Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients

Liza Grosman-Rimon, Evan Wright, Solomon Sabovich, Jordan Rimon, Sagi Gleitman, Doron Sudarsky, Alla Lubovich, Itzhak Gabizon, Spencer D. Lalonde, Sharon Tsuk, Michael A. McDonald, Vivek Rao, David Gutterman, Ulrich P. Jorde, Shemy Carasso, Erez Kachel

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of β-adrenergic receptors, β-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalHeart Failure Reviews
Issue number1
StatePublished - Jan 2023


  • Chronotropic responses
  • Exercise capacity
  • Heart failure
  • Norepinephrine
  • Rate-adaptive pacing

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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