Determinants of submaximal exercise capacity in patients at risk for heart failure with preserved ejection fraction-results from the DIAST-CHF study

Raoul Stahrenberg; André Duvinage; Meinhard Mende; Götz Gelbrich; Wiebke Auf der Heide; Hans-Dirk Düngen; Lutz Binder; Kathleen Nolte; Christoph Herrmann-Lingen; Gerd Hasenfuß; Burkert Pieske; Rolf Wachter; Frank Edelmann

doi:10.1002/ehf2.12034

Determinants of submaximal exercise capacity in patients at risk for heart failure with preserved ejection fraction-results from the DIAST-CHF study

ESC Heart Fail. 2015 Jun;2(2):76-84. doi: 10.1002/ehf2.12034. Epub 2015 Apr 27.

Authors

Affiliations

¹ Department of Cardiology and Pneumology, Göttingen University Medical Center, Göttingen, Germany.
² Department of Prevention, Rehabilitation and Sports Medicine, Technische Universität München, Germany.
³ Center for Clinical Trials, University of Leipzig, Leipzig, Germany.
⁴ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
⁵ Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
⁶ Department of Clinical Chemistry, Göttingen University Medical Center, University of Göttingen, Göttingen, Germany.
⁷ Department of Psychosomatic Medicine and Psychotherapy, Göttingen University Medical Center, Göttingen, Germany.

Abstract

Objectives and background: The aim of this study was to identify determinants of submaximal exercise capacity as measured by 6 min walking distance in patients at risk for heart failure with preserved ejection fraction (HFpEF).

Methods: A cross-sectional analysis from the prospective cohort programme Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST-CHF) that included a total of 1937 patients (age, 50-85 years) with >1 risk factor (hypertension, atherosclerotic disease, diabetes mellitus, and obstructive sleep apnoea) was carried out. Besides comprehensive clinical phenotyping, standardized 6 min walk test and state-of-the-art echocardiography were performed, and blood samples for biomarker assessment were obtained. Patients with an ejection fraction <50% or without evaluable exercise test were excluded from this analysis.

Results: One thousand three hundred eighty-seven patients fulfilled all criteria for this analysis. In the univariate analysis, 6 min walk distance was inversely related to E/e' values (P < 0.001). In the multivariate analysis, 6 min walk distance decreased significantly with age, female sex, increasing body mass index, diabetes, chronic obstructive lung disease, and peripheral artery disease. However, the association of 6 min walk distance with resting parameters of diastolic function was significantly attenuated with multivariate regression. In contrast, mid-regional pro-adrenomedullin, mid-regional pro-atrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide were independently associated with submaximal exercise capacity when added to the base model (all P < 0.001).

Conclusions: Classical risk factors for heart failure and neuroendocrine activation are independently associated with sub-maximal exercise capacity, while diastolic function parameters obtained at rest were not. This observation substantiates the role of co-morbidities as relevant contributors to the clinical picture of HFpEF and the limitation of resting indices of diastolic function for diagnosing HFpEF.

Keywords: Biomarkers; Diastolic dysfunction; Exercise capacity.