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The SENIORS trial recently demonstrated that nebivolol reduces the composite risk of all-cause mortality and cardiovascular hospital admission in elderly patients with chronic heart failure and, importantly, that ejection fraction does not influence the clinical effects of nebivolol. An echocardiographic substudy was designed to evaluate the effects of nebivolol on systolic and diastolic left ventricular (LV) function in patients stratified according to the presence or absence of systolic LV dysfunction.The substudy randomized 112 patients in 29 European centres, of whom 104 were evaluable for the study; 43 had an ejection fraction (EF)or=35% and 61 had an EF35%. LV end-systolic volume (ESV), EF, mitral valve E/A ratio, and E-wave deceleration time were assessed at baseline and after 12 months. Echocardiograms were submitted to a core laboratory to perform quantitative analysis in blinded condition. In the group with EF/=35%, nebivolol reduced ESV (adjusted difference between treatments 25.8 mL, 95%CI: -46.6; -5.0, P=0.016) and improved EF (adjusted difference between treatments 4.6%, 95%CI: 1.3;7.9, P=0.008); no changes were observed in the E/A ratio or E-wave deceleration time. In EF35% group, no significant changes in either systolic or diastolic parameters were observed.In patients with heart failure and advanced systolic LV dysfunction, nebivolol reduces ventricular size and improves EF. The absence of detectable changes with standard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients.