ObjectiveThis study seeks to decompose QT variability (QTV) into physiological sources and assess their role for risk stratification in patients post myocardial infarction (MI). We hypothesize that the magnitude of QTV that cannot be explained by heart rate or respiration carries important prognostic information.BackgroundElevated beat-to-beat QTV is predictive of cardiac mortality, but the underlying mechanisms, and hence its interpretation, remain opaque.MethodsWe decomposed the QTV of 895 patients post MI into contributions by heart rate, respiration, and unexplained sources.ResultsCox proportional hazard analysis demonstrates that augmented oscillations in QTV and their level of dissociation from heart rate are associated with a higher 5-year mortality rate (18.4% vs. 4.7%, p < 0.0001). In patients with left ventricular ejection fraction (LVEF) > 35%, a higher QTV risk score was associated with a significantly higher 5-year mortality rate (16% vs. 4%, p < 0.0001). In patients with a GRACE score ≥ 120, a higher QTV risk score was associated with a significantly higher 5-year mortality (25% vs. 11%, p < 0.001).ConclusionAugmented oscillations in QTV and discordance from heart rate, possibly indicative of excessive sympathetic outflow to the ventricular myocardium, predict high risk in patients post MI independent from established risk markers.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT00196274.