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      Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction

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          Abstract

          Background

          In acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into circulation and contribute to inflammation and adverse cardiac remodelling. We aimed to investigate gut leakage markers and their associations with inflammation, infarct size and cardiac function.

          Methods

          We examined 61 ST-elevation myocardial infarction (STEMI) patients who developed acute HF within 48 hours of successful percutaneous coronary intervention (PCI). Serial blood samples were taken to measure lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14) and intestinal fatty acid binding protein (I-FABP). Cumulative areas under the curve (AUCs) from baseline to day 5 were calculated. Serial echocardiography was performed to assess left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and wall motion score index (WMSI). Single-photon emission CT (SPECT) was performed at 6 weeks to determine infarct size and LVEF.

          Results

          I-FABP AUC correlated positively with infarct size (r s=0.45, p=0.002), GLS (r s=0.32, p=0.035) and WMSI (r s=0.45, p=0.002) and negatively with LVEF measured by SPECT (r s=−0.40, p=0.007) and echocardiography (r s=−0.33, p=0.021) at 6 weeks. LPS AUC, LBP AUC and sCD14 AUC did not correlate to any cardiac function marker or infarct size. Patients, who at 6 weeks had above median GLS and WMSI, and below-median LVEF measured by SPECT, were more likely to have above median I-FABP AUC during admission (adjusted OR (aOR) 5.22, 95% CI 1.21 to 22.44; aOR 5.05, 95% CI 1.25 to 20.43; aOR 5.67, 95% CI 1.42 to 22.59, respectively). The same was observed for patients in the lowest quartile of LVEF measured by echocardiography (aOR 9.99, 95% CI 1.79 to 55.83) and three upper quartiles of infarct size (aOR 20.34, 95% CI 1.56 to 264.65).

          Conclusions

          In primary PCI-treated STEMI patients with acute HF, I-FABP, a marker of intestinal epithelial damage, was associated with larger infarct size and worse cardiac function after 6 weeks.

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          Most cited references31

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          2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

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            The inflammatory response in myocardial injury, repair, and remodelling.

            Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of postinfarction remodelling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited to the infarcted area, remove dead cells and matrix debris by phagocytosis, while preparing the area for scar formation. Timely repression of the inflammatory response is critical for effective healing, and is followed by activation of myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor β family are critically involved in suppression of inflammation and activation of a profibrotic programme. Translation of these concepts to the clinic requires an understanding of the pathophysiological complexity and heterogeneity of postinfarction remodelling in patients with myocardial infarction. Individuals with an overactive and prolonged postinfarction inflammatory response might exhibit left ventricular dilatation and systolic dysfunction and might benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated fibrogenic reaction can develop heart failure with preserved ejection fraction and might require inhibition of the Smad3 (mothers against decapentaplegic homolog 3) cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies.
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              Proton pump inhibitors affect the gut microbiome

              Background and aims Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10−38). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. Conclusions The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.
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                Author and article information

                Contributors
                Journal
                Open Heart
                Open Heart
                openhrt
                openhrt
                Open Heart
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2053-3624
                2024
                13 September 2024
                : 11
                : 2
                : e002868
                Affiliations
                [1 ]departmentOslo Center for Clinical Heart Research, Department of Cardiology Ullevaal , Ringgold_155272Oslo University Hospital , Oslo, Norway
                [2 ]departmentInstitute of Clinical Medicine, Faculty of Medicine , Ringgold_6305University of Oslo , Oslo, Norway
                [3 ]departmentDepartment of Cardiology Ullevaal , Ringgold_155272Oslo University Hospital , Oslo, Norway
                [4 ]departmentSection of Clinical Immunology and Infectious Diseases Rikshospitalet , Ringgold_155272Oslo University Hospital , Oslo, Norway
                Author notes

                Supplemental material: Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

                Additional supplemental material is published online only. To view, please visit the journal online ( https://doi.org/10.1136/openhrt-2024-002868).

                The Department of Cardiology, Oslo University Hospital Ullevaal received an unrestricted educational grant from the manufacturer of levosimendan, Orion Pharma in 2005. Orion Pharma did not, however, provide study medication or participate in the design, monitoring or analyses of the present study. The authors declare no conflict of interest.

                Author information
                http://orcid.org/0000-0003-2524-4389
                Article
                openhrt-2024-002868
                10.1136/openhrt-2024-002868
                11404232
                39277188
                16ab22ef-b956-4908-a2fb-17b7b453beac
                Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 29 July 2024
                : 24 August 2024
                Funding
                Funded by: The Research Council of Norway;
                Award ID: N/A
                Funded by: South-Eastern Norway Regional Health Authority;
                Award ID: N/A
                Funded by: Orion Pharma;
                Award ID: N/A
                Funded by: University of Oslo;
                Award ID: N/A
                Funded by: The Scientific Council at Oslo University Hospital;
                Award ID: N/A
                Funded by: The Centre for Heart Failure Research;
                Award ID: N/A
                Categories
                Original Research
                Heart Failure and Cardiomyopathies
                1506

                myocardial infarction,heart failure,biomarkers,inflammation

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