The failing diabetic heart: focus on diastolic left ventricular dysfunction.
Diabetes mellitus (DM) is highly prevalent and is an important risk factor for congestive heart failure (HF). Increased left ventricular (LV) diastolic stiffness is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. Mechanisms whereby DM increases LV diastolic stiffness differ between HF with normal LV ejection fraction (EF) (HFNEF) and HF with reduced LVEF (HFREF). In diabetic HFREF, fibrosis and deposition of advanced glycation end products (AGEs) are the most important contributors to high LV diastolic stiffness, whereas in diabetic HFNEF, elevated resting tension of hypertrophied cardiomyocytes is the most important contributor to high LV diastolic stiffness. As HF mortality remains high in DM despite proven efficacy of current treatments, better understanding of the pathophysiology of high LV diastolic stiffness could be beneficial for novel therapeutic strategies.
van Heerebeek
Loek
L
Laboratory of Physiology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Somsen
Aernout
A
Paulus
Walter J
WJ
D006152:Cyclic GMP / Q000502:physiology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003971:Diastole; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D054144:Heart Failure, Diastolic / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology
D017127:Glycation End Products, Advanced; D009569:Nitric Oxide; D006152:Cyclic GMP