Effect of Ranolazine on Left Ventricular Dyssynchrony in Patients With Coronary Artery Disease

Study Questions:

What is the impact of short-term therapy with ranolazine on left ventricular (LV) systolic and diastolic dyssynchrony indices measured by automated analysis of gated single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (MPI)?

Methods:

This was an open-label, single-center study in which patients (n = 32) with known or suspected coronary artery disease and reversible perfusion defects on a clinically indicated stress MPI were given add-on ranolazine (500-1000 mg twice daily). Indices of LV systolic and diastolic dyssynchrony (bandwidth and SD) were determined using post-stress automated phase analysis before the addition of ranolazine, and 4 weeks following therapy.

Results:

Systolic and diastolic LV dyssynchrony improved following ranolazine therapy, with significant decreases in the systolic phase SD (21 ± 17 vs. 18 ± 13, p = 0.04), systolic bandwidth (69 ± 60 vs. 53 ± 38, p = 0.03), diastolic SD (29 ± 18 vs. 24 ± 15, p = 0.047), and diastolic bandwidth (91 ± 61 vs. 72 ± 45, p = 0.002). No changes were seen in LV ejection fraction (EF) after short-term treatment with ranolazine (but mean EF was normal to start with). None of the patients had a left bundle branch block. Of note, the perfusion pattern improved in 13 of 18 patients who had undergone exercise stress testing; this was seen in fewer (3 of 14) patients who required pharmacologic stress.

Conclusions:

In this proof-of-concept open-label trial of 4 weeks of ranolazine therapy in patients with coronary artery disease and preserved EF already on conventional medical therapy, systolic and diastolic phases of LV dyssynchrony improved with short-term therapy.

Perspective:

While limited by an open-label trial design without a control arm and a small sample size, this study adds to our understanding of ranolazine and its potential clinical benefits. Results from randomized trials to more clearly understand the effect of ranolazine on diastolic function are eagerly anticipated.

Keywords: Myocardial Perfusion Imaging, Coronary Artery Disease, Tomography, Emission-Computed, Single-Photon, Bundle-Branch Block, Piperazines, Diastole, Heart Ventricles, Systole


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