Changes in autonomic nervous activity during vaso-occlusive crisis in patients with sickle cell anaemia

Charlot, Keyne; Hierso, Régine; Lemonne, Nathalie; Romana, Marc; Tressières, Benoît; Lalanne-Mistrih, Marie-Laure; Etienne‐Julan, Maryse; Tarer, Vanessa; Ferracci, Serge; Hardy‐Dessources, Marie‐Dominique; Connes, Philippe

doi:10.1111/bjh.14064

Cited by 9 publications

(9 citation statements)

References 8 publications

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“…Our group previously showed that SCD subjects had marked parasympathetic withdrawal in response to transient hypoxia (Sangkatumvong et al, 2011). Other studies found that decreased parasympathetic activity was associated with higher frequency of painful VOC (Nebor et al, 2011) and reported increased sympathetic activity in SCD during VOC compared to their steady state (Charlot et al, 2017). While many studies have employed heart rate variability (HRV) analysis to assess autonomic function, HRV provides information that is directly representative of only cardiac autonomic activity but not peripheral vascular control.…”

Section: Introductionmentioning

confidence: 99%

Sickle Cell Disease Subjects Have a Distinct Abnormal Autonomic Phenotype Characterized by Peripheral Vasoconstriction With Blunted Cardiac Response to Head-Up Tilt

et al. 2019

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In sickle cell disease (SCD), prolonged capillary transit times, resulting from reduced peripheral blood flow, increase the likelihood of rigid red cells entrapment in the microvasculature, predisposing to vaso-occlusive crisis. Since changes in peripheral flow are mediated by the autonomic nervous system (ANS), we tested the hypothesis that the cardiac and peripheral vascular responses to head-up tilt (HUT) are abnormal in SCD. Heart rate, respiration, non-invasive continuous blood pressure and finger photoplethysmogram (PPG) were monitored before, during, and after HUT in SCD, anemic controls and healthy subjects. Percent increase in heart rate from baseline was used to quantify cardiac ANS response, while percent decrease in PPG amplitude represented degree of peripheral vasoconstriction. After employing cluster analysis to determine threshold levels, the HUT responses were classified into four phenotypes: (CP) increased heart rate and peripheral vasoconstriction; (C) increased heart rate only; (P) peripheral vasoconstriction only; and (ST) subthreshold cardiac and peripheral vascular responses. Multinomial logistic regression (MLR) was used to relate these phenotypic responses to various parameters representing blood properties and baseline cardiovascular activity. The most common phenotypic response, CP, was found in 82% of non-SCD subjects, including those with chronic anemia. In contrast, 70% of SCD subjects responded abnormally to HUT: C-phenotype = 22%, P-phenotype = 37%, or ST-phenotype = 11%. MLR revealed that the HUT phenotypes were significantly associated with baseline cardiac parasympathetic activity, baseline peripheral vascular variability, hemoglobin level and SCD diagnosis. Low parasympathetic activity at baseline dramatically increased the probability of belonging to the P-phenotype in SCD subjects, even after adjusting for hemoglobin level, suggesting a characteristic autonomic dysfunction that is independent of anemia. Further analysis using a mathematical model of heart rate variability revealed that the low parasympathetic activity in P-phenotype SCD subjects was due to impaired respiratory-cardiac coupling rather than reduced cardiac baroreflex sensitivity. By having strong peripheral vasoconstriction without compensatory cardiac responses, P-phenotype subjects may be at increased risk for vaso-occlusive crisis. The classification of autonomic phenotypes based on HUT response may have potential use for guiding therapeutic interventions to alleviate the risk of adverse outcomes in SCD.

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Section: Introductionmentioning

confidence: 99%

Sickle Cell Disease Subjects Have a Distinct Abnormal Autonomic Phenotype Characterized by Peripheral Vasoconstriction With Blunted Cardiac Response to Head-Up Tilt

et al. 2019

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“…Along this line, salbutamol administration in SCD children further modified the ANS balance toward a deregulated profile similar to that observed during VOC. Charlot et al (2017) showed that HFa decreased during VOC compared to the steady state, suggesting parasympathetic withdrawal that certainly caused the dominance of the sympathetic activity over the parasympathetic activity, as reflected by the increase in LF/HF during VOC. Finally, we show that markers of SCD severity (hospitalization for VOC or occurrence of ACS) were associated with ANS modifications that may suggest parasympathetic withdrawal, as previously evidenced for ACS (Knight-Madden et al, 2013).…”

Section: Hrv Interpretationmentioning

confidence: 99%

Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease

et al. 2020

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Background: Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS). Methods: Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity. Results: SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV 1 /FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups: reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions. Conclusion: SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration.

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“…HRV in the time domain, frequency domain, and Poincaré plot non-linear analysis were performed as described by the Task Force recommendations (21)(22)(23). Time domain analysis included the following variables: (1) mean iRR; (2) maximum heart rate (maximum HR); (3) standard deviation of all normal iRRs (SDNN), which shows the general ANS activity; (4) root-mean-square difference of successive normal iRRs (RMSSD), showing the parasympathetic nervous system (PNS) modulation; (5) percentage of pairs of consecutive iRRs whose difference is > 50 m (pNN50), which also shows PNS modulation; and (6) triangular interpolation of the iRR histogram (TINN), which shows the general ANS activity (21).…”

Section: Autonomic Nervous System Activitymentioning

confidence: 99%

“…The frequency domain measures were mainly total power (TP, 0.04 -0.15 Hz), which shows the general ANS activity, and its low-frequency component [LF, (0.04 -0.15 Hz)], which is predominant an indicator of SNS activity, and its highfrequency component [HF, (0.15 -0.4 Hz)], which is an indicator of PNS activity. Last, the LF/HF ratio shows the sympathovagal balance, a high value indicating SNS dominance (22,23). At the end, Poincaré plot non-linear measures were evaluated: standard deviation of instantaneous beat-tobeat variability (SD1), which describes short-term variability (shows PNS modulation); standard deviation of longterm continuous iRRs (SD2), which describes long-term variability (shows general ANS activity); the SD2/SD1 ratio; and approximate entropy (ApEn), which detects changes in a time series, indicating ANS complexity.…”

Section: Autonomic Nervous System Activitymentioning

confidence: 99%

Heart Rate Variability in Adults with Sickle Cell Anemia During a Multitasking Field Test

et al. 2021

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Background: The integrity of the autonomic nervous system (ANS) is essential for keeping physiological processes stable, even under stress. Since there is growing interest in heart rate variability (HRV) analysis for the noninvasive assessment of the ANS in sickle cell anemia (SCA) patients, we studied the behavior of the ANS in the presence of a stressor that simulates daily-life multitasking, the Glittre ADL test (GA-T). Objectives: To evaluate the involvement of the ANS using HRV in adults with SCA during the GA-T and to quantify the strength of the correlation of HRV with lung and muscle functions. Methods: In this cross-sectional study, 16 adults with SCA and 12 healthy controls without sickle cell disease underwent HRV assessment during the GA-T, pulmonary function tests (spirometry, diffusing capacity for carbon monoxide (DLCO), and respiratory muscle testing). Peripheral muscle function [handgrip strength (HGS) and quadriceps strength (QS)] were also measured. Results: Compared to the healthy controls, adults with SCA showed lower HRV, with worse parasympathetic modulation due to reductions in the following indices: the root-mean-square difference of successive normal iRRs (iRR) (RMSSD); the percentage of pairs of consecutive iRRs whose difference is > 50 m (pNN50); the high-frequency component of heart rate variability (HF); and the standard deviation of instantaneous beat-to-beat variability (SD1) (P < 0.001 for all). Compared to healthy controls, individuals with SCA showed greater sympathovagal imbalance (higher ratio between low-frequency and HF components) and lower complexity of the ANS (lower approximate entropy). The GA-T time was correlated with parasympathetic activity indices: RMSSD (rs = -0.650, P < 0.01); pNN50 (rs = -0.932, P < 0.0001), HF (rs = -0.579, P < 0.01), and SD1 (rs = -0.814, P < 0.0001). Correlations between parasympathetic activity indices and DLCO, HGS, and QS measures were also significant. Conclusions: Adults with SCA have low HRV, with low parasympathetic activity, sympathovagal imbalance, and abnormal ANS complexity. In addition, lower HRV is associated with longer GA-T time, greater impairment of pulmonary diffusion, and greater muscle strength dysfunction.

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Changes in autonomic nervous activity during vaso-occlusive crisis in patients with sickle cell anaemia

Cited by 9 publications

References 8 publications

Sickle Cell Disease Subjects Have a Distinct Abnormal Autonomic Phenotype Characterized by Peripheral Vasoconstriction With Blunted Cardiac Response to Head-Up Tilt

Sickle Cell Disease Subjects Have a Distinct Abnormal Autonomic Phenotype Characterized by Peripheral Vasoconstriction With Blunted Cardiac Response to Head-Up Tilt

Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease

Heart Rate Variability in Adults with Sickle Cell Anemia During a Multitasking Field Test

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