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

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Abstract

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.

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Authors and Affiliations

  1. Lea and Benjamin Davidai Division of Cardiovascular Medicine and Surgery, The Lydia and Carol Kittner, Poriya Medical Center, affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Lower Galilee, Tiberias, Israel

    Liza Grosman-Rimon, Sagi Gleitman, Doron Sudarsky, Alla Lubovich, Shemy Carasso & Erez Kachel

  2. The Academic College at Wingate, Wingate Institute, Netanya, Israel

    Liza Grosman-Rimon & Sharon Tsuk

  3. Lewis M. Fraad Department of Pediatrics, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Evan Wright

  4. Faculty of Medicine, University of Toronto, Toronto, Canada

    Solomon Sabovich

  5. Faculty of Health, York University, Toronto, Canada

    Jordan Rimon

  6. Department of Cardiology, Faculty of Health Sciences, Soroka Hospital, Ben-Gurion University, Beer Sheva, Israel

    Itzhak Gabizon

  7. Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Canada

    Spencer D. Lalonde, Michael A. McDonald & Vivek Rao

  8. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA

    David Gutterman

  9. Division of Cardiology, Montefiore Einstein Center for Heart and Vascular Care, Bronx, NY, USA

    Ulrich P. Jorde

  10. The Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel

    Erez Kachel

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  1. Liza Grosman-Rimon
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Contributions

Conception: Liza Grosman-Rimon, Erez Kachel Writing the manuscript: Liza Grosman-Rimon, Even Wright, Solomon Sabovich Drafting sections of the manuscript: Even Wright, Solomon Sabovich, Jordan Rimon, Spencer D. Lalonde Critically revising of the manuscript: David Gutterman, Michael A. McDonald, Sagi Gleitman, Doron Sudarsky, Alla Lubovich, Itzhak Gabizon, Sharon Tsuk Preparing figures: Jordan Rimon, David Gutterman Preparing tables: Liza Grosman-Rimon, Even Wright, Solomon Sabovich, Spencer D. Lalonde Approval of the version of the manuscript: Ulrich P. Jorde, Vivek Rao, Shemy Carasso, Erez Kachel

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Correspondence to Liza Grosman-Rimon or Erez Kachel.

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Grosman-Rimon, L., Wright, E., Sabovich, S. et al. Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients. Heart Fail Rev 28, 35–45 (2023). https://doi.org/10.1007/s10741-022-10232-y

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  • DOI: https://doi.org/10.1007/s10741-022-10232-y

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