Myocardial Recovery in Chronic Heart Failure

Graphic- Myocardial Recovery in Chronic Heart Failure
The recovering heart increases the production of a mitochondrial pyruvate carrier protein (MPC), which transports pyruvate into the mitochondria where it is oxidized and fuels energy production.

Chronic heart failure is a disease with poor prognosis and currently is a global epidemic. University of Utah Health investigator Stavros George Drakos, MD, and colleagues analyzed human heart tissue and produced evidence refuting the widely held notion that prolonged off-loading of the failing heart induced by cardiac assist devices results in disuse atrophy that further deteriorates heart function. In contrast, there was significant heart recovery following the implantation of cardiac assist devices. These beneficial outcomes were recently validated in a multicenter trial co-led by the University of Utah.

To elucidate the mechanisms driving these favorable outcomes, they performed microstructural and metabolic studies. They discovered that, in humans and animals, the recovering heart exhibited preference for glucose oxidation over lactate production. To accomplish this, the recovering heart increases the production of a mitochondrial pyruvate carrier protein (MPC), which transports pyruvate into the mitochondria where it is oxidized and fuels energy production. This research has been conducted through the multidisciplinary Utah Cardiac Recovery Program, comprising investigators from the Nora Eccles Harrison Cardiovascular Research & Training Institute, multiple U of U departments, Intermountain Healthcare, Salt Lake VA as well as international collaborators. These recent discoveries provide critical scientific and clinical insights and novel therapeutic targets for heart failure.

References:

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The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure. Cluntun AA, Badolia R, Lettlova S, Parnell KM, Shankar TS, Diakos NA, Olson KA, Taleb I, Tatum SM, Berg JA, Cunningham CC, Krokidi AT, Skedros S, Navankasattusas S, Cox JE, Ducker GS, Holland WL, McKellar SH, Rutter J, Drakos SG. Cell Metabolism. 2021 Mar 2;33(3):629.

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The role of non-glycolytic glucose metabolism in myocardial recovery upon mechanical unloading and circulatory support in chronic heart failure. Badolia R, Ramadurai D, Abel ED, Ferrin P, Taleb I, Sankar T, McKellar S, Yin M, Kfoury AG, Wever-Pinzon O, Fang JC, Selzman CH, Chaudhuri D, Rutter J, Drakos SG. Circulation. 2020 July 21;142(3):259.

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A prospective multicentre study of myocardial recovery using left ventricular assist devices (remission from Stage D heart failure: RESTAGE-HF): medium term and primary endpoint results. Birks EJ*, Drakos SG* (*co-corresponding authors), Patel SR, Lowes BD, Selzman CH, Starling RC, Trivedi J, Slaughter MS, Goldstein D, et al. Circulation. 2020 November 24;142(21):2016.

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The human heart contains distinct macrophage subsets with divergent origins and functions. Bajpai G, Schneider C, Bredemeyer A, Hulsman M, Nahrendorf MP, Epelman S, Kreisel D, Itoh A, Selzman C, Sankar T, Drakos SG, Lavine KJ. Nature Medicine. 2018 August; 24(8):1234.

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Cardiac rotational mechanics as a predictor of myocardial recovery in heart failure patients undergoing chronic mechanical circulatory support. Bonios MJ, Koliopoulou A, Wever-Pinzon O, Taleb I, Xu W, Stehlik J, Kfoury AG, Horne BD, Selzman CH, Fang JC, Bax JJ, Drakos SG. Circulation: Cardiovascular Imaging. 2018 April;11(4):e007117.

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Sheet-like remodeling of the transverse tubular system in human heart failure impairs excitation-contraction coupling and functional recovery by mechanical unloading. Seidel T, Navankasattusas S, Ahmad A, Diakos NA, Xu WD, Tristani-Firouzi M, Bonios MJ, Taleb I, Li DY, Selzman CH, Drakos SG*, Sachse FB* (*Co-Corresponding authors). Circulation. 2017 April 25;135(17):1632. 

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Evidence of glycolysis upregulation and pyruvate mitochondrial oxidation mismatch during mechanical unloading of the failing human heart: implications for cardiac reloading and conditioning. Diakos NA, Navankasattusas S, Abel ED, Rutter J, McCreath L, Ferrin P, McKellar SH, Richardson R, Deberardinis R, Kfoury AG, Selzman CH, Stehlik J, Fang JC, Li DY, Drakos SG. JACC Basic Transl Sci. 2016 October;1(6):432.

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Myocardial atrophy and chronic mechanical unloading of the failing human heart: implications for ventricular assist devices-induced cardiac recovery. Diakos NA, Selzman CH, Sachse FB, Stehlik J, Kfoury AG, Reid BB, Miller DV, Salama ME, Fang JC, Drakos SG. J Am Coll Cardiol. 2014 October 14;64(15):1602.

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Impact of heart failure etiology on the incidence of cardiac recovery during mechanical unloading: a prospective study from the utah cardiac recovery program. Wever-Pinzon J, Selzman CH, Wever-Pinzon O, Catino A, Kfoury AG, Stehlik J, Al- Sarie M, Stoddard G, McKellar S, Bonios MJ, Koliopoulou A, Fang JC, Drakos SG. J Am Coll Cardiol. 2016 October 18;68(16):1741.

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Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery. Drakos SG, Wever-Pinzon O, Selzman CH, Stehlik J, Gilbert EM, Alharethi EM, Reid BB, Budge D, Movsesian M, Li DY, Kfoury AG (UCAR Investigators). J Am Coll Cardiol. 2013 May 14;61(19):1985.

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U of U Health Key Faculty Collaborators:

Craig H. Selzman, MD
Jared P. Rutter, PhD
Omar WeverPinzon, MD
Frank Bernd Sachse, Dr.-Ing