Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial

David M MacDonald; Takudzwa Mkorombindo; Sharon X Ling; Selcuk Adabag; Richard Casaburi; John E Connett; Erika S Helgeson; Janos Porszasz; Harry B Rossiter; William W Stringer; Helen Voelker; Dongxing Zhao; Mark T Dransfield; Ken M Kunisaki

doi:10.15326/jcopdf.2021.0264

Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial

Chronic Obstr Pulm Dis. 2022 Apr 29;9(2):226-236. doi: 10.15326/jcopdf.2021.0264.

Authors

David M MacDonald^{1

2}, Takudzwa Mkorombindo³, Sharon X Ling⁴, Selcuk Adabag⁵, Richard Casaburi⁶, John E Connett⁴, Erika S Helgeson⁴, Janos Porszasz⁶, Harry B Rossiter⁶, William W Stringer⁶, Helen Voelker⁴, Dongxing Zhao⁷, Mark T Dransfield³, Ken M Kunisaki^{1

2}

Affiliations

¹ Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States.
² Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States.
³ Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, United States.
⁴ Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States.
⁵ Cardiology Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States.
⁶ Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States.
⁷ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Abstract

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD.

Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment.

Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV₁ ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group.

Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Keywords: BLOCK-COPD; acute exacerbation of COPD; autonomic nervous system; electrocardiogram; heart rate variability.

Abstract

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