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Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease of massive heterotopic ossification caused by a highly recurrent <jats:italic>R206H<\/jats:italic> mutation in <jats:italic>ACVR1\/ALK2<\/jats:italic>. This mutation causes abnormal activation of the bone morphogenetic protein (BMP) pathway in response to Activin A. Prior studies suggested increased risks of cardiopulmonary complications in FOP. We examined participants in a Natural History Study (NHS) of FOP (ClinicalTrials.gov #NCT02322255) to better understand their cardiovascular status.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The NHS is an ongoing 3 year international multi-center longitudinal study of 114 patients (ages 4\u201356\u2009years) with genetically confirmed <jats:italic>ACVR1\/ALK2<\/jats:italic><jats:sup><jats:italic>R206H<\/jats:italic><\/jats:sup> FOP. Patients were clinically assessed at baseline and 12\u2009months. Electrocardiograms (ECGs) were reviewed in a central ECG laboratory. Conduction abnormalities were compared against clinical data collected in the NHS, and echocardiograms collected from NHS and non-NHS patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Conduction abnormalities were present in 45.3% of baseline ECGs, with the majority of abnormalities classified as nonspecific intraventricular conduction delay (37.7%). More specifically, 22.2% of patients &gt;\u200918\u2009years old had conduction abnormalities, which was significantly higher than a prior published study of a healthy population (5.9%; <jats:italic>n<\/jats:italic>\u00a0=\u20093978) (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.00001). Patients with FOP\u2009&lt;\u200918\u2009years old also had a high prevalence of conduction abnormalities (62.3%). The 12-month follow up data was similar to baseline results. Conduction abnormalities did not correlate with chest wall deformities, scoliosis, pulmonary function test results, or increased Cumulative Analog Joint Involvement Scale scores. Echocardiograms from 22 patients with FOP revealed 8 with structural cardiac abnormalities, only 1 of which correlated with a conduction abnormality.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We found that patients with FOP may have subclinical conduction abnormalities manifesting on ECG, independent of heterotopic ossification. Although clinically significant heart disease is not typically associated with FOP, and the clinical implications for cardiovascular risk remain unclear, knowledge about ECG and echocardiogram changes is important for clinical care and research trials in patients with FOP. Further studies on how <jats:italic>ACVR1\/ALK2<\/jats:italic><jats:sup><jats:italic>R206H<\/jats:italic><\/jats:sup> affects cardiac health will help elucidate the underlying mechanism.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13023-020-01465-x","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T09:03:59Z","timestamp":1596013439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Patients with ACVR1R206H mutations have an increased prevalence of cardiac conduction abnormalities on electrocardiogram in a natural history study of Fibrodysplasia Ossificans Progressiva"],"prefix":"10.1186","volume":"15","author":[{"given":"Samuel","family":"Kou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"De Cunto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Wentworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna R.","family":"Grogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Di Rocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Keen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Al Mukaddam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim-Hanh","family":"le Quan Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Masharani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick S.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8924-106X","authenticated-orcid":false,"given":"Edward C.","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"issue":"4","key":"1465_CR1","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1002\/med.21476","volume":"38","author":"P Mladenka","year":"2018","unstructured":"Mladenka P, Applova L, Patocka J, Costa VM, Remiao F, Pourova J, et al. 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The Natural History Study was approved by The Committee on Human Research at the University of California (approval number: 14\u201313854) and also approved by the ethics committees at the five other study sites institutions (University of Pennsylvania Institutional Review Board; Comit\u00e9 de Protection des Personnes, Ile de France II; Comitado Etico Regionale San Martino, Hospital Italiano Comit\u00e9 de \u00c9tica de Protocolos de Investigacion; NHS Health Research Authority, London-Stanmore Research Ethics Committee; Metro South Human Research Ethics Committee). The study was registered at  (), and performed in accordance with the Declaration of Helsinki (2013). All study participants were fully consented before participation in this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DRG was a Clementia employee at the time the study was conducted and data were obtained. CDC, GB, MAB, MDR, RK, MAM, FSK, RJP, UM, KLW, and ECH received funding from Clementia to support the Natural History Study and separate interventional studies sponsored by Clementia, an Ipsen company. ECH, MDR, MAM, FSK and RJP, RK, MAB received clinical trials research funding from Regeneron Pharmaceuticals.ECH, DRG, GB, CDC, RK, MAB, MAM, FSK and RJP serve in a volunteer capacity on the Medical Registry Advisory Board of the International Fibrodysplasia Ossificans Progressiva Association. ECH serves in a volunteer capacity on the Fibrous Dysplasia Foundation Medical Advisory Board. ECH, CDC, GB, MAB, MDR, RK, MAM, FSK, and RJP are elected members of the International Clinical Council on FOP. These pose no conflicts for this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"193"}}