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The pathophysiology of heart failure: a tale of two old paradigms revisited

Houman Ashrafian, Lynne Williams and Michael P Frenneaux
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DOI: https://doi.org/10.7861/clinmedicine.8-2-192
Clin Med April 2008
Houman Ashrafian
Department of Cardiovascular Medicine, University of Oxford
Roles: Wellcome Trust Clinical Research Fellow
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Lynne Williams
Department of Cardiovascular Medicine, University of Birmingham
Roles: Clinical Lecturer
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Michael P Frenneaux
Department of Cardiovascular Medicine, University of Oxford
Roles: British Heart Foundation Chair of Cardiovascular Medicine
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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).

KEY WORDS
  • diastolic ventricular interactions
  • energetics
  • fatty acid oxidation
  • Frank–Starling law
  • glucose
  • GLP-1
  • heart failure
  • perhexiline
  • pulmonary embolism
  • trimetazidine
  • uncoupling
  • © 2008 Royal College of Physicians
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The pathophysiology of heart failure: a tale of two old paradigms revisited
Houman Ashrafian, Lynne Williams, Michael P Frenneaux
Clinical Medicine Apr 2008, 8 (2) 192-197; DOI: 10.7861/clinmedicine.8-2-192

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The pathophysiology of heart failure: a tale of two old paradigms revisited
Houman Ashrafian, Lynne Williams, Michael P Frenneaux
Clinical Medicine Apr 2008, 8 (2) 192-197; DOI: 10.7861/clinmedicine.8-2-192
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