Background: The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study. Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death. Results: We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33–1.11) or all-cause death (RR 0.90; 95% CI 0.72–1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15–0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69–1.24) or all-cause death (RR 1.02; 95% CI 0.75–1.38). Conclusion: Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.

Recent multiomics advancements have improved our understanding of immune dysregulation in dilated cardiomyopathy (DCM). However, specific immune cell subsets and their regulatory genes are still ambiguous. This study aimed to explore immune cell imbalances and regulatory genes in DCM, discover diagnostic biomarkers, and identify potential therapeutic targets. Immune cell infiltration in DCM patients was quantified via deconvolution algorithms and single-cell RNA sequencing. Flow cytometry validation in 40 DCM patients and 40 healthy controls confirmed a notable increase in CD4⁺ effector memory T cells (CD4⁺ TEM cells) in DCM patients. Differential expression analysis of the GSE101585 dataset revealed 1783 genes. Weighted gene coexpression network analysis (WGCNA) identified a core immune-regulatory gene set, and protein–protein interaction (PPI) analysis highlighted 36 hub genes. Machine learning cross-validation identified four diagnostic biomarkers (LRRTM4, PTPN22, FAM175B, and PROM2) whose transcriptional changes had been validated by qPCR. Among these genes, PTPN22 was strongly correlated with CD4⁺ TEM cell abundance. Additionally, DSigDB analysis predicted 87 potential therapeutic drugs, with PTPN22 being the target of the most drugs. This study reveals a CD4⁺ T cell subset-centered immunoregulatory network in DCM, identifying novel diagnostic biomarkers and druggable targets to guide precision immunomodulatory strategies for DCM management.

Background Left bundle branch-optimized CRT (LOT-CRT), combining left bundle branch area pacing (LBBAP) with coronary venous pacing, may enhance resynchronization.WE aimed to compare LOT-CRT efficacy versus conventional biventricular CRT (BiV-CRT) or LBBAP-only. Methods This prospective study included 70 patients (66 ± 9 years, 68.6% male) (30 LOT-CRT, 40 BiV-CRT). Apart from QRS duration (QRSd), interventricular mechanical delay (IVMD), peak strain dispersion (PSD), global longitudinal strain (GLS) and myocardial work (MW) as global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were assessed by speckle-tracking echocardiography. LOT-CRT responders were switched to LBBAP-only mode for one month. Results During 6-month follow-up, the LOT-CRT group had a more profound reduction in QRSd (42.0 [23.3, 74.5] vs. 17.0 [16.3, 23.8]ms, P < 0.001) and PSD (72.0 [43.0, 114.3] vs. 35.5 [4.3, 82.0]ms, P = 0.001). Similar improvement was achieved in left ventricular ejection fraction (LVEF) (16.5 [3.8, 24.0] vs. 15.5 [5.3, 20.8]%) and GLS (-4.5 [-6.0, -3.0] vs. -3 [-6.0, -1.3]%) but the LOT-CRT group displayed better increase in GWE (24.0 [11.0, 29.3] vs. 10.0 [6.3, 14.8] %, P < 0.001). Both echocardiographic and clinical responses were achieved in 66.7% patients receiving LOT-CRT and 72.5% receiving BiV-CRT (P = 0.598). After switching to LBBAP, LOT-CRT responders (n = 20) showed QRSd widening (131.5 ± 26.4 vs. 142.2 ± 29.4ms, P < 0.001) accompanied by worsening LVEF (55.6 ± 7.7 vs 51.1 ± 7.7%, P = 0.002) and GLS (-10.9 ± 2.8 vs. -10.0 ± 2.3%, P = 0.006). Conclusions LOT-CRT represented as a viable alternative to BiV-CRT with superior intraventricular resynchronization, whereas LBBAP alone failed to maintain the benefits in cardiac synchrony and function of LOT-CRT. Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR) at http://www.chictr.org.cn/ (registration number: ChiCTR2500110771).