Abstract
Background Lung cancer survivors are at increased risk for autonomic dysfunction. We aimed to identify determinants of parasympathetic nervous system (PNS) function as reflected by heart rate recovery (HRR) and heart rate variability (HRV) in lung cancer survivors eligible for long-term cure.
Methods We performed a cross-sectional study of consecutive lung cancer survivors who completed curative-intent therapy for stage I-IIIA ≥1 month previously. We tested a comprehensive list of variables related to baseline demographics, comorbidities, lung cancer characteristics, and physiological/functional measures using univariable and multivariable (MVA) linear regression analyses. We defined HRR as the difference in heart rate (HR) at 1-minute following and the end of the six-minute walk test (6MWT), and HRV the standard deviation of normal-to-normal R-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine single 10-s electrocardiographs (ECGs).
Results In 69 participants, the mean (standard deviation, SD) HRR was -10.6 (6.7) beats. In MVAs, significant independent determinants of HRR [β (95% confidence interval)] were: age [0.17 (0.04, 0,30) for each year] and HR change associated with the 6MWT [0.01 (0.007, 0.02) for each beats/min. In 41 participants who had ECGs available for HRV measurements, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. In MVAs, significant determinants of HRV were: total lung capacity [0.01 (0.00, 0.02), p=0.047 for each % predicted] and HRR [-0.04 (-0.07, -0.003) for each beat] for natural logarithm (Ln-)SDNN; and [0.01 (0.00, 0.02)] and [-0.04 (-0.07, -0.01)] for Ln-rMSSD, respectively.
Conclusions We measured determinants of HRR and HRV in lung cancer survivors eligible for long-term cure. HRR and/or HRV may be useful as indicators to stratify patients in interventional studies aimed at improving PNS function in lung cancer survivors, including through exercise training.
- Abbreviations
- 6MWD
- six-minute walk distance
- 6MWT
- six-minute walk test
- AD
- autonomic dysfunction
- ANS
- autonomic nervous system
- ATS
- American Thoracic Society
- CAD
- coronary artery disease
- CI
- confidence interval
- COPD
- chronic obstructive pulmonary disease
- DLCO
- diffusion capacity of the lung for carbon monoxide
- DM
- diabetes mellitus
- ECG
- electrocardiograph
- FEV1
- forced expiratory volume in 1 second
- HR
- heart rate
- HRR
- heart rate recovery
- HRV
- heart rate variability
- MVA
- multivariable linear regression analysis
- NSCLC
- non-small cell lung cancer
- O2
- oxygen
- PAC
- premature atrial contraction
- PNS
- parasympathetic nervous system
- PVC
- premature ventricular contraction
- QoL
- quality of life
- rMSSD
- root mean square of successive differences
- RPE
- ratings of perceived exertion
- SDNN
- standard deviation of normal-to-normal R-R intervals
- TLC
- total lung capacity
- UVA
- univariable linear regression analysis
- VASDHS
- VA San Diego Healthcare System
Footnotes
Funding This work was supported by the American Cancer Society (PF-17-020-01-CPPB) and National Institutes of Health (1T32HL134632-01, from the NHLBI; and L30CA208950, from the National Cancer Institute).
Conflict of Interest Statement On behalf of all authors, the corresponding author states that there is no conflict of interest.
Ethical Standards Statement All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.