Background-Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium. Methods and Results-Monophasic action potentials were recorded from the right ventricular septum in 24 patients with structural heart disease (SHD) and in 12 patients without SHD. Standard and dynamic restitution relations were constructed by plotting APD as a function of the preceding diastolic interval. The dynamic restitution relation of both groups showed a steeply sloped segment at short diastolic intervals that was associated with the occurrence of APD alternans. Patients with SHD had a wider diastolic interval range over which APD alternans was present (meanϮSEM 68Ϯ11 versus 12Ϯ2 ms) and showed an earlier onset (168Ϯ7 versus 225Ϯ4 bpm) and an increased magnitude (20Ϯ2 versus 11Ϯ2 ms) of APD alternans compared with patients without SHD. The occurrence of APD alternans during induced ventricular tachycardia (6 episodes) and during rapid pacing could be derived from the dynamic restitution function. Conclusions-There are marked differences in the dynamics of APD restitution and alternans in the ventricular myocardium of patients with SHD compared with patients without SHD. These differences may contribute importantly to cardiac electrical instability in diseased human hearts and may represent a promising target for antiarrhythmic substrate modification.

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We present a systematic approach for detecting nonlinear components in heart rate variability (HRV). The analysis is based on twenty-three 48-h Holter recordings in healthy persons during sinus rhythm. Although many segments of 1,024 R-R intervals are stationary, only few stationary segments of 8,192–32,768 R-R intervals can be found using a test of Isliker and Kurths ( Int. J. Bifurcation Chaos 3:1573–1579, 1993.). By comparing the correlation integrals from these segments and corresponding surrogate data sets, we reject the null hypothesis that these time series are realization of linear processes. On the basis of a test statistic exploring the differences of consecutive R-R intervals, we reject the hypothesis that the R-R intervals represent a static transformation of a linear process using optimized surrogate data. Furthermore, time irreversibility of the heartbeat data is demonstrated. We interpret these results as a strong evidence for nonlinear components in HRV. Thus R-R intervals from healthy persons contain more information than can be extracted by linear analysis in the time and frequency domain.

Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

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