{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:13:16Z","timestamp":1779322396229,"version":"3.51.4"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HO 6446\/1"],"award-info":[{"award-number":["HO 6446\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1550"],"award-info":[{"award-number":["SFB1550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1550"],"award-info":[{"award-number":["SFB1550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health and Life Science Alliance Heidelberg\/Mannheim"},{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislaufforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BMBF"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cardiovasc Res"],"DOI":"10.1038\/s44161-026-00818-2","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:02:22Z","timestamp":1777885342000},"page":"479-491","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CAMK2D causes heart failure in mice with RBM20 cardiomyopathy"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2768-3457","authenticated-orcid":false,"given":"Maarten M. G.","family":"van den Hoogenhof","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Duran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"Britto-Borges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-7674","authenticated-orcid":false,"given":"Vasco","family":"Sequeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Kemmling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Konrad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7405-8064","authenticated-orcid":false,"given":"Friederike","family":"Schreiter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-0693","authenticated-orcid":false,"given":"David C.","family":"Lennermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4504-8926","authenticated-orcid":false,"given":"Laura","family":"Schraft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-230X","authenticated-orcid":false,"given":"Julia","family":"Kornienko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Bock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-6941","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-4559","authenticated-orcid":false,"given":"Christoph","family":"Maack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-6311","authenticated-orcid":false,"given":"Christoph","family":"Dieterich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars M.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Dewenter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-2699","authenticated-orcid":false,"given":"Johannes","family":"Backs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"818_CR1","doi-asserted-by":"publisher","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","volume":"149","author":"SS Martin","year":"2024","unstructured":"Martin, S. S. et al. 2024 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation 149, e347\u2013e913 (2024).","journal-title":"Circulation"},{"key":"818_CR2","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","volume":"37","author":"YM Pinto","year":"2016","unstructured":"Pinto, Y. M. et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur. Heart J. 37, 1850\u20131858 (2016).","journal-title":"Eur. Heart J."},{"key":"818_CR3","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1093\/eurheartj\/ehu301","volume":"36","author":"J Haas","year":"2015","unstructured":"Haas, J. et al. Atlas of the clinical genetics of human dilated cardiomyopathy. Eur. Heart J. 36, 1123\u20131135 (2015).","journal-title":"Eur. Heart J."},{"key":"818_CR4","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/nrcardio.2013.105","volume":"10","author":"RE Hershberger","year":"2013","unstructured":"Hershberger, R. E., Hedges, D. J. & Morales, A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat. Rev. Cardiol. 10, 531\u2013547 (2013).","journal-title":"Nat. Rev. Cardiol."},{"key":"818_CR5","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1093\/eurheartj\/ehm342","volume":"29","author":"P Elliott","year":"2008","unstructured":"Elliott, P. et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 29, 270\u2013276 (2008).","journal-title":"Eur. Heart J."},{"key":"818_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0703-1","volume":"12","author":"ER Malone","year":"2020","unstructured":"Malone, E. R., Oliva, M., Sabatini, P. J. B., Stockley, T. L. & Siu, L. L. Molecular profiling for precision cancer therapies. Genome Med. 12, 8 (2020).","journal-title":"Genome Med."},{"key":"818_CR7","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/S0140-6736(20)31792-X","volume":"396","author":"I Olivotto","year":"2020","unstructured":"Olivotto, I. et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 396, 759\u2013769 (2020).","journal-title":"Lancet"},{"key":"818_CR8","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s11897-020-00475-x","volume":"17","author":"D Lennermann","year":"2020","unstructured":"Lennermann, D., Backs, J. & van den Hoogenhof, M. M. G. New insights in RBM20 cardiomyopathy. Curr. Heart Fail. Rep. 17, 234\u2013246 (2020).","journal-title":"Curr. Heart Fail. Rep."},{"key":"818_CR9","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1172\/JCI74523","volume":"124","author":"H Maatz","year":"2014","unstructured":"Maatz, H. et al. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. J. Clin. Invest. 124, 3419\u20133430 (2014).","journal-title":"J. Clin. Invest."},{"key":"818_CR10","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nm.2693","volume":"18","author":"W Guo","year":"2012","unstructured":"Guo, W. et al. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat. Med. 18, 766\u2013773 (2012).","journal-title":"Nat. Med."},{"key":"818_CR11","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1093\/nar\/gks1362","volume":"41","author":"S Li","year":"2013","unstructured":"Li, S., Guo, W., Dewey, C. N. & Greaser, M. L. Rbm20 regulates titin alternative splicing as a splicing repressor. Nucleic Acids Res. 41, 2659\u20132672 (2013).","journal-title":"Nucleic Acids Res."},{"key":"818_CR12","doi-asserted-by":"publisher","first-page":"eabe8952","DOI":"10.1126\/scitranslmed.abe8952","volume":"13","author":"MH Radke","year":"2021","unstructured":"Radke, M. H. et al. Therapeutic inhibition of RBM20 improves diastolic function in a murine heart failure model and human engineered heart tissue. Sci. Transl. Med. 13, eabe8952 (2021).","journal-title":"Sci. Transl. Med."},{"key":"818_CR13","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1161\/CIRCULATIONAHA.116.023003","volume":"134","author":"M Methawasin","year":"2016","unstructured":"Methawasin, M. et al. Experimentally increasing the compliance of titin through RNA binding motif-20 (RBM20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction. Circulation 134, 1085\u20131099 (2016).","journal-title":"Circulation"},{"key":"818_CR14","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/s41556-019-0380-8","volume":"21","author":"M Zhang","year":"2019","unstructured":"Zhang, M. et al. CaMKII-delta9 promotes cardiomyopathy through disrupting UBE2T-dependent DNA repair. Nat. Cell Biol. 21, 1152\u20131163 (2019).","journal-title":"Nat. Cell Biol."},{"key":"818_CR15","doi-asserted-by":"publisher","first-page":"644630","DOI":"10.3389\/fcell.2021.644630","volume":"9","author":"J Duran","year":"2021","unstructured":"Duran, J., Nickel, L., Estrada, M., Backs, J. & van den Hoogenhof, M. M. G. CaMKII\u03b4 splice variants in the healthy and diseased heart. Front. Cell Dev. Biol. 9, 644630 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"818_CR16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.yjmcc.2019.01.001","volume":"127","author":"B Hegyi","year":"2019","unstructured":"Hegyi, B., Bers, D. M. & Bossuyt, J. CaMKII signaling in heart diseases: emerging role in diabetic cardiomyopathy. J. Mol. Cell Cardiol. 127, 246\u2013259 (2019).","journal-title":"J. Mol. Cell Cardiol."},{"key":"818_CR17","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1161\/CIRCRESAHA.111.248401","volume":"109","author":"S Mishra","year":"2011","unstructured":"Mishra, S., Gray, C. B., Miyamoto, S., Bers, D. M. & Brown, J. H. Location matters: clarifying the concept of nuclear and cytosolic CaMKII subtypes. Circ. Res. 109, 1354\u20131362 (2011).","journal-title":"Circ. Res."},{"key":"818_CR18","doi-asserted-by":"publisher","first-page":"7219","DOI":"10.1074\/jbc.M604281200","volume":"282","author":"GH Little","year":"2007","unstructured":"Little, G. H., Bai, Y., Williams, T. & Poizat, C. Nuclear calcium\/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. J. Biol. Chem. 282, 7219\u20137231 (2007).","journal-title":"J. Biol. Chem."},{"key":"818_CR19","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1172\/JCI27438","volume":"116","author":"J Backs","year":"2006","unstructured":"Backs, J., Song, K., Bezprozvannaya, S., Chang, S. & Olson, E. N. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J. Clin. Invest. 116, 1853\u20131864 (2006).","journal-title":"J. Clin. Invest."},{"key":"818_CR20","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.yjmcc.2008.12.022","volume":"46","author":"K Odagiri","year":"2009","unstructured":"Odagiri, K. et al. Local control of mitochondrial membrane potential, permeability transition pore and reactive oxygen species by calcium and calmodulin in rat ventricular myocytes. J. Mol. Cell Cardiol. 46, 989\u2013997 (2009).","journal-title":"J. Mol. Cell Cardiol."},{"key":"818_CR21","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1161\/01.RES.0000069685.20258.F1","volume":"92","author":"LS Maier","year":"2003","unstructured":"Maier, L. S. et al. Transgenic CaMKII\u03b4C overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ. Res. 92, 904\u2013911 (2003).","journal-title":"Circ. Res."},{"key":"818_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26623-y","volume":"12","author":"AM Fenix","year":"2021","unstructured":"Fenix, A. M. et al. Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies. Nat. Commun. 12, 6324 (2021).","journal-title":"Nat. Commun."},{"key":"818_CR23","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1038\/s41591-020-1087-x","volume":"26","author":"JW Schneider","year":"2020","unstructured":"Schneider, J. W. et al. Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs. Nat. Med. 26, 1788\u20131800 (2020).","journal-title":"Nat. Med."},{"key":"818_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39965-6","volume":"14","author":"J Kornienko","year":"2023","unstructured":"Kornienko, J. et al. Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3. Nat. Commun. 14, 4312 (2023).","journal-title":"Nat. Commun."},{"key":"818_CR25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.yjmcc.2022.01.004","volume":"165","author":"C Wang","year":"2022","unstructured":"Wang, C. et al. RBM20S639G mutation is a high genetic risk factor for premature death through RNA-protein condensates. J. Mol. Cell Cardiol. 165, 115\u2013129 (2022).","journal-title":"J. Mol. Cell Cardiol."},{"key":"818_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74800-8","volume":"10","author":"K Ihara","year":"2020","unstructured":"Ihara, K. et al. A missense mutation in the RSRSP stretch of Rbm20 causes dilated cardiomyopathy and atrial fibrillation in mice. Sci. Rep. 10, 17894 (2020).","journal-title":"Sci. Rep."},{"key":"818_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39352-1","volume":"14","author":"M Grosch","year":"2023","unstructured":"Grosch, M. et al. Striated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy. Nat. Commun. 14, 3714 (2023).","journal-title":"Nat. Commun."},{"key":"818_CR28","doi-asserted-by":"publisher","first-page":"H1296","DOI":"10.1152\/ajpheart.00328.2022","volume":"323","author":"DC Lennermann","year":"2022","unstructured":"Lennermann, D. C. et al. Deep phenotyping of two preclinical mouse models and a cohort of RBM20 mutation carriers reveals no sex-dependent disease severity in RBM20 cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol. 323, H1296\u2013H1310 (2022).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"818_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24484-z","volume":"12","author":"C Zhu","year":"2021","unstructured":"Zhu, C. et al. Single-molecule, full-length transcript isoform sequencing reveals disease-associated RNA isoforms in cardiomyocytes. Nat. Commun. 12, 4203 (2021).","journal-title":"Nat. Commun."},{"key":"818_CR30","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1161\/CIRCULATIONAHA.117.031947","volume":"138","author":"MMG van den Hoogenhof","year":"2018","unstructured":"van den Hoogenhof, M. M. G. et al. RBM20 mutations induce an arrhythmogenic dilated cardiomyopathy related to disturbed calcium handling. Circulation 138, 1330\u20131342 (2018).","journal-title":"Circulation"},{"key":"818_CR31","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1085\/jgp.201511484","volume":"147","author":"F Kobirumaki-Shimozawa","year":"2016","unstructured":"Kobirumaki-Shimozawa, F. et al. Nano-imaging of the beating mouse heart in vivo: Importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function. J. Gen. Physiol. 147, 53\u201362 (2016).","journal-title":"J. Gen. Physiol."},{"key":"818_CR32","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1073\/pnas.0813013106","volume":"106","author":"J Backs","year":"2009","unstructured":"Backs, J. et al. The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc. Natl Acad. Sci. USA 106, 2342\u20132347 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"818_CR33","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1161\/CIRCULATIONAHA.121.055920","volume":"145","author":"J Zhang","year":"2022","unstructured":"Zhang, J. et al. Novel CaMKII-delta inhibitor hesperadin exerts dual functions to ameliorate cardiac ischemia\/reperfusion injury and inhibit tumor growth. Circulation 145, 1154\u20131168 (2022).","journal-title":"Circulation"},{"key":"818_CR34","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1016\/j.jacc.2021.12.011","volume":"79","author":"PA Heidenreich","year":"2022","unstructured":"Heidenreich, P. A. et al. 2022 AHA\/ACC\/HFSA guideline for the management of heart Failure: executive summary: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 79, 1757\u20131780 (2022).","journal-title":"J. Am. Coll. Cardiol."},{"key":"818_CR35","doi-asserted-by":"publisher","first-page":"eade1633","DOI":"10.1126\/scitranslmed.ade1633","volume":"14","author":"T Nishiyama","year":"2022","unstructured":"Nishiyama, T. et al. Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Sci. Transl. Med. 14, eade1633 (2022).","journal-title":"Sci. Transl. Med."},{"key":"818_CR36","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1083\/jcb.200208092","volume":"161","author":"S Hauf","year":"2003","unstructured":"Hauf, S. et al. The small molecule hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J. Cell. Biol. 161, 281\u2013294 (2003).","journal-title":"J. Cell. Biol."},{"key":"818_CR37","doi-asserted-by":"publisher","first-page":"113982","DOI":"10.1016\/j.celrep.2024.113982","volume":"43","author":"CN Brown","year":"2024","unstructured":"Brown, C. N. & Bayer, K. U. Studying CaMKII: tools and standards. Cell Rep. 43, 113982 (2024).","journal-title":"Cell Rep."},{"key":"818_CR38","doi-asserted-by":"publisher","first-page":"eabq7839","DOI":"10.1126\/scitranslmed.abq7839","volume":"15","author":"OE Reyes Gaido","year":"2023","unstructured":"Reyes Gaido, O. E. et al. An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor. Sci. Transl. Med. 15, eabq7839 (2023).","journal-title":"Sci. Transl. Med."},{"key":"818_CR39","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s40265-015-0351-8","volume":"75","author":"GL Plosker","year":"2015","unstructured":"Plosker, G. L. Ruxolitinib: a review of its use in patients with myelofibrosis. Drugs 75, 297\u2013308 (2015).","journal-title":"Drugs"},{"key":"818_CR40","doi-asserted-by":"publisher","first-page":"abstr. A12726","DOI":"10.1161\/circ.148.suppl_1.12726","volume":"148","author":"S Takagahara","year":"2023","unstructured":"Takagahara, S. et al. Abstract 12726: novel, potent, and highly selective calcium\/calmodulin-dependent protein kinase II (CaMKII) inhibitors reduce substrate phosphorylation in rat hearts and prolong survival in a mouse model of severe heart failure. Circulation 148, abstr. A12726 (2023).","journal-title":"Circulation"},{"key":"818_CR41","unstructured":"A phase 2A, investigator & subject blinded, sponsor unblinded, placebo-controlled, clinical study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics of CRD-4730 in participants with catecholaminergic polymorphic ventricular tachycardia. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06005428?term=CRD-4730&viewType=Card&rank=2 (2023)."},{"key":"818_CR42","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/ehf2.12145","volume":"4","author":"C Seyler","year":"2017","unstructured":"Seyler, C. et al. TranslatiOnal Registry for CardiomyopatHies (TORCH) - rationale and first results. ESC Heart Fail. 4, 209\u2013215 (2017).","journal-title":"ESC Heart Fail."},{"key":"818_CR43","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","volume":"383","author":"M Packer","year":"2020","unstructured":"Packer, M. et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 383, 1413\u20131424 (2020).","journal-title":"N. Engl. J. Med."},{"key":"818_CR44","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1056\/NEJMoa1409077","volume":"371","author":"JJ McMurray","year":"2014","unstructured":"McMurray, J. J. et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med. 371, 993\u20131004 (2014).","journal-title":"N. Engl. J. Med."},{"key":"818_CR45","doi-asserted-by":"crossref","unstructured":"Effect of metoprolol CR\/XL in chronic heart failure: metoprolol CR\/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 353, 2001\u20132007 (1999).","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"818_CR46","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199909023411001","volume":"341","author":"B Pitt","year":"1999","unstructured":"Pitt, B. et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 341, 709\u2013717 (1999).","journal-title":"N. Engl. J. Med."},{"key":"818_CR47","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1126\/science.aad3456","volume":"351","author":"EM Green","year":"2016","unstructured":"Green, E. M. et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science 351, 617\u2013621 (2016).","journal-title":"Science"},{"key":"818_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1012-2","volume":"17","author":"M Haeussler","year":"2016","unstructured":"Haeussler, M. et al. Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 17, 148 (2016).","journal-title":"Genome Biol."},{"key":"818_CR49","doi-asserted-by":"publisher","first-page":"e015735","DOI":"10.1161\/CIRCIMAGING.123.015735","volume":"16","author":"MJ Zhang","year":"2023","unstructured":"Zhang, M. J. et al. Atrial myopathy quantified by speckle-tracking echocardiography in mice. Circ. Cardiovasc. Imaging 16, e015735 (2023).","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"818_CR50","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1038\/nprot.2008.138","volume":"3","author":"P Pacher","year":"2008","unstructured":"Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S. & Kass, D. A. Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nat. Protoc. 3, 1422\u20131434 (2008).","journal-title":"Nat. Protoc."},{"key":"818_CR51","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1113\/JP270354","volume":"593","author":"V Sequeira","year":"2015","unstructured":"Sequeira, V. et al. Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness. J. Physiol. 593, 3899\u20133916 (2015).","journal-title":"J. Physiol."},{"key":"818_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"818_CR53","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","volume":"19","author":"S Xu","year":"2024","unstructured":"Xu, S. et al. Using clusterProfiler to characterize multiomics data. Nat. Protoc. 19, 3292\u20133320 (2024).","journal-title":"Nat. Protoc."},{"key":"818_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37266-6","volume":"14","author":"KC Cotto","year":"2023","unstructured":"Cotto, K. C. et al. Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer. Nat. Commun. 14, 1589 (2023).","journal-title":"Nat. Commun."},{"key":"818_CR55","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1074\/mcp.TIR117.000518","volume":"17","author":"CM Potel","year":"2018","unstructured":"Potel, C. M., Lin, M. H., Heck, A. J. R. & Lemeer, S. Defeating major contaminants in Fe3+- immobilized metal ion affinity chromatography (IMAC) phosphopeptide enrichment. Mol. Cell. Proteomics 17, 1028\u20131034 (2018).","journal-title":"Mol. Cell. Proteomics"},{"key":"818_CR56","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1021\/acs.jproteome.2c00850","volume":"22","author":"A Chang","year":"2023","unstructured":"Chang, A., Leutert, M., Rodriguez-Mias, R. A. & Villen, J. Automated enrichment of phosphotyrosine peptides for high-throughput proteomics. J. Proteome Res. 22, 1868\u20131880 (2023).","journal-title":"J. Proteome Res."},{"key":"818_CR57","doi-asserted-by":"publisher","first-page":"15941","DOI":"10.1021\/acs.analchem.9b04474","volume":"91","author":"A Thompson","year":"2019","unstructured":"Thompson, A. et al. TMTpro: design, synthesis, and initial evaluation of a proline-based isobaric 16-plex tandem mass tag reagent set. Anal. Chem. 91, 15941\u201315950 (2019).","journal-title":"Anal. Chem."},{"key":"818_CR58","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nmeth.4256","volume":"14","author":"AT Kong","year":"2017","unstructured":"Kong, A. T., Leprevost, F. V., Avtonomov, D. M., Mellacheruvu, D. & Nesvizhskii, A. I. MSFragger: ultrafast and comprehensive peptide identification in mass spectrometry-based proteomics. Nat. Methods 14, 513\u2013520 (2017).","journal-title":"Nat. Methods"},{"key":"818_CR59","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"818_CR60","doi-asserted-by":"publisher","first-page":"S96","DOI":"10.1093\/bioinformatics\/18.suppl_1.S96","volume":"18","author":"W Huber","year":"2002","unstructured":"Huber, W., von Heydebreck, A., Sultmann, H., Poustka, A. & Vingron, M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18, S96\u2013S104 (2002).","journal-title":"Bioinformatics"},{"key":"818_CR61","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/bioinformatics\/btr645","volume":"28","author":"L Gatto","year":"2012","unstructured":"Gatto, L. & Lilley, K. S. MSnbase-an R\/Bioconductor package for isobaric tagged mass spectrometry data visualization, processing and quantitation. Bioinformatics 28, 288\u2013289 (2012).","journal-title":"Bioinformatics"},{"key":"818_CR62","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287 (2012).","journal-title":"OMICS"},{"key":"818_CR63","doi-asserted-by":"publisher","first-page":"W304","DOI":"10.1093\/nar\/gkab359","volume":"49","author":"MV Kuleshov","year":"2021","unstructured":"Kuleshov, M. V. et al. KEA3: improved kinase enrichment analysis via data integration. Nucleic Acids Res. 49, W304\u2013W316 (2021).","journal-title":"Nucleic Acids Res."},{"key":"818_CR64","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/cvr\/cvu174","volume":"104","author":"S Werfel","year":"2014","unstructured":"Werfel, S. et al. Rapid and highly efficient inducible cardiac gene knockout in adult mice using AAV-mediated expression of Cre recombinase. Cardiovasc Res. 104, 15\u201323 (2014).","journal-title":"Cardiovasc Res."},{"key":"818_CR65","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1089\/hgtb.2017.192","volume":"28","author":"A Jungmann","year":"2017","unstructured":"Jungmann, A., Leuchs, B., Rommelaere, J., Katus, H. A. & Muller, O. J. Protocol for efficient generation and characterization of adeno-associated viral vectors. Hum. Gene Ther. Methods 28, 235\u2013246 (2017).","journal-title":"Hum. Gene Ther. Methods"}],"container-title":["Nature Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00818-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00818-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00818-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:02:35Z","timestamp":1779321755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44161-026-00818-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["818"],"URL":"https:\/\/doi.org\/10.1038\/s44161-026-00818-2","relation":{},"ISSN":["2731-0590"],"issn-type":[{"value":"2731-0590","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"assertion":[{"value":"23 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"V.S. received research funding from Bristol Myers Squibb unrelated to this work. C.M. is an advisory board member for Bristol Myers Squibb, Cytokinetics, Boehringer Ingelheim, AstraZeneca, Servier, Amgen, Novo Nordisk, Bayer, Novartis, Edwards and Berlin Chemie. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}