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Background: There is still limited information about the functional effective cardiac improvement of myocardial deformation dynamics during direct renin inhibition therapy. Aim of the study was to determine if the combination of first orally active direct renin inhibitor, aliskiren, and valsartan is more effective than highly-dosed valsartan alone in the progressive improvement of left ventricular (LV) and atrial (LA) remodeling, analyzed by speckle tracking echocardiography, in patients with hypertension and LV hypertrophy.Methods: In this prospective study, 19 patients with hypertension and LV hypertrophy were randomized to once-daily highly-dosed valsartan (160 mg titrated to 320 mg after 4 weeks; n=10) or the combination of valsartan (160 mg) with aliskiren (150 mg titrated to 300 mg after 4 weeks; n=9) for 6 months. Patients were treated to standard blood pressure targets with add-on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone system and beta-blockers. Before and 3 and 6 months after the start of therapy, LV and LA longitudinal strain parameters were measured in all patients.Results: Systolic and diastolic blood pressures were reduced similarly in both treatment groups (7.6±14.9/3.9±10.1 mmHg in the highly-dosed valsartan group and 7.9±15.6/3.9±10.7 mmHg in the combination arm; p<0.0001 within both groups, P=0.69 between groups). LV mass index was reduced significantly from baseline in both treatment groups only after 6 months (6.2- and 6.0- g/m2 reductions in the valsartan, and combination arms, respectively; p<0.0001 for both). No significant changes in LV longitudinal strain parameters were found either 3 months or 6 months after in both groups. Global atrial longitudinal strain increased significantly after 6 months of therapy in both groups (22.4±6.1 vs 31.8±7.0% and 22.3±6.2 vs 33.9±6.8%; in the valsartan, and combination arms, respectively p=0.001 for both). Aliskiren+valsartan was as effective as highly-dosed valsartan in increasing LA longitudinal strain (p<0.0001 for noninferiority). Safety and tolerability were similar across both treatment groups.Conclusions: The combination of aliskiren and valsartan was as effective as highly-dosed valsartan in promoting LA function recovery, independently of blood pressure lowering in hypertensive patients with LV hypertrophy. No changes were demonstrated for the LV myocardial deformation.