Impact of atrial fibrillation on the cardiovascular system through a lumped-parameter approach

Atrial fibrillation (AF) is the most common arrhythmia affecting millions of people in the Western countries and, due to the widespread impact on the population and its medical relevance, is largely investigated in both clinical and bioengineering sciences. However, some important feedback mechanisms are still not clearly established. The present study aims at understanding the global response of the cardiovascular system during paroxysmal AF through a lumped-parameter approach, which is here performed paying particular attention to the stochastic modeling of the irregular heartbeats and the reduced contractility of the heart. AF can be here analyzed by means of a wide number of hemodynamic parameters and avoiding the presence of other pathologies, which usually accompany AF. Reduced cardiac output with correlated drop of ejection fraction and decreased amount of energy converted to work by the heart during blood pumping, as well as higher left atrial volumes and pressures are some of the most representative results aligned with the existing clinical literature and here emerging during acute AF. The present modeling, providing new insights on cardiovascular variables which are difficult to measure and rarely reported in literature, turns out to be an efficient and powerful tool for a deeper comprehension and prediction of the arrythmia impact on the whole cardiovascular system.Comment: 16 pages, 8 figures, 2 tables, Medical & Biological Engineering & Computing, 2014, Print ISSN: 0140-0118, Online ISSN: 1741-044

A study on stability analysis of atrial repolarization variability using ARX model in sinus rhythm and atrial tachycardia ECGs

© 2016 Elsevier Ireland Ltd Background The interaction between the PTa and PP interval dynamics from the surface ECG is seldom explained. Mathematical modeling of these intervals is of interest in finding the relationship between the heart rate and repolarization variability. Objective The goal of this paper is to assess the bounded input bounded output (BIBO) stability in PTa interval (PTaI) dynamics using autoregressive exogenous (ARX) model and to investigate the reason for causing instability in the atrial repolarization process. Methods Twenty-five male subjects in normal sinus rhythm (NSR) and ten male subjects experiencing atrial tachycardia (AT) were included in this study. Five minute long, modified limb lead (MLL) ECGs were recorded with an EDAN SE-1010 PC ECG system. The number of minute ECGs with unstable segments (N us ) and the frequency of premature activation (PA) (i.e. atrial activation) were counted for each ECG recording and compared between AT and NSR subjects. Results The instability in PTaI dynamics was quantified by measuring the numbers of unstable segments in ECG data for each subject. The unstable segments in the PTaI dynamics were associated with the frequency of PA. The presence of PA is not the only factor causing the instability in PTaI dynamics in NSR subjects, and it is found that the cause of instability is mainly due to the heart rate variability (HRV). C onclusion The ARX model showed better prediction of PTa interval dynamics in both groups. The frequency of PA is significantly higher in AT patients than NSR subjects. A more complex model is needed to better identify and characterize healthy heart dynamics

Impaired coronary blood flow at higher heart rates during atrial fibrillation: investigation via multiscale modelling

Background. Different mechanisms have been proposed to relate atrial fibrillation (AF) and coronary flow impairment, even in absence of relevant coronary artery disease (CAD). However, the underlying hemodynamics remains unclear. Aim of the present work is to computationally explore whether and to what extent ventricular rate during AF affects the coronary perfusion. Methods. AF is simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) through a 0D-1D multiscale validated model, which combines the left heart-arterial tree together with the coronary circulation. Artificially-built RR stochastic extraction mimics the \emph{in vivo} beating features. All the hemodynamic parameters computed are based on the left anterior descending (LAD) artery and account for the waveform, amplitude and perfusion of the coronary blood flow. Results. Alterations of the coronary hemodynamics are found to be associated either to the heart rate increase, which strongly modifies waveform and amplitude of the LAD flow rate, and to the beat-to-beat variability. The latter is overall amplified in the coronary circulation as HR grows, even though the input RR variability is kept constant at all HRs. Conclusions. Higher ventricular rate during AF exerts an overall coronary blood flow impairment and imbalance of the myocardial oxygen supply-demand ratio. The combined increase of heart rate and higher AF-induced hemodynamic variability lead to a coronary perfusion impairment exceeding 90-110 bpm in AF. Moreover, it is found that coronary perfusion pressure (CPP) is no longer a good measure of the myocardial perfusion for HR higher than 90 bpm.Comment: 8 pages, 5 figures, 3 table

How random is your heart beat?

We measure the content of random uncorrelated noise in heart rate variability using a general method of noise level estimation using a coarse grained entropy. We show that usually - except for atrial fibrillation - the level of such noise is within 5 - 15% of the variance of the data and that the variability due to the linearly correlated processes is dominant in all cases analysed but atrial fibrillation. The nonlinear deterministic content of heart rate variability remains significant and may not be ignored.Comment: see http://urbanowicz.org.p

Nonlinear physics of electrical wave propagation in the heart: a review

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that are triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media and their application to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact in cardiac arrhythmias.Peer ReviewedPreprin

Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity

It has become widely accepted that the most dangerous cardiac arrhythmias are due to re- entrant waves, i.e., electrical wave(s) that re-circulate repeatedly throughout the tissue at a higher frequency than the waves produced by the heart's natural pacemaker (sinoatrial node). However, the complicated structure of cardiac tissue, as well as the complex ionic currents in the cell, has made it extremely difficult to pinpoint the detailed mechanisms of these life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac action potential (AP), which can be fitted to a wide variety of experimentally and numerically obtained mesoscopic characteristics of cardiac tissue such as AP shape and restitution of AP duration and conduction velocity, is used to explain many different mechanisms of spiral wave breakup which in principle can occur in cardiac tissue. Some, but not all, of these mechanisms have been observed before using other models; therefore, the purpose of this paper is to demonstrate them using just one framework model and to explain the different parameter regimes or physiological properties necessary for each mechanism (such as high or low excitability, corresponding to normal or ischemic tissue, spiral tip trajectory types, and tissue structures such as rotational anisotropy and periodic boundary conditions). Each mechanism is compared with data from other ionic models or experiments to illustrate that they are not model-specific phenomena. The fact that many different breakup mechanisms exist has important implications for antiarrhythmic drug design and for comparisons of fibrillation experiments using different species, electromechanical uncoupling drugs, and initiation protocols.Comment: 128 pages, 42 figures (29 color, 13 b&w

Rate Control Management of Atrial Fibrillation: May a Mathematical Model Suggest an Ideal Heart Rate?

Background. Despite the routine prescription of rate control therapy for atrial fibrillation (AF), clinical evidence demonstrating a heart rate target is lacking. Aim of the present study was to run a mathematical model simulating AF episodes with a different heart rate (HR) to predict hemodynamic parameters for each situation. Methods. The lumped model, representing the pumping heart together with systemic and pulmonary circuits, was run to simulate AF with HR of 50, 70, 90, 110 and 130 bpm, respectively. Results. Left ventricular pressure increased by 56.7%, from 33.92+-37.56 mmHg to 53.15+-47.56 mmHg, and mean systemic arterial pressure increased by 27.4%, from 82.66+-14.04 mmHg to 105.29+-7.63 mmHg, at the 50 and 130 bpm simulations, respectively. Stroke volume (from 77.45+-8.5 to 39.09+-8.08 mL), ejection fraction (from 61.1+-4.4 to 39.32+-5.42%) and stroke work (SW, from 0.88+-0.04 to 0.58+-0.09 J) decreased by 49.5, 35.6 and 34.2%, at the 50 and 130 bpm simulations, respectively. In addition, oxygen consumption indexes (rate pressure product, RPP, tension time index per minute, TTI/min, and pressure volume area per minute, PVA/min) increased from the 50 to the 130 bpm simulation, respectively, by 185.7% (from 5598+-1939 to 15995+-3219 mmHg/min), 55.5% (from 2094+-265 to 3257+-301 mmHg s/min) and 102.4% (from 57.99+-17.9 to 117.37+-25.96 J/min). In fact, left ventricular efficiency (SW/PVA) decreased from 80.91+-2.91% at 50 bpm to 66.43+-3.72% at the 130 bpm HR simulation. Conclusion. Awaiting compulsory direct clinical evidences, the present mathematical model suggests that lower HRs during permanent AF relates to improved hemodynamic parameters, cardiac efficiency, and lower oxygen consumption.Comment: 9 page

Na/K pump regulation of cardiac repolarization: Insights from a systems biology approach

The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the Systems Biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most\ud important ionic mechanisms in regulating key properties of cardiac repolarization and its rate-dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies

Constitutively active acetylcholine-dependent potassium current increases atrial defibrillation threshold by favoring post-shock re-initiation

Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (I-K,I-ACh -> I-K,I-ACh-c), which is associated with ECV failure. This study investigated the role of I-K,I-ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25-100 V to determine aDFT. Blocking I-K,I-ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate I-K,I-ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. re-initiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by I-K,I-ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after I-K,I-ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies I-K,I-ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness