Molecular and Cellular Basis for Diastolic Dysfunction

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and is frequently associated with metabolic risk factors. Patients with HFpEF have only a slightly lower mortality than patients with HF and reduced EF. The pathophysiology of HFpEF is currently incompletely understood, which...

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Bibliographic Details
Published in:Current heart failure reports 2012-12, Vol.9 (4), p.293-302
Main Authors: van Heerebeek, Loek, Franssen, Constantijn P. M., Hamdani, Nazha, Verheugt, Freek W. A., Somsen, G. Aernout, Paulus, Walter J.
Format: Article
Language:English
Subjects:
Cardiac Surgery
Cardiology
Cyclic GMP - physiology
Cyclic GMP-Dependent Protein Kinases - physiology
Extracellular Matrix - physiology
Heart Failure, Diastolic - pathology
Heart Failure, Diastolic - physiopathology
Humans
Imaging
Internal Medicine
Medicine
Medicine & Public Health
Myocytes, Cardiac - physiology
Nitric Oxide - physiology
Oxidative Stress - physiology
Prevention of Heart Failure After Myocardial Infarction (M St. John Sutton
Radiology
Section Editor
Signal Transduction - physiology
Vascular Surgery
Ventricular Function, Left - physiology
Ventricular Remodeling - physiology
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Summary:Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and is frequently associated with metabolic risk factors. Patients with HFpEF have only a slightly lower mortality than patients with HF and reduced EF. The pathophysiology of HFpEF is currently incompletely understood, which precludes specific therapy. Both HF phenotypes demonstrate distinct cardiac remodeling processes at the macroscopic, microscopic, and ultrastructural levels. Increased diastolic left-ventricular (LV) stiffness and impaired LV relaxation are important features of HFpEF, which can be explained by changes in the extracellular matrix and the cardiomyocytes. In HFpEF, elevated intrinsic cardiomyocyte stiffness contributes to high diastolic LV stiffness. Posttranslational changes in the sarcomeric protein titin, affecting titin isoform expression and phosphorylation, contribute to elevated cardiomyocyte stiffness. Increased nitrosative/oxidative stress, impaired nitric oxide bioavailability, and down-regulation of myocardial cyclic guanosine monophosphate and protein kinase G signaling could trigger posttranslational modifications of titin, thereby augmenting cardiomyocyte and LV diastolic stiffness.
ISSN:1546-9530
1546-9549
DOI:10.1007/s11897-012-0109-5