Mathematical modelling of cardiovascular fluid mechanics: physiology, pathology and clinical practice

The cardiovascular apparatus is a complex dynamical system that carries oxygen and nutrients to cells, removes carbon dioxide and wastes and performs several other tasks essential for life. The physically-based modelling of the cardiovascular system has a long history, which begins with the simple lumped Windkessel model by O. Frank in 1899. Since then, the development has been impressive and a great variety of mathematical models have been proposed. The purpose of this Thesis is to analyse and develop two different mathematical models of the cardiovascular system able to (i) shed new light into cardiovascular ageing and atrial fibrillation and to (ii) be used in clinical practice. To this aim, in-house codes have been implemented to describe a lumped model of the complete circulation and a multi-scale (1D/0D) model of the left ventricle and the arterial system. We then validate each model. The former is validated against literature data, while the latter against both literature data and numerous in-vivo non-invasive pressure measurements on a population of six healthy young subjects. Afterwards, the confirmed effectiveness of the models has been exploited. The lumped model has been used to analyse the effect of atrial fibrillation. The multi-scale one has been used to analyse the effect of ageing and to test the feasibility of clinical use by means of central-pressure blind validation of a parameter setting unambiguously defined with only non-invasive measurements on a population of 52 healthy young men. All the applications have been successful, confirming the effectiveness of this approach. Pathophysiology studies could include mathematical model in their setting, and clinical use of multi-scale mathematical model is feasible

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

Fluid dynamics of heart valves during atrial fibrillation: a lumped parameter-based approach

Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm (NSR) in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF both atrial valves do not seem to worsen their performance, while the ventricular efficiency is remarkably reduced

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions—A Review from the VascAgeNet COST Action

Vascular aging; Atrial fibrillation; Arterial stiffnessEnvejecimiento vascular; Fibrilación auricular; Rigidez arterialEnvelliment vascular; Fibril·lació auricular; Rigidesa arterialAtrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.This article is based upon work from COST Action “Network for Research in Vascular Ageing” (VascAgeNet, CA18216), supported by European Cooperation in Science and Technology (COST, cost.eu). Guala A. has received funding from “la Caixa” Foundation (LCF/BQ/PR22/11920008)

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action

Arteriosclerosis; Ultrasound; Vascular ageingArteriosclerosi; Ecografia; Envelliment vascularArteriosclerosis; Ecografía; Envejecimiento vascularNon-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.This article is based upon work from COST Action CA18216 VascAgeNet, supported by COST (European Cooperation in Science and Technology, www.cost.eu). A.G. has received funding from “La Caixa” Foundation (LCF/BQ/PR22/11920008). R.E.C is supported by the National Health and Medical Research Council of Australia (reference: 2009005) and by a National Heart Foundation Future Leader Fellowship (reference: 105636). J.A. acknowledges support from the British Heart Foundation [PG/15/104/31913], the Wellcome EPSRC Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z], and the Cardiovascular MedTech Co-operative at Guy's and St Thomas' NHS Foundation Trust [MIC-2016-019]

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices

Cardiovascular diseases; Pulse wave analysis; Vascular stiffnessMalalties cardiovasculars; Anàlisi d'ona de pols; Rigidesa vascularEnfermedades cardiovasculares; Análisis de ondas de pulso; Rigidez vascularBACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.B. Spronck received funding from the European Union’s Horizon 2020 Research and Innovation Program (No. 793805). A. Guala received funding from the La Caixa Foundation (LCF/BQ/PR22/11920008). A. Jerončić was funded by the Croatian Science Foundation (No. HRZZ IP-2018-01-4729). J.A. Chirinos was supported by National Institutes of Health grants R01-HL121510, U01-TR003734, 3U01-TR003734-01W1, U01-HL160277, R33-HL146390, R01-HL153646, K24-AG070459, R01-AG058969, R01-HL104106, P01-HL094307, R03-HL146874, R56-HL136730, R01-HL155599, R01-HL157264, and 1R01-HL153646-01. S.S. Daskalopoulou is a senior clinician-scientist supported by a Fonds de recherche du Québec-Santé Senior Salary award. VascAgeNet (CA18216: Network for Research in Vascular Ageing) is supported by European Cooperation in Science and Technology (COST; www.cost.eu). G.L. Pierce was funded by grants from the National Institutes of Health (R01-AG063790) and the American Heart Association (19TPA34910016). A.E. Schutte was supported by a National Health and Medical Research Council Leadership Investigator Grant (application ID: 2017504). I. Tan was cofunded by ATCOR Medical

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

Dilatació aòrtica; Aneurisma de l'aorta ascendent; Anàlisi espai-temporalDilatación aórtica; Aneurisma de la aorta ascendente; Análisis espacio-temporalAortic dilation; Ascending aorta aneurysm; Spatiotemporal analysisMotivated 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.Open access funding provided by Politecnico di Torino within the CRUI-CARE Agreement

Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet

Aging; Arteriosclerosis; HemodynamicsEnvelliment; Arteriosclerosi; HemodinàmicaEnvejecimiento; Arteriosclerosis; HemodinámicaArterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.This article is based upon work from COST Action “Network for Research in Vascular Ageing” (VascAgeNet, CA18216), supported by COST (European Cooperation in Science and Technology, www.cost.eu). This work was supported by British Heart Foundation Grants PG/15/104/31913 (to J.A. and P.H.C.), FS/20/20/34626 (to P.H.C.), and AA/18/6/34223, PG/17/90/33415, SPG 2822621, and SP/F/21/150020 (to A.D.H.); Kaunas University of Technology Grant INP2022/16 (to B.P.); European Research Executive Agency, Marie-Sklodowska Curie Actions Individual Fellowship Grant 101038096 (to S.P.); Istinye University, BAP Project Grant 2019B1 (to S.P.); “la Caixa” Foundation Grant LCF/BQ/PR22/11920008 (to A.G.); and National Institute for Health and Care Research Grant AI AWARD02499 and EU Horizon 2020 Grant H2020 848109 (to A.D.H.)

Malaria in pediatric age in the Piedmont Region

Introduction. Pediatric malaria, even in countries considered as free as Italy, is an important problem of public health because children have a high variability of the clinical picture. The objective of this brief note is to determine the incidence of pediatric malaria in the Piedmont Region during the period 1989-2015.Materials and methods. All cases of pediatric malaria notified were considered thanks to the regional information flow over the period 1989-2015. Cases of congenital malaria, unconfirmed malaria cases, and aged 14 and older were excluded of the study.Results. In Piedmont in the period 1989-2015, pediatric malaria accounts for 8.8% of the total (172/1946 cases). 74% of patients are of foreign nationality, to which must be added the 14% represented by those born in Italy from foreign parents, while it is 100% the fraction of patients who have made a trip to the abroad. The notification of cases is greater in the autumn months. Only 7.6% of the sample carried out a complete chemoprophylaxis. In 79% of cases, the primary care physician advised chemoprophylaxis on trips to endemic areas.Conclusions. At present, lacking an effective vaccine, the prevention and implementation of standard precautions such as chemoprophylaxis, represent the safest strategy to put into practice to eradicate the disease especially for the groups at greater risk as visiting friends and relatives