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Heart rate elevations over time predict a higher CV risk in HFpEF

Literature - Vazir A, Claggett B, Pitt B, et al. - J Am Coll Cardiol HF 2017; published online ahead of print


Studies have shown that an increase in heart rate (HR) over time was associated with a higher risk for adverse events in subjects without known CVD, and in subjects with hypertension and HF [1-4]. The prognostic value of baseline HR and change in HR over time in patients with HFpEF is, however, not known. This analysis of the TOPCAT study [5] aimed to determine whether baseline resting HR, time-updated resting HR and temporal changes in HR from the preceding visit are of prognostic importance in patients with HFpEF.

This analysis of the TOPCAT study concerned 1767 patients with HFpEF, defined as symptomatic HF and an LVEF ≥45%, with either an admission with decompensated HF in the past 12 months or elevated natriuretic peptide, and assigned to either spironolactone (15 to 45 mg/day) or placebo. The primary outcome was a composite of CV death, aborted cardiac arrest, or HF hospitalization.

To assess the temporal change in HR, a time-updated covariate was created, named “HR at any visit”, representing the most recent available HR value for each patient at each visit over the course of the trial. There were up to 16 trial visits in the program, with a median time interval of 135 days (IQR: 61-182 days), and the resting HR was updated up to 15 times after baseline for each patient. The temporal change in resting HR was calculated from the preceding visit by subtracting the time-updated visit HR value from the value of the preceding visit. These changes in HR reflect changes occurring between visits.

Main results

  • The mean LVEF was 58 ± 8%. More than 40% out of 1767 patients had AF at baseline, and a third of the patients were receiving anticoagulation.
  • The median values of resting HR measured at any visit were almost identical to the resting baseline HR of 68 beats/min (IQR: 61-76 beats/min)
  • Most patients had no change of HR since the preceding visit (median 0 beats/min; IQR: -6 to 6 beats/min).
  • 522 patients (11.5% [95% CI: 10.5-12.5]) experienced the primary outcome during a median follow-up time of 3.3 years.
  • As a continuous covariate, both baseline HR (adjusted HR: 1.08; 95% CI: 1.04-1.12) and time-updated HR (adjusted HR: 1.11; 95% CI: 1.07-1.15) were associated with the primary outcome, as well as with most other adverse outcomes.
  • For each 5 beats/min increase in HR at any time, the primary endpoint and all-cause mortality were 11% and 17% higher, respectively.
  • As a continuous covariate, change in HR from the preceding visit was associated with the primary outcome (adjusted HR: 1.09; 95% CI: 1.05-1.14) and all other outcomes, except for fatal and non-fatal MI. Each 5 beats/min increase in HR from the preceding visit was associated with a 9% higher risk for the primary outcome and a 17% higher risk for all-cause mortality, as well as with a 14%, 11%, and 20% higher risk for CV death, hospitalization for HF, and non-CV death, respectively.
  • Any rise in HR was associated with elevated risk for the primary endpoint, while a decline in HR did not show a significant association with lower risk.
  • In patients experiencing the primary endpoint, a rise in HR of >10 beats/min was seen 5 to 10 days prior to the primary endpoint.
  • When the data were categorically analyzed, a rise in HR of >10 beats/min was associated with a 70% higher risk of the primary endpoint, and even greater risk increases were seen for other adverse outcomes. Conversely, a drop in HR >10 beats/min did show significant risk reductions for all-cause mortality and non-CV death.


In patients with HFpEF, including those with AF, a higher baseline resting HR and time-updated HR, and an increase in resting HR over time from the preceding clinic visit were independently associated with an elevated risk for CV events. However, a decline in HR over time was not associated with a lower risk for CV events. These findings support the importance of measuring resting HR in everyday clinical practice, to identify HFpEF patients at higher risk for readmission and death.


1. Nauman J, Janszky I, Vatten LJ, et al. Temporal changes in resting heart rate and deaths from ischemic heart disease. JAMA 2011;306:2579–87.

2. Jouven X, Empana JP, Escolano S, et al. Relation of heart rate at rest and long-term (>20 years) death rate in initially healthy middle-aged men. Am J Cardiol 2009;103:279–83.

3. Paul L, Hastie CE, Li WS, et al. Resting heart rate pattern during follow-up and mortality in hypertensive patients. Hypertension 2010;55:567–74.

4. Vazir A, Claggett B, Jhund P, et al. Prognostic importance of temporal changes in resting heart rate in heart failure patients: an analysis of the CHARM program. Eur Heart J 2015;36:669–75.

5. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014;370:1383–92.

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Schedule27 May 2024