Heart Rate Variability in Patients with Spontaneous Intracerebral Hemorrhage and its Relationship with Clinical Outcomes.

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.

Heart Rate Variability Parameter Changes in Patients With Acute Ischemic Stroke Undergoing Intravenous Thrombolysis.

Background Autonomic dysfunction has been revealed in patients with acute ischemic stroke and is associated with poor prognosis. However, autonomic nervous system function assessed by heart rate variability (HRV) and its relationship with clinical outcomes in patients undergoing intravenous thrombolysis (IVT) remain unknown. Methods and Results Patients who did and did not undergo IVT between September 2016 and August 2021 were prospectively and consecutively recruited. HRV values were measured at 1 to 3 and 7 to 10 days after stroke to assess autonomic nervous system function. A modified Rankin scale score ≥2 at 90 days was defined as an unfavorable outcome. Finally, the analysis included 466 patients; 224 underwent IVT (48.1%), and 242 did not (51.9%). Linear regression showed a positive correlation of IVT with parasympathetic activation-related HRV parameters at 1 to 3 days (high frequency: ß=0.213, P=0.002) and with both sympathetic (low frequency: ß=0.152, P=0.015) and parasympathetic activation-related HRV parameters (high frequency: ß=0.153, P=0.036) at 7 to 10 days after stroke. Logistic regression showed HRV values and autonomic function within 1 to 3 and 7 to 10 days after stroke were independently associated with 3-month unfavorable outcomes after adjusting for confounders in patients who underwent IVT (all P<0.05). Furthermore, addition of HRV parameters to conventional risk factors significantly improved risk-predictive ability of 3-month outcome (the area under the receiver operating characteristic curve significantly improved from 0.784 [0.723-0.846] to 0.855 [0.805-0.906], P=0.002). Conclusions IVT positively affected HRV and autonomic nervous system activity, and autonomic function assessed by HRV in acute stroke phase was independently associated with unfavorable outcomes in patients undergoing IVT.

Clinical factors associated with cerebral autoregulation in ischemic stroke related to small artery occlusion.

BACKGROUND: Existing data suggest that cerebral autoregulation (CA) varies among different subtypes of ischaemic stroke. CA is globally impaired in patients with small artery occlusion (SAO). However, the factors influencing CA impairment in patients remains to be elucidated. METHODS: Stroke patients with SAO who underwent brain magnetic resonance imaging (MRI) were prospectively studied. Within 7 days after stroke onset, CA was recorded from the middle cerebral artery blood flow velocity and arterial blood pressure was simultaneously measured. Transfer function analysis was used to derive CA parameters, including gain and phase. Clinical characteristics, mean arterial pressure (MAP), biochemical findings, and cerebral small vessel disease (CSVD) markers on MRI were assessed in each patient. Factors associated with CA parameters were investigated. Univariate and multivariate linear regression analyses were conducted to determine the relationship between clinical factors and CA parameters. RESULTS: Sixty-three SAO patients (age, 56.3 ± 9.9 years; 55 men) were enrolled in the study. In the multiple linear regression analysis, after controlling for relevant clinical factors, MAP on admission (ipsilateral OR = 0.99 and contralateral OR = 0.99, both P < 0.005) was a significant independent predictor of bilateral gain. MAP > 105 mmHg on admission (OR = 0.77, P = 0.019) was significantly associated with ipsilateral gain. Diabetes mellitus was a significant predictive factor for bilateral gain (ipsilateral OR = 1.32 and contralateral OR = 1.22, both P < 0.005). No correlations were found between CA parameters and CSVD characteristics. CONCLUSION: In SAO-related ischaemic stroke, patients with MAP > 105 mmHg on admission tended to have better ipsilateral CA. Diabetes mellitus appears to be an independent risk factor for CA impairment in patients with SAO-related stroke. CSVD may not be the main factor affecting bilateral CA in patients with SAO.

Time course of beat-to-beat blood pressure variability and outcome in patients with spontaneous intracerebral haemorrhage.

OBJECTIVES: Increased blood pressure variability (BPV) over 24 h or longer was associated with poor clinical outcomes in patients with intracerebral haemorrhage (ICH). However, the characteristics of beat-to-beat BPV, a rapid assessment of BPV and its association with outcome in ICH patients remain unknown. METHODS: We consecutively and prospectively recruited patients with ICH between June 2014 and December 2020. Five-minute noninvasive beat-to-beat recordings were measured serially at three time points, 1-2, 4-6 and 10-12 days after ICH onset. BPV was calculated using standard deviation (SD) and variation independent of mean (VIM). Favourable outcome was defined as modified Rankin Scale score of less than 2 at 90 days. RESULTS: The analysis included 66 participants (54.12 ±â€Š10.79 years; 71.2% men) and 66 age and sex-matched healthy controls. Compared with that in healthy adults, beat-to-beat BPV was significantly increased 1-2 days after ICH and was completely recovered 10-12 days later. BPV recorded 1-2 days after ICH onset was higher among patients with unfavourable outcomes than among those with favourable outcomes (all P < 0.05) and higher BPV on days 1-2 was independently associated with a 3-month unfavourable outcome after adjustment for major covariates. CONCLUSION: Beat-to-beat BPV was significantly increased among patients with ICH and could be completely recovered 10-12 days later. In addition, beat-to-beat BPV 1-2 days after ICH was independently associated with prognosis and could be regarded as a potential prognostic predictor and effective therapeutic target in the future.

Association Between Cerebral Autoregulation and Long-Term Outcome in Patients With Acute Ischemic Stroke.

BACKGROUND: Dynamic cerebral autoregulation (CA) is known to be impaired in patients with acute ischemic stroke (AIS), but whether or not dynamic CA can predict long-term outcomes is unclear. MATERIALS AND METHODS: This prospective study included 103 patients with AIS between September 2017 and April 2019. We measured the middle cerebral artery blood flow velocity and blood pressure within 7 days of AIS onset using a transcranial Doppler and Finometer, respectively. We conducted transfer function analysis to calculate dynamic CA indices (phase and gain), with lower phase and higher gain parameters reflecting less efficient CA. We followed up all patients after 3 and 12 months. Patients with 12-month modified Rankin Scale scores of <2 and ≥2 were defined as having favorable and unfavorable outcomes, respectively. We then analyzed the predictors of unfavorable outcomes after 3 and 12 months using logistic regression. RESULTS: The ipsilesional phase parameter was significantly lower in patients with unfavorable outcomes than in those with favorable outcomes. Multiple logistic regression analysis revealed that the ipsilesional phase parameter and the National Institutes of Health Stroke Scale score were nonmodifiable predictors of short-term and long-term outcomes. Moreover, in receiver operating characteristic analysis, the area under the curve of the ipsilesional phase parameter was 0.646 (95% confidence interval: 0.513-0.779, P =0.044). Notably, the optimal cut-off value was 20.33 degrees (sensitivity: 63%, specificity: 70%). CONCLUSION: Dynamic CA is an independent predictor of outcomes at 3 and 12 months in patients with AIS.

The Impact of Serial Remote Ischemic Conditioning on Dynamic Cerebral Autoregulation and Brain Injury Related Biomarkers.

Objective: Recent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are related to the prognosis of cerebrovascular disease. Methods: This was a self-controlled interventional study in healthy adults. The RIC was conducted twice a day for 7 consecutive days (d1-d7) and comprised 4 × 5-min single arm cuff inflation/deflation cycles at 200 mmHg. All participants underwent assessments of dCA ten times, including baseline, d1, d2, d4, d7, d8, d10, d14, d21, and d35 of the study. Blood samples were collected four times (baseline, d1, d7, and d8) immediately after dCA measurements. The transfer function parameters [phase difference (PD) and gain] were used to quantify dCA. Four serum biomarkers associated with brain injury, ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, glial fibrillary acidic protein, and S100ß were tested. Results: Twenty-two healthy adult volunteers (mean age 25.73 ± 1.78 years, 3 men [13.6%], all Asian) were enrolled in this study. Bilateral PD values were significantly higher since four times of RIC were completed (d2) compared with PD values at baseline (left: 53.31 ± 10.53 vs. 45.87 ± 13.02 degree, p = 0.015; right: 54.90 ± 10.46 vs. 45.96 ± 10.77 degree, p = 0.005). After completing 7 days of RIC, the significant increase in dCA was sustained for at least 28 days (d35, left: 53.11 ± 14.51 degree, P = 0.038; right: 56.95 ± 14.57 degree, p < 0.001). No difference was found in terms of different serum biomarkers related to brain injury before and after RIC. Conclusion: The elevation in dCA was detected immediately after four repeated times of RIC, and 7-day consecutive RIC induced a sustained increase in dCA for at least 28 days and did not affect blood biomarkers of brain injury in healthy adults. These results will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease.

Impaired dynamic cerebral autoregulation in young adults with mild depression.

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18-35 years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty-three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression.

The consistency of invasive and non-invasive arterial blood pressure for the assessment of dynamic cerebral autoregulation in NICU patients.

Background: Studies of the clinical application of dynamic cerebral autoregulation show considerable variations, and differences in blood pressure devices may be one of the reasons for this variation. Few studies have examined the consistency of invasive and non-invasive arterial blood pressure for evaluating cerebral autoregulation. We attempted to investigate the agreement between invasive and non-invasive blood pressure methods in the assessment of dynamic cerebral autoregulation with transfer function analysis. Methods: Continuous cerebral blood flow velocity and continuous invasive and non-invasive arterial blood pressure were simultaneously recorded for 15 min. Transfer function analysis was applied to derive the phase shift, gain and coherence function at all frequency bands from the first 5, 10, and 15 min of the 15-min recordings. The consistency was assessed with Bland-Altman analysis and intraclass correlation coefficient. Results: The consistency of invasive and noninvasive blood pressure methods for the assessment of dynamic cerebral autoregulation was poor at 5 min, slightly improved at 10 min, and good at 15 min. The values of the phase shift at the low-frequency band measured by the non-invasive device were higher than those measured with invasive equipment. The coherence function values measured by the invasive technique were higher than the values derived from the non-invasive method. Conclusion: Both invasive and non-invasive arterial blood pressure methods have good agreement in evaluating dynamic cerebral autoregulation when the recording duration reaches 15 min. The phase shift values measured with non-invasive techniques are higher than those measured with invasive devices. We recommend selecting the most appropriate blood pressure device to measure cerebral autoregulation based on the disease, purpose, and design.

The Effect of Data Length on the Assessment of Dynamic Cerebral Autoregulation with Transfer Function Analysis in Neurological ICU Patients.

BACKGROUND: Cerebral autoregulation plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury, which is highly important for patients in the neurological intensive care unit (neuro-ICU). Although the consensus white paper suggests that a minimum of 5 min of data are needed for assessing dynamic cerebral autoregulation with transfer function analysis (TFA), it remains unknown if the length of these data is valid for patients in the neuro-ICU, of whom are notably different than the general populations. We aimed to investigate the effect of data length using transcranial Doppler ultrasound combined with invasive blood pressure measurement for the assessment of dynamic cerebral autoregulation in patients in the neuro-ICU. METHODS: Twenty patients with various clinical conditions (severe acute encephalitis, ischemic stroke, subarachnoid hemorrhage, brain injury, cerebrovascular intervention operation, cerebral hemorrhage, intracranial space-occupying lesion, and toxic encephalopathy) were recruited for this study. Continuous invasive blood pressure, with a pressure catheter placed at the radial artery, and bilateral continuous cerebral blood flow velocity with transcranial Doppler ultrasound were simultaneously recorded for a length of 10 min for each patient. TFA was applied to derive phase shift, gain, and coherence function at all frequency bands from the first 2, 3, 4, 5, 6, 7, 8, 9, and 10 min of the 10-min recordings in each patient on both hemispheres. The variability in the autoregulatory parameters in each hemisphere was investigated by repeated measures analysis of variance. RESULTS: Forty-one recordings (82 hemispheres) were included in the study. According to the critical values of coherence provided by the Cerebral Autoregulation Research Network white paper, acceptable rates for the data were 100% with a length ≥ 7 min. The final analysis included 68 hemispheres. The effects of data length on trends in phase shift in the very low frequency (VLF) band (F1.801,120.669 = 6.321, P = 0.003), in the LF band (F1.274,85.343 = 4.290, P = 0.032), and in the HF band (F1.391,93.189 = 3.868, P = 0.039) were significant for 3-7 min, for 4-7 min, and for 5-8 min, respectively. Effects were also significant on the gain in the VLF band (F1.927,129.134 = 3.215, P = 0.045) for 2-8 min and on the coherence function in all frequency bands (VLF F2.846,190.671 = 90.247, P < 0.001, LF F2.515,168.492 = 55.770, P < 0.001, HF F2.411, 161.542 = 33.833, P < 0.001) for 2-10 min. CONCLUSIONS: Considering the acceptable rates for the data and the variation in the TFA variables (phase shift and gain), we recommend recording data for a minimum length of 7 min for TFA in patients in the neuro-ICU.

Separation of normal and impaired dynamic cerebral autoregulation using deep embedded clustering: a proof-of-concept study.

Objective. A previous study has shown that a data-driven approach can significantly improve the discriminative power of transfer function analysis (TFA) used to differentiate between normal and impaired cerebral autoregulation (CA) in two groups of data. The data was collected from both healthy subjects (assumed to have normal CA) and symptomatic patients with severe stenosis (assumed to have impaired CA). However, the sample size of the labeled data was relatively small, owing to the difficulty in data collection. Therefore, in this proof-of-concept study, we investigate the feasibility of using an unsupervised learning model to differentiate between normal and impaired CA on TFA variables without requiring labeled data for learning.Approach. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), which were recorded simultaneously for approximately 10 min, were included from 148 subjects (41 healthy subjects, 31 with mild stenosis, 13 with moderate stenosis, 22 asymptomatic patients with severe stenosis, and 41 symptomatic patients with severe stenosis). Tiecks' model was used to generate surrogate data with normal and impaired CA. A recently proposed unsupervised learning model was optimized and applied to separate the normal and impaired CA for both the surrogate data and real data.Main results. It achieved 98.9% and 74.1% accuracy for the surrogate and real data, respectively.Significance. To our knowledge, this is the first attempt to employ an unsupervised data-driven approach to assess CA using TFA. This method enables the development of a classifier to determine the status of CA, which is currently lacking.

A Data-Driven Approach to Transfer Function Analysis for Superior Discriminative Power: Optimized Assessment of Dynamic Cerebral Autoregulation.

Transfer function analysis (TFA) is extensively used to assess human physiological functions. However, extracting parameters from TFA is not usually optimized for detecting impaired function. In this study, we propose to use data-driven approaches to improve the performance of TFA in assessing blood flow control in the brain (dynamic cerebral autoregulation, dCA). Data were collected from two distinct groups of subjects deemed to have normal and impaired dCA. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) were simultaneously recorded for approximately 10 mins in 82 subjects (including 41 healthy controls) to give 328 labeled samples of the TFA variables. The recordings were further divided into 4,294 short data segments to generate 17,176 unlabeled samples of the TFA variables. We optimized TFA post-processing with a generic semi-supervised learning strategy and a novel semi-supervised stacked ensemble learning (SSEL) strategy for classification into normal and impaired dCA. The generic strategy led to a performance with no significant difference to that of the conventional dCA analysis methods, whereas the proposed new strategy boosted the performance of TFA to an accuracy of 93.3%. To our knowledge, this is the best dCA discrimination performance obtained to date and the first attempt at optimizing TFA through machine learning techniques. Equivalent methods can potentially also be applied to assessing a wide spectrum of other human physiological functions.

The Impact of Remote Ischaemic Conditioning on Beat-to-Beat Heart Rate Variability Circadian Rhythm in Healthy Adults.

BACKGROUND: Remote ischaemic conditioning (RIC) is an intervention that may exert a protective effect over multiple tissues or organs by regulating neuronal signal transduction. Heart rate variability (HRV) can assess the state of the autonomic nervous system. However, whether RIC can also regulate HRV in humans remains unknown. METHOD: This was a self-controlled interventional study in which serial beat-to-beat monitoring was performed at the same seven time points (7, 9, and 11 AM; 2, 5, and 8 PM; and 8 AM on the next day) with or without RIC in 50 healthy adults. The seven time points on the RIC day were defined as baseline, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours after RIC. The RIC protocol consisted of 4×5-minute inflation/deflation in one arm and one thigh cuff at 200 mmHg pressure from 7:20 to 8 AM. This study is registered on ClinicalTrials.gov (NCT02965547). RESULTS: We included 50 healthy adult volunteers (aged 34.54±12.01 years, 22 men [44%], all Asian). The variables analysed in frequency-domain measures performed as power of low-frequency in normalised units (0.04-0.15 Hz), high-frequency in normalised units (0.15-0.40 Hz), and ratio of low frequency to high frequency. The time-domain parameters standard deviation (SD) of all normal to normal (NN) intervals (SDNN), mean of the 5-minute SD of the NN intervals, SD of the consecutive 5-minute averages of NN intervals, and the root mean square of successive differences of NN intervals, and time-domain parameters calculated from Poincaré plots, SD of the short diagonal axis in Poincaré plot (SD1), SD of the long diagonal axis in Poincaré plot (SD2), and SD1/SD2 were also obtained. The SDNN and SD2 significantly increased 1 hour after RIC (p=0.029 and p=0.045, respectively). Additionally, the SD2 increased a second time 12 hours after RIC (p=0.041), which represented inhibited sympathetic activity. CONCLUSIONS: Heart rate variability increase and sympathetic inhibition induced by RIC appeared both on the early and delayed protective window of RIC, which may indicate some of the underlying mechanisms by which RIC may offer protection.

Which Parameters of Beat-to-Beat Blood Pressure Best Predict Poor In-Hospital Outcome in Spontaneous Intracerebral Hemorrhage?

Objective: There is increasing evidence that high blood pressure (BP) levels and BP variability (BPV) over 24 h or longer are associated with poor clinical outcomes in patients with intracerebral hemorrhage (ICH). The objective of this study was to examine the association between different beat-to-beat BP parameters and in-hospital outcomes. Methods: Patients with a diagnosis of acute spontaneous ICH were recruited consecutively and prospectively between September 2018 and January 2019. Beat-to-beat recordings were measured non-invasively for 5 min within the first 72 h after the onset of symptoms. BPV was analyzed by standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variation independent of mean (VIM). Outcome was assessed at discharge using the modified Rankin Scale (mRS) score. Multivariate logistic regression analysis was used to assess the association between BP levels, BPV, and clinical outcomes. Results: A total of 66 patients were included, of whom 34 had poor outcomes (mRS score, 3-6). Patients with poor outcomes had significantly higher National Institute of Health Stroke Scale scores (4.5 vs. 9, p < 0.001), a larger ICH volume (8 vs. 14.5 mL, p = 0.004), and an increased systolic BP (SBP) -CV (3.2 vs. 4.8, p < 0.001) and diastolic BP (DBP) -CV (3.7 vs. 4.9, p = 0.015). After adjustment for major covariates, multivariate logistic regression analysis revealed that SBP-CV was independently associated with an increased risk of poor in-hospital outcomes [odds ratio (OR) 2.535; 95% confidence interval (CI), 1.211-5.305; p = 0.014]. The receiver operating characteristic area for SBP-CV in predicting poor in-hospital outcome was 0.827 (95% CI, 0.730-0.925; p < 0.001), and the best cutoff point was 3.551 (sensitivity, 82.35%; specificity, 68.75%). Conclusion: A higher beat-to-beat BPV in the first 72 h of admission was associated with unfavorable in-hospital outcomes in patients with ICH. The stabilization of BPV during the acute phase may be a therapeutic target; this could be tested in future clinical trials.

The Hemodynamic Effect of Enhanced External Counterpulsation Treatment on Atherosclerotic Plaque in the Carotid Artery: A Framework of Patient-Specific Computational Fluid Dynamics Analysis.

Long-term enhanced external counterpulsation (EECP) therapy has been recommended for antiatherogenesis in recent clinical observations and trials. However, the precise mechanism underlying the benefits has not been fully clarified. To quantify the effect of EECP intervention on arterial hemodynamic environment, a framework of numerical assessment was introduced using a parallel computing algorithm. A 3D endothelial surface of the carotid artery with mild atherosclerotic plaque was constructed from images of magnetic resonance angiography (MRA). Physiologic boundary conditions were derived from images of the ultrasound flow velocity spectrum measured at the common carotid artery and before and during EECP intervention. Hemodynamic factors relating to wall shear stress (WSS) and its spatial and temporal fluctuations were calculated and analyzed, which included AWSS, OSI, and AWSSG. Measuring and computational results showed that diastole blood pressure, perfusion, and WSS level in carotid bifurcation were significantly increased during EECP intervention. Mean AWSS level throughout the model increased by 16.9%, while OSI level did not show a significant change during EECP. We thus suggested that long-term EECP treatment might inhibit the initiation and development of atherosclerotic plaque via improving the hemodynamic environment in the carotid artery. Meanwhile, EECP performance induced a 19.6% increase in AWSSG level, and whether it would influence the endothelial functions may need a further study. Moreover, the numerical method proposed in this study was expected to be useful for the instant assessment of clinical application of EECP .

Reconstruction of Continuous Brachial Arterial Pressure From Continuous Finger Arterial Pressure Using a Two-Level Optimization Strategy.

OBJECTIVE: We attempt to reconstruct brachial arterial pressure (BAP) waves from finger arterial pressure waves measured using the vascular unloading technique without arm-cuff calibration. A novel method called two-level optimization (TOP) strategy is proposed as follows. METHODS: We first derive a simplified transfer function (TF) based on a tube-load model with only two parameters to be estimated, a coefficient B and a time delay ∆t. Then, at level one, two minimization problems are formulated to estimate the optimal coefficient Bopt and time delay ∆topt. Then, we can derive an optimal TF hopt(t). However, this derivation requires true (or reference) BAP waves. Therefore, at level two, we apply multiple linear regression (MLR) to further model the relationship between the derived optimal parameters and subjects' physiologic parameters. Hence, eventually, one can estimate coefficient BMLR and time delay ∆tMLR from subject's physiologic parameters to derive the MLR-based TF hMLR(t) for the BAP reconstruction. RESULTS: Twenty-one volunteers were recruited for the data collection. The mean ± standard deviation of the root mean square errors between the reference BAP waves and the BAP waves reconstructed by hopt(t), hMLR(t), and a generalized transfer function (GTF) were 3.46 ± 1.42 mmHg, 3.61 ± 2.28 mmHg, and 6.80 ± 3.73 mmHg (significantly larger with p < 0.01), respectively. CONCLUSIONS: The proposed method can be considered as a semi-individualized TF which reconstructs significantly better BAP waves than a GTF. SIGNIFICANCE: The proposed TOP strategy can potentially be useful in more general reconstruction of proximal BP waves.

Reconstruction of continuous brachial artery pressure wave from continuous finger arterial pressure in humans.

Generalized transfer functions (GTFs) are available to compute the more relevant proximal blood pressure (BP) waveform from a more easily measured peripheral BP waveform. However, GTFs are based on the black box model. This paper presents a practical approach to reconstruct brachial artery pressure (BAP) distally from finger artery pressure (FAP). We assume that continuous BAP can be simply approximated by summing two halves of the continuous FAP shifted by the time delay. We firstly showed that the pressure wave in the finger artery can be considered twice as much as the forward/backward wave in the finger. A simplified individualized transfer function was then derived so as to estimate BAP from FAP. The effectiveness of the method was examined by experiment involving 26 healthy volunteers (26.7 ± 3.8 years old) in a resting state. By comparing with a reference BAP, we found that the proposed method can correct the FAP. The errors of the proposed method in estimating systolic and diastolic pressures are - 0.6 ± 6.0 and - 0.6 ± 3.7 mmHg, respectively. These results agree with the standard of Association for the Advancement of Medical Instrumentation (AAMI). We also found that the reconstructed BAP from FAP by terminal arterial occlusion technology (TAOT) is comparable to that of the artery occlusion technology (AOT). Our method or TAOT is promising in estimating continuous proximal blood pressure from peripheral blood pressure in practice.

Rapid pressure-to-flow dynamics of cerebral autoregulation induced by instantaneous changes of arterial CO2.

Continuous assessment of CA is desirable in a number of clinical conditions, where cerebral hemodynamics may change within relatively short periods. In this work, we propose a novel method that can improve temporal resolution when assessing the pressure-to-flow dynamics in the presence of rapid changes in arterial CO2. A time-varying multivariate model is proposed to adaptively suppress the instantaneous effect of CO2 on CBFV by the recursive least square (RLS) method. Autoregulation is then quantified from the phase difference (PD) between arterial blood pressure (ABP) and CBFV by calculating the instantaneous PD between the signals using the Hilbert transform (HT). A Gaussian filter is used prior to HT in order to optimize the temporal and frequency resolution and show the rapid dynamics of cerebral autoregulation. In 13 healthy adult volunteers, rapid changes of arterial CO2 were induced by rebreathing expired air, while simultaneously and continuously recording ABP, CBFV and end-tidal CO2 (ETCO2). Both simulation and physiological studies show that the proposed method can reduce the transient distortion of the instantaneous phase dynamics caused by the effect of CO2 and is faster than our previous method in tracking time-varying autoregulation. The normalized mean square error (NMSE) of the predicted CBFV can be reduced significantly by 38.7% and 37.7% (p<0.001) without and with the Gaussian filter applied, respectively, when compared with the previous univariate model. These findings suggest that the proposed method is suitable to track rapid dynamics of cerebral autoregulation despite the influence of confounding covariates.

Assessment of dynamic cerebral autoregulation in patients with basilar artery stenosis.

BACKGROUND AND AIMS: Previous studies have shown impaired cerebral autoregulation (CA) in carotid and middle cerebral artery (MCA) stenosis/occlusion. Little is known about CA in patients with basilar artery (BA) stenosis. We therefore investigated dynamic CA patterns in BA stenosis using transfer function analysis (TFA). METHODS: We measured spontaneous oscillations of blood flow velocity (CBFV) in the right posterior cerebral artery (PCA), and left MCA and mean arterial pressure (ABP) continuously in 25 patients with BA stenosis (moderate n=16 with 50-69% occlusion and severe n=9 with ≥ 70% occlusion) and 22 healthy volunteers in supine position during 6 circles per minute deep breath. Analysis was based on the 'black-box' model of transfer function deriving phase and gain in both PCA and MCA. RESULTS: Though changes of phase shift and gain between the patients and healthy controls were observed in MCA, the differences are however not significant. Phase shift in PCA was significantly decreased in severe stenosis when comparing with healthy controls and moderate stenosis (4.2 ± 34.2° VS 41.1 ± 40.4°, 4.2 ± 34.2° VS 34.2 ± 27.2°, both p<0.05), whilst the gain in PCA is increased for moderate BA stenosis and decreased for severe BA stenosis. Furthermore, we found that phase shift were almost abolished in patients with ischemic stroke who developed unfavorable clinical outcome (mRs>2) on the 90 days after stroke onset. CONCLUSION: Dynamic CA in PCA reduces in patients with severe BA stenosis and those with ischemic stroke who present poor outcome in 90 days after stroke onset. Phase shift might be a sensitive index prompting impaired CA in posterior circulation.