Energetics and metabolism in the failing heart: important but poorly understood.
OBJECTIVE
Profound abnormalities in myocardial energy metabolism occur in heart failure and correlate with clinical symptoms and survival. Available comprehensive human metabolic data come from small studies, enrolling patients across heart failure causes, at different disease stages, and using different methodologies, and is often contradictory. Remaining fundamental gaps in knowledge include whether observed shifts in cardiac substrate utilization are adaptive or maladaptive, causal or an epiphenomenon of heart failure.


RESULTS
Recent studies have characterized the temporal changes in myocardial substrate metabolism involved in progression of heart failure, the role of insulin resistance, and the mechanisms of mitochondrial dysfunction in heart failure. The concept of metabolic inflexibility has been proposed to explain the lack of energetic and mechanical reserve in the failing heart.


CONCLUSIONS
Despite current therapies, which provide substantial benefits to patients, heart failure remains a progressive disease, and new approaches to treatment are necessary. Developing metabolic interventions would be facilitated by systems-level integration of current knowledge on myocardial metabolic control. Although preliminary evidence suggests that metabolic modulators inducing a shift towards carbohydrate utilization seem generally beneficial in the failing heart, such interventions should be matched to the stage of metabolic deregulation in the progression of heart failure.
Turer
Aslan T
AT
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9047, USA. aslan.turer@utsouthwestern.edu
Malloy
Craig R
CR
Newgard
Christopher B
CB
Podgoreanu
Mihai V
MV
D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D005227:Fatty Acids; D005947:Glucose
J Card Fail. 1998 Jun;4(2):121-6
9730105
Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H313-8
10899071
Am J Physiol. 1995 Mar;268(3 Pt 2):H1265-75
7900881
Circ Res. 1999 Aug 20;85(4):357-63
10455064
PLoS One. 2009 Oct 21;4(10):e7533
19844574
Circulation. 2006 Nov 14;114(20):2130-7
17088453
Circulation. 1993 May;87(5):1513-23
8491006
J Am Coll Cardiol. 2006 Dec 5;48(11):2225-31
17161251
Circulation. 2009 Apr 7;119(13):1736-46
19307475
Am Heart J. 1991 Sep;122(3 Pt 1):795-801
1877457
Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E197-206
11739101
Metabolism. 2010 Jul;59(7):1020-8
20045149
J Card Fail. 2006 Dec;12(9):694-9
17174230
Mol Cell Biochem. 1998 Mar;180(1-2):171-7
9546644
Circulation. 1996 Oct 15;94(8):1894-901
8873665
J Clin Invest. 1968 Aug;47(8):1787-94
4233124
Am J Cardiol. 1999 May 1;83(9):1338-44
10235092
Cardiovasc Res. 2009 Oct 1;84(1):111-8
19509029
Lancet. 2004 Nov 13-19;364(9447):1786-8
15541452
Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3270-8
17921325
Circ Res. 2001 Mar 16;88(5):529-35
11249877
Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H2098-105
18820029
Cardiovasc Res. 2009 Feb 15;81(3):420-8
18854380
Mol Cell Biol. 1997 Sep;17(9):5400-9
9271417
Circulation. 2001 May 22;103(20):2441-6
11369683
Circulation. 1996 Dec 1;94(11):2837-42
8941110
Circulation. 2001 Dec 11;104(24):2923-31
11739307
J Clin Invest. 2005 Mar;115(3):547-55
15765136
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H936-43
18083902
Eur J Clin Invest. 1999 Jun;29(6):469-77
10354207
Metabolism. 1994 Feb;43(2):174-9
8121298
J Am Coll Cardiol. 1991 Oct;18(4):1059-66
1680132
Am Heart J. 2010 Jan;159(1):90-7
20102872
J Nucl Med. 2001 Jan;42(1):55-62
11197981
Cardiovasc Res. 2010 Jun 1;86(3):461-70
20035032
J Am Coll Cardiol. 2002 Oct 2;40(7):1267-74
12383574
Circulation. 2005 May 17;111(19):2477-85
15883212
Circulation. 1992 Dec;86(6):1810-8
1451253
Circulation. 2009 Jun 2;119(21):2818-28
19451348
Eur J Heart Fail. 2010 Feb;12(2):106-13
20083620
Lancet. 2004 Nov 13-19;364(9447):1733-4
15541431
J Am Coll Cardiol. 1994 Nov 1;24(5):1310-20
7930255
J Card Fail. 2006 Oct;12(8):644-52
17045185
Am Heart J. 2006 Jan;151(1):91
16368297
Circ Heart Fail. 2009 Jul;2(4):342-50
19808358
Eur J Heart Fail. 2005 Jun;7(4):618-23
15921803
J Card Fail. 2004 Apr;10(2):132-40
15101025
J Biol Chem. 2002 Oct 25;277(43):40265-74
12181319
J Am Coll Cardiol. 2002 Dec 18;40(12):2174-81
12505231
Circulation. 2002 Oct 15;106(16):2125-31
12379584
Nature. 1995 Sep 14;377(6545):151-5
7675081
J Am Coll Cardiol. 2002 Jul 17;40(2):271-7
12106931
J Am Coll Cardiol. 2009 Jul 28;54(5):422-8
19628117
Circulation. 2006 Nov 14;114(20):2092-3
17101867
Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1538-43
15191896
Circulation. 2002 Jul 30;106(5):606-12
12147544
Heart Fail Rev. 2007 Dec;12(3-4):331-43
17516164
J Mol Cell Cardiol. 2004 Sep;37(3):613-23
15350834
J Mol Cell Cardiol. 2006 Jun;40(6):838-45
16697005
Circulation. 2009 Mar 10;119(9):1272-83
19237663