AimsTo test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation.Methods and resultsWe included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD.ConclusionIn post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.

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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...

Deceleration capacity is a strong and independent predictor of short-term mortality among patients admitted to a medical emergency department.