Effect of late sodium current inhibition on MRI measured diastolic dysfunction in aortic stenosis: a pilot study

Abstract

BackgroundRanolazine is a new anti-anginal drug that acts via late sodium current inhibition, and has been shown to improve diastolic dysfunction in isolated myocytes. Diastolic dysfuntion is common in patients with aortic stenosis (AS), and precedes symptom development and systolic dysfunction. The purpose of this study was to assess the effects of ranolazine on peak early diastolic strain rate (PEDSR) and exercise capacity in patients with AS.MethodsPatients with asymptomatic moderate to severe AS and diastolic dysfunction underwent trans-thoracic echocardiography, exercise testing and cardiac magnetic resonance (CMR) imaging at baseline, 6 weeks after commencing ranolazine and at 10 weeks (4 weeks after discontinuation). Diastolic function was assessed using PEDSR measured on tagged CMR images.ResultsFifteen patients (peak pressure gradient 48.8 ± 12.4 mmHg, mean pressure gradient 27.1 ± 7.5 mmHg, aortic valve area 1.26 ± 0.31 cm2) completed the week-6 visit and 13 completed the final visit. Global PEDSR did not significantly increase from baseline (0.79 ± 0.15) to week-6 (0.86 ± 0.18, p = 0.198). There was a borderline significant increase in total exercise duration from 10.47 ± 3.68 min to 11.60 ± 3.25 min (p = 0.06).ConclusionThis small pilot study did not show a significant improvement in diastolic function with the use of ranolazine in asymptomatic patients with moderate-severe AS. Further studies with a larger population may be indicated.EduraCT number 2011-000111-26Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-1874-0) contains supplementary material, which is available to authorized users.

Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with ranolazine

“…To test whether ranolazine is equally effective in subjects with CMD who have no obstructive CAD, we leveraged the recently completed randomized, placebo‐controlled trial of late sodium current inhibition with ranolazine in CMD (NCT01342029) . In line with a recent study in subjects with aortic stenosis, we observed no major differences in diastolic or systolic function between the placebo arm and the ranolazine arm. Although the reason for this negative finding remains unclear, we acknowledge that it may be related to the treatment regimen.…”

Left Ventricular Diastolic Function Studied with Magnetic Resonance Imaging: A Systematic Review of Techniques and Relation to Established Measures of Diastolic Function

“…The control groups were slightly younger than patient groups, but this was probably not a difference that could explain the effect seen ( Table 2 ) [ 29 , 32 ]. In patients with moderate-to-severe AS, the global diastolic peak circumferential strain rate closely resembled estimates for patients with DM2 and arterial hypertension ( Table 2 ) [ 30 ]. One study was found on inter-observer and inter-study reproducibility of global diastolic peak circumferential strain rate in patients with moderate-to-severe AS for both 1.5T and 3T [ 31 ]: the inter-observer variability was good for both 1.5T-CSAPMM (coefficient of variation 4%) and 3T-SPAMM (6%), but the inter-study reproducibility was only good-to-moderate for 1.5T-CSAPMM (coefficient of variation 19%) and poor for 3T-SPAMM (34%).…”