Resting heart rate and heart rate reserve in advanced heart failure have distinct pathophysiologic correlates and prognostic impact: A prospective pilot study

Jan Benes, Martin Kotrc, Barry A. Borlaug, Katerina Lefflerova, Petr Jarolim, Bela Bendlova, Antonin Jabor, Josef Kautzner, Vojtech Melenovsky

Research output: Contribution to journalArticle

25 Scopus citations


Objectives: The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. Background: The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. Methods: In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. Results: Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. Conclusions: Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalJACC: Heart Failure
Issue number3
StatePublished - Jun 1 2013



  • Biomarkers
  • CI
  • Chronotropic incompetence
  • Exercise
  • HF
  • HR
  • HRR
  • Heart failure
  • Heart rate
  • LV
  • NYHA
  • RV
  • VCo
  • VE
  • Vo

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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