Highlights     

• Coronary microvascular dysfunction (CMD) is a pathophysiological condition characterized by impaired regulation of coronary microvascular tone and structure in the absence of obstructive epicardial artery disease. CMD is now recognized as a major contributor to myocardial ischemia, particularly in patients with angina and normal coronary angiograms (INOCA), as well as in cases of myocardial infarction with non-obstructive coronary arteries (MINOCA). The key mechanisms underlying CMD include impaired endothelium-dependent vasodilation, excessive vasoconstriction, inflammation, and capillary remodeling.
• The molecular regulation of coronary blood flow involves a complex network of signaling cascades, including ion channels, nitric oxide (NO), endothelin-1, cytokines, and regulatory non-coding RNAs. Single nucleotide polymorphisms (SNPs) in genes encoding these mediators and enzymes significantly affect microvascular function. Notably, SNPs in NOS3, KCNJ11, JAK2, HMOX1, VEGFA, and other genes have been associated with altered vasomotor reactivity, oxidative stress, inflammatory activation, and impaired angiogenesis.
• MicroRNAs (miRNAs) play a particularly important role in the pathogenesis of CMD by regulating gene expression at the post-transcriptional level. Dysregulation of miRNAs such as miR-126, miR-155, and miR-30 has been linked to endothelial dysfunction, reduced capillary density, and impaired myocardial energy metabolism. The interplay of molecular and genetic factors provides a mechanistic framework for CMD and offers new opportunities for personalized approaches in the diagnosis, prognosis, and treatment of microvascular forms of ischemic heart disease.

Abstract

Coronary microvascular dysfunction (CMD) has increasingly been recognized as an independent and clinically significant pathophysiological mechanism of myocardial ischemia, even in the absence of obstructive coronary artery disease. CMD is caused by both functional impairments, such as imbalance between vasodilation and vasoconstriction–and structural alterations of the microcirculatory network. Recent research highlights the crucial role of molecular and genetic factors in the development of CMD, including single nucleotide polymorphisms (SNPs) in genes encoding endothelial nitric oxide synthase (NOS3), ion channel subunits (KCNJ11, CACNA1C), inflammatory and angiogenic mediators (JAK2, VEGFA, HMOX1). In addition, the antioxidant system plays an important role in the pathogenesis of coronary microcirculatory dysfunction, which is involved in maintaining vascular homeostasis and protecting against oxidative stress. The main studied genes of the antioxidant system include SOD1–3, GPX1, CAT, HMOX1 and NOX2/NOX4, which provide a balance of production and utilization of reactive oxygen species and play a significant role in the pathophysiology of the vascular wall. Of particular interest are microRNAs that regulate the expression of genes involved in vascular reactivity, angiogenesis, oxidative stress, and inflammation. Dysregulation of microRNAs such as miR-126, miR-155, and miR-30 has been associated with endothelial dysfunction and capillary remodeling. This review explores key signaling pathways and molecular mechanisms underlying CMD, with a focus on their genetic and epigenetic modulation. A better understanding of these processes opens new perspectives for the development of personalized diagnostic and therapeutic approaches in microvascular forms of ischemic heart disease.

Highlights

• Sudden cardiac death (SCD) in children and adolescents engaged in sports is a rare but serious event that demands special attention from both medical and athletic communities. The main causes of SCD include cardiomyopathies, coronary artery anomalies, channelopathies, congenital heart defects, and aortopathies. Physical exertion can trigger fatal arrhythmias, especially in predisposed individuals.
• Modern approaches emphasize individualized risk assessment using ECG, stress testing, cardiac imaging, and, when necessary, genetic testing. Instead of strict restrictions, a shared decision-making model is promoted, taking into account both clinical data and the athlete’s personal goals.
• Emergency preparedness plays a key role: availability of defibrillators, CPR training, and established response protocols are essential. This personalized approach helps ensure safety while preserving the quality of life for young athletes.

Abstract

Sudden cardiac death (SCD) in children and adolescents is a rare but potentially catastrophic event, particularly in the context of athletic activity. Despite its low incidence, SCD significantly impacts strategies for screening, clearance, and monitoring of young athletes. The aim of this review is to summarize current data on the epidemiology, etiology, risk factors, and clinical management of pediatric patients at risk of sudden cardiac arrest during physical exertion. The most common causes of SCD in the pediatric population include hypertrophic cardiomyopathy, coronary artery anomalies, dilated and arrhythmogenic cardiomyopathies, inherited channelopathies (including long QT syndrome and catecholaminergic polymorphic ventricular tachycardia), as well as congenital heart defects and aortopathies. This review emphasizes the underlying pathophysiological mechanisms linking exercise to arrhythmogenesis and highlights the importance of individualized risk stratification using ECG, exercise testing, cardiac imaging, and genetic evaluation. Contemporary guidelines from major professional organizations (AHA/ACC/AMSSM/HRS/PACES/SCMR) increasingly advocate for a shared decision-making approach, moving away from blanket restrictions. This model considers both clinical risk and the athlete’s personal goals and values. Emergency preparedness in athletic settings is also discussed, including staff training and the strategic placement and maintenance of automated external defibrillators. This review aims to inform a personalized, evidence-based approach to sports eligibility for children and adolescents with cardiovascular conditions, helping to ensure a careful balance between safety and quality of life through collaborative planning, education, and emergency readiness.

Highlights

• Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is an effective treatment option for patients with refractory angina, contributing to improved quality of life and reduction of ischemic symptoms, provided that patient selection and procedural planning are carefully performed.
• Preprocedural planning, including dual-contrast angiography, coronary computed tomography angiography, and the use of validated scoring systems (J-CTO, PROGRESS-CTO, CT-RECTOR), plays a critical role in selecting the optimal interventional strategy and minimizing the risk of complications.
• An algorithmic approach and multidisciplinary collaboration enhance the success and safety of CTO PCI, particularly when hybrid and global strategies are employed and tailored to the anatomical features of the lesion.

Abstract

Chronic total occlusions of the coronary arteries (CTO) represent one of the most complex forms of coronary artery disease, occurring in approximately 15–20% of patients with ischemic heart disease undergoing coronary angiography. Despite the long-standing absence of a unified treatment strategy, the interventional approach to CTO has undergone significant transformation in recent decades. This evolution is largely driven by advancements in imaging technologies, improvements in guidewire and catheter systems, and the implementation of algorithmic decision-making in procedural planning. Percutaneous coronary intervention (PCI) for CTO enables effective relief of anginal symptoms, improvement in quality of life, and enhancement of functional status, while minimizing the risk of serious complications. A critical factor in procedural success is thorough preprocedural planning, which includes dual-injection coronary angiography, coronary computed tomography angiography (CTCA), and assessment of anatomical complexity using scores such as J-CTO, PROGRESS-CTO, and CT-RECTOR. The use of hybrid and global CTO management algorithms, tailored to lesion morphology, facilitates individualized strategies and improves procedural outcomes. Operator experience, availability of dedicated equipment, and cohesive team coordination are also pivotal to clinical success. This review summarizes current approaches to the diagnosis, planning, and execution of PCI in CTO cases, emphasizing the importance of a multidisciplinary approach and the role of advanced imaging modalities in enhancing the safety and efficacy of interventional treatment.

Highlights      

• Sorbs2 is an adaptor and cytoskeletal protein predominantly expressed in the cardiovascular system-specifically in cardiomyocytes, vascular smooth muscle cells, and endothelial cells. It plays a critical role in maintaining myocardial structural integrity, regulating contractility, and facilitating intercellular communication. In addition, Sorbs2 functions as an RNA-binding protein, influencing the stability and translation of mRNAs that encode essential ion channels and junctional proteins.
• Sorbs2 dysfunction is associated with a wide range of cardiovascular diseases, from cardiomyopathies and arrhythmias to dyslipidemia, hypertension, and diabetic angiopathy. Sorbs2 expression varies depending on the type of pathology and disease stage. For example, in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, Sorbs2 levels are decreased, correlating with the severity of fibrosis, disruption of intercalated disc structure, and reduced ejection fraction. In pressure overload conditions (aortic constriction model), a compensatory increase in Sorbs2 expression has been observed during myocardial hypertrophy. Conversely, in diabetic vasculopathy, Sorbs2 expression in coronary arteries is reduced, which is linked to impaired BK-channel activity and decreased coronary perfusion.
• Given its multifunctionality and involvement in key processes underlying cardiovascular pathology, Sorbs2 is emerging as a promising molecular target. Its role in regulating inflammation, ion homeostasis, and myocardial structure suggests that Sorbs2 could serve as both a biomarker and a therapeutic target in cardiovascular diseases. However, further experimental and clinical studies are required to validate its diagnostic value and explore its full therapeutic potential.

Abstract

Sorbin and SH3 domain-containing protein 2 (Sorbs2) is a multifunctional adaptor protein that plays a key role in regulating cellular architecture, signal transduction, and gene expression in the cardiovascular system. Sorbs2 is highly expressed in cardiomyocytes, vascular smooth muscle cells, and endothelial cells, contributing to both the mechanical stability and electrical excitability of cardiac tissue. Recent studies have demonstrated that Sorbs2 is involved in the pathogenesis of a wide range of cardiovascular diseases, including dyslipidemia, atherosclerosis, hypertension, cardiomyopathies, arrhythmias, atrial fibrillation, congenital heart defects, diabetic vasculopathy, and aortic aneurysms. Beyond its structural role as part of the cytoskeleton, Sorbs2 functions as an RNA-binding protein that regulates the stability and translation of mRNAs encoding proteins of ion channels and intercellular junctions, which are essential for cardiac conduction.. Dysregulation of Sorbs2 has been associated with myocardial fibrosis, atrial remodeling, and impaired cardiac contractility. Notably, the data on its role in inflammation are contradictory, highlighting the need for further investigation. This review summarizes current knowledge on the molecular biology of Sorbs2, its regulatory mechanisms, and its pathophysiological relevance in the context of cardiovascular diseases. The potential of Sorbs2 as a diagnostic biomarker and therapeutic target is discussed. A deeper understanding of Sorbs2 may open new avenues for personalized medicine and targeted treatment strategies in cardiovascular pathology.