Abstract Background Speckle-tracking echocardiography studies in inherited long QT syndrome (LQTS) have recently shown myocardial relaxation disturbances at rest in the form of delayed onset of relaxation as a result of prolonged and dispersed mechanical contraction. The aim of this study was to assess disturbances in left ventricular regional myocardial relaxation sequence during exercise. Methods Forty seven (age 45±15 years, 25 female, LVEF: 65±6%, 36 LQT1 and 11 LQT2 whereof 20 symptomatic) patients underwent cardiac exercise test using Bruce protocol. ECG and echo parameters were recorded at rest, during peak exercise (p.e.) and at were compared with 35 healthy individuals. All time intervals were calculated from onset of R wave on superimposed ECG and were corrected to R-R interval. Results LQTS patients had longer QTc interval than controls at all the three exercise phases. LV longitudinal tESR, a reflector of relaxation delay was examined separately in the LV basal, mid and apical segments. At rest, no significant differences were noted between the two groups at the basal (490±59 vs. 486±36, p=0.6) and mid LV cavity regions (488±45 vs. 498±39, p=0.3); whereas in patients were seen more prolonged tESR in the apical regions (467±52 vs. 512±44, p<0.0001). At peak exercise, patients had longer tESR at all three LV segments; basal (394±67 vs. 316±30, p<0.0001), mid cavity (363±64 vs. 340±32, p=0.03) and apical (348±60 vs. 368±28, p=0.03). The apico-basal relaxation dispersion (Δt ESRbase-apex) was significantly more pronounced in patients than in controls both at rest (49±43 vs. −29±19, p<0.0001) and at p.e. (46±38 vs. −40±22, p<0.0001). Moreover, the longitudinal relaxation sequence was reversed in patients (positive values for Δt ESRbase-apex); the early relaxation phase at the base was more delayed than at the apex, opposite to controls in whom the early relaxation onset occurred earlier in LV base than at apex. The magnitude of this apico-basal relaxation dispersion (Δt ESRbase-apex) correlated with longer QTc interval (r=0.9, p<0.0001), lower ESR (r=−0.8, p<0.0001) and attenuated LV stroke volume (r=−0.9, p<0.0001). This difference in Δt ESRbase-apex was more pronounced in symptomatic patients at p.e. than in asymptomatic (69±44 vs. 32±26, p<0.0007). Conclusion Our results showed reversed longitudinal relaxation sequence with more delayed early relaxation contraction phase at LV base than at LV apex in LQTS mutation carriers opposite to controls. These disturbances worsened at peak exercise and were related to longer QTc intervals and symptomatic patients. Funding Acknowledgement Type of funding sources: None.