Periodic repolarization dynamics: Different methods for quantifying low-frequency oscillations of repolarization.

BACKGROUND: Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that quantifies low-frequency (LF) instabilities of repolarization. PRD is a strong predictor of mortality in patients with ischaemic and non-ischaemic cardiomyopathy. Until recently, two methods for calculating PRD have been proposed. The wavelet analysis has been widely tested and quantifies PRD in deg2 units by application of continuous wavelet transformation (PRDwavelet). The phase rectified signal averaging method (PRDPRSA) is an algebraic method, which quantifies PRD in deg. units. The correlation, as well as a conversion formula between the two methods remain unknown. METHOD: The first step for quantifying PRD is to calculate the beat-to-beat change in the direction of repolarization, called dT°. PRD is subsequently quantified by means of either wavelet or PRSA-analysis. We simulated 1.000.000 dT°-signals. For each simulated signal we calculated PRD using the wavelet and PRSA-method. We calculated the ratio between PRDwavelet and PRDPRSA for different values of dT° and RR-intervals and applied this ratio in a real-ECG validation cohort of 455 patients after myocardial infarction (MI). We finally calculated the correlation coefficient between real and calculated PRDwavelet. PRDwavelet was dichotomized at the established cut-off value of ≥5.75 deg2. RESULTS: The ratio between PRDwavelet and PRDPRSA increased with increasing heart-rate and mean dT°-values (p < 0.001 for both). The correlation coefficient between PRDwavelet and PRDPRSA in the validation cohort was 0.908 (95% CI 0.891-0.923), which significantly (p < 0.001) improved to 0.945 (95% CI 0.935-0.955) after applying the formula considering the ratio between PRDwavelet and PRDPRSA obtained from the simulation cohort. The calculated PRDwavelet correctly classified 98% of the patients as low-risk and 87% of the patients as high-risk and correctly identified 97% of high-risk patients, who died within the follow-up period. CONCLUSION: This is the first analytical investigation of the different methods used to calculate PRD using simulated and clinical data. In this article we propose a novel algorithm for converting PRDPRSA to the widely validated PRDwavelet, which could unify the calculation methods and cut-offs for PRD.

Long-Term Microgravity Exposure Increases ECG Repolarization Instability Manifested by Low-Frequency Oscillations of T-Wave Vector.

Ventricular arrhythmias and sudden cardiac death during long-term space missions are a major concern for space agencies. Long-duration spaceflight and its ground-based analog head-down bed rest (HDBR) have been reported to markedly alter autonomic and cardiac functioning, particularly affecting ventricular repolarization of the electrocardiogram (ECG). In this study, novel methods are developed, departing from previously published methodologies, to quantify the index of Periodic Repolarization Dynamics (PRD), an arrhythmic risk marker that characterizes sympathetically-mediated low-frequency oscillations in the T-wave vector. PRD is evaluated in ECGs from 42 volunteers at rest and during an orthostatic tilt table test recorded before and after 60-day -6° HDBR. Our results indicate that tilt test, on top of enhancing sympathetic regulation of heart rate, notably increases PRD, both before and after HDBR, thus supporting previous evidence on PRD being an indicator of sympathetic modulation of ventricular repolarization. Importantly, long-term microgravity exposure is shown to lead to significant increases in PRD, both when evaluated at rest and, even more notably, in response to tilt test. The extent of microgravity-induced changes in PRD has been associated with arrhythmic risk in prior studies. An exercise-based, but not a nutrition-based, countermeasure is able to partially reverse microgravity-induced effects on PRD. In conclusion, long-term exposure to microgravity conditions leads to elevated low-frequency oscillations of ventricular repolarization, which are potentiated following sympathetic stimulation and are related to increased risk for repolarization instabilities and arrhythmias. Tested countermeasures are only partially effective in counteracting microgravity effects.