Background Participation in regular exercise activities is recommended for patients with chronic heart failure. However, less is known about the effect of exercise in patients with genetic dilated cardiomyopathy (DCM). We sought to examine the effect of vigorousintensity training on physical capacity in patients with DCM caused by truncating titin variants (TTNtv).

Trial design Non-randomised clinical pre-post trial of exercise training.

Methods Individuals with DCM-TTNtv were included from outpatient clinics for inherited cardiac diseases. The trial consisted of 8 weeks of usual care followed by 8 weeks of regular vigorous-intensity cycling exercise, enclosed by three test days. The primary outcome was change in peak oxygen uptake (VO₂). Secondary outcomes included change in blood volume, total haemoglobin mass, measures of systolic function and cardiac output/stroke volume during exercise.

Results Thirteen out of 14 included participants (43% women, age 48±11 years, body mass index: 30±6 kg/m²) completed the trial. In the exercise training period, peak VO₂ increased by +1.9 mL/kg^/min (95% CI +0.9 to +2.9, p=0.002). Compared with usual care, exercise training improved peak VO₂ by +2.9 mL/kg/min (95% CI +1.2 to +4.5, p=0.002), corresponding to a 10% increase. Adaptations to exercise training included an increase in resting cardiac output (+0.8 L/min, p=0.042), total blood volume (+713 mL, p<0.001), total haemoglobin mass (+73 g, p<0.001), and improved left ventricular (LV) systolic function (LV ejection fraction: +3.2% (p=0.053) and global longitudinal strain: −2.0% (p=0.044)). No exercise-related adverse events or change in plasma biomarkers of cardiac or skeletal muscle damage were observed.

Conclusions Our study shows that vigorous intensity exercise training improved peak VO₂ in patients with DCM-TTNtv. Exercise training was associated with improved LV systolic function and increased blood volume and oxygen carrying capacity. Future research should investigate the effect of long-term exercise in this group.

Trial registration number NCT05180188.