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      Overcoming the Limits of Ejection Fraction and Ventricular-Arterial Coupling in Heart Failure

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          Abstract

          Left ventricular ejection fraction (LVEF) and ventricular-arterial coupling (VAC) [VAC = Ea/Ees; Ea: effective arterial elastance; Ees: left ventricle (LV) elastance] are both dimensionless ratios with important limitations, especially in heart failure setting. The LVEF to VAC relationship is a divergent non-linear function, having a point of intersection at the specific value of 0.62, where V0 = 0 ml (V0: the theoretical extrapolated value of the volume-axis intercept at end-systolic pressure 0 mmHg). For the dilated LV, both LVEF and VAC are highly dependent on V0 which is inconclusive when derived from single-beat Ees formulas. VAC simplification should be avoided. Revisiting the relationship between systolic time intervals (STI), pressure, and volumes could provide simple-to-use guiding formulas, affordable for daily clinical practice. We have analyzed by echocardiography the hemodynamics of 21 patients with severe symptomatic heart failure with reduced ejection (HFrEF) compared to 12 asymptomatic patients (at risk of heart failure with mild structural disease). The groups were unequivocally separated by ‘classic’ measures (LVEF, LV end-systolic volume (ESV), LV mass, STI). Chen's Ees formula was weakly correlated with LVEF and indexed ESV (ESVi) but better correlated to the pre-ejection period (PEP); PEP/total ejection time (PEP/TET); systolic blood pressure/PEP (SBP/PEP) ( P < 0.001). Combining the predictability of the LVEF to the determinant role of SBP/PEP on the Ees variations, we obtained: (SBP *LVEF)/PEP mm Hg/ms, with an improved R 2 value ( R 2 = 0.848; P < 0.001). The strongest correlations to VAC were for LVEF ( R = −0.849; R 2 = 0.722) and PEP/TET ( R = 0.925; R 2 = 0.857). By multiple regression, the VAC was strongly predicted ( N = 33): ( R = 0.975; R 2 = 0.95): VAC = 0.553–0.009 *LVEF + 3.463 *PEP/TET, and natural logarithm: Ln (VAC) = 0.147–1.4563 *DBP/SBP *0.9–0.010 *LVEF + 4.207 *PEP/TET ( R = 0.987; R 2 = 0.975; P = 0) demonstrating its exclusive determinants: LVEF, PEP/TET, and DBP/SBP. Considering Ea as a known value, the VAC-derived Ees formula: Ees_d ≈ Ea/(0.553–0.009 *LVEF+3.463 *PEP/TET) was strongly correlated to Chen's Ees formula ( R = 0.973; R 2 = 0.947) being based on SBP, ESV, LVEF, and PEP/TET and no exponential power. Thus, the new index supports our hypothesis, in the limited sample of patients with HFrEF. Indices like SBP/PEP, (SBP *LVEF)/PEP, PEP/TET, and DBP/SBP deserve further experiments, underlining the major role of the forgotten STI.

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          Most cited references48

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          2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

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            2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America

            Circulation, 136(6)
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              Universal definition and classification of heart failure: A report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by Canadian Heart Failure Society, Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

              In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                21 January 2022
                2021
                : 8
                : 750965
                Affiliations
                [1] 1Emergency Institute for Cardiovascular Diseases “Prof. Dr. C.C. Iliescu” , Bucharest, Romania
                [2] 2“Carol Davila” University of Medicine and Pharmacy , Bucharest, Romania
                [3] 3Institut Mutualiste Montsouris , Paris, France
                Author notes

                Edited by: Peter L. Kerkhof, VU Medical Center, Netherlands

                Reviewed by: Guilherme Fialho, Federal University of Santa Catarina, Brazil; John K-J. Li, Rutgers, The State University of New Jersey, United States

                *Correspondence: Elena-Laura Antohi laura.antohi@ 123456gmail.com

                This article was submitted to General Cardiovascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine

                Article
                10.3389/fcvm.2021.750965
                8813963
                35127846
                336c1c86-5e9a-4a11-af0f-028baa594ea4
                Copyright © 2022 Antohi, Chioncel and Mihaileanu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 July 2021
                : 21 December 2021
                Page count
                Figures: 7, Tables: 4, Equations: 2, References: 48, Pages: 14, Words: 8683
                Categories
                Cardiovascular Medicine
                Hypothesis and Theory

                heart failure,ventricular-arterial coupling,left ventricular ejection fraction,systolic times,left ventricular elastance,blood pressure

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