Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flow-mediated vasodilation: Analysis of 672 individual repeated measurements

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.Objectives: Brachial artery flow-mediated dilation (FMD) is a popular technique to examine endothelial function in humans. Identifying volunteer and methodological factors related to variation in FMD is important to improve measurement accuracy and applicability. Methods: Volunteer-related and methodology-related parameters were collected in 672 volunteers from eight affiliated centres worldwide who underwent repeated measures of FMD. All centres adopted contemporary expert-consensus guidelines for FMD assessment. After calculating the coefficient of variation (%) of the FMD for each individual, we constructed quartiles (n = 168 per quartile). Based on two regression models (volunteer-related factors and methodology-related factors), statistically significant components of these two models were added to a final regression model (calculated as β-coefficient and R 2). This allowed us to identify factors that independently contributed to the variation in FMD%. Results: Median coefficient of variation was 17.5%, with healthy volunteers demonstrating a coefficient of variation 9.3%. Regression models revealed age (β = 0.248, P < 0.001), hypertension (β = 0.104, P < 0.001), dyslipidemia (β = 0.331, P < 0.001), time between measurements (β = 0.318, P < 0.001), lab experience (β = -0.133, P < 0.001) and baseline FMD% (β = 0.082, P < 0.05) as contributors to the coefficient of variation. After including all significant factors in the final model, we found that time between measurements, hypertension, baseline FMD% and lab experience with FMD independently predicted brachial artery variability (total R2 = 0.202). Conclusion: Although FMD% showed good reproducibility, larger variation was observed in conditions with longer time between measurements, hypertension, less experience and lower baseline FMD%. Accounting for these factors may improve FMD% variability

Central and local arterial stiffness in White Europeans compared to age-, sex-, and BMI-matched South Asians

Background Ethnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness. Methods Data were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness. Results We included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans. Conclusion Ethnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors

Coronary–aortic interaction during ventricular isovolumic contraction

In earlier work, we suggested that the start of the isovolumic contraction period could be detected in arterial pressure waveforms as the start of a temporary pre-systolic pressure perturbation (AICstart, start of the Arterially detected Isovolumic Contraction), and proposed the retrograde coronary blood volume flow in combination with a backwards traveling pressure wave as its most likely origin. In this study, we tested this hypothesis by means of a coronary artery occlusion protocol. In six Yorkshire × Landrace swine, we simultaneously occluded the left anterior descending (LAD) and left circumflex (LCx) artery for 5 s followed by a 20-s reperfusion period and repeated this sequence at least two more times. A similar procedure was used to occlude only the right coronary artery (RCA) and finally all three main coronary arteries simultaneously. None of the occlusion protocols caused a decrease in the arterial pressure perturbation in the aorta during occlusion (P > 0.20) nor an increase during reactive hyperemia (P > 0.22), despite a higher deceleration of coronary blood volume flow (P = 0.03) or increased coronary conductance (P = 0.04) during hyperemia. These results show that the pre-systolic aortic pressure perturbation does not originate from the coronary arteries

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker

The effect of oxygenator mechanical characteristics on energy transfer during clinical cardiopulmonary bypass

The hollow-fibre oxygenator is a key component of any extracorporeal circuit used to provide cardiopulmonary bypass (CPB) during open-heart surgery. Since the oxygenator is placed downstream of the pump, the energy losses over it have a direct impact on the quality of pulsatile pressure and flow waveforms. The objective of this study was to describe the effects of hydrodynamic characteristics of the oxygenator on energy transfer during pulsatile, normothermic CPB. Twenty-three adult patients scheduled for coronary bypass surgery were divided randomly into two groups, using either an oxygenator (Group 1) with a relatively high-resistance and low-compliance (2079 ± 148 dyn.s.cm-5 and 0.00348 ± 0.00071 ml.mmHg-1, respectively) or an oxygenator (Group 2) with a relatively low-resistance and high-compliance (884 ± 464 dyn.s.cm-5 and 0.01325 ± 0.00161 ml .mmHg-1, respectively). During perfusion, pre- and post-oxygenator pressures, radial artery pressure, and blood flow were recorded simultaneously. A 32% decline of mean pressure was observed in Group 1 and a 16% decline in Group 2 (p&lt;0.0001). Another decrease by approximately 73% in mean pressure in the rest of the perfusion system was noted in both groups. The mean radial artery pressure did not differ between the groups (74 ± 6 mmHg in Group 1 and 73 ± 6 mmHg in Group 2, p=0.608). Although lower total energy transfer indices were noticed through the low-resistance oxygenator (Group 2), both oxygenators showed a decrease of the generated pump oscillatory energy of approximately 50%. Despite the differences in resistance and compliance of the hollow-fibre oxygenators used, both oxygenators cause a comparable loss of generated oscillatory energy. Exclusion of the oxygenator downstream of the pulsatile pump would improve energy transfer during CPB. </jats:p

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 (pbw, 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 1.0ms-1 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 multi-step parametric analysis, both vs,LV and arterial stiffness were about equal determinants of AIx, whereas pbw was only determined by arterial stiffness. Furthermore, the relation between increased AIx and LV stroke work was only for about 50% explained by an increase in arterial stiffness, the other factor being vs,LV. The pbw, 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

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

\u3cp\u3eWe 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.\u3c/p\u3

Linking diastolic function to cardiac exercise performance in heart failure with preserved ejection fraction: a virtual patient study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO-ZonMw Background The relative impact of left ventricular (LV) diastolic dysfunction (LVDD) and impaired left atrial (LA) function on cardiac exercise performance (CEP) in heart failure with preserved ejection fraction (HFpEF) remains largely unknown Purpose To elucidate the relative effects of LVDD and impaired LA function on hemodynamics at rest and on cardiac performance during exercise by performing virtual HFpEF patient simulations. Methods Using a well-validated cardiovascular system model (CircAdapt), impaired LV relaxation was simulated by increasing the rate of myocardial relaxation (tau) from 35 to 65 ms. To study the effect of moderate and sever LV myocardial stiffness increase, LV end-diastolic elastance was increased from 0.15 mmHg/ml to 0.60 mmHg/ml and 2.00 mmHg/ml, respectively. In each simulation, LV diastolic function at rest (cardiac output (CO) and heart rate (HR) of 5.1 l/min and 70 bpm, respectively) was assessed using LV ejection fraction (LVEF), mitral E/A ratio, maximum LA volume (LAV), and mean left atrial (LA) pressure (mLAP). To investigate the relative effect of these cardiac abnormalities on exercise capacity, CO and HR were gradually increased using a fixed CO-HR relationship until mLAP exceeded a threshold pressure of 35 mmHg, which was assumed to be a physiological limit of exercise intensity. Results Simulations showed that regardless of the modelled LV and LA function, LVEF was preserved (&amp;gt;50%). Impaired LV relaxation function was associated with decreased E/A-ratio and a small increase in mLAP at rest, regardless of LA function. Increased LV passive stiffness resulted in increased E/A-ratio, LA dilation and markedly elevated mLAP at rest, regardless of LA function (Figure: top-left). Impaired LA function resulted in reduced A-peak velocity, and increased E/A–ratio, LAV and mLAP at rest regardless of LV function (Figure: top-right) Exercise simulations showed that increased LV passive stiffness exerts a stronger exercise-limiting effect than impaired LV relaxation function, in particular when LA function is impaired (Figure: bottom). Conclusions Through simple and well-controlled variations in LV and LA function, we were able to simulate virtual HFpEF patients with a wide range of LVDD severities at rest, preserved LVEF, and reduced cardiac exercise performance. In general, our simulations suggest that increased LV passive stiffness, rather than impaired LV relaxation function, reduces exercise tolerance, especially in the presence of LA dysfunction. Abstract Figure. Simulating rest &amp; exercise hemodynamics </jats:sec