{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:19:23Z","timestamp":1790759963146,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4\u20132.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction &lt;45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9\u20138.1) and 2.6 (95% confidence interval, 1.5\u20134.5), respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction &lt;45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.113.000374","type":"journal-article","created":{"date-parts":[[2014,6,9]],"date-time":"2014-06-09T00:08:35Z","timestamp":1402272515000},"page":"455-465","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":190,"title":["Outcome in Phospholamban R14del Carriers"],"prefix":"10.1161","volume":"7","author":[{"given":"Ingrid A.W.","family":"van Rijsingen","sequence":"first","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"van der Zwaag","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Groeneweg","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline A.","family":"Nannenberg","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan D.H.","family":"Jongbloed","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeilko H.","family":"Zwinderman","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald H. Lekanne","family":"dit Deprez","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G.","family":"Post","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno L.","family":"Tan","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard N.W.","family":"Hauer","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"Christiaans","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Peter","family":"van Tintelen","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.M.","family":"Wilde","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (I.A.W.v.R., Y.M.P., H.L.T., A.A.M.W.), Genetics (E.A.N., R.H.L.d.D., I.C.), and Epidemiology (A.H.Z.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Genetics (P.A.v.d.Z., J.D.H.J., J.P.v.T.) and Cardiology (R.A.d.B., M.P.v.d.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands (J.A.G., Y.M.P., R.N.W.H., A.A.M.W.); Departments of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90274-I"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr260"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eur245"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6966"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1151"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.01.016"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510519103"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.016"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs119"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.12.020"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12471-013-0401-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.06.017"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.660241"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.1998.1145"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.641472"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq025"},{"key":"e_1_3_4_18_2","volume-title":"Braunwald\u2019s Heart Disease: A Textbook of Cardiovascular Medicine","author":"Robert O","year":"2001","unstructured":"Robert O, Bonow DLM, Zipes DP, Libby PBraunwald\u2019s Heart Disease: A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia: W.B. Saunders Company; 2001.","edition":"6"},{"key":"e_1_3_4_19_2","volume-title":"The Minnesota Code Manual of Electrocardiographic Findings","author":"Ronald J","year":"2010","unstructured":"Ronald J, Prineas RSC, Zhu-ming ZThe Minnesota Code Manual of Electrocardiographic Findings. 2nd ed. London: Springer; 2010.","edition":"2"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp327"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.015"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.07.044"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.961102"},{"key":"e_1_3_4_24_2","unstructured":"Graphics Sefsca. Software Environment for Statistical Computing and Graphics."},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.2307\/2532797"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1989.10478873"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.178233"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.03.002"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.06.044"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.06.033"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm342"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000143375.93288.82"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr451"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.07.041"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.65.2.384"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11799"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.08.078"}],"container-title":["Circulation: Cardiovascular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGENETICS.113.000374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:47:28Z","timestamp":1715564848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGENETICS.113.000374"}},"subtitle":["Results of a Large Multicentre Cohort Study"],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1161\/CIRCGENETICS.113.000374"],"URL":"https:\/\/doi.org\/10.1161\/circgenetics.113.000374","relation":{},"ISSN":["1942-325X","1942-3268"],"issn-type":[{"value":"1942-325X","type":"print"},{"value":"1942-3268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}