Conduction system pacing (CSP) combined with atrioventricular node ablation (AVNA) is a feasible option for symptomatic atrial fibrillation (AF), but comparative studies with pulmonary vein isolation (PVI) are limited.

The aim of this study was to compare the clinical outcomes of CSP+AVNA and PVI in patients with persistent AF and a left atrial size.

This observational study included patients with persistent AF and a left atrial size >50 mm received PVI or CSP+AVNA (ablate and pace [AP]) from 2016 to 2022. Clinical outcomes, AF recurrence, and the composite endpoint of heart failure hospitalization and cardiac death were assessed.

Out of 718 screened patients, 473 received PVI and 245 received AP. The AP strategy was associated with higher composite risk in univariate analysis (HR: 2.84; 95% CI: 1.79-4.50; P < 0.001) but not after multivariate adjustment (HR: 1.10; 95% CI: 0.54-2.23; P = 0.795). After 1:1 matching (n = 174), left ventricular ejection fraction improved similarly in both groups. Over an average 40 months' follow-up, the composite endpoint was similar between groups (propensity score matching [PSM]-AP: 14.9% vs PSM-PVI: 16.1%; P = 0.864). AF recurred in 54.0% in the PSM-PVI group and atrioventricular conduction recurred in 1.2% in the PSM-AP group.

In this observational study, outcomes were numerically similar between PVI and AP in patients with persistent AF and enlarged left atria. Given the limited sample size and residual confounding, these results should be considered hypothesis-generating pending confirmation from randomized trials.

Programmed cell death (PCD) is a genetically regulated, orderly cell death process essential for tissue homeostasis. Contemporary PCD comprises a broad spectrum, including apoptosis, pyroptosis, ferroptosis, necroptosis, autophagy-dependent cell death, NETosis, parthanatos, and entotic cell death. Kawasaki disease (KD) is an acute pediatric systemic vasculitis and a leading cause of acquired childhood heart disease, with coronary artery lesions as the most severe complication. Mounting evidence confirms that PCD is tightly associated with KD-related vascular endothelial injury and inflammatory amplification. Among all PCD subtypes, apoptosis, pyroptosis, and ferroptosis have the most sufficient and direct evidence in KD pathogenesis, mediating vascular wall damage and inflammatory imbalance via distinct molecular pathways. This review focuses on these three well-documented PCD forms (with a brief overview of other PCD subtypes and their potential KD relevance), systematically elaborates their crosstalk with KD pathogenesis, summarizes current research progress, and proposes targeted therapeutic strategies for KD.

Renal ischemia-reperfusion injury (IRI) poses a significant challenge in kidney transplantation, contributing to acute kidney injury and chronic kidney fibrosis. In the present study, we investigated renoprotective effects of BX-001N, a synthetic polyethylene glycol-conjugated bilirubin nanoparticle, against renal IRI after kidney transplantation. A murine syngeneic kidney transplantation model was used to study renal IRI. BX-001N was administered intravenously at 0 and 2.5 h post-transplantation. Renal functions (creatinine and BUN), histopathological injury, oxidative stress, renal regeneration, and fibrotic changes were assessed at post-transplant day (POD) 1 and 7. BX-001N significantly improved renal function and attenuated renal tissue injury and tubular cell apoptosis at POD 1, following cold IRI. It markedly reduced neutrophil infiltration and suppressed the expression of pro-inflammatory cytokines (TNF-α and IFN-γ) and chemokines (MCP-1 and CXCL2). Antioxidant responses were enhanced, as evidenced by increased expression of heme oxygenase-1 and decreased accumulation of nitrotyrosine. Furthermore, at POD 7, BX-001N promoted renal regeneration with increased Ki-67 and vascular endothelial growth factor expression. It also inhibited renal fibrosis and suppressed epithelial-mesenchymal transition with decreased expression of α-smooth muscle actin, while preserving E-cadherin expression. In conclusion, BX-001N effectively mitigates IRI-induced renal injury by reducing oxidative stress, inflammation, and fibrosis, indicating its potential therapeutic value in kidney transplantation.

Metabolic syndrome substantially elevates venous thromboembolism (VTE) risk, increasing health care burdens. The Metabolic Score for Visceral Fat (METS-VF) offers a novel, simplified approach to assess visceral fat. This study evaluates METS-VF's association with VTE risk and its utility for risk stratification in patients with metabolic syndrome.

Using UK Biobank data, we included 118 619 participants with metabolic syndrome free of VTE at baseline. Time-dependent area under the curve analysis with bootstrap validation identified the strongest VTE predictor. Multivariable Cox models assessed associations of METS-VF, a VTE-specific polygenic risk score, and their combination with incident VTE. Mediation analysis evaluated potential mediators. Robustness was assessed through subgroup and sensitivity analyses, including competing risk of death.

Over a median 12-year follow-up, 5162 participants developed VTE. METS-VF demonstrated stronger association with VTE than traditional metabolic indicators. Highest quartile participants showed significantly increased risks of VTE (hazard ratio [HR], 1.46 [95% CI, 1.33-1.61]), pulmonary embolism (HR, 1.50 [95% CI, 1.33-1.70]), deep vein thrombosis (HR, 1.52 [95% CI, 1.34-1.73]), and lower-extremity deep vein thrombosis (HR, 1.59 [95% CI, 1.38-1.82]). Stratified analysis revealed synergistic interaction between METS-VF and genetic susceptibility. CRP (C-reactive protein) and estimated glomerular filtration rate significantly mediated the METS-VF-VTE association.

METS-VF is a significant, independent risk indicator for VTE in patients with metabolic syndrome, demonstrating synergistic effects with genetic risk. The CRP- and estimated glomerular filtration rate-mediated association supports METS-VF's clinical utility in VTE risk stratification.

COVID-19 and other respiratory viral infections can cause cardiovascular complications. SARS-CoV-2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID-19 and enrolled in the ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy.

We quantified SARS-CoV-2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine-Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death.

In 93 patients, SARS-CoV-2 RNA and N-antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90-day death (hazard ratio [HR], 1.31 [95% CI, 1.17-1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24-1.47]). Viral RNA more effectively predicted survivorship than N-antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%-32.3%; P=0.048) after adjustment for age and sex of the relationship between viral RNA and the 90-day mortality rate.

Elevated plasma SARS-CoV-2 RNA levels are associated with death in ACTIV-4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung-blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses.

URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04505774.

Recurrence of acute myocarditis (AM) is challenging. The management and natural history of patients who experience a recurrence of AM (Re-AM) remain poorly characterized. The aim of this study is to investigate clinical characteristics and outcomes of patients with Re-AM.

In this international multicenter study, 141 consecutive patients with biopsy-proven or cardiac magnetic resonance-proven Re-AM (35 [26-45] years, 77% male, median left ventricular ejection fraction 55%) were investigated and compared with 372 consecutive patients with single acute myocarditis (S-AM). The primary outcome was a composite of all-cause mortality, heart transplant and major ventricular arrhythmias.

Patients with Re-AM had more frequently a family history of cardiomyopathy (19% in Re-AM versus 2.8% in S-AM, P<0.001) and a diffuse late gadolinium enhancement compared with patients with S-AM (46% in Re-AM versus 34% in S-AM, P=0.019). The extent of late gadolinium enhancement also increased between the first and the second AM episode in patients with Re-AM (P=0.001). During a median follow-up of 33 months (interquartile range, 23-52) patients with Re-AM had a higher risk of primary outcome (P=0.001) compared with patients with S-AM, as well as a significantly elevated competing risk of major ventricular arrhythmias (P<0.001), which remained independently associated even after adjustment (hazard ratio, 2.15 [95% CI, 1.15-4.04], P=0.017). A family history of cardiomyopathy, autoimmune diseases, and ring-like late gadolinium enhancement was independently associated with a higher risk of recurrent AM.

Re-AM is a distinct clinical subgroup of AM associated with generally worse prognosis and a specific increased arrhythmic risk compared with S-AM.

Diffuse large B cell lymphoma (DLBCL) presents a critical clinical challenge due to declining chemosensitivity and difficult-to-manage dose-limiting toxicities. Although gut microbiota modulation shows potential for "toxicity reduction and efficacy enhancement", its mechanism in DLBCL remains unclear. Comparative analysis revealed a marked reduction of beneficial bacteria in patients with DLBCL versus healthy volunteers, with a marked decrease in the abundance of core probiotics, particularly Limosilactobacillus reuteri. Fecal microbiota transplantation from healthy donors into DLBCL mouse models reduced tumor burden, improved chemosensitivity, and alleviated intestinal toxicity. A core probiotic strain, L. reuteri HG001, was isolated and shown to replicate these effects alone, with the tryptophan metabolite indole-3-carbaldehyde (ICAld) identified as the key component responsible for its adjunctive antitumor activity. Mechanistic studies demonstrated that ICAld exerts significant adjunctive antitumor effects both in vitro and in vivo in a dose-dependent manner in mouse models; it acts by activating the aryl hydrocarbon receptor (AHR)/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/reactive oxygen species (ROS) axis, inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway, promoting apoptosis, and synergizing with cyclophosphamide. An aryl hydrocarbon receptor antagonist reversed both the chemosensitizing and intestinal protective effects of L. reuteri HG001 and ICAld. This study elucidates a microbiota-mediated mechanism in DLBCL and supports L. reuteri HG001 as a probiotic adjuvant to enhance therapy while reducing toxicity.

Pediatric heart failure (PHF) is a heterogeneous syndrome whose etiologies, developmental biology, and clinical trajectories differ fundamentally from adult heart failure. Beyond age-specific hemodynamics and neurohormonal activation, inflammatory and immune programs can serve as primary drivers (e.g., myocarditis, multisystem inflammatory syndrome in children [MIS-C]) or as potent amplifiers of decompensation (e.g., postoperative inflammation after cardiopulmonary bypass, infection-associated stress). This review integrates contemporary pediatric heart failure practice with insights from cardio-immunology and proposes a pragmatic, bedside framework that: (i) links common triggers and clinical contexts to likely effector pathways; (ii) uses multimodal assessment to distinguish active immune-mediated injury from chronic remodeling; (iii) applies trajectory-based monitoring with feasible inflammatory-immune context bundles rather than research-grade immunophenotyping; and (iv) aligns immunomodulatory decisions with probability of immune causality, time window, and safety constraints to avoid indiscriminate immunosuppression. We highlight pediatric-specific challenges (reference ranges, sampling feasibility, imaging constraints, and limits of adult extrapolation), summarize emerging pharmacologic and device advances, and outline priorities for harmonized pediatric biomarker standards, prospective phenotype validation, and safer implementation of targeted immunomodulation. A graphical abstract summarizes the proposed phenotype-to-management framework.

Intestinal ischemia/reperfusion (I/R) injury is a critical clinical syndrome precipitated by the restoration of blood flow following intestinal ischemia, a common occurrence in perioperative settings such as abdominal aortic surgery, hemorrhagic shock, and cardiopulmonary bypass. This injury extends beyond the local gut, as the disruption of the intestinal mucosal barrier facilitates bacterial and endotoxin translocation into the systemic circulation, triggering a systemic inflammatory response that can progress to sepsis and multiple organ dysfunction syndrome (MODS). Despite advances in critical care, the mortality rate associated with severe intestinal I/R injury remains formidable. The microcirculatory disturbances and organ damage following intestinal I/R involve complex pathological processes, including metabolic injury and oxidative stress. In recent years, rapid developments in the understanding of cell death mechanisms, gut microbiota, microRNAs, and fundamental medical technologies have significantly advanced research on the prevention and treatment of I/R injury. This review aims to comprehensively summarize the occurrence and progression of intestinal I/R, its impact on extraintestinal organ injury, diagnostic strategies and biomarkers, as well as current treatment methods, thereby providing guidance for the future prediction, diagnosis, and treatment of intestinal I/R injury.