Kosmala, W and Przewlocka-Kosmala, M and Marwick, TH, 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. ISSN 1936-878X (2017) [Refereed Article]
© 2017 by the American College of Cardiology Foundation. Published by Elsevier.
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:||Refereed Article|
|Keywords:||E/e′ ratio, aldosterone antagonism, heart failure with preserved ejection fraction, left ventricular filling, untwisting rate|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Cardiology (incl. cardiovascular diseases)|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Kosmala, W (Professor Wojciech Kosmala)|
|UTAS Author:||Marwick, TH (Professor Tom Marwick)|
|Web of Science® Times Cited:||12|
|Deposited By:||Menzies Institute for Medical Research|
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