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A Study of the Effects of Ranolazine Using Automated Quantitative Analysis of Serial Myocardial Perfusion Images

Rajesh Venkataraman, MD, MPH^_*,_*, Luiz Belardinelli, MD, Brent Blackburn, PhD, Jaekyeong Heo, MD^_*, Ami E. Iskandrian, MD^_*

^_* Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
Gilead Sciences Inc., Foster City, California

^_* Reprint requests and correspondence: Dr. Rajesh Venkataraman, University of Alabama at Birmingham, Division of Cardiovascular Disease, 314 LHRB, 1900 University Boulevard, Birmingham, Alabama 35294-0007 (Email: rajeshv{at}uab.edu).

Objectives: This study examined the hypothesis that the improvement in myocardial blood flow (MBF) with ranolazine therapy could be detected by serial automated quantitative myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) and myocardial ischemia.

Background: Myocardial ischemia enhances late sodium current, which then causes cellular calcium overload leading to mechanical left ventricular dysfunction and arrhythmias. Ranolazine inhibits late sodium current and improves diastolic tension and MBF in the animal model.

Methods: In this open-label, nonrandomized pilot study, we recruited 20 patients with known or a high probability of CAD and who had reversible perfusion defects on exercise treadmill gated single-photon emission computed tomography MPI while receiving conventional antianginal therapy. Ranolazine (up to 1,000 mg twice daily) was added to baseline therapy and a repeat treadmill MPI was obtained after 4 weeks. The extent and severity of total and reversible left ventricular perfusion abnormality (based on polar maps and a 17-segment model) were determined quantitatively using automated methods.

Results: We screened 100 patients for 27 potential candidates; 5 declined and 2 did not complete the follow-up study. The mean age of the remaining 20 patients was 64 ± 9 years; 30% were women and 50% had diabetes mellitus. The exercise time increased (425 ± 105 s vs. 393 ± 116 s, p = 0.017), and angina improved in 15 (75%) patients after ranolazine treatment. In the entire cohort, summed stress scores (10 ± 7 vs. 13 ± 8, p = 0.04) and summed difference scores (4.7 ± 4 vs. 7.4 ± 5, p = 0.0037) decreased at follow-up. An improvement in perfusion pattern and severity was noted in 14 (70%) patients. In these patients, the polar maps showed a decrease in total abnormality from 26 ± 17% to 19 ± 15% and a decrease in the reversible abnormality from 16 ± 10% to 8 ± 6% (all p values <0.05).

Conclusions: In this preliminary hypothesis-driven study, short-term ranolazine therapy was shown to improve myocardial perfusion and decrease the ischemic burden in patients with CAD.

Key Words: ranolazine • myocardial perfusion imaging • coronary artery disease • single-photon emission computed tomography • ischemia • exercise testing

Abbreviations and Acronyms   CAD = coronary artery disease   LV = left ventricular   MBF = myocardial blood flow   MPI = myocardial perfusion imaging   SDS = summed difference score   SPECT = single-photon emission computed tomography

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				F. J. Klocke Ranolazine and the Myocardial Demand-Supply Balance J. Am. Coll. Cardiol. Img., November 1, 2009; 2(11): 1310 - 1312. [Full Text] [PDF]