A Novel Paradigm for Heart Failure with Preserved Ejection Fraction: Comorbidities Drive Myocardial Dysfunction and Remodeling Through Coronary Microvascular Endothelial Inflammation.

Link to article at PubMed

A Novel Paradigm for Heart Failure with Preserved Ejection Fraction: Comorbidities Drive Myocardial Dysfunction and Remodeling Through Coronary Microvascular Endothelial Inflammation.

J Am Coll Cardiol. 2013 May 15;

Authors: Paulus WJ, Tschöpe C

Abstract
Over the last decennium, myocardial structure, cardiomyocyte function and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) A high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease and salt sensitive hypertension induce a systemic proinflammatory state; 2) A systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) Coronary microvascular endothelial inflammation reduces nitric oxide (NO) bioavailability, cyclic guanosine monophosphate (cGMP) content and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) Low PKG activity favours hypertrophy development and raises resting tension because of hypophosphorylation of titin; 5) Both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and HF development. The new HFPEF paradigm shifts emphasis from left ventricular (LV) afterload excess to coronary microvascular inflammation. This shift is supported by a favourable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction (HFREF), where remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation or vascular hyperaemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity with NO-donors, phosphodiesterase 5 inhibitors and statins.

PMID: 23684677 [PubMed - as supplied by publisher]

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