{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:44:42Z","timestamp":1787589882418,"version":"build-2736575974"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Mavacamten is the first targeted therapy for obstructive hypertrophic cardiomyopathy (oHCM). It is metabolised via cytochrome p450 enzymes, with variations in the\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      gene having predominant influence on plasma concentrations of mavacamten. We aimed to outline the effect of CYP2C19 metaboliser status on outcomes in patients taking mavacamten.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analysed clinical and echocardiographic data in patients with symptomatic oHCM taking mavacamten.\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      genotyping was undertaken by loop-mediated isothermal amplification (LAMP) on EDTA whole blood (LaCAR MDx, Liege Belgium) followed by Sanger sequencing of the coding exons of\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      . Logistical regression was used to assess time taken to optimisation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-five patients (59\u00b113 years; 73% male) were included. Genotyping of\n                      <jats:italic>CYP2C19*2<\/jats:italic>\n                      ,\n                      <jats:italic>CYP2C19*3<\/jats:italic>\n                      , and\n                      <jats:italic>CYP2C19*17<\/jats:italic>\n                      alleles was conducted. Due to low numbers in the ultrarapid (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) and poor (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092) groups, statistical analysis was performed in intermediate, normal and rapid metabolisers. Using normal metabolisers as the reference, there was a non-significant trend towards faster optimisation in intermediate metabolisers (odds ratio 0.63 [95% CI: 0.12\u20133.19]) and rapid metabolisers (OR 0.55 [95% CI: 0.11\u20132.53]). While reductions in peak resting (40 \u00b1 34.37 mmHg) and Valsalva (64 \u00b1 35.23 mmHg) left ventricular outflow tract gradients were statistically significant across the cohort (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), there was no interaction between differing CYP2C19 groups and time (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.69).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Excluding poor metabolisers, variations in the\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      gene do not explain different clinical outcomes in patients with oHCM on mavacamten. Beyond genotyping of the targeted variants,\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      sequencing did not provide any additional clinically relevant information.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-025-03991-8","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T07:10:40Z","timestamp":1770361840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CYP2C19 genotyping and mavacamten: predicting outcomes in normal, intermediate and rapid metabolisers in obstructive hypertrophic cardiomyopathy"],"prefix":"10.1007","volume":"82","author":[{"given":"Yande","family":"Kasolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Burford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Obeidat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M","family":"Beaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Monk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Bastiaenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"issue":"4","key":"3991_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1161\/01.cir.92.4.785","volume":"92","author":"BJ Maron","year":"1995","unstructured":"Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE (1995) Prevalence of hypertrophic cardiomyopathy in a general population of young adults. 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All data were collected in accordance with institutional and national guidelines for clinical reporting and patient confidentiality. Patient confidentiality was maintained throughout.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The study was conducted using anonymised retrospective data with no patient identifiers present in the manuscript. As laid down in the Declaration of Helsinki (1964), consent to participate was not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Consent for publication is not applicable as this study does not contain any identifiable person\u2019s data in any form.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"William G Newman is a co-founder of an early-stage health technology start-up, Fava Health Ltd. Rachel Bastiaenen has received speaker fees for Bristol Myers Squibb, consulting fees for Pfizer and speaker fees for Medtronic. Robert M Cooper is Chief Investigator UK for SEQUOIA and ACACIA trials of Aficamten in HCM. Rachel Bastiaenen and Robert M Cooper have received consulting fees from Bristol Myers Squibb. Yande Kasolo is a sub-investigator for ACACIA, FOREST and MAPLE trials of Aficamten in HCM.\u00a0Edward Burford has received honoraria from Bristol Myers Squibb for speaking at educational events.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}