ESC Congress 2026 Abstract · Oct 26, 2026
Effect of high-intensity exercise in carriers of Titin truncating variants
By Hellstrand C, Castrini AI, Hasselberg NE et al.
Background: Truncating variants of the Titin gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM). Factors promoting disease penetrance and genetic expression are poorly identified. Data on the effect of high-intensity exercise on development of DCM phenotype in TTNtv (TTNtv-DCM) carriers are lacking. Purpose: To explore whether high-intensity exercise is associated with penetrance and severity of TTNtv-DCM. Methods: We performed a retrospective cohort study inviting all TTNtv genotype positive patients followed at our outpatient clinic to answer an exercise questionnaire. Reported exercise type and duration from age 6 years to first clinical follow-up was quantified as metabolic equivalents (METs), according to the 2024 Compendium of Physical Activities. Athletes were defined as patients with ≥ 4 hours high-intensity exercise/week [≥ 1440 MET*minutes/week] during a minimum of 6 consecutive years. At first clinical follow-up, we assessed left ventricular (LV) and right ventricular (RV) dimensions and function by echocardiography. Data from cardiac magnetic resonance imaging (CMR) were collected in a subset of patients. The burden of supraventricular and ventricular arrhythmias was reported. DCM was defined according to the ESC 2023 guidelines on Cardiomyopathies. Results: We included 161 TTNtv patients, (18% probands, 60% female). The median age at first follow-up was 43 years [IQR 32-53]. Median MET-intensity for all reported exercise was 7 METs [IQR 5-8] and athlete definition was fulfilled in 81 (50%) patients. Seven patients performed professional sports at an elite level. At the time of first follow-up, 41 (25%) patients were diagnosed with DCM. There was no difference in frequency of DCM diagnosis between athletes and non-athletes (27% vs 24%, p=0.62). By echocardiography, LV ejection fraction was not significantly different between athletes and non-athletes (p=0.12). Left ventricular end-diastolic diameter (LVEDD) and volume (LVEDV) were significantly increased in athletes compared to non-athletes (p <0.01 and p=0.05). However, there were no differences in LVEDD and LVEDV when adjusted for age and sex (p=0.27 and p=0.96). By CMR, LVEDV did not differ between athletes and non-athletes (p=0.56). We did not observe differences in neither the burden of atrial fibrillation (p=0.16), nor in ventricular arrhythmias (p=0.99) between athletes and non-athletes. Conclusion: High-intensity exercise was not associated with penetrance and severity of DCM in TTNtv carriers. We observed an increased LVEDD and LVEDV by echocardiography in athletes compared to non-athletes, possibly due to higher exercise load rather than presence of TTNtv genotype.Characteristics of TTNtv cohort