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ABSTRACTBackground and ObjectiveSeladelpar is an oral, once‐daily medication that improves cholestasis through its selective peroxisome proliferator‐activated receptor (PPAR‐δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.MethodsA systematic review and meta‐analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).ResultsThree RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: −1.47 with 95% CI [−2.73, −0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).ConclusionSeladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC.Trial Registration: PROSPERO: CRD42024521208

ABSTRACT Background Mitral transcatheter edge‐to‐edge repair (TEER) is approved for patients with severe functional mitral regurgitation (FMR) beyond optimal medical therapy (OMT). Aims We aimed to assess TEER's efficacy beyond OMT in patients with severe FMR. Methods A systematic review and meta‐analysis were conducted, including randomized controlled trials from PubMed, Cochrane, Scopus, and EMBASE up to September 2024. Primary outcome: heart failure hospitalization (HFH); secondary outcomes: cardiovascular (CV) mortality, all‐cause mortality, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Time‐to‐event data from Kaplan−Meier curves were reconstructed for individual patient data. Results Three studies (1423 patients) were included. TEER significantly reduced HFH (RR 0.73, 95% CI 0.58−0.92, p < 0.01) and CV mortality (RR 0.79, 95% CI 0.66−0.95, p = 0.01), and improved KCCQ scores (mean difference 14.32, 95% CI 10.85−17.80, p < 0.01) compared to OMT. No significant difference was found for all‐cause mortality (RR 0.80, 95% CI 0.63−1.02, p = 0.07). Prognostic meta‐analysis showed a 34% reduced risk of HFH (HR 0.66, 95% CI 0.45−0.96, p = 0.03), but no effect on all‐cause or CV mortality. Reconstructed Kaplan−Meier analysis confirmed a 34% reduced risk of HFH (HR 0.65, p < 0.001), with effect attenuation after 15 months in landmark analysis (HR 0.64, p = 0.07). RMST analysis showed a 2.9‐month longer HFH‐free survival with TEER ( p < 0.01). Conclusion In patients with FMR, TEER significantly reduces HFH, improves functional status, and lowers CV mortality at 24 months but does not significantly affect all‐cause mortality. The device group experienced a modest, but significant, 2.9‐month longer HFH‐free survival compared to the control group. However, the reduction in HFH showed attenuation beyond 15 months.

BACKGROUND: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation. METHODS: We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure. RESULTS: Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups ( P <0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality ( P <0.01) and showed a trend toward an association with a lower incidence of stroke ( P =0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year. CONCLUSIONS: Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/display_record.php? ; Unique identifier: CRD42024525542.

ABSTRACTBackgroundAnemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.MethodsWe comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024 and conducted a prognostic systematic review and meta‐analysis. All analyses were performed using R V. 4.3.1. This meta‐analysis was registered at PROSPERO (CRD42024556023).ResultsWe included 23 studies comprising 286,781 patients for analysis. Anemia had a significant association with an 84% increase in risk of major bleeding (HR: 1.84 with 95% CI [1.59, 2.13], p < 0.01), a 32% increase in the risk of intracranial hemorrhage (HR: 1.32 with 95% CI [1.10, 1.58], p < 0.01), a 98% increase in the risk of gastrointestinal bleeding (HR: 1.98 with 95% CI [1.67, 2.35], p < 0.01), and a 91% increase in the risk of all‐cause mortality (HR: 1.91 with 95% CI [1.46, 2.51], p < 0.01). However, the impact of anemia did not significantly affect the risk of stroke, transient ischemic stroke (TIA), or systemic embolism (HR: 1.07 with 95% CI [0.93, 1.22], p = 0.36).ConclusionAnemia was significantly associated with an increased risk of major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause mortality. However, anemia did not significantly impact stroke, TIA, or systemic embolism.

Background: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing after diagnosing atrial fibrillation (AF). Purpose: We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on AF recurrence, all-cause mortality, stroke, and heart failure (HF) after AF catheter ablation. Methods: We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through February 2024. We conducted a pair-wise and prognostic systematic review and meta-analysis with a reconstructed time-to-event data meta-analysis. All analyses were performed using R V. 4.3.1. PROSPERO ID: CRD42024525542. Results: With the inclusion of 22 studies, our cohort comprised a total of 42,101 patients. Regarding pair-wise meta-analysis, shorter DAT was significantly associated with a decreased incidence of AF recurrence across paroxysmal and persistent AF subgroups. Moreover, DAT ≤ one year was significantly associated with a decreased incidence of all-cause mortality (RR: 0.73 with 95% CI [0.59, 0.92], P< 0.01) with a trend toward lowering the risk of stroke (RR: 0.80 with 95% CI [0.62, 1.03], P= 0.08). However, there was no significant difference between DAT ≤ one year and DAT > one year in HF. Regarding adjusted prognostic meta-analysis, longer DAT was significantly associated with an increased risk of AF recurrence (P < 0.01). Our reconstructed Kaplan Meier showed that DAT > one year was significantly associated with a 50% increase in the risk of AF recurrence compared to DAT ≤ one year (HR: 1.50 with 95% CI [1.42, 1.58], P< 0.00001) over 60 months follow-up. Conclusion: Our meta-analysis strongly underscores the critical importance of a short DAT in significantly reducing AF recurrence and all-cause mortality, with a trend toward lowering stroke risk, though no significant impact on HF was observed. Early ablation proves beneficial not only for patients with paroxysmal AF but also for those with persistent AF. These findings suggest that minimizing DAT can markedly improve AF outcomes, warranting further investigation to optimize treatment strategies.

Background: Heart failure (HF) is associated with systemic inflammation and hypercatabolic syndrome, impacting body metabolism. The advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional biomarker. Purpose: We aimed to investigate the prognostic role of ALI in patients with HF. Methods: We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024. We conducted a pair-wise and prognostic systematic review and meta-analysis with a reconstructed time-to-event data meta-analysis. All analyses were performed using R V. 4.3.1. This meta-analysis was registered at PROSPERO (CRD42024535227). Results: We included four studies with 2,247 patients. In the pair-wise meta-analysis, ALI ≤ 25 was significantly associated with an increased incidence of all-cause mortality compared with ALI > 25 (risk ratio [RR] 1.73, 95% confidence interval [CI] 1.36-2.21, P< 0.01). On the adjusted prognostic meta-analysis, higher ALI (>25) was significantly associated with a reduction in the incidence of all-cause mortality (hazards ratio [HR] 0.45, 95% CI 0.35-0.58, P< 0.01). The reconstructed Kaplan Meier showed that ALI > 25 was significantly associated with a 56% reduction in the incidence of all-cause mortality compared with ALI ≤ 25 (HR 0.44, 95% CI 0.38-0.50, P< 0.000001). Conclusion: Among patients with HF, a low ALI was associated with a higher incidence of all-cause mortality rate than those with a high ALI. These findings suggest that ALI can be used for prognostic stratification and aid clinical decision-making in HF management.

Abstract Background Since pulsed-field ablation (PFA) specifically targets myocardial tissue, it has become a cutting-edge substitute for radiofrequency (RF) and cryoablation. Purpose We aim to compare the safety and efficacy of PFA vs thermal ablation for AF ablation. Methods We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) and observational comparative studies, which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through September 2023. RevMan version 5.4 software was used to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results Seventeen studies with a total of 2,255 patients were included. PFA was significantly associated with a decreased AF recurrence (RR: 0.65, 95% CI [0.51, 0.84], P= 0.0010) but not any arrhythmia recurrence (RR: 0.87, 95% CI [0.69, 1.09], P= 0.22). Also, PFA was significantly associated with decreased total procedure time (MD: -15.15, 95% CI [-20.23, -10.07], P&lt; 0.00001) and heart rate (MD: -7.56, 95% CI [-12.78, -2.34], P= 0.005); however, there was no significant difference between PFA and thermal ablation in fluoroscopy time (MD: 2.83, 95% CI [-0.38, 6.04], P= 0.08). PFA decreased phrenic nerve palsy (RR: 0.38, 95% CI [0.15, 0.98], P= 0.05) and esophageal lesions (RR: 0.09, 95% CI [0.01, 0.69], P= 0.02); however, PFA was significantly associated with increased pericardial tamponade (RR: 6.14 with 95% CI [1.43, 26.33], P= 0.01). Conclusion PFA was significantly associated with decreased AF recurrence, heart rate, total procedure time, phrenic nerve palsy, esophageal lesion, and increased incidence of pericardial tamponade compared with thermal ablation. However, current evidence is mainly weighted by observational studies, requiring further large-scale randomized trials.Figure