Time, frequency and information domain analysis of heart period and QT variability in asymptomatic long QT syndrome type 2 patients.

none8siThis study was designed to characterize in time, frequency and information domains heart period (HP) and QT interval variabilities in asymptomatic (ASYMP) long QT syndrome type 2 (LQT2) subjects. HP, approximated as the temporal distance between two consecutive R-wave peaks, and QT, approximated as the temporal distance between the R-wave peak and the T-wave offset, were automatically derived from 24h Holter recordings in 10 ASYMP LQT2 patients and 13 healthy non mutation carriers (NMC) subjects. All analyses were carried out during DAY (from 2 to 6 PM) and NIGHT (from 12 to 4 AM). Mean, variance, spectral power and complexity indices at short, medium and long time scales were assessed over HP and QT beat-to-beat series. Circadian rhythmicity was evident in both NMC and ASYMP LQT2 but ASYMP LQT2 subjects were characterized by higher HP, QT interval and HP variability during both DAY and NIGHT. In addition, multiscale complexity analysis was able to differentiate the groups by showing a higher HP complexity and a lower QT complexity at long time scales in ASYMP LQT2 during DAY. ASYMP LQT2 exhibited a different autonomic control compared to NMC and such a differentiation could be protective and assure them a lower risk profile.Bari V, 11.; Girardengo, G; Marchi, A; De Maria, B; Brink, Pa; Crotti, L; Schwartz, Pj; Porta, ABari V, 1. 1.; Girardengo, Giulia; Marchi, A; De Maria, B; Brink, Pa; Crotti, Lia; Schwartz, Peter; Porta, A

Multiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1

Abstract The study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population

Autonomic control of heart rate and QT interval variability influences arrhythmic risk in long QT syndrome type 1.

BACKGROUND: A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes. OBJECTIVES: This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation. METHODS: Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes. RESULTS: The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest. CONCLUSIONS: The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential "autonomic make-up," likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management

Multiscale complexity analysis of short QT interval variability series stratifies the arrhythmic risk of long QT syndrome type 1 patients

A linear model-based multiscale complexity (MSC) approach was here applied to short heart period (HP) and QT interval variability series derived from 24 hours Holter ECG recordings in a group of long QT syndrome type 1 (LQT1) patients. The MSC approach allows to assess complexity in the typical frequency bands of HP and QT variability, i.e. low frequency (LF, from 0.04 to 0.15 Hz) and high frequency (HF, from 0.15 to 0.5 Hz). MSC was computed along with a single scale complexity over 7 LQT1 asymptomatic mutation carriers (AMC), 22 symptomatic mutation carriers (SMC) and 13 healthy non-mutation carriers (NMC) belonging to the same family line during daytime and nighttime. Time domain markers and HP variability complexity analyses were unable to separate groups. While single scale QT variability complexity analysis could distinguish NMC from mutation carriers, solely MSC of QT variability distinguished AMCs from SMCs, showing that AMCs have a reduced complexity in LF band during daytime. We conclude that a reduced complexity of the sympathetic drive directed to the ventricles might be protective against life threatening arrhythmias especially during day being the most risky period for LQT1 patients. MSC of QT variability could be fruitfully exploited to improve risk stratification in LQT1 population

Filtering approach based on empirical mode decomposition improves the assessment of short scale complexity in long QT syndrome type 1 population

This study assesses the complexity of heart period (HP) and QT variability series through sample entropy (SampEn) in long QT syndrome type 1 individuals. In order to improve signal-to-noise ratio SampEn was evaluated over the original series (SampEn(0)) and over the residual computed by subtracting the first oscillatory mode identified by empirical mode decomposition (SampEnEMD1R). HP and QT interval were continuously extracted during daytime (2:00-6:00 PM) from 24 hour Holter recordings in 14 non mutation carriers (NMCs) and 34 mutation carriers (MCs) subdivided in 11 asymptomatic (ASYMP) and 23 symptomatic (SYMP). Both NMCs and MCs belonged to the same family line. While SampEn(0) did not show differences among the three groups, SampEn(EMD1R) assessed over the QT series significantly decreased in ASYMP subjects. SampEn(EMD1R) identified a possible factor (i.e. the lower short scale QT complexity) that might contribute to the different risk profile of the ASYMP group

Symbolic analysis of heart period and QT interval variabilities in LQT1 patients.

Heart period and QT interval variabilities carry important information about the state of the autonomic nervous system. Autonomic function is impaired in the long QT syndrome type 1 (LQT1) and this impairment plays a central role in triggering fatal arrhythmias. Twenty-four hour Holter recordings from 26 mutation carrier (MC) subjects and 11 non mutation carrier (NMC) coming from the same family with founder effects were analyzed. After the extraction of heart period, approximated as the time distance between two consecutive R peak on the ECG (RR), and QT interval, approximated as the temporal distance between R apex and the apex or the end of T wave (RTa and RTe respectively), we performed symbolic analysis over the obtained RR, RTa and RTe beat-to-beat series. Results showed that, while the two groups could not be discriminated by symbolic analysis of RR series, the same analysis carried out on RTa and RTe series evidenced significant differences reflecting the impairment of the autonomic control directed to ventricles and remarking the different information achieved from RR and QT variabilities

Refined multiscale entropy analysis of heart period and QT interval variabilities in long QT syndrome type-1 patients

This study assesses complexity of cardiovascular control in patients affected by type-1 variant of long QT (LQT1) syndrome. Complexity was assessed by refined multiscale entropy of heart period (HP) and QT interval variabilities. HP was taken as the time distance between two consecutive R peaks (RR) and QT interval was approximated as the time distance between the R-peak and T-wave apex (RTa) and between R-peak and T-wave end (RTe). RR, RTa and RTe intervals were automatically extracted from 24h Holter recordings and the daytime period was analyzed (from 02-00 to 06:00 PM). Non mutation carrier (NMC) individuals (n=11), utilized as a control group, were taken from the same family line of the mutation carrier (MC) subjects (n=26). We found that, while NMC and MC groups were indistinguishable based on time domain and complexity analyses of RR dynamics, complexity analysis of RTa and RTe variabilities clearly separates the two populations and suggests an impairment in the cardiac control mechanisms acting on the ventricles

Multiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1.

The study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population