Creation and application of virtual patient cohorts of heart models Niederer, S A; Aboelkassem, Y; Cantwell, C D ...
Philosophical transactions - Royal Society. Mathematical, Physical and engineering sciences/Philosophical transactions - Royal Society. Mathematical, physical and engineering sciences,
06/2020, Volume:
378, Issue:
2173
Journal Article
Peer reviewed
Open access
Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts ...of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
Reliable assessment of the microcirculation is important to investigate microcirculatory properties in various disease states. The GlycoCheck system automatically analyzes sublingual sidestream dark ...field images to determine the perfused boundary region (PBR; a measure of glycocalyx thickness), red blood cell filling percentage, and microvascular vessel density. Although GlycoCheck has been used to study the microcirculation in patients, little is known about the reproducibility of measurements in healthy volunteers. We assessed intra- and interobserver agreement by having two experienced observers perform three consecutive microcirculation measurements with the GlycoCheck system in 49 healthy volunteers. Intraobserver agreement of single measurements were poor (intraclass correlation coefficients (ICCs) < 0.4) for PBR, red blood cell filling percentage and microvascular vessel density. ICCs increased to values > 0.6 (indicating good reproducibility) for all parameters when performing and averaging three consecutive measurements. No systematic differences were observed between observers for any parameter. Interobserver variability was fair for PBR (ICC = 0.53) and red blood cell filling percentage (ICC = 0.58) and poor for perfused vessel density (ICC = 0.20). In conclusion, GlycoCheck software can be used with acceptable reliability and reproducibility for microcirculation measurements on a population level when averaging three consecutive measurements. Repeated measurements are preferably performed by the same observer.
Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce.
To record current practice and ...results of CRT in paediatric and congenital heart disease.
Retrospective multicentre European survey.
Paediatric cardiology and cardiac surgery centres.
One hundred and nine patients aged 0.24-73.8 (median 16.9) years with structural congenital heart disease (n = 87), congenital atrioventricular block (n = 12) and dilated cardiomyopathy (n = 10) with systemic left (n = 69), right (n = 36) or single (n = 4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n = 25) or associated with pacing (n = 84).
CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109).
Functional improvement and echocardiographic change in systemic ventricular function.
The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p<0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p<0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p<0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p = 0.002) and poor NYHA class (p = 0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p<0.001). Results were independent of the number of patients treated in each contributing centre.
Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate.
The new SinMod method extracts motion from magnetic resonance imaging (MRI)-tagged (MRIT) image sequences. Image intensity in the environment of each pixel is modeled as a moving sine wavefront. ...Displacement is estimated at subpixel accuracy. Performance is compared with the harmonic-phase analysis (HARP) method, which is currently the most common method used to detect motion in MRIT images. SinMod can handle line tags, as well as speckle patterns. In artificial images (tag distance six pixels), SinMod detects displacements accurately (error < pixels). Effects of noise are suppressed effectively. Sharp transitions in motion at the boundary of an object are smeared out over a width of 0.6 tag distance. For MRIT images of the heart, SinMod appears less sensitive to artifacts, especially later in the cardiac cycle when image quality deteriorates. For each pixel, the quality of the sine-wave model in describing local image intensity is quantified objectively. If local quality is low, artifacts are avoided by averaging motion over a larger environment. Summarizing, SinMod is just as fast as HARP, but it performs better with respect to accuracy of displacement detection, noise reduction, and avoidance of artifacts.
Long QT syndrome (LQTS) is associated with malignant arrhythmias and sudden death from birth to advanced age. Prolongation of the QT-interval, may however be concealed on standard electrocardiograms ...(ECG). The brisk-standing-test (BST) was developed to guide LQTS-diagnosis and treatment in adults. We hypothesized that the BST may be used in prepubertal children to identify LQTS subjects. Accordingly, reference values for the BST should be available to prevent incorrect diagnosis and treatment of LQTS. In this study, we aim to present reference values for prepubertal children.
Healthy, prepubertal children, aged 7-13 years underwent a standard supine resting ECG and during continuous ECG recording performed a BST. The QT-interval and heart rate corrected QTc were measured during the different BST stages. Fifty-seven children, 29 boys (10.2 ± 1.1 years) and 28 girls (9.9 ± 1.1 years) were included. Baseline characteristics and response to standing were not statistically different for boys and girls: mean supine pre-standing heart rate 74 ± 9 vs. 77 ± 9 bpm, supine pre-standing QTc 406 ± 27 vs. 407 ± 17 ms, maximal heart rate upon standing 109 ± 11 vs. 112 ± 11 bpm, and QTc at maximal heart rate 484 ± 29 vs. 487 ± 35 ms. The QT interval corrected for heart rate-prolongation at maximal tachycardia after standing was 79 ± 26 (19-144) ms, which is significantly longer than previously published values in adults (50± 30 ms).
The QT interval corrected for heart rate prolongation after brisk standing in healthy prepubertal children is more pronounced than in healthy adults. This finding advocates distinct prepubertal cut-off values because using adult values for prepubertal children would yield false positive results with the risk of incorrect LQTS-diagnosis and overtreatment.
Glycocalyx shedding and subsequent endothelial dysfunction occur in many conditions, such as in sepsis, in critical illness, and during major surgery such as in coronary artery bypass grafting (CABG) ...where it has been shown to associate with organ dysfunction. Hitherto, there is no consensus about the golden standard in measuring glycocalyx properties in humans. The objective of this study was to compare different indices of glycocalyx shedding and dysfunction. To this end, we studied patients undergoing elective CABG surgery, which is a known cause of glycocalyx shedding.
Sublingual glycocalyx thickness was measured in 23 patients by: 1) determining the perfused boundary region (PBR)-an inverse measure of glycocalyx thickness-by means of sidestream dark field imaging technique. This is stated double, 2) measuring plasma levels of the glycocalyx shedding products syndecan-1, hyaluronan, and heparan sulfate and 3) measuring plasma markers of impaired glycocalyx function and endothelial activation (Ang-2, Tie-2, E-selectin, and thrombomodulin). Measurements were performed directly after induction, directly after onset of cardiopulmonary bypass (CPB), and directly after cessation of CPB. We assessed changes over time as well as correlations between the various markers.
The PBR increased from 1.81 ± 0.21 μm after induction of anesthesia to 2.27 ± 0.25 μm (
< 0.0001) directly after CPB was initiated and did not change further during CPB. A similar pattern was seen for syndecan-1, hyaluronan, heparan sulfate, Ang-2, Tie-2, and thrombomodulin. E-selectin levels also increased between induction and the start of CPB and increased further during CPB. The PBR correlated moderately with heparan sulfate, E-selectin, and thrombomodulin and weakly with Syndecan-1, hyaluronan, and Tie-2. Shedding markers syndecan-1 and hyaluronan correlated with all functional markers. Shedding marker heparan sulfate only correlated with Tie-2, thrombomodulin, and E-selectin. Thrombomodulin correlated with all shedding markers.
Our results show that glycocalyx thinning, illustrated by increased sublingual PBR and increased levels of shedding markers, is paralleled with impaired glycocalyx function and increased endothelial activation in CABG surgery with CPB. As correlations between different markers were limited, no single marker could be identified to represent the glycocalyx in its full complexity.
It is unclear how the position of the left ventricular (LV) lead relative to a scar affects the haemodynamic response in patients with dyssynchronous heart failure receiving cardiac resynchronization ...therapy. We investigated this complex interaction using a computational model.
The CircAdapt computational cardiovascular system model was used to simulate heart failure with left bundle branch block (LBBB). Myocardial scar was induced in four different regions of the LV free wall (LVFW). We then simulated biventricular pacing (BVP) in each heart, in which LV lead position was varied. The LV lead position leading to maximal acute change in LV stroke volume (SV) was defined as optimal lead position. In LBBB without scar, SV increase was maximal when pacing the LVFW region most distant from the septum. With a scar adjacent to the septum, maximal response was achieved when pacing remote from both the septum and the scar. When the scar was located further from the septum, the BVP-induced increase of SV was small. For all hearts, pacing from the optimal LV lead position resulted in the most homogeneous distribution of local ventricular myofibre work and the largest increase in summed left and right ventricular pump work.
These computer simulations suggest that, in hearts with LBBB and scar, the optimal LV lead position is a compromise between a position distant from the scar and from the septum. In infarcted hearts, the best haemodynamic effect is achieved when electromechanical resynchronization of the remaining viable myocardium is most effective.
The aim of this study was to develop and verify a model that provides an accurate estimation of the trans-lesion hyperemic pressure gradient in iliac artery stenoses in seconds by only using ...patient-specific geometric properties obtained from 3-dimensional rotational angiography (3DRA).
Twenty-one patients with symptomatic peripheral arterial disease (PAD), iliac artery stenoses and an ultrasound based peak systolic velocity ratio between 2.5 and 5.0 underwent 3DRA and intra-arterial pressure measurements under hyperemic conditions. For each lesion, geometric properties were extracted from the 3DRA images using quantitative vascular analysis software. Hyperemic blood flow was estimated based on stenosis geometry using an empirical relation. The geometrical properties and hyperemic flow were used to estimate the pressure gradient by means of the geometry-based model. The predicted pressure gradients were compared with in vivo measured intra-arterial pressure measurements performed under hyperemic conditions.
The developed geometry-based model showed good agreement with the measured hyperemic pressure gradients resulting in a concordance correlation coefficient of 0.86. The mean bias ± 2SD between the geometry-based model and in vivo measurements was comparable to results found by evaluating the actual computational fluid dynamics model (−1.0 ± 14.7 mmHg vs −0.9 ± 12.7 mmHg).
The developed model estimates the trans-lesional pressure gradient in seconds without the need for an additional computational fluid dynamics software package. The results justify further study to assess the potential use of a geometry-based model approach to estimate pressure gradient on non-invasive CTA or MRA, thereby reducing the need for diagnostic angiography in patients suffering from PAD.
PDF
