7th Dutch Bio-Medical Engineering Conference
January 24th & 25th 2019, Egmond aan Zee, the Netherlands
13:00   Cardiovascular diseases
Chair: Joost van Kordelaar
15 mins
Photoplethysmography – Unobtrusive Means to Measure Force-Interval Relationships of the Heart During Atrial Fibrillation?
Linda Eerikäinen, Alberto Bonomi, Lukas Dekker, Fons Schipper, Rik Vullings, Ronald Aarts
Abstract: Background: Mechanical restitution and post-extrasystolic potentiation are the two aspects of force-interval relationship (FIR) of the heart, and represent the change in the contractile strength in relation to change in inter-beat intervals (IBI) [1]. Studies with invasive measures have shown that these relationships are present during atrial fibrillation (AF) [2], an arrhythmia in which the IBIs vary beat-by-beat. Moreover, these relationships are altered in heart failure (HF) compared to non-failing hearts [1]. AF and HF often coexist and one of the conditions can cause the other. Therefore, an unobtrusive continuous measurement of FIRs could be beneficial, possibly showing indications of deterioration in the patient’s condition. We hypothesize that FIRs could be assessed during AF with IBIs and hemodynamic changes captured unobtrusively by photoplethysmography (PPG) at the wrist, assuming a stronger correlation between the IBIs and PPG waveform changes during irregular rhythms. Methods: 14 subjects with continuous AF and 18 subjects with sinus rhythm were measured during the night with PPG at the wrist and with electrocardiography as a reference. The FIRs were assessed by correlation between either the preceding or pre-preceding IBIs and pulse onset change in the PPG waveform. The correlation coefficients r_(pre) and r_(pre-pre) were calculated in 5-minute windows over the measurement period [3]. The difference in the correlation coefficients between the two rhythms was analysed with Mann-Whitney U test and Receiver Operating Characteristics (ROC). Results: The mean and standard deviation of r_(pre) were -0.25 ± 0.08 and 0.05 ± 0.12 (p < 0.0001), and of r_(pre-pre) 0.60 ± 0.09 and 0.16 ± 0.14 (p < 0.0001), during AF and sinus rhythm, respectively. Areas under the ROC curve were 0.987 and 0.998, respectively. Conclusion: A stronger correlation between the IBIs and the PPG waveform changes was observed during atrial fibrillation, possibly representing presence of FIRs. Significance: An unobtrusive method to measure FIR in long-term in patients with AF, who therefore have the risk of developing HF, could be useful for disease management and be of interest for further studies. REFERENCES [1] Sprenkeler, D. J. & Vos, M. A., 2016. Post-extrasystolic Potentiation: Link between Ca2+ Homeostasis and Heart Failure?. Arrhythm Electrophysiol Rev, 5(1), pp. 20-26. [2] Brookes, C. I. O., White, P. A., Staples, M., Oldershaw, P. J., Redington, A. N., Collings, P. D., Noble, M. I. M., 1998. Myocardial Contractility Is Not Constant During Spontaneous Atrial Fibrillation in Patients. Circulation, 98, pp. 1762-68. [3] Eerikäinen, L.M., Bonomi, A.G., Dekker L., Schipper, F. Vullings, R., Aarts, R.M. Force-interval Relationships of the Heart Measured with Photoplethysmography during Atrial Fibrillation. Computing in Cardiology, Maastricht, Netherlands, Sep 23-26, 2018.
15 mins
Investigating Subendocardial Ischemia in Aortic Valve Stenosis Patients Using Speckle Tracking
Esther Maas, Richard Lopata, Frans van de Vosse, Arthur Bouwman, Patrick Houthuizen, Peter Bovendeerd
Abstract: The diagnosis and timing of treatment in aortic valve stenosis patients are currently predominantly based on aortic valve parameters. It is however known that aortic valve stenosis increases left ventricular pressure, which may reduce subendocardial perfusion and can lead to subendocardial dysfunction and subendocardial infarction. Subendocardial ischemia is expected to affect apex-to-base rotation of the left ventricle, since this rotation represents mechanical equilibrium between the subepicardial fibers and the subendocardial fibers. More specifically, rotation is expected to increase with increasing endocardial ischemia. In this study, rotation is investigated using speckle tracking on short-axis B-mode images of the heart. First, we investigated the accuracy of rotations obtained by performing speckle tracking, using a mathematical model of left ventricular kinematics. This is done by performing speckle tracking on simulated B-mode images created using the Field II software. The maximal rotation determined with speckle tracking was 30% lower than the rotation prescribed in the model. Tracking seemed most hindered in regions rotating lateral to the transducer, most likely caused by the low precision of lateral displacement estimates. Secondly, we analysed B-mode images of aortic stenosis patients before (pre, n=5) and immediately after (post, n=3) a TAVI procedure and healthy volunteers (n=4). The apex-to-base rotation during the ejection phase is plotted against the circumferential strain, to correct for the decreased overall contractility. The negative slope of this plot is the parameter RRTC, the relative-rotation-to-contraction. The average RRTC is 50 degrees for the pre group, 42 degrees for the post group and 29 degrees for the healthy volunteers. While these results support our hypothesis, no statistically significant conclusions can be drawn because of the small numbers and errors in the speckle tracking. However, this method seems promising to determine subendocardial ischemia in aortic valve stenosis patients, which can in the future be used to improve the timing of aortic valve replacement.
15 mins
In Vitro Patient Specific Tavi-Procedure Assessment: a Tool for Clinical Decision Support and Training
Roel Meiburg, Jorn J.D. Roijen, Sjors J.A. van Velthoven, Jo M. Zelis, Marcel C.M. Rutten, Frans F.N. van de Vosse
Abstract: Aortic stenosis (AS) is a degenerative valve disease, where the leaflets stiffen due to calcifications and thickening, leading to a reduction in blood flow from the heart. It affects mainly the elderly, meaning that possibility of adverse effects of (surgical) treatment becomes a significant parameter in the treatment decision process. For patients who are excluded from surgical procedures, e.g., due to frailty, transcatheter aortic valve implantation (TAVI) is a minimally invasive alternative. In TAVI, a replacement valve is delivered via a catheter and placed over the diseased valve. While TAVI is generally successful, adverse effects such as post-placement leakage or even annulus rupture can occur, resulting in minimal patient improvement or even death. A 3D printed valve model can help clinicians in several ways. First, it allows them to more easily and intuitively inspect the valve. Second, by placing the valve inside a mock-circulation, it allows them to test the TAVI-procedure and assess the outcome. Finally, it can be used as a training tool, as it allows practice and easy assessment of TAVI placement. For 14 AS patients, CT and US images were obtained, along with pressure measurements inside the left ventricle and aorta, and thermo-dilution cardiac output measurements. The geometry of the stenotic valve was obtained by segmenting the aortic valve and root from CT data. The geometry is then digitally placed inside a cylindrical shape, so that it can be housed inside the mock circulation. A negative mould is then created using a 3D-printer. The final valve is created by injection moulding, using a soft, two-component silicone compound. Since the valve is segmented and printed in the closed position, the leaflets are separated based on transverse ultrasound images, using a scalpel. The valve is then placed inside the mock circulation, which is tuned to the patient’s data, leading to a patient specific in vitro simulator of the AS patient. The TAVI procedure is then performed, monitored via US and captured with a camera inside the aortic root. Afterwards, the change in haemodynamics and the success of the placement can be assessed. This way, the procedural outcome can be evaluated prior to the actual treatment, and possible valve consistency-related may be mitigated.
15 mins
In Aortic Coarctation Is the Age at Curative Reconstruction Correlated with Aortic Vessel Wall Stiffening: an Evaluation of Pulse Wave Velocity and Wall Shear Stress From 4D Flow MRI.
Joe Juffermans, Ineke Nederend, Pieter van den Boogaard, Hildo Lamb, Arno Roest, Jos Westenberg
Abstract: Background: Uncertainties exists whether the abnormal hemodynamic situation in coarctation (CoA) patients before curative reconstruction causes aortic wall deterioration Therefore, this study evaluated the effect of age at curative reconstruction on the arterial wall stiffness expressed in pulse wave velocity (PWV) and the 3D wall shear stress (WSS) in CoA patients with curative reconstruction. Additionally, effects of valve morphology was evaluated. Methods: 21 patients (13.7±2.6 years) were included; incorporating 14 subjects with a bicuspid aortic valve. MRI was performed at a mean time after curative reconstruction of 12.6±3.0 years. For normal PWV comparison 19 volunteers (13.3±2.8 years) were included. PWV was determined from two high-temporal 1-directional velocity encoded acquisitions, for the ascending aorta (AO) plus the aortic arch and the descending AO. The peak WSS was determined from 4D flow MRI, acquired on 3T MRI (Ingenia, Philips Healthcare) using CAAS MR Solutions v5.0 (Pie Medical Imaging). The peak WSS over 5 systolic phases was determined for three segments: ascending AO, aortic arch and descending AO. Results: There were no significant differences between volunteers and patients neither in subject characteristics nor for PWV. A positive correlation between age and PWV in both aortic segments for the entire population was found (proximal AO: r=.322, p=.042; descending AO: r=.361, p=.022). For patients with a tricuspid aortic valve (TAV), a significant good positive correlation was found between age at reconstruction and descending AO PWV (r=.796, p=.010). Conclusion: In line with the scientific literature, the correlation between age and PWV describes AO vessel wall stiffening over time. The absence of significant PWV differences between volunteers and patients indicates that curative reconstruction does not result in AO wall stiffening. However, the correlation within TAV patients between the age at curative reconstruction and descending AO PWV suggests that a prolonged period of abnormal hemodynamic exposure before reconstruction may result in increased AO vessel wall stiffening.
15 mins
Temporal and Spatial Changes in Wall Shear Stress During Atherosclerotic Plaque Progression in Mice
Ruoyu Xing, Astrid Moerman, Yanto Ridwan, Anton van der Steen, Frank Gijsen, Kim van der Heiden
Abstract: ABSTRACT Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE-/- mice (n=7). At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased (see figure). Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant [1]. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyze individual animals and plaques when studying correlations between WSS and plaque composition. [1] Xing et al., Royal Society, 2018, 5(3)
15 mins
Dual-Spect Translational Cardiovascular Imaging of Inflammatory Cellular Protagonists
Hilary Barrett, Eric Meester, Monique Bernsen, Kim van der Heiden, Anton van der Steen, Marion de Jong, Frank Gijsen
Abstract: The clinical application of nuclear imaging is a rapidly emerging diagnostic technique for atherosclerotic disease which holds prodigious promise to differentiate vulnerable symptomatic patients from the safe asymptomatic cohorts through the detection of molecular mechanisms linked to the disease manifestation. Specifically, inflammation is advocated as the key driver in the atherosclerotic disease progression and plays an instrumental role in causing life-threatening clinical complications. Recent advancements in non-invasive molecular single photon emission computed tomography (SPECT) imaging technology permit dual-radioisotope imaging. Thus, this study evaluates the potential of novel radiotracers targeting inflammatory cell types leukocytes and activated macrophages simultaneously in human diseased arteries. Human carotid plaque samples were obtained from eight endarterectomy patients in the Erasmus Medical Center, The Netherlands in a manner that conformed to the declaration of Helsinki and was approved by the hospital’s Ethical Research Committee. The plaques were sectioned into 2 mm segments, isolating a total of 23 segments including segments from each of the three anatomical regions of the carotid artery vessel (Internal ICA, bifurcation BIF and common CCA). The plaque slices were incubated in radioactive solution of (99mTc-Demotate + 111In-Danbirt) (radioactivity = 100MBq/nmol). Ultra-high resolution focused imaging high-energy (HE) VECTor collimators was used which has a <500um reconstructed resolution and sensitivity >2800cps/MBq (Vector 5, MiLabs Utrecht). Scans were reconstructed using the 0.2mm voxel size SROSEM (Similarity Regulated Ordered Subset Expectation Maximization). Simultaneous dual-energy windows were used for separated quantification of counts with the nuclear properties of are 99mTc [gamma photon peaks of 140 keV] and 111In [gamma photon peaks of 171, 245 keV]. The samples were further cryo-sectioned into 5um slices and were immunohistochemically stained to assess co-localization of LFA-1 and SSTR-2 positive cells in the plaque segments. This study develops an optimal dual-tracer protocol for imaging dual inflammation targets in human diseased arteries. Quantification of the radiotracer uptake (MBq) per plaque segment with respect to histological analysis revealed the co-localisation between hot regions of uptake and high area fractions of the inflammatory cells. LFA-1 uptake was significantly higher compared to the SSTR-2 receptor and this measurement was further verified through histological analysis. Subsequently, a quantitative metric based on the extent of the two interrelated inflammation targets was developed. Simultaneous dual-radiotracer SPECT imaging of 99m-Tc and 111-In labelled radiotracers can be utilised to quantify the intricate interplay between the inflammatory processes in human diseased arteries.