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Purpose: To evaluate the effects of ranolazine (RN), a novel anti-ischemic drug influencing intracellular sodium and calcium concentrations, on global left ventricular (LV) longitudinal function in patients referring for primary percutaneous coronary angioplasty (PTCA) after ST segment elevation myocardial infarction (STEMI).Methods: After primary PTCA following STEMI, 29 patients treated by RN (500 mg bid) + standard anti-ischemic therapy were compared to 30 controls (C) treated by only standard anti-ischemic therapy, according to a single-blind design. At baseline and after therapy, the patients underwent a complete echo-Doppler examination including pulsed Tissue Doppler of mitral annulus. Automated function Imaging (AFI), a software which utilizes Speckle Tracking Echocardiography (STE) principles by simple recording of 2-D imaging (> 40 fps), was also performed. Peak longitudinal regional strain was measured at the 18 LV segments obtained in the 3 apical views and global longitudinal strain (GLS) calculated as the average of measurements.Results: At baseline, ejection fraction and GLS were similar between the 2 groups. After therapy heart rate, systolic and diastolic blood pressure did not differ significantly between the 2 groups. Ejection fraction improved significantly in both RN (from 51 ± 9% to 53 ± 8%, p<0.02) and C (from 52 ± 10% to 55 ± 9%, p<0.02), without significant percent change between the 2 groups. Also GLS was improved by both the treatments (from -14.5 ± 5% to -17 ± 8% in RN, p<0.01; from -14.4 ± 4% to -16 ± 5% in C, p<0.02). The percent increase of GLS was greater in RN (18%) than in C group (12%) (p<0.02). The percent reduction of E/e' ratio, as an estimate of degree in LV filling pressure, was greater in RN than in C (p<0.01). A negative relation was found between percent increase of GLS and percent reduction of E/e' ratio in RN group (r = -0.45, p<0.01) but not in C (r = -0.10, NS).Conclusions: Three month ranolazine therapy significantly improves LV global longitudinal function and filling pressure in STEMI patients after PTCA. The negative association found between changes of global longitudinal function and filling pressure degree highlights indirectly the mechanisms of this drug, able to improve myocardial perfusion of subendocardial fibers throughout the enhancement of myocardial diastolic relaxation.