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OBJECTIVE: The aim of this study was to validate the hyperbaric index (HBI) for first trimester prediction of preeclampsia and gestational hypertension. METHODS: Participants were low-risk and high-risk nulliparous women and high-risk multiparous women, and were recruited between April 2004 and June 2006. At a gestational age of 9 weeks (range 8-11 weeks), blood pressure (BP) was measured first by sphygmomanometry and thereafter by ambulatory BP measurement (ABPM) for 48 h. The first 90 low-risk women who had an uneventful pregnancy formed the reference group for calculation of a time-specified tolerance interval with 90% confidence limits. In the validation group, consisting of the remaining women, the HBI was calculated as the time-specified BP excess over this tolerance limit for SBP, DBP and mean arterial pressure. RESULTS: The validation group contained 101 women. Fifteen women developed preeclampsia and 13 developed gestational hypertension. For preeclampsia, the maximum HBI had the best predictive capacity with a sensitivity of 73% and a specificity of 86%. However, the difference with standard ABPM measurement or sphygmomanometry was small with a sensitivity between 75 and 73% and a specificity between 86 and 95%. The predictive efficacy for gestational hypertension was poor with all methods (sensitivity between 54 and 77%, specificity between 41 and 78%). CONCLUSION: Standardized sphygmomanometry, ABPM measurement and the HBI calculated from 48-h ABPM had a comparable, restricted predictive efficacy. The high predictive value of HBI as observed in earlier studies could not be reproduced. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Westerhof N.,VU University Amsterdam | Westerhof B.E.,BMEYE Inc | Westerhof B.E.,Heart Failure Research Center
Journal of Hypertension | Year: 2013

Objectives: In treatment of hypertension not only the pressure response is of interest, but also the effect on arterial parameters, for example, stiffness and resistance, is essential. We therefore reviewed what quantitative information on arterial stiffness can be obtained from pressure wave analysis. Methods: Using data from published large cohort studies, we derived relations between stiffness and the pressure-derived variables systolic pressure, pulse pressure, augmentation index (AIx), return time of reflected wave and reflection magnitude. Results: All pressure-derived variables give limited information on arterial function in terms of stiffness and resistance, except AIx (in low stiffness range only). Input impedance as a comprehensive description of the arterial system is too complex to derive and interpret in practice, but is accurately described by three parameters: systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance (outflow tract size and proximal aortic stiffness). These parameters predict aortic pressure well in terms of magnitude and shape: with measured flow the predicted (p) and measured (m) systolic, Ps, and diastolic, Pd pressures relate as P sp = 0.997Psm- 1.63 and Pd, p = 1.03P dm-3.12mmHg (n=17). Therefore, methods should be developed to determine, preferably noninvasively, these three arterial parameters. Conclusion: Variables derived from pressure wave shape alone (e.g. inflection point, AIx among others), and wave separation (e.g. reflection magnitude), while predicting cardiovascular events, give little information on arterial function. We propose to develop new, and improve existing, noninvasive methods to determine systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance. This will allow quantifying the response of arterial function to treatment. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.

Westerhof N.,VU University Amsterdam | Segers P.,Ghent University | Westerhof B.E.,BMEYE Inc | Westerhof B.E.,Heart Failure Research Center
Hypertension | Year: 2015

Wave separation analysis and wave intensity analysis (WIA) use (aortic) pressure and flow to separate them in their forward and backward (reflected) waves. While wave separation analysis uses measured pressure and flow, WIA uses their derivatives. Because differentiation emphasizes rapid changes, WIA suppresses slow (diastolic) fluctuations of the waves and renders diastole a seemingly wave-free period. However, integration of the WIA-obtained forward and backward waves is equal to the wave separation analysis-obtained waves. Both the methods thus give similar results including backward waves spanning systole and diastole. Nevertheless, this seemingly wave-free period in diastole formed the basis of both the reservoir-wave concept and the Instantaneous wave-Free Ratio of (iFR) pressure and flow. The reservoir-wave concept introduces a reservoir pressure, Pres, (Frank Windkessel) as a wave-less phenomenon. Because this Windkessel model falls short in systole an excess pressure, Pexc, is introduced, which is assumed to have wave properties. The reservoir-wave concept, however, is internally inconsistent. The presumed wave-less Pres equals twice the backward pressure wave and travels, arriving later in the distal aorta. Hence, in contrast, Pexc is minimally affected by wave reflections. Taken together, Pres seems to behave as a wave, rather than Pexc. The iFR is also not without flaws, as easily demonstrated when applied to the aorta. The ratio of diastolic aortic pressure and flow implies division by zero giving nonsensical results. In conclusion, presumptions based on WIA have led to misconceptions that violate physical principles, and reservoir-wave concept and iFR should be abandoned. © 2015 American Heart Association, Inc.

Boly C.A.,VU University Amsterdam | Reesink K.D.,Maastricht University | Reesink K.D.,Imperial College London | Van Den Tol M.P.,VU University Amsterdam | And 5 more authors.
British Journal of Anaesthesia | Year: 2013

BackgroundLeft-ventricular end-systolic elastance (Ees) is an index of cardiac contractility, but the invasive nature of its assessment has limited perioperative application. We explored the feasibility of a minimally invasive method of Ees estimation for perioperative assessment of cardiac function and evaluated the suitability of phenylephrine as a loading intervention.MethodsIn 17 surgical patients, Ees was determined as the slope of the end-systolic pressure-volume relation, which was obtained from non-invasive or invasive continuous arterial pressure measurements and left-ventricular volume determinations using transoesophageal echocardiography (TOE). Ees was determined using as loading interventions preload reduction by inferior vena cava compression (IVCC) and afterload increase by phenylephrine administration. ResultsMedian invasive Ees determined with phenylephrine estimated 1.05 (0.59-1.21) mm Hg ml-1 and with IVCC 0.58 (0.31-1.13) mm Hg ml -1. Bland-Altman analysis to evaluate the level of agreement between minimally invasive and invasive Ees estimation revealed a bias of -0.03 (0.12) mm Hg ml-1 with limits of agreement from -0.27 to 0.21 mm Hg ml -1 and the percentage error was 33%. Agreement between Ees obtained with phenylephrine and IVCC revealed a bias of 0.15 (0.69) mm Hg ml-1 with limits of agreement from -1.21 to 1.51 mm Hg ml-1 and a percentage error of 149%.ConclusionsIt is feasible to determine Ees combining continuous non-invasive arterial pressure measurements and left-ventricular volume determinations with TOE. However, administration of phenylephrine cannot substitute IVCC as a loading intervention, indicating that estimation of Ees in the intraoperative setting remains a challenge. © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

Westerhof B.E.,BMEYE Inc | Westerhof B.E.,University of Amsterdam
Journal of Hypertension | Year: 2013

BACKGROUND:: The vasodilating beta-blocker nebivolol is thought to be superior in lowering wave reflection and central blood pressure (BP) compared to nonvasodilating beta-blockers. The results from studies comparing nebivolol with either metoprolol or atenolol, with or without hydrochlorothiazide (HCTZ), are not unequivocal. METHODS:: We examined the effects of nebivolol 5âŠmg and metoprolol 100âŠmg with HCTZ 12.5âŠmg on aortic wave augmentation, central BP and hemodynamics using a randomized, double-blind, crossover design. We included 22 patients (17 men, age 59.9⊱âŠ6.4 years) with office SBP of 155⊱âŠ16âŠmmHg and DBP of 93⊱âŠ10âŠmmHg. Radial applanation tonometry and noninvasive, continuous finger arterial BP measurement was performed at baseline and after 4 weeks of treatment with either drug regimen, separated by a 4-week washout period. RESULTS:: Neither treatment affected aortic wave augmentation significantly. Augmentation index increased 1.0⊱âŠ7.8% (PâŠ= âŠ0.5) for nebivolol/HCTZ and 2. 4⊱âŠ6.6% (PâŠ=âŠ0. 07) for metoprolol/HCTZ. Nebivolol/HCTZ lowered central SBP by 15.8⊱âŠ14.9âŠmmHg and DBP 10.5⊱âŠ8.4âŠmmHg, and with metoprolol/HCTZ by 13.5⊱âŠ12. 3âŠmmHg for SBP and 9.5⊱âŠ6. 8âŠmmHg for DBP (all PâŠ<âŠ0.001). Heart rate was lowered 8.1⊱âŠ5.4 beats/min by nebivolol/HCTZ and 8.6⊱âŠ4.9 beats/min by metoprolol/HCTZ. Peripheral BP was reduced to a similar extent as central BP. Peripheral BP decreased by 16.3⊱âŠ14. 9âŠmmHg systolic and 10.1⊱âŠ8. 2âŠmmHg diastolic with nebivolol/HCTZ, and by 15. 2⊱â̌13.0â̌mmHg systolic and 9.1â̌±âŠ6.9 mmHg diastolic with metoprolol/HCTZ. Both treatment modalities had a similar effect on stroke volume, cardiac output, left-ventricular contractility and peripheral resistance. CONCLUSION:: Nebivolol was not superior to metoprolol in reducing aortic wave augmentation or central BP when combined with HCTZ. © 2013 Wolkers Kluwer Health.

de Kinkelder R.,University of Amsterdam | de Kinkelder R.,Topcon Europe Medical BV | Kalkman J.,University of Amsterdam | Faber D.J.,University of Amsterdam | And 5 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011

PURPOSE. To investigate the cause of axial eye motion artifacts that occur in optical coherence tomography (OCT) imaging of the retina. Understanding the cause of these motions can lead to improved OCT image quality and therefore better diagnoses. METHODS. Twenty-seven measurements were performed on 5 subjects. Spectral domain OCT images at the macula were collected over periods up to 30 seconds. The axial shift of every average A-scan was calculated with respect to the previous average A-scan by calculating the cross-correlation. The frequency spectrum of the calculated shifts versus time was determined. The heart rate was determined from blood pressure measurements at the finger using an optical blood pressure detector. The fundamental frequency and higher order harmonics of the axial OCT shift were compared with the frequency spectrum of blood pressure data. In addition, simultaneous registration of the movement of the cornea and the retina was performed with a dual reference arm OCT setup, and movements of the head were also analyzed. RESULTS. A correlation of 0.90 was found between the fundamental frequency in the axial OCT shift and the heart rate. Cornea and retina move simultaneously in the axial direction. The entire head moves with the same amplitude as the retina. CONCLUSIONS. Axial motion artifacts during OCT volume scanning of the retina are caused by movements of the whole head induced by the heartbeat. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Westerhof B.E.,BMEYE Inc | Westerhof B.E.,Heart Failure Research Center | Westerhof N.,VU University Amsterdam
Journal of Hypertension | Year: 2012

Background: Increased large artery stiffness is a major determinant of systolic pressure and indicator of cardiovascular events. The reflected wave, its arrival time (return time) and magnitude, contributes to systolic pressure, and is a supposed indicator of aortic stiffness. With aortic stiffening, the return time is assumed to decrease inversely with PWV as 2L/PWV, where L is the aortic length. However, several studies reported that the inflection point of aortic pressure, a surrogate of return time, varies little with aortic stiffness. Methods: We studied the effects of aortic stiffness on wave reflection in an anatomically accurate arterial model. Return time is time difference of forward, Pf, and backward, Pb, pressure. Return time, inflection and shoulder points, augmentation index, and reflection magnitude (Pb/Pf) were calculated by standard rules. Results: Peripheral resistance does not affect reflection directly, but only through pressure (stiffness) changes. Magnitude of reflected waves depend about equally on aortic geometry (taper, branches) and distal aortic reflection. Therefore, relations of augmentation index and reflection magnitude with stiffness are nonlinear and complex; augmentation index is most sensitive to stiffness. Between PWV 6 and 12 m/s, representing ages of 20-80 years, return time and inflection and shoulder points change differently with stiffness and PWV cannot be derived from them. Pulse pressure is strongly dependent on aortic stiffness. Taper changes return time by a factor 2, but has little effect on reflection magnitude, augmentation index, and inflection point. Conclusion: Accurate quantitative information on arterial stiffness cannot be obtained from reflection parameters. The augmentation index is most sensitive to stiffness changes. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

BMEYE Inc | Date: 2011-11-22

Scientific instruments for cardiovascular and physiological research, namely, electronic measuring tools and sensors for the measurement of blood pressure, cardiac output and physiological and cardiovascular parameters; computer software for the display and analysis of physiological signals; apparatus for data processing. Medical instruments to measure blood pressure, cardiac output and other physiological and cardiovascular parameters; medical instruments to monitor patients, namely, cardiovascular monitors. Scientific and technological services, namely, research and design services for others in the field of patient care and physiological research; industrial analysis and research in the field of medical device manufacturing and analysis of physiological data; design and development of computer software.

News Article | October 12, 2012

Earlybird portfolio company BMEYE has been sold to Edwards Lifesciences Corporation for €32.5 million, the Berlin-based VC firm has announced. Health technology firm BMEYE specialises in developing non-invasive technology for advanced monitoring of blood flow, while California-based Edwards Lifesciences is a world leader in manufacturing heart valves. The exit is the final strage in a big success story for Earlybird, which led the Series B investment of €6 million in BMEYE three years ago. With more than $500 million in assets currently under management, Earlybird – which moved its headquarters to Berlin from Munich earlier this year – focuses both on technology and health tech startups. BMEYE was founded in 2005 as a spin off from the Netherlands Organisation for Applied Scientific Research. At the time of Earlybird’s investment, partner Thom Rasche joined the BMEYE board, while the company was shortlisted as one of Europe’s most innovative in the 2010 Red Herring Awards. Carlyn Solomon, Edwards Lifesciences’ corporate vice president, said in a statement: “BMEYE’s unique non-invasive technology platform complements our existing portfolio and will provide clinicians with critical, comprehensive hemodynamic monitoring information for a broader range of patients.” The exit comes after Earlybird announced a €75 million fund for Berlin startups in April. And the company has also being working with LinkedIn co-founder Konstantin Guericke, who told Silicon Allee earlier this month: “Earlybird has the desire to take some risks with things that are less proven than maybe other investors would be, and they’re working with me to help people get to the market.” The investment in BMEYE has certainly paid off.

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