Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope

doi:10.1016/S0167-5273(98)00039-4

International Journal of Cardiology

Volume 64, Issue 2, 1 April 1998, Pages 185-194

https://doi.org/10.1016/S0167-5273(98)00039-4 Get rights and content

Abstract

Spectral analysis of heart rate variability was used to assess changes in autonomic function in 44 patients with vasovagal syndrome and 20 normal controls before and during postural tilt and to attempt to relate such changes to specific types of haemodynamic response to tilt. Frequency domain measurements of the high (HF) and low (LF) frequency bands and the ratio LF/HF were derived from Holter recordings, computed by Fast Fourier Analysis for 4 min intervals immediately before tilt testing, immediately after tilting and just before the end of the test. In the syncopal patients the mean values of LF and HF decreased significantly in response to tilting, while the LF/HF ratio remained constant. All parameters showed a statistically significant increase just before the onset of syncope. In the control group there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. The three subgroups of patients had similar patterns of changes in autonomic activity. The results of this study show that syncopal patients have a different pattern of response to the tilting test. The pathological mechanism leading to vasovagal syncope appears to be independent of the specific type of haemodynamic response to tilt testing.

Introduction

Vasovagal syncope has attracted a great deal of research interest, since it occurs in a large number of patients 1, 2, 3, 4and its pathophysiology is still unclear 5, 6, 7, 8, 9, 10, 11, 12. Vagal activation during syncope produces cardioinhibition and/or vasodepression and seems to be the last stage of other pathophysiological phenomena.

The tilting test, which allows the reproduction of syncope under controlled conditions, has undoubtedly contributed to the study of this problem 13, 14, 15, 16, 17, 18, 19. In recent years, a small number of valuable studies have employed temporal and/or spectral analysis of heart rate variability during tilt testing, in order to investigate the role of the autonomic nervous system in the pathophysiology of vasovagal syncope 20, 21, 22, 23, 24, 25, 26. Although these studies agree that the autonomic nervous system appears to play an important role in the pathogenesis of vasovagal syndrome, many questions remain regarding the precise aetiology and pathophysiological mechanism of the parasympathetic response. This is because of the relatively small numbers of patients involved in previous studies and also because no adequate comparisons have been made between different categories of syncopal patients, between patients and normal controls, or between different stages of the tilting procedure.

The present study used spectral analysis of heart rate variability to investigate the role of the autonomic nervous system in vasovagal syncope via inter- and intra-group comparisons of findings from three distinct groups of syncopal patients, classified according to their haemodynamic response to tilt testing, and a control group, before and during tilt testing.

Section snippets

Materials and methods

The study population consisted of 44 patients (30 men, 14 women, mean age [SD] 52.08 [13.94] years) who had reported at least two syncopal episodes of unknown origin during the previous three months and who had a recurrence of syncope during tilt testing. Patients with heart failure, diabetes mellitus, neuropathy, coronary heart disease or arterial hypertension, i.e. conditions which could affect the autonomic nervous system, were excluded. None of the patients were taking any medication,

Results

Of the 44 patients who had syncope during the tilting test 12 (27%) had a response of the cardioinhibitory type, 15 (34%) had a vasodepressor type response and 17 (39%) had a mixed response, as defined above. The mean test duration for all the patients was 27 min and the test durations for the individual subgroups did not differ significantly from this or from each other. There were no differences in age, number of syncopal episodes, duration of symptoms, systolic blood pressure or resting

Discussion

Previous studies have used temporal and/or spectral analysis to investigate RR variability before and during tilt testing, mostly in normal individuals 31, 35, 36, 37. These studies tend to agree that, in normal subjects, a change in posture from lying to standing causes a decrease in vagal modulation of the RR interval and an increase in sympathetic nervous system activity. However, their findings conflict with regard to the relationship between autonomic tone and syncope 20, 24, 25, 26, 31, 35

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Cited by (35)

Predictive value of very low frequency at spectral analysis among patients with unexplained syncope assessed by head-up tilt testing
2018, Archives of Cardiovascular Diseases
Citation Excerpt :
Heart rate variability (HRV) describes variations in both instantaneous heart rate and RR intervals [7]. It is an easy, cheap and non-invasive tool used to study the sympathetic and parasympathetic activity of the autonomic nervous system [8], but its role in the prediction of vasovagal syncope during HUTt remains unclear [9–14]. The aim of this study was, therefore, to evaluate the ability of the spectral components of HRV at rest to predict vasovagal syncope among patients with unexplained syncope referred for HUTt.
The role of heart rate variability (HRV) in the prediction of vasovagal syncope during head-up tilt testing (HUTt) is unclear.
To evaluate the ability of the spectral components of HRV at rest to predict vasovagal syncope among patients with unexplained syncope referred for HUTt.
Twenty-six consecutive patients with unexplained syncope were enrolled in the study. All patients underwent HRV evaluation at rest (very low frequency [VLF], low frequency [LF], high frequency [HF] and LF/HF ratio) and during HUTt. HUTt was performed using the Westminster protocol. Continuous electrocardiogram and blood pressure monitoring were performed throughout the test.
Eight (31%) patients developed syncope during HUTt. There were no baseline differences in terms of clinical features and HRV variables among patients who developed syncope and those who did not, except for VLF (2421 vs 896 ms²; P < 0.001). In the multivariable logistic regression analysis, including age and sex, VLF was the only independent variable associated with syncope during HUTt (odds ratio 1.002, 95% confidence interval 1.0003–1.0032; P = 0.02). The area under the curve at rest was 0.889 for VLF, 0.674 for HF and 0.611 for LF. A value of VLF > 2048 ms² was the optimal cut-off to predict syncope during HUTt (sensitivity 87.5%, specificity 72.2%).
VLF at rest predicted the incidence of syncope during HUTt. Further studies are warranted to confirm these preliminary data.
Le but de cette étude était d’évaluer le rôle des composantes spectrales de la variabilité de la fréquence cardiaque au repos chez des patients ayant une syncope de cause inexpliquée adressés pour un test d’inclinaison (Tilt test).
Vingt-six patients consécutifs ayant une syncope inexpliquée ont été inclus dans l’étude. Tous les patients ont bénéficié d’une étude de la variabilité de la fréquence cardiaque au repos, à très basse fréquence, à très haute fréquence, avec également détermination du rapport, ainsi que la réalisation systématique d’un Tilt test. Le Tilt test a été réalisé en utilisant le protocole de Westminster. Tout au long du test, un enregistrement continu de l’électrocardiogramme et de la pression artérielle a été réalisé.
Huit patients (31 %) ont présenté une syncope pendant le Tilt test. Il n’y avait pas de différence dans les caractéristiques cliniques de base ainsi que les paramètres de variabilité de la fréquence cardiaque parmi les patients qui ont présenté une syncope comparativement aux autres, en dehors de l’analyse spectrale à très faible fréquence (2421 ms² versus 895 ms², p < 0,001). Dans la régression logistique multivariée incluant l’âge et le genre, seule l’analyse spectrale à très basse fréquence était indépendamment associée à la survenue d’une syncope lors du Tilt test (odds ratio 1,002, IC 95 % 1,003–1,0032, p = 0,02). La surface sous la courbe ROC pour l’analyse spectrale à très basse fréquence au repos était de 0,889, 0,674 pour la haute fréquence et 0,611 pour la basse fréquence. Une valeur de l’analyse spectrale à très basse fréquence > 2048 ms² constituait la valeur seuil optimale pour prédire la survenue d’une syncope pendant le Tilt test (sensibilité 87,5 %, spécificité 72,2 %).
L’analyse spectrale à très basse fréquence au repos pourrait prédire la survenue d’une syncope survenant lors d’un Tilt test. D’autres études complémentaires sont nécessaires pour confirmer ces données préliminaires.
Recurrence plot of heart rate variability signal in patients with vasovagal syncopes
2016, Biomedical Signal Processing and Control
Citation Excerpt :
On the other hand, results yielded by frequency domain analysis did not point to any significant differences between the groups in any phase of the test. Based on our results, it is not possible to verify the claim [29,35] that HRV analysis is capable of identifying differences between patients and the control group, with respect to autonomic nervous system activation as a reaction to orthostasis, or of reflecting changes in the autonomic nervous system related to the onset of vasovagal episodes. In any case, the measuring protocol is partly divided in our study, with the main focus on the total test duration of 10 minutes without using tilt table.
Currently, heart rate variability (HRV) is commonly evaluated using time and frequency domain analysis in the clinical practice. Due to the fact that cardiovascular system is regulated by the autonomic nervous system (ANS) that also influences HRV, however exhibits rather nonlinear behaviour, it appears more appropriate to apply nonlinear methods to evaluate functioning of ANS. This study presents recurrence analysis as a tool to test the presence of ANS dysfunction that is responsible i.e. for orthostatic (vasovagal) syncope by which abnormal HRV has been demonstrated in the past.
Study included 18 patients that experienced vasovagal syncope (mean age 23.7 ± 5.2 years) and 18 healthy subjects (mean age 24.5 ± 3.2, p = 0.85). In all tested subjects, ECG recording was performed during active orthostatic test that comprised two phases (5 min of resting in a supine position and 5 min of active standing). Sequence of R-R intervals (time intervals between two consecutive heart beats derived from ECG) was analysed using standard time (mean RR, mean HR, SDNN, SDHR, RMSSD, NN50 and pNN50) and frequency domain (LF, HF and LF/HF ratio) analysis. Moreover, recurrence analysis was performed (RATIO, DIV, AVDL, MAXV, DET, ENTR, LMAX, TT and LAM).
Frequency domain analysis did not demonstrate significant difference between the two groups in any of the parameters during both phases of the test. On the contrary, both time domain analysis and recurrence analysis showed comparable findings in both groups during resting phase of the orthostatic test with a significant change of most tested parameters after stand-up.
As the use of time domain HRV may be perceived as problematic regarding their interpretation in short ECG recordings, recurrence analysis appears to be a sensitive tool for detecting ANS dysfunction in patients with vasovagal syncope.
Pain-related autonomic response is modulated by the medial prefrontal cortex: An ECG-fMRI study in men
2015, Journal of the Neurological Sciences
Citation Excerpt :
The NRS is the most often cause of syncope [42], while pain is one of the most frequent causes of the NRS [8]. The increase of HF–HRV just before the onset of syncope suggests that measuring HF parameter during pain-evoked fMRI could be a reasonable approach for investigating the mechanism of the NRS [15,21]. Although due to safety precautions we did not include subjects with a history of syncope in this study and none of them had syncope during the examination, we suggest that our pain-evoked simultaneous ECG–fMRI technique may be a new method modeling NRS in an experimental situation.
Our goal was to identify brain structures responsible for pain-related autonomic changes by the correlation of simultaneously acquired functional magnetic resonance imaging (fMRI) and electrocardiogram (ECG) data.
Eighteen healthy men (age: 22.89 ± 1.96) were involved. Painful sensation was evoked by heat. Simultaneously recorded brain fMRI and ECG data during pain were compared to data acquired during a non-painful heat sensation. From the ECG data, time- and frequency domain parameters of heart rate variability (HRV) were extracted.
We found that: (1) among the common elements of both pain network and central autonomic network (CAN) only the medial prefrontal frontal cortex (MPFC) showed significant correlation with HRV; (2) the parasympathetic response to the painful stimuli showed a positive, while the sympathetic response a negative association with pain related BOLD-signal change observed in MPFC; (3) time domain parameters of HRV were negatively associated with MPFC activation.
The novelty of our study—compared to previous ECG–fMRI studies—is that we used pain as stimulus and investigated both frequency- and time-domain parameters of HRV. Compared to other stimuli used in earlier studies to activate the CAN, pain sensation can be standardized easier and might allow us to better understand the functional organization of CAN. The results of the current ECG–fMRI study may have direct clinical relevance in understanding the pathomechanisms of several clinical conditions.
There are some simultaneous ECG–fMRI and ECG–Positron Emission Tomography (PET) studies, but limited information is available about the pain-related brain function–HRV relations. The novelty of our study is that we used pain as stimulus to activate the central autonomic network and investigated both frequency- and time-domain parameters of HRV.
Autonomic modulation and cardiac contractility in vasovagal syncope
2010, International Journal of Cardiology
Citation Excerpt :
Furthermore, it was previously demonstrated by echocardiography that there is no significant decrease in cardiac volume before syncope that could serve as a trigger of vasovagal syncope [21]. The studies that evaluated heart rate variability during the upright tilt test had very different results [22–25]. These inconsistencies are due to the different algorithms and recording timings utilized, but also to the variability of the autonomic nervous system, particularly if tested during an unstable condition such as passive orthostatism.
Previous studies proposed as one of the main mechanisms involved in neurally mediated syncope, the stimulation of ventricular mechanoreceptors as the final trigger for vagal discharge.
This study aimed to verify the presence of a sympathetic driven increase of cardiac contractility before vasovagal syncope.
We studied 23 patients with recurrent syncope. All underwent a 60° tilt with pharmacologic challenge (sublingual spray nitrate). Two conditions were used to assess autonomic activity by heart rate variability analysis: in a supine position after 5 min of rest and after 15 min of tilt. Simultaneously, cardiac contractility was quantified by tissue-Doppler echocardiography at the base of the free walls of left ventricle. The peak myocardial velocities during systole (Sw) and late diastole (Aw) were considered.
Passive tilt induced a significant increase of the low frequency component (LF) as well as a decrease of the high frequency component (HF) in positive patients (LF: from 49 ± 18 to 65 ± 18 nu, p < 0.05; HF: from 41 ± 21 to 26 ± 16 nu, p < 0.05). Tissue-Doppler showed a similar increase in Sw in both positive and negative patients but showed a significant decrease of Aw in syncopal subjects (p < 0.005).
Our results do not show an increase in ventricular contractility before tilt-induced syncope, or in presence of a valuable increase of sympathetic activity. Instead, we observe a reduction of atrial contractility, which may be a contributory component in the pathogenesis of vasovagal syncope.
Vulnerability to simple faints is predicted by regional differences in brain anatomy
2009, NeuroImage
Neurocardiogenic syncope (NCS, simple fainting) is a common and typically benign familial condition, which rarely may result in traumatic injury or hypoxic convulsions. NCS is associated with emotional triggers, anxiety states and stress. However, the etiology of NCS, as a psychophysiological process, is poorly understood. We therefore investigated the relationship between NCS and brain anatomy. We studied a non-clinical sample of eighteen individuals with histories characteristic of NCS, and nineteen matched controls who had never fainted. We recorded fainting frequency, resting heart rate variability measures and anxiety levels. Structural T1-weighted magnetic resonance images (MRI) were acquired at 1.5 T. Associations between brain morphometry (regional gray and white matter volumes) and NCS, resting physiology and anxiety were tested using voxel-based morphometry (VBM). Compared to controls, NCS participants had lower regional brain volume within medulla and midbrain (a priori regions of interest). Moreover, across NCS individuals, lower gray matter volume in contiguous regions of left caudate nucleus predicted enhanced parasympathetic cardiac tone, fainting frequency and anxiety levels. Our findings provide preliminary evidence for a hierarchical anatomical basis to NCS. First, differences in the volume of brainstem centers supporting cardiovascular homeostasis may relate to constitutional predisposition to NCS. Second, differences in the structural organization of the caudate nucleus in NCS individuals may relate to fainting frequency via interactions between emotional state and parasympathetic control of the heart. These observations highlight the application of VBM to the identification of neurovisceral mechanisms relevant to psychosomatic medicine and the neuroscience of emotion.
Modulations of autonomic activity leading to tilt-mediated syncope
2007, International Journal of Cardiology
Vasovagal syncope (VVS) results from a complex interaction among afferent vagal and sympathetic signals, cortical modulation and bulbar integration. The aim of our study was to evaluate the modifications of autonomic activity during Upright Tilt Test (UTT) in patients with unexplained syncope, and to correlate these changes with the specific cardiovascular reactions induced.
We studied 90 patients with a mean age of 44 ± 17 yrs. Frequency domain analysis of heart rate variability (HRV) (normalized units) was performed on 2 periods of 300 beats: at baseline and after 5 min of 60° tilt. UTT was positive in 56 patients (62%). The responses were cardioinhibitory in 8, vasodepressive in 15, mixed in 33. Baseline LF and HF components did not show significant difference between subjects with positive or negative test (HF: 39 ± 21 versus 41 ± 22; LF: 50 ± 22 versus 49 ± 23). HRV during UTT showed similar changes in patients with positive or negative test. However, subjects with mixed or cardioinhibitory reactions were characterized by a relevant increase of LF during UTT (from 47 ± 23 to 66 ± 21), whereas the others by a non-significant decrease of the same component (from 57 ± 19 to 51 ± 31).
Patients developing a reflex cardioinhibitory reaction during UTT were characterized by an increase of sympathetic activity during the test, that might represent an essential factor to induce a stronger vagal reaction on the sinus node. On the contrary, in subjects with vasodepressive reactions an inadequate enhancement of the sympathetic drive, probably causing a failure of peripheral vasoconstriction, was evidenced.

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Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Am Heart J.

Am J Cardiol.

Am J Med.

Am J Cardiol.

J Am Coll Cardiol.

J Am Coll Cardiol.

Am J Cardiol.

Am J Cardiol.

J Am Coll Cardiol.

Am J Cardiol.

J Am Coll Cardiol.

Am J Cardiol.

Am J Cardiol.

Am J Cardiol.

J Am Coll Cardiol.

Int J Cardiol.

The incidence of malignant vasovagal syndrome in patients with recurrent syncope

Eur Heart J.

Long-term follow up of patients with unexplained syncope and negative electrophysiologic study

Eur Heart J.

Diagnostic evaluation of syncope

Am J Med.

A prospective evaluation and follow-up of patients with syncope

N Engl J Med

Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of vaso-vagal reaction

Acta Physiol Scand.

Behavior of left ventricular mechanoreceptors with myelined and nonmyelinated afferent vagal fibers in cats

Circ Res.