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Advances in ME/CFS Research and Clinical Care

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2019.00082

Chronotropic incompetence: an overlooked determinant of symptoms and activity limitation in myalgic encephalomyelitis/chronic fatigue syndrome?

  • 1Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, United States
  • 2Workwell Foundation, United States
  • 3Department of Health, Exercise, and Sport Sciences, College of the Pacific, University of the Pacific, United States

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM. In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship. However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic incompetence (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.

Keywords: Myalgic encephalomyelitis (ME), Exercise, Exercise Test, Heart Rate, Chronotropic incompetence (CI), Chronic fatigue sydrome

Received: 24 Aug 2018; Accepted: 26 Feb 2019.

Edited by:

Kenneth J. Friedman, Medical School, Rutgers, The State University of New Jersey, United States

Reviewed by:

Jonathan Ipser, University of Cape Town, South Africa
Tim Takken, University Medical Center Utrecht, Netherlands  

Copyright: © 2019 Davenport, Lehnen, Stevens, VanNess, Stevens and Snell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Todd E. Davenport, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, United States,