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Cited by 699Cardiovascular and exercise physiologyCardiovascular Function and Risk FactorsHeart rate and cardiovascular health

Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction

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Borlaug, Barry A., Melenovsky, Vojtech, Russell, Stuart D., Kessler, Kristy, Pacak, Karel, Becker, Lewis C., Kass, David A.·2006·Circulation
DOI 10.1161/circulationaha.106.632745
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Abstract

Background— Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Methods and Results— Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180±71 versus 455±184 seconds; peak oxygen consumption 9.0±3.4 versus 14.4±3.4 mL · kg −1 · min −1 ; both P <0.001). At matched low-level workload, HFpEF subjects displayed ≈40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P <0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. Conclusions— HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

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  • In mammalian hearts, HFpEF is associated with impaired cardiac relaxation, or lusitropy, which is evident both at rest and during exercise in the majority of HFpEF patients.

    “In mammalian hearts, HFpEF is associated with impaired cardiac relaxation, or lusitropy, which is evident both at rest and during exercise in the majority of HFpEF patients.6,44”

    From Reversal of contractile defects by mediating calcium homeostasis in human mini-heart models of heart failure with preserved ejection fraction (HFpEF) leads to first-in-human gene therapy clinical trial (2024) · cites this paper as [44]

    In “HFpEF and Exercise Intolerance” (page unavailable), the paper describes slower relaxation and abnormal diastolic properties at rest as a generally accepted theory, but says what happens during exercise remains unsettled. Its “Baseline Characteristics” section also reports that other diastolic-function measures were similarly abnormal in HFpEF patients and controls. It does not establish impaired relaxation both at rest and during exercise in a majority of HFpEF patients. (LLM, conf=0.88)

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  1. [18]18. Melenovsky V, Borlaug BA, Rosen BD, Hay I, Ferrucci L, Morell CH, Lakatta EG, Najjar S, Kass DA. Cardiovascular features distinguishing heart failure with normal ejection fraction from non-failure subjects with hypertensive left ventricular hypertrophy. J Am Coll Cardiol. In press.

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Authors
Borlaug, B. A., Melenovsky, V., Russell, S. D., Kessler, K., Pacak, K., Becker, L. C., & Kass, D. A.
Affiliations
  • National Institutes of Health (US)
  • From the Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore (B.A.B., V.M., S.D.R., K.K., L.C.B., D.A.K.), and Reproductive Biology and Medicine Branch, National Institutes of Child Health and Human Development, NIH, Bethesda (K.P.), Md. Dr Borlaug is currently at the Division of Cardiovascular Disease, Department of Medicine, The Mayo Clinic College of Medicine, Rochester, Minn.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2006-11-14
Volume
114
Issue
20
Pages
2138-2147
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.106.632745
OpenAlex
W2101791328
Cited by
699
References
45
Citations by year
2026: 21 · 2025: 32 · 2024: 38 · 2023: 25 · 2022: 36 · 2021: 28 · 2020: 46 · 2019: 31 · 2018: 38 · 2017: 49 · 2016: 50 · 2015: 44 · 2014: 59 · 2013: 41 · 2012: 33
FWCI
54.52
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R01AG018324)
  • National Heart, Lung, and Blood Institute (HL-07227, T32HL007227)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
Keywords
heart failure with preserved ejection fraction, exercise capacity, chronotropic reserve, vasodilator reserve, cardiac output reserve, heart rate recovery, peak oxygen uptake, diastolic dysfunction, left ventricular hypertrophy, systemic vascular resistance, norepinephrine, exercise intolerance
MeSH terms
Aged, Autonomic Nervous System, Blood Volume, Cardiac Output, Cardiac Output, Low, Epinephrine, Exercise Test, Female, Heart Rate, Humans, Male, Middle Aged, Norepinephrine, Physical Endurance, Pulmonary Circulation, Stroke Volume, Vasodilation, Exercise

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