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Strong recent clinical evidence links the presence of prominent oscillations of ventricular repolarization in the low-frequency range (0.04-0.15 Hz) to the incidence of ventricular arrhythmia and sudden death in post-MI patients and patients with ischaemic and non-ischaemic cardiomyopathy. It has been proposed that these oscillations reflect oscillations of ventricular action potential duration at the sympathetic nerve frequency. Here we review emerging evidence to support that contention and provide insight into possible underlying mechanisms for this association., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Recent clinical, experimental and modeling studies link oscillations of ventricular repolarization in the low frequency (LF) (approx. 0.1 Hz) to arrhythmogenesis. Sympathetic provocation has been shown to enhance both LF oscillations of action potential duration (APD) and beat-to-beat variability (BVR) in humans. We hypothesized that beta-adrenergic blockade would reduce LF oscillations of APD and BVR of APD in humans and that the two processes might be linked., Methods and Results: Twelve patients with normal ventricles were studied during routine electrophysiological procedures. Activation-recovery intervals (ARI) as a conventional surrogate for APD were recorded from 10 left and 10 right ventricular endocardial sites before and after acute beta-adrenergic adrenergic blockade. Cycle length was maintained constant with right ventricular pacing. Oscillatory behavior of ARI was quantified by spectral analysis and BVR as the short-term variability. Beta-adrenergic blockade reduced LF ARI oscillations (8.6 ± 4.5 ms 2 vs. 5.5 ± 3.5 ms 2 , p = 0.027). A significant correlation was present between the initial control values and reduction seen following beta-adrenergic blockade in LF ARI ( r s = 0.62, p = 0.037) such that when initial values are high the effect is greater. A similar relationship was also seen in the beat-to beat variability of ARI ( r s = 0.74, p = 0.008). There was a significant correlation between the beta-adrenergic blockade induced reduction in LF power of ARI and the witnessed reduction of beat-to-beat variability of ARI ( r s = 0.74, p = 0.01). These clinical results accord with recent computational modeling studies which provide mechanistic insight into the interactions of LF oscillations and beat-to-beat variability of APD at the cellular level., Conclusion: Beta-adrenergic blockade reduces LF oscillatory behavior of APD (ARI) in humans in vivo . Our results support the importance of LF oscillations in modulating the response of BVR to beta-adrenergic blockers, suggesting that LF oscillations may play role in modulating beta-adrenergic mechanisms underlying BVR., (Copyright © 2020 Van Duijvenboden, Porter, Pueyo, Sampedro-Puente, Fernandez-Bes, Sidhu, Gould, Orini, Bishop, Hanson, Lambiase, Razavi, Rinaldi, Gill and Taggart.)

Impaired capacity to increase heart rate (HR) during exercise (ΔHR ex ), and a reduced rate of recovery post-exercise (ΔHR rec ) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHR ex and ΔHR rec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHR ex and ΔHR rec , respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHR ex and nine for ΔHR rec are genome-wide significant (P ≤ 5 × 10 -8 ). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.