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

H Ashrafian, L Williams, Michael Frenneaux

Research output: Contribution to journalEditorial

8 Citations (Scopus)


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 HE 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).
Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalClinical Medicine
Issue number2
Publication statusPublished - 1 Apr 2008


  • perhexiline
  • Frank-Starling law
  • glucose
  • energetics
  • GLP-1
  • heart failure
  • fatty acid oxidation
  • diastolic ventricular interactions
  • trimetazidine
  • pulmonary embolism
  • uncoupling


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