BACKGROUND: Experimental evidence suggests that ranolazine decreases susceptibility to ischemia-induced arrhythmias independent of effects on coronary artery blood flow. OBJECTIVE: In symptomatic diabetic patients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T-wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death. METHODS: We studied all 16 patients with analyzable ECG recordings during rest and exercise tolerance testing before and after 4 weeks ofranolazine in the double-blind, crossover, placebo-controlled RAND-CFR trial (NCT01754259). TWH was quantified without knowledge of treatment assignment by second central moment analysis, which assesses the interlead splay of T waves in precordial leads about a mean waveform. Myocardial blood flow (MBF) was measured by positron emission tomography. RESULTS: At baseline, prior to randomization, TWH during rest was 54 ± 7 μV and was not altered following placebo (47 ± 6 μV, p = .47) but was reduced by 28% (to 39 ± 5 μV, p = .002) after ranolazine. Ranolazine did not increase MBF at rest. Exercise increased TWH after placebo by 49% (to 70 ± 8 μV, p = .03). Ranolazine did not reduce TWH during exercise (to 75 ± 16 μV), and there were no differences among the groups (p = .95, ANOVA). TWH was not correlated with MBF at rest before (r2 = .07, p = .36) or after ranolazine (r2 = .23, p = .06). CONCLUSIONS: In symptomatic diabetic patients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, ranolazine reduced TWH at rest but not during exercise. Reduction in repolarization abnormalities appears to be independent of alterations in MBF.
RCT Entities:
BACKGROUND: Experimental evidence suggests that ranolazine decreases susceptibility to ischemia-induced arrhythmias independent of effects on coronary artery blood flow. OBJECTIVE: In symptomatic diabeticpatients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T-wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death. METHODS: We studied all 16 patients with analyzable ECG recordings during rest and exercise tolerance testing before and after 4 weeks of ranolazine in the double-blind, crossover, placebo-controlled RAND-CFR trial (NCT01754259). TWH was quantified without knowledge of treatment assignment by second central moment analysis, which assesses the interlead splay of T waves in precordial leads about a mean waveform. Myocardial blood flow (MBF) was measured by positron emission tomography. RESULTS: At baseline, prior to randomization, TWH during rest was 54 ± 7 μV and was not altered following placebo (47 ± 6 μV, p = .47) but was reduced by 28% (to 39 ± 5 μV, p = .002) after ranolazine. Ranolazine did not increase MBF at rest. Exercise increased TWH after placebo by 49% (to 70 ± 8 μV, p = .03). Ranolazine did not reduce TWH during exercise (to 75 ± 16 μV), and there were no differences among the groups (p = .95, ANOVA). TWH was not correlated with MBF at rest before (r2 = .07, p = .36) or after ranolazine (r2 = .23, p = .06). CONCLUSIONS: In symptomatic diabeticpatients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, ranolazine reduced TWH at rest but not during exercise. Reduction in repolarization abnormalities appears to be independent of alterations in MBF.
Authors: Tuomas V Kenttä; Bruce D Nearing; Kimmo Porthan; Jani T Tikkanen; Matti Viitasalo; Markku S Nieminen; Veikko Salomaa; Lasse Oikarinen; Antti Jula; Kimmo Kontula; Chris Newton-Cheh; Heikki V Huikuri; Richard L Verrier Journal: Heart Rhythm Date: 2015-11-23 Impact factor: 6.343
Authors: Venkatesh L Murthy; Masanao Naya; Courtney R Foster; Jon Hainer; Mariya Gaber; Gilda Di Carli; Ron Blankstein; Sharmila Dorbala; Arkadiusz Sitek; Michael J Pencina; Marcelo F Di Carli Journal: Circulation Date: 2011-10-17 Impact factor: 29.690
Authors: Richard L Verrier; Thomas Klingenheben; Marek Malik; Nabil El-Sherif; Derek V Exner; Stefan H Hohnloser; Takanori Ikeda; Juan Pablo Martínez; Sanjiv M Narayan; Tuomo Nieminen; David S Rosenbaum Journal: J Am Coll Cardiol Date: 2011-09-20 Impact factor: 24.094
Authors: Kapil Kumar; Bruce D Nearing; Carlo R Bartoli; Kevin F Kwaku; Luiz Belardinelli; Richard L Verrier Journal: J Cardiovasc Electrophysiol Date: 2008-05-09
Authors: Mikhail Kosiborod; Suzanne V Arnold; John A Spertus; Darren K McGuire; Yan Li; Patrick Yue; Ori Ben-Yehuda; Amos Katz; Philip G Jones; Ann Olmsted; Luiz Belardinelli; Bernard R Chaitman Journal: J Am Coll Cardiol Date: 2013-03-10 Impact factor: 24.094
Authors: Nishant R Shah; Michael K Cheezum; Vikas Veeranna; Stephen J Horgan; Viviany R Taqueti; Venkatesh L Murthy; Courtney Foster; Jon Hainer; Karla M Daniels; Jose Rivero; Amil M Shah; Peter H Stone; David A Morrow; Michael L Steigner; Sharmila Dorbala; Ron Blankstein; Marcelo F Di Carli Journal: J Am Heart Assoc Date: 2017-05-04 Impact factor: 5.501
Authors: Ederson Evaristo; Fernando G Stocco; Nishant R Shah; Michael K Cheezum; Jon Hainer; Courtney Foster; Bruce D Nearing; Marcelo Di Carli; Richard L Verrier Journal: Ann Noninvasive Electrocardiol Date: 2017-06-27 Impact factor: 1.468