Lei Zhou

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD) and a leading cause of mortality in affected patients. Although the COMPERA 2.0 model is widely used for risk stratification in PAH, its ability to discriminate prognosis among low-risk patients remains limited. This study aimed to explore the prognostic predictive role of cardiopulmonary exercise testing (CPET) in CTD-PAH patients classified as low or intermediate-low risk by COMPERA 2.0. This ambispective cohort included 33 CTD-PAH patients confirmed by right heart catheterization (RHC) and classified as low or intermediate-low risk via COMPERA 2.0 after standardized therapy. All patients underwent CPET. According to the 2022 ESC/ERS criteria, participants were stratified by peak oxygen uptake (PeakVO₂) and ventilatory equivalent for carbon dioxide (VE/VCO₂) slope. The primary endpoint was a composite of clinical deterioration, analyzed using Kaplan-Meier survival curves. The non-attainment group presented with significantly worse baseline and follow-up characteristics, including reduced exercise tolerance, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and more impaired echocardiographic and hemodynamic parameters compared to the attainment group. Over a mean follow-up of 23.7 ± 12.3 months, the non-attainment group had significantly poorer event-free survival (p = 0.031). CPET provides additional prognostic information beyond COMPERA 2.0, identifying CTD-PAH patients with greater disease severity and a higher risk of adverse outcomes, even within the low and intermediate-low risk strata. Failure to achieve CPET thresholds was independently associated with increased disease burden and reduced event-free survival. Key Points • This study demonstrates that cardiopulmonary exercise testing (CPET) offers significant prognostic value beyond the COMPERA 2.0 risk stratification model in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) classified as low or intermediate-low risk. • Patients failing to meet CPET criteria (PeakVO₂ > 15 mL/min/kg and VE/VCO₂ slope < 36) exhibited more severe disease, including worse hemodynamics, right ventricular dysfunction, and higher NT-proBNP levels, despite similar COMPERA 2.0 risk categories. • The CPET non-attainment group had significantly lower event-free survival, underscoring the utility of CPET in identifying high-risk patients who might otherwise be underestimated by conventional risk assessment tools. • Inadequate use of immunosuppressive therapy in the non-attainment group suggests that optimizing management of the underlying connective tissue disease may be critical for improving cardiopulmonary outcomes in CTD-PAH.

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. 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. 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. 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.

Objectives To identify echocardiographic parameters that predict prognosis in pulmonary arterial hypertension (PAH) patients with low and intermediate risk. Methods This single-center retrospective cohort study included PAH patients classified as low or intermediate risk according to WSPH criteria. All patients were regularly followed at the First Affiliated Hospital of Nanjing Medical University. Baseline and follow-up data were collected using standardized case report forms. Missing data were imputed using the random forest method. Statistical analyses were performed using SPSS 26.0 and R 4.3.1, with a two-sided p < 0.05 considered significant. Results A total of 116 PAH patients (57 low risk, 59 intermediate risk) were enrolled. During a median follow-up of 34.8 months, 28 patients (24.1%) experienced clinical failure events. The TAPSE/PASP ratio was an independent predictor of poor prognosis (HR = 0.002, 95% CI 1.09e-5–0.294, p = 0.015). Kaplan–Meier analysis showed that patients with TAPSE/PASP < 0.33 and IVC ≥ 16 mm had significantly worse event-free survival (p < 0.001). Conclusions The combination of TAPSE/PASP < 0.33 and IVC ≥ 16 mm identifies poor prognosis among low- and intermediate-risk PAH patients, providing a simple echocardiographic tool for early risk stratification. Key Points • TAPSE/PASP ratio combined with IVC diameter provides a simple, non-invasive index to identify poor prognosis in low- and intermediate-risk CTD-PAH patients. • This combined echocardiographic assessment may facilitate early recognition of right ventricular–pulmonary arterial uncoupling and guide timely treatment adjustment. • It refines risk evaluation beyond conventional WSPH stratification, supporting individualized long-term management in CTD-PAH.

Objectives: Idiopathic inflammatory myopathy (IIM) is increasingly recognized as a systemic disorder with frequent subclinical myocardial involvement. However, its coexistence with heart failure with preserved ejection fraction (HFpEF) remains poorly understood. This study aimed to comprehensively characterize the clinical, serological and radiological features of IIM patients with HFpEF and assess the prognostic utility of the HFA-PEFF score in this setting. Methods: In this cohort study, 134 patients with IIM were stratified into low-, intermediate- and high-risk categories according to their HFA-PEFF score. Clinical characteristics and long-term outcomes were compared across groups. Results: Of the 134 patients, 22 (16.4%) were classified as high risk (HFA-PEFF ≥5). This group was significantly older and exhibited lower free triiodothyronine levels, higher CRP and cardiac troponin T levels (all P < 0.05), and a greater prevalence of interstitial lung disease with advanced pulmonary fibrosis. Late gadolinium enhancement on cardiac MRI was observed in 78.5% of high-risk patients. The high-risk group also had significantly higher positivity rates for ANA, anti-SSA, anti-Jo-1, and anti-Ro52 antibodies (P < 0.05), implicating a possible link between autoimmunity and myocardial remodelling. Kaplan–Meier analysis revealed a markedly reduced 5-year survival in the high-risk group (47.1%) compared with the low- and intermediate-risk groups (88.7% and 84.5%, respectively; P < 0.001). In multivariable Cox regression, an HFA-PEFF score ≥5 remained an independent predictor of all-cause mortality (HR 3.124, P < 0.05). Conclusion: Our findings underscore the prognostic relevance of specific autoantibodies and cardiac fibrosis in IIM. Incorporating HFA-PEFF–based risk stratification into clinical practice may enable earlier interventions and personalized monitoring for high-risk patients.

Background Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with sterile inflammation and immune dysregulation driving cardiac injury. Itaconate, a mitochondria-derived immunometabolite synthesized by ACOD1, has emerged as a key regulator of myeloid cell function, exhibiting anti-inflammatory and metabolic effects. However, its role and downstream targets in sterile myocardial inflammation remain poorly understood. Objective This study aimed to systematically dissect the immunometabolic role of itaconate in AMI by identifying itaconate-responsive genes, uncovering their cell-type specificity and functional dynamics, and evaluating their diagnostic and therapeutic potential. Methods We established a novel systems-level framework that integrates bulk and single-cell/single-nucleus transcriptomics, network pharmacology, machine learning-based feature selection, and molecular docking. This multi-layered strategy was applied to human and murine datasets covering infarcted cardiac tissue and peripheral immune compartments to identify robust, itaconate-responsive immune targets in AMI. Results Single-cell data show that ACOD1 induction is disease-specific and characteristic of AMI. And we identified 36 itaconate-associated genes enriched in myeloid populations and dynamically regulated during infarction. Among them, MMP9, TLR2, and ANPEP were consistently prioritized by multiply machine learning algorithms, showed robust diagnostic performance across independent cohorts, and exhibited potential binding to itaconate in silico. Single-cell analyses confirmed spatial and temporal regulation of these targets in infarcted myocardium. Functional analyses revealed that 4-octyl-itaconate (4-OI) induced dose- and context-dependent transcriptional programs in myeloid cells, including NRF2 and ATF3 activation. Conclusions This study identifies a core immunometabolic program downstream of itaconate in myeloid cells and highlights MMP9, TLR2, and ANPEP as key effectors linking metabolic sensing to inflammation and tissue remodeling in AMI. Our integrative approach offers new insights into context-specific immunomodulation and supports the development of metabolite-guided therapeutic strategies for cardiovascular inflammation.

Background: The inflammatory burden index (IBI) is a novel and useful inflammatory marker. However, the association between IBI and new-onset atrial fibrillation (NOAF) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. This study focuses on exploring the predictive ability of IBI for NOAF after percutaneous coronary intervention (PCI) in STEMI patients.Materials and methods: This study is a single-center retrospective observational study. Patients diagnosed with STEMI and undergoing primary PCI between October 2022 and February 2025 were continuously enrolled. All enrolled patients received continuous electrocardiogram (ECG) monitoring (>72 h) and were grouped according to whether NOAF occurred during hospitalization. Logistic regression analysis was used to identify potential risk factors for NOAF. Meanwhile, restricted cubic spline (RCS) analysis was employed to thoroughly investigate the possible dose-response relationship between IBI and NOAF.Results: A total of 696 STEMI patients were finally included in this study. The incidence of NOAF during hospitalization was 62/696 (8.9%). After adjusting for potential confounding factors, the results of multivariate logistic regression analysis showed that left ventricular ejection fraction (OR = 0.928, 95% CI: 0.895–0.962), age (OR = 1.048, 95% CI: 1.022–1.075), and IBI (OR = 1.007, 95% CI: 1.003–1.011) were independent factors for NOAF in STEMI patients (P < 0.05). RCS results suggested that there was a non-linear dose-response relationship between IBI and NOAF. After integrating IBI, the ability of the new model to predict NOAF was significantly improved (NRI = 0.617, 95% CI: 0.360–0.873, P < 0.01; IDI = 0.026, 95% CI: 0.007–0.046, P = 0.008).Conclusions: Elevated IBI is an independent risk factor for NOAF after PCI in STEMI patients. Integrating IBI can improve the risk stratification for NOAF in STEMI patients.

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) patients with left heart dysfunction may have worse prognosis. This study was to investigate the prognostic value of HFA-PEFF score in connective tissue disease-associated PAH. This single-center retrospective cohort study enrolled 147 CTD-PAH patients diagnosed via right heart catheterization (RHC), divided into two groups based on their HFA-PEFF scores: < 5 (n = 74) and ≥ 5 (n = 73). The clinical characteristics were compared between the two groups. The primary end point was all-cause mortality, and the secondary end point was clinical worsening events. Survival was analyzed using Kaplan–Meier analysis and Cox proportional hazards models. Compared to the HFA-PEFF score < 5 group, the ≥ 5 group exhibited significantly higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a greater proportion of WHO functional class III-IV, shorter 6-min walk distance (6MWD), larger right ventricular (RV) volume, worse RV function, smaller left ventricular (LV) volume, and higher native T1 values. An HFA-PEFF score ≥ 5 was a predictor for all-cause mortality in CTD-PAH (HR 5.022, P = 0.020) and for clinical worsening events (HR 2.670, P = 0.020). At follow-up, 17.9% of CTD-PAH had an HFA-PEFF score ≥ 5. Patients with follow-up HFA-PEFF scores ≥ 5 had a significantly lower event-free survival rate (P < 0.001). An HFA-PEFF score ≥ 5 was associated with all-cause mortality and clinical worsening events in CTD-PAH patients. NCT05980728. Connective Tissue Disease Patients With Pulmonary Hypertension. Oct 17, 2023.

Objectives: The primary objective of this study is to investigate the potential of cardiac magnetic resonance (CMR) parameters to augment prognostic evaluation in patients with CTD-associated pulmonary arterial hypertension (CTD-PAH). Methods: A retrospective, single-centre cohort study was conducted on 110 patients with CTD-PAH who were diagnosed via right heart catheterization between 2017 and 2023. These patients underwent CMR examinations based on clinical indications. Results: After a mean follow-up period of 27 months, 27 patients experienced clinical deterioration events. After adjusting for age, sex and COMPERA 2.0 risk assessment model parameters, five CMR metrics were identified as independent risk factors for clinical deterioration in CTD-PAH patients. Receiver operating characteristic curve analysis showed that combining COMPERA 2.0 risk assessment model with CMR metrics improved predictive performance, with interventricular septum extracellular volume (IVS ECV) providing the greatest benefit among tissue metrics and right ventricular ejection fraction (RVEF) showing the most improvement among right heart function metrics. Kaplan-Meier（KM） survival curves revealed that patients with RVEF 31.4% had the poorest prognosis. Calibration curves indicated that integrating RVEF and IVS ECV significantly enhanced the accuracy and reliability of the COMPERA 2.0 risk assessment model in predicting 1-, 2- and 3-year event-free survival rates in CTD-PAH patients, with the C-index improving from 0.626 to 0.805. Conclusion: Combining RVEF and IVS ECV with COMPERA 2.0 risk assessment model significantly enhances the model’s predictive accuracy for clinical deterioration in CTD-PAH patients.