Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.


Journal

Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676

Informations de publication

Date de publication:
Feb 2024
Historique:
received: 06 12 2022
accepted: 26 12 2023
medline: 28 8 2024
pubmed: 28 8 2024
entrez: 28 8 2024
Statut: ppublish

Résumé

Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA)

Identifiants

pubmed: 39196193
doi: 10.1038/s44161-023-00419-3
pii: 10.1038/s44161-023-00419-3
doi:

Substances chimiques

Biomarkers 0
Anti-Arrhythmia Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

145-165

Subventions

Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : APP1194139/APP1126276
Organisme : National Heart Foundation of Australia (Heart Foundation)
ID : 101889

Informations de copyright

© 2024. The Author(s).

Références

Laflamme, M. A. & Murry, C. E. Heart regeneration. Nature 473, 326–335 (2011).
pubmed: 21593865 pmcid: 4091722 doi: 10.1038/nature10147
Nguyen, P. K., Rhee, J.-W. & Wu, J. C. Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review. JAMA Cardiol. 1, 831–841 (2016).
pubmed: 27557438 pmcid: 5349705 doi: 10.1001/jamacardio.2016.2225
Fisher, S. A., Doree, C., Mathur, A., Taggart, D. P. & Martin-Rendon, E. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst. Rev. 12, CD007888 (2016).
pubmed: 28012165
Menasché, P. Cell therapy trials for heart regeneration — lessons learned and future directions. Nat. Rev. Cardiol. 15, 659–671 (2018).
pubmed: 29743563 doi: 10.1038/s41569-018-0013-0
Eschenhagen, T. et al. Cardiomyocyte regeneration: a consensus statement. Circulation 136, 680–686 (2017).
pubmed: 28684531 pmcid: 5557671 doi: 10.1161/CIRCULATIONAHA.117.029343
van Berlo, J. H. et al. c-kit
pubmed: 24805242 pmcid: 4127035 doi: 10.1038/nature13309
Mummery, C. L. et al. Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview. Circ. Res. 111, 344–358 (2012).
pubmed: 22821908 pmcid: 3578601 doi: 10.1161/CIRCRESAHA.110.227512
Chong, J. J. et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510, 273–277 (2014).
pubmed: 24776797 pmcid: 4154594 doi: 10.1038/nature13233
Liu, Y.-W. et al. Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nat. Biotechnol. 36, 597–605 (2018).
pubmed: 29969440 pmcid: 6329375 doi: 10.1038/nbt.4162
Shiba, Y. et al. Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature 538, 388–391 (2016).
pubmed: 27723741 doi: 10.1038/nature19815
Romagnuolo, R. et al. Human embryonic stem cell-derived cardiomyocytes regenerate the infarcted pig heart but induce ventricular tachyarrhythmias. Stem Cell Reports 12, 967–981 (2019).
pubmed: 31056479 pmcid: 6524945 doi: 10.1016/j.stemcr.2019.04.005
Nakamura, K. et al. Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes. Stem Cell Reports 16, 2473–2487 (2021).
Zhao, M. et al. Cyclin D2 overexpression enhances the efficacy of human induced pluripotent stem cell-derived cardiomyocytes for myocardial repair in a swine model of myocardial infarction. Circulation 144, 210–228 (2021).
pubmed: 33951921 pmcid: 8292228 doi: 10.1161/CIRCULATIONAHA.120.049497
National Library of Medicine. Safety and Efficacy of Induced Pluripotent Stem Cell-Derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure (BioVAT-HF). Identifier: NCT04396899 www.clinicaltrials.gov/ct2/show/NCT04396899 (2020).
National Library of Medicine. A Study of iPS Cell-Derived Cardiomyocyte Spheroids (HS-001) in Patients with Heart Failure (LAPiS Study). Identifier: NCT04945018 www.clinicaltrials.gov/ct2/show/NCT04945018 (2021).
National Library of Medicine. Treating Heart Failure with hPSC-CMs (HEAL-CHF). Identifier: NCT03763136 www.clinicaltrials.gov/ct2/show/NCT03763136 (2018).
National Library of Medicine. Treating Congestive HF with hiPSC-CMs through Endocardial Injection. Identifier: NCT04982081 www.clinicaltrials.gov/ct2/show/NCT04982081 (2021).
Eschenhagen, T., Ridders, K. & Weinberger, F. How to repair a broken heart with pluripotent stem cell-derived cardiomyocytes. J. Mol. Cell. Cardiol. 163, 106–117 (2021).
pubmed: 34687723 doi: 10.1016/j.yjmcc.2021.10.005
Selvakumar, D., Clayton, Z. E. & Chong, J. J. H. Robust cardiac regeneration: fulfilling the promise of cardiac cell therapy. Clin. Ther. 42, 1857–1879 (2020).
pubmed: 32943195 doi: 10.1016/j.clinthera.2020.08.008
Selvakumar, D., Reyes, L. & Chong, J. J. H. Cardiac cell therapy with pluripotent stem cell-derived cardiomyocytes: what has been done and what remains to do? Curr. Cardiol. Rep. 24, 445–461 (2022).
Lee, J. H., Protze, S. I., Laksman, Z., Backx, P. H. & Keller, G. M. Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Cell Stem Cell 21, 179–194 (2017).
pubmed: 28777944 doi: 10.1016/j.stem.2017.07.003
He, J.-Q., Ma, Y., Lee, Y., Thomson, J. A. & Kamp, T. J. Human embryonic stem cells develop into multiple types of cardiac myocytes. Circ. Res. 93, 32–39 (2003).
pubmed: 12791707 doi: 10.1161/01.RES.0000080317.92718.99
Moore, J. C. et al. Distinct cardiogenic preferences of two human embryonic stem cell (hESC) lines are imprinted in their proteomes in the pluripotent state. Biochem. Biophys. Res. Commun. 372, 553–558 (2008).
pubmed: 18503758 pmcid: 2665880 doi: 10.1016/j.bbrc.2008.05.076
Zhao, M.-T., Shao, N.-Y. & Garg, V. Subtype-specific cardiomyocytes for precision medicine: where are we now? Stem Cells 38, 822–833 (2020).
pubmed: 32232889 doi: 10.1002/stem.3178
Chen, V. C. et al. Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells. Stem Cell Res. 15, 365–375 (2015).
pubmed: 26318718 pmcid: 4600677 doi: 10.1016/j.scr.2015.08.002
Stevenson, W. G. et al. Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping. J. Am. Coll. Cardiol. 29, 1180–1189 (1997).
pubmed: 9137211 doi: 10.1016/S0735-1097(97)00065-X
de Bakker, J. M. et al. Slow conduction in the infarcted human heart. ‘Zigzag’ course of activation. Circulation 88, 915–926 (1993).
pubmed: 8353918 doi: 10.1161/01.CIR.88.3.915
Hundley, W. G. et al. ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J. Am. Coll. Cardiol. 55, 2614–2662 (2010).
pubmed: 20513610 doi: 10.1016/j.jacc.2009.11.011
Funakoshi, S. et al. Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells. Nat. Commun. 12, 3155 (2021).
pubmed: 34039977 pmcid: 8155185 doi: 10.1038/s41467-021-23329-z
Nelson, D. O. et al. Irx4 marks a multipotent, ventricular-specific progenitor cell. Stem Cells 34, 2875–2888 (2016).
pubmed: 27570947 doi: 10.1002/stem.2486
O’Brien, T. X., Lee, K. J. & Chien, K. R. Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube. Proc. Natl Acad. Sci. USA 90, 5157–5161 (1993).
pubmed: 8506363 pmcid: 46674 doi: 10.1073/pnas.90.11.5157
Liang, D. et al. Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing. Nat. Commun. 12, 287 (2021).
pubmed: 33436583 pmcid: 7804277 doi: 10.1038/s41467-020-20448-x
Espinoza-Lewis, R. A. et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev. Biol. 327, 376–385 (2009).
pubmed: 19166829 pmcid: 2694185 doi: 10.1016/j.ydbio.2008.12.028
Houweling, A. C., van Borren, M. M., Moorman, A. F. & Christoffels, V. M. Expression and regulation of the atrial natriuretic factor encoding gene Nppa during development and disease. Cardiovasc. Res. 67, 583–593 (2005).
pubmed: 16002056 doi: 10.1016/j.cardiores.2005.06.013
Li, G. et al. Transcriptomic profiling maps anatomically patterned subpopulations among single embryonic cardiac cells. Dev. Cell 39, 491–507 (2016).
pubmed: 27840109 pmcid: 5130110 doi: 10.1016/j.devcel.2016.10.014
Mohamed, T. M. A. et al. Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173, 104–116 (2018).
pubmed: 29502971 pmcid: 5973786 doi: 10.1016/j.cell.2018.02.014
Li, W.-C. et al. Regulatory role of hexokinase 2 in modulating head and neck tumorigenesis. Front. Oncol. 10, 176 (2020).
Veevers, J. et al. Cell-surface marker signature for enrichment of ventricular cardiomyocytes derived from human embryonic stem cells. Stem Cell Reports 11, 828–841 (2018).
pubmed: 30122443 pmcid: 6135222 doi: 10.1016/j.stemcr.2018.07.007
Skelton, R. J. et al. SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development. Stem Cell Res. 13, 172–179 (2014).
pubmed: 24968096 doi: 10.1016/j.scr.2014.04.016
Palpant, N. J. et al. Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nat. Protoc. 12, 15–31 (2017).
pubmed: 27906170 doi: 10.1038/nprot.2016.153
Doppler, S. A. et al. Cardiac fibroblasts: more than mechanical support. J. Thorac. Dis. 9, S36–S51 (2017).
pubmed: 28446967 pmcid: 5383558 doi: 10.21037/jtd.2017.03.122
Skelton, R. J. et al. CD13 and ROR2 permit isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells. Stem Cell Reports 6, 95–108 (2016).
pubmed: 26771355 pmcid: 4720015 doi: 10.1016/j.stemcr.2015.11.006
Protze, S. I. et al. Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker. Nat. Biotechnol. 35, 56–68 (2017).
pubmed: 27941801 doi: 10.1038/nbt.3745
Cable, D. M. et al. Robust decomposition of cell type mixtures in spatial transcriptomics. Nat. Biotechnol. 40, 517–526 (2022).
pubmed: 33603203 doi: 10.1038/s41587-021-00830-w
DiFrancesco, D. Pacemaker mechanisms in cardiac tissue. Annu. Rev. Physiol. 55, 455–472 (1993).
pubmed: 7682045 doi: 10.1146/annurev.ph.55.030193.002323
DiFrancesco, D. The role of the funny current in pacemaker activity. Circ. Res. 106, 434–446 (2010).
pubmed: 20167941 doi: 10.1161/CIRCRESAHA.109.208041
Psotka, M. A. & Teerlink, J. R. Ivabradine. Circulation 133, 2066–2075 (2016).
pubmed: 27217432 doi: 10.1161/CIRCULATIONAHA.115.018094
Waks, J. W. & Zimetbaum, P. Antiarrhythmic drug therapy for rhythm control in atrial fibrillation. J. Cardiovasc. Pharmacol. Ther. 22, 3–19 (2017).
pubmed: 27260643 doi: 10.1177/1074248416651722
Karbassi, E. et al. Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine. Nat. Rev. Cardiol. 17, 341–359 (2020).
Guo, Y. & Pu, W. T. Cardiomyocyte maturation: new phase in development. Circ. Res. 126, 1086–1106 (2020).
pubmed: 32271675 pmcid: 7199445 doi: 10.1161/CIRCRESAHA.119.315862
Maroli, G. & Braun, T. The long and winding road of cardiomyocyte maturation. Cardiovasc. Res. 117, 712–726 (2021).
pubmed: 32514522 doi: 10.1093/cvr/cvaa159
Marchianò, S., Bertero, A. & Murry, C. E. Learn from your elders: developmental biology lessons to guide maturation of stem cell-derived cardiomyocytes. Pediatr. Cardiol. 40, 1367–1387 (2019).
pubmed: 31388700 pmcid: 6786957 doi: 10.1007/s00246-019-02165-5
Zhang, Q. et al. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals. Cell Res. 21, 579–587 (2011).
pubmed: 21102549 doi: 10.1038/cr.2010.163
Wiesinger, A., Boink, G. J. J., Christoffels, V. M. & Devalla, H. D. Retinoic acid signaling in heart development: application in the differentiation of cardiovascular lineages from human pluripotent stem cells. Stem Cell Reports 16, 2589–2606 (2021).
Zhao, Y. et al. A platform for generation of chamber-specific cardiac tissues and disease modeling. Cell 176, 913–927 (2019).
pubmed: 30686581 pmcid: 6456036 doi: 10.1016/j.cell.2018.11.042
Devalla, H. D. et al. Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology. EMBO Mol. Med. 7, 394–410 (2015).
pubmed: 25700171 pmcid: 4403042 doi: 10.15252/emmm.201404757
Lian, X. et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl Acad. Sci. USA 109, E1848–E1857 (2012).
pmcid: 3390875 doi: 10.1073/pnas.1200250109
Karakikes, I. et al. Small molecule-mediated directed differentiation of human embryonic stem cells toward ventricular cardiomyocytes. Stem Cells Transl. Med. 3, 18–31 (2014).
pubmed: 24324277 doi: 10.5966/sctm.2013-0110
Ren, J. et al. Canonical Wnt5b signaling directs outlying Nkx2.5
pubmed: 31402282 pmcid: 6759400 doi: 10.1016/j.devcel.2019.07.014
Marchiano, S. et al. Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy. Cell Stem Cell 30, 396–414 (2023).
pubmed: 37028405 doi: 10.1016/j.stem.2023.03.010
Stüdemann, T. et al. Contractile force of transplanted cardiomyocytes actively supports heart function after injury. Circulation 146, 1159–1169 (2022).
Tachibana, A. et al. Paracrine effects of the pluripotent stem cell-derived cardiac myocytes salvage the injured myocardium. Circ. Res. 121, e22–e36 (2017).
pubmed: 28743804 pmcid: 5783162 doi: 10.1161/CIRCRESAHA.117.310803
Chen, X. et al. Methods for expansion of three-dimensional cultures of human embryonic stem cells using a thermoresponsive polymer. Tissue Eng. Part C Methods 24, 146–157 (2018).
pubmed: 29239281 doi: 10.1089/ten.tec.2017.0331
Qiu, X. X. et al. Rapamycin and CHIR99021 coordinate robust cardiomyocyte differentiation from human pluripotent stem cells via reducing p53-dependent apoptosis. J. Am. Heart Assoc. 6, e005295 (2017).
Laflamme, M. A. et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol. 25, 1015–1024 (2007).
pubmed: 17721512 doi: 10.1038/nbt1327
van der Maaten, L. & Hinton, G. Visualizing data using t-SNE J. Mach. Learn. Res. 9, 2579–2605 (2008).
Van Gassen, S. et al. FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data. Cytometry A 87, 636–645 (2015).
pubmed: 25573116 doi: 10.1002/cyto.a.22625
Takaki, T. & Yoshida, Y. Application of FluoVolt membrane potential dye for induced pluripotent stem cell-derived cardiac single cells and monolayers differentiated via embryoid bodies. Methods Mol. Biol. 2320, 101–110 (2021).
pubmed: 34302652 doi: 10.1007/978-1-0716-1484-6_11
Heitmann, S., Shpak, A., Vandenberg, J. I. & Hill, A. P. Arrhythmogenic effects of ultra-long and bistable cardiac action potentials. PLoS Comput. Biol. 17, e1008683 (2021).
pubmed: 33591969 pmcid: 7909657 doi: 10.1371/journal.pcbi.1008683
Thavapalachandran, S. et al. Platelet-derived growth factor-AB improves scar mechanics and vascularity after myocardial infarction. Sci. Transl. Med. 12, eaay2140 (2020).
pubmed: 31894101 doi: 10.1126/scitranslmed.aay2140
Schulz-Menger, J. et al.Standardized image interpretation and post-processing in cardiovascular magnetic resonance — 2020 update. J. Cardiovasc. Magn. Reson. 22, 19 (2020).
pubmed: 32160925 pmcid: 7066763 doi: 10.1186/s12968-020-00610-6
Andreu, D. et al. 3D delayed-enhanced magnetic resonance sequences improve conducting channel delineation prior to ventricular tachycardia ablation. Europace 17, 938–945 (2015).
pubmed: 25616406 doi: 10.1093/europace/euu310
Fernandez-Armenta, J. et al. Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation. Circ. Arrhythm. Electrophysiol. 6, 528–537 (2013).
pubmed: 23685537 doi: 10.1161/CIRCEP.113.000264
Ustunkaya, T. et al. Association of regional myocardial conduction velocity with the distribution of hypoattenuation on contrast-enhanced perfusion computed tomography in patients with postinfarct ventricular tachycardia. Heart Rhythm 16, 588–594 (2019).
pubmed: 30935494 doi: 10.1016/j.hrthm.2018.10.029
Selvakumar, D. et al. Delivery of cardioactive therapeutics in a porcine myocardial infarction model. J. Vis. Exp. https://doi.org/10.3791/64177 e64177 (2023).
Kistler, P. M. et al. Validation of three-dimensional cardiac image integration: use of integrated CT image into electroanatomic mapping system to perform catheter ablation of atrial fibrillation. J. Cardiovasc. Electrophysiol. 17, 341–348 (2006).
pubmed: 16643352 doi: 10.1111/j.1540-8167.2006.00371.x
Marchlinski, F. E., Callans, D. J., Gottlieb, C. D. & Zado, E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation 101, 1288–1296 (2000).
pubmed: 10725289 doi: 10.1161/01.CIR.101.11.1288
Polin, G. M. et al. Endocardial unipolar voltage mapping to identify epicardial substrate in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm 8, 76–83 (2011).
pubmed: 20933099 doi: 10.1016/j.hrthm.2010.09.088
Hummel, J. D. et al. Results and efficiency of programmed ventricular stimulation with four extrastimuli compared with one, two, and three extrastimuli. Circulation 90, 2827–2832 (1994).
pubmed: 7994827 doi: 10.1161/01.CIR.90.6.2827
Campbell, T. et al. Prognostic significance of extensive versus limited induction protocol during catheter ablation of scar-related ventricular tachycardia. J. Cardiovasc. Electrophysiol. 31, 2909–2919 (2020).
pubmed: 32905634 doi: 10.1111/jce.14740

Auteurs

Dinesh Selvakumar (D)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.
Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Zoe E Clayton (ZE)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Andrew Prowse (A)

Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland, Australia.

Steve Dingwall (S)

Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland, Australia.

Sul Ki Kim (SK)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.
Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Leila Reyes (L)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Jacob George (J)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Haisam Shah (H)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Siqi Chen (S)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Halina H L Leung (HHL)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Robert D Hume (RD)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Laurentius Tjahjadi (L)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Sindhu Igoor (S)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Rhys J P Skelton (RJP)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Alfred Hing (A)

Department of Cardiothoracic Surgery, Westmead Hospital, Westmead, New South Wales, Australia.

Hugh Paterson (H)

Sydney Imaging, Core Research Facility, the University of Sydney, Sydney, New South Wales, Australia.

Sheryl L Foster (SL)

Department of Radiology, Westmead Hospital, Westmead, New South Wales, Australia.
Sydney School of Health Sciences, Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, Australia.

Lachlan Pearson (L)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Emma Wilkie (E)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Alan D Marcus (AD)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.

Prajith Jeyaprakash (P)

Department of Cardiology, Nepean Hospital, Kingswood, New South Wales, Australia.

Zhixuan Wu (Z)

Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Han Shen Chiu (HS)

Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Cherica Felize J Ongtengco (CFJ)

Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland, Australia.

Onkar Mulay (O)

Genomics and Machine Learning Lab, Division of Genetics and Genomics, Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Jeffrey R McArthur (JR)

Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
St. Vincent's Clinical School, UNSW, Darlinghurst, New South Wales, Australia.

Tony Barry (T)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Juntang Lu (J)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Vu Tran (V)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Richard Bennett (R)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Yasuhito Kotake (Y)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Timothy Campbell (T)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Samual Turnbull (S)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Anunay Gupta (A)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Quan Nguyen (Q)

Genomics and Machine Learning Lab, Division of Genetics and Genomics, Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Guiyan Ni (G)

Genomics and Machine Learning Lab, Division of Genetics and Genomics, Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Stuart M Grieve (SM)

Imaging and Phenotyping Laboratory, Faculty of Medicine and Health, Charles Perkins Centre, the University of Sydney, Sydney, New South Wales, Australia.

Nathan J Palpant (NJ)

Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia.

Faraz Pathan (F)

Department of Cardiology, Nepean Hospital, Kingswood, New South Wales, Australia.
Sydney Medical School, Charles Perkins Centre Nepean, Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, Australia.

Eddy Kizana (E)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia.
Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Saurabh Kumar (S)

Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.

Peter P Gray (PP)

Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland, Australia.

James J H Chong (JJH)

Centre for Heart Research, the Westmead Institute for Medical Research, the University of Sydney, Westmead, New South Wales, Australia. james.chong@sydney.edu.au.
Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia. james.chong@sydney.edu.au.

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