Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation

Peter Hämmerle, Christian Eick, Sven Poli, Steffen Blum, Vincent Schlageter, Axel Bauer, Konstantinos D Rizas, Ceylan Eken, Michael Coslovsky, Stefanie Aeschbacher, Philipp Krisai, Pascal Meyre, Jens Wuerfel, Tim Sinnecker, Jean-Marc Vesin, Jürg H Beer, Giorgio Moschovitis, Leo H Bonati, Christian Sticherling, David Conen, Stefan Osswald, Michael Kühne, Christine S Zuern, Peter Hämmerle, Christian Eick, Sven Poli, Steffen Blum, Vincent Schlageter, Axel Bauer, Konstantinos D Rizas, Ceylan Eken, Michael Coslovsky, Stefanie Aeschbacher, Philipp Krisai, Pascal Meyre, Jens Wuerfel, Tim Sinnecker, Jean-Marc Vesin, Jürg H Beer, Giorgio Moschovitis, Leo H Bonati, Christian Sticherling, David Conen, Stefan Osswald, Michael Kühne, Christine S Zuern

Abstract

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03-2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) -0.47 (-0.84; -0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment. Clinical Trials Gov Identifier: NCT02105844.

Keywords: HRV triangular index; atrial fibrillation; autonomic dysfunction; heart rate variability; silent brain infarct.

Conflict of interest statement

CSZ reports a research grant from Medtronic and honoraria from Vifor Pharma and Novartis. MK has received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, Daiichi-Sankyo, Bayer, and Pfizer-BMS and lecture/consulting fees from Daiichi-Sankyo, Boehringer Ingelheim, Bayer, Pfizer-BMS, AstraZeneca, Sanofi-Aventis, Novartis, MSD, Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sorin, Zoll and Biosense Webster. PK is supported by the University of Basel, the Mach-Gaensslen foundation and the Bangerter-Rhyner foundation. SP received research grants from Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, and speakers' honoraria and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo and Werfen. JW is CEO of the Medical Image Analysis Center, Basel; has served on advisory boards for Actelion, Biogen, Genzyme-Sanofi, Novartis, Roche, and the Guthy Jackson Charitable Foundation; has received research grants from Novartis; has received speaker honoraria from Bayer, Biogen, Genzyme, Novartis, and Teva. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Hämmerle, Eick, Poli, Blum, Schlageter, Bauer, Rizas, Eken, Coslovsky, Aeschbacher, Krisai, Meyre, Wuerfel, Sinnecker, Vesin, Beer, Moschovitis, Bonati, Sticherling, Conen, Osswald, Kühne and Zuern.

Figures

Figure 1
Figure 1
Flow chart of patient selection.
Figure 2
Figure 2
Volumes of silent brain infarcts in the sinus rhythm group (left) and in the atrial fibrillation group (right, exploratory analysis) stratified by heart rate variability triangular index (HRVI).
Figure 3
Figure 3
Impairment of heart rate variability triangular index (HRVI) according silent brain infarct topography.

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