Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models

Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment–elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg). Cardiac MRI was performed in the patients (2 days & 6 months post-STEMI) and the volunteers, and biomechanical heart models were synthesized for each subject. The candidate parameters included normalized active tension (ATnorm) and active tension at the resting sarcomere length (Treq, reflecting required contractility). Myocardial contractility was inversely determined from personalized heart models by matching CMR-imaged LV dynamics. Compared with controls, patients with recent STEMI exhibited increased LV wall active tension when normalized by SBP. We observed a linear relationship between Treq 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p = 0.03). Treq may be associated with changes in LV function in the longer term in STEMI patients complicated by LV dysfunction. Further studies seem warranted

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

Automated left ventricular diastolic function evaluation from phase-contrast cardiovascular magnetic resonance and comparison with Doppler echocardiography

International audienceBACKGROUND: Early detection of diastolic dysfunction is crucial for patients with incipient heart failure. Although this evaluation could be performed from phase-contrast (PC) cardiovascular magnetic resonance (CMR) data, its usefulness in clinical routine is not yet established, mainly because the interpretation of such data remains mostly based on manual post-processing. Accordingly, our goal was to develop a robust process to automatically estimate velocity and flow rate-related diastolic parameters from PC-CMR data and to test the consistency of these parameters against echocardiography as well as their ability to characterize left ventricular (LV) diastolic dysfunction. RESULTS: We studied 35 controls and 18 patients with severe aortic valve stenosis and preserved LV ejection fraction who had PC-CMR and Doppler echocardiography exams on the same day. PC-CMR mitral flow and myocardial velocity data were analyzed using custom software for semi-automated extraction of diastolic parameters. Inter-operator reproducibility of flow pattern segmentation and functional parameters was assessed on a sub-group of 30 subjects. The mean percentage of overlap between the transmitral flow segmentations performed by two independent operators was 99.7 ± 1.6%, resulting in a small variability ( 0.71) and receiver operating characteristic (ROC) analysis revealed their ability to separate patients from controls, with sensitivity > 0.80, specificity > 0.80 and accuracy > 0.85. Slight superiority in terms of correlation with echocardiography (r = 0.81) and accuracy to detect LV abnormalities (sensitivity > 0.83, specificity > 0.91 and accuracy > 0.89) was found for the PC-CMR flow-rate related parameters. CONCLUSIONS: A fast and reproducible technique for flow and myocardial PC-CMR data analysis was successfully used on controls and patients to extract consistent velocity-related diastolic parameters, as well as flow rate-related parameters. This technique provides a valuable addition to established CMR tools in the evaluation and the management of patients with diastolic dysfunction

A finite strain nonlinear human mitral valve model with fluid structure interaction

A simulated human mitral valve under a physiological pressure loading is developed using a hybrid finite element immersed boundary method, which incorporates experimentally based constitutive laws in a three-dimensional fluid-structure interaction framework. A transversely isotropic material constitutive model is used for characterizing the mechanical behaviour of the mitral valve tissue based on recent mechanical tests of healthy human mitral leaflets. Our results show good agreement, in terms of the flow rate and the closing and opening configurations, with the measurements from the magnetic resonance images. The stresses in the anterior leaflet are found to be higher than those in the posterior leaflet, and concentrated around the annulus trigons and free edges of the valve leaflets. Those areas are located where the leaflet has the highest curvature. Effects of the chordae tendineae in the material model are studied and the results show that these chordae play an important role in providing a secondary orifice for the flow when valve opens. Although there are some discrepancies to be overcome in future works, our simulations show that the developed computational model is promising in mimicking the in vivo mitral valve dynamics and providing important information that are not obtainable by in vivo measurements. This article is protected by copyright. All rights reserved

Shape Analysis Based Strategies for Evaluation of Adaptations in In Vivo Right Ventricular Geometry and Mechanics as Effected by Pulmonary Hypertension

Pulmonary hypertension (PH) is a deadly disease, which as it progresses over time alters many aspects of the afflicted heart, and particularly the right ventricle (RV), such as its size, shape, and mechanical material properties. However, due to the limitations of what can be measured noninvasively in a standard clinical setting and the difficulty caused by the intrinsic complexity of the human RV, there has been little success to-date to identify clinically obtainable metrics of RV shape, deformation, or material properties that are quantitatively linked to the onset and progression of PH. Towards addressing this challenge, this work proposes the use of the shape and shape change of the RV, which is measurable from standard clinical imaging, along with statistical analysis and inverse material characterization strategies to identify new metrics of RV mechanical function that will be uniquely predictive of the state of the heart subject to PH. Thus, this thesis can be broken into two components: the first is statistical shape analysis of the RV, and the second is inverse characterization of heart wall mechanical material properties from RV shape change and measurable hemodynamics. For the statistical shape analysis investigation, a custom approach using harmonic mapping and proper orthogonal decomposition is applied to determine the fundamental components of shape (i.e., modes) from a dataset of 50 patients with varying states of PH, including some without PH at all. For the inverse characterization work, a novel method was developed to estimate the heterogeneous properties of a structure, given only the target shape of that structure, after a known excitation is applied to deform the structure. Lastly, the inverse characterization algorithm was extended to be applicable to actual in vivo cardiac data, particularly through the inclusion of a registration step to account for the organ-scale rotation and translation of the heart. Future work remains to expand on the computational efficiency of this inverse solution estimation procedure, and to further evaluate and improve upon the consistency and clinical interpretability of the material property estimates

Biophysical Analyses of Left Ventricular Remodeling Secondary to Myocardial Infarction and Left Ventricular Pressure Overload

Left ventricular (LV) remodeling is nominally an adaptive process that restores biomechanical function following myocardial injury and/or sustained alterations in loading conditions. This remodeling can materialize as changes in myocardial geometry, composition, and mechanical properties. When these changes fail to restore LV biomechanical function, remodeling is termed maladaptive. It is generally accepted that maladaptive LV remodeling underlies the progression to heart failure in various forms of heart disease. The central hypothesis of this study is that we can leverage echocardiographic imaging techniques to non-invasively quantify changes in biomechanical function and mechanical properties in a serial manner throughout the progression towards heart failure. The corollary to this hypothesis is that the observed changes in function and mechanical properties can, at least in part, be attributed to a reorganization of collagen within the extracellular matrix. Large animal models of myocardial infarction and left ventricular pressure overload were integrated with echocardiographic imaging, computational modeling, and multi-photon microscopy to test this hypothesis. We posit that this delineation of disease-specific LV remodeling outcomes, with focus on regional mechanical changes throughout the myocardium, will promote translational strategies that can interrupt this deterministic process

Hierarchical template matching for 3D myocardial tracking and cardiac strain estimation

Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers

Model-based quantification of systolic and diastolic left ventricular mechanics

Het linker ventrikel (LV) is de meest gespierde kamer van het hart. Door het gecoördineerd samentrekken van de spiercellen in de LV-wand wordt zuurstofrijk bloed in de aorta gepompt (systolische fase). Daarna ontspannen de spiercellen zich snel waardoor het LV opnieuw met bloed wordt gevuld (diastolische fase). In de kliniek en de onderzoekswereld bestaat er een waaier van modelgebaseerde methoden en concepten om de performantie en de mechanische eigenschappen van het LV te kwantificeren. Invasief bekomen druk- en volumedata laten toe om de systolische en diastolische mechanica van het LV met grote nauwkeurigheid te kennen. In de klinische praktijk wordt echter vaker gebruik gemaakt van (Doppler-) echocardiografie, een snelle en veilige niet-invasieve beeldtechniek. In een eerste deel van dit doctoraatsonderzoek werd een originele methode voorgesteld om, op basis van echocardiografie en klassieke bloeddrukmetingen, de intrinsieke krachtontwikkeling (contractiliteit) van het LV te schatten. De methode werd toegepast bij 2524 mensen die deelnemen aan de Asklepios-studie. De onderzoeksresultaten verschaften ons nieuwe informatie over hoe de evolutie van de krachtontwikkeling verschilt tussen gezonde mannen en vrouwen. De mechanische en vloeistofdynamische fenomenen tijdens de diastole vormden het onderwerp van het tweede deel van het onderzoek. Met behulp van een hydraulisch model van het LV werd nagegaan welke factoren een belangrijke invloed uitoefenen op het gedrag van het LV tijdens de isovolumetrische ontspanningsfase. In dit deel werd eveneens een uitgebreid overzicht gegeven van de meest recente echocardiografische methoden om de diastolische LV-mechanica te begroten. Daarbij werden de bloedstroming, de wandbeweging en de interactie tussen beiden gedetailleerd behandeld

Load-Independent And Regional Measures Of Cardiac Function Via Real-Time Mri

LOAD-INDEPENDENT AND REGIONAL MEASURES OF CARDIAC FUNCTION VIA REAL-TIME MRI Francisco Jose Contijoch Robert C Gorman, MD Expansion of infarcted tissue during left ventricular (LV) remodeling after a myocardial infarction is associated with poor long-term prognosis. Several interventions have been developed to limit infarct expansion by modifying the material properties of the infarcted or surrounding borderzone tissue. Measures of myocardial function and material properties can be obtained non-invasively via imaging. However, these measures are sensitive to variations in loading conditions and acquisition of load-independent measures have been limited by surgically invasive procedures and limited spatial resolution. In this dissertation, a real-time magnetic resonance imaging (MRI) technique was validated in clinical patients and instrumented animals, several technical improvements in MRI acquisition and reconstruction were presented for improved imaging resolution, load-independent measures were obtained in animal studies via non-invasive imaging, and regional variations in function were measured in both na�ve and post-infarction animals. Specifically, a golden-angle radial MRI acquisition with non-Cartesian SENSE-based reconstruction with an exposure time less than 95 ms and a frame rate above 89 fps allows for accurate estimation of LV slice volume in clinical patients and instrumented animals. Two technical developments were pursued to improve image quality and spatial resolution. First, the slice volume obtained can be used as a self-navigator signal to generate retrospectively-gated, high-resolution datasets of multiple beat morphologies. Second, cross-correlation of the ECG with previously observed values resulted in accurate interpretation of cardiac phase in patients with arrhythmias and allowed for multi-shot imaging of dynamic scenarios. Synchronizing the measured LV slice volume with an LV pressure signal allowed for pressure-volume loops and corresponding load-independent measures of function to be obtained in instrumented animals. Acquiring LV slice volume at multiple slice locations revealed regional differences in contractile function. Motion-tracking of the myocardium during real-time imaging allowed for differences in contractile function between normal, borderzone, and infarcted myocardium to be measured. Lastly, application of real-time imaging to patients with arrhythmias revealed the variable impact of ectopic beats on global hemodynamic function, depending on frequency and ectopic pattern. This work established the feasibility of obtaining load-independent measures of function via real-time MRI and illustrated regional variations in cardiac function

Assessment and management of structural heart disease in an ageing population.

Structural heart disease interventions represent a rapidly evolving branch of percutaneous treatments to correct valvular lesions that were previously treated surgically, or simply not addressed. In the past decade, the therapeutic landscape for patients with degenerative aortic valve stenosis (AS) and secondary mitral regurgitation (MR) has changed dramatically. As transcatheter innovations continue to develop, cardiac physiologists and clinicians alike are challenged by the need to more accurately discriminate between those who will benefit from intervention, and those who will not. Interpreting valvular function in the setting of impaired contractile performance and/or poor arterial compliance is especially difficult. Hemodynamic loading conditions in these settings are often unique, and not adequately accounted for using traditional cardiac imaging techniques. Load independent assessment of contractile function requires the simultaneous measurement of left ventricular (LV) pressure, volume and flow in order to determine the relationship between these parameters at various points in the cardiac cycle. Our work incorporates advances in cardiac magnetic resonance and echocardiography imaging techniques to allow better non-invasive assessment of ventricular mechanics and ventricular-vascular interactions in response to structural aortic and mitral valve interventions. We have devised precise and accurate non-invasive tools to quantify LV and aortic pressure, LV volume and aortic flow, and have coalesced this data to determine the LV pressure-volume and aortic pressure-flow relationships in patients with degenerative AS and secondary MR. It is our intention that the development of high-quality non-invasive data on ventricular contractility and ventricular-vascular coupling, will provide a better platform to evaluate cardiovascular performance in those with valvular heart disease