Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction

Barry A Borlaug, Vojtech Melenovsky, Stuart D. Russell, Kristy Kessler, Karel Pacak, Lewis C. Becker, David A. Kass

Research output: Contribution to journalArticle

413 Citations (Scopus)

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 • min; 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.

Original languageEnglish (US)
Pages (from-to)2138-2147
Number of pages10
JournalCirculation
Volume114
Issue number20
DOIs
StatePublished - Nov 2006

Fingerprint

Vasodilator Agents
Heart Failure
Exercise
Cardiac Output
Heart Rate
Stroke Volume
Radionuclide Ventriculography
Ergometry
Plasma Volume
Cardiomegaly
Left Ventricular Hypertrophy
Workload
Vasodilation
Oxygen Consumption
Vascular Resistance
Dyspnea
Norepinephrine
Diabetes Mellitus
Obesity
Hypertension

Keywords

  • Diastole
  • Exercise
  • Heart failure
  • Heart rate
  • Hemodynamics
  • Nervous system, autonomic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. / Borlaug, Barry A; Melenovsky, Vojtech; Russell, Stuart D.; Kessler, Kristy; Pacak, Karel; Becker, Lewis C.; Kass, David A.

In: Circulation, Vol. 114, No. 20, 11.2006, p. 2138-2147.

Research output: Contribution to journalArticle

Borlaug, Barry A ; Melenovsky, Vojtech ; Russell, Stuart D. ; Kessler, Kristy ; Pacak, Karel ; Becker, Lewis C. ; Kass, David A. / Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. In: Circulation. 2006 ; Vol. 114, No. 20. pp. 2138-2147.
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AU - Borlaug, Barry A

AU - Melenovsky, Vojtech

AU - Russell, Stuart D.

AU - Kessler, Kristy

AU - Pacak, Karel

AU - Becker, Lewis C.

AU - Kass, David A.

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N2 - 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 • min; 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.

AB - 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 • min; 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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KW - Exercise

KW - Heart failure

KW - Heart rate

KW - Hemodynamics

KW - Nervous system, autonomic

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