European Journal of Clinical Investigation最新文献

{"title":"Early Hemolysis, Myolysis and Renal Stress Following Pentaspline Pulsed Field Versus Radiofrequency Ablation of Atrial Fibrillation","authors":"Paul Felix Harbich,&nbsp;Lisa Auer,&nbsp;Florian Tinhofer,&nbsp;Achim Leo Burger,&nbsp;Tobias Eberl,&nbsp;Patrick Weltler,&nbsp;Stephan Dobner,&nbsp;Alexander Geppert,&nbsp;Kurt Huber,&nbsp;Christoph Clemens Kaufmann","doi":"10.1111/eci.70248","DOIUrl":"10.1111/eci.70248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pulsed field ablation (PFA) is an effective alternative to radiofrequency ablation (RFA) for pulmonary vein isolation (PVI) in atrial fibrillation (AF), offering procedural advantages and a favourable safety profile. However, single-shot PFA (ssPFA) has been associated with biochemical evidence of haemolysis and myocardial injury, raising concerns regarding potential renal impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective observational study, 40 patients undergoing first-time PVI were analysed (20 RFA and 20 pentaspline ssPFA). Blood samples were obtained pre-procedure and 1, 4 and 24 h post-ablation. Markers of myolysis (myoglobin), haemolysis (haptoglobin and bilirubin), renal function (creatinine, eGFR and Cystatin C) and tubular stress (NGAL and KIM-1) were assessed. Biomarker trajectories were analysed using two-way repeated-measures ANOVA and correlation analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significantly higher postprocedural myoglobin levels, greater reductions in haptoglobin and greater elevations in bilirubin were observed after ssPFA than after RFA (all interaction effects <i>p</i> &lt; 0.001). Changes in renal function and tubular stress biomarkers were modest and largely comparable between modalities. Exploratory correlation analyses demonstrated inverse associations between changes in myoglobin and eGFR, with the strongest correlation observed at 24 h (<i>ρ</i> = −0.55). The association between early myoglobin release and subsequent eGFR changes was confined to the ssPFA cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ssPFA induces substantially greater acute myolysis and haemolysis than RFA following PVI. No patient met serum creatinine-defined criteria of acute kidney injury within the observation period. Myoglobin release was associated with transient renal functional changes and may represent a mechanistically plausible, non-causal marker of early renal stress following ssPFA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Electrical Morphology to Physiological Dynamics: Lessons From ECG Adoption for the Clinical Integration of Heart Rate Variability","authors":"José Luis Puglisi,&nbsp;Gurpreet Sodhi,&nbsp;Samuel Minucci Carmargo,&nbsp;Daniel Gustavo Goroso","doi":"10.1111/eci.70249","DOIUrl":"10.1111/eci.70249","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Heart rate variability (HRV) has remained a relatively finite and niche tool in cardiology despite decades of research supporting its physiological and clinical relevance. This limited adoption may resemble the early history of electrocardiography (ECG), which was initially regarded by many physicians as a laboratory instrument rather than a routine clinical tool. The delayed acceptance of ECG reflected technological limitations, cultural resistance and the need for clinicians to master unfamiliar concepts derived from physics and electrophysiology. HRV faces comparable barriers today. Although derived from ECG RR intervals, HRV requires interpretation of time-domain, frequency-domain, geometric and nonlinear indices that may appear mathematically complex and distant from conventional bedside reasoning.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We argue that HRV should not be viewed as a replacement for ECG, but as an extension of ECG from electrical morphology to physiological dynamics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Lessons from ECG history were examined and compared with the current state of HRV adoption in clinical practice. The complementary diagnostic roles of ECG morphology and HRV analysis were considered, together with the potential contribution of wearable sensors, remote monitoring, artificial intelligence and large language models to facilitate HRV interpretation, education and clinical integration.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Whereas conventional ECG morphology identifies arrhythmias, conduction disturbances, ischemic alterations and overt electrical abnormalities, HRV provides insight into autonomic modulation, cardiovascular adaptability and systemic physiological regulation. The emergence of wearable sensors, remote monitoring, artificial intelligence and large language models creates an opportunity to overcome barriers that have limited HRV adoption. Artificial intelligence may serve as an educational and interpretive bridge, translating complex HRV metrics into clinically meaningful concepts while supporting medical training, artefact awareness, case-based learning and workflow integration.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;HRV faces barriers comparable to those encountered during the early adoption of ECG, including technological limitations, educational challenges and resistance to incorporating unfamiliar physiological concept","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Inflammation and Risk of Thromboembolism, Mortality, and Treatment Response in Patients With Cancer Receiving Immune Checkpoint Inhibitors","authors":"Leyla Ay,&nbsp;Ingrid Pabinger,&nbsp;Matthias Preusser,&nbsp;Anna Sophie Berghoff,&nbsp;Christoph Hoeller,&nbsp;Cihan Ay,&nbsp;Florian Moik","doi":"10.1111/eci.70243","DOIUrl":"https://doi.org/10.1111/eci.70243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICI) are widely used in cancer therapy, but biomarkers for thromboembolic risk, treatment response, and survival remain limited. We evaluated the association of systemic inflammatory indices with these clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective cohort study, 580 ICI-treated patients at the Medical University of Vienna, Austria, were included. Inflammatory indices including neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), lymphocyte-monocyte-ratio (LMR), systemic immune-inflammation-index (SII) and C-reactive-protein-albumin-ratio (CAR) were calculated at ICI-start and longitudinally within 3 months. Co-primary outcomes were risk of venous thromboembolism (VTE), assessed using competing risk analysis, and overall- and progression-free-survival (OS/PFS), evaluated with Cox regression, whereas longitudinal biomarker dynamics were analysed using time-dependent analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher baseline NLR (HR 1.65, 95% CI: 1.28–2.12), CAR (HR 1.99, 95% CI: 1.67–2.38), and SII (HR 1.18, 95% CI: 1.00–1.39) were independently associated with shorter OS, while higher LMR (HR 0.44, 95% CI: 0.30–0.67) was associated with longer survival. For PFS, elevated NLR (HR 1.29, 95% CI: 1.05–1.57), higher PLR (HR 1.18, 95% CI: 1.00–1.39), lower LMR (HR 0.57, 95% CI: 0.43–0.70), and higher CAR (HR 1.42, 95% CI: 1.28–1.62) predicted poorer outcomes. None of the indices at treatment start were associated with VTE, yet doubling of levels within 3 months indicated higher VTE risk for PLR (sub-distribution hazard ratio [SHR]: 3.03 95% confidence interval [CI]: 1.05–8.08) and a borderline-significant association for CAR (SHR: 2.02, 95% CI: 0.89–4.60).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found that selected inflammatory indices were associated with poor OS and PFS in ICI-treated patients, and longitudinal dynamics might identify patients at higher risk for VTE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Intensity Statin Treatment Is Associated With Reduced Growth Differentiation Factor-15 in Patients With Coronary Artery Disease","authors":"Konrad Stępień,&nbsp;Michał Ząbczyk,&nbsp;Joanna Natorska,&nbsp;Jarosław Zalewski,&nbsp;Jacek Jawień,&nbsp;Anetta Undas","doi":"10.1111/eci.70241","DOIUrl":"https://doi.org/10.1111/eci.70241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growth differentiation factor-15 (GDF-15) is upregulated in coronary artery disease (CAD). The relationship of intensive statin therapy with circulating GDF-15 levels has not been explored yet. In the current secondary analysis of an observational cohort, we investigated whether high-intensity statin treatment is associated with GDF-15 in patients with advanced CAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 102 CAD patients we measured GDF-15 levels before and after median 7 [6–8] months from initiation atorvastatin 80 mg/day (<i>n</i> = 63, 61.8%) or rosuvastatin 40 mg/day (<i>n</i> = 39, 38.2%). At the two time points we also determined C-reactive protein (CRP), thrombin generation and fibrinolysis inhibitors. There was no concurrent control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline GDF-15 levels (median 942; interquartile range 639–1284 pg/mL) were associated solely with age (<i>R</i> = 0.567, <i>p</i> &lt; 0.001) and CRP (<i>R</i> = 0.464, <i>p</i> &lt; 0.001), but not with lipid profile. On high-intensity statin therapy GDF-15 reduction by 17.8% was observed (<i>p</i> = 0.006), which was associated with CRP lowering by 46.4% (<i>R</i> = 0.788, <i>p</i> &lt; 0.001), but not with changes in total cholesterol (by 17.6%) and low-density lipoprotein cholesterol (LDL-C) (by 28.1%). However, GDF-15 levels were lower by 28.5% (<i>p</i> &lt; 0.001) and 18.9% (<i>p</i> = 0.013) in 43 patients (42.2%) who achieved the target LDL-C &lt; 1.8 mmol/L and 19 (18.6%) with LDL-C &lt; 1.4 mmol/L, respectively, as compared to the remainder. The type of statin was not associated with follow-up GDF-15. Age (<i>p</i> = 0.029), baseline GDF-15 (<i>p</i> &lt; 0.001) and CRP (<i>p</i> &lt; 0.001), but not LDL-C, were independently associated with follow-up GDF-15.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrated that high-dose statin therapy is associated with lower GDF-15 in CAD patients and this effect is largely related to the anti-inflammatory properties of statins.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 7","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pacemaker Status and 5-Year Mortality After TAVI: A Sex-Specific Analysis","authors":"Cecilia Veraar,&nbsp;Gudrun Lamm,&nbsp;Maximilian Will,&nbsp;Matthias Hammerer,&nbsp;Matthias Granner,&nbsp;Lion Merl,&nbsp;Konstantin Schwarz,&nbsp;Julia Mascherbauer","doi":"10.1111/eci.70242","DOIUrl":"10.1111/eci.70242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sex-specific differences regarding the prognostic impact of permanent pacemaker (PM) implantation after transcatheter aortic valve implantation (TAVI) remain largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate sex-specific associations between pre-existing and new post-procedural PM implantation and short- and long-term mortality after TAVI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This post hoc analysis of a prospective registry included consecutive patients who underwent TAVI between 2016 and 2020. Patients were stratified by sex and assigned to three groups: no PM, pre-existing PM (pre-PM) and PM implantation within 30 days of TAVI (post-PM). The primary endpoint was 5-year all-cause mortality; the secondary endpoint was 30-day mortality. Sex-stratified multivariable proportional hazards models and Kaplan–Meier analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1114 patients (81 ± 5 years, 49.8% female), women more frequently had no PM (80.2% vs. 70.8%, <i>p</i> &lt; 0.001) and less often had a pre-existing PM (7.0% vs. 14.5%, <i>p</i> &lt; 0.001). Post-PM rates were similar between sexes (12.8% vs. 14.7%, <i>p</i> = 0.172). Thirty-day survival differed by PM status only in women, with worse outcomes in the post-PM group (log-rank <i>p</i> = 0.033), whereas no difference was observed in men (<i>p</i> = 0.542). Five-year survival did not differ by PM status among women (<i>p</i> = 0.572) but differed significantly among men (<i>p</i> &lt; 0.001), with the lowest survival in men with pre-PM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Post-procedural PM implantation was associated with higher 30-day mortality in women, whereas pre-existing PM predicted reduced 5-year survival in men, supporting sex-specific risk assessment before and after TAVI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 7","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Scientific Research: Renegotiated Principles of Science, Proposals, Failures, and Successes","authors":"John P. A. Ioannidis","doi":"10.1111/eci.70240","DOIUrl":"10.1111/eci.70240","url":null,"abstract":"<p>Science is a self-correcting process, and scientific research aims to improve adequacy, accuracy, and utility. However, improving scientific research is a demanding task, especially when currently some key principles of science are challenged and renegotiated. Key challenges in the current environment include the increasing loss of trust in scientists; the production of most of the published scientific literature in countries without full democracy and/or in countries without fundamental freedoms, e.g., freedom of the press; limited public availability and transparency as most research is funded by non-public sponsors that do not prioritize or even seek publication of results; and rapid developments on the frontier of artificial intelligence where non-human agents can supplement and/or replace human researchers. Concurrently, there have been many proposals on how to improve research. Among a plethora of suggestions and guidance, some may not be useful or may even be harmful, and most lack evidence. Revisiting some key proposals shows mixed track records of failures and successes. Examples are provided from efforts to enhance collaboration, team science, and large studies; replication culture; registration and open science; containment of conflicts of interest; and statistical, computational, and informatics improvements. The optimal stages to improve research (early and/or late in the scientific process) may be debated, and the role, function, and mode of optimal peer review are also under scrutiny. Eventually, science and scientific research are demanding, hard enterprises. Genuine progress requires openness, honesty, and selflessness.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 7","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effects of Time-Varying Treatments: The G-Formula","authors":"Carmine Zoccali,&nbsp;Giovanni Tripepi","doi":"10.1111/eci.70239","DOIUrl":"10.1111/eci.70239","url":null,"abstract":"<div>\u0000 \u0000 <p>The g formula is a cornerstone method for estimating causal effects of time-varying treatments using longitudinal observational data in the presence of time-varying confounders that are affected by prior treatment. Standard regression techniques often fail in this setting because adjustment for such covariates can distort the very effects under study. The g-formula addresses this problem by expressing the mean potential outcome under specified static or dynamic treatment regimes as a function of the joint distribution of covariates, treatments and outcomes, which can be approximated via parametric or semi-parametric models and simulation. This review presents the g-formula, emphasizing intuitive explanations. After outlining the causal framework and the core identification assumptions—consistency, sequential exchangeability and positivity—the article describes practical parametric g-formula: model specification for covariate and outcome processes, implementation via forward simulation, and the interpretation of marginal causal contrasts between clinically relevant regimes. The g-formula is then situated within the family of g-methods alongside inverse probability weighting and targeted maximum likelihood estimation, highlighting complementary strengths and limitations. A dedicated section discusses concrete applications, including analyses of highly active antiretroviral therapy and AIDS or death, dynamic ‘when to start’ antiretroviral strategies in HIV and electronic health record-based evaluations of blood pressure treatment targets. Practical guidance on modelling choices, diagnostics and transparent reporting is provided to support applied researchers considering g-formula in clinical and epidemiological investigations.</p>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 7","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-Blockers After Myocardial Infarction With Preserved and Mildly Reduced Ejection Fraction: A Meta-Analysis With Trial Sequential Analysis","authors":"Michele Maremmani,&nbsp;Paolo Gianfico,&nbsp;Christian Templin,&nbsp;Fabrizio Montecucco,&nbsp;Luca Liberale,&nbsp;Simon Kraler,&nbsp;Victor Schweiger,&nbsp;Sergio Berti,&nbsp;Michele Emdin,&nbsp;Davide Di Vece","doi":"10.1111/eci.70238","DOIUrl":"10.1111/eci.70238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to evaluate the efficacy of β-blockers after myocardial infarction (MI) across left ventricular ejection fraction (LVEF) strata and to assess the conclusiveness of the available evidence using trial sequential analysis (TSA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, Embase and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) evaluating β-blockers in post-MI patients with LVEF ≥ 40%. A time-to-event meta-analysis was performed for the primary composite (as defined by each trial) and for individual endpoints. The Mantel–Haenszel method was used to pool risk ratios (RR) for major adverse cardiovascular events (MACE; death, MI or heart failure), including LVEF-stratified analyses. TSA estimated the required information size (RIS) and generated adjusted significance and futility boundaries, assuming a 5% type I error and 90% power.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across 19,826 post-MI patients (17,941 with LVEF ≥ 50% and 1885 with LVEF 40%–49%), β-blockers did not reduce time to the primary endpoint (HR 0.92, 95% CI 0.85–1.01; <i>p</i> = 0.08; <i>I</i>² = 35%) or mortality. In patients with preserved LVEF (≥ 50%), β-blocker therapy did not reduce the risk of death or MACE (RR 0.96, 95% CI 0.87–1.05; <i>I</i>² = 42%), with TSA confirming futility. Among those with mildly reduced LVEF (40%–49%), β-blockers reduced MACE (RR 0.74, 95% CI 0.58–0.94; <i>I</i>² = 0%), although TSA failed to establish conclusiveness (RIS of 5717 [14.4%]). A significant interaction by LVEF subgroup was observed for cardiac death (<i>p</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>β-blockers conferred no benefit in post-MI patients with preserved LVEF, with conclusive evidence of futility, whereas therapy was associated with reduced MACE in those with mildly reduced LVEF, pending confirmation in further adequately powered randomized trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Role of Serum Albumin Levels in Elderly Patients With Non-Valvular Atrial Fibrillation","authors":"Giuseppe Armentaro,&nbsp;Giulia Crudo,&nbsp;Danilo Menichelli,&nbsp;Mario Daidone,&nbsp;Giandomenico Severini,&nbsp;Carlo Fuoco,&nbsp;Alberto Panza,&nbsp;Pasquale Pignatelli,&nbsp;Francesco Andreozzi,&nbsp;Giorgio Sesti,&nbsp;Francesco Violi,&nbsp;Daniele Pastori,&nbsp;Antonino Tuttolomondo,&nbsp;Angela Sciacqua","doi":"10.1111/eci.70237","DOIUrl":"10.1111/eci.70237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Atrial fibrillation (AF) is the most common arrhythmia in the elderly, and is associated with an increased risk of cardiovascular events (CVE). Hypoalbuminemia is an independent predictor of all-cause and cardiovascular mortality in general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The purpose of this work is to evaluate the possible predictive value of serum albumin (SA) on MACE occurrence, in a cohort of elderly patients with non-valvular AF and several comorbidities for long-term follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>1057 elderly with non-valvular AF were enrolled (75.92 ± 6.1years; 295 on VKAs and 762 on DOACs) and stratified according to median value of SA, 532 patients with SA ≤ 3.6 g/dL and 525 patients with SA &gt; 3.6 g/dL. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction and cardiovascular death), and non-cardiovascular mortality occurrence were evaluated during a median follow-up of 5.5 years (IQR 2.1–7.2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the whole observational study, patients with SA ≤ 3.6 g/dL are associated with an increased risk of MACEs by 59%. In addition, 10-year ageing are associated with an increased risk of MACE; in contrast, a MNA score &gt; 24 pt and therapy with DOACs are associated with a reduced risk of MACE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elderly patients with non-valvular AF with SA ≤ 3.6 g/dL show a higher risk of MACE and non-cardiovascular mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Mitral Annular Disjunction on Magnetic Resonance Imaging With Cardiovascular Outcomes","authors":"Katharina Mascherbauer,&nbsp;Nikolai Nantschev,&nbsp;Christina Kronberger,&nbsp;Carolina Donà,&nbsp;Matthias Koschutnik,&nbsp;Varius Dannenberg,&nbsp;Michael Poledniczek,&nbsp;Lena Schmid,&nbsp;Katharina Singer,&nbsp;Laura Lunzer,&nbsp;Sophia Koschatko,&nbsp;Charlotte Jantsch,&nbsp;Gregor Heitzinger,&nbsp;Kseniya Halavina,&nbsp;Christian Nitsche,&nbsp;Franz Duca,&nbsp;Dietrich Beitzke,&nbsp;Christian Loewe,&nbsp;Philipp Bartko,&nbsp;Julia Mascherbauer,&nbsp;Christian Hengstenberg,&nbsp;Andreas Kammerlander","doi":"10.1111/eci.70235","DOIUrl":"10.1111/eci.70235","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitral annular disjunction (MAD) is increasingly recognised on cardiac magnetic resonance (CMR) imaging, yet its clinical significance remains under discussion. We aimed to determine the prevalence, prognostic impact, and association with native T1 relaxation time of MAD assessed in both end-systole and end-diastole in an all-comer CMR cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed data from 1969 patients enrolled in a prospective CMR registry at the Vienna General Hospital. MAD was defined as ≥ 1 mm separation between the left atrial wall at the mitral valve hinge point and the adjacent left ventricular myocardium. Native T1 relaxation times were measured at septal and lateral positions of the mitral annulus in the 4-chamber view. All-cause mortality was analysed by Cox proportional hazards regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>End-systolic MAD was present in 509 patients (25.9%), end-diastolic in 366 (18.6%). MAD patients were younger (59.6 ± 18.5 vs. 65.2 ± 17.9 years, <i>p</i> &lt; 0.001), had fewer comorbidities, and had higher left ventricular ejection fractions (58.8% ± 10.4% vs. 56.8% ± 14.4%, <i>p</i> = 0.009). MAD distance correlated with native annular T1 relaxation time (<i>r</i> = 0.24, <i>p</i> &lt; 0.001), and patients with MAD ≥ 5 mm showed higher T1 relaxation time than those &lt; 5 mm (1041 ± 148 vs. 1010 ± 72 ms, <i>p</i> = 0.028), while mid-septal T1 relaxation time showed no difference (<i>r</i> = 0.06, <i>p</i> = 0.252). During 63.7 months median follow-up, 485 deaths occurred. After multivariable adjustment, end-diastolic MAD was not associated with mortality (HR 0.95, 95%-CI 0.74–1.23, <i>p</i> = 0.712).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MAD is common and prognostically neutral after adjustment. However, larger disjunction distances are associated with higher native T1 relaxation time values at the annulus, suggesting local subclinical myocardial remodelling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}