Electrocardiographic estimates of action potential durations and transmural repolarization time gradients in healthy subjects and in acute coronary syndrome patients--profound differences by sex and by presence vs absence of diagnostic ST elevation

Abstract

Action potential duration (APD) changes increasing repolarization time (RT) dispersion are potentially arrhythmogenic. A repolarization model developed from electrocardiographic data of 5376 healthy men and women was used to derive parameter estimates for APD and RT and their transmural gradients (RT(grad) and APD(grad), respectively) in myocardial infarction patients, 126 with and 658 without diagnostic ST elevation (STEMI and NSTEMI, respectively). The model uses, as covariates, rate-adjusted QT and QT peak intervals (QT(a) and QT(pa), respectively) and diagonal crossmural RT(grad) derived as T(p)-T(xd), the interval from T(p) to the inflection point at descending limb of global T wave. An additional parameter is Θ(T|T(ref)), the spatial angle between a subject's T vector and the average T vector of the normal reference group. If Θ(T|T(ref)) >0, QT(pa) is assigned to RT(epi) and QT(pa) + RT(grad) to RT(endo), with RT(epi) and RT(endo) assignments reversed if Θ(T|T(ref)) ≤0. Parameter estimates for APD(epi) and APD(endo) were shorter in men than in women (by 17 ms and 14 ms, respectively, P < .001 for both). Compared to the reference group, RT(epi) in the STEMI group was shortened by 14 ms in men and by 18 ms in women (P < .001 for both) with a lesser decrease in RT(endo) suggesting predominantly subepicardial ischemia. In NSTEMI only RT(endo) was shortened, by 6 ms in males (P < .01) and 10 ms in females (P < .001), suggesting subendocardial ischemia. RT(grad) signifying local crossmural RT dispersion was prolonged in STEMI by 8 ms in men and by 11 ms in men (P < .001 for both). RT(grad) was not changed significantly in NSTEMI. Rate-adjusted T(p)-T(e) interval signifying global RT dispersion was increased in both MI and in both sex groups (P <.001 for all). In conclusion, QT prolongation observed in NSTEMI without prolongation of RT(grad) and APD(epi) suggests a delay during terminal repolarization, and in contrast, in STEMI, QT is not changed significantly in spite of prolonged RT(grad) because of shortened APD(epi) and RT(epi). These repolarization abnormalities are not revealed by QT alone but readily by the repolarization model.