Human Heart

Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1-2% and incidence approaching 5-10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function – from structure and mechanics to metabolism and electrophysiology – leading to impaired mechanical contraction and sudden cardiac death. Implantable cardioverter defibrillator (ICD) therapy remains the primary HF management strategy, as pharmacotherapy is generally ineffective. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. Our research focusses on the human HF investigations of electrophysiology remodeling, metabolic remodeling, and β-adrenergic remodeling and on promising new technologies for HF research.

Publications:

 2016 | 2015 | 2014 | 2013 | 2012 | 2011  

2016  

  • Gloschat CR, Koppel AC, Aras KK, Brennan JA, Holzem KM, Efimov IR. Arrhythmogenic and metabolic remodeling of failing human heart. J Physiol. 2016 Mar 28. doi: 10.1113/JP271992. [Epub ahead of print] PubMed PMID: 27019074. [PubMed]

2015

  • Boukens BJ, Gutbrod SR, Efimov IR. Imaging of Ventricular Fibrillation and Defibrillation: The Virtual Electrode Hypothesis. Adv Exp Med Biol. 2015;859:343-65. doi: 10.1007/978-3-319-17641-3_14. Review. PMID: 26238060 [PubMed]
  • Boukens BJ, Sulkin MS, Gloschat CR, Ng FS, Vigmond EJ, Efimov IR. Transmural APD gradient synchronizes repolarization in the human left ventricular wall. Cardiovasc Res. 2015 Oct 1;108(1):188-96. doi: 10.1093/cvr/cvv202. Epub 2015 Jul 24. PMID: 26209251 [PubMed]
  • Holzem KM, Gomez JF, Glukhov AV, Madden EJ, Koppel AC, Ewald GA, Trenor B, Efimov IR. Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure. J Mol Cell Cardiol. 2015 Jun 17. pii: S0022-2828(15)00194-7. doi: 10.1016/j.yjmcc.2015.06.008. PMID: 26093152[PubMed]
  • Doshi AN, Walton RD, Krul SP, de Groot JR, Bernus O, Efimov IR, Boukens BJ, Coronel R. Feasibility of a semi-automated method for cardiac conduction velocity analysis of high-resolution activation maps. Comput Biol Med. 2015 Oct 1;65:177-83. doi: 10.1016/j.compbiomed.2015.05.008. Epub 2015 May 21.PMID: 26045101 [PubMed]
  • Child N, Bishop MJ, Hanson B, Coronel R, Opthof T, Boukens BJ, Walton RD, Efimov IR, Bostock J, Hill Y, Rinaldi CA, Razavi R, Gill J, Taggart P. An activation-repolarization time metric to predict localized regions of high susceptibility to reentry. Heart Rhythm. 2015 Jul;12(7):1644-53. doi: 10.1016/j.hrthm.2015.04.013. Epub 2015 Apr 9. PMID: 25863160 [PubMed]
  • Kurian T, Doshi A, Kessman P, Nguyen B, Edwards J, Pieper S, Efimov I, Janardhan AH, Sanchez M. Rotors in patients with persistent atrial fibrillation: case report of a left atrial appendage rotor identified by a novel computational mapping algorithm integrated into 3-dimensional mapping and termination of atrial fibrillation with ablation. Card Electrophysiol Clin. 2015 Mar;7(1):157-63. doi: 10.1016/j.ccep.2014.11.009. Epub 2014 Dec 18. PMID: 25784031 [PubMed]
  • Bear L, Cuculich PS, Bernus O, Efimov I, Dubois R. Introduction to noninvasive cardiac mapping. Card Electrophysiol Clin. 2015 Mar;7(1):1-16. doi: 10.1016/j.ccep.2014.11.015. Review. PMID: 25784020 [PubMed]
  • Lang D, Holzem K, Kang C, Xiao M, Hwang HJ, Ewald GA, Yamada KA, Efimov IR. Arrhythmogenic remodeling of β2 versus β1 adrenergic signaling in the human failing heart. Circ Arrhythm Electrophysiol. 2015 Apr;8(2):409-19. doi: 10.1161/CIRCEP.114.002065. Epub 2015 Feb 11. PMID: 25673629 [PubMed]

2014

  • Holzem KM, Madden EJ, Efimov IR. Human cardiac systems electrophysiology and arrhythmogenesis: iteration of experiment and computation. Europace, 2014 Nov;16 Suppl 4:iv77-iv85. doi: 10.1093/europace/euu264. PMID: 25362174. [PubMed]
  • Gutbrod SR, Sulkin MS, Rogers JA, Efimov IR. Patient-Specific Flexible and Stretchable Devices for Cardiac Diagnostics and Therapy, Progress in Biophysics and Molecular Biology, 2014 Aug;115(2-3):244-51. doi: 10.1016/j.pbiomolbio.2014.07.011. Epub 2014 Aug 5. PMID: 25106701. [PubMed]
  • Xu L, Gutbrod SR, Bonifas AP, Su Y, Sulkin MS, Lu N, Chung HJ, Jang KI, Liu Z, Ying M, Lu C, Webb RC, Kim JS, Laughner JI, Cheng H, Liu Y, Ameen A, Jeong JW, Kim GT, Huang Y, Efimov IR, Rogers JA. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat Commun. 2014 Feb 25;5:3329. doi: 10.1038/ncomms4329. PMID: 24569383. [PubMed] [PDF]
  • Chung HJ, Sulkin MS, Kim JS, Goudeseune C, Chao HY, Song JW, Yang SY, Hsu YY, Ghaffari R, Efimov IR, Rogers JA. Stretchable, Multiplexed pH Sensors With Demonstrations on Rabbit and Human Hearts Undergoing Ischemia. Adv Healthc Mater. 2014 Jan;3(1):59-68. doi: 10.1002/adhm.201300124. Epub 2013 Jul 19. PMID: 23868871. [PubMed]
  • Arakel EC, Brandenburg S, Uchida K, Zhang H, Lin YW, Kohl T, Schrul B, Sulkin MS, Efimov IR, Nichols CG, Lehnart SE, Schwappach B. Tuning the electrical properties of the heart by differential trafficking of KATP ion channel complexes. J Cell Sci. 2014 May 1;127(Pt 9):2106-19. doi: 10.1242/jcs.141440. Epub 2014 Feb 25. PMID: 24569881. [PubMed]
  • Gutbrod SR, Sulkin MS, Rogers JA, Efimov IR. Patient-specific flexible and stretchable devices for cardiac diagnostics and therapy. Prog Biophys Mol Biol. 2014 Aug;115(2-3):244-51. doi: 10.1016/j.pbiomolbio.2014.07.011. Epub 2014 Aug 5. PMID: 25106701. [PubMed]
  • Ng FS, Holzem KM, Koppel AC, Janks D, Gordon F, Wit AL, Peters NS, Efimov IR. Adverse Remodeling of the Electrophysiological Response to Ischemia-Reperfusion in Human Heart Failure Is Associated with Remodeling of Metabolic Gene Expression. Circ Arrhythm Electrophysiol. 2014 Oct;7(5):875-82. doi: 10.1161/CIRCEP.113.001477. Epub 2014 Aug 11. PMID: 25114062. [PubMed]
  • Boukens B, Efimov I. A Century of Optocardiography. IEEE Rev Biomed Eng. 2014;7:115-25. doi: 10.1109/RBME.2013.2286296. Epub 2013 Oct 23. PMID: 24158521. [PubMed]
  • Sulkin MS, Yang F, Holzem KM, Van Leer B, Bugge C, Laughner JI, Green K, Efimov IR. Nanoscale three-dimensional imaging of the human myocyte. J Struct Biol. 2014 Oct;188(1):55-60. doi: 10.1016/j.jsb.2014.08.005. Epub 2014 Aug 23. PMID: 25160725 [PubMed]
  • Sulkin MS, Boukens BJ, Tetlow M, Gutbrod SR, Ng FS, Efimov IR. Mitochondrial depolarization and electrophysiological changes during ischemia in the rabbit and human heart. Am J Physiol Heart Circ Physiol. 2014 Oct 15;307(8):H1178-86. doi: 10.1152/ajpheart.00437.2014. Epub 2014 Aug 15. PMID: 25128175. [PubMed]

2013

  • Ambrosi CM, Yamada KA, Nerbonne JM, Efimov IR. Gender differences in electrophysiological gene expression in failing and non-failing human hearts. PLoS One. 2013;8(1):e54635. doi: 10.1371/journal.pone.0054635. Epub 2013 Jan 23. PMID: 23355885. [PubMed]
  • Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B, Jarman S, Efimov IR, Janks DL, Srivastava A, Bhayani SB, Drewry A, Swanson PE, Hotchkiss RS. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med. 2013 Mar 1;187(5):509-17. doi: 10.1164/rccm.201211-1983OC. Epub 2013 Jan 24. PMID: 23348975. [PubMed]
  • Glukhov AV, Uchida K, Efimov IR, Nichols CG. Functional roles of KATP channel subunits in metabolic inhibition. J Mol Cell Cardiol. 2013 Sep;62:90-8. doi: 10.1016/j.yjmcc.2013.04.016. Epub 2013 Apr 23. PMID: 23624089. [PubMed]
  • Smith AW, Hoyne JD, Nguyen PK, McCreedy DA, Aly H, Efimov IR, Rentschler S, Elbert DL. Direct reprogramming of mouse fibroblasts to cardiomyocyte-like cells using Yamanaka factors on engineered poly(ethylene glycol) (PEG) hydrogels. Biomaterials. 2013 Sep;34(28):6559-71. doi: 10.1016/j.biomaterials.2013.05.050. Epub 2013 Jun 14. PMID: 23773820 [PubMed]
  • Liu M, Gu L, Sulkin MS, Liu H, Jeong EM, Greener I, Xie A, Efimov IR, Dudley SC Jr. Mitochondrial dysfunction causing cardiac sodium channel downregulation in cardiomyopathy. J Mol Cell Cardiol. 2013 Jan;54:25-34. doi: 10.1016/j.yjmcc.2012.10.011. Epub 2012 Nov 1. PMID: 23123323. [PubMed]
  • Rutledge CA, Ng FS, Sulkin MS, Greener ID, Sergeyenko AM, Liu H, Gemel J, Beyer EC, Sovari AA, Efimov IR, Dudley SC. c-Src Kinase Inhibition Reduces Arrhythmia Inducibility and Connexin43 Dysregulation after Myocardial Infarction. J Am Coll Cardiol. 2014 Mar 11;63(9):928-34. doi: 10.1016/j.jacc.2013.10.081. Epub 2014 Jan 8. PMID: 24361364. [PubMed]
  • Wang Y, Laughner JI, Efimov IR, Zhang S. 3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique. Opt Express. 2013 Mar 11;21(5):5822-32. doi: 10.1364/OE.21.005822. PMID: 23482151. [PubMed]
  • Walmsley J, Rodriguez JF, Mirams GR, Burrage K, Efimov IR, Rodriguez B. mRNA expression levels in failing human hearts predict cellular electrophysiological remodeling: a population-based simulation study. PLoS One. 2013;8(2):e56359. doi: 10.1371/journal.pone.0056359. Epub 2013 Feb 20. PMID: 23437117. [PubMed]
  • Sulkin MS, Widder E, Shao C, Holzem KM, Gloschat C, Gutbrod SR, Efimov IR. Three-dimensional printing physiology laboratory technology. Am J Physiol Heart Circ Physiol. 2013 Dec;305(11):H1569-73. doi: 10.1152/ajpheart.00599.2013. Epub 2013 Sep 16. PMID: 24043254. [PubMed]

2012

  • Rantner LJ, Arevalo HJ, Constantino JL, Efimov IR, Plank G, Trayanova NA. Three-Dimensional Mechanisms of Increased Vulnerability to Electric Shocks in Myocardial Infarction: Altered Virtual Electrode Polarizations and Conduction Delay in the Peri-Infarct Zone. J Physiol. 2012 Sep 15;590(Pt 18):4537-51. doi: 10.1113/jphysiol.2012.229088. Epub 2012 May 14. PMID: 22586222. [PubMed]
  • Lou Q, Janardhan A, Efimov IR. Remodeling of calcium handling in human heart failure. Adv Exp Med Biol. 2012;740:1145-74. doi: 10.1007/978-94-007-2888-2_52. PMID: 22453987. [PubMed]
  • Glukhov AV, Fedorov VV, Kalish PW, Ravikumar VK, Lou Q, Janks D, Schuessler RB, Moazami N, Efimov IR. Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy. Circulation. 2012 Apr 17;125(15):1835-47. doi: 10.1161/CIRCULATIONAHA.111.047274. Epub 2012 Mar 12. PMID: 22412072. [PubMed]
  • Nikolaidou T, Aslanidi OV, Zhang H, Efimov IR. Structure-Function Relationship in the Sinus and Atrioventricular Nodes. Pediatr Cardiol. 2012 Aug;33(6):890-9. doi: 10.1007/s00246-012-0249-0. Epub 2012 Mar 3. PMID: 22391764. [PubMed]
  • Lou Q, Janks DL, Holzem K, Lang D, Onal B, Ambrosi CM, Fedorov VV, Wang IW, Efimov IR. Right Ventricular Arrhythmogenesis in Failing Human Heart: The Role of Conduction and Repolarization Remodeling. Am J Physiol Heart Circ Physiol. 2012 Dec 15;303(12):H1426-34. doi: 10.1152/ajpheart.00457.2012. Epub 2012 Oct 5. PMID: 23042951. [PubMed]
  • Lou Q, Li W, Efimov IR. The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin vs. 2,3-butanedione monoxime. Am J Physiol Heart Circ Physiol. 2012 Jan;302(1):H262-9. Epub 2011 Oct 28. PMID: 22037192. [PubMed]
  • Holzem KM, Efimov IR. Arrhythmogenic remodelling of activation and repolarization in the failing human heart. Europace 2012 Nov;14 Suppl 5:v50-v57. doi: 10.1093/europace/eus275. PMID: 23104915. [PubMed]

2011

  • Fedorov VV, Ambrosi CM, Kostecki G, Hucker WJ, Glukhov AV, Wuskell J, Loew LM, Moazami N, Efimov IR. Anatomic localization and autonomic modulation of atrioventricular junctional rhythm in failing human hearts. Circ Arrhythm Electrophysiol. 2011 Aug;4(4):515-25. Epub 2011 Jun 6. PMID: 21646375. [PubMed]
  • Greener ID, Monfredi O, Inada S, Chandler NJ, Tellez JO, Atkinson A, Taube MA, Billeter R, Anderson RH, Efimov IR, Molenaar P, Sigg DC, Sharma V, Boyett MR, Dobrzynski H. Molecular architecture of the human specialised atrioventricular conduction axis. J Mol Cell Cardiol. 2011 Apr;50(4):642-51. doi: 10.1016/j.yjmcc.2010.12.017. Epub 2011 Jan 21. PMID: 21256850. [PubMed]
  • Lou Q, Fedorov VV, Glukhov AV, Fast VG, Moazami N, Efimov IR. Transmural heterogeneity and remodeling of ventricular excitation-contraction coupling in human heart failure. Circulation. 2011 May 3;123(17):1881-90. doi: 10.1161/CIRCULATIONAHA.110.989707. Epub 2011 Apr 18. PMID: 21502574. [PubMed]
  • Fedorov VV, Glukhov AV, Ambrosi CM, Kostecki G, Chang R, Janks D, Schuessler RB, Moazami N, Nichols CG, Efimov IR. Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts. J Mol Cell Cardiol. 2011 Aug;51(2):215-25. doi: 10.1016/j.yjmcc.2011.04.016. Epub 2011 May 7. PMID: 21586291. [PubMed]