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Relatively few data have been reported on prospective changes in global longitudinal strain ( GLS) following cardiac resynchronization therapy ( CRT), and none are available on GLS during physical exercise. We investigated the effects of CRT on GLS, assessed by speckle tracking two-dimensional (2 D) echocardiography, at rest and during exercise after a mid-term follow-up. Twenty consecutive CRT patients (45% ischaemic) were assessed prospectively by speckle tracking 2 D echocardiography before implant (at rest) and at mid-term follow-up (during rest and bicycle exercise). GLS, septum and lateral wall longitudinal strain, left ventricular ejection fraction ( LVEF), and conventional functional variables were evaluated at baseline and follow-up. All patients completed the study protocol at rest. Exercise images were available in 90% of the patients. At follow-up, GLS improved at rest from −7·1 ± 2·6% to −9·1 ± 4·5% ( P<0·01), with a further increase to −11 ± 5·1% during exercise ( P<0·001). Longitudinal strain increased at rest both in the septum and in the lateral wall, with an additional increase during exercise in the lateral wall ( P<0·05). GLS correlated with LVEF both at rest ( r = −0·55 and r = −0·91 at baseline and 3 months, respectively; P<0·05) and during exercise ( r = −0·89, P<0·05). Improvement in GLS during rest and exercise can be observed in CRT patients at mid-term follow-up and seems to correlate with changes in LVEF. GLS may be a valuable method to assess left ventricular function during rest and exercise. [ABSTRACT FROM AUTHOR]