Publications by authors named "Christophe Herry"

42 Publications

Fetal Cardiovascular Decompensation During Labor Predicted From the Individual Heart Rate Tracing: A Machine Learning Approach in Near-Term Fetal Sheep Model.

Front Pediatr 2021 5;9:593889. Epub 2021 May 5.

Department of Obstetrics and Gynecology and Center on Human Development and Disability, University of Washington, Seattle, WA, United States.

When exposed to repetitive umbilical cord occlusions (UCO) with worsening acidemia, fetuses eventually develop cardiovascular decompensation manifesting as pathological hypotensive arterial blood pressure (ABP) responses to fetal heart rate (FHR) decelerations. Failure to maintain cardiac output during labor is a key event leading up to brain injury. We reported that the timing of the event when a fetus begins to exhibit this cardiovascular phenotype is highly individual and was impossible to predict. We hypothesized that this phenotype would be reflected in the individual behavior of heart rate variability (HRV) as measured by root mean square of successive differences of R-R intervals (RMSSD), a measure of vagal modulation of HRV, which is known to increase with worsening acidemia. This is clinically relevant because HRV can be computed in real-time intrapartum. Consequently, we aimed to predict the individual timing of the event when a hypotensive ABP pattern would emerge in a fetus from a series of continuous RMSSD data. Fourteen near-term fetal sheep were chronically instrumented with vascular catheters to record fetal arterial blood pressure, umbilical cord occluder to mimic uterine contractions occurring during human labor and ECG electrodes to compute the ECG-derived HRV measure RMSSD. All animals were studied over a ~6 h period. After a 1-2 h baseline control period, the animals underwent mild, moderate, and severe series of repetitive UCO. We applied the recently developed machine learning algorithm to detect physiologically meaningful changes in RMSSD dynamics with worsening acidemia and hypotensive responses to FHR decelerations. To mimic clinical scenarios using an ultrasound-based 4 Hz FHR sampling rate, we recomputed RMSSD from FHR sampled at 4 Hz and compared the performance of our algorithm under both conditions (1,000 Hz vs. 4 Hz). The RMSSD values were highly non-stationary, with four different regimes and three regime changes, corresponding to a baseline period followed by mild, moderate, and severe UCO series. Each time series was characterized by seemingly randomly occurring (in terms of timing of the individual onset) increase in RMSSD values at different time points during the moderate UCO series and at the start of the severe UCO series. This event manifested as an increasing trend in RMSSD values, which counter-intuitively emerged as a period of relative stationarity for the time series. Our algorithm identified these change points as the individual time points of cardiovascular decompensation with 92% sensitivity, 86% accuracy and 92% precision which corresponded to 14 ± 21 min before the visual identification. In the 4 Hz RMSSD time series, the algorithm detected the event with 3 times earlier detection times than at 1,000 Hz, i.e., producing false positive alarms with 50% sensitivity, 21% accuracy, and 27% precision. We identified the overestimation of baseline FHR variability by RMSSD at a 4 Hz sampling rate to be the cause of this phenomenon. The key finding is demonstration of FHR monitoring to detect fetal cardiovascular decompensation during labor. This validates the hypothesis that our HRV-based algorithm identifies individual time points of ABP responses to UCO with worsening acidemia by extracting change point information from the physiologically related fluctuations in the RMSSD signal. This performance depends on the acquisition accuracy of beat to beat fluctuations achieved in trans-abdominal ECG devices and fails at the sampling rate used clinically in ultrasound-based systems. This has implications for implementing such an approach in clinical practice.
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http://dx.doi.org/10.3389/fped.2021.593889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132964PMC
May 2021

Machine learning model on heart rate variability metrics identifies asymptomatic toddlers exposed to zika virus during pregnancy.

Physiol Meas 2021 Jun 17;42(5). Epub 2021 Jun 17.

Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States of America.

. Although the Zika virus (ZIKV) seems to be prominently neurotropic, there are some reports of involvement of other organs, particularly the heart. Of special concern are those children exposed prenatally to ZIKV and born without microcephaly or other congenital anomalies. Electrocardiogram (ECG)-derived heart rate variability (HRV) metrics represent an attractive, low-cost, widely deployable tool for early identification of developmental functional alterations in exposed children born without such overt clinical symptoms. We hypothesized that HRV in such children would yield a biomarker of fetal ZIKV exposure. Our objective was to test this hypothesis in young children exposed to ZIKV during pregnancy.. We investigated the HRV properties of 21 children aged 4-25 months from Brazil. The infants were divided into two groups, the ZIKV-exposed ( = 13) and controls ( = 8). Single-channel ECG was recorded in each child at ∼15 months of age and HRV was analyzed in 5 min segments to provide a comprehensive characterization of the degree of variability and complexity of the heart rate.Using a cubic support vector machine classifier we identified babies as Zika cases or controls with a negative predictive value of 92% and a positive predictive value of 86%. Our results show that a machine learning model derived from HRV metrics can help differentiate between ZIKV-affected, yet asymptomatic, and non-ZIKV-exposed babies. We identified the box count as the best HRV metric in this study allowing such differentiation, regardless of the presence of microcephaly.We show that it is feasible to measure HRV in infants and toddlers using a small non-invasive portable ECG device and that such an approach may uncover the memory ofexposure to ZIKV. We discuss putative mechanisms. This approach may be useful for future studies and low-cost screening tools involving this challenging to examine population.
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http://dx.doi.org/10.1088/1361-6579/ac010eDOI Listing
June 2021

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers.

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Departments of Critical Care Medicine and Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ∼48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (∼50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.
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http://dx.doi.org/10.1016/j.jtct.2021.04.023DOI Listing
May 2021

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

N Engl J Med 2021 01;384(4):345-352

From the Children's Hospital of Eastern Ontario (S.D.), Children's Hospital of Eastern Ontario Research Institute (S.D., L.H., A. van Beinum, M.H., H.T.), Faculty of Medicine (S.D.) and Centre for Health Law, Policy, and Ethics (J.A.C.), University of Ottawa, Canadian Blood Services (L.H., S.D.S.), Carleton University (A. van Beinum), the Dynamical Analysis Lab (N.B.S., C.H., A.S.), Clinical Epidemiology Program (N.B.S., C.H., A.S.), and Clinical Epidemiology Program Methods Centre (T.R.), Ottawa Hospital Research Institute, the Departments of Critical Care and General Surgery (G.P.) and Surgery (A.S.) and Division of Thoracic Surgery (A.S.), Ottawa Hospital, and Interventional Cardiology Program, University of Ottawa Heart Institute (D. So), Ottawa, the Department of Critical Care, Trauma and Neurosurgery Program, St. Michael's Hospital (A. Baker), Li Ka Shing Knowledge Institute, Unity Health-St. Michael's Hospital (J.O.F., D. Scales), University of Toronto (J.O.F.), Mount Sinai Hospital (S.M., L.M.) and Interdepartmental Division of Critical Care Medicine (S.M., L.M., D. Scales), University of Toronto, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre (D. Scales), and the Canadian Donation and Transplantation Research Program (H.T.), Toronto, the Departments of Critical Care and Anesthesia, Dalhousie University, Halifax, NS (S.B.), the Departments of Medicine and Critical Care Medicine, Queen's University, Kingston, ON (J.G.B., D.M.M.), the Department of Medicine (Critical Care), Research Centre of the University of Montreal Hospital (M.C.), the Department of Critical Care, Division of Pulmonary Medicine, McGill University (J.S.), McGill University Health Centre and Research Institute (J.S., S.D.S.), Transplant Québec (M.W.), and the Division of Critical Care, Montreal Children's Hospital (S.D.S.), Montreal, the Department of Anesthesiology, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Sherbrooke, Sherbrooke, QC (F. D'Aragon), the Departments of Critical Care Medicine, Community Health Sciences, and Medicine, Cumming School of Medicine (C.J.D.), and the Departments of Critical Care Medicine and Clinical Neurosciences (A.H.K.), University of Calgary, and Calgary Zone, Alberta Health Services (C.J.D.), Calgary, the Department of Clinical Neurological Sciences, London Health Sciences Centre (T.G.), Schulich School of Medicine and Dentistry (T.G.), the Department of Psychology, King's University College (L.N.), and the Department of Medicine and the Brain and Mind Institute (M. Slessarev), Western University, London, ON, the Division of Critical Care, Departments of Medicine and Anesthesia, University of British Columbia, Vancouver (G.I.), the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton (D.J.K.), the Department of Medicine, McMaster University, and Hamilton Health Sciences Centre, Hamilton, ON (M.M.), and the Division of Pediatric Intensive Care, CHU de Québec, Centre Mère-Enfant Soleil, and the Department of Pediatrics, Faculté de Médecine, Université Laval, Quebec City, QC (M.W.) - all in Canada; Safar Center for Resuscitation Research, Critical Care Medicine Department, University of Pittsburgh School of Medicine, Pittsburgh (C.D.); Charles University, Third Faculty of Medicine and FNKV University Hospital (F. Duska, M. Schmidt, P.W.), and the Department of Palliative Medicine, First Faculty of Medicine, Charles University and General University Hospital (K.R.), Prague, Czech Republic; NHS Blood and Transplant, Bristol (D.G., D.H.), and Adult Critical Care, Nottingham University Hospitals NHS Trust, Nottingham (D.G., D.H.) - both in the United Kingdom; and the Department of Intensive Care Medicine, Maastricht University Medical Center, and the School of Health Professions Education, Maastricht University (W.N.K.A.M.), and the Heart and Vascular Center, Maastricht University Medical Center (J.T.W.), Maastricht, the Netherlands.

Background: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied.

Methods: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity.

Results: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients.

Conclusions: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).
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http://dx.doi.org/10.1056/NEJMoa2022713DOI Listing
January 2021

Multimodal pathophysiological dataset of gradual cerebral ischemia in a cohort of juvenile pigs.

Sci Data 2021 01 7;8(1). Epub 2021 Jan 7.

Institute of Molecular Cell Biology, Jena University Hospital, Jena, Germany.

Ischemic brain injuries are frequent and difficult to detect reliably or early. We present the multi-modal data set containing cardiovascular (blood pressure, blood flow, electrocardiogram) and brain electrical activities to derive electroencephalogram (EEG) biomarkers of corticothalamic communication under normal, sedation, and hypoxic/ischemic conditions with ensuing recovery. We provide technical validation using EEGLAB. We also delineate the corresponding changes in the electrocardiogram (ECG)-derived heart rate variability (HRV) with the potential for future in-depth analyses of joint EEG-ECG dynamics. We review an open-source methodology to derive signatures of coupling between the ECoG and electrothalamogram (EThG) signals contained in the presented data set to better characterize the dynamics of thalamocortical communication during these clinically relevant states. The data set is presented in full band sampled at 2000 Hz, so the additional potential exists for insights from the full-band EEG and high-frequency oscillations under the bespoke experimental conditions. Future studies on the dataset may contribute to the development of new brain monitoring technologies, which will facilitate the prevention of neurological injuries.
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http://dx.doi.org/10.1038/s41597-020-00781-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791136PMC
January 2021

Effect of exercise-heat acclimation on cardiac autonomic modulation in type 2 diabetes: a pilot study.

Appl Physiol Nutr Metab 2021 Mar 17;46(3):284-287. Epub 2020 Nov 17.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

The effects of exercise-heat acclimation on heart rate variability (HRV) in individuals with type 2 diabetes (T2D) remains unclear. We assessed electrocardiogram recordings during exercise-heat stress in middle-aged-to-older individuals (50-70 years) with ( = 6) and without (control;  = 8;) T2D, before and after 7 days of exercise-heat acclimation. Exercising heart rate was reduced (control, -9 ± 5 bpm; T2D, -14 ± 9 bpm) yet HRV was not significantly different. Given the negative correlations between diminished HRV and cardiac risk observed in the scientific literature, further research is warranted. Our observations indicate that 7 days exercise-heat acclimation may not effectively attenuate the deviation toward reduced overall HRV and unfavourable cardiac autonomic modulation in individuals with T2D.
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http://dx.doi.org/10.1139/apnm-2020-0785DOI Listing
March 2021

Variability Predictors of Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study.

Can J Neurol Sci 2021 03 20;48(2):226-232. Epub 2020 Jul 20.

Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.

Background: Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not.

Methods: Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003-0.040 Hz), low (0.040-0.150 Hz), and high-frequency (0.15-0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics.

Results: We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not.

Conclusions: A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.
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http://dx.doi.org/10.1017/cjn.2020.157DOI Listing
March 2021

Heart rate variability in older workers during work under the Threshold Limit Values for heat exposure.

Am J Ind Med 2020 09 16;63(9):787-795. Epub 2020 Jul 16.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Canada.

Background: The Threshold Limit Values (TLV) of the American Conference of Governmental and Industrial Hygienists indicate the levels of heat stress that all workers may be repeatedly exposed to without adverse health effects. In this study, we evaluated heart rate variability (HRV) during moderate-to-heavy work performed continuously or according to different TLV work-rest (WR) allocations in healthy physically active older workers.

Methods: Nine healthy older (58 ± 5 years) males performed three different 120-minute conditions in accordance with TLV guidelines for moderate-to-heavy intensity work (360 W fixed rate of heat production) in different wet-bulb globe temperatures (WBGT): continuous cycling at 28°C WBGT (CON), as well as intermitted work performed at WR of 3:1 in 29°C WBGT (WR3:1), and at WR of 1:1 at 30°C (WR1:1). Rectal temperature and HRV (3-lead electrocardiogram [ECG]) were assessed throughout.

Results: Coefficient of Variation, Poincaré SD2, and Shannon Entropy were decreased during the CON compared with the WR3:1 when core temperature exceeded 38°C and after 1 hour of continuous work (P < .05). Also, 4 of the 12 HRV indices studied were reduced at CON compared with WR1:1 after 2 hours of accumulated work time (P < .05). Participants worked longer before core temperature reached 38°C during the WR1:1 and the WR3:1, compared with CON (P < .05).

Conclusions: Incorporating breaks during moderate-to-heavy work in the heat for older adults can reduce autonomic stress and prolong the work performed at safe core temperature levels. The TLV WR1:1 provides increased cardiac protection for older workers, as compared with the CON and the WR3:1.
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http://dx.doi.org/10.1002/ajim.23156DOI Listing
September 2020

Heart rate variability in older men on the day following prolonged work in the heat.

J Occup Environ Hyg 2020 09 10;17(9):383-389. Epub 2020 Jul 10.

School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.

Susceptibility to heat illness during physically demanding work in hot environments is greater on the second of two consecutive workdays. While it has been demonstrated that heat storage is exacerbated on the second compared to first workday in older workers (50-65 yr), the effects on heart rate variability (HRV), an established surrogate of cardiac autonomic modulation, remain unclear. This study evaluated HRV in older workers on the day following prolonged work in the heat. Electrocardiogram was recorded in nine older (53-64 yr) males at rest, during three 30-min bouts of semi-recumbent cycling at fixed rates of metabolic heat production (150, 200, 250 W/m), each separated by 15-min recovery. Experiments were conducted in hot-dry conditions (40 °C, 20% relative humidity), immediately prior to (Day 1), and on the day following (Day 2), a prolonged work simulation (∼7.5 hr) involving moderate intensity intermittent exercise in hot-dry conditions (38 °C, 34% relative humidity). Core temperature, as well as time, frequency, and nonlinear HRV indices were derived for analysis during rest, the final 5-min of exercise at the highest heat production and recovery. The change in core temperature at the end of work (mean ±SD) was significantly greater on Day 2 (1.0 °C ±0.3) relative to Day 1 (0.8 °C ±0.2;  < 0.01). Heart rate, however, did not significantly differ between days 1 and 2 at rest (Day 1, 59 ±11 bpm; Day 2, 62 ±13 bpm), during exercise (Day 1, 113 ±21 bpm; Day 2, 114 ±18 bpm ) and at the end of recovery (Day 1, 75 ±16 bpm; Day 2, 76 ±12 bpm). Likewise, there were no significant differences in any HRV indices derived from time, frequency, and nonlinear domains (all  > 0.05). Prolonged work in the heat did not modulate next-day heart rhythms, as reflected by HRV, despite augmented core temperature. While HRV can reflect physiological aspects of cardiac autonomic stressors, these findings indicate it does not provide a means to identify exacerbated heat strain in older workers over consecutive work shifts in the heat.
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http://dx.doi.org/10.1080/15459624.2020.1779932DOI Listing
September 2020

Cardiac autonomic modulation in type 1 diabetes during exercise-heat stress.

Acta Diabetol 2020 Aug 6;57(8):959-963. Epub 2020 Mar 6.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University, Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada.

Aims: Cardiac autonomic modulation, as assessed by heart rate variability (HRV), is independently attenuated by both type 1 diabetes (T1D) and exercise-heat stress, although their combined effects remain unclear. We therefore assessed HRV during exercise-heat stress in young individuals (18-37 years) with (n = 14) and without type 1 diabetes (n = 14).

Methods: Participants completed 30-min seated rest and three, 30-min bouts of semi-recumbent cycling at light, moderate, and vigorous metabolic heat productions (200, 250, 300 W/m, respectively), each followed by 30-min recovery. Body core temperature (T) and electrocardiogram were recorded throughout and analyzed during the final 5-min of rest and each exercise period.

Results: Relative to baseline, T was increased in both groups, albeit to a greater extent in type 1 diabetes during vigorous exercise (T1D, 1.1 ± 0.3 °C; control, 0.8 ± 0.3 °C; P < 0.05). Overall HRV (as reflected by entropy) was attenuated throughout exercise relative to baseline in both groups, with the magnitude of the reduction greater in type 1 diabetes during vigorous exercise (T1D, - 108%; control, - 70%; P < 0.05).

Conclusions: Given the negative correlations between decreased HRV and cardiac risk, our novel observations indicate that vigorous exercise in hot environments may pose a health concern for individuals with type 1 diabetes.
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http://dx.doi.org/10.1007/s00592-020-01505-9DOI Listing
August 2020

Diminished heart rate variability in type 2 diabetes is exacerbated during exercise-heat stress.

Acta Diabetol 2020 07 1;57(7):899-901. Epub 2020 Feb 1.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University, Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada.

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http://dx.doi.org/10.1007/s00592-020-01482-zDOI Listing
July 2020

Age-related reductions in heart rate variability do not worsen during exposure to humid compared to dry heat: A secondary analysis.

Temperature (Austin) 2019 4;6(4):341-345. Epub 2019 Nov 4.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada.

We conducted a secondary analysis to investigate whether age-related attenuations in heart rate variability (HRV) worsen during exposure to moderate, dry (36.5°C, 20% RH) or humid (36.5°C, 60% RH) heat conditions that resulted in greater body heat storage among older compared to young participants, and during humid compared to dry heat, regardless of age. Six HRV indices [heart rate (HR), coefficient of variation (CoV), detrended fluctuation analysis: α1, low frequency power, high frequency power, and low/high frequency ratio] were assessed in 10 young (21 ± 3 y) and 9 older (65 ± 5 y) adults for 15-min prior to (baseline), and at the end of a 120-min exposure to dry and humid heat while seated at rest. Our results demonstrated a condition (dry and humid) x time (baseline and end) interaction effect on HR (p = 0.047) such that HR gradually increased during humid heat exposure yet remained similar during dry heat exposure across groups. We also found an age-related attenuation in CoV at baseline for both the dry (young: 0.097 ± 0.023%; older: 0.054 ± 0.016%) and humid (young: 0.093 ± 0.034%; older: 0.056 ± 0.014%) heat conditions (p < 0.02). Those age-related attenuations in CoV, however, were not magnified throughout the exposure nor different between conditions (p > 0.05). While older adults stored more heat during a brief 120-min exposure to dry heat compared to their young counterparts, this was not paralleled by further age-related impairments in HRV even when body heat storage and cardiovascular strain were exacerbated by exposure to humid heat.
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http://dx.doi.org/10.1080/23328940.2019.1684791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949029PMC
November 2019

Age differences in cardiac autonomic regulation during intermittent exercise in the heat.

Eur J Appl Physiol 2020 Feb 1;120(2):453-465. Epub 2020 Jan 1.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University Private, Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada.

Purpose: This study aimed to detect potential differences in heart-rate variability (HRV) during a moderate-intensity intermittent exercise in the heat among physically active young (25.8 ± 1.9 years), middle-aged (43.5 ± 2.8 years), and older (62.9 ± 3.7 years) men.

Methods: Thirty-three participants (11/group) performed four successive bouts of 15-min cycling at a moderate fixed rate of metabolic heat production of ~ 400 W; each separated by a 15-min recovery with 1 h of final recovery in a hot and dry environment (35 °C, 20% relative humidity). Twelve HRV indices were computed that have been commonly described in the literature, and characterized various domains of the variability and complexity of heart rate.

Results: Cardiac autonomic regulation during intermittent exercise in the heat, as well as during pre-exercise rest and recovery was significantly affected by age, as changes were observed among the three different aged groups in five indices (p ≤ 0.05). Similarly, time influenced cardiac autonomic regulation as three indices showed changes across time (p ≤ 0.05) during intermittent exercise, whilst five indices displayed significant changes (p ≤ 0.05) during rest and recovery in the heat.

Conclusions: This study supports that moderate-intensity intermittent exercise in the heat is associated with significant cardiac autonomic dysregulation in older men, as compared to young and middle-aged men, yet it highlights the importance of developing preventative health strategies for heat-related illness in aged individuals.
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http://dx.doi.org/10.1007/s00421-019-04290-8DOI Listing
February 2020

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy.

J Physiol 2020 01 9;598(2):249-263. Epub 2020 Jan 9.

Department of Physiology Development & Neuroscience, University of Cambridge, Cambridge, UK.

Key Points: We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy.

Abstract: Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ∼145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4-fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4-fold reduction in the scale-dependent Lyapunov exponent slope. We also detected a 2-fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end-diastolic pressure across both groups (average R  = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale-dependent higher complexity in iFHRV.
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http://dx.doi.org/10.1113/JP278773DOI Listing
January 2020

Fluid Loss during Exercise-Heat Stress Reduces Cardiac Vagal Autonomic Modulation.

Med Sci Sports Exerc 2020 02;52(2):362-369

Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, CANADA.

Purpose: Sweat-induced fluid loss during prolonged exercise-heat stress can compromise cardiovascular and thermoregulatory function, although its effects on cardiac autonomic modulation remain unclear. We therefore examined heart rate variability (HRV) and recovery (HRRec), as surrogates of cardiac autonomic modulation, during and after prolonged exercise in the heat with and without fluid replacement.

Methods: Eleven young and healthy men performed 90 min of semi-recumbent cycling in dry heat (40°C; 20% relative humidity) at a fixed rate of metabolic heat production (600 W; ~46% V˙O2peak) followed by 40-min resting recovery without fluid replacement (No-FR; ~3.4% reduction in body mass). On a separate day, participants completed the same protocol with fluid replacement (FR; 500-700 mL timed boluses) to offset sweat losses. Esophageal temperature and ECG were recorded throughout, with measurements analyzed over 10-min averaged epochs during baseline, each 30-min interval during exercise and 20-min interval during recovery.

Results: Esophageal temperature and heart rate were elevated in No-FR relative to FR throughout exercise (all P ≤ 0.02). The HRV indices reflecting vagal influence of heart rate including the cardiac vagal index (CVI = log10[16 × SD1 × SD2]) and root-mean-square of successive differences were attenuated throughout exercise relative to baseline in both conditions (all P < 0.05), with the magnitude of the reduction greater in the No-FR condition (all P < 0.05). Further, sample entropy was reduced throughout all time points measured during exercise in the No-FR relative to FR condition (all P ≤ 0.03).

Conclusions: Our unique observations indicate that while prolonged exercise heat stress attenuates the vagal influence and complexity of cardiac rhythms, that reduction is further exacerbated by fluid loss, highlighting the importance of fluid replacement in such conditions.
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http://dx.doi.org/10.1249/MSS.0000000000002136DOI Listing
February 2020

Vagal contributions to fetal heart rate variability: an omics approach.

Physiol Meas 2019 07 1;40(6):065004. Epub 2019 Jul 1.

Ottawa Hospital Research Institute, University of Ottawa, ON, Canada. PB and CH contributed equally to this manuscript.

Objective: Fetal heart rate variability (fHRV) is an important indicator of health and disease, yet its physiological origins, neural contributions, in particular, are not well understood. We aimed to develop novel experimental and data analytical approaches to identify fHRV measures reflecting the vagus nerve contributions to fHRV.

Approach: In near-term ovine fetuses, a comprehensive set of 46 fHRV measures was computed from fetal pre-cordial electrocardiogram recorded during surgery and 72 h later without (n  =  24) and with intra-surgical bilateral cervical vagotomy (n  =  15).

Main Results: The fetal heart rate did not change due to vagotomy. We identify fHRV measures specific to the vagal modulation of fHRV: multiscale time irreversibility asymmetry index (AsymI), detrended fluctuation analysis (DFA) α , Kullback-Leibler permutation entropy (KLPE) and scale-dependent Lyapunov exponent slope (SDLE α).

Significance: We provide a systematic delineation of vagal contributions to fHRV across signal-analytical domains which should be relevant for the emerging field of bioelectronic medicine and the deciphering of the 'vagus code'. Our findings also have clinical significance for in utero monitoring of fetal health during surgery. Key points •Fetal surgery causes a complex pattern of changes in heart rate variability measures with an overall reduction of complexity or variability. •At 72 h after surgery, many of the HRV measures recover and this recovery is delayed by an intrasurgical cervical bilateral vagotomy. •We identify HRV pattern representing complete vagal withdrawal that can be understood as part of 'HRV code', rather than any single HRV measure. •We identify HRV biomarkers of recovery from fetal surgery and discuss the effect of anticholinergic medication on this recovery.
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http://dx.doi.org/10.1088/1361-6579/ab21aeDOI Listing
July 2019

Heart rate variability dynamics during treatment for exertional heat strain when immediate response is not possible.

Exp Physiol 2019 06 19;104(6):845-854. Epub 2019 Apr 19.

Human Environmental Physiological Research Unit, University of Ottawa, Ottawa, ON, Canada.

New Findings: What is the central question of this study? Does a delay in cold water immersion treatment affect the cardiac autonomic control of exertionally heat-strained individuals? What is the main finding and its importance? Cold water immersion is effective for treating exertionally heat-strained individuals even when treatment is commenced with a significant delay. However, that treatment delay leads to only partial/transient restoration of cardiac autonomic control. Therefore, we recommend that exertional heatstroke patients are continuously monitored for several hours even after core temperature has returned to normal values.

Abstract: Immediate cold water immersion (CWI) is the gold-standard treatment for exertional heatstroke. In the field, however, treatment is often delayed, primarily owing to a delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5°C) delays of 5 (short), 20 (moderate) and 40 (prolonged) min on cardiac autonomic control [as assessed via heart rate variability (HRV)] in eight exertionally heat-strained (40.0°C rectal temperature) individuals. Eleven HRV indices were computed that have been described commonly in the literature and characterize almost all known domains of the variability and complexity of the cardiopulmonary system. We found that the cardiac autonomic control (as assessed via HRV) of exertionally heat-strained individuals was significantly affected by the amount of time it took for the CWI treatment to be applied. Six out of 11 HRV indices studied, from all variability domains, displayed strong (P ≤ 0.005) time × delay interaction effects. Moreover, the number of significantly (P ≤ 0.005) abnormal (i.e. different from the short delay) HRV indices more than doubled (seven versus 15) from the moderate delay to the prolonged delay. Finally, our results demonstrated that a CWI treatment applied with delays of 20 and, primarily, 40 min did not lead to a full restoration of cardiac autonomic control of exertionally heat-strained individuals. In conclusion, this study supports CWI for treating exertionally heat-strained individuals even when applied with prolonged delay, but it highlights the importance of continued cardiac monitoring of patients who have suffered exertional heatstroke for several hours after restoration of core temperature to normal.
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http://dx.doi.org/10.1113/EP087297DOI Listing
June 2019

Comment on: "Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients With Sepsis Is Specific, but Not Sensitive for Future Deterioration".

J Emerg Med 2019 02;56(2):228-229

Division of Critical Care, Department of Medicine, and Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1016/j.jemermed.2018.11.006DOI Listing
February 2019

Age alters cardiac autonomic modulations during and following exercise-induced heat stress in females.

Temperature (Austin) 2018 15;5(2):184-196. Epub 2018 Mar 15.

Human and Environmental Physiology Research Unit, University of Ottawa, Ontario, Canada.

The aim of this study was to examine the effect of natural ageing on heart rate variability during and following exercise-induced heat stress in females. Eleven young (∼24 years) and 13 older (∼51 years), habitually active females completed an experimental session consisting of baseline rest, moderate intensity intermittent exercise (four 15-min bouts separated by 15-min recovery) and 1-hour of final recovery in a hot and dry (35°C, 20% relative humidity) environment. Respiratory and heart rate recordings were continuously logged with 10-min periods analysed at the end of: baseline rest; each of the exercise and recovery bouts; and during the 1-hour final recovery period. Comparisons over time during exercise and recovery, and between groups were conducted via two-way repeated-measures ANCOVAs with rest values as the covariate. During baseline rest, older females exhibited lower heart rate variability compared to young females with similar levels of respiration and most (∼71-79%) heart rate variability measures during repeated exercise and recovery. However, older females exhibited heart rate variability metrics suggestive of greater parasympathetic modulation (greater long axis of Poincare plot, cardiac vagal index; lower low-high frequency ratio) during repeated exercise with lower indices during the latter stage of prolonged recovery (less very low frequency component, Largest Lyapunov Exponent; greater cardiac sympathetic index). The current study documented several unique, age-dependent differences in heart rate variability, independent of respiration, during and following exercise-induced heat stress for females that may assist in the detection of normal heat-induced adaptations as well as individuals vulnerable to heat stress.
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http://dx.doi.org/10.1080/23328940.2018.1432918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204987PMC
March 2018

Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis.

Neurosci Biobehav Rev 2020 10 30;117:165-183. Epub 2018 May 30.

Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Argentina.

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.
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http://dx.doi.org/10.1016/j.neubiorev.2018.05.026DOI Listing
October 2020

Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis.

Shock 2019 04;51(4):416-422

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

Background: Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population.

Methods: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h.

Results: Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65-0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54-0.83), laboratory (AUROC = 0.77, 95% CI, 0.63-0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61-0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2-5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1-0.4) risk of deterioration (incidence of deterioration: 2%).

Conclusions: A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.
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http://dx.doi.org/10.1097/SHK.0000000000001192DOI Listing
April 2019

Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific, but Not Sensitive for Future Deterioration.

J Emerg Med 2018 06 13;54(6):766-773. Epub 2018 Mar 13.

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Background: Early emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration.

Objective: Our aim was to determine the role of initial serum lactate for prediction of short-term deterioration in stable ED patients with suspected sepsis.

Methods: We conducted a prospective cohort study of adult ED sepsis patients. Venous lactate was obtained within 2 h of ED arrival. Main outcome was subsequent deterioration (defined as any of the following: death, intensive care admission > 24 h, intubation, vasoactive medications for > 1 h, or noninvasive positive pressure ventilation for > 1 h) within 72 h. Patients meeting any endpoint within 1 h of arrival were excluded.

Results: Nine hundred and eighty-five patients were enrolled, of whom 84 (8.5%) met the primary outcome of deterioration. Initial lactate ≥ 4.0 mmol/L had a specificity of 97% (95% confidence interval [CI] 94-100%), but a sensitivity of 27% (95% CI 18-37%) for predicting deterioration, with positive and negative likelihood ratios of 10.7 (95% CI 6.3-18.3) and 0.8 (95% CI 0.7-0.9), respectively. A lower threshold of lactate (≥2.0 mmol/L) had a sensitivity of 67% (95% CI 55-76%) and specificity of 66% (95% CI 63-69%), with corresponding positive and negative likelihood ratios of 2.0 (95% CI 1.7-2.3) and 0.5 (95% CI 0.4-0.7).

Conclusions: High ED lactate is predictive of subsequent deterioration from sepsis within 72 h, and may be useful in determining disposition, but low lactate is not effective in screening stable patients at risk of deterioration.
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http://dx.doi.org/10.1016/j.jemermed.2018.01.040DOI Listing
June 2018

A Doubly Stochastic Change Point Detection Algorithm for Noisy Biological Signals.

Front Physiol 2017 5;8:1112. Epub 2018 Jan 5.

Department of Mathematics and Statistics, York University, Toronto, ON, Canada.

Experimentally and clinically collected time series data are often contaminated with significant confounding noise, creating short, noisy time series. This noise, due to natural variability and measurement error, poses a challenge to conventional change point detection methods. We propose a novel and robust statistical method for change point detection for noisy biological time sequences. Our method is a significant improvement over traditional change point detection methods, which only examine a potential anomaly at a single time point. In contrast, our method considers all suspected anomaly points and considers the joint probability distribution of the number of change points and the elapsed time between two consecutive anomalies. We validate our method with three simulated time series, a widely accepted benchmark data set, two geological time series, a data set of ECG recordings, and a physiological data set of heart rate variability measurements of fetal sheep model of human labor, comparing it to three existing methods. Our method demonstrates significantly improved performance over the existing point-wise detection methods.
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http://dx.doi.org/10.3389/fphys.2017.01112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760503PMC
January 2018

Chronotropic Competence Indices Extracted from Wearable Sensors for Cardiovascular Diseases Management.

Sensors (Basel) 2017 Oct 25;17(11). Epub 2017 Oct 25.

Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada.

Chronotropic incompetence (CI) has been proven to be an important factor in the diagnosis and management of cardiovascular diseases. In this paper, we extend the existing CI parameters and propose chronotropic competence indices (CCI) to describe the exercise response of the cardiopulmonary system. A cardiac chronotropic competence Test (3CT), dedicated to CCI measurement using a wearable device, is also presented. Preliminary clinical trials are presented for the validation of 3CT measurement accuracy, and to show the potential of CCI in the prevention and rehabilitation of cardiovascular diseases.
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http://dx.doi.org/10.3390/s17112441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713041PMC
October 2017

Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis.

Emerg Med J 2018 Feb 18;35(2):96-102. Epub 2017 Aug 18.

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

Objective: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration.

Methods: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration.

Results: 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups.

Conclusions: While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.
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http://dx.doi.org/10.1136/emermed-2017-206625DOI Listing
February 2018

Heart beat classification from single-lead ECG using the synchrosqueezing transform.

Physiol Meas 2017 02 5;38(2):171-187. Epub 2017 Jan 5.

Ottawa Hospital Research Institute, Ottawa, ON, Canada.

The processing of ECG signal provides a wealth of information on cardiac function and overall cardiovascular health. While multi-lead ECG recordings are often necessary for a proper assessment of cardiac rhythms, they are not always available or practical, for example in fetal ECG applications. Moreover, a wide range of small non-obtrusive single-lead ECG ambulatory monitoring devices are now available, from which heart rate variability (HRV) and other health-related metrics are derived. Proper beat detection and classification of abnormal rhythms is important for reliable HRV assessment and can be challenging in single-lead ECG monitoring devices. In this manuscript, we modelled the heart rate signal as an adaptive non-harmonic model and used the newly developed synchrosqueezing transform (SST) to characterize ECG patterns. We show how the proposed model can be used to enhance heart beat detection and classification between normal and abnormal rhythms. In particular, using the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database and the Association for the Advancement of Medical Instrumentation (AAMI) beat classes, we trained and validated a support vector machine (SVM) classifier on a portion of the annotated beat database using the SST-derived instantaneous phase, the R-peak amplitudes and R-peak to R-peak interval durations, based on a single ECG lead. We obtained sentivities and positive predictive values comparable to other published algorithms using multiple leads and many more features.
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http://dx.doi.org/10.1088/1361-6579/aa5070DOI Listing
February 2017

Heart rate variability during high heat stress: a comparison between young and older adults with and without Type 2 diabetes.

Am J Physiol Regul Integr Comp Physiol 2016 10 10;311(4):R669-R675. Epub 2016 Aug 10.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada;

We examined whether older individuals with and without Type 2 diabetes (T2D) experience differences in heart rate variability (HRV) during a 3-h exposure to high heat stress compared with young adults. Young (Young; n = 22; 23 ± 3 yr) and older individuals with (T2D; n = 11; 59 ± 9 yr) and without (Older; n = 25; 63 ± 5 yr) T2D were exposed to heat stress (44°C, 30% relative humidity) for 3 h. Fifty-five HRV measures were assessed for 15 min at baseline and at minutes 82.5-97.5 (Mid) and minutes 165-180 (End) during heat stress. When compared with Young, a similar number of HRV indices were significantly different (P < 0.05) in Older (Baseline: 35; Mid: 29; End: 32) and T2D (Baseline: 31; Mid: 30; End: 27). In contrast, the number of HRV indices significantly different (P < 0.05) between Older and T2D were far fewer (Baseline: 13, Mid: 1, End: 3). Within-group analyses demonstrated a greater change in the Young group's HRV during heat stress compared with Older and T2D; the number of significantly different (P < 0.05) HRV indices between baseline and End were 42, 29, and 20, for Young, Older, and T2D, respectively. Analysis of specific HRV domains suggest that the Young group experienced greater sympathetic activity during heat stress compared with Older and T2D. In conclusion, when compared with young, older individuals with and without T2D demonstrate low HRV at baseline and less change in HRV (including an attenuated sympathetic response) during 3 h high heat stress, potentially contributing to impaired thermoregulatory function.
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http://dx.doi.org/10.1152/ajpregu.00176.2016DOI Listing
October 2016

Practice Variation in Spontaneous Breathing Trial Performance and Reporting.

Can Respir J 2016 29;2016:9848942. Epub 2016 Mar 29.

The Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.

Background. Spontaneous breathing trials (SBTs) are standard of care in assessing extubation readiness; however, there are no universally accepted guidelines regarding their precise performance and reporting. Objective. To investigate variability in SBT practice across centres. Methods. Data from 680 patients undergoing 931 SBTs from eight North American centres from the Weaning and Variability Evaluation (WAVE) observational study were examined. SBT performance was analyzed with respect to ventilatory support, oxygen requirements, and sedation level using the Richmond Agitation Scale Score (RASS). The incidence of use of clinical extubation criteria and changes in physiologic parameters during an SBT were assessed. Results. The majority (80% and 78%) of SBTs used 5 cmH2O of ventilator support, although there was variability. A significant range in oxygenation was observed. RASS scores were variable, with RASS 0 ranging from 29% to 86% and 22% of SBTs performed in sedated patients (RASS < -2). Clinical extubation criteria were heterogeneous among centres. On average, there was no change in physiological variables during SBTs. Conclusion. The present study highlights variation in SBT performance and documentation across and within sites. With their impact on the accuracy of outcome prediction, these results support efforts to further clarify and standardize optimal SBT technique.
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http://dx.doi.org/10.1155/2016/9848942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904518PMC
July 2017

Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics.

PLoS One 2016 21;11(4):e0153515. Epub 2016 Apr 21.

Department of OBGYN and Department of Neurosciences, CHU Ste-Justine Research Centre, l'Université de Montréal, Montréal, QC, Canada.

Fetal inflammation is associated with increased risk for postnatal organ injuries. No means of early detection exist. We hypothesized that systemic fetal inflammation leads to distinct alterations of fetal heart rate variability (fHRV). We tested this hypothesis deploying a novel series of approaches from complex signals bioinformatics. In chronically instrumented near-term fetal sheep, we induced an inflammatory response with lipopolysaccharide (LPS) injected intravenously (n = 10) observing it over 54 hours; seven additional fetuses served as controls. Fifty-one fHRV measures were determined continuously every 5 minutes using Continuous Individualized Multi-organ Variability Analysis (CIMVA). CIMVA creates an fHRV measures matrix across five signal-analytical domains, thus describing complementary properties of fHRV. We implemented, validated and tested methodology to obtain a subset of CIMVA fHRV measures that matched best the temporal profile of the inflammatory cytokine IL-6. In the LPS group, IL-6 peaked at 3 hours. For the LPS, but not control group, a sharp increase in standardized difference in variability with respect to baseline levels was observed between 3 h and 6 h abating to baseline levels, thus tracking closely the IL-6 inflammatory profile. We derived fHRV inflammatory index (FII) consisting of 15 fHRV measures reflecting the fetal inflammatory response with prediction accuracy of 90%. Hierarchical clustering validated the selection of 14 out of 15 fHRV measures comprising FII. We developed methodology to identify a distinctive subset of fHRV measures that tracks inflammation over time. The broader potential of this bioinformatics approach is discussed to detect physiological responses encoded in HRV measures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153515PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839772PMC
August 2016