title: What mechanisms underlie diastolic dysfunction in heart failure?
abstract: Abnormalities of diastolic function are common to virtually all forms of cardiac failure. However, their underlying mechanisms, precise role in the generation and phenotypic expression of heart failure, and value as specific therapeutic targets remain poorly understood. A growing proportion of heart failure patients, particularly among the elderly, have apparently preserved systolic function, and this is fueling interest for better understanding and treating diastolic abnormalities. Much of the attention in clinical and experimental studies has focused on relaxation and filling abnormalities of the heart, whereas chamber stiffness has been less well studied, particularly in humans. Nonetheless, new insights from basic and clinical research are helping define the regulators of diastolic dysfunction and illuminate novel targets for treatment. This review puts these developments into perspective with the major aim of highlighting current knowledge gaps and controversies.
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Md, USA. dkass@jhmi.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: Jean G F
authors.initials: JG
authors.lastname: Bronzwaer
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
mesh_terms: D000328:Adult; D000368:Aged; D001696:Biomechanical Phenomena; D020013:Calcium Signaling; D064211:Connectin; D003971:Diastole / Q000502:physiology*; D004548:Elasticity; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000145:classification / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000502:physiology; D009126:Muscle Relaxation; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology
chemical_list: D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases