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Aims: While factors associated with adverse events are well elucidated in setting of isolated left ventricular dysfunction, clinical and imaging-based prognosticators of adverse outcomes are lacking in context of biventricular dysfunction. The purpose of this study was to establish role of clinical variables in prognosis of biventricular heart failure (HF), as assessed by cardiac magnetic resonance imaging., Methods: Study cohort consisted of 840 patients enrolled in DERIVATE registry with coexisting CMR-derived right ventricular (RV) and left ventricular (LV) dysfunction, as defined by RV and LV ejection fractions ≤45 % and ≤ 50 %, respectively. The primary objective was to identify factors associated with adverse long-term outcomes, defined as composite of all-cause death and HF hospitalizations (DHFH). Kaplan-Meir curves were plotted for survival analysis. Cox proportional hazard models were constructed to estimate adjusted hazard ratios (aHRs) and associated 95 % confidence intervals for clinical variables and their correlation with adverse events., Results: Mean age was 61.0 years; 83.1 % were male, 26.6 % had diabetes mellitus (DM), and 45.9 % had non-ischemic cardiomyopathy. At median follow-up of 2 years, DHFH occurred in 32.5 % of the cohort. Kaplan-Meir analysis showed higher rate of DHFH in patients with DM (35.2 % vs. 22.6 %, p < 0.001). Multivariate Cox regression analysis showed that DM was independently associated with DHFH (aHR 1.61 [95 % CI: 1.15-2.25]; p = 0.003). Importantly, ACE-inhibitor/ARB usage in patients with DM was associated with significant reduction in DHFH (aHR 0.53 [95 % CI: 0.31-0.90]; p = 0.02)., Conclusion: In patients with biventricular HF, DM was a strong predictor of DHFH, with ACE-inhibitor/ARB usage having cardioprotective effect., Competing Interests: Declaration of competing interest Subhi J. Al’Aref is supported by NIH: National Institutes of Health, USA 2R01 HL12766105 & 1R21 EB030654 and receives royalty fees from Elsevier. Carlo De Cecco received grant from Siemens. Gianluca Pontone received institutional fees by General Electric, Bracco, Heartflow, Medtronic, Bayer, Bhoeringher. Juerg Schwitter received research support by Bayer Healthcare Switzerland. U. Joseph Schoepf received grant by Astellas, Bayer, General Electric, and Siemens Healthcare, personal fees by Guerbet, speaking honorarium by Heartflow. Akos Varga-Szemes received grant from Siemens Healthcare and personal fees from Elucid Bioimaging. The other authors have no conficts of interestes relevant to this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation., Objectives: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM., Methods: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints., Results: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007)., Conclusions: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care., Competing Interests: Funding Support and Author Disclosures The Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698) has provided funding for this study. Dr De Cecco has received a grant from Siemens. Dr Pontone has received institutional fees from General Electric, Bracco, Heartflow, Medtronic, Bayer, and Bhoeringher. Dr Schwitter has received research support from Bayer Healthcare Switzerland. Dr Schoepf has received grants from Astellas, Bayer, General Electric, and Siemens Healthcare; personal fees from Guerbet; and speaking honoraria from Heartflow. Dr Varga-Szemes has received grants from Siemens Healthcare and personal fees from Elucid Bioimaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Proton pump inhibitors (PPIs) are widely prescribed in all age groups, and their use is increasing. However, their safety profile has been frequently questioned., Aims: The aim of this study was to analyze the characteristics of PPI-related adverse drug reactions (ADRs) reported to the Italian spontaneous reporting system (SRS) database and relative to an Italian region (Sicily)., Methods: A 20-year observational, retrospective study was conducted, evaluating PPI-related ADR reports from Sicily between January 1st, 2001, and June 30th, 2021. The factors associated with ADR seriousness were investigated., Results: A total of 148 spontaneous reports of ADRs related to PPIs were analyzed. Lansoprazole was the drug with the highest number of associated reports (30.87%). The most frequently reported ADRs were cutaneous (24.56%) and/or gastrointestinal manifestations (18.10%), the latter especially in the case of lansoprazole-related ADRs (p<0.006). The great majority of ADR reports were relative to on-label prescriptions. Serious ADRs were 39 (26.35%). Serious ADRs were more common in reports including omeprazole than in reports containing other PPIs (p<0.008) and in reports presenting PPIs combined with other drugs than in reports with PPI single therapies (p<0.001)., Conclusion: Most PPI-related ADRs are non-serious. Omeprazole and combination therapy seem to be associated with ADR seriousness., Competing Interests: Conflict of interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Artificial intelligence (AI) is increasing its role in diagnosis of patients with suspicious coronary artery disease. The aim of this manuscript is to develop a deep convolutional neural network (CNN) to classify coronary computed tomography angiography (CCTA) in the correct Coronary Artery Disease Reporting and Data System (CAD-RADS) category., Methods: Two hundred eighty eight patients who underwent clinically indicated CCTA were included in this single-center retrospective study. The CCTAs were stratified by CAD-RADS scores by expert readers and considered as reference standard. A deep CNN was designed and tested on the CCTA dataset and compared to on-site reading. The deep CNN analyzed the diagnostic accuracy of the following three Models based on CAD-RADS classification: Model A (CAD-RADS 0 vs CAD-RADS 1-2 vs CAD-RADS 3,4,5), Model 1 (CAD-RADS 0 vs CAD-RADS>0), Model 2 (CAD-RADS 0-2 vs CAD-RADS 3-5). Time of analysis for both physicians and CNN were recorded., Results: Model A showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 47%, 74%, 77%, 46% and 60%, respectively. Model 1 showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 66%, 91%, 92%, 63%, 86%, respectively. Conversely, Model 2 demonstrated the following sensitivity, specificity, negative predictive value, positive predictive value and accuracy: 82%, 58%, 74%, 69%, 71%, respectively. Time of analysis was significantly lower using CNN as compared to on-site reading (530.5 ± 179.1 vs 104.3 ± 1.4 sec, p=0.01) CONCLUSIONS: Deep CNN yielded accurate automated classification of patients with CAD-RADS., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Animals administered the nitric oxide (NO) synthase inhibitor N-w-nitro-L-arginine methyl ester (NAME) for five days exhibited severe deficits in acquisition of a place-navigation learning task. The effect of NAME was selective to place-navigation learning. NAME had no effect on sensorimotor or motivational processes in a related task. These results are consistent with the view that NO participates in learning and execution of memory tasks.