title: Myocardial hypertrophy and its role in heart failure with preserved ejection fraction.
abstract: Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca(2+) turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; frank.heinzel@charite.de.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Heinzel
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany;
authors.forename: Felix
authors.initials: F
authors.lastname: Hohendanner
authors.affiliation: Cardiology Department, The Second Affiliated Hospital & YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P. R. China; and Division of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Ge
authors.initials: G
authors.lastname: Jin
authors.affiliation: Division of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Sedej
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany;
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D013318:Stroke Volume / Q000502:physiology*
keywords: HFpEF; cardiac myocytes; diastolic dysfunction; left ventricular hypertrophy; remodeling