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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.
JACC Cardiovasc Imaging. 2019 05; 12(5):784-794.JC

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'.

Authors+Show Affiliations

Cardiology Department, Wroclaw Medical University, Wroclaw, Poland; Baker Heart and Diabetes Institute, Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.Cardiology Department, Wroclaw Medical University, Wroclaw, Poland; Baker Heart and Diabetes Institute, Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.Baker Heart and Diabetes Institute, Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. Electronic address: tom.marwick@baker.edu.au.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29248640

Citation

Kosmala, Wojciech, et al. "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, vol. 12, no. 5, 2019, pp. 784-794.
Kosmala W, Przewlocka-Kosmala M, 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 Cardiovasc Imaging. 2019;12(5):784-794.
Kosmala, W., Przewlocka-Kosmala, M., & Marwick, T. H. (2019). 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, 12(5), 784-794. https://doi.org/10.1016/j.jcmg.2017.10.007
Kosmala W, Przewlocka-Kosmala M, 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 Cardiovasc Imaging. 2019;12(5):784-794. PubMed PMID: 29248640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kosmala,Wojciech, AU - Przewlocka-Kosmala,Monika, AU - Marwick,Thomas H, Y1 - 2017/12/13/ PY - 2017/06/29/received PY - 2017/10/03/revised PY - 2017/10/04/accepted PY - 2017/12/19/pubmed PY - 2020/3/19/medline PY - 2017/12/18/entrez KW - E/e′ ratio KW - aldosterone antagonism KW - heart failure with preserved ejection fraction KW - left ventricular filling KW - untwisting rate SP - 784 EP - 794 JF - JACC. Cardiovascular imaging JO - JACC Cardiovasc Imaging VL - 12 IS - 5 N2 - 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'. SN - 1876-7591 UR - https://www.unboundmedicine.com/medline/citation/29248640/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1936-878X(17)30979-8 DB - PRIME DP - Unbound Medicine ER -