{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:15:18Z","timestamp":1780388118075,"version":"3.54.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020948","name":"AstraZeneca M\u00f6lndal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neth Heart J"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Phospholamban (<jats:italic>PLN<\/jats:italic>) p.Arg14del (R14del, R14<jats:sup>\u2206\/+<\/jats:sup>) is the most commonly identified pathogenic variant that causes cardiomyopathy in the Netherlands. Many disease characteristics are still unclear, including the phenotypic triggers, disease progression and disease-specific biomarkers. We aim to gain a\u00a0better understanding of the R14<jats:sup>\u2206\/+<\/jats:sup> pathophysiology by establishing a\u00a0cohort across the R14<jats:sup>\u2206\/+<\/jats:sup> disease spectrum.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The Disease spECifIc PatHways and modifiERs in PhosphoLambaN r14del cardiomyopathy <jats:bold>(<\/jats:bold>DECIPHER-PLN) cohort includes 101 participants, categorised as unaffected R14<jats:sup>\u2206\/+<\/jats:sup> (<jats:italic>n<\/jats:italic>\u202f=\u200921), early affected R14<jats:sup>\u2206\/+<\/jats:sup> (<jats:italic>n<\/jats:italic>\u202f=\u200942), end-stage R14<jats:sup>\u2206\/+<\/jats:sup> (<jats:italic>n<\/jats:italic>\u202f=\u200928) and heart failure (HF) of another aetiology (<jats:italic>n<\/jats:italic>\u202f=\u200910). R14<jats:sup>\u2206\/+<\/jats:sup> category was based on left ventricular ejection fraction, HF symptoms, electrocardiogram (ECG) and N\u2011terminal pro-brain natriuretic peptide concentrations. Of the 91\u00a0included R14<jats:sup>\u2206\/+<\/jats:sup> carriers, 46 (51%) were female, with a\u00a0mean age of 55\u00a0years (standard deviation: 14). Low-voltage ECG older age, arrhythmias, and conduction and repolarisation abnormalities were common in (early) affected R14<jats:sup>\u2206\/+<\/jats:sup> carriers. Serum and plasma were collected from all participants. Induced pluripotent stem cells were generated from fibroblasts of end-stage R14<jats:sup>\u2206\/+<\/jats:sup> patients and unaffected R14<jats:sup>\u2206\/+<\/jats:sup> family members (<jats:italic>n<\/jats:italic>\u202f=\u20094) and differentiated into cardiomyocytes. Explanted heart tissue was obtained from R14<jats:sup>\u2206\/+<\/jats:sup> patients undergoing cardiac surgery and patients with other HF aetiologies as control. Abnormal PLN protein localisation was confirmed in R14<jats:sup>\u2206\/+<\/jats:sup> carriers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>DECIPHER-PLN comprises R14<jats:sup>\u2206\/+<\/jats:sup> carriers across the disease and non-disease spectrum and can be used to identify disease-specific biological pathways and modifiers that play a\u00a0role in R14<jats:sup>\u2206\/+<\/jats:sup> cardiomyopathy. Using a\u00a0multi-omics approach and in vitro disease modelling, we aim to identify novel biomarkers and improve our understanding of R14<jats:sup>\u2206\/+<\/jats:sup> pathophysiology. Material is available upon request.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s12471-025-01941-8","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T11:11:35Z","timestamp":1741259495000},"page":"112-119","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of disease-specific pathways and modifiers in phospholamban R14del cardiomyopathy: rationale, design and baseline characteristics of DECIPHER-PLN cohort"],"prefix":"10.1007","volume":"33","author":[{"given":"Frederik E.","family":"Deiman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco","family":"de Brouwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Baumhove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Bomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Grote Beverborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"1941_CR1","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra0902923","volume":"364","author":"H Watkins","year":"2011","unstructured":"Watkins H, Ashrafian H, Redwood C. Inherited Cardiomyopathies. New Engl J Med. 2011;364:1643\u201356.","journal-title":"New Engl J Med"},{"key":"1941_CR2","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrm1151","volume":"4","author":"DH MacLennan","year":"2003","unstructured":"MacLennan DH, Kranias EG. Phospholamban: a\u00a0crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol. 2003;4:566\u201377.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1941_CR3","first-page":"2011","volume":"8","author":"PA Van Der Zwaag","year":"2012","unstructured":"Van Der Zwaag PA, Van Rijsingen IAW, Asimaki A, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: Evidence supporting the concept of arrhythmogenic cardiomyopathy. 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Neth Heart\u00a0J. 2023;31:16\u201320.","journal-title":"Neth Heart J"}],"container-title":["Netherlands Heart Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12471-025-01941-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12471-025-01941-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12471-025-01941-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:46:43Z","timestamp":1743392803000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12471-025-01941-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["1941"],"URL":"https:\/\/doi.org\/10.1007\/s12471-025-01941-8","relation":{},"ISSN":["1568-5888","1876-6250"],"issn-type":[{"value":"1568-5888","type":"print"},{"value":"1876-6250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]},"assertion":[{"value":"28 January 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"P.\u00a0van der Meer has received grants from AstraZeneca, Ionis Pharmaceuticals, Novo Nordisk, Novartis, Pharmacosmos, Vifor Pharma, Pfizer, Pharma Nord and BridgeBio, outside the submitted work. F.E.\u00a0Deiman, R.\u00a0de Brouwer, L.\u00a0Baumhove, N.\u00a0Bomer and N.\u00a0Grote Beverborg declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}