Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock

被引:29
作者
Berg-Hansen, Kristoffer [1 ,2 ,5 ]
Christensen, Kristian Hylleberg [1 ,2 ]
Gopalasingam, Nigopan [1 ,2 ]
Nielsen, Roni [1 ]
Eiskjaer, Hans [1 ,2 ]
Moller, Niels [2 ,3 ]
Birkelund, Thomas [4 ]
Christensen, Steffen [2 ,4 ]
Wiggers, Henrik [1 ,2 ]
机构
[1] Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark
[2] Aarhus Univ, Fac Hlth, Dept Clin Med, Aarhus, Denmark
[3] Aarhus Univ Hosp, Dept Endocrinol & Metab, Aarhus, Denmark
[4] Aarhus Univ Hosp, Dept Anesthesiol & Intens Care, Aarhus, Denmark
[5] Aarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
关键词
3-hydroxybutyrate; cardiac output; cardiogenic shock; invasive hemodynamics; ketone ester; metabolism; CONGESTIVE-HEART-FAILURE; PERFORMANCE; DOBUTAMINE; EXPRESSION; MILRINONE; OUTCOMES; BODIES; TRIAL;
D O I
10.1016/j.jchf.2023.05.029
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Cardiogenic shock (CS) is a life-threatening condition with sparse treatment options. The ketone body 3-hydroxybutyrate has favorable hemodynamic effects in patients with stable chronic heart failure. Yet, the hemodynamic effects of exogenous ketone ester (KE) in patients with CS remain unknown.OBJECTIVES The authors aimed to assess the hemodynamic effects of single-dose enteral treatment with KE in patients with CS.METHODS In a double-blind, crossover study, 12 patients with CS were randomized to an enteral bolus of KE and isocaloric, isovolumic placebo containing maltodextrin. Patients were assessed with pulmonary artery catheterization, arterial blood samples, echocardiography, and near-infrared spectroscopy for 3 hours following each intervention separated by a 3-hour washout period. RESULTS KE increased circulating 3-hydroxybutyrate (2.9 +/- 0.3 mmol/L vs 0.2 +/- 0.3 mmol/L, P < 0.001) and was associated with augmented cardiac output (area under the curve of relative change: 61 +/- 22 L vs 1 +/- 18 L, P = 0.044). Also, KE increased cardiac power output (0.07 W [95% CI: 0.01-0.14]; P = 0.037), mixed venous saturation (3 percentage points [95% CI: 1-5 percentage points]; P = 0.010), and forearm perfusion (3 percentage points [95% CI: 0-6 percentage points]; P = 0.026). Right (P = 0.048) and left (P = 0.017) ventricular filling pressures were reduced whereas heart rate and mean arterial and pulmonary arterial pressures remained similar. Left ventricular ejection fraction improved by 4 percentage points (95% CI: 2-6 percentage points; P = 0.005). Glucose levels decreased by 2.6 mmol/L (95% CI: -5.2 to 0.0; P = 0.047) whereas insulin levels remained unaltered.CONCLUSIONS Treatment with KE improved cardiac output, biventricular function, tissue oxygenation, and glycemic control in patients with CS (Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock [KETO-SHOCK1]; NCT04642768) (J Am Coll Cardiol HF 2023;11:1337-1347) (c) 2023 by the American College of Cardiology Foundation.
引用
收藏
页码:1337 / 1347
页数:11
相关论文
共 39 条
[1]   EFFICACY AND SAFETY OF SUSTAINED (48 HOUR) INTRAVENOUS INFUSIONS OF MILRINONE IN PATIENTS WITH SEVERE CONGESTIVE-HEART-FAILURE - A MULTICENTER STUDY [J].
ANDERSON, JL ;
BAIM, DS ;
FEIN, SA ;
GOLDSTEIN, RA ;
LEJEMTEL, TH ;
LIKOFF, MJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1987, 9 (04) :711-722
[2]   The Failing Heart Relies on Ketone Bodies as a Fuel [J].
Aubert, Gregory ;
Martin, Ola J. ;
Horton, Julie L. ;
Lai, Ling ;
Vega, Rick B. ;
Leone, Teresa C. ;
Koves, Timothy ;
Gardell, Stephen J. ;
Krueger, Marcus ;
Hoppel, Charles L. ;
Lewandowski, E. Douglas ;
Crawford, Peter A. ;
Muoio, Deborah M. ;
Kelly, Daniel P. .
CIRCULATION, 2016, 133 (08) :698-705
[3]   Multi-site and multi-depth near-infrared spectroscopy in a model of simulated (central) hypovolemia: lower body negative pressure [J].
Bartels, Sebastiaan A. ;
Bezemer, Rick ;
de Vries, Floris J. Wallis ;
Milstein, Dan M. J. ;
Lima, Alexandre ;
Cherpanath, Thomas G. V. ;
van den Meiracker, Anton H. ;
van Bommel, Jasper ;
Heger, Michal ;
Karemaker, John M. ;
Ince, Can .
INTENSIVE CARE MEDICINE, 2011, 37 (04) :671-677
[4]   Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure [J].
Bedi, Kenneth C., Jr. ;
Snyder, Nathaniel W. ;
Brandimarto, Jeffrey ;
Aziz, Moez ;
Mesaros, Clementina ;
Worth, Andrew J. ;
Wang, Linda L. ;
Javaheri, Ali ;
Blair, Ian A. ;
Margulies, Kenneth B. ;
Rame, J. Eduardo .
CIRCULATION, 2016, 133 (08) :706-716
[5]   Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes [J].
Cox, Pete J. ;
Kirk, Tom ;
Ashmore, Tom ;
Willerton, Kristof ;
Evans, Rhys ;
Smith, Alan ;
Murray, Andrew J. ;
Stubbs, Brianna ;
West, James ;
McLure, Stewart W. ;
King, M. Todd ;
Dodd, Michael S. ;
Holloway, Cameron ;
Neubauer, Stefan ;
Drawer, Scott ;
Veech, Richard L. ;
Griffin, Julian L. ;
Clarke, Kieran .
CELL METABOLISM, 2016, 24 (02) :256-268
[6]   Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction [J].
de Koning, Marie-Sophie L. Y. ;
Westenbrink, B. Daan ;
Assa, Solmaz ;
Garcia, Erwin ;
Connelly, Margery A. ;
van Veldhuisen, Dirk J. ;
Dullaart, Robin P. F. ;
Lipsic, Erik ;
van der Harst, Pim .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2021, 78 (14) :1421-1432
[7]   DIFFERENTIAL-EFFECTS OF MILRINONE AND DOBUTAMINE ON RIGHT VENTRICULAR PRELOAD, AFTERLOAD AND SYSTOLIC PERFORMANCE IN CONGESTIVE-HEART-FAILURE SECONDARY TO ISCHEMIC OR IDIOPATHIC DILATED CARDIOMYOPATHY [J].
EICHHORN, EJ ;
KONSTAM, MA ;
WEILAND, DS ;
ROBERTS, DJ ;
MARTIN, TT ;
STRANSKY, NB ;
SALEM, DN .
AMERICAN JOURNAL OF CARDIOLOGY, 1987, 60 (16) :1329-1333
[8]   CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis [J].
Ferrannini, Ele ;
Mark, Michael ;
Mayoux, Eric .
DIABETES CARE, 2016, 39 (07) :1108-1114
[9]   Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: A report from the SHOCK trial registry [J].
Fincke, R ;
Hochman, JS ;
Lowe, AM ;
Menon, V ;
Slater, JN ;
Webb, JG ;
LeJemtel, TH ;
Cotter, G .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 44 (02) :340-348
[10]   COMPARATIVE HEMODYNAMIC-EFFECTS OF DOPAMINE AND DOBUTAMINE IN PATIENTS WITH ACUTE CARDIOGENIC CIRCULATORY COLLAPSE [J].
FRANCIS, GS ;
SHARMA, B ;
HODGES, M .
AMERICAN HEART JOURNAL, 1982, 103 (06) :995-1000