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.

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.

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.

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.