Demonstration of the Proarrhythmic Preconditioning of Single Premature Extrastimuli by Use of the Magnitude, Phase, and Distribution of Repolarization Alternans

BACKGROUND: We hypothesized that single premature extrastimuli (S(2)) insufficient to induce reentry produce proarrhythmic effects (proarrhythmic preconditioning) that are measurable by use of the magnitude, phase, and temporal distribution of repolarization alternans (RPA; alternate-beat fluctuations in ECG repolarization). METHODS AND RESULTS: Before programmed electrical stimulation (PES), surface ECG leads I, aVF, and V(1) were recorded in 30 patients during simultaneous atrial and ventricular pacing at 500 ms with S(2) coupling intervals (CIs) decreasing from 400 to 240 ms in 20-ms steps. We determined RPA magnitude (V(alt)) as the 0.5-cycle/beat peak after spectral decomposition of consecutive STU intervals over 64 beats immediately preceding and following each S(2), RPA phase reversals as discontinuities in the even/odd phase of STU alternation, and RPA distribution as the time point of median RPA magnitude within repolarization. Eighteen patients were induced into ventricular tachycardia (VT), whereas 12 were not. Extrastimuli dynamically modulated each characteristic of RPA. S(2) augmented V(alt) in inducible (8.2+/-2.3 versus 6.2+/-1.6 microV; P=0.003) but not noninducible patients. S(2) reversed RPA phase more in inducible than in noninducible patients (56.7% versus 45.3%; P=0.02 by chi(2)), particularly when CI was < or =300 ms (66.3% versus 46.5%; P=0.006). Finally, S(2) redistributed RPA significantly later within repolarization in inducible patients. Each effect was more marked for CI < or =300 ms. CONCLUSIONS: A single S(2) increases RPA magnitude, reverses its phase, and redistributes it later in repolarization in patients with the substrates for VT. These effects become more pronounced with shorter coupling intervals. These results suggest that it is possible to track the dynamic proarrhythmic preconditioning of single premature depolarizations.