{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:32:25Z","timestamp":1773379945899,"version":"3.50.1"},"reference-count":15,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>Background: Whether patients with subclinical cardiomyopathy (CMP) are more prone to experience Takotsubo syndrome (TTS) than patients without CMP, is unknown. We present a patient with TTS as the initial manifestation of a hitherto unrecognized genetic CMP. Method: case report. Results: At age 55 after the unexpected death of her father, a now 61-year-old female had developed precordial pressure. Work-up revealed moderately reduced systolic function, dyskinesia of the interventricular septum, and indications for a TTS. Coronary angiography was normal but ventriculography showed TTS. Cardiac MRI confirmed reduced systolic function and TTS. TTS resolved without treatment and sequelae. At age 57 atrial fibrillation was recorded. After deterioration of systolic function at age 59 dilated CMP was diagnosed. Despite application of levosimendan, sacubitril, valsartan, and ivabradine, complete remission could not be achieved. Upon genetic work-up by means of a gene panel, the heterozygous mutation c.1489G &gt; T (p. E497X) in exon 9 of the titin gene was detected and made responsible for the phenotype. Neurological work-up precluded involvement of the skeletal muscles. The further course was complicated by ventricular arrhythmias, requiring implantation of an implantable cardioverter defibrillator (ICD). Conclusions: previously subclinical CMP may initially manifest as TTS. Since patients with titin CMP are at risk of developing ventricular arrhythmias and thus to experience sudden cardiac death, appropriate anti-arrhythmic therapy needs to be established.<\/jats:p>","DOI":"10.3390\/medicines5030080","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T11:55:08Z","timestamp":1532951708000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Takotsubo as Initial Manifestation of Non-Myopathic Cardiomyopathy Due to the Titin Variant c.1489G &gt; T"],"prefix":"10.3390","volume":"5","author":[{"given":"Hans","family":"Keller","sequence":"first","affiliation":[{"name":"2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, 1030 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Neuhold","sequence":"additional","affiliation":[{"name":"Medical Department, Krems University Hospital, Krankenhaus Krems an der Donau, 3500 Krems an der Donau, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Weidinger","sequence":"additional","affiliation":[{"name":"2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, 1030 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund","family":"Gatterer","sequence":"additional","affiliation":[{"name":"2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, 1030 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"St\u00f6llberger","sequence":"additional","affiliation":[{"name":"2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, 1030 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Huber","sequence":"additional","affiliation":[{"name":"Genetic Laboratory, SMZO, 1220 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2839-7305","authenticated-orcid":false,"given":"Josef","family":"Finsterer","sequence":"additional","affiliation":[{"name":"Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"ref_1","first-page":"53","article-title":"Epidemiology, pathogenesis, and management of takotsubo syndrome","volume":"28","author":"Shams","year":"2017","journal-title":"Clin. Auton. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13073-017-0410-8","article-title":"Genetics and genomics of dilated cardiomyopathy and systolic heart failure","volume":"9","author":"Tayal","year":"2017","journal-title":"Genome Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12551-017-0265-7","article-title":"Genetic epidemiology of titin-truncating variants in the etiology of dilated cardiomyopathy","volume":"9","author":"Tabish","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_4","first-page":"24","article-title":"Magnetic resonance imaging of dilated cardiomyopathy","volume":"53","author":"Greif","year":"2013","journal-title":"Radiologe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.cjca.2015.08.016","article-title":"The Rapidly Evolving Role of Titin in Cardiac Physiology and Cardiomyopathy","volume":"31","author":"Gerull","year":"2015","journal-title":"Can. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1212\/WNL.0000000000003064","article-title":"Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study","volume":"87","author":"Steele","year":"2016","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.nmd.2017.06.013","article-title":"A \u2018second truncation\u2019 in TTN causes early onset recessive muscular dystrophy","volume":"27","author":"Harris","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1056\/NEJMoa1110186","article-title":"Truncations of titin causing dilated cardiomyopathy","volume":"366","author":"Herman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/HCO.0000000000000382","article-title":"Titin-truncating mutations in dilated cardiomyopathy: The long and short of it","volume":"32","author":"Fatkin","year":"2017","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Franaszczyk, M., Chmielewski, P., Truszkowska, G., Stawinski, P., Michalak, E., Rydzanicz, M., Sobieszczanska-Malek, M., Pollak, A., Szczygie\u0142, J., and Kosinska, J. (2017). Titin Truncating Variants in Dilated Cardiomyopathy\u2014Prevalence and Genotype-Phenotype Correlations. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169007"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.cjca.2017.05.020","article-title":"Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients with Hypertrophic Cardiomyopathy","volume":"33","author":"Zhang","year":"2017","journal-title":"Can. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cardfail.2017.03.003","article-title":"Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy","volume":"23","author":"Linschoten","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_13","first-page":"426","article-title":"Combination of Whole Genome Sequencing, Linkage, and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy with Features of Left Ventricular Noncompaction","volume":"9","author":"Hastings","year":"2016","journal-title":"Circulation"},{"key":"ref_14","first-page":"1","article-title":"Genetic basis of limb-girdle muscular dystrophies: The 2014 update","volume":"33","author":"Nigro","year":"2014","journal-title":"Acta Myol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jns.2015.03.001","article-title":"Adult onset limb-girdle muscular dystrophy\u2014A recessive titinopathy masquerading as myositis","volume":"351","author":"Dabby","year":"2015","journal-title":"J. Neurol. Sci."}],"container-title":["Medicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6320\/5\/3\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:15:19Z","timestamp":1760195719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6320\/5\/3\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,30]]},"references-count":15,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["medicines5030080"],"URL":"https:\/\/doi.org\/10.3390\/medicines5030080","relation":{},"ISSN":["2305-6320"],"issn-type":[{"value":"2305-6320","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,30]]}}}