Association of the Heart Rate Variability Response to Active Standing with the Severity of Calcific Aortic Valve Disease: Novel Insights of a Neurocardiovascular Pathology.

The aim of this work was to obtain insights of the participation of the autonomic nervous system in different stages of calcific aortic valve disease (CAVD) by heart rate variability (HRV) analysis. Studying subjects with no valve impairments and CAVD patients, we also sought to quantify the independent contribution or explanatory capacity of the aortic valve echocardiographic parameters involved in the HRV changes caused by active standing using hierarchical partitioning models to consider other variables or potential confounders. We detected smaller adjustments of the cardiac autonomic response at active standing caused specifically by the aortic valve deterioration. The highest association (i.e., the highest percentage of independent exploratory capacity) was found between the aortic valve area and the active standing changes in the short-term HRV scaling exponent α1 (4.591%). The valve's maximum pressure gradient echocardiographic parameter was present in most models assessed (in six out of eight models of HRV indices that included a valve parameter as an independent variable). Overall, our study provides insights with a wider perspective to explore and consider CAVD as a neurocardiovascular pathology. This pathology involves autonomic-driven compensatory mechanisms that seem generated by the aortic valve deterioration.

Recurrence Quantitative Analysis of Wavelet-Based Surrogate Data for Nonlinearity Testing in Heart Rate Variability.

Exploring the presence of nonlinearity through surrogate data testing provides insights into the nature of physical and biological systems like those obtained from heart rate variability (HRV). Short-term HRV time series are of great clinical interest to study autonomic impairments manifested in chronic diseases such as the end stage renal disease (ESRD) and the response of patients to treatment with hemodialysis (HD). In contrast to Iterative Amplitude Adjusted Fourier Transform (IAAFT), the Pinned Wavelet Iterative Amplitude Adjusted Fourier Transform (PWIAAFT) surrogates preserve nonstationary behavior in time series, a common characteristic of HRV. We aimed to test synthetic data and HRV time series for the existence of nonlinearity. Recurrence Quantitative Analysis (RQA) indices were used as discriminative statistics in IAAFT and PWIAAFT surrogates of linear stationary and nonstationary processes. HRV time series of healthy subjects and 29 ESRD patients before and after HD were tested in this setting during an active standing test. Contrary to PWIAAFT, linear nonstationary time series may be erroneously regarded as nonlinear according to the IAAFT surrogates. Here, a lower proportion of HRV time series was classified as nonlinear with PWIAAFT, compared to IAAFT, confirming that the nonstationarity condition influences the testing of nonlinear behavior in HRV. A contribution of nonlinearity was found in the HRV data of healthy individuals. A lower proportion of nonlinear time series was also found in ESRD patients, but statistical significance was not found. Although this proportion tends to be lower in ESRD patients, as much as 60% of time series proved to be nonlinear in healthy subjects. Given the important contribution of nonlinearity in HRV data, a nonlinear point of view is required to achieve a broader understanding of cardiovascular physiology.

Evaluación de la frecuencia cardiaca durante la bipedestación activa inicial en pacientes que padecen síncope vasovagal / Evaluation of the heart rate during initial active standing in patients with vasovagal syncope

Introducción: El síncope vasovagal es la causa más frecuente de pérdida breve de la conciencia, en su etiopatogenia se reporta una disfunción autonómica que puede ponerse de manifiesto en la bipedestación activa inmediata. Objetivo: Comparar la dinámica de los cambios de la frecuencia cardíaca durante la bipedestación activa inmediata, de pacientes que padecen síncope vasovagal y sujetos controles. Métodos: Se evaluaron 132 sujetos supuestamente sanos (grupo A) entre 18 y 25 años y 156 pacientes con síncopes vasovagales; fueron divididos por su respuesta ante la bipedestación prolongada, negativa 111 (grupo B) y positiva 45 (grupo C). Se registró la actividad electrocardiográfica en decúbito supino y al inicio de la bipedestación activa, se obtuvo las secuencias de intervalos RR. Se comparó la frecuencia cardíaca en los 3 grupos, con 22 indicadores (posicionales, temporales, ordinales y relacionales, promedio y de la velocidad de los cambios). Resultados: No hubo diferencias en los indicadores promedio, sin embargo, algunos que evalúan la velocidad del cambio inicial, fueron significativamente menores en el grupo A comparado con B y C (p < 0,05), mientras que los que evalúan la velocidad de recuperación, fueron significativamente menores en el grupo C comparado con A y B. Conclusión: La dinámica de los cambios de frecuencia, permitió encontrar indicadores que pueden considerarse posibles predictores de una respuesta cardiovascular inadecuada en pacientes con síncope vasovagal(AU)

Introduction: Vasovagal syncope is the most frequent cause of brief loss of consciousness, in its etiopathogenesis an autonomic dysfunction is reported that can be manifested in immediate active standing. Objective: To compare the dynamics of heart rate changes during immediate active standing of patients suffering from vasovagal syncope with control subjects. Methods: 132 supposedly healthy subjects (group A) between 18 and 25 years old and 156 patients with vasovagal syncope were evaluated, which were divided by their response to prolonged standing, negative 111 (group B) and positive 45 (group C). Electrocardiographic activity was recorded in the supine position and at the beginning of active standing, the sequences of RR intervals were obtained. The heart rate was compared in the 3 groups, using 22 indicators (positional, temporal, ordinal and relational, average and of the speed of changes). Results: Differences were not found in the average indicators in the analyzed period, however, some that evaluate the speed of the initial change were significantly lower in group A compared to B and C (p < 0.05), while others that evaluate the speed recovery rates were significantly lower in group C compared to A and B. This allows to characterize, compare and differentiate the groups studied during the complex and rapid interactions that occur in the change of position. Conclusion: The dynamic of frequency changes, allowed to find indicators, which can be considered as possible predictors of an inadequate cardiovascular response in patients with vasovagal syncope(AU)

Cardiac Autonomic Response to Active Standing in Calcific Aortic Valve Stenosis.

Aortic stenosis is a progressive heart valve disorder characterized by calcification of the leaflets. Heart rate variability (HRV) analysis has been proposed for assessing the heart response to autonomic activity, which is documented to be altered in different cardiac diseases. The objective of the study was to evaluate changes of HRV in patients with aortic stenosis by an active standing challenge. Twenty-two volunteers without alterations in the aortic valve (NAV) and twenty-five patients diagnosed with moderate and severe calcific aortic valve stenosis (AVS) participated in this cross-sectional study. Ten minute electrocardiograms were performed in a supine position and in active standing positions afterwards, to obtain temporal, spectral, and scaling HRV indices: mean value of all NN intervals (meanNN), low-frequency (LF) and high-frequency (HF) bands spectral power, and the short-term scaling indices (α1 and αsign1). The AVS group showed higher values of LF, LF/HF and αsign1 compared with the NAV group at supine position. These patients also expressed smaller changes in meanNN, LF, HF, LF/HF, α1, and αsign1 between positions. In conclusion, we confirmed from short-term recordings that patients with moderate and severe calcific AVS have a decreased cardiac parasympathetic supine response and that the dynamic of heart rate fluctuations is modified compared to NAV subjects, but we also evidenced that they manifest reduced autonomic adjustments caused by the active standing challenge.

Association between Mean Heart Rate and Recurrence Quantification Analysis of Heart Rate Variability in End-Stage Renal Disease.

Linear heart rate variability (HRV) indices are dependent on the mean heart rate, which has been demonstrated in different models (from sinoatrial cells to humans). The association between nonlinear HRV indices, including those provided by recurrence plot quantitative analysis (RQA), and the mean heart rate (or the mean cardiac period, also called meanNN) has been scarcely studied. For this purpose, we analyzed RQA indices of five minute-long HRV time series obtained in the supine position and during active standing from 30 healthy subjects and 29 end-stage renal disease (ESRD) patients (before and after hemodialysis). In the supine position, ESRD patients showed shorter meanNN (i.e., faster heart rate) and decreased variability compared to healthy subjects. The healthy subjects responded to active standing by shortening the meanNN and decreasing HRV indices to reach similar values of ESRD patients. Bivariate correlations between all RQA indices and meanNN were significant in healthy subjects and ESRD after hemodialysis and for most RQA indices in ESRD patients before hemodialysis. Multiple linear regression analyses showed that RQA indices were also dependent on the position and the ESRD condition. Then, future studies should consider the association among RQA indices, meanNN, and these other factors for a correct interpretation of HRV.

The additional impact of type 2 diabetes on baroreflex sensitivity of coronary artery disease patients might be undetectable in presence of deterioration of mechanical vascular properties.

Both deterioration of the mechanical vascular properties of barosensitive vessels and autonomic derangement lead to modification of baroreflex sensitivity (BRS) in coronary artery disease (CAD) individuals. Type 2 diabetes (T2D) reduces BRS as well even in absence of cardiac autonomic neuropathy. The aim of the study is to clarify whether, assigned the degree of mechanical vascular impairment and without cardiac autonomic neuropathy, the additional autonomic dysfunction imposed in CAD patients by T2D (CAD-T2D) decreases BRS further. We considered CAD (n = 18) and CAD-T2D (n = 19) males featuring similar increases of average carotid intima media thickness (ACIMT) and we compared them to age- and gender-matched healthy (H, n = 19) subjects. BRS was computed from spontaneous beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP) at supine resting (REST) and during active standing (STAND). BRS was estimated via methods including time domain, spectral, cross-spectral, and model-based techniques. We found that (i) at REST BRS was lower in CAD and CAD-T2D groups than in H subjects but no difference was detected between CAD and CAD-T2D individuals; (ii) STAND induced an additional decrease of BRS visible in all the groups but again BRS estimates of CAD and CAD-T2D patients were alike; (iii) even though with different statistical power, BRS markers reached similar conclusions with the notable exception of the BRS computed via model-based approach that did not detect the BRS decrease during STAND. In presence of a mechanical vascular impairment, indexes estimating BRS from spontaneous HP and SAP fluctuations might be useless to detect the additional derangement of the autonomic control in CAD-T2D without cardiac autonomic neuropathy compared to CAD, thus limiting the applications of cardiovascular variability analysis to typify CAD-T2D individuals. Graphical abstract Graphical representation of the baroreflex sensitivity (BRS) estimated from spontaneous fluctuations of heart period and systolic arterial pressure via transfer function (TF) in low frequency (LF) band (from 0.04 to 0.15 Hz). BRS was reported as a function of the group (i.e., healthy (H), coronary artery disease (CAD) and CAD with type 2 diabetes (CAD-T2D) groups) at REST (black bars) and during STAND (white bars). Values are shown as mean plus standard deviation. The symbol "*" indicates a significant difference between conditions within the same group (i.e., H, CAD, or CAD-T2D) and the symbol "§" indicates a significant difference between groups within the same experimental condition (i.e., REST or STAND). BRS cannot distinguish CAD and CAD-T2D groups both at REST and during STAND, while it is useful to distinguish experimental conditions and separate pathological groups from H subjects.

Influence of age and gender on the phase and strength of the relation between heart period and systolic blood pressure spontaneous fluctuations.

Aging affects baroreflex regulation. The effect of senescence on baroreflex control was assessed from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase and strength are usually disregarded. This study checks whether the HP-SAP phase and strength, as estimated, respectively, via the phase of the HP-SAP cross spectrum (PhHP-SAP) and squared coherence function (K2HP-SAP), vary with age in healthy individuals and trends are gender-dependent. We evaluated 110 healthy volunteers (55 males) divided into five age subgroups (21-30, 31-40, 41-50, 51-60, and 61-70 yr). Each subgroup was formed by 22 subjects (11 males). HP series was extracted from electrocardiogram and SAP from finger arterial pressure at supine resting (REST) and during active standing (STAND). PhHP-SAP and K2HP-SAP functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high-frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND PhHP-SAP(LF) showed a negative correlation with age regardless of gender even though values were more negative in women. This trend was shown to be compatible with a progressive increase of the baroreflex latency with age. At REST K2HP-SAP(LF) decreased with age regardless of gender, but during STAND the high values of K2HP-SAP(LF) were more preserved in men than women. At REST and during STAND the association of PhHP-SAP(HF) and K2HP-SAP(HF) with age was absent. The findings points to a greater instability of baroreflex control with age that seems to affect to a greater extent women than men. NEW & NOTEWORTHY Aging increases cardiac baroreflex latency and decreases the degree of cardiac baroreflex involvement in regulating cardiovascular variables. These trends are gender independent but lead to longer delays and asmaller degree of cardiac baroreflex involvement in women than in men, especially during active standing, with important implications on the tolerance to an orthostatic stressor.