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San Donato di Ninea, Italy

Porta A.,University of Milan | Porta A.,IRCCS Galeazzi Orthopedic Institute | Girardengo G.,Center for Cardiac Arrhythmias of Genetic Origin | Bari V.,Vascular Anesthesia and Intensive Care | And 7 more authors.
Journal of the American College of Cardiology

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. © 2015 American College of Cardiology Foundation. Source

Catai A.M.,Federal University of Sao Carlos | Takahashi A.C.M.,Federal University of Sao Carlos | Perseguini N.M.,Federal University of Sao Carlos | Milan J.C.,Federal University of Sao Carlos | And 6 more authors.

Short-term complexity of heart period (HP) and systolic arterial pressure (SAP) was computed to detect age and gender influences over cardiovascular control in resting supine condition (REST) and during standing (STAND). Healthy subjects (n = 110, men = 55) were equally divided into five groups (21-30; 31-40; 41-50; 51-60; and 61-70 years of age). HP and SAP series were recorded for 15 min at REST and during STAND. A normalized complexity index (NCI) based on conditional entropy was assessed. At REST we found that both NCIHP and NCISAP decreased with age in the overall population, but only women were responsible for this trend. During STAND we observed that both NCIHP and NCISAP were unrelated to age in the overall population, even when divided by gender. When the variation of NCI in response to STAND (ΔNCI = NCI at REST-NCI during STAND) was computed individually, we found that ΔNCIHP progressively decreased with age in the overall population, and women were again responsible for this trend. Conversely, ΔNCISAP was unrelated to age and gender. This study stresses that the complexity of cardiovascular control and its ability to respond to stressors are more importantly lost with age in women than in men. © 2014 by the authors. Source

Porta A.,University of Milan | Porta A.,IRCCS Galeazzi Orthopedic Institute | Bari V.,Vascular Anesthesia and Intensive Care | Marchi A.,Humanitas Clinical and Research Center | And 6 more authors.
Frontiers in Physiology

Two diverse complexity metrics quantifying time irreversibility and local prediction, in connection with a surrogate data approach, were utilized to detect nonlinear dynamics in short heart period (HP) variability series recorded in fetuses, as a function of the gestational period, and in healthy humans, as a function of the magnitude of the orthostatic challenge. The metrics indicated the presence of two distinct types of nonlinear HP dynamics characterized by diverse ranges of time scales. These findings stress the need to render more specific the analysis of nonlinear components of HP dynamics by accounting for different temporal scales. © 2015 Porta, Bari, Marchi, De Maria, Cysarz, Van Leeuwen, Takahashi, Catai and Gnecchi-Ruscone. Source

Bari V.,Vascular Anesthesia and Intensive Care | Marchi A.,Humanitas Clinical and Research Center | de Maria B.,I.R.C.C.S. Maugeri Foundation | Girardengo G.,Center for Cardiac Arrhythmias of Genetic Origin | And 12 more authors.

Entropy-based complexity of cardiovascular variability at short time scales is largely dependent on the noise and/or action of neural circuits operating at high frequencies. This study proposes a technique for canceling fast variations from cardiovascular variability, thus limiting the effect of these overwhelming influences on entropy-based complexity. The low-pass filtering approach is based on the computation of the fastest intrinsic mode function via empirical mode decomposition (EMD) and its subtraction from the original variability. Sample entropy was exploited to estimate complexity. The procedure was applied to heart period (HP) and QT (interval from Q-wave onset to T-wave end) variability derived from 24-hour Holter recordings in 14 non-mutation carriers (NMCs) and 34 mutation carriers (MCs) subdivided into 11 asymptomatic MCs (AMCs) and 23 symptomatic MCs (SMCs). All individuals belonged to the same family developing long QT syndrome type 1 (LQT1) via KCNQ1-A341V mutation. We found that complexity indexes computed over EMD-filtered QT variability differentiated AMCs from NMCs and detected the effect of beta-blocker therapy, while complexity indexes calculated over EMD-filtered HP variability separated AMCs from SMCs. The EMD-based filtering method enhanced features of the cardiovascular control that otherwise would have remained hidden by the dominant presence of noise and/or fast physiological variations, thus improving classification in LQT1. © 2014 by the authors; licensee MDPI, Basel, Switzerland. Source

Porta A.,University of Milan | Bari V.,Vascular Anesthesia and Intensive Care | Marchi A.,Polytechnic of Milan | De Maria B.,IRCCS Fondazione Salvatore Maugeri | Cerutti S.,Polytechnic of Milan
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS

The study exploits a Wiener-Granger causality (WGC) approach in the time domain to assess directionality of the dynamical interactions between QT interval and heart period (HP) during a graded head-up tilt protocol challenging the cardiovascular control as a function of the tilt table inclination. QT interval and HP are approximated from the surface ECG as the temporal distance between the R-wave apex and T-wave offset and between two consecutive R-wave peaks respectively. The adopted WGC approach accounts for the confounding effect of respiration (RESP) affecting both QT and HP. Causality ratios (CRs) from HP to QT given RESP (CRHP→QT-RESP) and from QT to HP given RESP (CRQT→HP-RESP) were computed and their significance was tested via F-test. We found that, regardless of the tilt table angle, CRHP→QT-RESP is significant, while CRQT→HP-RESP is negligible. CRHP→QT-RESP showed a trend towards a decrease with tilt table angle. These findings suggested that the causal direction from HP over QT is dominant compared to the reverse one and sympathetic activation induced a QT-HP uncoupling. © 2015 IEEE. Source

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