Spatial Correlation Between Myocyte's Repolarization Times and their Alternans Drives T-Wave Alternans on the ECG

Objective: T-wave alternans (TWA) manifests as beat-to-beat fluctuations of T-wave morphology on the electrocardiogram (ECG), with physiological bases not fully understood. Using a biophysical model of the ECG, we demonstrate and give explicit relations that TWA depends on the i) spatial covariance between myocytes' repolarization time and alternans; and ii) global alternans (common to every myocyte). Methods: We quantified the spatial covariance and global alternans by means of two new metrics, $\mathcal{R}$ index and $\bar{\delta}$, respectively. They were validated on both synthetic and real signals. Computerized simulations were generated using a biophysical model linking the action potentials with the surface ECG. Then, the metrics were computed in STAFF-III dataset, containing ECGs from patients who underwent coronary angioplasty with prolonged balloon inflations, and the time courses of the metrics were analyzed together with TWA measured on the surface ECG. Results: The metrics properly estimated the spatial covariance and global alternans in the synthetic data. In the STAFF-III dataset, the $\mathcal{R}$ index progressively increased from baseline to the fourth minute of inflation (median $\Delta \mathcal{R}=0.81$ ms; p$<$0.05), whereas $\bar{\delta}$ was mostly unaltered during the intervention ($\bar{\delta}=0$ ms). Conclusion: We reported, for the first time, that TWA is significantly driven by the myocyte's spatial covariance between their repolarization times and alternans, and not by global alternans, when TWA is generated by regional ischemia. Significance: The metrics may reveal new complementary insights into the mechanisms underlying TWA.