Mathematical modelling of the cardiovascular system

In this paper we will address the problem of developing mathematical models for the numerical simulation of the human circulatory system. In particular, we will focus our attention on the problem of haemodynamics in large human arteries

Spatio-Temporal Modelling of Perfusion Cardiovascular MRI

Myocardial perfusion MRI provides valuable insight into how coronary artery and microvascular diseases affect myocardial tissue. Stenosis in a coronary vessel leads to reduced maximum blood flow (MBF), but collaterals may secure the blood supply of the myocardium but with altered tracer kinetics. To date, quantitative analysis of myocardial perfusion MRI has only been performed on a local level, largely ignoring the contextual information inherent in different myocardial segments. This paper proposes to quantify the spatial dependencies between the local kinetics via a Hierarchical Bayesian Model (HBM). In the proposed framework, all local systems are modelled simultaneously along with their dependencies, thus allowing more robust context-driven estimation of local kinetics. Detailed validation on both simulated and patient data is provided

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Regression calibration for Cox regression under heteroscedastic measurement error - Determining risk factors of cardiovascular diseases from error-prone nutritional replication data

For instance nutritional data are often subject to severe measurement error, and an adequate adjustment of the estimators is indispensable to avoid deceptive conclusions. This paper discusses and extends the method of regression calibration to correct for measurement error in Cox regression. Special attention is paid to the modelling of quadratic predictors, the role of heteroscedastic measurement error, and the efficient use of replicated measurements of the surrogates. The method is used to analyze data from the German part of the MONICA cohort study on cardiovascular diseases. The results corroborate the importance of taking into account measurement error carefully

Mathematical modelling of the cardiovascular system

This paper is an introduction to the special issue of the Journal of Engineering Mathematic (Volume 47/3–4, 2003) on the mathematical modelling of the cardiovascular system. This issue includes the 2003 James Lighthill Memorial Paper written by Pedley [1] on the mathematical modelling of arterial fluid dynamics. This introduction is written to bring cardiovascular biomechanics to readers with a background in mathematical modelling and computational mechanics. The importance of mathematical modelling for physiological understanding, diagnostics, prosthesis development, patient selection and medical planning is indicated and discussed shortly. A subdivision into models for cardiac mechanics, pressure- and flow-wave propagation, mass transfer and fully three-dimensional fluid-structure interaction is made and references are given to the different contributions of the issue

Computational fluid dynamics modelling in cardiovascular medicine

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length-And time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, populationaveraged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education-And service-related challenges

Use of evidence to support healthy public policy: a policy effectiveness-feasibility loop

Public policy plays a key role in improving population health and in the control of diseases, including non-communicable diseases. However, an evidence-based approach to formulating healthy public policy has been difficult to implement, partly on account of barriers that hinder integrated work between researchers and policy-makers. This paper describes a “policy effectiveness–feasibility loop” (PEFL) that brings together epidemiological modelling, local situation analysis and option appraisal to foster collaboration between researchers and policy-makers. Epidemiological modelling explores the determinants of trends in disease and the potential health benefits of modifying them. Situation analysis investigates the current conceptualization of policy, the level of policy awareness and commitment among key stakeholders, and what actually happens in practice, thereby helping to identify policy gaps. Option appraisal integrates epidemiological modelling and situation analysis to investigate the feasibility, costs and likely health benefits of various policy options. The authors illustrate how PEFL was used in a project to inform public policy for the prevention of cardiovascular diseases and diabetes in four parts of the eastern Mediterranean. They conclude that PEFL may offer a useful framework for researchers and policy-makers to successfully work together to generate evidence-based policy, and they encourage further evaluation of this approach

Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners