI) has made significant progress as one of the main treatments for coronary artery disease (CAD), but the risk of major adverse cardiovascular events (MACE) after PCI remains high. Therefore, early identification of high-risk CAD patients after PCI and improvement of risk factors are crucial for patient prognosis. Although various prognostic biomarkers related to CAD have been identified, most of them have not been widely applied in clinical practice. Recent studies have found that some simple and easily obtainable metabolic indicators have early predictive value for the prognosis of CAD patients after PCI, mainly including four categories: blood lipids and related metabolites, blood glucose and related metabolites, nutrition-related metabolites, and kidney-related metabolites. This review synthesizes the four aforementioned categories of indicators with the aim of integrating their unique characteristics to enable precise prognostication in patients after PCI, deepen mechanistic insights, and furnish evidence-based guidance for clinical decision-making.

Vitamin D is a key regulator of calcium and phosphorus homeostasis; meanwhile, the dietary absence of vitamin D represents the most common nutritional deficiency worldwide. The discovery of vitamin D receptors and conversion enzymes within the cardiovascular system has fueled growing interest in the potential roles of vitamin D beyond bone health. Indeed, preclinical studies have suggested that vitamin D might regulate vascular tone and exert antifibrotic and anti-remodeling effects on the myocardium. Furthermore, a deficit in vitamin D has been associated with an increased risk of hypertension, atherosclerosis, and heart failure. These findings have prompted several interventional studies to investigate whether vitamin D supplementation can mitigate cardiovascular risk. However, current evidence regarding the cardiovascular benefits of vitamin D intake remains inconsistent and inconclusive. This review aims to provide a comprehensive overview of the “good”, the “bad”, and the “unknown” aspects of the relationship between vitamin D and cardiovascular disease.

Climate change poses a significant threat to cardiovascular health through the combined effects of extreme temperatures, air pollution, and extreme weather events. Short-term heat exposure raises mortality risk by 3.80%, while long-term exposure to particulate matter (PM_2.5, with an aerodynamic diameter of ≤2.5 micrometers) increases cardiovascular mortality by 11–20%. Key mechanisms include thermoregulatory stress, inflammation, autonomic nervous system dysfunction, prothrombotic state, and psychosocial stress. Vulnerable groups, such as older individuals and those with cardiovascular diseases, also face a higher risk. Epidemiological studies have shown that for every one-standard-deviation increase in the number of days with excess heat factor, the overall mortality risk rises by 3.80%. Proposed interventions include high-efficiency particulate air (HEPA) purifiers, optimized cooling centers, and low-emission zones. However, key research gaps remain in the effects of multi-stressors, protection strategies, exposure assessment, and climate-driven disease projections. Multidisciplinary collaboration is crucial for mitigating climate-related cardiovascular risks. This review provides a comprehensive overview of the current situation regarding climate change and cardiovascular health, summarizing the results of epidemiological, pathological mechanisms, and policy research.

Invasive coronary angiography remains the gold standard for assessing and treating coronary artery disease (CAD). While the decision to intervene on a severely stenotic lesion in acute coronary syndrome (ACS) can be straightforward, assessing the potential benefits of treating an intermediate lesion, especially in patients with stable symptoms, often requires hemodynamic assessment or intravascular imaging. Fractional flow reserve (FFR) is a well-established invasive hemodynamic assessment that is the gold standard for determining the functional significance of intermediate lesions by analyzing the pressure loss across an area of stenosis during maximal hyperemia. The association between the use of FFR and improved clinical outcomes has been validated by numerous clinical trials, leading to societal guidelines for the use of FFR. Recently, invasive hemodynamic indices have been developed that do not require the induction of hyperemia. These non-hyperemic pressure ratios (NHPRs) include the resting full-cycle ratio (RFR), instantaneous wave-free ratio (iFR), diastolic hyperemia-free ratio (DFR), and diastolic pressure ratio (dPR). Clinical studies have suggested “discordance” in FFR and NHPRs in approximately 20% of patients with NHPR-/FFR+ being slightly more prevalent than NHPR+/FFR-. Discordance has been associated with clinical factors, including advanced age, female sex, presence of diabetes, and microvascular dysfunction. Data are inconsistent about whether deferral of revascularization is safe in patients with discordance; however, patients who are NHPR-/FFR+ are more likely to have focal than diffuse disease okand more likely to observe a symptomatic benefit from percutaneous coronary intervention (PCI). Nonetheless, large-scale studies are needed to improve understanding of this discordance, particularly in relation to clinical outcomes.

Owing to the aging global population, cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. The aging process is closely associated with cardiac neurovascular interface deterioration, particularly autonomic nervous system (ANS) dysfunction, which has profound effects on cardiovascular health. Recent studies have suggested that long-term moderate exercise can improve ANS function and alleviate CVD risk. This review evaluates the effects of exercise on the cardiac neurovascular interface and ANS function, with a particular focus on the distinct roles of aerobic and anaerobic exercise on cardiac health. Research has shown that exercise significantly enhances heart rate variability, improves autonomic regulation of the heart, and reduces oxidative stress and inflammation, thereby improving cardiac function and reducing the incidence of CVD. Specifically, high-intensity interval exercise and combination training incorporating both aerobic and anaerobic exercise improve the cardiac neurovascular interface and promote cardiac repair. However, while the benefits of exercise are widely recognized, understanding of the factors such as individual differences, exercise intensity, and exercise type needs to be improved to optimize the effectiveness of exercise interventions. Thus, future research should focus on personalized exercise interventions and the identification of biomarkers, such as microRNAs, to enhance the effectiveness of exercise intervention as a clinical treatment strategy.

Heart failure with preserved ejection fraction (HFpEF) represents a major phenotype of heart failure and accounts for over 50% of clinical cases. The complex pathophysiological mechanism involved in HFpEF promotes diagnostic difficulties and limited treatment options, posing a significant challenge in modern cardiology. Conventional imaging methods have significant limitations in comprehensively evaluating the heterogeneous etiologies and key pathological mechanisms of HFpEF. Radionuclide myocardial imaging, through the application of targeted radioactive tracers, enables in vivo, non-invasive quantitative assessment of multiple pathological and physiological processes such as myocardial perfusion, energy metabolism, sympathetic nervous activity, inflammatory responses, and fibrotic progression. Moreover, this technology offers a transformative approach to the precise diagnosis, molecular phenotyping, risk stratification, therapeutic monitoring, and prognostic assessment of HFpEF. Therefore, this review systematically summarizes the latest progress in radionuclide myocardial imaging techniques in diagnosing and treating HFpEF, with a particular focus on analyzing the unique clinical value of this technology in identifying specific etiologies (such as cardiac amyloidosis, cardiac sarcoidosis, and coronary microvascular dysfunction) and elucidating pathological mechanisms (including metabolic remodeling, inflammatory, fibrosis, and alterations in sympathetic innervation). Furthermore, we discuss the future directions of this imaging modality, including the development of novel molecular probes, integration with multimodal imaging techniques, and the application of artificial intelligence-assisted analysis. These innovations are expected to facilitate a paradigm shift from symptom-oriented management to mechanism-targeted therapy, offering new perspectives for the precise classification and clinical management of HFpEF.

This article reviews the latest research progress (2018–2025) on the molecular mechanisms linking glucose and lipid metabolism disorders (GLMDs) to cardiovascular injury, specifically atherosclerotic cardiovascular disease (ASCVD), diabetic cardiomyopathy (DbCM), heart failure (HF), and cardiac autonomic neuropathy (CAN). This review employed a targeted analysis of key publications from the PubMed, Web of Science, and EMBASE databases, as well as citation tracking, prioritizing molecular pathways and interventions for these four complications. The key mechanisms include: metabolic inflammation: the advanced glycation end products (AGEs)–receptor of AGE (RAGE) axis activates NF-κB, promotes vascular cell adhesion molecule-1 (VCAM-1)/monocyte chemoattractant protein-1 (MCP-1) overexpression, and accelerates monocyte infiltration; myocardial lipotoxicity: CD36 mediates fatty acid overload → mitochondrial damage → cyclic guanosine monophosphate-adenylate synthetase (cGAS)-STING pathway activation → myocardial apoptosis; metabolic memory: hyperglycemia continuously releases small extracellular vesicle (sEV) miR-15-16 clusters through the O-GlcNAc–CaMKIIδ–STAT1 loop, mediating remote myocardial injury; gut–heart axis disorder: Trimethylamine N-Oxide (TMAO) promotes thrombosis and endothelial injury. Precision strategies based on the above mechanisms, such as SGLT2 inhibitors to improve myocardial energy metabolism, targeting acyl-coenzyme A binding protein (ACBP)/TGR5 to alleviate lipotoxicity, and microbiota regulation, have demonstrated potential in clinical research. Future focus should include (1) GLMD heterogeneity typing; (2) tissue-targeted delivery system; (3) multi-omics–AI dynamic risk modeling.

Cardiac amyloidosis (CA) has emerged from the margins of cardiology to the forefront of research and practice on heart failure. Once regarded as rare and elusive, CA is now recognized as a significant cause of heart failure with preserved ejection fraction (HFpEF), arrhythmias, and valvular disease, especially in older patients. CA is characterized by extracellular deposition of misfolded protein fibrils, which infiltrate the myocardium and disrupt the structural and electrical integrity. Although CA can stem from multiple amyloid types, transthyretin amyloidosis (ATTR) and light-chain (AL) amyloidosis are the predominant subtypes with cardiac involvement, each carrying distinct implications for prognosis and therapy. This review explores CA as a clinical reality often obscured by more common cardiovascular syndromes. Moreover, this review focuses on the varied presentations of CA in real-world practice, how the condition overlaps with HFpEF, the subtle clues for CA amid common valvular disorders, and the complex rhythm manifestations of the condition. Particular attention is given to thromboembolic risk, microvascular dysfunction, and the evolving paradigm of preclinical or asymptomatic amyloidosis management. Furthermore, this review addresses contemporary challenges such as financial toxicity and the cost-effectiveness of screening, emphasizing the benefits of early detection and therapy. The paper also discusses risk stratification and staging, drawing from validated models to guide both prognosis and treatment decisions, and the role of histopathological characterization. Thus, this review underscores the importance of timely recognition and tailored intervention in transforming CA from a terminal diagnosis into a manageable chronic condition.

Cardiac rehabilitation (CR) has been categorized as a class Ia recommendation for secondary prevention after major cardiac interventions or in patients with certain cardiac comorbidities. The benefits of CR have been established and range from reducing readmissions to improving quality of life. Given the increasing amount of literature on CR over the past few years and the evolution of this field, there is a need to synthesize these data. Thus, this review aims to combine the latest research findings to provide a comprehensive review of CR literature. We discuss the components needed to create a successful CR program, including individualized training plans, routine clinical assessments, exercise supervision, and nutritional assessments. Overall rates of CR utilization remain low. Therefore, we explore potential reasons for this underutilization observed in the literature, including CR deserts, under-referral, and the lack of education on benefits, time, and transportation. Moreover, we discuss solutions for underutilization that have been analyzed in the literature, including motivational interviewing, gender-specific regimens, transportation assistance, and automatic referrals. Realizing the underutilization of CR, we also assess virtual CR (VCR) and variations in various regimens within the programs. We compare exercise and body metrics, patient outcomes, feasibility, and patient preferences between VCR and traditional CR published in the literature. VCR does not appear to be inferior to conventional CR in many metrics, although more research is needed to compare the two modalities. We recommend that providers explain the outcomes of the two modalities and allow patients to choose the regimen that works best for them. We discuss how VCR may be better suited to patient populations with specific barriers to care. We also discuss the ongoing current CR trials, many of which are focused on solutions to underutilization. Lastly, we further discuss the remaining gaps in the CR literature and areas where future research could be beneficial, such as establishing large-scale VCR studies and studies focused on expanding CR indications.

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Percutaneous coronary intervention (PCI) represents the standard treatment for CAD; however, significant challenges, such as in-stent restenosis, late thrombosis, and delayed endothelial healing, remain issues for long-term outcomes. The evolution of stents from bare metal and drug-eluting platforms to bioabsorbable and nanoengineered designs has reduced, but not eliminated, these complications. Meanwhile, exosome-mimetic nanovesicle (EMNV)-coated stents have emerged as a potential approach to address these limitations since EMNVs mimic the structure and biological function of natural exosomes. This mimetic ability enables targeted delivery of therapeutic agents such as microRNAs, growth factors, and anti-inflammatory molecules. Indeed, preclinical studies have previously demonstrated the ability of these stents to reduce neointimal hyperplasia, enhance endothelialization, and modulate inflammatory responses. Engineering strategies, including stimuli-responsive release triggered by pH or enzymatic activity, further improve the precision of therapeutic delivery. However, the transition to clinical application remains in its early stages, with key obstacles including the scalability and reproducibility of EMNV production, the stability of biologic coatings during application, and regulatory classification as combination products. Therefore, clinical translation will require standardized manufacturing standards, reliable potency testing, and long-term safety studies to overcome these challenges. Personalized medicine approaches using patient-derived exosomes and artificial intelligence (AI)-assisted stent design may provide additional opportunities to accelerate the transition. This review summarizes the evolution of coronary stent technology and discusses the potential and limitations of EMNV-based platforms. This article also outlines future directions that will guide the development of EMNV-based platforms as next-generation devices in interventional cardiology.

Lipoprotein(a) (Lp(a)) is an established independent risk factor for atherosclerotic cardiovascular disease, particularly in the development of high-risk coronary plaques (HRPs). Elevated Lp(a) contributes to lipid accumulation, vascular inflammation, and plaque instability, primarily through oxidized phospholipids that promote monocyte adhesion and foam cell formation. Genetic studies have identified variants in the LPA gene as major determinants of Lp(a) levels, with higher concentrations consistently associated with adverse cardiovascular outcomes. Intravascular imaging techniques, such as optical coherence tomography and intravascular ultrasound, along with coronary computed tomography angiography (CCTA), have confirmed strong correlations between elevated Lp(a) and increased plaque burden, lipid-rich necrotic cores, and thin fibrous caps. In addition to coronary involvement, Lp(a) is implicated in systemic atherosclerosis, contributing to peripheral artery disease, cerebrovascular disease, and calcific aortic stenosis. Although conventional lipid-lowering therapies exert minimal effects on Lp(a), novel treatments such as proprotein convertase subtilisin/kexin type 9 inhibitors and RNA-targeted agents offer promising approaches to mitigating Lp(a)-mediated risk. This review summarizes current insights into the pathophysiological role of Lp(a) in HRP formation and progression, integrating evidence from genetic, mechanistic, and imaging studies, while highlighting emerging therapeutic strategies. Nonetheless, continued research is essential to enhance our understanding of Lp(a)-driven plaque vulnerability and to inform precision-targeted cardiovascular prevention.

The fundamental mechanism of thoracic aneurysm dissection involves morphological and functional reorganization of the aorta, accompanied by a reduction in the biomechanical parameters of the arterial wall. Functional zones with high receptor density are distinguished along the aorta. The autonomic reflex arc ensures the functional feasibility for a virus to penetrate the functional zones of the aorta. Numerous clinical and experimental studies demonstrated that necrotic changes specific to aneurysms develop in the middle sheath of the aorta. Therefore, necrosis of the aortic media may result from damage by the virus to the middle layer of the aorta. Further research should focus on the potential role of herpesviruses in medial vascular wall necrosis. The development of antiviral therapy for patients with aortic aneurysms will help stop medial necrosis in the aortic wall and possibly reduce mortality rates.

Myocardial fibrosis represents a common pathological hallmark of various cardiovascular diseases progressing to heart failure, with the immunoinflammatory response playing a pivotal role in the pathogenesis of myocardial fibrosis. Accumulating evidence suggests that the immune microenvironment modulates myocardial fibrosis by regulating RNA epigenetic modifications, with 5-methylcytosine (m5C) methylation emerging as a key player in this process. This review systematically summarizes the characteristics of m5C methylation modification, the regulatory enzymes involved, and their biological functions in immunoinflammatory responses and myocardial fibrosis. Furthermore, this review examines the molecular mechanisms underlying m5C methylation-mediated regulation of myocardial fibrosis, encompassing the activation of immune cells, the transdifferentiation of cardiac fibroblasts, and the regulation of collagen metabolism. Moreover, the potential clinical implications of targeting m5C methylation for treating myocardial fibrosis are discussed, with an emphasis on future therapeutic prospects.

Acute type A aortic dissection (ATAAD) is a life-threatening cardiovascular surgical emergency with a mortality of 20–25%. This review offers an overview of current research on the morphology, taxonomy, epidemiology, and anesthetic, perfusion, and surgical strategies involved in ATAAD. Moreover, this review examines methods for predicting mortality risk and explores clinician–patient interactions, particularly those involving patients who refuse blood transfusions. The literature search included PubMed, Google Scholar, Web of Science, and ScienceDirect databases, as well as any relevant books. This review references 144 sources: 129 peer-reviewed articles and 15 book chapters or books. Modern classification systems utilize aortic zones based on the location of intimal tears and the extent of dissection; recent updates have included coronary artery dissection as an additional mapping criterion. Socioeconomic factors are linked to higher ATAAD incidence and poorer long-term survival post-surgery. The duration of global myocardial ischemia correlates with mortality and is a key element in the surgical strategy. Compared to deep hypothermic circulatory arrest (HCA), moderate HCA with cerebral perfusion provides benefits such as reduced bleeding and improved survival. Standard prediction models may not accurately assess risks in patients with life-threatening anemia who refuse blood transfusion. Therefore, incorporating Auckland and Hamilton anemia mortality risk scores alongside conventional tools can improve prognostic accuracy and support personalized management. An interpretive–deliberative model balances patient preferences with surgical outcomes, especially in bloodless surgery. Advances in surgical and endovascular management, as well as postoperative strategies for residual aortic disease, have also been explored. Significant progress has been made in assessing in-hospital mortality, improving doctor–patient communication, refining anesthetic and perfusion techniques, and enhancing surgical management of ATAAD. However, further research is needed to validate these approaches.

Mechanical complications following acute myocardial infarction (MI) represent some of the most challenging conditions in contemporary cardiology, often leading to rapid clinical deterioration and high mortality despite advances in reperfusion therapy. These complications span a spectrum of presentations, from early-phase structural disruptions such as ventricular septal rupture, papillary muscle rupture with acute mitral regurgitation (MR), and left ventricular free wall rupture (LVFWR), to later-stage manifestations, including true ventricular aneurysms and pseudoaneurysms. While surgical intervention has traditionally been considered the standard of care, surgical intervention is often associated with prohibitive risk in hemodynamically unstable or frail patients. In this context, transcatheter approaches have gained traction as viable, less invasive alternatives, offering the potential for hemodynamic stabilization, symptom relief, and improved short-term outcomes in selected patients. Nonetheless, data from observational studies and registry-based analyses remain limited, underscoring the need for further research. This review synthesizes the current evidence base and clinical experience related to transcatheter management of mechanical complications after MI, emphasizing patient selection, procedural strategies, device selection, and reported outcomes.

Pulsed field ablation (PFA) represents a paradigm shift in cardiac ablation technology. Indeed, PFA, a non-thermal technique, achieves homogeneous tissue effects by delivering ultrashort, high-frequency electric pulses. Moreover, PFA has emerged as a prominent ablation strategy in electrophysiology laboratories worldwide. While current clinical evidence demonstrated promising outcomes and expanded applications for existing PFA platforms, energy-specific difficulties complicated the definition of safety boundaries, particularly in patients with clinical complications. Furthermore, substantial heterogeneity among commercial PFA systems impeded procedural standardization. Therefore, this review aimed to synthesize contemporary perspectives on mitigating these energy-specific adverse events, with emphasis on modifiable perioperative factors. The evidence of safety across commercially available PFA systems with divergent catheter design philosophies was concurrently evaluated to examine how design strategies influence procedural safety profiles.

Hypertrophic cardiomyopathy (HCM) is a prevalent cardiac disease characterized by marked phenotypic variability. Recent advances in diagnosis and treatment have allowed a personalized approach to the treatment of this disease. Depending on the predominant phenotype, management can be tailored to address left ventricular outflow tract obstruction, heart failure, arrhythmia control, and/or sudden cardiac death prevention. This review highlights recent advances that have transformed the therapeutic landscape of HCM. Modern imaging techniques have improved sudden cardiac death risk stratification. The development of myosin inhibitors represents a paradigm shift in the treatment of symptomatic obstructive HCM. Invasive septal reduction techniques have also evolved, with novel approaches such as percutaneous intramyocardial septal radiofrequency ablation and transapical beating-heart septal myectomy. Finally, gene-targeted therapies including replacement, editing and silencing approaches, are emerging as promising strategies for HCM management.

Atherosclerosis (AS), the primary pathological basis for cardiovascular disease (CVD), is initiated by endothelial dysfunction. This review aimed to summarize the current understanding of endothelial cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of AS and to explore the potential of using PCSK9 as a therapeutic target. Endothelial PCSK9 contributes to AS progression by regulating lipid metabolism through low-density lipoprotein receptor (LDLR) degradation and promoting inflammatory responses, oxidative stress, endothelial apoptosis, and increased vascular permeability. Recent evidence indicates that endothelial-derived PCSK9 is upregulated under pathological conditions and exerts multiple atherogenic effects independent of circulating PCSK9. Experimental studies have demonstrated that silencing or inhibiting endothelial PCSK9 alleviates endothelial dysfunction, reduces plaque development, and mitigates inflammatory responses. Moreover, PCSK9 may modulate the redox balancing and cellular signaling pathways involved in vascular homeostasis. Endothelial PCSK9 plays a critical role in the initiation and progression of AS through mechanisms beyond lipid regulation. Targeting endothelial PCSK9 may represent a novel and promising strategy for preventing and treating AS, warranting further preclinical and clinical investigation.

Minimally invasive mitral valve repair (MI-MVr) is the preferred treatment approach in experienced centers for mitral valve disease (MVD), offering reduced surgical trauma and fast recovery. However, limited operative exposure and increased procedural complexity can represent a challenge in complex MVD. This narrative review provides an overview of current literature on clinical outcomes of MI-MVr in challenging MVD scenarios, such as mitral valve (MV) endocarditis, annulus calcification, and mitral annular disjunction, in the context of myxomatous MVD. Despite the complex anatomy and MVD, MI-MVr is non-inferior in long-term outcomes in treating MV endocarditis, MV calcification, and myxomatous MVD with mitral annular disjunction. Nonetheless, careful patient selection and referral to high-volume centers, where surgeons with expertise in MI-MVr operate, are key elements for achieving a durable, patient-tailored repair with an optimal long-term outcome in treating complex MVD.

Atherosclerosis (AS) is a significant contributor to cardiovascular disease, characterized by abnormal lipid metabolism, cellular apoptosis, oxidative stress, and chronic inflammation. Ferroptosis represents a form of non-apoptotic programmed cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and the peroxidation of membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). The ferroptosis of endothelial cells (ECs) and macrophages plays a crucial role in the development of atherosclerotic plaques. This review summarizes the mechanisms and associated therapeutic targets related to ferroptosis in macrophages and ECs within the context of AS. Recent research has made substantial progress in elucidating the mechanisms through which ferroptosis influences AS progression; however, a comprehensive understanding of the precise molecular basis for AS remains essential. Moreover, further clinical trials of drugs targeting ferroptosis are necessary. This review updates the knowledge of ferroptosis in ECs and macrophages related to AS, identifies potential links and the subsequent implications for plaque stability, and serves as a reference for developing new pharmacological strategies to address AS and stabilize vulnerable plaques.