Coronary artery aneurysm (CAA), coronary artery ectasia (CAE), and coronary slow flow phenomenon (CSFP) are coronary pathologies associated with altered hemodynamics and increased thrombotic risk. However, optimal antithrombotic management remains uncertain because of limited and heterogeneous evidence.

This systematic review aimed to synthesize data on the efficacy and safety of antiplatelet and anticoagulant therapies in patients with CAA, CAE, and CSFP.

Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and ProQuest were searched through September 2025 for randomized and observational studies evaluating antithrombotic therapy in adults with these conditions. Outcomes included major adverse cardiovascular events and major bleeding. Narrative synthesis was conducted using the SWiM framework. Risk of bias was assessed using ROBINS-I and RoB 2.0, and certainty of evidence using GRADE.

Eleven studies comprising 3271 participants were included: six on CAE (n = 895), four on CAA (n = 2356), and one on CSFP (n = 20). In CAE, dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC) were associated with fewer ischemic events than no therapy, although direct comparisons were inconsistent. The only randomized trial in CAE showed numerically lower recurrent myocardial infarction and cardiovascular death with single antiplatelet therapy (SAPT) plus direct oral anticoagulant (DOAC) versus DAPT, but findings were nonsignificant and based on few events. Evidence for CAA and CSFP remains limited and inconclusive.

Intensified antithrombotic therapy may benefit patients with CAE, but evidence remains inconclusive for CAA and CSFP. Large, multicenter randomized trials are warranted to establish condition-specific treatment recommendations.

Brain and muscle ARNT‑like 1 (BMAL1) is a core transcription factor of the molecular circadian clock and links daily timing with cardiovascular electrophysiology, metabolism, vascular function and inflammation. Altered BMAL1 expression or rhythmicity has been reported in arrhythmias, atherosclerosis, myocardial ischemia/reperfusion injury and heart failure. However, its specific role has remained elusive, as local effects in cardiovascular cells are often mixed with the broader effects of whole‑body circadian disruption. The present review addressed this gap by separating evidence from central and peripheral clocks, cell‑specific and systemic models, and experimental and human studies. Cardiomyocyte‑specific models provide relatively direct evidence that the local clock supports electrical stability, substrate use, mitochondrial homeostasis and contractile function. However, in endothelial cells, vascular smooth muscle cells and immune cells, the effects of BMAL1 are more variable and depend on cell type, metabolic conditions, disease stage and circadian phase. Human evidence remains mainly associative, whereas most mechanistic findings come from cell and animal studies. The present review also assessed small‑molecule clock modulators, chronotherapy and non‑pharmacological interventions, as well as time‑resolved multi‑omics and machine‑learning approaches. Current evidence does not support viewing BMAL1 as simply protective or harmful. A selective BMAL1‑binding small molecule has recently been identified, but its cardiovascular efficacy and safety have not been established. In addition, the clinical benefits of chronotherapy vary across treatments and patients. Further translation will require tissue‑specific human models, repeated sampling across biological time and prospective studies of treatment guided by individual circadian phases.

Neutrophil extracellular traps (NETs) are web‑like structures composed of decondensed chromatin and granular proteins. Initially identified as an antimicrobial defense mechanism, NETs have now been demonstrated to be profoundly involved in the processes of sterile inflammation, thrombosis and fibrosis in cardiovascular diseases. The present review systematically delineated the interaction networks between NETs and macrophages, monocytes, endothelial cells, fibroblasts and platelets, untangling NETs as a central hub that integrates the pathological triad of inflammation, thrombosis and fibrosis. Building on this foundation, the specific mechanisms of NETs in cardiac diseases, including acute myocardial infarction, atrial fibrillation and heart failure and in vascular diseases, such as atherosclerosis, hypertension and abdominal aortic aneurysm, are elaborated. Finally, from four dimensions, NETs degradation, targeting of NETs components, inhibition of NETosis formation and indirect intervention through inflammatory metabolic pathways, the preclinical evidence and translational bottlenecks of strategies such as DNase I, histone‑neutralizing agents and PAD4 inhibitors were systematically evaluated. The present review aimed to promote the transition of NETs from a fundamental pathological hub into a targetable node for cardiovascular therapy.

Permanent cardiac pacing has progressively evolved toward increasingly physiological strategies aimed at preserving or restoring ventricular electromechanical synchrony. Cardiac resynchronization therapy using biventricular pacing remains the established standard of care for patients with heart failure, reduced left ventricular ejection fraction and electrical dyssynchrony, particularly in the presence of left bundle branch block. However, anatomical constraints, suboptimal clinical and echocardiographic response, and procedural complexity have promoted the development of conduction system pacing. His bundle pacing and, more recently, left bundle branch area pacing directly recruit the His-Purkinje system and may provide faster and more physiological ventricular activation. This narrative review summarizes current indications, technical aspects, the most relevant clinical evidence in bradyarrhythmias and heart failure, and the evolution of dedicated tools and leads. Available data support conduction system pacing over conventional right ventricular pacing in patients with a high expected pacing burden, with potential benefits in terms of ventricular function and heart failure events. By contrast, its role as an alternative to conventional biventricular resynchronization remains debated.

The management of acute coronary syndromes remains largely grounded in the ST-elevation myocardial infarction (STEMI)/non-STEMI (NSTEMI) classification, a binary framework that assigns a central role to ST-segment elevation in guiding urgent revascularization. However, a substantial proportion of patients classified as NSTEMI may harbor an acute coronary occlusion, with consequent risk of delayed recognition and adverse clinical outcomes. This review focuses on how the suspicion of acute occlusive myocardial infarction (OMI) can be confirmed in the absence of traditional STEMI criteria. Emphasis is placed on the identification of subtle and dynamic ECG findings, including hyperacute T waves, reciprocal changes, posterior involvement, and evolving repolarization abnormalities, which may indicate ongoing coronary occlusion despite the lack of diagnostic ST-segment elevation. The emerging OMI/non-OMI paradigm challenges the traditional STEMI-centered approach by promoting a physiology-based interpretation of the ECG, integrating clinical presentation and serial biomarker assessment. In this context, the adoption of advanced tools, including artificial intelligence-powered ECG analysis, may enhance early recognition of occlusion patterns and support more timely decision-making. Improving the ability to identify OMI without STEMI criteria represents a critical step toward reducing treatment delays and optimizing clinical outcomes in patients with acute coronary syndromes.

Coronary artery fistulas (CAFs) are rare coronary anomalies, most often detected incidentally. Although frequently asymptomatic, complex fistulas may lead to myocardial ischaemia, heart failure, or other complications, and optimal management remains controversial.

A 68-year-old patient presented with exertional dyspnoea and dizziness. Coronary angiography revealed intermediate left anterior descending artery stenosis with negative fractional flow reserve and a large CAF. Multislice computed tomography demonstrated complex bilateral CAFs originating from both coronary arteries, with drainage into the superior vena cava, right atrium, and descending aorta. Cardiac magnetic resonance imaging showed preserved myocardial tissue characteristics without ischaemia or fibrosis. Following Heart Team discussion, conservative management with optimal medical therapy was chosen. At 2-year follow-up, the patient remained asymptomatic without adverse events.

This case illustrates an exceptionally rare presentation of bilateral CAFs with multiple atypical drainage sites. It highlights the value of multimodality imaging for comprehensive anatomical and functional assessment and supports individualized, Heart Team-guided management in the absence of clear guideline recommendations.

KAT6B-related disorders (KRDs) comprise a spectrum of developmental disorders ranging from Genitopatellar syndrome (GPS) to Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS), with increasing recognition of intermediate phenotypes. Although genotype-phenotype correlations have progressively emerged, the molecular basis of phenotypic variability remains incompletely understood. We performed comprehensive clinical phenotyping and trio-based whole-exome sequencing (WES) in two unrelated individuals carrying novel de novo KAT6B variants. Transcriptomic analysis was undertaken for the noncanonical intronic variant using peripheral blood-derived RNA. An updated review of molecularly confirmed KRDs was also performed to reassess genotype-phenotype correlations and protein domain-specific variant distribution. Patient 1 carried a novel nonsense variant (c.5347G>T, p.Glu1783Ter) and presented with a predominantly SBBYSS-like phenotype. Patient 2 harbored a novel noncanonical intronic variant (c.3665-21C>A) associated with a severe multisystem phenotype overlapping the GPS spectrum. RNA sequencing demonstrated preserved canonical exon 17-18 splicing but an approximately 50% reduction in KAT6B transcript abundance, supporting a dosage-sensitive pathogenic mechanism. Review of 203 published individuals identified 133 distinct pathogenic variants, confirmed exon 18 as the major mutational hotspot, and suggested domain-specific genotype-phenotype trends, including enrichment of SBBYSS-associated phenotypes among variants affecting the histone acetyltransferase (HAT) domain. Both patients also exhibited severe upper airway dysfunction with obstructive sleep apnea (OSA). These findings expand the molecular and phenotypic spectrum of KRDs, provide supportive transcriptomic evidence for a potential functional intronic variant, refine current genotype-phenotype correlations, and highlight upper airway dysfunction as a clinically relevant but likely underrecognized manifestation across the KRD spectrum.

Variants affecting minor (U12-type) intron splice sites are underreported, and their consequences are poorly understood, which makes predicting their pathogenicity challenging. We investigated the impact on splicing of an SCN5A minor intron donor variant in an individual with cardiac arrhythmias using patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs). Genetic testing in the proband identified an SCN5A c.392+3A>G variant of uncertain significance in a minor intron donor splice site, which segregated in affected family members with cardiac phenotypes, including Brugada syndrome. Transcriptome sequencing of proband-specific iPSC-CMs, treated with and without inhibition of nonsense-mediated decay, revealed aberrant SCN5A splicing. Four variant-associated isoforms were absent from control iPSC-CMs and control myectomy samples, and one skipped Exon 3 with a 96 bp extension of Exon 4. All alternatively spliced SCN5A transcripts were T/A cloned and confirmed by Sanger sequencing. These alternatively spliced transcripts used novel combinations of cryptic minor and major splice sites and introduced premature termination codons or an in-frame deletion, supporting reclassification of the variant as likely pathogenic. A genome-wide analysis of SpliceAI scores across minor intron splice sites retrieved from the Minor Intron Database revealed clear patterns of variants with high predicted splicing impact. This analysis also highlighted distinct splice site sequence motifs between minor and major splice sites that are not currently considered in ACMG/AMP variant interpretation guidelines. We further demonstrate that some cryptic donor-acceptor motif pairings are likely incompatible with splicing, which may inform future improvements in in silico splice site prediction tools. Integrating functional RNA sequencing with SpliceAI-based predictions at minor introns offers a pathway towards refining variant interpretation frameworks in clinical genomics.

The Fugl-Meyer Assessment of Lower Extremity (FMA-LE), Berg Balance Scale (BBS), and Brunnstrom lower-limb stage summarize lower-limb motor and balance function after stroke but do not directly reflect the electrical activity of distal muscles during a specific task. The tibialis anterior (TA) is a primary superficial agonist during active ankle dorsiflexion, and its surface electromyography (sEMG) may provide muscle-specific and task-specific complementary information relevant to foot drop and voluntary distal ankle-foot control.

To examine the relationships of TA sEMG measures obtained during active ankle dorsiflexion with lower-limb motor function, balance, and stage of motor recovery in inpatients with ischemic or hemorrhagic stroke within 1 year of onset, and to explore whether short-term improvements in clinical scales were accompanied by corresponding changes in sEMG measures.

This single-center observational study included 118 participants with supratentorial or infratentorial index stroke lesions. Bilateral TA and gastrocnemius sEMG was recorded during a standardized seated active ankle dorsiflexion task. The primary measures were paretic-side TA average rectified value (ARV) and the TA paretic/non-paretic ratio. Baseline sEMG analyses included 110 participants, clinical longitudinal analyses included 88, and sEMG longitudinal analyses included 81. Spearman correlation, multivariable linear regression, and paired Wilcoxon signed-rank tests were used, with adjustment for multiple comparisons.

At baseline, paretic-side TA ARV was lower than non-paretic-side TA ARV. Paretic-side TA ARV showed moderate positive correlations with the FMA-LE, BBS, and Brunnstrom lower-limb stage (ρ = 0.556, 0.492, and 0.496, respectively), as did the TA paretic/non-paretic ratio (ρ = 0.566, 0.440, and 0.417, respectively; all adjusted q < 0.001). Both TA measures remained associated with the FMA-LE and BBS after adjustment for age, sex, stroke type, time from stroke onset to baseline assessment, and paretic side. The FMA-LE, BBS, and Brunnstrom lower-limb stage improved during inpatient rehabilitation, whereas no sEMG measure showed a significant longitudinal change after FDR correction.

TA sEMG during active ankle dorsiflexion was associated with concurrent lower-limb motor and balance function and may provide muscle-specific and task-specific information complementary to routine clinical scales. Its longitudinal responsiveness and value in clinical practice require further investigation.

https://itmctr.ccebtcm.org.cn/mgt/search, identifier ITMCTR2026000773.

The paradigm of atherosclerosis has evolved from a passive lipid storage disease to a dynamic immuno-inflammatory disorder, yet the precise immune checkpoints governing its progression remain a therapeutic frontier. This review dissects the yin-yang regulation exerted by CD4⁺ T-cell subsets, with a particular focus on the pro-inflammatory T helper 17 cells (Th17) and the immunosuppressive regulatory T cells (Tregs). We posit that the net balance of the Th17/Treg axis, rather than the isolated activity of either subset, represents an important immunomodulatory determinant that influences plaque fate-operating in concert with other established contributors to atherosclerotic progression, including hemodynamic forces, lipid burden, plaque macrophage content, and coagulation pathways. By integrating recent advances in the metabolic and transcriptional control of this equilibrium, we highlight how its disruption fuels the chronic vascular inflammation central to atherosclerosis. Moreover, we critically evaluate the translational promise of strategically recalibrating this axis, examining next-generation immunotherapies that target lineage-specific pathways to restore homeostasis. This review not only consolidates mechanistic insights but also underscores the urgent clinical potential of harnessing the Th17/Treg balance as a viable strategy to attenuate atherosclerotic disease burden.