Abstract: Obstructive Sleep Apnea is a prevalent condition characterized by recurrent upper airway collapse during sleep, leading to intermittent hypoxemia and sleep fragmentation, with significant implications for cardiovascular health (Yeghiazarians et al., 2021). Alarmingly, between 40% and 80% of individuals with cardiovascular diseases, including acute coronary syndrome, ischemic heart disease, chronic heart failure, cerebrovascular accidents, and arrhythmias, also suffer from OSA (Nguyen et al., 2024). This high comorbidity underscores the critical need for understanding the intricate pathophysiological links between OSA and cardiovascular morbidity (Deviaene et al., 2017). Despite its significant prevalence, OSA remains underdiagnosed in a substantial portion of the population, particularly in middle-aged cohorts, where cardiovascular disease risk begins to escalate (Peker et al., 2002). The presence of OSA is a significant risk factor for various cardiovascular comorbidities, including hypertension, coronary artery disease, and heart failure, with its prevalence ranging from 2% to 26% in the general population depending on demographic factors (Ivanovski et al., 2023; Jaswal et al., 2024). Furthermore, global epidemiological data indicate a rising prevalence of OSA, largely attributed to the increasing rates of obesity and the enhanced sensitivity of diagnostic methodologies like advanced polysomnography (Frangopoulos et al., 2021). This rise in prevalence contributes to a significant burden of associated comorbidities, including neuropsychiatric dysfunction and metabolic syndrome, beyond the well-established cardiovascular and cerebrovascular risks (Bikov et al., 2020). Given this context, our cross-sectional analysis aims to elucidate the specific relationships between OSA severity and various indicators of cardiovascular morbidity within a middle-aged cohort.

Abstract: Background: Acute pulmonary embolism (PE), particularly massive and high-risk submassive PE, carries mortality rates exceeding 50% and 15%, respectively. Anticoagulation alone does not effectively reduce mortality. Thrombolytic therapy improves outcomes but poses a substantial bleeding risk. Indigo aspiration thrombectomy alleviates right ventricular pressure overload in acute massive or high-risk submassive PE; however, its effect on PE-related mortality is unknown. This study aimed to determine whether Indigo aspiration thrombectomy improved right heart function and reduced PE-related mortality. Methods: This retrospective cohort study included 46 patients diagnosed with acute massive or high-risk submassive PE who underwent Indigo aspiration thrombectomy between January 2020 and August 2025. The study was conducted in the intensive care unit at China Medical University Hospital, Taichung, Taiwan. Efficacy endpoints were right heart parameters; safety endpoints included major bleeding events and 90-day mortality. Kaplan–Meier survival curve analysis was also performed. Results: Indigo aspiration thrombectomy significantly improved right heart parameters. Pulmonary artery (PA) systolic and mean pressures decreased by 23% (from 57.2 to 44.3 mmHg, p = 0.001; from 35.0 to 26.8 mmHg, p < 0.001). PA pulsatility index increased by 50%, and the right ventricular to left ventricular diameter ratio decreased by 30%. For acute massive PE, the major bleeding rate was 31.3% and PE-related mortality was 25.0%. For acute high-risk submassive PE, the major bleeding and PE-related mortality rates were both 3.3%. Conclusions: Indigo aspiration thrombectomy considerably improves right heart failure and may reduce PE-related mortality in patients with acute massive or high-risk submassive PE.

Abstract: Obesity, sleep-disordered breathing (SDB), and epicardial adipose tissue (EAT) are increasingly recognized as interconnected contributors to cardiometabolic and cardiovascular disease, although they are often addressed as distinct clinical conditions. This narrative review aims to integrate current evidence on the reciprocal pathophysiological interactions linking these entities and their contribution to cardiovascular remodeling. A comprehensive literature search up to May 2025 was performed, focusing on clinical, imaging, and mechanistic studies examining obesity, SDB, EAT, and cardiovascular outcomes. Available data indicate that obesity promotes visceral and epicardial fat expansion, systemic inflammation, and altered cardiopulmonary mechanics, thereby facilitating the development of SDB. In turn, intermittent hypoxia and sympathetic activation associated with SDB further aggravate adipose tissue dysfunction and inflammatory activation of EAT. As a metabolically active fat depot in direct anatomical continuity with the myocardium and coronary arteries, EAT contributes to myocardial fibrosis, atrial remodeling, diastolic dysfunction, and coronary atherosclerosis through paracrine inflammatory and neurohumoral pathways. The convergence of these mechanisms delineates a high-risk cardiometabolic phenotype associated with atrial fibrillation, coronary artery disease, and heart failure with preserved ejection fraction. Recognizing obesity, SDB, and EAT as components of an integrated cardiometabolic system may support improved phenotypic stratification and inform more comprehensive approaches to residual cardiovascular risk.

Abstract: Vascular dysfunction lies at the core of cardiovascular diseases—the leading cause of global morbidity and mortality. Despite their prevalence, therapeutic options remain limited, in part due to an incomplete understanding of the molecular mechanisms driving vascular pathology. The Integrated Stress Response (ISR), an evolutionarily conserved signaling network activated by di-verse stressors, represents a critical but underexplored mechanism in vascular biology. This re-view examines the dual roles of the core ISR kinases—PERK, GCN2, HRI and PKR—in vascular homeostasis and pathology, including atherosclerosis, pulmonary hypertension, and angiogenesis. We advance a conceptual framework in which the ISR functions as a context-dependent, double-edged sword: while PERK and PKR promote inflammation, apoptosis, and vascular re-modeling, GCN2 mediates protective effects. The outcome of ISR activation is shaped by cell type, stress duration and intensity, and downstream signaling bias (e.g., ATF4 vs. CHOP dominance). We further discuss pharmacological ISR modulators—including 2-aminopurine, C16, salubrinal, halofuginone, GSK2606414, and GSK2656157—which have demonstrated beneficial effects in preclinical models by suppressing inflammation, reducing apoptosis, and attenuating disease progression. Collectively, the ISR emerges as a critical regulatory node in vascular pathophysiology, and its selective, context-aware modulation represents a promising avenue for therapeutic intervention.

Abstract: Introduction: Hyperkalemia is a common complication in patients with heart failure (HF) and is associated with increased mortality, a higher risk of hospitalization, and interruption of evidence-based neurohormonal therapies. In Costa Rica, however, information regarding its frequency, clinical characteristics, and management remains limited. Methods: This observational, descriptive, and retrospective study was conducted at the Heart Failure Clinic of Hospital Clínica Bíblica (San José, Costa Rica) between June 2015 and June 2025. Cases were identified through the institutional dis-pensing registry of sodium polystyrene sulfonate (SPS), allowing capture of episodes specifically treated with this med-ication. Patients with confirmed HF were included, while those with stage V chronic kidney disease (CKD), those on dialysis, and individuals with incomplete medical records were excluded. The observed proportion of SPS-treated hy-perkalemia was estimated using the total number of unique HF patients treated during the same period as the denomi-nator. Demographic data, comorbidities, pharmacologic therapy, hyperkalemia severity, and clinical management were collected. Results: A total of 355 medical records were reviewed, of which 42 corresponded to HF patients who experienced hyperkalemia treated with SPS. Among 11,805 unique HF patients in the institutional database during the study period, the observed proportion was 0.37%, with annual variation between 0.26% and 2.1%. The cohort consisted predominantly of older adults, 74% of whom were aged 80 years or older. Thirty-five patients had CKD (mainly stages 3 and 4), and 21 had diabetes mellitus. Severe hyperkalemia was the most common presentation (61.9%), followed by moderate (28.6%) and mild (9.5%) cases. According to chronic treatment lists, 30 patients were re-ceiving RAAS inhibitors and 21 were receiving MRAs at the time of the episode. Discontinuation of spironolactone was the most frequent therapeutic intervention, while RAAS inhibitors were generally maintained or dose-adjusted. Two deaths occurred during follow-up, both attributed to HF decompensation, with no arrhythmias documented before death. Conclusions: In this private-center registry, the observed proportion of SPS-treated hyperkalemia in HF patients was low, although this reflects methodological constraints and does not represent the true incidence of hyperkalemia. The identified cases occurred in a clinically vulnerable population characterized by advanced age, multimorbidity, and a high prevalence of CKD. The predominance of severe hyperkalemia and frequent MRA discontinuation underscore the challenge of bal-ancing hyperkalemia risk with the need to maintain therapies with established prognostic benefit. These findings high-light the importance of strategies that support continuation of guideline-directed medical therapy and underscore the need for future multicenter studies,i ncluding patients with advanced CKD to better characterize the burden of hyper-kalemia in HF populations in Costa Rica.

Abstract:

Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Although substantial therapeutic advances have been made over the past decades, the years 2024–2025 mark a turning point characterized by the emergence of mechanistically innovative, disease-modifying therapies that go beyond conventional risk-factor control. This narrative review aims to synthesize transformative pharmacological and regulatory milestones reshaping contemporary cardiovascular practice and establishing a roadmap for precision medicine implementation. Methods: We conducted a comprehensive narrative review of pivotal clinical trials, regulatory approvals and mechanistic frameworks for emerging cardiovascular therapeutics approved or under investigation during 2024–2025. The analysis encompasses novel agents across multiple disease domains including transthyretin amyloid cardiomyopathy (ATTR-CM), resistant hypertension, dyslipidemia, pulmonary arterial hypertension, hypertrophic cardiomyopathy, and cardiometabolic disease, with emphasis on their molecular targets, clinical efficacy, and practice-changing implications. Results: Key therapeutic advances include acoramidis and vutrisiran for ATTR-CM demonstrating significant reductions in cardiovascular mortality and hospitalization; aprocitentan for resistant hypertension alongside investigational angiotensinogen silencers and aldosterone synthase inhibitors; RNA-based dyslipidemia therapies (inclisiran, lepodisiran, pelacarsen, olezarsen) enabling durable lipid control; sotatercept introducing disease modification in pulmonary arterial hypertension; cardiac myosin inhibitors (mavacamten, aficamten) transforming hypertrophic cardiomyopathy management; and GLP-1 receptor agonist semaglutide receiving FDA approval for cardiovascular risk reduction in obesity. These agents collectively demonstrate mechanistic targeting, genetic precision, and disease modification beyond traditional risk-factor management. Conclusions: Cardiovascular medicine is transitioning from symptomatic palliation toward an era defined by molecular pathway targeting, individualized therapy, and durable disease control, establishing a new paradigm for precision cardiovascular care.

Abstract: Neonatal arrhythmias, though relatively uncommon, can range from benign self-limiting conditions to life-threatening disorders requiring intensive management. Data on their clinical spectrum, management, and outcomes remain limited. This study aimed to evaluate the types, frequency, clinical characteristics, treatment strategies, and prognosis of neonatal arrhythmias in a tertiary pediatric cardiac center. We retrospectively reviewed neonates diagnosed with arrhythmia within the first 28 days of life at Basaksehir Cam and Sakura City Hospital between January 1, 2021, and May 1, 2025. Demographic data, electrocardiographic and echocardiographic findings, treatment modalities, recurrence, morbidity, and mortality were analyzed. Patients were categorized as having benign or non-benign arrhythmias. 65 neonates (57% male, mean weight 3,2 kg) were included. Non-benign arrhythmias were more frequent (77%) compared to benign arrhythmias (23%). Supraventricular tachycardia (35%) was the most common non-benign arrhythmia, followed by long QT syndrome (10,7%) and complete atrioventricular block (9,2%). Antiarrhythmic therapy was required in 55% of patients. Pacemaker implantation was performed in seven infants with conduction disorders. Recurrence occurred in 3% of cases, exclusively among patients with supraventricular tachycardia. During a median follow-up of 12,8 months, no mortality was observed. Prenatal diagnosis and early management contribute to favorable outcomes, as reflected in the absence of mortality in this cohort. Larger, prospective studies are warranted to define optimal management strategies and treatment durations for neonatal arrhythmias.

Abstract:

Background/Objectives: Atrial fibrillation (AF) is closely associated with adverse remodeling of the left atrium (LA). This study evaluated the impact of LA diameter on long-term outcomes following radiofrequency ablation (RFA) of the pulmonary veins and assessed LA and left ventricular (LV) remodeling over a seven-year follow-up period. Methods: A total of 117 patients with symptomatic, drug-refractory AF underwent RFA. Structural remodeling was evaluated using echocardiography. Long-term outcomes were categorized using the Pulmonary Vein Isolation Outcome Degree (PVIOD), a four-level classification reflecting procedural and clinical success. Results: After seven years, 32.5% of patients who achieved successful sinus rhythm maintenance after a single RFA (PVIOD 1) demonstrated significant reverse remodeling of LA and LV. LA diameter decreased from 39.3±0.6 mm to 36.5±0.6 mm (p=0.0007); LV end-diastolic diameter (LVEDD) from 53.1±0.6 mm to 50.9±0.7 mm (p=0.008); LV end-systolic diameter (LVESD) from 34.7±0.8 mm to 32.0±0.1 mm (p=0.005); and LV ejection fraction (LVEF) increased from 56.8±0.8% to 62.1±1.1% (p=0.000008). Among patients with long-term success after multiple procedures (PVIOD 2; 29.1%), LA diameter decreased significantly from 41.9±0.7 mm to 40.2±0.6 mm (p=0.04), without significant ventricular changes. Patients achieving clinical success (PVIOD 3; 14.5%) showed no significant structural changes. Those with procedural and clinical failure (PVIOD 4; 23.9%) exhibited progressive negative remodeling: LA diameter increased from 44.7±0.7 mm to 47.4±0.7 mm (p=0.006); LVEDD from 52.8±0.9 mm to 57.1±0.6 mm (p=0.0006); LVESD from 36.5±1.1 mm to 40.7±1.2 mm (p=0.006); and LVEF decreased from 50.7±1.7% to 43.8±1.8% (p=0.004). Conclusions: Early and successful single RFA performed in patients with normal LA diameter is associated with complete reverse remodeling and prevention of AF recurrence. As LA size increases, the likelihood of achieving durable procedural success decreases, emphasizing the importance of timely intervention before significant left atrial enlargement develops.

Abstract: Background: Large language models (LLMs) are becoming progressively integrated into clinical practice; however, their role in cardiovascular (CV) prevention remains unclear. This review synthesises current evidence on LLM applications in preventive cardiology and proposes a governance framework for their safe translation into practice. Methods: We conducted a comprehensive narrative review of literature published be-tween January 2015 and November 2025. Evidence was synthesised across three func-tional domains: (1) patient applications for health literacy and behaviour change; (2) clinician applications for decision support and workflow efficiency; and (3) system ap-plications for automated data extraction, registry construction, and quality surveillance. Results: Evidence suggests that while LLMs generate empathetic, guideline-concordant patient education, they lack the nuance required for unsupervised, personalized advice. For clinicians, LLMs effectively summarise clinical notes and draft documentation but remain unreliable for deterministic risk calculations and autonomous decision-making. System-facing applications demonstrate potential for automated phenotyping and mul-timodal risk prediction. However, safe deployment is constrained by hallucinations, temporal obsolescence, automation bias, and data privacy concerns. Conclusions: LLMs could help mitigate structural barriers in CV prevention but should presently be deployed only as supervised “reasoning engines” that augment, rather than replace, clinician judgment. To guide the transition from in silico performance to bedside practice, we propose the C.A.R.D.I.O. framework (Clinical validation, Auditability, Risk stratification, Data privacy, Integration, and Ongoing vigilance) as a roadmap for re-sponsible integration.

Abstract:

DES encodes the muscle specific intermediate filament protein desmin and mutations in this gene cause different cardiomyopathies. Here, we functionally validate DES-p.L112Q using SW-13, H9c2 cells and cardiomyocytes derived from induced pluripotent stem cells by confocal microscopy. These experiments reveal an aberrant cytoplasmic aggregation of mutant desmin. In conclusion, these functional analyses support the re-classification of DES-p.L112Q as a likely pathogenic variant leading to dilated cardiomyopathy.

Abstract: Objective: This study explores the utility of electrocardiogram parameters in conjunction with machine learning models for the early diagnosis of neonatal transient tachypnea (TTN). TTN is a common cause of respiratory distress in neonatal intensive care units, and early diagnosis has the potential to reduce invasive interventions and shorten hospital stays. Methods: The study retrospectively examined data from 101 neonates diagnosed with TTN and 82 healthy neonates, utilizing parameters such as P, QRS, T angles, and frontal QRS-T angle obtained from ECG. Results: Decision Tree, Neural Network, Random Forest, Boosting, and Support Vector Machine models were utilized among the machine learning algorithms. The dataset was split into 65% for training, 20% for validation, and 15% for testing. According to the findings, the Random Forest classification model demonstrated superior performance compared to other models, achieving 71.4% test accuracy, an average AUC value of 0.790, and a Matthews Correlation Coefficient of 0.443. The MCC value indicated that the Random Forest model possesses reliable predictive power even with imbalanced datasets. Notably, ECG parameters such as PR interval, V2 T voltage, and SV1 voltage were identified as the most significant features influencing the model's predictive performance. Conclusions: These findings suggest that ECG-based machine learning models can enhance clinical decision-making by facilitating non-invasive, rapid, and accurate diagnosis of TTN. Such artificial intelligence-driven systems hold the potential to mitigate unnecessary interventions, expedite treatment initiation, and improve neonatal prognoses. Future efforts should focus on enhancing model interpretability through the incorporation of explainable AI methodologies to facilitate their seamless integration into clinical practice.

Abstract: Lipoproteinassociated phospholipase A₂(Lp-PLA₂) connects oxidised lipid metabolism to vascular inflammation, however evidence of its role in Middle Eastern populations' cardiovascular disease (CVD) is lacking. We analysed circulating LpPLA₂, inflammatory markers, and mRNA expression in a Saudi population. To compare Lp-PLA₂, markers TNF α and IL 6, oxidised LDL, LP-a, and lipid profile between CVD patients and healthy controls, assess mRNA upregulation, and analyse correlations between Lp-PLA₂ and markers.30 healthy people and 30 people with CVD who had been diagnosed with atherosclerosis were compared in an investigation. Fasting blood plasma was analyzed via ELISA to determine hematological, biochemical, and cardiovascular biomarkers. Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), whole blood messenger RNA (mRNA) was analyzed for Lp-PLA₂, TNF α and IL 6. Compared with Healthy, CVD patients showed higher LpPLA₂ (419 ± 188 vs 101 ± 32 ng/mL; P<0.001), IL6 (74 ± 17 vs 40 ± 19 pg/mL; P<0.001), TNFα (4.4 ± 0.9 vs 3.7 ± 0.8 pg/mL; P<0.01), oxLDL (430 ± 143 vs 242 ± 67 pg/mL; P<0.001), and LP-a (134 ± 31 vs 90 ± 33 ng/mL; P<0.001), with a more atherogenic lipid profile (LDL 3.02 ± 0.63 vs 1.72 ± 0.63 mmol/L; P<0.001; HDL lower: P<0.01). mRNA expression of LpPLA₂, IL6, and TNFα was upregulated in CVD. LpPLA₂ correlated with IL6 (r=0.75, P<0.001), TNFα (r=0.36, P<0.01), oxLDL (r=0.85, P<0.001), and LDL (r=0.80, P<0.001). CVD is associated with concordant proteinlevel elevations and mRNA upregulation of LpPLA₂, IL6, and TNFα, supporting a feedforward inflammatory–oxidative axis. These data from a Saudi cohort extend international evidence and support targeting the LpPLA₂ cytokine oxidative pathway in atherosclerosis.

Abstract: Background: Transthyretin cardiac amyloidosis (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A structured narrative review of PubMed and Google Scholar was performed through November 2025 using predefined terms related to LBBAP and ATTR-CM. Peer-reviewed articles, case reports, case series, and relevant abstracts were included. Studies exclusively on light-chain cardiac amyloidosis were excluded. Results: Ten publications met inclusion criteria, comprising three case reports, five case series, one retrospective cohort without a comparator, and one cohort comparing LBBAP with cardiac resynchronization therapy (CRT). In total, 56 patients with ATTR-CM underwent LBBAP. Implantation success was high, with stable acute and mid-term electrical parameters. Follow-up (typically 3–12 months) showed stable electrical parameters with narrow paced QRS complexes and preserved or improved left ventricular ejection fraction in most reports. Symptomatic improvement and reductions in natriuretic peptides were variably described. No major lead-related complications were reported. Comparative data remain sparse and inconclusive. Conclusions: This review suggests that LBBAP is a feasible and safe pacing approach in patients with ATTR-CM and may help stabilize or improve heart failure symptoms. Further prospective studies are needed to confirm its clinical effectiveness.

Abstract:

Background: Channelopathies represent a heterogeneous group of rare inherited cardiac diseases associated with life-threatening arrhythmias. Our knowledge of their epidemiology in childhood is limited. The aim of this study is to evaluate the epidemiology of pediatric channelopathies on a Mediterranean island (Crete, Greece). Methods: Retrospective study of children < 18 years followed in the Regional Tertiary Pediatric Cardiology Unit during a 23-year period (2002-2024) and meeting the disease-specific diagnostic criteria. Results: A total of 34 children (27 families) were enrolled, corresponding to an average annual incidence of 1.2 (95% C.I.: 0.8 – 1.6) and a cumulative prevalence of 23.9 (95% C.I.: 16.1 – 34.1) cases per 100, 000 children, with significant though regional incidence differences. Long QT syndrome (n=33) was predominant, with a single exception of catecholaminergic polymorphic tachycardia. Diagnosis was based on symptomatic presentation (n=15, 44 %), preparticipation screening (n=6, 18%) or affected family cascade screening (n=13, 38%). They represented the first diagnosis within affected families (index cases) in 20/34 (58%) of cases. Genetic testing was performed in 27/34 (79%) channelopathy cases and it was positive in a single case of CPVT and in 23 out of 27 (89%) LQT cases in which it was performed, with a genotype of LQT2 in 13 (39%), LQT1 in 7 (21%), LQT3 in 1 (3%) and LQT5 in 2 (6%) cases. Conclusion: The incidence of pediatric channelopathies on the Mediterranean island of Crete was comparable to that reported in the literature, with regional though clusters of significant increased incidence. Further study of the epidemiology of pediatric channelopathies is needed, to document any regional or ethnic differences and for the best design of large-scale screening programs.

Abstract:

Background: Nanosecond pulsed electric field (nsPEF) is a nonthermal ablation technique that utilizes ultra-rapid electrical pulses to induce selective cell death with minimal inflammatory response. The objective of this study was to evaluate the safety and efficacy of percutaneous intramyocardial septal nsPEF ablation (PIMSNA) for septal reduction therapy (SRT) in a canine model (Labrador dogs). Methods: The acute and chronic effects of this novel PIMSNA approach under transthoracic echocardiography (TTE) guidance were comprehensively assessed. The optimal ablation parameters for inducing the targeted myocardial pathological process were selected. The major adverse events monitored included post-ablation endocardial regional edema, arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, atrioventricular conduction block), pericardial effusion, and cardiac tamponade. The assessment of acute and chronic effects was conducted over a 90-day follow-up period using serial TTE imaging, electrocardiographic parameters, blood biochemistry analyses, and histopathological evaluation. The intervention was performed on Labrador canines. Results: The experimental findings demonstrated that an applied voltage of 3,000 volts yielded the most effective ablation outcome. TTE-guided PIMSNA procedures resulted in a 10% impedance decline within the targeted region, indicative of successful ablation. The motion amplitude and systolic wall thickening rate demonstrated a substantial decrease and remained persistently low in the ablated septal region. However, septal thickness exhibited no substantial alterations subsequent to PIMSNA. Histological examination confirmed the presence of cardiomyocyte death, characterized by progressive cytoplasmic hyperchromasia and nuclear pyknosis. A notable observation is the minimal presence of acute-phase inflammatory cell infiltration. There were no instances of sustained ventricular tachycardia, ventricular fibrillation, or atrioventricular conduction block during PIMSNA. Conclusion: The novel PIMSNA technique effectively induced myocardial injury and regional hypokinesis without significant acute edema. Histopathological analysis revealed significant programmed cell death of cardiomyocytes accompanied by minimal inflammatory cell infiltration.

Abstract: Advances in computed tomography (CT) technology have made it possible to perform non-invasive imaging with detailed characterization and quantification of the myocardium. Cardiac CT (CCT) has emerged as a technique useful for providing deeper insights into cardiovascular diseases, as a valuable alternative when cardiac magnetic resonance imaging or echocardiography are contraindicated, technically unfeasible, inconclusive, or non-diagnostic. Cardiac tissue characterization by the advances in CT technology lead to differentiate myocardial tissue types with high resolution. CCT allows the assessment of tissue properties such as myocardial perfusion, fibrosis and fat infiltration, which are critical in diagnosing ischemic heart disease, microvascular obstruction, heart failure, cardiomyopathies, and other cardiac conditions 1. Thin surgical complications and prosthesis studies are possible through high resolution scanners, allowing to detect HALT, pannus, thrombosis, endocarditis, abscesses and other characterizations. The use of contrast agents, along with advanced imaging techniques such as photon-counting CT, allows for high-resolution imaging of tissue heterogeneity, making it a valuable tool for non-invasive evaluation. Dual-energy computed tomography (DECT) has emerged as a transformative tool in the non-invasive assessment of cardiac tissue, enabling a more precise characterization of myocardial structures and pathologies. Employing two distinct energy levels, it provide unique advantages in tissue differentiation through the energy-dependent attenuation of various tissues, allowing for better delineation of tissue properties such as fat, fibrosis, calcification, and water content, improving also quantitative imaging and iodine mapping. Furthermore, new methodologies like CT-based tissue characterization models and artificial intelligence algorithms are enhancing the accuracy of differentiating normal and pathological cardiac tissues. The integration of cardiac CT with other imaging modalities, such as cardiac magnetic resonance (CMR), is also highlighted as a promising approach for comprehensive cardiac tissue assessment in several clinical settings. [*] Aim and scope of the Special Issue: This paper reviews the current techniques for cardiac tissue characterization using CT, explores the role of texture analysis, and discusses the challenges in achieving precise tissue differentiation, outlining the current applications and future perspective of cardiac CT in myocardial tissue characterization.

Abstract: Background: A sternum-sparing approach of minimally invasive total coronary revascularization via left anterior thoracotomy (TCRAT) demonstrated favorable early and midterm results in unselected patients with coronary artery multivessel disease. However, safety and outcomes in elderly patients remain less well defined. Particularly in octogenarians with relevant comorbidities, data are scarce, and the role of TCRAT compared to conventional coronary artery bypass grafting (CABG) remains uncertain. This study aimed to evaluate in-hospital and midterm outcomes of TCRAT in patients aged ≥ 80 years. Method: From 11/2019 to 10/2025, CABG via left anterior minithoracotomy on cardiopulmonary bypass and cardioplegic arrest was performed as a routine procedure in 859 consecutive, nonemergency patients. Among them, 82 patients (9.5%) were octogenarians, all presenting with multivessel coronary artery disease. In this subgroup, mean BMI was 26.5 ± 3.1 kg/m², left ventricular ejection fraction was 49.2 ± 9.1% (range 20–55 %), and mean EuroSCORE II was 5.1 ± 2.4. Comorbidities included diabetes mellitus (24.4 %), chronic lung disease (7.3 %), prior PCI (23.2 %), and peripheral vascular disease (78.5 %). The mean follow-up (100 %) was 9.1 months. Results: Left internal thoracic artery was used in 98.8 %, radial artery was used in 43.9 %. A mean of 3.0 ± 0.9 (range 2-5) anastomoses per patient was performed. Total operation time was 299 ± 64 min (range 164 - 480). In-hospital mortality was 1.2 %, stroke rate was 1.2 %, myocardial infarction rate was 0 % and repeat revascularization rate was 1.2 %. At follow-up, all-cause mortality, myocardial infarction, repeat revascularization, and stroke was 4.9 %, 0 %, 2.4 %, and 1.2 %, respectively. Overall major adverse cardiac and cerebrovascular events rate (MACCE) was 7.3 % at follow up. Conclusion: TCRAT enables complete coronary artery revascularization in multivessel coronary artery disease without sternotomy and can be safely performed in octogenarians. Both in-hospital and midterm outcomes were favorable and comparable to contemporary outcomes of conventional CABG in elderly patients.

Abstract: It is now widely recognized that adipocytes have the ability to produce a myriad of bioactive compounds released into the circulation and affecting distal organs including the heart. These factors, termed adipokines, are also produced by various tissues in addition to adipocytes including cardiac tissue and have the ability to modulate cardiac function and the response to pathology. Among the processes greatly affected by adipokines is myocardial remodelling due to hypertrophy and fibrosis, two processes which contribute to the development of heart failure. This is particularly relevant under conditions of obesity and the accompanied increased adiposity in general resulting in increased adipokine production. The effects of adipokines on cardiac remodelling can be both beneficial or adverse, depending on adipokine type such as adiponectin and leptin, respectively. The molecular bases underlying the effects of adipokines on myocardial remodelling have been extensively studied and likely involved a multiplicity of cell signalling processes thus demonstrating substantial complexity. Emerging evidence suggests that these proteins play an important role in cardiac pathology. Their precise contribution is yet to be determined with certainly as this likely reflects a balance between pro-remodelling and anti-remodelling factors.

Abstract: Background/Objectives: Cardiac arrhythmias are among the leading causes of sudden cardiac death (SCD). Pathogenic variants in potassium channel genes play a key role in inherited arrhythmia syndromes, yet their contribution in Central Asian populations remains poorly characterized. Methods: We performed targeted next-generation sequencing (NGS) using a 96-gene custom Haloplex panel in 79 Kazakhstani patients with clinically diagnosed arrhythmias, including atrioventricular block, sick sinus syndrome, and atrial fibrillation. Detected variants in potassium channel genes were classified according to ACMG guidelines and correlated with clinical phenotypes. Results: A total of 52 variants were identified across 11 potassium channel genes. Two likely pathogenic variants (KCNH2 p.Cys66Gly and p.Arg176Trp) and six variants of uncertain significance (VUS) in KCNQ1, KCNE2, KCNE3, and KCNJ8 were detected. Two novel previously unreported variants were found in KCNE5 and KCND3. Patients harboring pathogenic variants commonly presented with early-onset arrhythmias or a positive family history of cardiovascular disease. Carriers of KCNH2 variants exhibited mild QT prolongation and recurrent syncope. Conclusions: This is the first genetic study of potassium channel gene mutations in Kazakhstani patients with cardiac arrhythmias. Detection of pathogenic and novel variants highlights the clinical utility of integrating genetic testing into diagnostic and management pathways for arrhythmia syndromes. Population-specific genomic data are essential for improving risk stratification, guiding medication safety, and enabling cascade family screening in Central Asia.

Abstract: Background Stage B heart failure (SBHF) increases the risk of symptomatic HF. Current guideline criteria for SBHF lack sex and ethnic thresholding and cardiac magnetic resonance (CMR) imaging cut-offs. We aimed to assess the prevalence of SBHF in a large cohort of people with T2D and healthy controls, and propose a refined CMR definition for SBHF. Methods Sex and ethnic specific thresholds for imaging criteria were derived from 373 healthy controls, who underwent CMR cine imaging. The current definition for SBHF and refined criteria were applied to our prospectively recruited and intensively phenotyped cohort of asymptomatic people with T2D and no evidence of cardiovascular disease. The prevalence of SBHF by different definitions was calculated and patient characteristics, including exercise capacity, were compared between those classified as Stage A vs. B HF. Finally, the refined criteria were also applied to two historical cohorts with symptomatic cardiovascular disease: severe aortic stenosis (AS n=70) and HF with preserved Ejection Fraction (HFpEF n=136). Results A total of 423 people with T2D and a subset of 102 healthy controls who underwent echocardiography were prospectively recruited. Current guideline criteria classified 91% of those with T2D and 69% of the healthy controls as SBHF, suggesting a lack of specificity. Applying derived sex and ethnicity specific thresholds, combining echo and CMR measures, the prevalence of SBHF was reduced to 30% in those with T2D. Those with Stage B HF in the refined definition had lower exercise capacity than those with Stage A HF (percentage predicted maximal oxygen consumption 81 ± 16% vs 91 ± 20%, p< 0.001). Applying the refined definition to symptomatic AS and HFpEF participants classified 89% and 85% with abnormal cardiac remodelling. Conclusion Current guideline criteria for SBHF are non-specific and likely of limited value in clinical practice. Refining these criteria with sex- and ethnic-specific thresholds may improve identification of those at risk of developing symptomatic disease. Further research is required to validate these criteria.