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

Alteration of cerebrovascular haemodynamic patterns due to atrial fibrillation: an in silico investigation

There has recently been growing evidence that atrial fibrillation (AF), the most common cardiac arrhythmia, is independently associated with the risk of dementia. This represents a very recent frontier with high social impact for the number of individuals involved and for the expected increase in AF incidence in the next 40 years. Although a number of potential haemodynamic processes, such as microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise as connecting links between the two pathologies, the causal mechanisms are far from clear. An in silico approach is proposed that combines in sequence two lumped-parameter schemes, for the cardiovascular system and the cerebral circulation. The systemic arterial pressure is obtained from the cardiovascular system and used as the input for the cerebral circulation, with the aim of studying the role of AF on the cerebral haemodynamics with respect to normal sinus rhythm (NSR), over a 5000 beat recording. In particular, the alteration of the haemodynamic (pressure and flowrate) patterns in the microcirculation during AF is analysed by means of different statistical tools, from correlation coefficients to autocorrelation functions, crossing times, extreme values analysis and multivariate linear regression models. A remarkable signal alteration, such as a reduction in signal correlation (NSR, about 3 s; AF, less than 1 s) and increased probability (up to three to four times higher in AF than in NSR) of extreme value events, emerges for the peripheral brain circulation. The described scenario offers a number of plausible cause-effect mechanisms that might explain the occurrence of critical events and the haemodynamic links relating to AF and dementia.Comment: 13 pages, 9 Figures, 3 Table

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

Higher ventricular rate during atrial fibrillation relates to increased cerebral hypoperfusions and hypertensive events

Atrial fibrillation (AF) is associated with cognitive impairment/dementia, independently of clinical cerebrovascular events (stroke/TIA). One of the plausible mechanisms is the occurrence of AF-induced transient critical hemodynamic events; however, it is presently unknown, if ventricular response rate during AF may impact on cerebral hemodynamics. AF was simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) by two coupled lumped parameter validated models (systemic and cerebral circulation), and compared to corresponding control normal sinus rhythm simulations (NSR). Hemodynamic outcomes and occurrence of critical events (hypoperfusions and hypertensive events) were assessed along the internal carotid artery-middle cerebral artery pathway up to the capillary-venous bed. At the distal cerebral circle level (downstream middle cerebral artery), increasing ventricular rates lead to a reduced heart rate-related dampening of hemodynamic signals compared to NSR (p=0.003 and 0.002 for flow rate and pressure, respectively). This response causes a significant progressive increase in critical events in the distal cerebral circle (p<0.001) as ventricular rate increases during AF. On the other side, at the lowest ventricular response rates (HR 50 bpm), at the systemic-proximal cerebral circle level (up to middle cerebral artery) hypoperfusions (p<0.001) occur more commonly, compared to faster AF simulations. This computational study suggests that higher ventricular rates relate to a progressive increase in critical cerebral hemodynamic events (hypoperfusions and hypertensive events) at the distal cerebral circle. Thus, a rate control strategy aiming to around 60 bpm could be beneficial in terms on cognitive outcomes in patients with permanent AF.Comment: 9 pages, 4 figures, 2 table

Higher resting heart rate relates to greater rise in pulmonary vein pressure under exercise during permanent atrial fibrillation: a computational study

BACKGROUND. Clinical data indicating a heart rate (HR) target during rate control therapy for permanent atrial fibrillation (AF) and regarding its eventual relationship with reduced exercise tolerance are lacking. OBJECTIVE. The present study aims at investigating the impact of resting HR on cardiovascular response to exercise in permanent AF patients by a computational cardiovascular model. METHODS. The AF lumped-parameter model was run to simulate resting (1 Metabolic Equivalent of Task-MET) and various exercise conditions (4 METs: brisk walking; 6 METs: skiing; 8 METs: running) starting from different resting HR (70 bpm for the slower resting HR-SHR-simulations, and 100 bpm for the higher resting HR-HHR-simulations). To allow comparison of relative variations of cardiovascular variables upon exertion, the variation comparative index (VCI)-the absolute variation between the exercise and the resting values in SHR simulations referred to the absolute variation in HHR simulations-was calculated at each exercise grade (VCI 4 , VCI 6 and VCI 8). RESULTS. Pulmonary vein pressure (VCI 4 = 0.71, VCI 6 = 0.73 and VCI 8 = 0.77) underwent a greater increase, while systemic arterial pressure variations (VCI 4 = 1.15, VCI 6 = 1.36, VCI 8 = 1.56) experienced a less sustained increase than expected in HHR compared to SHR simulations. CONCLUSIONS. In terms of exercise tolerance, a slower resting HR could be preferable in permanent AF patients, since pulmonary vein pressure undergoes a slighter increase and systemic blood pressure a more appropriate increase with respect to a higher resting HR