Michal Mestanik

Alterations in vagal-immune pathway in long-lasting mental stress.

We studied a potential impact of chronic psychosocial load on the allostatic biomarkers--cardiac vagal activity, inflammation, and oxidative stress in healthy undergraduate students. Continuous resting ECG signals were monitored in a group of 16 female healthy students (age: 23.2±0.2 years, BMI: 20.9±0.5 kg/m2) at two time periods: right after holiday (rest period) and a day before final exams (stress period). Vagal activity was quantified by spectral analysis of heart rate variability at high frequency band (HF-HRV). The immune response was assessed from the level of tumor necrosis factor-alpha (TNF-α) in plasma. In addition, mean RR intervals were evaluated. We found that HF-HRV was significantly reduced and the TNF-α was increased in the stress period compared with the rest period. No significant changes were found in the RR interval. In conclusion, allostatic load induced by stress and the accompanying greater immune response decreased cardiovagal regulation in healthy young subjects. These findings may help understand the pathway by which stress can influence health and disease.

Direct means of obtaining CAVI0—a corrected cardio-ankle vascular stiffness index (CAVI)—from conventional CAVI measurements or their underlying variables

OBJECTIVE Cardio-ankle vascular index (CAVI) as measured using the VaSera device (CAVIVS, Fukuda Denshi), has been proposed as a stiffness index that does not depend on blood pressure. We have recently shown theoretically that CAVIVS still exhibits blood pressure dependence, and proposed the corrected index CAVI0. The present study aims to establish a method of calculating [Formula: see text] either (i) from VaSera-reported values of cardiac-brachial and brachial-ankle pulse transit times (tb and tba, respectively) and blood pressure, or (ii) directly from CAVIVS. To derive this method, the relationship among CAVIVS and its scale constants a and b, tb, tba, and blood pressure has to be established. APPROACH From data of 497 subjects, eight candidate CAVI parameters were defined and calculated, containing all combinations of left or right tb/tba/blood pressure. Candidates were evaluated through correlation with measured left and right CAVIVS. Correlations were compared statistically. Once the correct candidates were determined, two constants (a and b) required for converting CAVIVS to CAVI0 were estimated through linear regression. MAIN RESULTS Left and right CAVIVS are calculated using left and right tba; however, both left and right CAVIVS are calculated using right brachial blood pressures and right tb. Constants a and b for conversion of CAVIVS to CAVI0 were estimated to be 0.842 [0.836 0.848] and 0.753 [0.721 0.786] (mean [95%CI]), respectively. Equations to estimate CAVI0 from CAVIVS, and to directly calculate CAVI0 from the VaSera output are provided in this paper, as well as in a directly usable spreadsheet supplement. SIGNIFICANCE Our results permit straightforward calculation of [Formula: see text] during a study, as well as retrospective estimation of [Formula: see text] from CAVIVS in already published studies or where the original transit time values are not available, paving the way for thorough comparison of CAVI0 to CAVIVS in clinical and research settings. Novelty and significance Cardio-ankle vascular index (CAVI) as measured using the VaSera device (CAVIVS, Fukuda Denshi), has been proposed as a blood pressure-independent arterial stiffness index. We have recently shown theoretically that CAVIVS still exhibits pressure dependence, and proposed a corrected index, CAVI0. In the present study, we derived equations to directly obtain CAVI0 using data from the VaSera device. Our results permit straightforward calculation of [Formula: see text] during a study, as well as retrospective estimation of [Formula: see text] from CAVIVS in already published studies, paving the way for thorough comparison of CAVI0 to CAVIVS in clinical and research settings.

The complexity of electrodermal activity is altered in mental cognitive stressors

The aim of this study was to evaluate potential changes in the electrodermal activity (EDA) to enable the detection of variations in the sympathetic nervous system during mental load and recovery period. Several EDA parameters were used: SCA (skin conductance amplitude), frequency of NS-EDR (nonspecific electrodermal responses), SIE (symbolic information entropy), and ApEn (approximate entropy). The cohort consisted of 50 healthy students (average age: 23.33±0.24yr., 25 women). The stress profile consisted of five phases: baseline (P1), Stroop test (P2), recovery (P3), mental arithmetic test (P4), and recovery (P5). All phases of the stress profile lasted six minutes. The results indicate that the three EDA indices have sufficient sensitivity to detect changes in the sympathetic nervous system. The SCA, SIE and ApEn were significantly increased during mental loads and decreased during recovery periods. However, SCA remained significantly elevated during recovery periods versus baseline, and SIE and ApEn decreased significantly during recovery versus baseline. The frequency of NS-EDR had no significant changes during stress. The EDA is a sensitive marker for evaluation of changes during the activation of sympathetic nervous system under the influence of a load. Detailed knowledge of EDA regulatory mechanisms associated with stress could provide important information associated with autonomic dysregulation.

Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension

Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 ± 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 ± 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension-atherosclerosis interaction.

Symbolic dynamics of heart rate variability — a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Respiratory sinus arrhythmia – testing the method of choice for evaluation of cardiovagal regulation

Respiratory sinus arrhythmia (RSA) is an index of cardiovagal regulation, emotional and cognitive processing. RSA is quantified using heart rate variability (HRV) spectral analysis at respiratory-linked high-frequency band (HF-HRV) using Fast Fourier transformation (FFT) or autoregressive (AR) method, both requiring resampling of recordings - a potential source of error. We hypothesized that rarely used HRV time-frequency analysis with Lomb-Scargle periodogram (LSP) without resampling could be more sensitive to detect neurocardiac response to posture change than FFT and AR. Orthostasis (posture change from supine to standing) evoked significant decrease of HF-HRV well detectable by FFT, AR, and LSP. In contrast, during posture change from sitting to lying, significant increase of HF-HRV and peak HF was best detected using LSP. In regression analysis, the associations between RR-interval, HF-HRV, and peak HF were best detected when evaluated using LSP. Time-frequency HRV analysis with LSP could represent an important alternative to conventional FFT and AR methods for assessment of cardiovagal regulation indexed by RSA.

Heart rate variability in healthy term newborns is related to delivery mode: a prospective observational study

BackgroundEarly postnatal period is characterized by dramatic adaptation changes of cardiovascular and respiratory systems in newborns. There is still insufficient data regarding maturation of autonomic regulatory mechanisms in neonates early after delivery. Aim of this study was to analyze cardiac autonomic regulation in newborns within the first few postnatal days in relation to different modes of delivery using time and spectral heart rate variability analysis.MethodsEutrophic healthy term newborns (n = 46) were divided into three groups according to the delivery mode: vaginal delivery (VD group; n = 16), vaginal delivery with epidural analgesia (EDA group; n = 16), and caesarean section under general anesthesia (CS group; n = 14). Heart rate variability (HRV), blood pressure (BP), and blood oxygen saturation (SpO2) were measured within the first two hours after birth and on the third to fourth postnatal day. HRV parameters were evaluated in the time domain (RR intervals, mean square of successive differences – MSSD) and frequency domain (total spectral power – TP, absolute and relative low and high frequency powers).ResultsThe HRV spectral analysis showed significantly higher relative power of the high-frequency band (HF%) in the VD group compared to the CS group early after delivery (p = 0.002). HRV parameters and BP significantly increased on the third to fourth postnatal day in all groups (p < 0.05). No significant differences in basic characteristics, BP and SpO2 were identified between groups during both measurements.ConclusionsHRV analysis revealed higher cardiovagal modulation in spontaneously born newborns without analgesia compared to neonates born by caesarean section. It could represent a potential pathomechanism that leads to discrete abnormal neurocardiac regulation associated with higher risk for worsened postnatal adaptation of cardiovascular system in surgically delivered neonates.

Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy

Abstract Introduction LEOPARD syndrome is a rare genetic disorder characterised by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth and sensorineural deafness. Clinical manifestations are often mild, which may result in difficult and late diagnosis. Cardiac involvement may have a significant impact on the prognosis, however, appearance of severe abnormalities such as hypertrophic cardiomyopathy usually precedes the occurrence of multiple lentigines and may be asymptomatic. Case presentation We report two cases of LEOPARD syndrome with hypertrophic cardiomyopathy in a 10-year-old girl and an 18-year-old boy. In both cases, multiple lentigines, ocular hypertelorism and growth retardation were present. The first patient was followed up at the paediatric cardiology clinic due to the risk of progression of septal hypertrophy and pressure gradient across the left ventricular outflow tract, the second patient underwent surgery for a moderate obstruction of the left ventricular outflow tract with uncomplicated post-operative follow-up. Conclusion In both presented patients, hypertrophic cardiomyopathy was clinically silent and the murmur over the precordium was the sole cardiac abnormality revealed during routine visit. A detailed cardiologic examination should be considered in the patients with suspicion of LEOPARD syndrome since the ventricular hypertrophy is thought to precede the occurrence of lentigines and progress over time.

Improved assessment of arterial stiffness using corrected cardio-ankle vascular index (CAVI0) in overweight adolescents with white-coat and essential hypertension

Abstract Arterial stiffness is a marker of vascular damage. Although adiposity increases cardiovascular risk, the relationship between paediatric overweight and arterial stiffness is unclear. The study aimed to evaluate the simultaneous effect of hypertension and overweight on arterial stiffness using cardio-ankle vascular index (CAVI) and related novel, theoretically blood pressure (BP)-independent, index CAVI0. CAVI and CAVI0 were measured in 140 adolescent boys (16.0 ± 1.9 years) divided into age-matched groups: normal-weight normotensives, overweight normotensives, overweight white-coat hypertensives, and overweight essential hypertensives. Overweight normotensives had significantly lower CAVI and CAVI0 compared to normal-weight normotensives (4.81 ± 0.64 vs. 5.33 ± 0.66, p < .01; 7.10 ± 0.99 vs. 7.81 ± 1.00, p < .01, respectively). CAVI and CAVI0 in overweight essential hypertensives showed no significant difference compared to normal-weight normotensives and were significantly higher compared to overweight normotensives (5.32 ± 0.77 vs. 4.81 ± 0.64, p < .01; 7.77 ± 1.19 vs. 7.10 ± 0.99, p < .01, respectively). CAVI, but not CAVI0, was associated positively with diastolic pressure (0.022 mmHg−1, p = .002) and negatively with pulse pressure (−0.022 mmHg−1, p = .001), and it was significantly higher in overweight white-coat hypertensives compared to overweight normotensives (5.20 ± 0.63 vs. 4.81 ± 0.64, p < .05). The lowering effect of overweight on arterial stiffness indexed by CAVI and CAVI0 in hypertensive adolescents seems to counterbalance the early arteriosclerotic effect of essential hypertension. The increase in CAVI, but not CAVI0, in overweight white-coat hypertensives could be attributable to residual BP dependence of CAVI, which is not present in CAVI0. Under certain conditions, CAVI0 may offer a clinically relevant improved assessment of arterial stiffness superior to CAVI.

Potential Effect of Pharmacotherapy on Sympathetic Arousal in Autism

Abstract Background: Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder associated with autonomic nervous system (ANS) abnormalities. Moreover, at least 50% of children with ASD suffer from other comorbid diseases such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD) associated with receiving psychotropic medication. From this context we aimed to evaluate changes in sympathetic arousal using analysis of electrodermal activity (EDA) as an index of sympathetic cholinergic activity in treated and non-treated autistic children under resting conditions. Methods: We examined 23 children with ASD and 14 healthy age- and gender-matched children at the age of 7–15 years. The ASD patients were divided into ASD non-treated group (n=12) and ASD treated group (n=11). The EDA was continuously monitored during resting phase in a supine position. The EDA amplitude (μS) was computed as an average of 5 min baseline period. Results: We found significantly lower EDA in ASD non-treated subgroup compared to controls indicating subtle abnormalities in the regulation of the sympathetic nervous system. Although no significant differences were found between the ASD treated and non-treated subgroups the ASD treated group showed comparable sympathetic activity relative to controls indicating a potential ameliorated treatment effect on sympathetic arousal in ASD. Conclusions: These findings could help to determine differences in sympathetic arousal in treated and non-treated children with ASD, which is important for assessment of autism-linked cardiovascular risk depending on pharmacotherapy.