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Aims: In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being., Methods and Results: From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P > 0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results., Conclusion: Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting., Patients and Methods: Next-generation sequencing with FoundationOne® CDx was conducted primarily on primary tumor tissue from 112 consecutive patients with mTNBC. Genomic alterations were subdivided into canonical oncogenic pathways and noted for their involvement in homologous recombination deficiency (HRD). Altered genes and pathways were correlated with overall survival (OS) and evaluated regarding their association with real-world progression-free survival (rwPFS) in patients treated with different chemotherapy agents. Occurrence of alterations were compared between patients with exceptional response and rapid progression to chemotherapy., Results: After exclusion due to insufficient tumor tissue or clinical data, material from 97 patients was analyzed. The most frequently altered genes were TP53 (82 %), RAD21 (25 %) and PIK3CA (23 %). Altogether, 26 % of patients had an alteration leading to HRD. None of the analyzed alterations were associated with OS. Variants leading to HRD were associated with a prolonged rwPFS in patients treated with platinum-based chemotherapy in the first line setting (hazard ratio [HR], 0.31 [95 % CI: 0.12-0.84]). Exceptional responders more often exhibited alterations in the MYC and RAS/RTK pathways compared to rapid progressors., Conclusions: Patients with tumor alterations in HRD-related genes seem to define subgroups that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to different treatment strategies can provide insights into mechanisms of resistance and identify predictive biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)