Comparative Analysis of Short-Term Variability of RR and QT Intervals for the Assessment of Autonomic Nerve Activity

Abstract The purpose of this study is to investigate the behavior of autonomic nervous system (ANS), reflected by shortterm variability (STV

Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p < 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p < 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p < 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p < 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p < 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated

QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESCWorking Group on Cardiac Cellular Electrophysiology

This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients

Introduction Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. Objectives The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. Methods We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. Results There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. Conclusions Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation

A Time-Varying Non-Parametric Methodology for Assessing Changes in QT Variability Unrelated to Heart Rate Variability

OBJECTIVE: To propose and test a novel methodology to measure changes in QT interval variability (QTV) unrelated to RR interval variability (RRV) in non-stationary conditions. METHODS: Time-frequency coherent and residual spectra representing QTV related (QTVrRRV) and unrelated (QTVuRRV) to RRV, respectively, are estimated using time-frequency Cohen's class distributions. The proposed approach decomposes the non-stationary output spectrum of any two-input one-output model with uncorrelated inputs into two spectra representing the information related and unrelated to one of the two inputs, respectively. An algorithm to correct for the bias of the time-frequency coherence function between QTV and RRV is proposed to provide accurate estimates of both QTVuRRV and QTVrRRV. Two simulation studies were conducted to assess the methodology in challenging non-stationary conditions and data recorded during head-up tilt in 16 healthy volunteers were analyzed. RESULTS: In the simulation studies, QTVuRRV changes were tracked with only a minor delay due to the filtering necessary to estimate the non-stationary spectra. The correlation coefficient between theoretical and estimated patterns was >0.92 even for extremely noisy recordings (SNR in QTV =-10dB). During head-up tilt, QTVrRRV explained the largest proportion of QTV, whereas QTVuRRV showed higher relative increase than QTV or QTVrRRV in all spectral bands (P<0.05 for most pairwise comparisons). CONCLUSION: The proposed approach accurately tracks changes in QTVuRRV. Head-up tilt induced a slightly greater increase in QTVuRRV than in QTVrRRV. SIGNIFICANCE: The proposed index QTVuRRV may represent an indirect measure of intrinsic ventricular repolarization variability, a marker of cardiac instability associated with sympathetic ventricular modulation and sudden cardiac death

Clinical studies of the renin-angiotensin-aldosterone system and cardiac autonomic regulation in man

The work embodied in this thesis was designed to explore the interaction between the renin -angiotensin -aldosterone system (RAAS) and the autonomic nervous system. It was stimulated by the observations that the neurohormonal suppression of the RAAS by ACE inhibitors in chronic heart failure (CHF) is inadequate, and that high residual levels of circulating aldosterone have been shown to have detrimental autonomic modulating effects independent of angiotensin II in experimental models.The effects of aldosterone blockade with spironolactone therapy were examined in CHF patients already established on ACE inhibitors. It was observed that spironolactone has beneficial parasympathomimetic properties, improving heart rate variability and reducing heart rate, particularly during the early morning hours of the day when ACTH -induced aldosterone secretion is maximal. The interaction between the RAAS and the parasympathetic tone was explored further in a series of normal volunteer studies. Although the effects of ACE inhibitors are well recognised, not much is known about the parasympathomimetic properties of direct angiotensin II or aldosterone receptor antagonism. In this thesis, it was demonstrated that losartan, an angiotensin II receptor antagonist, and enalapril, an ACE inhibitor, were equally effective in improving the vagally-mediated baroreflex response in salt depleted normotensive subjects. It was also demonstrated that direct intravenous aldosterone administration impaired the baroreflex response to vasopressor agents in healthy subjects.The observed vagomimetic effects of aldosterone blockade may have important therapeutic implications, suggesting the possibility that spironolactone may have anti -ischaemic or anti -arrhythmic properties. However, aldosterone blockade did not appear to have any significant impact on either autonomic tone or ischaemic events when administered to patients with ischaemic heart disease but preserved LV function. The reasons for the latter remain unclear but may reflect differences in disease -state (less neurohormonal activation, and a larger proportion of these patients was established on beta -blockers -which may influence autonomic tone - and only a minority was taking concomitant ACE inhibitors, compared to the CHF cohort). In CHF however, spironolactone was shown to improve QT dispersion, a surrogate marker of arrhythmic activity and sudden cardiac death. Mechanisms in which aldosterone may contribute towards dispersion of the QT intervals on the electrocardiogram are probably multifactorial. Aldosterone increases cardiac afterload (by increasing vascular tone and potentiating vascular smooth muscle hypertrophy) and it is demonstrated that cardiac afterload would increase QT dispersion through mechano- electrical feedback. Vagal tone modulation itself however did not contribute towards QT dispersion.These studies demonstrate how inextricably linked the RAAS and the autonomic nervous system is. In particular, the detrimental autonomic effects of aldosterone in CHF have been highlighted. The findings of these studies highlight possible mechanisms and provide valuable insights as to why further therapeutic mileage is gained by the addition of an aldosterone antagonist in CHF patients who have already been established on ACE inhibitors

Autonomic function in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition with poorly understood pathophysiology and increased cardiovascular risk. The mechanisms for increased cardiovascular risk are not fully known, however one novel mechanism explored in this thesis is autonomic nervous system (ANS) dysfunction. The thesis comprises of: a systematic literature review; two case-control studies (n=30 RA patients, n=34 controls; a longitudinal case-study (n=1 RA patient); a cohort study (n=112 RA patients); and a randomised placebo controlled crossover study (n=10 healthy controls). The work presented in this thesis demonstrates that ANS dysfunction is prevalent in ~60 % of RA patients and characterised by heightened sympathetic outflow to the peripheral vasculature (determined by muscle sympathetic nerve activity using microneurography), depressed baroreflex control of heart rate (determined using the modified Oxford technique), depressed heart rate variability and heightened vascular responses to stressors (cold pressor test and mental stress). Inflammation was associated with ANS dysfunction, and may well contribute to the increased cardiovascular risk seen in RA. Further studies are required to: confirm these findings; determine whether therapeutic strategies to restore ANS function improve prognosis in RA; and further explore the precise mechanisms by which inflammatory cytokines may influence ANS function in health and disease