A Quantitative Assessment of Cerebral Hemodynamic Perturbations Associated with Long R-R Intervals in Atrial Fibrillation: A Pilot-Case-Based Experience.

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus.

A review of multiscale 0D-1D computational modeling of coronary circulation with applications to cardiac arrhythmias.

Computational hemodynamics is becoming an increasingly important tool in clinical applications and surgical procedures involving the cardiovascular system. Aim of this review is to provide a compact summary of state of the art 0D-1D multiscale models of the arterial coronary system, with particular attention to applications related to cardiac arrhythmias, whose effects on the coronary circulation remain so far poorly understood. The focus on 0D-1D models only is motivated by the competitive computational cost, the reliability of the outcomes for the whole cardiovascular system, and the ability to directly account for cardiac arrhythmias. The analyzed studies show that cardiac arrhythmias by their own are able to promote significant alterations of the coronary hemodynamics, with a worse scenario as the mean heart rate (HR) increases. The present review can stimulate future investigation, both in computational and clinical research, devoted to the hemodynamic effects induced by cardiac arrhythmias on the coronary circulation.

Increased beat-to-beat variability of cerebral microcirculatory perfusion during atrial fibrillation: a near-infrared spectroscopy study.

AIMS: Atrial fibrillation (AFib) is associated with cognitive decline/dementia, independently from clinical strokes or transient ischaemic attacks (TIA). Recent in silico data suggested that AFib may induce transient critical haemodynamic events in the cerebral microcirculation. The aim of this study is to use non-invasive spatially resolved cerebral near-infrared spectroscopy (SRS-NIRS) to investigate in vivo beat-to-beat microcirculatory perfusion during AFib and after sinus rhythm (SR) restoration. METHODS AND RESULTS: Cerebral SRS-NIRS with high-frequency sampling (20 Hz) and non-invasive systemic haemodynamic monitoring were recorded before and after elective electrical cardioversion (ECV) for AFib or atrial flutter (AFL). To assess beat-to-beat effects of the rhythm status, the frequency distribution of inter-beat differences in tissue haemoglobin index (THI), a proxy of microcirculatory cerebral perfusion, was compared before and after SR restoration. Fifty-three AFib/AFL patients (mean age 69 ± 8 years, 79% males) were ultimately enrolled. Cardioversion was successful in restoring SR in 51 (96%) patients. In front of a non-significant decrease in arterial blood pressure extreme events between pre- and post-ECV measurements, a significant decrease of both hypoperfusive and hyperperfusive/hypertensive microcirculatory events was observed after SR restoration (P < 0.001 and P = 0.041, respectively). CONCLUSION: The present is the first in vivo demonstration that SR restoration by ECV significantly reduces the burden of extreme single-beat haemodynamic events in cerebral microcirculation. Future studies are needed to assess whether SR maintenance might slow long-term AFib-correlated cognitive decline/dementia.

From time-series to complex networks: Application to the cerebrovascular flow patterns in atrial fibrillation.

A network-based approach is presented to investigate the cerebrovascular flow patterns during atrial fibrillation (AF) with respect to normal sinus rhythm (NSR). AF, the most common cardiac arrhythmia with faster and irregular beating, has been recently and independently associated with the increased risk of dementia. However, the underlying hemodynamic mechanisms relating the two pathologies remain mainly undetermined so far; thus, the contribution of modeling and refined statistical tools is valuable. Pressure and flow rate temporal series in NSR and AF are here evaluated along representative cerebral sites (from carotid arteries to capillary brain circulation), exploiting reliable artificially built signals recently obtained from an in silico approach. The complex network analysis evidences, in a synthetic and original way, a dramatic signal variation towards the distal/capillary cerebral regions during AF, which has no counterpart in NSR conditions. At the large artery level, networks obtained from both AF and NSR hemodynamic signals exhibit elongated and chained features, which are typical of pseudo-periodic series. These aspects are almost completely lost towards the microcirculation during AF, where the networks are topologically more circular and present random-like characteristics. As a consequence, all the physiological phenomena at the microcerebral level ruled by periodicity-such as regular perfusion, mean pressure per beat, and average nutrient supply at the cellular level-can be strongly compromised, since the AF hemodynamic signals assume irregular behaviour and random-like features. Through a powerful approach which is complementary to the classical statistical tools, the present findings further strengthen the potential link between AF hemodynamic and cognitive decline.

Linking cerebral hemodynamics and ocular microgravity-induced alterations through an in silico-in vivo head-down tilt framework.

Head-down tilt (HDT) has been widely proposed as a terrestrial analog of microgravity and used also to investigate the occurrence of spaceflight-associated neuro-ocular syndrome (SANS), which is currently considered one of the major health risks for human spaceflight. We propose here an in vivo validated numerical framework to simulate the acute ocular-cerebrovascular response to 6° HDT, to explore the etiology and pathophysiology of SANS. The model links cerebral and ocular posture-induced hemodynamics, simulating the response of the main cerebrovascular mechanisms, as well as the relationship between intracranial and intraocular pressure to HDT. Our results from short-term (10 min) 6° HDT show increased hemodynamic pulsatility in the proximal-to-distal/capillary-venous cerebral direction, a marked decrease (-43%) in ocular translaminar pressure, and an increase (+31%) in ocular perfusion pressure, suggesting a plausible explanation of the underlying mechanisms at the onset of ocular globe deformation and edema formation over longer time scales.

Role of the vessel morphology on the lenticulostriate arteries hemodynamics during atrial fibrillation: A CFD-based multivariate regression analysis.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF. METHODS: By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions. RESULTS: Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF. CONCLUSIONS: The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

Arterial wave dynamics preservation upon orthostatic stress: a modelling perspective.

Pressure-flow travelling waves are a key topic for understanding arterial haemodynamics. However, wave transmission and reflection processes induced by body posture changes have not been thoroughly explored yet. Current in vivo research has shown that the amount of wave reflection detected at a central level (ascending aorta, aortic arch) decreases during tilting to the upright position, despite the widely proved stiffening of the cardiovascular system. It is known that the arterial system is optimized when in the supine position, i.e. propagation of direct waves is enabled and reflected waves are trapped, protecting the heart; however, it is not known whether this is preserved with postural changes. To shed light on these aspects, we propose a multi-scale modelling approach to inquire into posture-induced arterial wave dynamics elicited by simulated head-up tilting. In spite of remarkable adaptation of the human vasculature following posture changes, our analysis shows that, upon tilting from supine to upright: (i) vessel lumens at arterial bifurcations remain well matched in the forward direction, (ii) wave reflection at central level is reduced due to the backward propagation of weakened pressure waves produced by cerebral autoregulation, and (iii) backward wave trapping is preserved.

Beat-to-beat finger photoplethysmography in atrial fibrillation patients undergoing electrical cardioversion.

Atrial fibrillation (AF)-induced peripheral microcirculatory alterations have poorly been investigated. The present study aims to expand current knowledge through a beat-to-beat analysis of non-invasive finger photoplethysmography (PPG) in AF patients restoring sinus rhythm by electrical cardioversion (ECV). Continuous non-invasive arterial blood pressure and left middle finger PPG pulse oximetry waveform (POW) signals were continuously recorded before and after elective ECV of consecutive AF or atrial flutter (AFL) patients. The main metrics (mean, standard deviation, coefficient of variation), as well as a beat-to-beat analysis of the pulse pressure (PP) and POW beat-averaged value (aPOW), were computed to compare pre- and post-ECV phases. 53 patients (mean age 69 ± 8 years, 79% males) were enrolled; cardioversion was successful in restoring SR in 51 (96%) and signal post-processing was feasible in 46 (87%) patients. In front of a non-significant difference in mean PP (pre-ECV: 51.96 ± 13.25, post-ECV: 49.58 ± 10.41 mmHg; p = 0.45), mean aPOW significantly increased after SR restoration (pre-ECV: 0.39 ± 0.09, post-ECV: 0.44 ± 0.06 a.u.; p < 0.001). Moreover, at beat-to-beat analysis linear regression yielded significantly different slope (m) for the PP (RR) relationship compared to aPOW(RR) [PP(RR): 0.43 ± 0.18; aPOW(RR): 1.06 ± 0.17; p < 0.001]. Long (> 95th percentile) and short (< 5th percentile) RR intervals were significantly more irregular in the pre-ECV phases for both PP and aPOW; however, aPOW signal suffered more fluctuations compared to PP (p < 0.001 in both phases). Present findings suggest that AF-related hemodynamic alterations are more manifest at the peripheral (aPOW) rather than at the upstream macrocirculatory level (PP). Restoring sinus rhythm increases mean peripheral microvascular perfusion and decreases variability of the microvascular hemodynamic signals. Future dedicated studies are required to determine if AF-induced peripheral microvascular alterations might relate to long-term prognostic effects.

Network-Based Characterization of Blood Large-Scale Coherent Motion in the Healthy Human Aorta With 4D Flow MRI.

OBJECTIVE: The need for distilling the hemodynamic complexity of aortic flows into clinically relevant quantities resulted in a loss of the information hidden in 4D aortic fluid structures. To reduce information loss, this study proposes a network-based approach to identify and characterize in vivo the large-scale coherent motion of blood in the healthy human aorta. METHODS: The quantitative paradigm of the aortic flow as a "social network" was applied on 4D flow MRI acquisitions performed on forty-one healthy volunteers. Correlations between the aortic blood flow rate waveform at the proximal ascending aorta (AAo), assumed as one of the drivers of aortic hemodynamics, and the waveforms of the axial velocity in the whole aorta were used to build "one-to-all" networks. The impact of the driving flow rate waveform and of aortic geometric attributes on the transport of large-scale coherent fluid structures was investigated. RESULTS: The anatomical length of persistence of large-scale coherent motion was the 29.6% of the healthy thoracic aorta length (median value, IQR 23.1%-33.9%). Such length is significantly influenced by the average and peak-to-peak AAo blood flow rate values, suggesting a remarkable inertial effect of the AAo flow rate on the transport of large-scale fluid structures in the distal aorta. Aortic geometric attributes such as curvature, torsion and arch shape did not influence the anatomical length of persistence. CONCLUSION: The proposed in vivo approach allowed to quantitatively characterize the transport of large-scale fluid structures in the healthy aorta, strengthening the definition of coherent hemodynamic structures and identifying flow inertia rather than geometry as one of its main determinants. SIGNIFICANCE: The findings on healthy aortas may be used as reference values to investigate the impact of aortic disease or implanted devices in disrupting/restoring the physiological spatiotemporal coherence of large-scale aortic flow.

A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers.

Patients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).

Cardiovascular Response to Posture Changes: Multiscale Modeling and in vivo Validation During Head-Up Tilt.

In spite of cardiovascular system (CVS) response to posture changes have been widely studied, a number of mechanisms and their interplay in regulating central blood pressure and organs perfusion upon orthostatic stress are not yet clear. We propose a novel multiscale 1D-0D mathematical model of the human CVS to investigate the effects of passive (i.e., through head-up tilt without muscular intervention) posture changes. The model includes the main short-term regulation mechanisms and is carefully validated against literature data and in vivo measures here carried out. The model is used to study the transient and steady-state response of the CVS to tilting, the effects of the tilting rate, and the differences between tilt-up and tilt-down. Passive upright tilt led to an increase of mean arterial pressure and heart rate, and a decrease of stroke volume and cardiac output, in agreement with literature data and present in vivo experiments. Pressure and flow rate waveform analysis along the arterial tree together with mechano-energetic and oxygen consumption parameters highlighted that the whole system approaches a less stressed condition at passive upright posture than supine, with a slight unbalance of the energy supply-demand ratio. The transient dynamics is not symmetric in tilt-up and tilt-down testing, and is non-linearly affected by the tilting rate, with stronger under- and overshoots of the hemodynamic parameters as the duration of tilt is reduced. By enriching the CVS response to posture changes, the present modeling approach shows promise in a number of applications, ranging from autonomic system disorders to spaceflight deconditioning.

Insights from computational modeling on the potential hemodynamic effects of sinus rhythm versus atrial fibrillation.

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia, posing a significant burden to patients, physicians, and healthcare systems worldwide. With the advent of more effective rhythm control strategies, such as AF catheter ablation, an early rhythm control strategy is progressively demonstrating its superiority not only in symptoms control but also in prognostic terms, over a standard strategy (rate control, with rhythm control reserved only to patients with refractory symptoms). This review summarizes the different impacts exerted by AF on heart mechanics and systemic circulation, as well as on cerebral and coronary vascular beds, providing computational modeling-based hemodynamic insights in favor of pursuing sinus rhythm maintenance in AF patients.

Different Impact of Heart Rate Variability in the Deep Cerebral and Central Hemodynamics at Rest: An in silico Investigation.

Background: Heart rate variability (HRV), defined as the variability between consecutive heartbeats, is a surrogate measure of cardiac vagal tone. It is widely accepted that a decreased HRV is associated to several risk factors and cardiovascular diseases. However, a possible association between HRV and altered cerebral hemodynamics is still debated, suffering from HRV short-term measures and the paucity of high-resolution deep cerebral data. We propose a computational approach to evaluate the deep cerebral and central hemodynamics subject to physiological alterations of HRV in an ideal young healthy patient at rest. Methods: The cardiovascular-cerebral model is composed by electrical components able to reproduce the response of the different cardiovascular regions and their features. The model was validated over more than thirty studies and recently exploited to understand the hemodynamic mechanisms between cardiac arrythmia and cognitive deficit. Three configurations (baseline, increased HRV, and decreased HRV) are built based on the standard deviation (SDNN) of RR beats. For each configuration, 5,000 RR beats are simulated to investigate the occurrence of extreme values, alteration of the regular hemodynamics pattern, and variation of mean perfusion/pressure levels. Results: In the cerebral circulation, our results show that HRV has overall a stronger impact on pressure than flow rate mean values but similarly alters pressure and flow rate in terms of extreme events. By comparing reduced and increased HRV, this latter induces a higher probability of altered mean and extreme values, and is therefore more detrimental at distal cerebral level. On the contrary, at central level a decreased HRV induces a higher cardiac effort without improving the mechano-contractile performance, thus overall reducing the heart efficiency. Conclusions: Present results suggest that: (i) the increase of HRV per se does not seem to be sufficient to trigger a better cerebral hemodynamic response; (ii) by accounting for both central and cerebral circulations, the optimal HRV configuration is found at baseline. Given the relation inversely linking HRV and HR, the presence of this optimal condition can contribute to explain why the mean HR of the general population settles around the baseline value (70 bpm).

Testing a Patient-Specific In-Silico Model to Noninvasively Estimate Central Blood Pressure.

PURPOSE: To show some preliminary results about the possibility to exploit a cardiovascular mathematical model-made patient-specific by noninvasive data routinely measured during ordinary clinical examinations-in order to obtain sufficiently accurate central blood pressure (BP) estimates. METHODS: A closed-loop multiscale (0D and 1D) model of the cardiovascular system is made patient-specific by using as model inputs the individual mean heart rate and left-ventricular contraction time, weight, height, age, sex and mean/pulse brachial BPs. The resulting framework is used to determine central systolic, diastolic, mean and pulse pressures, which are compared with the beat-averaged invasive pressures of 12 patients aged 72 ± 6.61 years. RESULTS: Errors in central systolic, diastolic, mean and pulse pressures by the model are 4.26 ± 2.81, 5.86 ± 4.38, 4.98 ± 3.95 and 3.51±2.38 mmHg, respectively. CONCLUSION: The proposed modeling approach shows a good patient-specific response and appears to be potentially useful in clinical practice. However, this approach needs to be evaluated in a larger cohort of patients and could possibly be improved through more accurate oscillometric BP measurement methods.

Combining 4D Flow MRI and Complex Networks Theory to Characterize the Hemodynamic Heterogeneity in Dilated and Non-dilated Human Ascending Aortas.

Motivated by the evidence that the onset and progression of the aneurysm of the ascending aorta (AAo) is intertwined with an adverse hemodynamic environment, the present study characterized in vivo the hemodynamic spatiotemporal complexity and organization in human aortas, with and without dilated AAo, exploring the relations with clinically relevant hemodynamic and geometric parameters. The Complex Networks (CNs) theory was applied for the first time to 4D flow magnetic resonance imaging (MRI) velocity data of ten patients, five of them presenting with AAo dilation. The time-histories along the cardiac cycle of velocity-based quantities were used to build correlation-based CNs. The CNs approach succeeded in capturing large-scale coherent flow features, delimiting flow separation and recirculation regions. CNs metrics highlighted that an increasing AAo dilation (expressed in terms of the ratio between the maximum AAo and aortic root diameter) disrupts the correlation in forward flow reducing the correlation persistence length, while preserving the spatiotemporal homogeneity of secondary flows. The application of CNs to in vivo 4D MRI data holds promise for a mechanistic understanding of the spatiotemporal complexity and organization of aortic flows, opening possibilities for the integration of in vivo quantitative hemodynamic information into risk stratification and classification criteria.

Cardiovascular deconditioning during long-term spaceflight through multiscale modeling.

Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes-from blood volume shift and reduction to altered cardiac function-induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts' safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D-0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary-venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.

Exploring wall shear stress spatiotemporal heterogeneity in coronary arteries combining correlation-based analysis and complex networks with computational hemodynamics.

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress-based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries.

Spatiotemporal Hemodynamic Complexity in Carotid Arteries: An Integrated Computational Hemodynamics and Complex Networks-Based Approach.

OBJECTIVE: The study of the arterial hemodynamics is essential for a better understanding of the risks associated with the onset/progression of vascular disease. However, conventional quantification and visualization paradigms are not sufficient to fully capture the spatiotemporal evolution of correlated blood flow patterns and their "sphere of influence" in complex vascular geometries. In the attempt to bridge this knowledge gap, an integrated computational hemodynamics and complex networks-based approach is proposed to unveil organization principles of cardiovascular flows. METHODS: The approach is applied to ten patient-specific hemodynamic models of carotid bifurcation, a vascular bed characterized by a complex hemodynamics and clinically-relevant disease. Correlation-based networks are built starting from time-histories of two fluid mechanics quantities of physiological significance, respectively (1) the blood velocity vector axial component locally aligned with the main flow direction, and (2) the kinetic helicity density. RESULTS: Unlike conventional hemodynamic analyses, here the spatiotemporal similarity of dynamic intravascular flow structures is encoded in a distance function. In the case of the carotid bifurcation, this study measures for the first time to what extent flow similarity is disrupted by vascular geometric features. CONCLUSION: It emerges that a larger bifurcation expansion, a hallmark of vascular disease, significantly disrupts the network topological connections between axial flow structures, reducing also their anatomical persistence length. On the contrary, connections in helical flow patterns are overall less geometry-sensitive. SIGNIFICANCE: The integrated approach proposed here, by exploiting the connections of hemodynamic patterns undergoing similar dynamical evolution, opens avenues for further comprehension of vascular physiopathology.

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.