Effect of cardiac sympathetic nervous activity on mode of death in congestive heart failure

Eur Heart J. 2001 Jul;22(13):1136-43. doi: 10.1053/euhj.2000.2407.


Aims: To investigate whether strong cardiac sympathetic activity contributes primarily to sudden death or to worsening heart failure, and to determine the relationship of the size of cardiac noradrenaline stores to the mode of death.

Methods and results: The study population comprised 116 patients with congestive heart failure (ejection fraction 19+/-7%) and a mean follow-up of 18+/-19 months. Cardiac sympathetic nervous function was measured using coronary sinus blood sampling and noradrenaline isotope dilution methodology. Cardiac sympathetic activity was estimated from cardiac noradrenaline spillover, and noradrenaline stores from the overflow of the tritiated noradrenaline metabolite [(3)H]dihydroxyphenylglycol, which is produced by monoamine oxidase inside nerve endings. Small cardiac noradrenaline stores (below median) predicted death from worsening heart failure (hazard ratio=4.18, P<0.05), particularly if cardiac noradrenaline spillover was elevated (hazard ratio=2.36 per tertile, P<0.01), indicating progression of disease associated with defective sympathetic innervation. In contrast, large stores (hazard ratio=2.81, P<0.05), especially if coupled with increased noradrenaline spillover (hazard ratio=1.64 per tertile, P<0.05), were related to sudden death.

Conclusion: High cardiac sympathetic activity is a risk factor for sudden death, particularly in the presence of intact cardiac sympathetic innervation. Conversely, progression of myocardial disease and heart failure is closely associated with depletion of sympathetic nerves in the heart, especially if rates of noradrenaline release paradoxically remain high.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology*
  • Female
  • Follow-Up Studies
  • Heart / innervation*
  • Heart Failure / mortality*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / metabolism
  • Middle Aged
  • Norepinephrine / metabolism*
  • Proportional Hazards Models
  • Risk Factors
  • Survival Analysis
  • Sympathetic Nervous System / physiopathology*
  • Time Factors


  • Methoxyhydroxyphenylglycol
  • 3,4-dihydroxyphenylglycol
  • Norepinephrine