Truncations of titin (TTNtv) is the most common genetic cause of dilated cardiomyopathy (DCM). In this study, we investigated the long-term natural history of DCM caused by TTNtv. In our study, we report longer follow-up times (median of 8 years) than previous studies and found that most patients were diagnosed with severe heart failure in the 4^th-6^th decade of life. While ¼ patients died or had a heart transplantation during the study, medical therapy led to a significant reversibility of cardiac function in 68% of patients. The prevalence of cardiac arrhythmias was found to be approximately twice as high as previously reported and was notably the presenting symptom in 1/3 patients. Finally, we observed a 2:1 male to female sex ratio and discovered women to have milder disease-courses with an older age at disease onset, a better treatment response and fewer malignant arrhythmias. (https://jmg.bmj.com/content/early/2020/10/25/jmedgenet-2020-107178 )