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Association of active and passive components of LV diastolic filling with exercise intolerance in heart failure with preserved ejection fraction. Mechanistic insights from spironolactone response

Kosmala, W, Przewlocka-Kosmala, M and Marwick, TH ORCID: 0000-0001-9065-0899 2017 , 'Association of active and passive components of LV diastolic filling with exercise intolerance in heart failure with preserved ejection fraction. Mechanistic insights from spironolactone response' , JACC: Cardiovascular Imaging , pp. 1-11 , doi: 10.1016/j.jcmg.2017.10.007.

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Abstract

Objectives: This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e' ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF).Background: In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e' ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction).Methods: In 194 patients with HFpEF (64 ± 8 years), a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) was performed. Echocardiography following maximal exercise was undertaken to assess LV systolic and diastolic responses to stress. A subset of 105 patients with an exercise-induced increase in estimated LV filling pressure were randomly assigned to spironolactone 25 mg (n = 51) or placebo (n = 54) for 6 months.Results: Baseline peak Vo2 was associated with UT (β = 0.19; p = 0.01) and E/e' (β = -0.16; p = 0.03), independent of clinical data and exercise reserve in longitudinal deformation and ventricular-arterial coupling. An increase in peak Vo2 with treatment was independently associated with changes in UT (β = 0.28; p = 0.003) and exertional increase in E/e' (β = -0.23; p = 0.01) from baseline to follow-up. A significant interaction with the use of spironolactone on peak Vo2 was found for E/e' (p = 0.02) but not for UT (p = 0.62).Conclusions: Both active and passive determinants of LV filling, as reflected by UT and E/e', contribute to reduced exercise capacity in HFpEF. Improvement in functional capacity with a 6-month therapy with spironolactone is associated with improvements in both indices. However, the possible mediating effect of this medication is observed only on E/e'.

Item Type: Article
Authors/Creators:Kosmala, W and Przewlocka-Kosmala, M and Marwick, TH
Keywords: E/e′ ratio, aldosterone antagonism, heart failure with preserved ejection fraction, left ventricular filling, untwisting rate
Journal or Publication Title: JACC: Cardiovascular Imaging
Publisher: Elsevier Inc.
ISSN: 1936-878X
DOI / ID Number: 10.1016/j.jcmg.2017.10.007
Copyright Information:

© 2017 by the American College of Cardiology Foundation. Published by Elsevier.

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