title: Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model.
abstract: BACKGROUND
  Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation.
  
  
  RESULTS
  All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97+/-0.004, 0.010+/-0.002, and 78+/-1 milliseconds, respectively. With dilation alone, CURE decreased 2.0+/-0.07%, ISF increased 58+/-47%, and WTpeak increased 31+/-3%. With dyssynchronous activation alone, CURE decreased 15+/-0.6%, ISF increased 14-fold (+/-3), and WTpeak increased 121+/-4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23+/-0.8%, ISF increased 20-fold (+/-5), and WTpeak increased 147+/-5%.
  
  
  CONCLUSIONS
  Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.
authors.affiliation: Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, Calif, USA.
authors.forename: Roy C P
authors.initials: RC
authors.lastname: Kerckhoffs
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Mulligan
mesh_terms: D002037:Bundle-Branch Block / Q000150:complications / Q000175:diagnosis; D003198:Computer Simulation; D004108:Dilatation, Pathologic / Q000150:complications / Q000175:diagnosis; D004594:Electrophysiology; D054144:Heart Failure, Diastolic / Q000175:diagnosis / Q000209:etiology*; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000209:etiology*; D006334:Heart Function Tests; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D012016:Reference Values; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology*
references.citation: Am J Cardiol. 2003 Mar 15;91(6):684-8
references.pmid: 12633798
references.citation: Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H1864-70
references.pmid: 12855422
references.citation: Circ Res. 1984 Mar;54(3):294-300
references.pmid: 6230171
references.citation: Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H1889-97
references.pmid: 15964924
references.citation: Circulation. 2007 Feb 27;115(8):953-61
references.pmid: 17296857
references.citation: J Am Coll Cardiol. 1999 May;33(6):1735-42
references.pmid: 10334450
references.citation: J Am Coll Cardiol. 2003 Aug 6;42(3):558-67
references.pmid: 12906989
references.citation: J Am Coll Cardiol. 2007 Oct 9;50(15):1484-90
references.pmid: 17919569
references.citation: Ann Biomed Eng. 2009 Nov;37(11):2234-55
references.pmid: 19718527
references.citation: Ann Biomed Eng. 2003 May;31(5):536-47
references.pmid: 12757198
references.citation: Heart. 2001 Oct;86(4):397-404
references.pmid: 11559677
references.citation: Am J Physiol. 1986 Aug;251(2 Pt 2):H428-35
references.pmid: 3740295
references.citation: Cardiovasc Ultrasound. 2006 Nov 17;4:45
references.pmid: 17109761
references.citation: Circulation. 1998 Aug 11;98(6):588-95
references.pmid: 9714117
references.citation: Eur J Heart Fail. 2009 Sep;11(9):863-71
references.pmid: 19696058
references.citation: Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H640-6
references.pmid: 18515652
references.citation: JACC Cardiovasc Imaging. 2008 Sep;1(5):561-8
references.pmid: 19356481
references.citation: Circ Res. 1985 Nov;57(5):706-17
references.pmid: 4053304
references.citation: J Am Coll Cardiol. 2005 Sep 20;46(6):1067-75
references.pmid: 16168293
references.citation: Am Heart J. 2002 Mar;143(3):398-405
references.pmid: 11868043
references.citation: Am J Physiol Heart Circ Physiol. 2001 Dec;281(6):H2661-79
references.pmid: 11709436
references.citation: Circulation. 1995 Jun 1;91(11):2717-20
references.pmid: 7758175
references.citation: J Cardiovasc Electrophysiol. 2003 Oct;14(10 Suppl):S196-202
references.pmid: 14760924
references.citation: J Investig Med. 1999 Sep;47(8):369-77
references.pmid: 10510589
references.citation: Heart Fail Clin. 2008 Jul;4(3):371-8
references.pmid: 18598988
references.citation: Circulation. 2006 Dec 12;114(24):2627-35
references.pmid: 17130342
references.citation: Circ Res. 1987 Sep;61(3):318-28
references.pmid: 3621495
references.citation: Basic Res Cardiol. 1999 Aug;94(4):267-73
references.pmid: 10505427
references.citation: Pflugers Arch. 1993 Apr;423(1-2):78-87
references.pmid: 8488095
references.citation: J Thorac Cardiovasc Surg. 1997 Aug;114(2):169-78
references.pmid: 9270632
references.citation: Cardiovasc Res. 2002 Mar;53(4):831-40
references.pmid: 11922893
references.citation: Circ Res. 2005 Aug 5;97(3):207-9
references.pmid: 16002750
references.citation: Nat Med. 2004 Apr;10(4):422-8
references.pmid: 15034569
references.citation: J Clin Invest. 1996 Aug 1;98(3):764-76
references.pmid: 8698869
references.citation: Proc IEEE Inst Electr Electron Eng. 2006 Apr;94(4):819-830
references.pmid: 20463841
references.citation: Circulation. 2008 Mar 18;117(11):1369-77
references.pmid: 18316490
references.citation: J Electrocardiol. 2003;36 Suppl:57-61
references.pmid: 14716593
references.citation: Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1471-9
references.pmid: 14670817
references.citation: Am J Physiol. 1999 Mar;276(3):H881-91
references.pmid: 10070071
references.citation: Circulation. 2002 Oct 1;106(14):1760-3
references.pmid: 12356626