Circulation最新文献

Background: Tissue-specific regulatory T cells (Tregs) accumulate in the heart after myocardial infarction (MI) and play a vital role in limiting inflammation and promoting tissue repair. However, the developmental trajectory of heart Tregs and the molecular cues that guide their recruitment to the heart remain poorly understood, impeding therapeutic strategies that leverage Treg-mediated cardiac protection.

Methods: We used single-cell and bulk RNA sequencing in a murine MI model to delineate the differentiation trajectory of Tregs from mediastinal lymph nodes to the heart. Functional validation was performed using Treg-specific Ccr8 (CC motif chemokine receptor 8) knockout mice (Ccr8^flox/floxFoxp3^Cre), Ccl1 (CC motif chemokine ligand 1) knockout mice (Ccl1^-/-), macrophage-targeted Ccl1 knockdown mice, Ccl1-overexpressing mice, and DEREG mice. The CCL1-CCR8 axis was evaluated in cardiac tissues and circulating blood from patients with MI.

Results: Single-cell RNA sequencing revealed a stepwise differentiation of mediastinal lymph node-derived naive Tregs into heart Tregs, marked by the progressive acquisition of CCR8 expression and reparative capacity. CCR8⁺ Tregs in the heart exhibited enhanced immunosuppressive and tissue-repair signatures. Treg-specific Ccr8 deletion led to reduced Treg accumulation and worsened cardiac function after MI, along with increased proinflammatory macrophage features and number of CD8⁺ T cells and natural killer cells. In addition, Tregs promoted a shift of macrophages toward an anti-inflammatory phenotype by secreting IL-1R2 (interleukin 1 receptor, type 2). We identified cardiac macrophages as the main source of CCL1, which was essential for CCR8⁺ Treg recruitment. Ccl1 deficiency or macrophage-specific Ccl1 knockdown impaired Treg infiltration and aggravated ventricular remodeling; Ccl1 overexpression promoted Treg recruitment and improved cardiac outcomes. Moreover, the cardioprotective effects of CCL1 were abolished in DEREG mice upon Treg depletion and Ccr8^flox/floxFoxp3^Cre mice, establishing a CCR8⁺ Treg-dependent mechanism. Furthermore, circulating CCR8⁺ Tregs and cardiac CCL1 were elevated in humans with MI, and the presence of CCR8⁺ Tregs and CCL1-expressing macrophages was confirmed in the hearts of patients with MI, suggesting important clinical relevance.

Conclusions: Our findings reveal a 2-phase Treg specialization process and establish the CCL1-CCR8 axis as a crucial pathway for Treg recruitment and function in the infarcted heart. Therapeutic targeting of this axis may improve immune-regulated cardiac repair after MI.

Aim: The "2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults" is a de novo guideline that provides comprehensive recommendations for the evaluation, management, and follow-up of adult patients (≥18 years of age) with acute pulmonary embolism (PE). A key feature of this guideline is the introduction of the AHA/ACC Acute Pulmonary Embolism Clinical Categories, which enhance the precision of severity classification, prognosis assessment, and evidence-based therapeutic decision-making.

Methods: A comprehensive literature search was conducted from February 2024 to October 2024 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Select key studies published until April 2025 were added by the guideline writing committee as appropriate.

Structure: The focus of this clinical practice guideline is an evidence-based and patient-centered approach for acute PE evaluation and management of the adult patient. This guideline encompasses the period from the onset of symptoms through clinical follow-up, focusing on risk outcomes assessment, clinical diagnosis of acute PE, appropriate use of adjunctive cardiovascular testing, and management in both the acute and early post-acute phases of PE. It addresses evidence-based diagnostic and management strategies (including pharmacological therapies, advanced interventional therapies, and in-hospital support) for acute PE and associated outcomes.

Background: Limited data are available regarding the relative rates, etiology, and long-term prognostic implications of spontaneous myocardial infarction (MI) after percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery for left main coronary artery disease (LMCAD).

Methods: MIs after PCI and CABG for LMCAD were adjudicated from the EXCEL trial (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Cox proportional hazards regression was performed to assess the association between spontaneous (and procedural) MI and cardiovascular and all-cause mortality at 5 years.

Results: Among 1882 patients who underwent LMCAD revascularization, spontaneous MI during 5-year follow-up occurred in 60 (6.8%) patients after PCI and in 29 (3.4%) patients after CABG (adjusted hazard ratio [adjHR], 2.01; 95 CI, 1.29-3.15; P=0.002). By multivariable analysis, spontaneous MI (as a time-adjusted covariate) was a strong independent predictor of subsequent cardiovascular mortality (adjHR, 9.39; 95% CI, 5.22-16.87) and all-cause mortality (adjHR, 4.77; 95% CI, 2.92-7.80) within 5 years, with consistent effects after PCI and CABG (P_interaction=0.60 and 0.78, respectively). In the same models, procedural MI as defined by extensive myonecrosis was associated with 5-year cardiovascular (adjHR, 3.02; 95% CI, 1.64-5.56) and all-cause mortality (adjHR, 2.38; 95% CI, 1.48-3.80), with consistent effects after PCI and CABG (P_interaction=0.23 and 0.34, respectively).

Conclusions: In the EXCEL trial, spontaneous MI occurred relatively infrequently within 5 years after LMCAD revascularization but at a higher rate after PCI compared with CABG. Spontaneous MI after revascularization was strongly related to subsequent cardiovascular and all-cause mortality, consistently after PCI and CABG, and was more strongly associated with mortality than was large procedural MI.

Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01205776.