Intra- and Inter-Rater Reliability of Linear and Nonlinear Measures of Short-Term Heart Rate Variability Following Combat-Related Traumatic Injury.

BACKGROUND: Heart rate variability (HRV) is a marker of autonomic function. However, the reliability of short-term HRV measurement in individuals with combat-related traumatic injury (CRTI) remains undetermined. METHODS: An intra- and inter-rater reliability study was conducted using a subsample (n = 35) of British servicemen with CRTI enrolled in the ongoing ADVANCE study. A five-minute epoch of single-lead electrocardiogram data collected during spontaneous breathing was used to measure HRV. HRV analyses were independently performed by two examiners using Kubios. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC), and coefficient of variance were calculated for linear [root mean square of successive difference (RMSSD), standard deviation of NN interval, low-frequency, high-frequency, total power] and nonlinear (SD1-2, acceleration and deceleration capacities, sample entropy) measures. Bland-Altman %plots were used to assess bias in intra- and inter-rater HRV data. RESULTS: The mean age of participants was 39.3 ± 6.3 years. An excellent ICC score of 0.9998 (95% CI 0.9997, 0.9999) was observed for intra-rater analyses of RMSSD, and similar excellent ICC scores were seen for all other HRV measures. The inter-rater reliability analyses produced an excellent ICC score (range 0.97-1.00). Comparatively, frequency-domain measures produced higher MDC% and SEM% scores than time-domain and nonlinear measures in both inter- and intra-rater analyses. The Bland-Altman plots revealed relatively higher bias for frequency-domain and nonlinear measures than time-domain measures. CONCLUSION: ECG-related short-term HRV measures were reliable in injured servicemen under spontaneous breathing. However, the reliability appeared better with the time-domain measure than frequency-domain and nonlinear measures in this sample.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

Exploratory analysis of spontaneous versus paced breathing on heart rate variability in veterans with combat-related traumatic injury.

BACKGROUND: Respiration is a crucial determinant of autonomic balance and heart rate variability (HRV). The comparative effect of spontaneous versus paced breathing on HRV has been almost exclusively explored in healthy adults and never been investigated in an injured military cohort. OBJECTIVE: To examine the effect of spontaneous versus paced breathing on HRV in veterans with combat-related traumatic injury (CRTI). DESIGN: Observational cohort study. SETTING: ArmeD serVices trAuma rehabilitatioN outComE (ADVANCE) study, Stanford Hall, UK. PARTICIPANTS: The sample consisted of 100 randomly selected participants who sustained CRTI (eg, amputation) during their deployment (Afghanistan 2003-2014) and were recruited into the ongoing ADVANCE prospective cohort study. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: HRV was recorded using a single-lead ECG. HRV data were acquired during a sequential protocol of 5-minute spontaneous breathing followed immediately by 5 minutes of paced breathing (six cycles/minute) among fully rested and supine participants. HRV was reported using time domain (root mean square of successive differences), frequency domain (low frequency and high frequency) and nonlinear (sample entropy) measures. The agreement between HRV during spontaneous versus paced breathing was examined using the Bland-Altman analysis. RESULTS: The mean age of participants was 36.5 ± 4.6 years. Resting respiratory rate was significantly higher with spontaneous versus paced breathing (13.4 ± 3.4 vs. 7.6 ± 2.0 breaths/minute; p < .001), respectively. Resting mean heart rate and root mean square of successive differences were significantly higher with paced breathing than spontaneous breathing (p < .001). Paced breathing significantly increased median low frequency power than spontaneous breathing (p < .001). No significant difference was found in the absolute power of high frequency between the two breathing protocols. The Bland-Altman analysis revealed poor agreement between HRV values during spontaneous and paced breathing conditions with wide limits of agreement. CONCLUSION: Slow-paced breathing leads to higher HRV than spontaneous breathing and could overestimate resting "natural-state" HRV.

The Influence of Physical and Mental Health Mediators on the Relationship Between Combat-Related Traumatic Injury and Ultra-Short-Term Heart Rate Variability in a U.K. Military Cohort: A Structural Equation Modeling Approach.

INTRODUCTION: Combat-related traumatic injury (CRTI) adversely affects heart rate variability (HRV). The mediating effect of mental and physical health factors on the relationship between CRTI, its severity and HRV has not been previously studied and investigated. MATERIALS AND METHODS: A cross-sectional mediation analysis of the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study was performed. The sample consisted of injured and uninjured British male servicemen who were frequency-matched based on their age, rank, role-in-theater, and deployment to Afghanistan (2003-2014). CRTI and injury severity (the New Injury Severity Scores [NISS] [NISS < 25 and NISS ≥ 25]) were included as exposure variables. HRV was quantified using the root mean square of successive differences (RMSSD) obtained using pulse waveform analysis. Depression and anxiety mediators were quantified using the Patient Health Questionnaire and Generalized Anxiety Disorder, respectively. Body mass index and the 6-minute walk test (6MWT) represented physical health measures. Two mediation pathways between exposure and outcome variables were examined in comparison with the uninjured group using structural equation modeling. RESULTS: Of 862 servicemen, 428 were injured and 434 were uninjured with the mean age at assessment of 33.9 ± 5.4 (range 23-59) years. Structural equation modeling revealed that depression, anxiety, and body mass index did not significantly mediate the relationship between injury/injury severity and RMSSD. However, the 6MWT significantly mediated the relationship between CRTI and RMSSD (27% mediation). The indirect effect of 6MWT on the relationship between injury severity (NISS ≥ 25 vs. uninjured) and RMSSD was -0.06 (95% CI: -0.12, -0.00, P < .05). CONCLUSIONS: The findings suggest that greater physical function may improve HRV following CRTI. Longitudinal studies are warranted to further validate these findings.

Reliability of carotid-femoral arterial waveforms for the derivation of ultra-short term heart rate variability in injured British servicemen: An inter-rater reliability study.

In this study, the comparative precision of carotid versus femoral arterial waveforms to measure ultra-short term heart rate variability (HRVUST) following traumatic injury was investigated for the first time. This was an inter-rater reliability study of 50 British servicemen (aged 23-44 years) with non-acute combat-related traumatic injury (CRTI). Paired continuous arterial waveform data for HRVUST analysis, were simultaneously sampled at the carotid and femoral arterial sites (14-16 seconds) during pulse wave velocity (PWV) measurement. HRVUST was reported as the root mean square of the successive differences (RMSSD). Following the determination of the superior sampling site (carotid versus femoral), the blinded inter-rater agreement in RMSSD for the preferred site was quantified using the Intra-class Correlation Coefficient (ICC) and the Bland-Altman plot. The mean age of participants was 34.06±4.88 years. The femoral site was superior to the carotid site with a significantly higher number of reliable signals obtained (Fisher's Exact test; p<0.001). The inter-rater agreement in femoral-derived RMSSD was excellent [ICC 0.99 (95%CI: 0.994-0.997)] with a moderate level of agreement (mean difference [bias]: 0.55; 95% CI: -0.13-1.24 ms). In this study, we demonstrated that the femoral artery is a more reliable site than the carotid artery for HRVUST measurement and post-trauma risk stratification following CRTI.

Relationship between combat-related traumatic injury and ultrashort term heart rate variability in a UK military cohort: findings from the ADVANCE study.

INTRODUCTION: Combat-related traumatic injury (CRTI) has been linked to an increased cardiovascular disease (CVD) risk. The long-term impact of CRTI on heart rate variability (HRV)-a robust CVD risk marker-has not been explored. This study investigated the relationship between CRTI, the mechanism of injury and injury severity on HRV. METHODS: This was an analysis of baseline data from the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study. The sample consisted of UK servicemen with CRTI sustained during deployment (Afghanistan, 2003-2014) and an uninjured comparison group who were frequency matched to the injured group based on age, rank, deployment period and role in theatre. Root mean square of successive differences (RMSSD) was measured as a measure of ultrashort term HRV via <16 s continuous recording of the femoral arterial pulse waveform signal (Vicorder). Other measures included injury severity (New Injury Severity Scores (NISS)) and injury mechanism. RESULTS: Overall, 862 participants aged 33.9±5.4 years were included, of whom 428 (49.6%) were injured and 434 (50.3%) were uninjured. The mean time from injury/deployment to assessment was 7.91±2.05 years. The median (IQR) NISS for those injured was 12 (6-27) with blast being the predominant injury mechanism (76.8%). The median (IQR) RMSSD was significantly lower in the injured versus the uninjured (39.47 ms (27.77-59.77) vs 46.22 ms (31.14-67.84), p<0.001). Using multiple linear regression (adjusting for age, rank, ethnicity and time from injury), geometric mean ratio (GMR) was reported. CRTI was associated with a 13% lower RMSSD versus the uninjured group (GMR 0.87, 95% CI 0.80-0.94, p<0.001). A higher injury severity (NISS ≥25) (GMR 0.78, 95% CI 0.69-0.89, p<0.001) and blast injury (GMR 0.86, 95% CI 0.79-0.93, p<0.001) were also independently associated with lower RMSSD. CONCLUSION: These results suggest an inverse association between CRTI, higher severity and blast injury with HRV. Longitudinal studies and examination of potential mediating factors in this CRTI-HRV relationship are needed.

Association between non-acute Traumatic Injury (TI) and Heart Rate Variability (HRV) in adults: A systematic review and meta-analysis.

Heart rate variability (HRV) is a non-invasive measure of autonomic function. The relationship between unselected long-term traumatic injury (TI) and HRV has not been investigated. This systematic review examines the impact of non-acute TI (>7 days post-injury) on standard HRV indices in adults. Four electronic databases (CINAHL, Medline, Scopus, and Web of Science) were searched. The quality of studies, risk of bias (RoB), and quality of evidence (QoE) were assessed using Axis, RoBANS and GRADE, respectively. Using the random-effects model, mean difference (MD) for root mean square of successive differences (RMSSD) and standard deviation of NN-intervals (SDNN), and standardized mean difference (SMD) for Low-frequency (LF): High-Frequency (HF) were pooled in RevMan guided by the heterogeneity score (I2). 2152 records were screened followed by full-text retrieval of 72 studies. 31 studies were assessed on the inclusion and exclusion criteria. Only four studies met the inclusion criteria. Three studies demonstrated a high RoB (mean RoBANS score 14.5±3.31) with a low QoE. TI was associated with a significantly higher resting heart rate. Meta-analysis of three cross-sectional studies demonstrated a statistically significant reduction in RMSSD (MD -8.45ms, 95%CI-12.78, -4.12, p<0.0001) and SDNN (MD -9.93ms, 95%CI-14.82, -5.03, p<0.0001) (low QoE) in participants with TI relative to the uninjured control. The pooled analysis of four studies showed a higher LF: HF ratio among injured versus uninjured (SMD 0.20, 95%CI 0.01-0.39, p<0.04) (very low QoE). Albeit low QoE, non-acute TI is associated with attenuated HRV indicating autonomic imbalance. The findings might explain greater cardiovascular risk following TI. Trial registration PROSPERO registration number: CRD: CRD42021298530.

Association between non-acute traumatic injury (TI) and heart rate variability (HRV) in adults: A systematic review protocol.

Heart Rate Variability (HRV) is an indirect measure of autonomic function. Attenuated HRV is linked to worsening health outcomes including Major Adverse Cardiovascular Events (MACE). The relationship between traumatic injury (TI) and HRV has been limitedly studied. This research protocol has been designed to conduct a systematic review of the existing evidence on the association between non-acute TI and HRV in adults. Four electronic bibliographic databases (Web of Science, CINAHL, Medline, and Scopus) will be searched. The studies on non-acute (>7 days post injury) TI and HRV in adults will be included, followed by title-abstract screening by two reviewers independently. The quality and risk of bias of the included studies will be assessed using Axis and a six-item Risk of Bias Assessment tool for of Non-randomized Studies (RoBANS) respectively. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will assess the quality of evidence. The extracted data will be synthesized using narrative syntheses and a Forest plot with or without meta-analysis- whichever permitted by the pooled data. This will be the first systematic review to examine the relationship between generalized TI and HRV in adults. Trial registration: (PROPSERO registration number: CRD: CRD42021298530) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021298530.