Effects of ranolazine on left ventricular diastolic and systolic function in patients with chronic coronary disease and stable angina.

INTRODUCTION: The present study examined the effect of ranolazine, which acts via the mechanism of selective inhibition of late INa+, on parameters of left ventricular systolic and diastolic function in patients suffering from angiographically confirmed chronic coronary artery disease, presenting with chronic stable angina. METHODS: We studied 40 patients (age 67 ± 9 years; 30 men, 10 women) with chronic coronary artery disease who reported angina symptoms on optimal medication and who were not suitable for invasive treatment. Patients were randomized to the ranolazine group (group A, 20 patients taking oral ranolazine 500 mg bid for 3 months) and the control group (group B, 20 patients who did not receive the drug). Left ventricular systolic and diastolic function was assessed echocardiographically at baseline and after the end of the three-month treatment period. Left ventricular ejection fraction by the modified Simpson's method, E and A left ventricular filling velocities, E/A ratio, deceleration time (DT) of E, isovolumic relaxation time (IVRT), E and A waves, and the E/E ratio were measured using 2-dimensional echocardiography, Doppler and tissue Doppler imaging (TDI). RESULTS: Group A patients demonstrated a clear improvement of their initial angina symptoms. There were no adverse effects from ranolazine requiring withdrawal from the study. There was no statistically significant change in left ventricular systolic function in either group. A statistically significant change was seen in indexes of diastolic function measured using both conventional Doppler and TDI in Group A patients compared with Group B patients after three months' ranolazine treatment period. The changes in left ventricular diastolic function indexes in Group A patients were as follows: E 0.58 ± 0.11 vs. 0.76 ± 0.12 m/s, p<0.001; A 0.71 ± 0.22 vs. 0.83 ± 0.19 m/s, p<0.001; E/A 0.81 ± 0.14 vs. 0.97 ± 0.17, p<0.005; 5.4 ± 0.7 vs. 6.8 ± 0.9 cm/s, p<0.005; 7.2 ± 0.8 vs. 8.3 ± 1.1 cm/s, p<0.005; E/ 10.7 ± 1.1 vs. 11.1 ± 0.8, p=ns; DT 251 ± 14 vs. 226 ± 17 ms, p<0.004; IVRT 95 ± 11 vs. 74 ± 9 ms, p<0.001. Systolic function did not change: EF 46.3 ± 3.4 vs. 46.7 ± 2.7%, p: ns. CONCLUSIONS: The use of ranolazine in patients suffering from chronic coronary artery disease has a favorable impact on diastolic function parameters. Accordingly, a clinical benefit could be observed due to an improvement in patients' symptoms.

Genetic Variant in the CYP19A1 Gene Associated with Coronary Artery Disease.

The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the biosynthesis of estrogens. The rs10046 polymorphism of CYP19A1 gene has been investigated in two studies on the occurrence of hypertension, but there are no studies on its correlation with coronary artery disease (CAD). We investigated 189 subjects who were hospitalized at "KAT" General Hospital of Athens and underwent coronary angiography. Of these, 123 were found with CAD with an average age of 60 years and constituted the patients group and 66 subjects with an average age of 58 years without damage in the coronary vessels and constituted the control group (healthy). The frequencies of genotypes CC, CT, and TT of rs10046 polymorphism are significantly different between the group of CAD patients and the control group (0.34, 0.48, and 0.18 versus 0.20, 0.48, and 0.32, resp., P = 0.034) as the frequency of C allele (0.58 versus 0.44, resp., OR = 1.771 and P = 0.010). We found similar results for men, but not for women (small sample). The results of this study show that the rs10046 (C/T) polymorphism of CYP19A1 gene exhibits correlation with CAD and that patients with C allele have an increased probability of manifesting the disease.