Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation

Abstract

Experimental and clinical studies have demonstrated that enhanced sympathetic autonomic nervous system (SANS) activity can destabilise myocardial repolarisation, 1-4 increasing vulnerability to developing fatal cardiac arrhythmias. [5][6][7][8] Accordingly, assessment of SANS activity has always been a major goal for cardiac risk stratification methods.Various non-invasive methods including assessment of heart rate variability (HRV) and baroreflex sensitivity have been employed to study the activity of the SANS under routine clinical conditions. 9 These methods are based on two principles. First, activation of the SANS evokes physiological effects on the cardiovascular system, such as acceleration of heart rate, increased vasomotor tone or systolic contractility.4 Second, as SANS activity is clustered in low-frequency bursts, SANS-induced physiological responses are likely to exhibit low-frequency dynamics. [10][11][12][13][14] Previous studies have shown that SANS assessment based on HRV and baroreflex sensitivity is a marker of increased vulnerability to fatal cardiac arrhythmias. 15,16 However, both methods are limited by the fact that they only provide an indirect probe of the sympathetic effect on cardiac repolarisation, as they reflect influences on the sinoatrial node and blood vessels and not on the ventricular myocardium. In addition, both HRV and baroreflex sensitivity are confounded by the concomitant action of other systems exhibiting periodic dynamics, such as the parasympathetic nervous system and the renin-angiotensinaldosterone system, respectively.We proposed a novel approach to SANS assessment that substantially differs from previous methods.17 So-called periodic repolarisation dynamics (PRD) evaluates sympathetic activity-associated lowfrequency periodic changes of cardiac repolarisation instability and opens new perspectives for identifying high-risk patients, who would potentially benefit from prophylactic interventions. The first section of this review briefly depicts the methodology of PRD assessments.The second section focuses on potential mechanisms of PRD. In the third section, the clinical application of PRD as risk predictor after myocardial infarction (MI) is presented. In the fourth section, we present an alternative method for PRD assessment, which provides some technical advantages over the standard method. The final sections are dedicated to ongoing and future projects aimed at developing individualised treatment strategies. Methodology of Periodic Repolarisation Dynamics AssessmentPRD is typically assessed using a high-resolution ECG recorded in or converted to the three orthogonal axes X, Y and Z ('Frank lead configuration'). As low-frequency patterns are of interest, the recording AbstractPeriodic repolarisation dynamics (PRD) refers to low-frequency (≤0.1Hz) modulations of cardiac repolarisation instability. Spontaneous PRD can be assessed non-invasively from 3D high-resolution resting ECGs. Physiological and experimental studies have indicated that PRD correlates with effere...

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

“…This study aimed at investigating alterations in ventricular repolarization associated with long-term exposure to simulated microgravity conditions elicited by 60-day HDBR. Two methods have been developed for quantification of low-frequency oscillations in the T-wave of the ECG, departing from the original methodology proposed in Rizas et al (2014Rizas et al ( , 2016. These methods, one using CWT and the other one using PRSA, have been shown to render concordant results in terms of the index of Periodic Repolarization Dynamics, PRD, a marker of lowfrequency repolarization oscillations whose increase has been shown to be predictor of ventricular arrhythmias and sudden cardiac death (Rizas et al, 2014(Rizas et al, , 2016.…”

“…Two different methods, based on Continuous Wavelet Transform (CWT) and Phase-Rectified Signal Averaging (PRSA), respectively, were developed based on the initial methodology proposed in Rizas et al (2014Rizas et al ( , 2016). These methods were tested for quantification of the low-frequency components of the beat-to-beat dT • series.…”

“…An index of Periodic Repolarization Dynamics (PRD) has been recently proposed to assess sympathetic modulation of ventricular repolarization by measuring low-frequency (below 0.1 Hz) oscillations in the Twave vector (Rizas et al, 2014). PRD accounts for variability not limited to a specific time interval, as the QT interval or the T-peak-to-T-end interval, but more generally integrating all the spatio-temporal information in the T-wave vector, which can allow for a more robust characterization of beat-to-beat repolarization variations and can provide a better marker to anticipate electrical instabilities (Rizas et al, 2014(Rizas et al, , 2016.…”

“…PRD is hypothesized to be able to characterize the effects of sustained simulated microgravity on ventricular repolarization, particularly in response to an orthostatic Tilt-Table Test (TTT), a common procedure used to assess autonomic nervous system function (Zygmunt and Stanczyk, 2010). To overcome identified issues related to angle quantification as part of the PRD technique, a number of updates on the originally reported methods (Rizas et al, 2014(Rizas et al, , 2016 are also proposed. Additionally, the effectiveness of two different countermeasures, based on exercise and nutrition, to mitigate or reduce microgravity-induced effects on ventricular repolarization during HDBR are assessed.…”

Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular Repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis

“…Ventricular repolarization has been shown to exhibit a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity. In humans, this has been demonstrated by quantification of so-called periodic repolarization dynamics in the T-wave vector of the electrocardiogram (ECG) (Rizas et al, 2014(Rizas et al, , 2016 as well as by in vivo evaluation of LF components in activation recovery intervals (ARI) of ventricular electrograms (Hanson et al, 2014;Porter et al, 2018). In post-infarction patients, an increased magnitude of LF oscillations in ECG repolarization has been proved to be a significant predictor of total mortality and sudden cardiac death (Rizas et al, 2017).…”