Chronotropic Incompetence in Patients with Heart Failure and a Preserved Ejection Fraction: Prevalence and Impact on Exercise Tolerance

BACKGROUND: An appropriate heart rate (HR) response to exercise is important, as it represents a key determinant of oxygen consumption (VO2). Furthermore the inability of HR to increase sufficiently, chronotropic incompetence (CI), has important functional and prognostic implications in heart failure (HF). While there have been several studies that have evaluated the prevalence and impact of CI in the HFrEF population, only one small study has examined this in HFpEF subjects. Furthermore, there are no published studies that have evaluated the effects of a pharmacologic or exercise intervention on the prevalence of CI in the HFpEF population. OBJECTIVE: The primary objective of this study was to determine the prevalence of CI in a large group of HFpEF patients. The secondary objective was to evaluate the effect of beta blockers on the prevalence of CI in an HFpEF population. The final objective of this study was to evaluate the effects of a four month aerobic intervention, as well as an enalapril and a spironolactone intervention on the prevalence of CI in HFrEF patients. METHODS: Prevalence and impact of CI on exercise tolerance was evaluated in 207 HFpEF subjects from three previously conducted studies (PARIS II, PIE I, PIE II). Symptom limited graded exercise tests with expired gas analyses were conducted on 207 HFpEF subjects using a bicycle ergometer protocol that started at 12 watts and progressed to 25 watts after 2 minutes. RESULTS: Determination of chronotropic incompetence (CI) indicated that 58 participants out of the total 207 HFpEF subjects evaluated had CI (28%). Prevalence rates of CI in PARIS II, PIE I and PIE II were 27.9% (19/68), 15.5% (11/71) and 41.8% (28/67) respectively. Further analysis of VO2peak in CI and non-CI participants revealed a significantly higher VO2peak in individuals without CI (14.5 ± 3.2 ml∙kg-1∙min-1) compared to participants with CI (12.3 ± 2.3 ml∙kg-1∙min-1). There was no significant difference in the prevalence of CI in beta blocked patients (36.5%, 23/65) as compared to non beta blocked patients (24.3%, 35/144). The change in HR from rest to peak exercise, HR reserve, was significantly (p<.001) correlated (r = 0.48) with VO2 reserve during baseline CPET. Moreover, these findings indicate that the increase in HR during exercise accounts for nearly one quarter (R2 = 23.4%) of the observed difference in VO2 reserve in these HFpEF subjects. Furthermore, peak HR was also significantly (p<.001) correlated (r = .42) with VO2peak. This relationship indicates that 18.4% of the observed difference in VO2peak can be explained by peak HR. In both PARIS II (exercise) and PIE II (spironolactone) trials, there was a significant reduction (p<.05, p = .03 respectively) in the number of patients that meet criteria for CI after the intervention. Additionally, there were no changes in number of patients with CI from baseline to follow up in PIE I (enalapril) study. CONCLUSION: The present study was the first to examine the prevalence and effect of CI on exercise tolerance in a larger sample of HFpEF patients. It was determined that the prevalence of CI (28%) in the HFpEF population was similar to that seen in several studies of HFrEF patients. Moreover, significantly lower VO2peak values in these older HFpEF patients with CI suggest there is a need to develop therapies to improve chronotropic function in HF patients. In fact, one pacemaker manufacturer has initiated a randomized controlled trial to test the effectiveness of rate-responsive pacing in older HFpEF patients. Other potential therapies, including medications, to improve chronotropic function in HFpEF patients should be explored.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2010

Author dc:creator

• Ozemek, Cemal

• Heart Failure with a Preserved Ejection Fraction

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10339/14835

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/14835