Task Progress:
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AIM 1: NEW TECHNIQUES TO ASSESS CARDIAC FUNCTION IN SPACE
We found that early diastolic IVPGs are associated with LV contractility. These findings may explain the proposed mechanism in which potential energy stored during systole is released during diastole to provide for adequate ventricular filling, even under low filling pressures. Left ventricular(LV) untwisting starts early during the isovolumic relaxation phase and proceeds throughout the early filling phase, releasing elastic energy stored by the preceding systolic deformation. Studies in our animal model demonstrated moderately strong correlation of peak LV twisting with peak LV untwisting rate. In a multivariate analysis, peak LV untwisting rate was an independent predictor of tau and IVPG. The start of LV untwisting coincided with the beginning of relaxation and preceded suction-aided filling resulting from elastic recoil.
AIM 2: USE EXERCISE ECHO TO DETECT CARDIAC DYSFUNCTION
We have shown that the ability to augment IVPG is the best predictor of maximum exercise capacity, and that the release of ventricular torsion during the isovolumic relaxation period is closely correlated with IVPG, thereby linking systolic contraction to diastolic filling. We have also shown that the loss of IVPG during exercise is strongly linked to the loss of untwisting velocity to and to the loss of torsion. We have studied the effects of exercise on left ventricular diastolic function using strain techniques from AIM 1 and found that the longitudinal strain rate in healthy volunteers was the best predictor of the increase of untwisting velocity and IVPG.
AIM 3: ASSESS PREDICTORS OF MASS REGRESSION FOLLOWING UNLOADING
Cardiac atrophy may be a serious limitation in long-term space flight, and understanding its significance and genetic determinants is critical to designing appropriate countermeasures. We have shown by 3D echo that aortic valve replacement can result in up to 50% mass reduction in patients with aortic insufficiency of stenosis. We are continuing this study obtaining comprehensive echo studies pre and post-op (3, 7 days, 6, 12 months) with volumes, mass, ejection fraction, strain, torsion, and IVPG.
AIM 4: DEVELOP A 3D FLUID-STRUCTURE INTERACTION MODEL OF THE HEART
Coding has been completed on a full 3D model of the left ventricle, using realistic myocardial fiber architecture and calcium-transient-based contraction and relaxation coupled with full Navier-Stokes description of blood flow. We also constructed a novel lumped-parameter model of the cardiovascular system, based on calcium transients (instead of previous model based on fixed systolic elastance). This novel model has been published in the Ann of Bio Eng, shows more realistic hemodynamics than the previous one, and is used to as an input to the 3D fluid-structure interaction model. A second manuscript was also submitted to Biomechanics and Modeling in Mechanobiology.
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Articles in Peer-reviewed Journals
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Firstenberg MS, Greenberg NL, Garcia MJ, Thomas JD. "Relationship between ventricular contractility and early diastolic intraventricular pressure gradients: a diastolic link to systolic function." J Am Soc Echocardiogr. 2008 May;21(5):501-6. PMID: 17928198 , May-2008
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Articles in Peer-reviewed Journals
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Lim P, Buakhamsri A, Popovic ZB, Greenberg NL, Patel D, Thomas JD, Grimm RA. "Longitudinal strain delay index by speckle tracking imaging: a new marker of response to cardiac resynchronization therapy." Circulation. 2008 Sep 9;118(11):1130-7. PMID: 18725491 , Sep-2008
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Articles in Peer-reviewed Journals
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Matsumura Y, Fukuda S, Tran H, Greenberg NL, Agler DA, Wada N, Toyono M, Thomas JD, Shiota T. "Geometry of the proximal isovelocity surface area in mitral regurgitation by 3-dimensional color Doppler echocardiography: difference between functional mitral regurgitation and prolapse regurgitation." Am Heart J. 2008 Feb;155(2):231-8. PMID: 18215591 , Feb-2008
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Articles in Peer-reviewed Journals
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Matsumura Y, Saracino G, Sugioka K, Tran H, Greenberg NL, Wada N, Toyono M, Fukuda S, Hozumi T, Thomas JD, Yoshikawa J, Yoshiyama M, Shiota T. "Determination of regurgitant orifice area with the use of a new three-dimensional flow convergence geometric assumption in functional mitral regurgitation." J Am Soc Echocardiogr. 2008 Nov;21(11):1251-6. PMID: 18992676 , Nov-2008
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Articles in Peer-reviewed Journals
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Notomi Y, Popovic ZB, Yamada H, Wallick DW, Martin MG, Oryszak SJ, Shiota T, Greenberg NL, Thomas JD. "Ventricular untwisting: a temporal link between left ventricular relaxation and suction." Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H505-13. PMID: 18032523 , Jan-2008
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Articles in Peer-reviewed Journals
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Lim P, Mitchell-Heggs L, Buakhamsri A, Thomas JD, Grimm RA. "Impact of left ventricular size on tissue Doppler and longitudinal strain by speckle tracking for assessing wall motion and mechanical dyssynchrony in candidates for cardiac resynchronization therapy." J Am Soc Echocardiogr. 2009 Jun;22(6):695-701. http://dx.doi.org/10.1016/j.echo.2009.04.015 ; PubMed PMID: 19501329 , Jun-2009
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Articles in Peer-reviewed Journals
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Buakhamsri A, Popovic ZB, Lin J, Lim P, Greenberg NL, Borowski AG, Tang WH, Klein AL, Lever HM, Desai MY, Thomas JD. "Impact of left ventricular volume/mass ratio on diastolic function." Eur Heart J. 2009 May;30(10):1213-21. Epub 2009 Mar 20. http://dx.doi.org/10.1093/eurheartj/ehp084 ; PubMed PMID: 1930474 , May-2009
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Articles in Peer-reviewed Journals
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Asada-Kamiguchi J, Tabata T, Popovic ZB, Greenberg NL, Kim YJ, Garcia MJ, Wallick DW, Mowrey KA, Zhuang S, Zhang Y, Mazgalev TN, Thomas JD, Grimm RA. "Non-invasive assessment of left ventricular relaxation during atrial fibrillation using mitral flow propagation velocity." Eur J Echocardiogr. 2009 Oct;10(7):826-32. PMID: 19692424 , Oct-2009
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Articles in Peer-reviewed Journals
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Phillips KP, Popovic ZB, Lim P, Meulet JE, Barrett CD, Di Biase L, Agler D, Thomas JD, Grimm RA. "Opposing wall mechanics are significantly influenced by longitudinal cardiac rotation in the assessment of ventricular dyssynchrony." JACC Cardiovasc Imaging. 2009 Apr;2(4):379-86. PMID: 19580717 , Apr-2009
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Articles in Peer-reviewed Journals
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Puwanant S, Park M, Popovic ZB, Tang WH, Farha S, George D, Sharp J, Puntawangkoon J, Loyd JE, Erzurum SC, Thomas JD. "Ventricular geometry, strain, and rotational mechanics in pulmonary hypertension." Circulation. 2010 Jan 19;121(2):259-66. PMID: 20048214 , Jan-2010
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Articles in Peer-reviewed Journals
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Saraiva RM, Matsumura Y, Yamano T, Greenberg N, Thomas JD, Shiota T. "Relation of left atrial dysfunction to pulmonary artery hypertension in patients with aortic stenosis and left ventricular systolic dysfunction." Am J Cardiol. 2010 Aug 1;106(3):409-16. PMID: 20643255 , Aug-2010
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Articles in Peer-reviewed Journals
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Beach JM, Mihaljevic T, Rajeswaran J, Marwick T, Edwards ST, Nowicki ER, Thomas J, Svensson LG, Griffin B, Gillinov AM, Blackstone EH. "Ventricular hypertrophy and left atrial dilatation persist and are associated with reduced survival after valve replacement for aortic stenosis." J Thorac Cardiovasc Surg. 2014 Jan;147(1):362-369.e8. Epub 2013 Jan 11. https://doi.org/10.1016/j.jtcvs.2012.12.016 ; PubMed PMID: 23312984 , Jan-2014
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