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Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this prospective study, a total of 386 Czech RODCM patients with symptom duration \u22646 months underwent genetic counselling and whole-exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy-related genes was correlated with the occurrence of all-cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and\/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to &amp;gt;50% or \u226510% absolute increase, with a left ventricular end-diastolic diameter \u226433 mm\/m2 or \u226510% relative decrease. Median follow-up was 41 months. RODCM was familial in 98 (25%) individuals. Class 4\u20135 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin-truncating variant (TTNtv) and 56 (14%) having non-titin (non-TTN) VOIs. The presence of class 4\u20135 non-TTN VOIs, but not of TTNtv, heralded a lower probability of 12-month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life-threatening ventricular arrhythmias. Detection of class 4\u20135 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life-threatening ventricular arrhythmias after 12 months. Class 4\u20135 VOIs of genes coding cytoskeleton were associated with an increased risk of life-threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12 months and at the final follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RODCM patients harbouring class 4\u20135 non-TTN VOIs are at higher risk of progressive heart failure and life-threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15009","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:49:57Z","timestamp":1723423797000},"page":"4127-4138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genotype is Associated with Left Ventricular Reverse Remodelling and Early Events in Recent-Onset Dilated Cardiomyopathy"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-0949","authenticated-orcid":false,"given":"Milos","family":"Kubanek","sequence":"first","affiliation":[{"name":"Department of Cardiology, Institute for Clinical and Experimental Medicine , Prague ,","place":["Czech Republic"]},{"name":"European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart, ERN GUARD-Heart, IKEM , Prague ,","place":["Czech 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Medicine, Research Unit for Rare Diseases, Charles University , Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dita","family":"Musalkova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Research Unit for Rare Diseases, Charles University , Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Stranecky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Research Unit for Rare Diseases, Charles University , Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Palecek","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Second Department of Medicine, First Faculty of Medicine, Charles University and General University 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