Marked exercise-induced T-wave heterogeneity in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis.

BACKGROUND: T-wave heterogeneity (TWH) independently predicted cardiovascular mortality in Health Survey 2000 based on 12-lead ECGs recorded at rest. We investigated whether TWH is elevated during exercise tolerance testing (ETT) in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis compared to control subjects without diabetes. METHODS: Cases were all patients (n = 20) with analyzable ECG recordings during both rest and ETT who were enrolled in the Effects of Ranolazine on Coronary Flow Reserve (CFR) in Symptomatic Patients with Diabetes and Suspected or Known Coronary Artery Disease (RAND-CFR) study (NCT01754259); median CFR was 1.44; 80% of cases had CFR <2. Control subjects (n = 9) were nondiabetic patients who had functional flow reserve (FFR) >0.8, a range not associated with inducible ischemia. TWH was analyzed from precordial leads V4 , V5 , and V6 by second central moment analysis, which assesses the interlead splay of T-waves about a mean waveform. RESULTS: During exercise to similar rate-pressure products (p = .31), RAND-CFR patients exhibited a 49% increase in TWH during exercise (rest: 49 ± 5 µV; exercise: 73 ± 8 µV, p = .003). By comparison, in control subjects, TWH was not significantly altered (rest: 52 ± 11 µV; ETT: 38 ± 5 µV, p = .19). ETT-induced ST-segment depression >1 mm (p = .11) and Tpeak -Tend (p = .18) and QTc intervals (p = .80) failed to differentiate cases from controls. CONCLUSIONS: TWH is capable of detecting latent repolarization abnormalities, which are present during ETT in diabetic patients with nonflow-limiting stenosis but not in control subjects. The technique developed in this study permits TWH analysis from archived ECGs and thereby enables mining of extensive databases for retrospective studies and hypothesis testing.

Ranolazine reduces repolarization heterogeneity in symptomatic patients with diabetes and non-flow-limiting coronary artery stenosis.

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 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 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.