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European Heart Journal Advance Access published online on August 30, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp341
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Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure

Rolf Wachter1,{dagger}, Stephan Schmidt-Schweda1,{dagger}, Dirk Westermann2, Heiner Post4, Frank Edelmann1, Mario Kasner2, Claus Lüers1, Paul Steendijk3, Gerd Hasenfuß1, Carsten Tschöpe2 and Burkert Pieske1,4,*

1 Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany
2 Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité University Hospital, Berlin, Germany
3 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
4 Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria

Received 4 December 2008; revised 13 May 2009; accepted 13 July 2009 * Corresponding author. Tel: +43 316 385 2544, Fax: +43 316 385 3733, Email: burkert.pieske{at}medunigraz.at

Aims: We tested the hypothesis that, in heart failure with normal ejection fraction (HFNEF), diastolic dysfunction is accentuated at increasing heart rates, and this contributes to impaired frequency-dependent augmentation of cardiac output.

Methods and results: In 17 patients with HFNEF (median age 69 years, 13 female) and seven age-matched control patients, systolic and diastolic function was analysed by pressure–volume loops at baseline heart rate and during atrial pacing to 100 and 120 min–1. At baseline, relaxation was prolonged and end-diastolic left ventricular stiffness was higher in HFNEF, whereas all parameters of systolic function were not different from control patients. This resulted in smaller end-diastolic volumes, higher end-diastolic pressure, and a lower stroke volume and cardiac index in HFNEF vs. control patients. During pacing, frequency-dependent upregulation of contractility indices (+dP/dtmax and Ees) occurred similarly in HFNEF and control patients, but frequency-dependent acceleration of relaxation (dP/dtmin) was blunted in HFNEF. In HFNEF, end-diastolic volume and stroke volume decreased with higher heart rates while both remained unchanged in control patients.

Conclusion: In HFNEF, frequency-dependent upregulation of cardiac output is blunted. This results from progressive volume unloading of the left ventricle due to limited relaxation reserve in combination with increased LV passive stiffness, despite preserved force–frequency relation.

Key Words: Diastolic function • Heart failure • Pressure volume loops • Force–frequency relation

{dagger} The first two authors contributed equally to the study.


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