Pressure-Corrected Carotid Stiffness and Young's Modulus: Evaluation in an Outpatient Clinic Setting.

BACKGROUND: Conventional measures for assessing arterial stiffness are inherently pressure dependent. Whereas statistical pressure adjustment is feasible in (larger) populations, it is unsuited for the evaluation of an individual patient. Moreover, statistical "correction" for blood pressure may actually correct for: (i) the acute dependence of arterial stiffness on blood pressure at the time of measurement; and/or (ii) the remodeling effect that blood pressure (hypertension) may have on arterial stiffness, but it cannot distinguish between these processes. METHODS: We derived-assuming a single-exponential pressure-diameter relationship-3 theoretically pressure-independent carotid stiffness measures suited for individual patient evaluation: (i) stiffness index ß0, (ii) pressure-corrected carotid pulse wave velocity (cPWVcorr), and (iii) pressure-corrected Young's modulus (Ecorr). Using linear regression analysis, we evaluated in a sample of the CATOD study cohort changes in mean arterial pressure (ΔMAP) and comparatively the changes in the novel (Δß0, ΔcPWVcorr, and ΔEcorr) as well as conventional (ΔcPWV and ΔE) stiffness measures after a 2.9 ± 1.0-year follow-up. RESULTS: We found no association between ΔMAP and Δß0, ΔcPWVcorr, or ΔEcorr. In contrast, we did find a significant association between ΔMAP and conventional measures ΔcPWV and ΔE. Additional adjustments for biomechanical confounders and traditional risk factors did neither materially change these associations nor the lack thereof. CONCLUSIONS: Our newly proposed pressure-independent carotid stiffness measures avoid the need for statistical correction. Hence, these measures (ß0, cPWVcorr, and Ecorr) can be used in a clinical setting for (i) patient-specific risk assessment and (ii) investigation of potential remodeling effects of (changes in) blood pressure on intrinsic arterial stiffness.

Complementing sparse vascular imaging data by physiological adaptation rules.

Mathematical modeling of pressure and flow waveforms in blood vessels using pulse wave propagation (PWP) models has tremendous potential to support clinical decision making. For a personalized model outcome, measurements of all modeled vessel radii and wall thicknesses are required. In clinical practice, however, data sets are often incomplete. To overcome this problem, we hypothesized that the adaptive capacity of vessels in response to mechanical load could be utilized to fill in the gaps of incomplete patient-specific data sets. We implemented homeostatic feedback loops in a validated PWP model to allow adaptation of vessel geometry to maintain physiological values of wall stress and wall shear stress. To evaluate our approach, we gathered vascular MRI and ultrasound data sets of wall thicknesses and radii of central and arm arterial segments of 10 healthy subjects. Reference models (i.e., termed RefModel, n = 10) were simulated using complete data, whereas adapted models (AdaptModel, n = 10) used data of one carotid artery segment only, and the remaining geometries in this model were estimated using adaptation. We evaluated agreement between RefModel and AdaptModel geometries, as well as that between pressure and flow waveforms of both models. Limits of agreement (bias ± 2 SD of difference) between AdaptModel and RefModel radii and wall thicknesses were 0.2 ± 2.6 mm and -140 ± 557 µm, respectively. Pressure and flow waveform characteristics of the AdaptModel better resembled those of the RefModels as compared with the model in which the vessels were not adapted. Our adaptation-based PWP model enables personalization of vascular geometries even when not all required data are available.NEW & NOTEWORTHY To benefit personalized pulse wave propagation (PWP) modeling, we propose a novel method that, instead of relying on extensive data sets on vascular geometries, incorporates physiological adaptation rules. The developed vascular adaptation model adequately predicted arterial radius and wall thickness compared with ultrasound and MRI estimates, obtained in humans. Our approach could be used as a tool to facilitate personalized modeling, notably in case of missing data, as routinely found in clinical settings.

Large vessels as a tree of transmission lines incorporated in the CircAdapt whole-heart model: A computational tool to examine heart-vessel interaction.

We developed a whole-circulation computational model by integrating a transmission line (TL) model describing vascular wave transmission into the established CircAdapt platform of whole-heart mechanics. In the present paper, we verify the numerical framework of our TL model by benchmark comparison to a previously validated pulse wave propagation (PWP) model. Additionally, we showcase the integrated CircAdapt-TL model, which now includes the heart as well as extensive arterial and venous trees with terminal impedances. We present CircAdapt-TL haemodynamics simulations of: 1) a systemic normotensive situation and 2) a systemic hypertensive situation. In the TL-PWP benchmark comparison we found good agreement regarding pressure and flow waveforms (relative errors ≤ 2.9% for pressure, and ≤ 5.6% for flow). CircAdapt-TL simulations reproduced the typically observed haemodynamic changes with hypertension, expressed by increases in mean and pulsatile blood pressures, and increased arterial pulse wave velocity. We observed a change in the timing of pressure augmentation (defined as a late-systolic boost in aortic pressure) from occurring after time of peak systolic pressure in the normotensive situation, to occurring prior to time of peak pressure in the hypertensive situation. The pressure augmentation could not be observed when the systemic circulation was lumped into a (non-linear) three-element windkessel model, instead of using our TL model. Wave intensity analysis at the carotid artery indicated earlier arrival of reflected waves with hypertension as compared to normotension, in good qualitative agreement with findings in patients. In conclusion, we successfully embedded a TL model as a vascular module into the CircAdapt platform. The integrated CircAdapt-TL model allows detailed studies on mechanistic studies on heart-vessel interaction.

Augmentation index is not a proxy for wave reflection magnitude: mechanistic analysis using a computational model.

The augmentation index (AIx) is deemed to capture the deleterious effect on left ventricular (LV) work of increased wave reflection associated with stiffer arteries. However, its validity as a proxy for wave reflection magnitude has been questioned. We hypothesized that, in addition to increased wave reflection due to increased pulse wave velocity, LV myocardial shortening velocity influences AIx. Using a computational model of the circulation, we investigated the isolated and combined influences of myocardial shortening velocity vs,LV and arterial stiffness on AIx. Aortic blood pressure waveforms were characterized using AIx and the reflected wave pressure amplitude (p̂bw, obtained using wave separation analysis). Our reference simulation (normal vs,LV and arterial stiffness) was characterized by an AIx of 21%. A realistic reduction in vs,LV caused AIx to increase from 21 to 42%. An arterial stiffness increase, characterized by a relevant 1.0 m/s increase in carotid-femoral pulse wave velocity, caused AIx to increase from 21 to 41%. Combining the reduced vs,LV and increased arterial stiffness resulted in an AIx of 54%. In a multistep parametric analysis, both vs,LV and arterial stiffness were about equal determinants of AIx, whereas p̂bw was only determined by arterial stiffness. Furthermore, the relation between increased AIx and LV stroke work was only ≈50% explained by an increase in arterial stiffness, the other factor being vs,LV. The p̂bw, on the other hand, related less ambiguously to LV stroke work. We conclude that the AIx reflects both cardiac and vascular properties and should not be considered an exclusively vascular parameter.NEW & NOTEWORTHY We used a state-of-the-art computational model to mechanistically investigate the validity of the augmentation index (AIx) as a proxy for (changes in) wave reflection. In contrary to current belief, we found that LV contraction velocity influences AIx as much as increased arterial stiffness, and increased AIx does not necessarily relate to an increase in LV stroke work. Wave reflection magnitude derived from considering pressure, as well as flow, does qualify as a determinant of LV stroke work.

Do treatment-induced changes in arterial stiffness affect left ventricular structure? A meta-analysis.

BACKGROUND: Vascular research demonstrated that pulse wave velocity (PWV), a measure of arterial stiffness, is inherently blood pressure dependent. Considering the hypothesized pathophysiological chain of increased arterial stiffness leading to increased blood pressure load with consequent left ventricular hypertrophy (LVH) development, we conducted a systematic review of antihypertensive and lifestyle intervention studies to determine the association between, on the one hand, changes in arterial stiffness and blood pressure, and, on the other hand, changes in left ventricular mass (LVM). METHODS: Using PubMed, EMBASE, Cochrane and Web of Science, we identified 23 studies, containing 2573 patients. Studies reported changes in arterial stiffness (assessed by means of PWV), SBP, DBP and LVM index (LVMI), respectively. RESULTS: Statistically significant reductions in SBP, PWV and LVMI were reported in 16, 14 and 20 studies, respectively. Pooled analysis of studies showed that the proportion in SBP reduction did not correlate significantly to the proportion in reductions of the other two variables. On the contrary, we found a significant positive correlation (r = 0.61, P = 0.003) between arterial stiffness and reduction of LVM, expressed as a relevant reduction in LVMI of 6.9 g/m per 1.0 m/s reduction in PWV. CONCLUSION: Our findings provide evidence that a decrease in arterial stiffness is associated with reduction of LVM. To investigate whether there exists a causal relation between LVH due to arterial stiffness increases and in turn blood pressure load increases, future studies should strive for a multiple follow-up design and use of blood pressure independent or corrected stiffness indices.

Uncertainty quantification and sensitivity analysis of an arterial wall mechanics model for evaluation of vascular drug therapies.

Quantification of the uncertainty in constitutive model predictions describing arterial wall mechanics is vital towards non-invasive assessment of vascular drug therapies. Therefore, we perform uncertainty quantification to determine uncertainty in mechanical characteristics describing the vessel wall response upon loading. Furthermore, a global variance-based sensitivity analysis is performed to pinpoint measurements that are most rewarding to be measured more precisely. We used previously published carotid diameter-pressure and intima-media thickness (IMT) data (measured in triplicate), and Holzapfel-Gasser-Ogden models. A virtual data set containing 5000 diastolic and systolic diameter-pressure points, and IMT values was generated by adding measurement error to the average of the measured data. The model was fitted to single-exponential curves calculated from the data, obtaining distributions of constitutive parameters and constituent load bearing parameters. Additionally, we (1) simulated vascular drug treatment to assess the relevance of model uncertainty and (2) evaluated how increasing the number of measurement repetitions influences model uncertainty. We found substantial uncertainty in constitutive parameters. Simulating vascular drug treatment predicted a 6% point reduction in collagen load bearing ([Formula: see text]), approximately 50% of its uncertainty. Sensitivity analysis indicated that the uncertainty in [Formula: see text] was primarily caused by noise in distension and IMT measurements. Spread in [Formula: see text] could be decreased by 50% when increasing the number of measurement repetitions from 3 to 10. Model uncertainty, notably that in [Formula: see text], could conceal effects of vascular drug therapy. However, this uncertainty could be reduced by increasing the number of measurement repetitions of distension and wall thickness measurements used for model parameterisation.

Carotid Artery Plaque Vulnerability Assessment Using Noninvasive Ultrasound Elastography: Validation With MRI.

OBJECTIVE: Vulnerable and nonvulnerable carotid artery plaques have different tissue morphology and composition that may affect plaque biomechanics. The objective of this study is to evaluate plaque vulnerability with the use of ultrasound noninvasive vascular elastography (NIVE). MATERIALS AND METHODS: Thirty-one patients (mean [± SD] age, 69 ± 7 years) with stenosis of the internal carotid artery of 50% or greater were enrolled in this cross-sectional study. Elastography parameters quantifying axial strain, shear strain, and translation motion were used to characterize carotid artery plaques as nonvulnerable, neovascularized, and vulnerable. Maximum axial strain, cumulated axial strain, mean shear strain, cumulated shear strain, cumulated axial translation, and cumulated lateral translations were measured. Cumulated measurements were summed over a cardiac cycle. The ratio of cumulated axial strain to cumulated axial translation was also evaluated. The reference method used to characterize plaques was high-resolution MRI. RESULTS: According to MRI, seven plaques were vulnerable, 12 were nonvulnerable without neovascularity, and 12 were nonvulnerable with neovascularity (a precursor of vulnerability). The two parameters cumulated axial translation and the ratio of cumulated axial strain to cumulated axial translation could discriminate between nonvulnerable plaques and vulnerable plaques or determine the presence of neovascularity in nonvulnerable plaques (which was also possible with the mean shear strain parameter). All parameters differed between the non-vulnerable plaque group and the group that combined vulnerable plaques and plaques with neovascularity. The most discriminating parameter for the detection of vulnerable neovascularized plaques was the ratio of cumulated axial strain to cumulated axial translation (expressed as percentage per millimeter) (mean ratio, 39.30%/mm ± 12.80%/mm for nonvulnerable plaques without neovascularity vs 63.79%/mm ± 17.59%/mm for vulnerable plaques and nonvulnerable plaques with neovascularity, p = 0.002), giving an AUC value of 0.886. CONCLUSION: The imaging parameters cumulated axial translation and the ratio of cumulated axial strain to cumulated axial translation, as computed using NIVE, were able to discriminate vulnerable carotid artery plaques characterized by MRI from nonvulnerable carotid artery plaques. Consideration of neovascularized plaques improved the performance of NIVE. NIVE may be a valuable alternative to MRI for carotid artery plaque assessment.

Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries.

The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R2 ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies.NEW & NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of microvascular pathologies.

Head orientation should be considered in ultrasound studies on carotid artery distensibility.

INTRODUCTION: During ultrasound distensibility assessment of the carotid artery, the patient's head is usually rotated sideward and slightly upward to optimize visibility of the carotid segment. Head rotation may affect vessel length and thus the longitudinal strain of the arterial segment. Because the longitudinal and circumferential mechanical behaviour of an artery are intrinsically related, head rotation may influence circumferential mechanics and thereby measured distensibility. METHODS: In 12 apparently healthy volunteers (age 22 ±â€Š3 years, mean ±â€ŠSD, 6 men/6 women), we investigated whether head rotation led to a change in absolute and relative distension of the common carotid artery (CCA) by performing ultrasound examinations with the head in two orientations. Additionally, CCA length was measured in both orientations with MRI to assess whether indeed a change in length occurred because of head rotation. Rotation-induced longitudinal strain was calculated from these lengths. RESULTS: We found a significant decrease of 0.054 mm (6.8%, P = 0.001) and 0.007 (5.6%, P = 0.019) in absolute and relative distension with head rotation, respectively. MRI measurements showed a significant rotation-induced longitudinal strain of 1.7 ±â€Š2.3% (P = 0.032). CONCLUSION: We conclude that consistent head rotation during a CCA ultrasound assessment causes a significant and clinically relevant bias in carotid artery distension measurements. The impact of unstandardized use of head rotation in studies with carotid distensibility as an outcome measure can therefore not be neglected; thus, standardization is highly recommendable.

Pressure-dependence of arterial stiffness: potential clinical implications.

BACKGROUND: Arterial 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. METHODS: Using 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. RESULTS: Follow-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. CONCLUSION: Our 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.

A constitutive modeling interpretation of the relationship among carotid artery stiffness, blood pressure, and age in hypertensive subjects.

Aging has a profound influence on arterial wall structure and function. We have previously reported the relationship among pulse wave velocity, age, and blood pressure in hypertensive subjects. In the present study, we aimed for a quantitative interpretation of the observed changes in wall behavior with age using a constitutive modeling approach. We implemented a model of arterial wall biomechanics and fitted this to the group-averaged pressure-area (P-A) relationship of the "young" subgroup of our study population. Using this model as our take-off point, we assessed which parameters had to be changed to let the model describe the "old" subgroup's P-A relationship. We allowed elastin stiffness and collagen recruitment parameters to vary and adjusted residual stress parameters according to published age-related changes. We required wall stress to be homogeneously distributed over the arterial wall and assumed wall stress normalization with age by keeping average "old" wall stress at the "young" level. Additionally, we required axial force to remain constant over the cardiac cycle. Our simulations showed an age-related shift in pressure-load bearing from elastin to collagen, caused by a decrease in elastin stiffness and a considerable increase in collagen recruitment. Correspondingly, simulated diameter and wall thickness increased by about 20 and 17%, respectively. The latter compared well with a measured thickness increase of 21%. We conclude that the physiologically realistic changes in constitutive properties we found under physiological constraints with respect to wall stress could well explain the influence of aging in the stiffness-pressure-age pattern observed.

Biomechanical studies on transverse olecranon and patellar fractures: a systematic review with the development of a new scoring method.

INTRODUCTION: Several methods of transverse patellar and olecranon fixation have been described. This article compares biomechanical studies of various fixation methods using a newly developed scoring method. SOURCE OF DATA: The databases PubMed, Web of Science, Science Direct, Google Scholar and Google were searched for relevant studies. AREAS OF AGREEMENT: Fixation hardware failure remains a problem. Various materials and fixation techniques have been tested to provide an improved fixation of transverse olecranon and patellar fractures. AREAS OF CONTROVERSY: The difference in biomechanical testing setup between the studies makes it hard to compare different fixation techniques. GROWING POINTS: The newly developed grading method was proved to be unbiased and reliable; however, extra specifications need to be added at some criteria when adopting the scoring method. AREAS TIMELY FOR DEVELOPING RESEARCH: Non-metallic constructs may provide an improvement to the currently used metallic tension band wiring technique; however, clinical research is required.

Treatment of transverse patellar fractures: a comparison between metallic and non-metallic implants.

INTRODUCTION: Several methods of transverse patellar fixation have been described. This study compares the clinical outcome and the occurrence of complications of various fixation methods. SOURCES OF DATA: The databases PubMed, Web of Science, Science Direct, Google Scholar and Google were searched. AREAS OF AGREEMENT: A direct comparison between fixation techniques using mixed or non-metallic implants and metallic K-wire and tension band fixation shows no significant difference in clinical outcome between both groups. Additionally, studies reporting novel operation techniques show good clinical results. AREAS OF CONTROVERSY: Studies describing the treatment of patients using non-metallic or mixed implants are fewer compared with those using metallic fixation. GROWING POINTS: A large variety of clinical scoring systems were used for assessing the results of treatment, which makes direct comparison difficult. AREAS TIMELY FOR DEVELOPING RESEARCH: More data of fracture treatment using non-metallic or mixed implants is needed to achieve a more balanced comparison.