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      Myofilament dysfunction in diastolic heart failure

      review-article
      1 , 2 , , 1 , 2 , 3 ,
      Heart Failure Reviews
      Springer US
      Cardiomyocyte, Diastolic dysfunction, Myofilament, Relaxation

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          Abstract

          Diastolic heart failure (DHF), in which impaired ventricular filling leads to typical heart failure symptoms, represents over 50% of all heart failure cases and is linked with risk factors, including metabolic syndrome, hypertension, diabetes, and aging. A substantial proportion of patients with this disorder maintain normal left ventricular systolic function, as assessed by ejection fraction. Despite the high prevalence of DHF, no effective therapeutic agents are available to treat this condition, partially because the molecular mechanisms of diastolic dysfunction remain poorly understood. As such, by focusing on the underlying molecular and cellular processes contributing to DHF can yield new insights that can represent an exciting new avenue and propose a novel therapeutic approach for DHF treatment. This review discusses new developments from basic and clinical/translational research to highlight current knowledge gaps, help define molecular determinants of diastolic dysfunction, and clarify new targets for treatment.

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          Most cited references134

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          The protein kinase complement of the human genome.

          G. Manning (2002)
          We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.
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            Empagliflozin in Heart Failure with a Preserved Ejection Fraction

            Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
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              2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

              The “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure” replaces the “2013 ACCF/AHA Guideline for the Management of Heart Failure” and the “2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.” The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.
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                Author and article information

                Contributors
                anahita@uic.edu
                mcaule1@uic.edu
                Journal
                Heart Fail Rev
                Heart Fail Rev
                Heart Failure Reviews
                Springer US (New York )
                1382-4147
                1573-7322
                14 October 2023
                14 October 2023
                2024
                : 29
                : 1
                : 79-93
                Affiliations
                [1 ]Division of Cardiology, Department of Medicine, College of Medicine, University of Illinois at Chicago, ( https://ror.org/02mpq6x41) 840 S. Wood St., 920S (MC 715), Chicago, IL 60612 USA
                [2 ]Jesse Brown VA Medical Center, ( https://ror.org/049qtwc86) Chicago, IL USA
                [3 ]Department of Physiology and Biophysics and the Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, ( https://ror.org/02mpq6x41) Chicago, IL USA
                Author information
                http://orcid.org/0000-0001-6213-6673
                Article
                10352
                10.1007/s10741-023-10352-z
                10904515
                37837495
                7a380002-6f54-4481-bbc6-63a3fde14342
                © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 September 2023
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2024

                Cardiovascular Medicine
                cardiomyocyte,diastolic dysfunction,myofilament,relaxation
                Cardiovascular Medicine
                cardiomyocyte, diastolic dysfunction, myofilament, relaxation

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