Characterization and prognostic importance of chronotropic incompetence in heart failure with preserved ejection fraction

Naoki Yuasa, Masaru Obokata, Tomonari Harada, Kazuki Kagami, Hidemi Sorimachi, Yuki Saito, Ayami Naito, Toshimitsu Kato, Naoki Wada, Hideki Ishii

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Background: Exercise intolerance is the primary symptom of patients with heart failure with preserved ejection fraction (HFpEF). Chronotropic incompetence has been considered to be common and contribute to poor exercise capacity in HFpEF. However, clinical characteristics, pathophysiology, and outcomes of chronotropic incompetence in HFpEF remain poorly understood. Methods: Patients with HFpEF (n = 246) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. The patients were divided into two groups based on the presence of chronotropic incompetence, which was defined by heart rate reserve <0.80. Results: Chronotropic incompetence was common in HFpEF (n = 112, 41 %). Compared to HFpEF patients with a normal chronotropic response (n = 134), those with chronotropic incompetence had higher body mass index, a higher prevalence of diabetes, more frequent β-blocker use, and worse New York Heart Association class. During peak exercise, patients with chronotropic incompetence demonstrated less increase in cardiac output and arterial oxygen delivery (cardiac output × saturation × hemoglobin × 1.34 × 10), higher metabolic work (peak oxygen consumption [VO2]/watt), an inability to increase arteriovenous oxygen difference, and poorer exercise capacity (lower peak VO2) than those without. Chronotropic incompetence was associated with higher rates of a composite of all-cause mortality or worsening HF events (hazard ratio, 2.66, 95 % confidence intervals, 1.16–6.09, p = 0.02). Conclusion: Chronotropic incompetence is common in HFpEF, and is associated with unique pathophysiologic characteristics during exercise and clinical outcomes.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalJournal of Cardiology
Issue number2
Publication statusPublished - Feb 2024


  • Chronotropic response
  • Exercise
  • Exercise capacity
  • Expired gas analysis
  • Heart failure with preserved ejection fraction


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