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Left ventricular dysfunction in heart failure with preserved ejection fraction-molecular mechanisms and impact on right ventricular function

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Item Type:Review
Title:Left ventricular dysfunction in heart failure with preserved ejection fraction-molecular mechanisms and impact on right ventricular function
Creators Name:Heinzel, F.R. and Hegemann, N. and Hohendanner, F. and Primessnig, U. and Grune, J. and Blaschke, F. and de Boer, R.A. and Pieske, B. and Schiattarella, G.G. and Kuebler, W.M.
Abstract:The current classification of heart failure (HF) based on left ventricular (LV) ejection fraction (EF) identifies a large group of patients with preserved ejection fraction (HFpEF) with significant morbidity and mortality but without prognostic benefit from current HF therapy. Co-morbidities and conditions such as arterial hypertension, diabetes mellitus, chronic kidney disease, adiposity and aging shape the clinical phenotype and contribute to mortality. LV diastolic dysfunction and LV structural remodeling are hallmarks of HFpEF, and are linked to remodeling of the cardiomyocyte and extracellular matrix. Pulmonary hypertension (PH) and right ventricular dysfunction (RVD) are particularly common in HFpEF, and mortality is up to 10-fold higher in HFpEF patients with vs. without RV dysfunction. Here, we review alterations in cardiomyocyte function (i.e., ion homeostasis, sarcomere function and cellular metabolism) associated with diastolic dysfunction and summarize the main underlying cellular pathways. The contribution and interaction of systemic and regional upstream signaling such as chronic inflammation, neurohumoral activation, and NO-cGMP-related pathways are outlined in detail, and their diagnostic and therapeutic potential is discussed in the context of preclinical and clinical studies. In addition, we summarize prevalence and pathomechanisms of RV dysfunction in the context of HFpEF and discuss mechanisms connecting LV and RV dysfunction in HFpEF. Dissecting the molecular mechanisms of LV and RV dysfunction in HFpEF may provide a basis for an improved classification of HFpEF and for therapeutic approaches tailored to the molecular phenotype.
Keywords:Heart Failure (HF), Cardiomyocytes, Metabolism, Calcium, Sodium, Right Ventricle, Pulmonary Hypertension (PH)
Source:Cardiovascular Diagnosis and Therapy
Publisher:AME Publishing Company
Page Range:1541-1560
Date:October 2020
Additional Information:Copyright©Cardiovascular Diagnosis and Therapy. All rights reserved.
Official Publication:https://doi.org/10.21037/cdt-20-477
PubMed:View item in PubMed

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