title: The pathophysiology of heart failure: a tale of two old paradigms revisited.
abstract: Although our current appreciation of the detrimental role of neurohumoral activation in heart failure (HF) has been intellectually appealing and has led to neurohumoral antagonism that has reduced morbidity and mortality from HF, the persisting disability and death rates remain unacceptably high. In the search for novel strategies to improve on these outcomes, we must reacquaint ourselves with basic cardiac physiology at levels ranging from the molecular to the systemic in order to identify new targets for the treatment of HF. This approach has already begun to yield results; in this review, two such aspects will be focused on: diastolic ventricular interaction and cardiac energetics. These two examples will be used to illuminate how fundamental research has elucidated age-old, although mechanistically elusive, principles (for example, the Frank-Starling law), explained why existing and emerging therapeutic approaches (for example, biventricular pacing in HF) have proved successful, and successfully identified novel therapy modes (for example, perhexiline as an energy augmentation agent).
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford.
authors.forename: Houman
authors.initials: H
authors.lastname: Ashrafian
authors.forename: Lynne
authors.initials: L
authors.lastname: Williams
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
mesh_terms: D002317:Cardiovascular Agents / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology; D010480:Perhexiline / Q000494:pharmacology; D014292:Trimetazidine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D014665:Vasodilator Agents; D010480:Perhexiline; D014292:Trimetazidine