Publications by authors named "Marcel C M Rutten"

62 Publications

Model-based aortic power transfer: A potential measure for quantifying aortic stenosis severity based on measured data.

Med Eng Phys 2021 04 26;90:66-81. Epub 2021 Feb 26.

Eindhoven University of Technology, Department of Biomedical Engineering, Postbus 513, Eindhoven 5600MB, the Netherlands.

Current aortic stenosis severity grading is based mainly on the local properties of the stenotic valve, such as pressure gradient or jet velocity. Success rates of valve replacement therapy are still suboptimal, so alternative grading of AS should be investigated. We suggest the efficiency of power transfer from the left ventricle to the aorta, as it takes into account heart, valve and circulatory system. Left ventricular and circulatory power were estimated using a 0D model, which was optimised to patient data: left ventricular and aortic pressure, aortic flow and diastolic left ventricular volume. Optimisation was performed using a data assimilation method. These data were available in rest as well as chemically induced exercise for twelve patients. Using this limited data set, we showed that aortic valve efficiency is highly heterogeneous between patients, but also often dependent on the haemodynamic load. This indicates that power transfer efficiency is a highly interesting metric for further research in aortic stenosis.
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http://dx.doi.org/10.1016/j.medengphy.2021.02.009DOI Listing
April 2021

Uncertainty in model-based treatment decision support: Applied to aortic valve stenosis.

Int J Numer Method Biomed Eng 2020 10 5;36(10):e3388. Epub 2020 Aug 5.

Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

Patient outcome in trans-aortic valve implantation (TAVI) therapy partly relies on a patient's haemodynamic properties that cannot be determined from current diagnostic methods alone. In this study, we predict changes in haemodynamic parameters (as a part of patient outcome) after valve replacement treatment in aortic stenosis patients. A framework to incorporate uncertainty in patient-specific model predictions for decision support is presented. A 0D lumped parameter model including the left ventricle, a stenotic valve and systemic circulatory system has been developed, based on models published earlier. The unscented Kalman filter (UKF) is used to optimize model input parameters to fit measured data pre-intervention. After optimization, the valve treatment is simulated by significantly reducing valve resistance. Uncertain model parameters are then propagated using a polynomial chaos expansion approach. To test the proposed framework, three in silico test cases are developed with clinically feasible measurements. Quality and availability of simulated measured patient data are decreased in each case. The UKF approach is compared to a Monte Carlo Markov Chain (MCMC) approach, a well-known approach in modelling predictions with uncertainty. Both methods show increased confidence intervals as measurement quality decreases. By considering three in silico test-cases we were able to show that the proposed framework is able to incorporate optimization uncertainty in model predictions and is faster and the MCMC approach, although it is more sensitive to noise in flow measurements. To conclude, this work shows that the proposed framework is ready to be applied to real patient data.
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http://dx.doi.org/10.1002/cnm.3388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583387PMC
October 2020

Ultrasound-based estimation of remaining cardiac function in LVAD-supported ex vivo hearts.

Artif Organs 2020 Aug 18;44(8):E326-E336. Epub 2020 Apr 18.

Cardiovascular Biomechanics group, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Left ventricular assist devices (LVAD) provide cardiac support to patients with advanced heart failure. Methods that can directly measure remaining LV function following device implantation do not currently exist. Previous studies have shown that a combination of loading (LV pressure) and deformation (strain) measurements enables quantitation of myocardial work. We investigated the use of ultrasound (US) strain imaging and pressure-strain loop analysis in LVAD-supported hearts under different hemodynamic and pump unloading conditions, with the aim of determining LV function with and without LVAD support. Ex vivo porcine hearts (n = 4) were implanted with LVADs and attached to a mock circulatory loop. Measurements were performed at hemodynamically defined "heart conditions" as the hearts deteriorated from baseline. Hemodynamic (including LV pressure) and radio-frequency US data were acquired during a pump-ramp protocol at speeds from 0 (with no pump outflow) to 10 000 revolutions per minute (rpm). Regional circumferential (ε ) and radial (ε ) strains were estimated over each heart cycle. Regional ventricular dyssynchrony was quantitated through time-to-peak strain. Mean change in LV pulse pressure and ε between 0 and 10 krpm were -21.8 mm Hg and -7.24% in the first condition; in the final condition -46.8 mm Hg and -19.2%, respectively. ε was not indicative of changes in pump speed or heart condition. Pressure-strain loops showed a degradation in the LV function and an increased influence of LV unloading: loop area reduced by 90% between 0 krpm in the first heart condition and 10 krpm in the last condition. High pump speeds and degraded condition led to increased dyssynchrony between the septal and lateral LV walls. Functional measurement of the LV while undergoing LVAD support is possible by using US strain imaging and pressure-strain loops. This can provide important information about remaining pump function. Use of novel LV pressure estimation or measurement techniques would be required for any future use in LVAD patients.
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http://dx.doi.org/10.1111/aor.13693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496524PMC
August 2020

A novel technique for the assessment of mechanical properties of vascular tissue.

Biomech Model Mechanobiol 2020 Oct 24;19(5):1585-1594. Epub 2020 Jan 24.

Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600MB, Eindhoven, The Netherlands.

Accurate estimation of mechanical properties of the different atherosclerotic plaque constituents is important in assessing plaque rupture risk. The aim of this study was to develop an experimental set-up to assess material properties of vascular tissue, while applying physiological loading and being able to capture heterogeneity. To do so, a ring-inflation experimental set-up was developed in which a transverse slice of an artery was loaded in the radial direction, while the displacement was estimated from images recorded by a high-speed video camera. The performance of the set-up was evaluated using seven rubber samples and validated with uniaxial tensile tests. For four healthy porcine carotid arteries, material properties were estimated using ultrasound strain imaging in whole-vessel-inflation experiments and compared to the properties estimated with the ring-inflation experiment. A 1D axisymmetric finite element model was used to estimate the material parameters from the measured pressures and diameters, using a neo-Hookean and Holzapfel-Gasser-Ogden material model for the rubber and porcine samples, respectively. Reproducible results were obtained with the ring-inflation experiment for both rubber and porcine samples. Similar mean stiffness values were found in the ring-inflation and tensile tests for the rubber samples as 202 kPa and 206 kPa, respectively. Comparable results were obtained in vessel-inflation experiments using ultrasound and the proposed ring-inflation experiment. This inflation set-up is suitable for the assessment of material properties of healthy vascular tissue in vitro. It could also be used as part of a method for the assessment of heterogeneous material properties, such as in atherosclerotic plaques.
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http://dx.doi.org/10.1007/s10237-020-01292-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502444PMC
October 2020

Image acquisition stability of fixated musculoskeletal sonography in an exercise setting: a quantitative analysis and comparison with freehand acquisition.

J Med Ultrason (2001) 2020 Jan 7;47(1):47-56. Epub 2019 Nov 7.

Cardiovascular Biomechanics Group, Department of Biomedical Engineering, Eindhoven University of Technology, Groene Loper, 5612 AP, Eindhoven, The Netherlands.

Purpose: In dynamic musculoskeletal sonography, probe fixation can contribute to field of view (FOV) consistency, which is necessary for valid analysis of architectural parameters. In this volunteer study, the achieved FOV consistency in fixated ultrasonography was quantified and compared with freehand acquisition.

Methods: During five resting periods during cycling exercise, longitudinal B-mode images of the vastus lateralis (VL) muscle were acquired on one thigh with a fixated probe, and by two trained observers on the other thigh. In each acquisition, the structural similarity compared to the first resting period was determined using the complex wavelet structural similarity index (CW-SSIM). Also, the pennation angle of the VL was measured. Both CW-SSIM and pennation angle were compared between fixated and freehand acquisition. Furthermore, the compression of tissue by the probe fixation was measured.

Results: In fixated acquisition, a significantly higher structural similarity (p < 0.05) and an improved repeatability of pennation angle measurement were obtained compared to freehand acquisition. Probe fixation compressed muscle tissue by 12% on average.

Conclusions: Quantification of the structural similarity showed an increase in FOV consistency with sonography compared to freehand acquisition. The demonstrated feasibility of long-term fixated acquisition might be attractive in many medical fields and sports, and for reduction of work-related ergonomic problems among sonographers.
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http://dx.doi.org/10.1007/s10396-019-00983-xDOI Listing
January 2020

Validation of a three-dimensional quantitative coronary angiography-based software to calculate fractional flow reserve: the FAST study.

EuroIntervention 2020 Sep;16(7):591-599

Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands.

Aims: The aim of this study was to validate novel software to calculate vessel fractional flow reserve (vFFR) based on 3D-QCA and to assess inter-observer variability in patients who underwent routine preprocedural FFR assessment for intermediate coronary artery stenosis.

Methods And Results: In vitro validation was performed in an experimental model. Clinical validation was performed in an observational, retrospective, single-centre cohort study. A total of 100 patients presenting with stable angina or non-ST-segment elevation myocardial infarction and an indication to perform FFR between January 2016 and October 2016 were included. vFFR was calculated based on the aortic root pressure along with two angiographic projections and validated against pressure wire-derived FFR. Mean FFR and vFFR were 0.82±0.08 and 0.84±0.07, respectively. A good linear correlation was found between FFR and vFFR (r=0.89; p<0.001). Assessment of vFFR had a low inter-observer variability (r=0.95; p<0.001). The diagnostic accuracy of vFFR in identifying lesions with an FFR ≤0.80 was higher as compared with 3D-QCA: AUC 0.93 (95% CI: 0.88-0.97) vs 0.66 (95% CI: 0.55-0.77), respectively.

Conclusions: The 3D-QCA-derived vFFR has a high linear correlation to invasively measured FFR, a high diagnostic accuracy to detect FFR ≤0.80 and a low inter-observer variability.
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http://dx.doi.org/10.4244/EIJ-D-19-00466DOI Listing
September 2020

Decoupling the Effect of Shear Stress and Stretch on Tissue Growth and Remodeling in a Vascular Graft.

Tissue Eng Part C Methods 2018 07;24(7):418-429

1 Department of Biomedical Engineering, Eindhoven University of Technology , Eindhoven, The Netherlands .

The success of cardiovascular tissue engineering (TE) strategies largely depends on the mechanical environment in which cells develop a neotissue through growth and remodeling processes. This mechanical environment is defined by the local scaffold architecture to which cells adhere, that is, the microenvironment, and by external mechanical cues to which cells respond, that is, hemodynamic loading. The hemodynamic environment of early developing blood vessels consists of both shear stress (due to blood flow) and circumferential stretch (due to blood pressure). Experimental platforms that recapitulate this mechanical environment in a controlled and tunable manner are thus critical for investigating cardiovascular TE. In traditional perfusion bioreactors, however, shear stress and stretch are coupled, hampering a clear delineation of their effects on cell and tissue response. In this study, we uniquely designed a bioreactor that independently combines these two types of mechanical cues in eight parallel vascular grafts. The system is computationally and experimentally validated, through finite element analysis and culture of tissue constructs, respectively, to distinguish various levels of shear stress (up to 5 Pa) and cyclic stretch (up to 1.10). To illustrate the usefulness of the system, we investigated the relative contribution of cyclic stretch (1.05 at 0.5 Hz) and shear stress (1 Pa) to tissue development. Both types of hemodynamic loading contributed to cell alignment, but the contribution of shear stress overruled stretch-induced cell proliferation and matrix (i.e., collagen and glycosaminoglycan) production. At a macroscopic level, cyclic stretching led to the most linear stress-stretch response, which was not related to the presence of shear stress. In conclusion, we have developed a bioreactor that is particularly suited to further unravel the interplay between hemodynamics and in situ TE processes. Using the new system, this work highlights the importance of hemodynamic loading to the study of developing vascular tissues.
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http://dx.doi.org/10.1089/ten.TEC.2018.0104DOI Listing
July 2018

Investigation on the Effect of Spatial Compounding on Photoacoustic Images of Carotid Plaques in the In Vivo Available Rotational Range.

IEEE Trans Ultrason Ferroelectr Freq Control 2018 03;65(3):440-447

Photoacoustic imaging (PAI) is a promising imaging modality due to its high optical specificity. However, the low signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo PA images are major challenges that prevent PAI from finding its place in clinics. This paper investigates the merit of spatial compounding of PA images in arterial phantoms and the achievable improvements of SNR, when in vivo conditions are mimicked. The analysis of the compounding technique was performed on a polyvinyl alcohol vessel phantom with black threads embedded in its wall. The in vivo conditions were mimicked by limiting the rotation range in ±30°, adding turbid surrounding medium, and filling the lumen with porcine blood. Finally, the performance of the technique was evaluated in ex vivo human carotid plaque samples. Results showed that spatial compounding elevates the SNR by 5-10 dB and CNR by 1-5 dB, depending on the location of the absorbers. This paper elucidates prospective in vivo PA characterization of carotid plaques by proposing a method to enhance PA image quality.
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http://dx.doi.org/10.1109/TUFFC.2018.2792903DOI Listing
March 2018

A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic Resonance Imaging.

JACC Cardiovasc Interv 2018 02 17;11(3):287-297. Epub 2018 Jan 17.

Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands; Cardialysis Clinical Trials Management and Core Laboratories, Rotterdam, the Netherlands. Electronic address:

Objectives: This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR).

Background: PVR after TAVR is challenging to quantify, especially during the procedure.

Methods: Post-replacement aortograms in 135 TAVR recipients were analyzed offline by videodensitometry to measure the ratio of the time-resolved contrast density in the left ventricular outflow tract to that in the aortic root (videodensitometric aortic regurgitation [VD-AR]). CMR was performed within an interval of ≤30 days (11 ± 6 days) after the procedure.

Results: The average CMR-RF was 6.7 ± 7.0% whereas the average VD-AR was 7.0 ± 7.0%. The correlation between VD-AR and CMR-RF was substantial (r = 0.78, p < 0.001). On receiver-operating characteristic curves, a VD-AR ≥10% corresponded to >mild PVR as defined by CMR-RF (area under the curve: 0.94; p < 0.001; sensitivity 100%, specificity 83%), whereas a VD-AR ≥25% corresponded to moderate-to-severe PVR (area under the curve: 0.99; p = 0.004; sensitivity 100%, specificity 98%). Intraobserver reproducibility was excellent for both techniques (for CMR-RF, intraclass correlation coefficient: 0.91, p < 0.001; for VD-AR intraclass correlation coefficient: 0.93, p < 0.001). The difference on rerating was -0.04 ± 7.9% for CMR-RF and -0.40 ± 6.8% for VD-AR.

Conclusions: The angiographic VD-AR provides a surrogate assessment of PVR severity after TAVR that correlates well with the CMR-RF.
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http://dx.doi.org/10.1016/j.jcin.2017.08.045DOI Listing
February 2018

A Numerical Simulation of HeartAssist5 Blood Pump Using an Advanced Turbulence Model.

ASAIO J 2018 Sep/Oct;64(5):673-679

From the Faculty of Mechanical Engineering, University of Ljubljana, Ljubljana, Slovenia.

The need for mechanical assistance of the failing heart has increased with improvements in medicine and a rapidly aging population. In recent decades, significant progress has been made in the development and refinement of ventricular assist devices (VADs). Such devices operate in mixed laminar, transitional, and turbulent flow regime. One tool that assists in the development of VADs by facilitating understanding of the physical and mechanical properties of these flow regimes is computational fluid dynamics (CFD). In our investigation, we tested an advanced turbulence model that is a further development from standard Reynolds-averaged Navier-Stokes (RANS) models. From estimated pump flow rates (Q0) and constant rotation speed (n), pressure head (Δp) was calculated and validated with experimental data. An advanced turbulence model called scale adaptive simulation (SAS) was used in the solving of six different working cases comparing numerical SAS-SST and standard SST-kω models to experimental results.
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http://dx.doi.org/10.1097/MAT.0000000000000703DOI Listing
March 2019

Ultrasound functional imaging in an ex vivo beating porcine heart platform.

Phys Med Biol 2017 Nov 14;62(23):9112-9126. Epub 2017 Nov 14.

Cardiovascular Biomechanics group, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, GEM-Z4.131, 5600 MB Eindhoven, Netherlands.

In recent years, novel ultrasound functional imaging (UFI) techniques have been introduced to assess cardiac function by measuring, e.g. cardiac output (CO) and/or myocardial strain. Verification and reproducibility assessment in a realistic setting remain major issues. Simulations and phantoms are often unrealistic, whereas in vivo measurements often lack crucial hemodynamic parameters or ground truth data, or suffer from the large physiological and clinical variation between patients when attempting clinical validation. Controlled validation in certain pathologies is cumbersome and often requires the use of lab animals. In this study, an isolated beating pig heart setup was adapted and used for performance assessment of UFI techniques such as volume assessment and ultrasound strain imaging. The potential of performing verification and reproducibility studies was demonstrated. For proof-of-principle, validation of UFI in pathological hearts was examined. Ex vivo porcine hearts (n  =  6, slaughterhouse waste) were resuscitated and attached to a mock circulatory system. Radio frequency ultrasound data of the left ventricle were acquired in five short axis views and one long axis view. Based on these slices, the CO was measured, where verification was performed using flow sensor measurements in the aorta. Strain imaging was performed providing radial, circumferential and longitudinal strain to assess reproducibility and inter-subject variability under steady conditions. Finally, strains in healthy hearts were compared to a heart with an implanted left ventricular assist device, simulating a failing, supported heart. Good agreement between ultrasound and flow sensor based CO measurements was found. Strains were highly reproducible (intraclass correlation coefficients  >0.8). Differences were found due to biological variation and condition of the hearts. Strain magnitude and patterns in the assisted heart were available for different pump action, revealing large changes compared to the normal condition. The setup provides a valuable benchmarking platform for UFI techniques. Future studies will include work on different pathologies and other means of measurement verification.
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http://dx.doi.org/10.1088/1361-6560/aa9515DOI Listing
November 2017

Videodensitometric quantification of paravalvular regurgitation of a transcatheter aortic valve: in vitro validation.

EuroIntervention 2018 01;13(13):1527-1535

Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Aims: Videodensitometric assessment of aortography provides a periprocedural quantitation of prosthetic valve regurgitation (PVR) after transcatheter aortic valve implantation. We sought to compare the videodensitometric parameters of PVR severity to the regurgitation fraction (RF) in a controlled in vitro setting.

Methods And Results: In a mock circulation system, a transcatheter balloon-expandable valve inserted at the aortic valve position was gradually deformed to induce different grades of paravalvular leakage and the RF was measured with a transonic flow probe. Contrast aortography was performed and the following videodensitometric parameters were generated: left ventricle aortic regurgitation (LV-AR), LV outflow tract AR (LVOT-AR), quantitative regurgitation assessment (qRA) index, relative maximum density (relative max), and maximum upslope of the LV time-density curve. The correlation was substantial between videodensitometric parameters (LV-AR, LVOT-AR, qRA index, relative max, and maximum upslope) and RF (r2=0.96, 0.96, 0.93, 0.87, and 0.93; p<0.001 for all). LV-AR (region of interest [ROI]=entire LV) and LVOT-AR (ROI=LVOT) were not different (p=0.51) and were strongly correlated (r2=0.99) with a mean difference of 1.92% (95% limits of agreement: ±2.83). The correlations of LV-AR and LVOT-AR with RF were stronger when more than one cardiac cycle was included in the analysis (one cycle: r2=0.85 and r2=0.83; four cycles: r2=0.96 and r2=0.96, for LV-AR and LVOT-AR, respectively). Including more cycles beyond four did not improve accuracy.

Conclusions: Quantitative assessment of PVR by videodensitometry of aortograms strongly correlates with the actual RF in a controlled in vitro setting. Accuracy is improved by including more than one cardiac cycle in the analysis.
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http://dx.doi.org/10.4244/EIJ-D-17-00595DOI Listing
January 2018

A novel synchronised diastolic injection method to reduce contrast volume during aortography for aortic regurgitation assessment: in vitro experiment of a transcatheter heart valve model.

EuroIntervention 2017 Dec;13(11):1288-1295

Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Aims: In the minimalist transcatheter aortic valve implantation (TAVI) era, the usage of transoesophageal echocardiography has become restricted. Conversely, aortography has gained clinical ground in quantifying prosthetic valve regurgitation (PVR) during the procedure. In a mock circulation system, we sought to compare the contrast volume required and the accuracy of aortographic videodensitometric PVR assessment using a synchronised diastolic and standard (non-synchronised) injection aortography.

Methods And Results: Synchronised diastolic injection triggered by the signal stemming from the mock circulation was compared with standard non-synchronised injection. A transcatheter heart valve was implanted and was deformed step by step by advancing a screw perpendicularly to the cage of the valve in order to create increasing PVR. Quantitative measurement of PVR was derived from time-density curves of both a reference area (aortic root) and a region of interest (left ventricle) developed by a videodensitometric software. The volume of contrast required for the synchronised diastolic injection was significantly less than in the non-synchronised injection (8.1 [7.9-8.5] ml vs. 19.4 [19.2-19.9] ml, p<0.001). The correlation between the two methods was substantial (Spearman's coefficient rho ranging from 0.991 to 0.968). Intraobserver intra-class correlation coefficient for both methods of injection was 0.999 (95% CI: 0.996-1.000) for the synchronised diastolic and 0.999 (95% CI: 0.996-1.000) for the non-synchronised injection group. The mean difference in the rating was 0.17% and limits of agreement were ±1.64% for both groups.

Conclusions: A short synchronised diastolic injection enables contrast volume reduction during aortography without compromising the accuracy of the quantitative assessment of PVR using videodensitometry.
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http://dx.doi.org/10.4244/EIJ-D-17-00355DOI Listing
December 2017

Relative contributions from the ventricle and arterial tree to arterial pressure and its amplification: an experimental study.

Am J Physiol Heart Circ Physiol 2017 Sep 2;313(3):H558-H567. Epub 2017 Jun 2.

Physikalisch-Technische Bundesanstalt, Medical Physics and Metrological Information Technology, Berlin, Germany.

Arterial pressure is an important diagnostic parameter for cardiovascular disease. However, relative contributions of individual ventricular and arterial parameters in generating and augmenting pressure are not understood. Using a novel experimental arterial model, our aim was to characterize individual parameter contributions to arterial pressure and its amplification. A piston-driven ventricle provided programmable stroke profiles into various silicone arterial trees and a bovine aorta. Inotropy was varied in the ventricle, and arterial parameters modulated included wall thickness, taper and diameter, the presence of bifurcation, and a native aorta (bovine) versus silicone. Wave reflection at bifurcations was measured and compared with theory, varying parent-to-child tube diameter ratios, and branch angles. Intravascular pressure-tip wires and ultrasonic flow probes measured pressure and flow. Increasing ventricular inotropy independently augmented pressure amplification from 17% to 61% between the lower and higher systolic gradient stroke profiles in the silicone arterial network and from 10% to 32% in the bovine aorta. Amplification increased with presence of a bifurcation, decreasing wall thickness and vessel taper. Pulse pressure increased with increasing wall thickness (stiffness) and taper angle and decreasing diameter. Theoretical predictions of wave transmission through bifurcations werre similar to measurements (correlation: 0.91, = 0.94) but underestimated wave reflection (correlation: 0.75, = 0.94), indicating energy losses during mechanical wave reflection. This study offers the first comprehensive investigation of contributors to hypertensive pressure and its propagation throughout the arterial tree. Importantly, ventricular inotropy plays a crucial role in the amplification of peripheral pressure wave, which offers opportunity for noninvasive assessment of ventricular health. The present study distinguishes contributions from cardiac and arterial parameters to elevated blood pressure and pressure amplification. Most importantly, it offers the first evidence that ventricular inotropy, an indicator of ventricular function, is an independent determinant of pressure amplification and could be measured with such established devices such as the SphygmoCor.
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http://dx.doi.org/10.1152/ajpheart.00844.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625171PMC
September 2017

A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

Tissue Eng Part C Methods 2017 06 29;23(6):377-387. Epub 2017 May 29.

1 Department of Biomedical Engineering, Eindhoven University of Technology , Eindhoven, The Netherlands .

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.
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http://dx.doi.org/10.1089/ten.TEC.2017.0141DOI Listing
June 2017

Visualization of vasculature using a hand-held photoacoustic probe: phantom and in vivo validation.

J Biomed Opt 2017 04;22(4):41013

Eindhoven University of Technology, Cardiovascular Biomechanics Group, Department of Biomedical Engineering, The Netherlands.

Assessment of microvasculature and tissue perfusion can provide diagnostic information on local or systemic diseases. Photoacoustic (PA) imaging has strong clinical potential because of its sensitivity to hemoglobin. We used a hand-held PA probe with integrated diode lasers and examined its feasibility and validity in the detection of increasing blood volume and (sub) dermal vascularization. Blood volume detection was tested in custom-made perfusion phantoms. Results showed that an increase of blood volume in a physiological range of 1.3% to 5.4% could be detected. The results were validated with power Doppler sonography. Using a motorized scanning setup, areas of the skin were imaged at relatively short scanning times ( < 10 ?? s / cm 2 ) with PA. Three-dimensional visualization of these structures was achieved by combining the consecutively acquired cross-sectional images. Images revealed the epidermis and submillimeter vasculature up to depth of 5 mm. The geometries of imaged vasculature were validated with segmentation of the vasculature in high-frequency ultrasound imaging. This study proves the feasibility of PA imaging in its current implementation for the detection of perfusion-related parameters in skin and subdermal tissue and underlines its potential as a diagnostic tool in vascular or dermal pathologies.
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http://dx.doi.org/10.1117/1.JBO.22.4.041013DOI Listing
April 2017

Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging.

J Biomed Opt 2017 04;22(4):41010

Eindhoven University of Technology, Department of Biomedical Engineering, Cardiovascular Biomechanics Group, De Zaale, Eindhoven 5612 AJ, The Netherlands.

Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser ( t pulse = 130 ?? ns , E pulse = 1 ?? mJ , ? = 808 ?? nm ) and a linear array transducer ( f c = 7.5 ?? MHz ). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.
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http://dx.doi.org/10.1117/1.JBO.22.4.041010DOI Listing
April 2017

Arterial pulsatility under phasic left ventricular assist device support.

Biomed Mater Eng 2016 Nov;27(5):451-460

Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

The aim of this study is to understand whether the phasic Continuous Flow Left Ventricular Assist Device (CF-LVAD) support would increase the arterial pulsatility. A Micromed DeBakey CF-LVAD was used to apply phasic support in an ex-vivo experimental platform. CF-LVAD was operated over a cardiac cycle by phase-shifting the pulsatile pump control with respect to the heart cycle, in 0.05 s increments in each experiment. The pump flow rate was selected as the control variable and a reference model was used to operate the CF-LVAD at a pulsatile speed. Arterial pulse pressure was the highest (9 mmHg) when the peak pump flow is applied at the peak systole under varying speed CF-LVAD support over a cardiac cycle while it was the lowest (2 mmHg) when the peak pump flow was applied in the diastolic phase. The mean arterial pressure and mean CF-LVAD output were the same in each experiment while arterial pulse pressure and pulsatility index varied depending on the phase of reference pump flow rate signal. CF-LVAD speed should be synchronized considering the timing of peak systole over a cardiac cycle to increase the arterial pulsatility. Moreover, it is possible to decrease the arterial pulsatility under counter-pulsating CF-LVAD support.
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http://dx.doi.org/10.3233/BME-161599DOI Listing
November 2016

A Comparison Between Compounding Techniques Using Large Beam-Steered Plane Wave Imaging for Blood Vector Velocity Imaging in a Carotid Artery Model.

IEEE Trans Ultrason Ferroelectr Freq Control 2016 11;63(11):1758-1771

Conventional color Doppler imaging is limited, since it only provides velocity estimates along the ultrasound beam direction for a restricted field of view at a limited frame rate. High-frame-rate speckle tracking, using plane wave transmits, has shown potential for 2-D blood velocity estimation. However, due to the lack of focusing in transmit, image quality gets reduced, which hampers speckle tracking. Although ultrafast imaging facilitates improved clutter filtering, it still remains a major challenge in blood velocity estimation. Signal dropouts and poor velocity estimates are still present for high beam-to-flow angles and low blood flow velocities. In this paper, ultrafast plane wave imaging was combined with multiscale speckle tracking to assess the 2-D blood velocity vector in a common carotid artery (CCA) flow field. A multiangled plane wave imaging sequence was used to compare the performance of displacement compounding, coherent compounding, and compound speckle tracking. Zero-degree plane wave imaging was also evaluated. The performance of the methods was evaluated before and after clutter filtering for the large range of velocities (0-1.5 m/s) that are normally present in a healthy CCA during the cardiac cycle. An extensive simulation study was performed, based on a sophisticated model of the CCA, to investigate and evaluate the performance of the methods at different pulse repetition frequencies and signal-to-noise levels. In vivo data were acquired of a healthy carotid artery bifurcation to support the simulation results. In general, methods utilizing compounding after speckle tracking, i.e., displacement compounding and compound speckle tracking, were least affected by clutter filtering and provided the most robust and accurate estimates for the entire velocity range. Displacement compounding, which uses solely axial information to estimate the velocity vector, provided most accurate velocity estimates, although it required sufficiently high pulse repetition frequencies in high blood velocity phases and reliable estimates for all acquisition angles. When this latter requirement was not met, compound speckle tracking was most accurate, because it uses the possibility to discard angular velocity estimates corrupted by clutter filtering. Similar effects were observed for in vivo data obtained at the carotid artery bifurcation. Investigating a combination of these two compounding techniques is recommended for future research.
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http://dx.doi.org/10.1109/TUFFC.2016.2606565DOI Listing
November 2016

Novel monorail infusion catheter for volumetric coronary blood flow measurement in humans: in vitro validation.

EuroIntervention 2016 Aug;12(6):701-7

Department of Cardiology, Catherina Hospital, Eindhoven, The Netherlands.

Aims: The aim of this study is to validate a novel monorail infusion catheter for thermodilution-based quantitative coronary flow measurements.

Methods And Results: Based on the principles of thermodilution, volumetric coronary flow can be determined from the flow rate of a continuous saline infusion, the temperature of saline when it enters the coronary artery, and the temperature of the blood mixed with the saline in the distal part of the coronary artery. In an in vitro set-up of the systemic and coronary circulation at body temperature, coronary flow values were varied from 50-300 ml/min in steps of 50 ml/min. At each coronary flow value, thermodilution-based measurements were performed at infusion rates of 15, 20, and 30 ml/min. Temperatures and pressures were simultaneously measured with a pressure/temperature sensor-tipped guidewire. Agreement of the calculated flow and the measured flow as well as repeatability were assessed. A total of five catheters were tested, with a total of 180 measurements. A strong correlation (ρ=0.976, p<0.0001) and a difference of -6.5±15.5 ml/min were found between measured and calculated flow. The difference between two repeated measures was 0.2%±8.0%.

Conclusions: This novel infusion catheter used in combination with a pressure/temperature sensor-tipped guidewire allows accurate and repeatable absolute coronary flow measurements. This opens a window to a better understanding of the coronary microcirculation.
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http://dx.doi.org/10.4244/EIJV12I6A114DOI Listing
August 2016

Enhancement of Arterial Pressure Pulsatility by Controlling Continuous-Flow Left Ventricular Assist Device Flow Rate in Mock Circulatory System.

J Med Biol Eng 2016;36:308-315. Epub 2016 Jun 25.

Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, GEM-Z 4.18, 5600 MB Eindhoven, The Netherlands.

Continuous-flow left ventricular assist devices (CF-LVADs) generally operate at a constant speed, which reduces pulsatility in the arteries and may lead to complications such as functional changes in the vascular system, gastrointestinal bleeding, or both. The purpose of this study is to increase the arterial pulse pressure and pulsatility by controlling the CF-LVAD flow rate. A MicroMed DeBakey pump was used as the CF-LVAD. A model simulating the flow rate through the aortic valve was used as a reference model to drive the pump. A mock circulation containing two synchronized servomotor-operated piston pumps acting as left and right ventricles was used as a circulatory system. Proportional-integral control was used as the control method. First, the CF-LVAD was operated at a constant speed. With pulsatile-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. Continuous and pulsatile-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility increased significantly for both arterial pressure and pump flow rate signals under pulsatile speed pump support. This study shows the possibility of improving the pulsatility of CF-LVAD support by regulating pump speed over a cardiac cycle without reducing the overall level of support.
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http://dx.doi.org/10.1007/s40846-016-0140-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935750PMC
June 2016

Assessment of mechanical properties of porcine aortas under physiological loading conditions using vascular elastography.

J Mech Behav Biomed Mater 2016 06 17;59:185-196. Epub 2015 Dec 17.

Cardiovascular Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. Electronic address:

Non-invasive assessment of the elastic properties of the arterial wall is often performed with ultrasound (US) imaging. The purpose of this study is to estimate mechanical properties of the vascular wall using in vitro inflation testing on biological tissue and two-dimensional (2-D) US elastography, and investigate the performance of the proposed methodology for physiological conditions. An inflation experiment was performed on 12 porcine aortas for (a) a large pressure range (0-140mmHg); and (b) physiological pressures (70-130mmHg) to mimic in vivo hemodynamic conditions. Two-dimensional radiofrequency (RF) data were acquired for one longitudinal and two transverse cross-sections for both experiments, and were analyzed to obtain the geometry and diameter-time behavior. The shear modulus (G) was estimated from these data for each pressure range applied. In addition, an incremental study based on the static data was performed to (1) investigate the changes in G for increasing mean arterial pressure (MAP) for a certain pressure difference (30, 40, 50 and 60mmHg); (2) compare the results with those from the dynamic experiment, for the same pressure range. The resulting stress-strain curves and shear moduli G (94±16kPa) for the static experimentare in agreement with literature and previous work. A linear dependency on MAP was found for G, yet the effect of the pulse pressure difference was negligible. The dynamic data revealed a G of 250±20kPa, whereas the incremental shear modulus (Ginc) was 240±39kPa. For all experiments, no significant differences in the values of G were found between different image planes. This study shows that 2-D US elastography of aortas during inflation testing is feasible and reproducible under controlled and physiological circumstances. In future studies, the in vivo, dynamic experiment should be repeated for a range of MAPs, and pathological vessels should be examined.
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http://dx.doi.org/10.1016/j.jmbbm.2015.12.009DOI Listing
June 2016

Inflation and Bi-Axial Tensile Testing of Healthy Porcine Carotid Arteries.

Ultrasound Med Biol 2016 Feb 1;42(2):574-85. Epub 2015 Dec 1.

Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. Electronic address:

Knowledge of the intrinsic material properties of healthy and diseased arterial tissue components is of great importance in diagnostics. This study describes an in vitro comparison of 13 porcine carotid arteries using inflation testing combined with functional ultrasound and bi-axial tensile testing. The measured tissue behavior was described using both a linear, but geometrically non-linear, one-parameter (neo-Hookean) model and a two-parameter non-linear (Demiray) model. The shear modulus estimated using the linear model resulted in good agreement between the ultrasound and tensile testing methods, GUS = 25 ± 5.7 kPa and GTT = 23 ± 5.4 kPa. No significant correspondence was observed for the non-linear model aUS = 1.0 ± 2.7 kPa vs. aTT = 17 ± 8.8 kPa, p ∼ 0); however, the exponential parameters were in correspondence (bUS = 12 ± 4.2 vs. bTT = 10 ± 1.7, p > 0.05). Estimation of more complex models in vivo is cumbersome considering the sensitivity of the model parameters to small changes in measurement data and the absence of intraluminal pressure data, endorsing the use of a simple, linear model in vivo.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2015.09.019DOI Listing
February 2016

Estimation of left ventricular pressure with the pump as "sensor" in patients with a continuous flow LVAD.

Int J Artif Organs 2015 Aug 31;38(8):433-43. Epub 2015 Aug 31.

Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven - The Netherlands.

Introduction: In long-term ventricular support of patients with LVADs, left ventricular pressure (p(lv)) is relevant for indicating the unloading level of the heart. Monitoring of p(lv) over time might give more insight into the increase or decrease in native ventricular function. In this study, we aim to assess dynamic p(lv) noninvasively, using the LVAD as a pressure sensor.

Methods: Pressure head (dp(lvad)) was estimated from pump flow with a dynamic pump model (1). Estimated dp(lvad) and measured aortic pressure were used to calculate left ventricular pressure. Moreover, parameters dp/dtmax and mean, minimum, and maximum p(lv) were derived.The method was validated with a porcine ex vivo beating heart model by measurements conducted in 4 hearts supported with a Micromed DeBakey VAD and 3 hearts with a Heartmate II VAD. During each measurement, aortic and left ventricular pressure, pump flow, and pressure head were recorded for 30 s with a sampling frequency of 1 kHz.

Results: The estimation of left ventricular pressure appeared to be accurate for both pumps. The parameters mean and minimum pressure were estimated with high accuracy. The degree of accuracy of the estimated p(lv) was proportional to the degree of accuracy of the dynamic pump model.

Conclusions: We proved that the LVAD model described in this paper can be used as a pressure indicator to determine LV pressure at any time based on noninvasive measurements of pump flow, aortic pressure, and the properties of the outlet graft.
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http://dx.doi.org/10.5301/ijao.5000424DOI Listing
August 2015

Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure.

Artif Organs 2015 Nov 1;39(11):931-8. Epub 2015 May 1.

Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.
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http://dx.doi.org/10.1111/aor.12470DOI Listing
November 2015

Aortic Valve Function Under Support of a Left Ventricular Assist Device: Continuous vs. Dynamic Speed Support.

Ann Biomed Eng 2015 Aug 6;43(8):1727-37. Epub 2014 Dec 6.

Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands,

Continuous flow left ventricular devices (CF-LVADs) support the failing heart at a constant speed and alters the loads on the aortic valve. This may cause insufficiency in the aortic valve under long-term CF-LVAD support. The aim of this study is to assess the aortic valve function under varying speed CF-LVAD support. A Medtronic freestyle valve and a Micromed DeBakey CF-LVAD were tested in a mock circulatory system. First, the CF-LVAD was operated at constant speeds between 7500 and 11,500 rpm with 1000 rpm intervals. The mean pump outputs obtained from these tests were applied in varying speed CF-LVAD support mode using a reference model for the pump flow. The peak of the instantaneous pump flow was applied at peak systole and mid-diastole, respectively. Ejection durations and in the aortic valve were the longest when the peak pump flow was applied at mid-diastole among the CF-LVAD operating modes. Furthermore, mean aortic valve area over a cardiac cycle was highest when the peak pump flow was applied at mid-diastole. The results show that changing phase of the reference flow rate signal may reduce the effects of the CF-LVADs on altered aortic valve closing behavior, without compromising the overall pump support level.
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http://dx.doi.org/10.1007/s10439-014-1204-4DOI Listing
August 2015

Intra-aortic balloon counterpulsation reduces mortality in large anterior myocardial infarction complicated by persistent ischaemia: a CRISP-AMI substudy.

EuroIntervention 2015 Jul;11(3):286-92

Department of Cardiology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.

Aims: This substudy investigated IABP support in large STEMI complicated by persistent ischaemia within the original CRISP-AMI trial.

Methods And Results: Patients were included if the ECG at admission showed summed ST deviation (ST-D) ≥15 mm and the ECG post PCI showed poor ST resolution (<50%). Endpoints evaluated were all-cause mortality at six months and the composite endpoint of death, cardiogenic shock or new or worsening heart failure at six months. One hundred and forty-nine patients had ST-D ≥15 mm (mean ST-D 24±8 mm). Of these patients, 36 (24%) showed poor ST resolution (15 patients in the IABP group; 21 patients in the control group). Mean age was 55±11 years, 89% were male. Mean systolic and diastolic blood pressures were 135±31 mmHg and 83±22 mmHg, respectively. The left anterior descending coronary artery was the infarct-related artery in all cases, primary PCI was successful in 94%. At six months, zero patients in the IABP group died versus five patients in the control group (0% versus 24%; p=0.046). There was a trend towards statistical significance in the composite endpoint (one patient [7%] versus seven patients [33%]; p=0.06).

Conclusions: In this substudy, use of IABP was associated with decreased six-month mortality in large STEMI complicated by persistent ischaemia after PCI.
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http://dx.doi.org/10.4244/EIJY14M09_10DOI Listing
July 2015

An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.

Comput Biol Med 2014 Oct 6;53:141-53. Epub 2014 Jul 6.

University College London, Mechanical Engineering Department, Torrington Place, WC1E 7JE London, UK. Electronic address:

Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.
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http://dx.doi.org/10.1016/j.compbiomed.2014.06.013DOI Listing
October 2014

Arterial pulsatility improvement in a feedback-controlled continuous flow left ventricular assist device: an ex-vivo experimental study.

Med Eng Phys 2014 Oct 25;36(10):1288-95. Epub 2014 Jul 25.

Eindhoven University of Technology, Department of Biomedical Engineering, The Netherlands.

Continuous flow left ventricular assist devices (CF-LVADs) reduce arterial pulsatility, which may cause long-term complications in the cardiovascular system. The aim of this study is to improve the pulsatility by driving a CF-LVAD at a varying speed, synchronous with the cardiac cycle in an ex-vivo experiment. A Micromed DeBakey pump was used as CF-LVAD. The heart was paced at 140 bpm to obtain a constant cardiac cycle for each heartbeat. First, the CF-LVAD was operated at a constant speed. At varying-speed CF-LVAD assistance, the pump was driven such that the same mean pump output was generated. For synchronization purposes, an algorithm was developed to trigger the CF-LVAD each heartbeat. The pump flow rate was selected as the control variable and a reference model was used for regulating the CF-LVAD speed. Continuous and varying-speed CF-LVAD assistance provided the same mean arterial pressure and flow rate, while the index of pulsatility doubled in both arterial pressure and pump flow rate signals under pulsatile pump speed support. This study shows the possibility of improving the pulsatility in CF-LVAD support by regulating pump speed over a cardiac cycle without compromising the overall level of support.
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http://dx.doi.org/10.1016/j.medengphy.2014.07.005DOI Listing
October 2014
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