Modeling cardiac electromechanics and mechanoelectrical coupling in dyssynchronous and failing hearts : insight from adaptive computer models

Computer models have become more and more a research tool to obtain mechanistic insight in the effects of dyssynchrony and heart failure. Increasing computational power in combination with increasing amounts of experimental and clinical data enables the development of mathematical models that describe electrical and mechanical behavior of the heart. By combining models based on data at the molecular and cellular level with models that describe organ function, so-called multi-scale models are created that describe heart function at different length and time scales. In this review, we describe basic modules that can be identified in multi-scale models of cardiac electromechanics. These modules simulate ionic membrane currents, calcium handling, excitation–contraction coupling, action potential propagation, and cardiac mechanics and hemodynamics. In addition, we discuss adaptive modeling approaches that aim to address long-term effects of diseases and therapy on growth, changes in fiber orientation, ionic membrane currents, and calcium handling. Finally, we discuss the first developments in patient-specific modeling. While current models still have shortcomings, well-chosen applications show promising results on some ultimate goals: understanding mechanisms of dyssynchronous heart failure and tuning pacing strategy to a particular patient, even before starting the therapy

Pressure-dependence of arterial stiffness:potential clinical implications

BACKGROUND: \u3cbr/\u3eArterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age.\u3cbr/\u3eMETHODS: \u3cbr/\u3eUsing a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80 mmHg) pressure ranges.\u3cbr/\u3eRESULTS: \u3cbr/\u3eFollow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10 mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings.\u3cbr/\u3eCONCLUSION: \u3cbr/\u3eOur study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements.\u3cbr/\u3

Combined 18F-FDG PET-CT and DCE-MRI to assess inflammation and microvascularization in atherosclerotic plaques

Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast-enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated. Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman ρ=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman ρ=0.29 [P=0.041]) was found. There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast-enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable. http://www.clinicaltrials.gov. Unique identifier: NCT0045152

Heart rate lowering treatment leads to a reduction in vulnerable plaque features in atherosclerotic rabbits - Fig 4

<p>Histological sections of atherosclerotic plaque for a non-treated (panels A-C) and Ivabradine treated (panels D-F) rabbit. Panel A and D show HE sections and panel B and E a slide stained for macrophages using RAM11 antibody (red), with magnifications in panel C and F.</p

Presence of macrophages in the proximity of the vascular lumen using a semi-quantitative three point scale for non-treated (eight animals, two sections per animal) and Ivabradine-treated animals (seven animals, 2 sections per animal).

<p>Histological sections are divided into three categories ranging from 0 (no luminal macrophages; example image shown in panel B) via 1 (partially luminal macrophages; example in panel C) to 2 (predominantly luminal macrophages; example in panel D). Macrophages in the histological images are indicated by an arrow head (^). The displayed scale bar is applicable for all histological images and the luminal side is indicated by an asterisk (*) in all histological images.</p

Number of successfully performed procedures in the present study.

<p>Number of successfully performed procedures in the present study.</p

Bar graphs showing the differences between non-treated and Ivabradine-treated animals (mean ± standard error).

<p>Panel A shows the conscious heart rate; panel B relative RAM11 positive area in histological sections; panel C and D show the area-under-the-curve (AUC) and K^trans determined from analysis of DCE-MR images.</p

The experimental design.

<p>Two weeks after initiation of 1.0% cholesterol-enriched diet, the animals receive a balloon injury. At week 10, they are switched from 1.0% to 0.3% cholesterol-enriched diet. Fourteen weeks after diet initiation the animals undergo measurement of the HR and US and MR imaging before euthanisation.</p

Study parameters for the present study.

<p>Parameters are reported as mean values ± standard error. Number of successful experiments that were performed is indicated (^§n = 9, ^lln = 8, ^¶n = 7, ^#n = 6). AUC 7 min and K^trans represent DCE-MRI parameters of the plaque microvasculature. The percentage of RAM11 is a measure of the plaque macrophage content. Used abbreviations: heart rate (HR); blood pressure (BP); Elastica von Gieson (EvG); area-under-the-curve (AUC); ^*p<0.05.</p