Background Mutations of LDLR, APOB and PCSK9 have been well-established to cause hypercholesterolemia while the pathogenic effects of LPL has been confirmed by cohorts and functional studies in hypertriglyceridemia. However, these mutations do not fully account for all dyslipidemia, and it remains unexplained why some patients with dyslipidemia develop coronary heart disease (CHD) while others do not.Methods We enrolled 108 patients with lipid disturbances (67 with hypercholesterolemia and 41 with hypertriglyceridemia) and 414 controls from Tongji Hospital, Wuhan, China. Whole exome sequencing (WES) was performed, and candidate genes were assessed using the optimal sequence kernel association test (SKAT-O). Subgroup analysis compared genetic profiles between CHD and non-CHD patients.Results We identified 13 pathogenic or likely pathogenic (PP/LPP) variants in LDLR in hypercholesterolemia patients and four in LPL as well as two in APOA5 in hypertriglyceridemia patients. With exclusion of patients with PP/LPP variants, SKAT-O identified 192 and 184 additional genes associated with hypercholesterolemia and hypertriglyceridemia, respectively. In subgroup analysis, 119 genes showed relevance to CHD by comparison of patients with and without CHD in hypercholesterolemia cohort. Further enrichment analysis identified COL5A1, COL24A1, COL6A6, COL6A2, SLC3A1, ATP1A4 and SLC7A9 as candidate causal genes of CHD.Conclusions This study described the genetic landscape of dyslipidemia in Chinese Han population, and revealed novel susceptibility genes beyond canonical lipid pathways. Genes implicated in CHD suggests extracellular matrix remodeling may mediate atherosclerotic progression in hypercholesterolemia. These findings provide novel mechanistic insights into CHD development and highlight promising targets for functional validation.

OBJECTIVE:Idiopathic inflammatory myopathy (IIM) is a collection of autoimmune disorders marked by muscle inflammation, with heart failure (HF) being a common and deadly complication. Exploring the underlying mechanisms and diagnostic markers for HF in IIM has significant clinical value. METHODS:We identified shared differentially expressed genes (DEGs) between HF and IIM using transcriptome data from the Gene Expression Omnibus (GEO). DEGs underwent functional enrichment analysis via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Key genes were screened using two machine-learning algorithms and a protein-protein interaction network. Immune cell infiltration was estimated using the CIBERSORT algorithm, and its correlation with key genes was assessed. The key gene-related regulatory transcription factors (TFs) and miRNAs were predicted using miRNet, followed by validation through both online datasets and clinical samples. RESULTS:Seventy DEGs were shared by IIM and HF, primarily involved in immune and inflammatory responses. Key genes, including DDX60, CCL5, and IFIT3, exhibited strong diagnostic potential in both IIM and HF cohorts. Expression of IFIT3 and CCL5 was negatively associated with Tregs. In order to uncover the control of important genes, we also constructed TF-gene and miRNA-gene networks. Lastly, we confirmed that IIM with HF had higher levels of miR-100-5p expression than those without HF. CONCLUSION:DDX60, CCL5, and IFIT3 are likely central to the development of HF in IIM. Additionally, serum levels of miR-100-5p may serve as a potential biomarker for detecting HF in IIM patients.

Fig. S1 DCA enhances the function of NK cells exhausted by huh7 tumor cells (A) Flow cytometry detection of NK cell phenotypes used in in vitro and in vivo experiments. (B) The flow cytometric data on a full panel of NK cell markers. (C) Left: The positive levels of Granzyme B, TNF-α, IFN-γ, perforin and CD107a in huh7 tumor-infiltration NK cells treated with or without 8mM DCA at an E:T ratio of 2:1 was detected by flow cytometry. Right: Statistical analysis of Granzyme B, TNF-α, IFN-γ, perforin and CD107a produced by huh7 tumor-infiltration NK cells with or without 8mM DCA. (n = 3, two independent samples t-test, two-sided). Statistical analysis of Granzyme B, TNF-α, IFN-γ and perforin produced by huh7 tumor-infiltration NK cells with or without 8mM DCA at E:T ratio of 5:1(D) and 10:1(E) was detected by flow cytometry (n=3, two independent samples t-test, two-sided). (F) Left: The positive levels of CD69 and TIM-3 in NK cells were detected by flow cytometry. Right: Statistical analysis of CD69 and TIM-3 expressed by NK cells. (n=3, two independent samples t-test, two-sided). Results represent the mean ± SEM, from three to four independent experiments. **P < 0.01; ***P < 0.001; ****P < 0.0001. Abbreviations: NK, natural killer; DCA, dichloroacetate.

Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) and has emerged as an important target for tumor imaging and therapy. Although numerous FAP-targeted PET tracers have demonstrated promising clinical performance, their high cost and limited accessibility restrict their widespread clinical application. In contrast, SPECT imaging is a more cost-effective and widely available alternative. Among the developed FAPI derivatives, FAPI-04 and FAPI-46 are two of the most extensively studied compounds with high translational potentials. In this study, we performed a systematic preclinical comparison of [99mTc]Tc-HYNIC-FAPI-04 and [99mTc]Tc-HYNIC-FAPI-46 to evaluate their imaging performance and provide guidance for optimal tracer selection in clinical SPECT. Bioinformatic analyses were performed to evaluate FAP expression and its association with prognosis and CAF-related markers. [99mTc]Tc-HYNIC-FAPI-04 and [99mTc]Tc-HYNIC-FAPI-46 were synthesized and assessed for their radiochemical purity and in vitro stability. FAP expression in FAP-HT1080 and HT1080 cells was validated using western blotting and immunofluorescence. Cellular uptake and saturation binding assays were conducted to evaluate the tracer affinity, and blocking experiments were conducted to confirm specificity. Small-animal SPECT/CT imaging and biodistribution studies were performed using FAP-HT1080 xenograft mouse models to assess in vivo tumor targeting. Immunohistochemical staining was used to further validate FAP expression in the tumor tissue. [99mTc]Tc-HYNIC-FAPI-04 and [99mTc]Tc-HYNIC-FAPI-46 exhibited high radiochemical purity and stability. FAP overexpression in FAP-HT1080 cells was confirmed by western blotting, immunofluorescence, and immunohistochemistry, and both tracers showed a high affinity for FAP. The cellular uptake of FAPI-04 was slightly higher than that of FAPI-46, and blocking experiments confirmed specific binding. SPECT/CT imaging demonstrated strong tumor accumulation with prolonged retention for both tracers, enabling clear visualization even 24 h post-injection. Quantitative analysis revealed no significant differences in tumor uptake or tumor-to-normal tissue ratios, despite the slightly higher tumor uptake of FAPI-04 observed in biodistribution studies. Consistently, comparable T/M, T/B, T/K, and T/L ratios were observed, indicating similar overall imaging performance. Bioinformatic analyses further revealed that FAP was upregulated in multiple tumors and correlated with CAF markers (COL1A1 and ACTA2). Both [99mTc]Tc-HYNIC-FAPI-04 and -46 showed high tumor uptake and clear visualization. Despite differences in pharmacokinetics, a similar tumor-to-normal tissue contrast was observed, supporting the suitability of both tracers for clinical SPECT imaging of FAP-expressing tumors.

The substantial burden of cardiovascular disease (CVD) attributable to air pollution remains a critical public health challenge, yet its combined effect with cardiometabolic factors is not fully understood. This study leveraged data from the Global Burden of Disease Study (GBD) and the China High Air Pollutants (CHAP) database to evaluate the CVD burden attributable to air pollution, which was found to increase progressively with age. We conducted a cross-sectional analysis using baseline (2011) data from 7420 participants aged ≥ 45 years in the China Health and Retirement Longitudinal Study (CHARLS), and a prospective cohort analysis in 8792 participants followed through 2020. In the longitudinal analysis, long-term exposure to PM2.5 (HR = 1.09, 95% CI: 1.03–1.16) and PM10 (HR = 1.07, 95% CI: 1.04–1.10) was significantly associated with an elevated risk of incident CVD, whereas the association for NO2 was nominally significant (HR = 1.12, 95% CI: 1.00–1.24) and that for O3 was not statistically significant (HR = 1.08, 95% CI: 0.93–1.27). Furthermore, prolonged exposure to these pollutants was associated with a higher prevalence of hypertension, diabetes, dyslipidemia, and obesity, and with adverse levels of metabolic indicators, including the TyG, TyG-BMI, and TyG-WC indices. A random forest model showed modest discrimination for incident CVD (AUC = 0.656), identifying PM10 and PM2.5 as the most important predictors. In conclusion, long-term exposure to ambient air pollution, particularly particulate matter, is associated with an increased risk of CVD and cardiometabolic disorders in middle-aged and older Chinese adults.

Atherosclerosis (AS) is a disease characterized by chronic vascular wall inflammation and lipid deposition. Although lipid-lowering drugs such as statins have significantly reduced cardiovascular event rates, "residual inflammatory risk" remains a key factor driving disease progression and plaque rupture. As a central regulator of the inflammatory response, the nuclear factor-κappaB (NF-κB) signaling network comprises both canonical pro-inflammatory pathways and functionally more complex non-canonical pathways. Increasing evidence in recent years indicates that abnormal and sustained activation of the non-canonical NF-κB signaling pathway plays a pivotal role in driving plaque rupture. This review first elaborates on the shift in AS strategies from "lipid-lowering" to "anti-inflammatory" approaches, followed by an in-depth analysis of the molecular activation mechanisms of the NF-κB signaling pathway and its distinctiveness in the AS pathological process, along with its epigenetic regulation. It emphasizes how this pathway drives pathological angiogenesis and regulates vascular smooth muscle cell (VSMC) phenotypic switching and macrophage function, thereby forming a vicious cycle that amplifies inflammation and structural damage, ultimately leading to acute cardiovascular events. Finally, we systematically summarize current progress and challenges in drug development targeting the NF-κB pathway (e.g., targeting key kinases like NIK and IKKα), aiming to provide theoretical foundations and future directions for novel therapeutic strategies to stabilize coronary plaques and prevent acute coronary syndromes.

Situs inversus totalis (SIT) is a rare congenital laterality anomaly characterized by complete mirror-image transposition of the thoracic and abdominal viscera. Although SIT is not a proven cancer-predisposition syndrome, cancer in this setting challenges the spatial assumptions that guide diagnosis, staging, surgery, radiotherapy, and surveillance. We conducted a retrospective, single-center observational study of patients with radiologically confirmed SIT treated at our cancer center between July 2017 and December 2025. Patients with histologically confirmed malignancy were included. Clinical, pathological, imaging, treatment, and follow-up data were extracted from medical records. Overall survival (OS) was summarized descriptively; Kaplan-Meier analysis was used only to visualize survival and censoring patterns. Among 11 patients with SIT, 6 had histologically confirmed malignancies. Median age was 66.5 years (range, 47–76), and median follow-up was 47.5 months (range, 30–55). Tumors included hepatocellular carcinoma, lung squamous cell carcinoma, lung adenocarcinoma, cervical adenocarcinoma, poorly differentiated abdominal adenocarcinoma, and follicular lymphoma transformed to high-grade B-cell lymphoma. Treatment included surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, transarterial chemoembolization, and autologous stem cell transplantation. 4 patients died, and 2 were alive at last contact. Pooled median OS was 50 months and was interpreted only descriptively. Across cases, outcomes reflected tumor type, stage, and molecular features, whereas SIT mainly affected lesion localization, laterality recognition, nodal or vascular mapping, operative orientation, and treatment planning. Malignancy in SIT is best understood as cancer within a reversed anatomical coordinate system. Standard oncologic care remains feasible but requires explicit anatomical verification and multidisciplinary planning.

Accurate imaging-based diagnosis of hepatocellular carcinoma (HCC) remains clinically challenging due to the limited specificity of conventional modalities. Glypican-3 (GPC3), which is highly expressed in most HCCs but absent in normal liver and benign lesions, represents a promising target for precision imaging. In this study, we designed and synthesized two GPC3-targeted 68Ga-labeled peptide PET tracers: a direct-targeting probe, [68Ga]Ga-HD3, and an albumin-binding-enhanced probe, [68Ga]Ga-HD4. Both probes were obtained in high radiochemical purity and demonstrated good in vitro stability. Their imaging performance was systematically evaluated in GPC3-positive and GPC3-negative xenograft models, as well as in an orthotopic HCC model. While both probes enabled GPC3-specific tumor visualization, [68Ga]Ga-HD4 showed significantly higher tumor uptake and prolonged tumor retention, leading to superior tumor-to-liver (T/L) and tumor-to-muscle (T/M) ratios, particularly at delayed imaging time points. Histological analysis confirmed that tumor uptake was GPC3-specific. In line with its albumin-binding design, [68Ga]Ga-HD4 showed elevated blood-pool activity and extended circulation time. Together, these results demonstrate that the incorporation of an albumin-affinity moiety effectively improves the pharmacokinetics and imaging performance of GPC3-targeted tracers. This work provides a solid practical foundation for the translational development of HCC imaging agents, with [68Ga]Ga-HD4 emerging as the more promising candidate owing to its improved tumor retention and imaging contrast.

Background:Ticagrelor is recommended as the preferred antiplatelet agent for patients with acute coronary syndrome (ACS), which is controversial in East Asians, Chinese patients in particular. This study aimed to compare the efficacy and safety of ticagrelor vs. clopidogrel in Chinese ACS patients following coronary stenting. Methods:Between August 2014 and October 2020, COSTIC recruited 9,040 patients prescribed with ticagrelor or clopidogrel. Applying propensity score matching, ticagrelor was compared with clopidogrel for 1-year risks of the primary efficacy endpoint (a composite of cardiovascular (CV) death, myocardial infarction and stroke) and bleeding endpoint. Results:The risk of the primary efficacy endpoint was comparable between the two groups but numerically higher after clopidogrel at 6 months (HR, 1.33 [95 % CI, 0.98-1.80]; P = 0.07). Clopidogrel was associated with high incidences of CV death (HR, 1.49 [95 % CI, 1.04-2.15]; P = 0.03 at 6 months; HR, 1.42 [95 % CI, 1.04-1.93]; P = 0.02 at 12 months) and all-cause death (HR, 1.43 [95 % CI, 1.02-1.99]; P = 0.04 at 6 months). BARC type 3 or 5 bleeding (OR, 0.60 [95 % CI, 0.40-0.88]; P = 0.008 at 6 months; OR, 0.71 [95 % CI, 0.52-0.96]; P = 0.03 at 12 months) and BARC type 2 bleeding risks (OR, 0.47 [95 % CI, 0.34-0.66] at 1 month, OR, 0.41 [95 % CI, 0.32-0.52] at 6 months, OR, 0.43 [95 % CI, 0.35-0.53] at 12 months, P < 0.001 at 1, 6 and 12 months) were higher with ticagrelor, as compared to clopidogrel. In terms of the net clinical benefit events, clopidogrel was comparable to ticagrelor in the total cohort. Conclusions:Among Chinese ACS patients with successful PCI, ticagrelor did not significantly reduce the risk of major ischemic events; instead, it was associated with a significant elevation bleeding risk.

BACKGROUND Chronic hepatitis B virus (HBV) infection remains a major global public health challenge. Accurate assessment of disease progression is essential for managing patients with chronic HBV infection. Despite the use of liver biopsy, imaging tests, and non-invasive models, their inherent limitations restrict widespread application. Thus, there is a pressing need to establish an effective non-invasive diagnostic model for assessing disease progression in patients with chronic HBV infection, particularly one that integrates imaging tests with demographic and hematologic parameters. AIM To develop novel non-invasive composite indices for evaluating the condition of chronic HBV-infected patients. METHODS This retrospective study enrolled 132 chronic HBV-infected patients who were admitted to the Department of Infectious Diseases, Shanxi Bethune Hospital, Taiyuan, China, between August 1, 2020 and June 30, 2024. Demographic variables, hematological parameters, and liver stiffness measurement (LSM) were recorded. Multivariable logistic regression was constructed to identify independent predictors of chronic hepatitis B (CHB), compensated and decompensated hepatitis B cirrhosis. The logistic regression diagnostic model was fitted with the selected predictors. Receiver operating characteristic (ROC) curves were generated to assess diagnostic performance of the model. RESULTS We developed three non-invasive models-A-index for CHB, MAPTAL for compensated hepatitis B cirrhosis, and APTAL for decompensated hepatitis B cirrhosis-which achieved area under the ROC curve of 0.948, 0.918, and 0.968, respectively. CONCLUSION The MAPTAL and APTAL indices, integrating LSM with routine demographic and hematologic variables, reliably predict progression to compensated and decompensated HBV-related cirrhosis, respectively.

BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS:Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS:In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

Pulsed field ablation (PFA) is an emerging innovative technology for treating paroxysmal atrial fibrillation (PAF), featured by its superior speed, accuracy, and reduced risk to adjacent tissues. The NOVA-AF study aimed to evaluate the efficacy and safety of a novel PFA system equipped with two PFA catheters: a circular PFA catheter and a linear PFA catheter integrating contact force-sensing capability, in patients with symptomatic PAF. This prospective, multicenter, single-arm study enrolled 161 patients with symptomatic PAF from seven medical centers in China. The composite primary effectiveness endpoint was defined as freedom from atrial tachyarrhythmia recurrence, device failure, multiple ablations during the blanking period, or antiarrhythmic drug failure during the evaluation period. The primary safety endpoint was the incidence of major adverse events (MAEs) related to the devices or procedures within three months of the procedure. All the ablated lesions (100 www.chictr.org.cn ), TRN: ChiCTR2400091941, Registration date: Nov 6 2024 (retrospectively registered).

Atherosclerosis is the leading cause of cardiovascular diseases worldwide. However, the molecular mechanisms underlying atherosclerosis remain incompletely understood. Here, we describe a previously unrecognized role of FES tyrosine kinase in macrophages and its therapeutic potential in atherosclerosis. First, we performed a proteome-wide Mendelian randomization analysis to investigate causal relationships between plasma proteins and atherosclerosis risk, utilizing GWAS data from FinnGen R10 and plasma protein data from the UK Biobank. Integrating Bayesian colocalization and single-cell expression profiling, we identified FES as a potential therapeutic target for atherosclerosis. We found that FES expression was significantly reduced in atherosclerotic plaques of ApoE- /- mice fed a high-fat diet. Notably, intravenous delivery of recombinant adeno-associated virus (rAAV)-mediated FES overexpression significantly reduced inflammatory responses and lipid deposition in atherosclerotic plaques. Computational predictions coupled with biochemical experiments revealed that FESmediated atheroprotection is accomplished through upregulation of Arg1. Furthermore, we observed that FES increases Arg1 expression by activating the transcription factor PU.1 and promoting its nuclear translocation. In summary, our study is the first to identify a novel role and mechanism for FES in atherosclerosis and provides a promising therapeutic strategy for atherosclerosis.

BACKGROUND:Chronic inflammatory pain lacks effective and non-addictive therapeutic options. Sinomenine (SIN), a non-opioid alkaloid derived from the traditional Chinese medicine Sinomenium acutum, has demonstrated analgesic potential in clinical practice, yet its precise mechanism remains incompletely understood. PURPOSE:This study aimed to investigate the analgesic mechanism of SIN and to identify a novel epigenetic pathway involved. METHODS:The effects of SIN were evaluated in complete Freund's adjuvant-induced chronic inflammatory pain models in rats and lipopolysaccharide stimulated BV2 microglial cells using behavioral tests, enzyme-linked immunosorbent assay, Western blot, reverse transcription quantitative PCR, immunohistochemistry, hematoxylin and eosin staining, calcium imaging, and amplicon bisulfite sequencing. Pharmacological interventions with a P2X2 purinergic receptor (P2X2R) agonist BZATP and antagonist A317491, as well as small interfering RNA mediated knockdown of DNA methyltransferase 1 (DNMT1) in BV2 cells, were employed to dissect the pathway. RESULTS:SIN dose-dependently alleviated pain hypersensitivity and inflammation, accompanied by downregulation of P2X2R expression. SIN inhibited P2X2R-dependentoveractivation of downstream extracellular signal-regulated kinase 1/2 signaling. Amplicon bisulfite sequencing revealed that SIN promoted methylation of the P2X2R gene promoter. Importantly, DNMT1 knockdown in BV2 cells completely abolished the suppressive effect of SIN on P2X2R expression. CONCLUSION:This study provides the first evidence that SIN suppresses P2X2R transcription via upregulation of DNMT1, leading to P2X2R promoter hypermethylation-a previously unrecognized epigenetic mechanism underlying the analgesic action of this natural product. This DNMT1-dependent pathway offers a novel therapeutic target for analgesic strategies focusing on epigenetic regulation.

Abstract Background Radiofrequency catheter ablation (RFCA) is a widely employed method for restoring sinus rhythm(SR) in patients with drug-refractory paroxysmal atrial fibrillation (PAF). Three-dimensional speckle tracking echocardiography (3DSTE) is a precise and practical imaging technique for clinically assessing myocardial function in the left atrium. The objective of this study was to assess alterations in three-dimensional strains and predict recurrence in patients with PAF following RFCA. Methods A total of 109 patients diagnosed with drug-refractory PAF and scheduled for RFCA were included in this study between September 2019 and June 2022. Conventional echocardiography and 3DSTE were performed prior to and one year(median period of 12.2 months) after RFCA. Global three-dimensional left atrial (LA) strain parameters, along with those of the left ventricle, were measured and analyzed statistically. The primary study endpoint was the recurrence of atrial fibrillation (AF). Results Among the 109 patients, 78 maintained a stable SR during the one-year follow-up after RFCA, while 31 experienced a recurrence of AF. Notably, patients who sustained SR demonstrated significant improvements in various LA strain parameters, including reservoir, pump, and conduit functions, compared to both their preoperative levels and those of patients who experienced recurrence(p < 0.05). Additionally, patients with sustained SR exhibited a significant reduction in LA volume compared to those with recurrence(p = 0.003). Furthermore, left ventricular global longitudinal strain (LVGLS) and left ventricular global area strain (LVGAS) of the left ventricle showed improvement while maintaining a preserved left ventricular ejection fraction (LVEF) after RFCA(p < 0.05). Our multivariate regression analysis revealed that left atrial reservoir strain (LASr) independently predicted the recurrence of AF [odds ratio (OR), 1.19, 95% confidence interval (CI), 1.05–1.35, p = 0.005]. Receiver operating characteristic(ROC) curve showed that the area under the curve(AUC) for LASr in assessing the risk of recurrence after RFCA in patients with PAF was 0.70 ( 95% CI, 0.60–0.81, P = 0.001). The calculated cutoff value was 16.5%. Conclusions RFCA plays a pivotal role in preserving SR and restoring LA function in patients with PAF. 3D-STE is highly effective for post-RFCA prognostic assessment. LASr, a predictive marker for the recurrence of PAF assists in the stratification of risk and contributes to informed treatment decisions, offering valuable points of reference.

Background Coronary heart disease (CHD) is a major cause of mortality worldwide, with an increasing trend of affecting younger populations. The asymptomatic early stages and rapid progression of CHD make diagnosis challenging, necessitating efficient diagnostic approaches. Methods We propose a novel algorithm that focuses on accumulating soft path costs to discern crucial indicators from extensive diagnostic tests, aiming to improve early CHD identification. Our approach emphasizes feature interaction using an interaction accumulation evaluation function to identify features with maximal interaction and minimal redundancy. A new stopping criterion based on information gain ratio is also introduced. Results Experimental outcomes demonstrate that our algorithm outperforms several classical algorithms in terms of classification accuracy and feature dimension reduction, while also identifying highly correlated feature subsets. Conclusion The proposed approach offers an efficient solution for early detection of CHD by identifying critical indicators, reducing diagnostic complexity, and improving predictive accuracy, thus potentially leading to more effective CHD management.

Background: Clinical trials have demonstrated mavacamten’s efficacy in improving health status of patients with obstructive hypertrophic cardiomyopathy (oHCM), but real-world data remain limited. Research Question: What is mavacamten’s impact on health status changes in patients with oHCM in real-world settings? Methods: The COMPASS-HCM study (NCT06551129) prospectively recruited US adults with oHCM prescribed mavacamten, excluding those with moderate lung disease, recent hospitalization (≤ 2 weeks), recent heart/lung surgery or stroke/transient ischemic attack (≤ 6 months), or mavacamten treatment ≥7 days prior to enrollment. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ; higher scores are better) and HCM Symptom Questionnaire (HCMSQ; lower scores are better) at baseline, weeks 2, 4, 8, 12, 24, and 30 after initially starting mavacamten. Patient characteristics and health status changes from baseline through week 30 were described. Results: A total of 108 patients (mean [± SD] age 66.7 ± 12.5 years, 61.1% women, and 94.4% White) completed baseline surveys and initiated mavacamten following enrollment. Baseline mean scores were 60.3 ± 20.9 for KCCQ Overall Summary Score (KCCQ-OSS), 65.9 ± 19.3 for KCCQ Clinical Summary Score (KCCQ-CSS), 6.9 ± 3.5 for HCMSQ Shortness of Breath (SoB) domain, and 4.5 ± 2.0 for HCMSQ Total score. At baseline, 85.2% of patients were on background oHCM therapy. Follow-up surveys were completed by 78, 74, 62, 52, 24, and 18 patients treated with mavacamten for 2, 4, 8, 12, 24, and 30 weeks, respectively. At last follow-up, daily mavacamten dose was 2.5 mg in 16.7%, 5 mg in 38.9%, 10 mg in 22.2%, and 15 mg in 22.2% of patients. Mean improvements from baseline to week 30 were 20.7 ± 17.1 for KCCQ-OSS (Figure 1), 16.4 ± 12.8 for KCCQ-CSS, -3.9 ± 3.5 for HCMSQ SoB domain, and -2.0 ± 2.0 for HCMSQ Total score. At week 12, 69.2% and 38.5% of patients achieved large (≥10 points) and very large (≥20 points) improvements in KCCQ-OSS, respectively, increasing to 83.3% and 50.0% at week 30 (Figure 2). A ≥ 2.5 point reduction in HCMSQ-SoB score was observed in 58.8% of patients at week 12, increasing to 70.6% at week 30 (Figure 3). Conclusion(s): Real-world mavacamten treatment led to rapid and substantial health status improvements that appear to accrue through week 30 in oHCM, highly consistent with the EXPLORER-HCM findings in a more restricted population.

Fulminant myocarditis (FM) is an acute inflammatory condition that results in a rapidly progressive, life-threatening circulatory failure and cardiogenic shock. This condition is characterized by severe endotheliitis and concurrent cytokine storm, which give rise to a wide spectrum of clinical manifestations and complications, including thromboembolism, myositis, and arrhythmia. Herein, we report an extremely rare case involving a 48-year-old woman diagnosed with FM associated with influenza virus type A, presenting with abdominal aortic occlusion due to acute thrombosis. Echocardiography revealed a significant reduction in global cardiac function (left ventricular ejection fraction, 26%), accompanied by left ventricular mural thrombosis. Enhanced computed tomography (CT) and angiography revealed an in situ aortic thrombosis affecting the infrarenal abdominal aorta and branches of the superior mesenteric artery, bilateral common iliac arteries, and internal and external iliac arteries. The patient was provided with a comprehensive treatment involving anticoagulants (enoxaparin, tirofiban), immunomodulatory agents (methylprednisolone, immunoglobulin), antiviral agent (oseltamivir), and intra-aortic thrombus aspiration via the right femoral artery. After undergoing these treatments for 19 days, her cardiac function returned to normal and subsequent CT images showed a dramatic reduction in aortic thrombosis. Moreover, full recovery of blood flow and movement function of the bilateral lower extremities was observed.

BACKGROUND:Transcatheter closure of perimembranous ventricular septal defects in children is a highly effective procedure, but it can result in tricuspid regurgitation (TR). The associated risk factors and long-term outcomes of TR following the procedure are not well understood. METHODS AND RESULTS:This retrospective study included 1343 pediatric patients (age, 4.41±2.56 years) who underwent successful transcatheter perimembranous ventricular septal defect closure between 2002 and 2022, with a median follow-up of 78 (range, 12-244) months. TR was evaluated using echocardiography, and multivariate logistic regression was performed to identify independent risk factors of postprocedural TR. Postprocedural TR occurred in 12.1% of patients, including 143 new-onset cases and 20 with progressed preexisting TR. The majority of cases (86.5%) were mild, while 20 were moderate, and 2 were severe requiring surgical intervention. Most TR cases (84%) developed within 24 hours after the procedure. A higher right disc diameter-to-body weight ratio was identified as an independent risk factor of TR (odds ratio, 2.816 [95% CI, 1.315-6.032]). During follow-up, 71.8% of TR cases improved or resolved, though moderate TR persisted in 7 cases, and 1 progressed to severe TR requiring surgery 2 years after the procedure. CONCLUSIONS:TR following perimembranous ventricular septal defect closure is common but typically mild and often resolves over time. A larger right disc diameter relative to body weight significantly increases the risk of TR, emphasizing the importance of careful device sizing, particularly in lighter patients. Long-term follow-up is crucial to detect potential late progression of TR.