Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), are at increased risk of cardiovascular events and mortality. The spectrum of arterial remodeling in CKD and ESRD includes atheromatosis of middle-sized conduit arteries and, most importantly, the process of arteriosclerosis, characterized by increased arterial stiffness of aorta and the large arteries. Longitudinal studies showed that arterial stiffness and abnormal wave reflections are independent cardiovascular risk factors in several populations, including patients with CKD and ESRD. Kidney transplantation is the treatment of choice for patients with ESRD, associated with improved survival and better quality of life in relation to hemodialysis or peritoneal dialysis. However, cardiovascular mortality in transplanted patients remains much higher than that in general population, a finding that is at least partly attributed to adverse lesions in the vascular tree of these patients, generated during the progression of CKD, which do not fully reverse after renal transplantation. This article attempts to provide an overview of the field of arterial stiffness in renal transplantation, discussing in detail available studies on the degree and the associations of arterial stiffness with other co-morbidities in renal transplant recipients, the prognostic significance of arterial stiffness for cardiovascular events, renal events and mortality in these individuals, as well as studies examining the changes in arterial stiffness following renal transplantation. Patients with chronic kidney disease (CKD) and particularly patients with end-stage renal disease (ESRD) are individuals with an early and marked increase in arterial stiffness, characterized by alterations in the viscoelastic properties of large arteries –3. AlthoSeveral epidemiological studies have shown that patients with reduced renal function are at increased risk for cardiovascular events and all-cause mortality . The assKidney transplantation is the treatment of choice in patients with ESRD as it is associated with at least 2-fold longer survival in relation to hemodialysis or peritoneal dialysis and significant benefits in the quality of life of patients. However, the risk of cardiovascular death in transplanted patients remains significantly higher than that in general population , 18. It Arterial stiffness is a term describing the loss of flexibility of elastic arteries, i.e., the aorta and the other major arteries. Elastic arteries (or conducting arteries) receive blood directly from the heart and are the largest arteries of the body, those closest to the heart. The walls of these arteries have abundant elastic fibers, which, apart from the solidity, offer the ability of dilatation of the vessels; thus aorta and major arteries can through dilatation to practically “store” part of the blood volume during heart systole and forward it to the periphery during diastole. This cushioning function is a fundamental part of the circulation as it helps to avoid major changes in BP and keep the flow of blood as smooth as possible in the time between two heart beats , 19–21. In cases of increased arterial stiffness, the normal functioning of the aorta and large vessels is disrupted resulting major changes in the circulatory system . NormallThis increase in arterial stiffness is considered to be the main mechanism for the creation of isolated systolic hypertension, left ventricular hypertrophy, and heart failure with decreased cardiac output . TypicalThe velocity of transmission of the pulse wave along the arterial wall increases as we move from central to peripheral parts of the arterial tree, due to the change in the properties of the arterial wall (progressive change from “elastic type” to “muscular type” arteries). Due to the different distance from the reflection points, the morphology of the final pulse wave  at each point of the arterial tree is different from the others. Thus, the maximum SBP and therefore PP are different along the arterial tree. In normal conditions, the SBP at the level of the brachial artery is higher than at the level of the central arteries, while the diastolic and mean BP differ much less between these points. Especially in healthy young people, central (aortic) systolic BP is lower than peripheral up to 30 mmHg or more . This phThe heart, the kidneys and the large vessels that feed the brain are anatomically closer and more strongly influenced by the effects of central rather than brachial BP. Therefore, it is reasonable to assume that central BP relates more closely to target-organ damage and that it has an important predictive value as far as cardiovascular mortality concerned. A plethora of data suggests that central BP is better correlated with target organ damage, cardiovascular risk and events, and mortality than peripheral BP , 30, 33.There are currently several methods available to determine arterial stiffness and central pressures in a non-invasive way. In clinical practice, pulse wave velocity (PWV) along the aorta is the main parameter used to determine arterial stiffness. PWV is defined as the speed of transmission of the pulse wave along the arterial wall and is calculated by the ratio of the distance between two points of the arterial tree to the time of transmission of the pulse wave between these two points , i.e.,With the modern ways of PWV determination, the speed at which the pulse wave travels between two superficial points of the arterial tree can be calculated. Tonometric techniques (with devices such as Sphygmocor), ultrasonographic techniques, plethysmography, and indirect identification techniques (with devices such as Mobilograph) are used to determine PWV , 38–40. p ≤ 0.01). The factors related to donor aortic PWV, evaluated at end of follow-up, were donor age, MAP, plasma glucose, smoking, and time since nephrectomy. The factors related to recipient PWV were age, MAP, and smoking habit (as in donors), but also graft rejection. When examining recipients with chronic allograft nephropathy, plasma creatinine doubling was associated with 2 factors after adjusting for age: acute rejection (p = 0.004) and donor PWV (p = 0.03)  .p < 0.01), LVH  and CVD . In multivariate regression analysis, PWV was associated with age  and presence of pre-transplantation diabetes   .p = 0.002) but borderline lower FMD  in patients that did not reach the therapeutic BP goal as compared to those with good or borderline BP control. Further analysis of patients in subgroups based on the number of antihypertensive drugs revealed a significant trend for increased LVH prevalence and higher PWV values with increased number of antihypertensive drugs . Interestingly, there was no significant difference in FMD, NMD, and IMT between these subgroups , PWV , and ankle-brachial pressure index, which was normal in 67 (72.8%) transplant and 20 (66.6%) CKD patients and abnormally high in 21 (22.8%) transplant and 8 (26.6%) CKD patients (p < 0.001). In univariate analysis CS was significantly correlated with age, duration of hypertension, waist circumference, PWV, hemoglobin levels and serum glucose, whereas in multiple linear regression analysis CS was independently associated only with age and not with PWV. Sensitivity and specificity of PWV > 7.6 m/s as cut-off for detecting CAC >0 was 0.889 and 0.406, respectively. Sensitivity and specificity of PWV > 10.2 m/s for detecting severe CAC (CS > 400) was 0.319 and 0.969, respectively, suggesting that PWV measurement could be useful in excluding severe CAC in renal transplant recipients  between overweight as defined by BMI and the PWV measurements. On multivariate linear regression analysis, with PWV as a dependent variable, the factors independently associated with it were age, hemoglobin levels and 24-h SBP. An age increase of 10 years was correlated with a 0.47 m/s increase in PWV, while a 1 g/dl hemoglobin increase correlated to a 0.933 m/s decrease in PWV. Finally, a 24-h SBP increase of 10 mm Hg was correlated with a PWV increase of 0.83 m/s , age , tacrolimus immunosuppression therapy  and central DBP   .In addition to the aforementioned cross-sectional studies, few retrospective and prospective cohort studies have tried to explore the association of arterial stiffness indices with cardiovascular risk, renal outcomes and mortality in renal transplant recipients .p < 0.05) and was proved to be a strong predictor of CVD . The optimal cut-off value of baPWV for the detection of CVD was 15.91 m/s with a sensitivity of 72.7% and specificity of 71.6% , and this value was an independent predictor of CVD in renal transplant recipients . Moreover, the occurrence rate of CVD was significantly higher in patients with “high coronary calcium score” compared to those with a “low coronary calcium score” and baPWV was also significantly higher in the first of the above two groups .A cohort study  by Kim ep = 0.001) (p < 0.001). Mortality was also significantly associated with c-f PWV 12 months after transplantation , but not with aortic stiffness change between 3 and 12 months   . An inte= 0.001) . Finally= 0.001)  included= 0.696) .p < 0.0001 for both genders), despite a lower MBP compared to normal controls . Moreover, independently of age and BP levels, PWV was influenced by two factors: presence of acute rejection  and increased tobacco consumption . These two factors, along with donor age also influenced the decrease in GFR observed after transplantation . Finally, the authors reported that the occurrence of renal and/or cardiovascular events following transplantation was influenced by two factors: heart rate  and PWV . When PP was multiplied by heart rate, this product was a significant  and independent factor influencing cardiovascular events in transplanted patients, in addition to a past history of cardiovascular events . The study is limited, however, by the lack of details on the methodology of the analysis  and PWV ratio (cfPWV/crPWV)  predicted cardiovascular events  in renal transplant recipients. When renal and cardiovascular outcomes were separately analyzed, recipient eGFR and donor PWV were significant determinants of the renal outcome  and previous history of cardiovascular events was the only significant determinant of the cardiovascular outcome   .p < 0.0001) (p < 0.05). Moreover, in an analysis stratified by age, this improvement was only present in patients older than 50 years of age as compared with patients younger than 50 years of age . As far as AIx75 is concerned, it decreased from 22 ± 11 to 14 ± 13% (p < 0.01), but this reduction was not age-dependent  . In a su 0.0001)  measuredependent .p = 0.01) (p < 0.01) at 6 months post-transplantation was observed (p = 0.0075). Respectively, AIx decreased from 41.97 ± 11.88 to 26.09 ± 10.92% the first postoperative day, to 23.02 ± 16.5% at postoperative day 7 and to 21.96 ± 11.98% at study end (p = 0.013)  . Another = 0.01)  brachialobserved . In anotobserved , arteria= 0.013) .p < 0.05) at 3 months and 13.8 ± 12.4 % (p < 0.05) at 6 months; a decrease in pulse pressure from 41.7 ± 13.9 before to 33.0 ± 11.1 (p < 0.05) at 3 months and to 30.1 ± 9.8 mm Hg (p < 0.05) at 6 months was also noted (p < 0.05), but there were no changes between 6 months and 2 years after transplantation (p < 0.05). Logistic regression analysis revealed that higher body mass index  and the degree of increase in calcium levels  were independent risk factors that affected baPWV after kidney transplantation (p = 0.46). AIx before transplantation was 6.93 ± 11.41% vs. −0.53 ± 17.05% post-transplantation (p = 0.15)  .p = 0.028), while it increased in recipients of old-donor (53–70 years of age) kidneys from 9.97 ± 1.70 to 10.25 ± 1.98 (p = 0.022) (p = 0.7)  . Subsequ= 0.022)  used Sphp = 0.7) .p < 0.001). PWV reduction from month 3 to month 12 was significantly larger in patients with the living donor allograft compared to those with the deceased donor allograft (p < 0.001). When the extended criteria donor (ECD) group were compared to the standard criteria donor (SCD) group, the change in PWV also differed significantly, −0.7 (−1 to −0.4) in ECD vs. +0.1 (−0.4 to +0.4) in SCD (p < 0.01) (p = 0.777)  . Finally < 0.01)  measured= 0.777) .Kidney transplantation is the treatment of choice in patients suffering from ESRD, yet cardiovascular risk in renal transplant recipients remains significantly higher than that of the general population. This excess risk is not fully explained by the burden of traditional cardiovascular risk factors present in renal transplant recipients. As increased arterial stiffness is a prominent feature of vascular changes in patients with CKD and ESRD and has been repeatedly associated with increased risk of cardiovascular events and mortality in these conditions, different types of studies have been conducted in order to assess the degree of arterial stiffness in renal transplant recipients and its associations with other risk factors but also with future cardiovascular risk, graft survival and overall mortality.Several cross-sectional studies discussed in detail herein, showed that higher PWV in renal transplant recipients was associated with various risk factors, co-morbidities, and associated target-organ damage including age, pre-transplant diabetes, increased ambulatory BP, increased waist circumference and visceral fat mass, smoking, coronary artery calcification, and left ventricular hypertrophy, but also with previous episodes of acute renal rejection, renal graft dysfunction and previous time on dialysis. Other studies have assessed the course of arterial stiffness before and after kidney transplantation. In most cases, arterial stiffness measured with PWV was markedly reduced after kidney transplantation. Of note, in some studies this improvement was shown to be age-dependent, suggesting an added cardiovascular risk reduction in older patients and was also more marked in cases of transplantation from living donors. In the subset of studies examining PWV in different timepoints after kidney transplantation (varying from 1 week to 2 years), mixed results were noted, with some studies showing that arterial stiffness was partly reversed during follow-up and that this improvement was dependent on donor age and greater in patients receiving a renal graft from a living donor, whereas other studies suggesting that arterial stiffness levels were similar in the early and late post-transplantation period Finally, and perhaps most importantly, in almost all studies evaluating the role of arterial stiffness as a predictor of future adverse outcomes, PWV was shown to be an independent predictor of cardiovascular events, loss of renal function and overall mortality. Thus, existing evidence suggests that increased arterial stiffness is a major pathophysiological player involved in the adverse cardiovascular profile of renal transplant recipients. As of this writing, however, there are not any clinical trials in transplant recipients (or any other population) aiming to assess whether therapeutic interventions to reduce of arterial stiffness would improve patient outcomes. To this scope, mechanistic studies to identify the major mechanisms through which renal transplantation beneficially affects PWV are also required. Overall, further studies are urgently warranted to better define the associations of PWV with other prominent risk factors, the change and evolution of arterial stiffness after kidney transplantation, its long-term prognostic significance and whether it could represent an additional therapeutic goal in order to improve patient and graft survival after renal transplantation.MK and EX wrote the first draft of the manuscript. SM wrote sections of the manuscript and checked the Tables for intellectual content. PS and JB conceptualized the article, wrote sections of the manuscript, and checked the manuscript for intellectual content.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Ka) and venous (Kv) compliances, and a cerebral autoregulation time constant (τ(AR)). The mean values (± standard errors) of these parameters across the twenty-two subjects were Ka) = 2.2 ± 1.3 s. Spatially resolved measurements in a subset of eight subjects reveal a spatial variability of these parameters that may exceed the inter-subject variability at a set location. This study sheds some light onto the role that ABP and cerebral blood flow (CBF) play in the dynamics of [HbT] measured with NIRS, and paves the way for new non-invasive optical studies of cerebral blood flow and cerebral autoregulation.We report a study on twenty-two healthy human subjects of the dynamic relationship between cerebral hemoglobin concentration ([HbT]), measured with near-infrared spectroscopy (NIRS) in the prefrontal cortex, and systemic arterial blood pressure (ABP), measured with finger plethysmography. [HbT] is a measure of local cerebral blood volume (CBV). We induced hemodynamic oscillations at discrete frequencies in the range 0.04–0.20 Hz with cyclic inflation and deflation of pneumatic cuffs wrapped around the subject’s thighs. We modeled the transfer function of ABP and [HbT] in terms of effective arterial ( Oscillations of systemic arterial blood pressure (ABP) drive hemodynamic changes in the body’s macro- and microvasculature, elicit local responses in the peripheral circulation, and induce oscillations in the cerebral blood volume (CBV), which is the focus of this work. The dynamics between systemic ABP and local CBV reflect a combination of effects due to passive vascular compliance and active vascular reactivity, which in turn elicit dynamic changes in cerebral blood flow (CBF). The passive response is determined by the mechanical properties of blood vessel walls. The active vascular reactivity is responsible for cerebral autoregulation (AR), which maintains a relatively stable CBF despite changes in cerebral perfusion pressure (CPP), defined as the difference between ABP and intracranial pressure (ICP). AR plays an important role in the CBF response to ABP oscillations. There has been an increasing interest in using metrics of AR to assess cerebrovascular health or to guide therapy at the bedside . The cha2] and [Hb], respectively), which may be combined to derive their difference ([HbD] = [HbO2] − [Hb]) and the oxygen saturation of hemoglobin (StO2 = [HbO2]/[HbT]), the latter being sometimes referred to as tissue oxygenation index (TOI). Over the years, a number of NIRS studies have investigated some aspects of the dynamic relationship between ABP and NIRS-measured quantities, as we describe below.Near-infrared spectroscopy (NIRS) is a technique that affords local measurements of CBV and features desirable properties such as non-invasiveness, safety, portability, and cost effectiveness. It is important to observe that the NIRS measurements of CBV are derived from measurements of the total concentration of hemoglobin in tissue ([HbT]), through a factor given by the concentration of hemoglobin in blood. In this way, [HbT] is a marker for CBV. However, not all blood vessels contribute equally to the NIRS signal, depending on their size and location. In particular, larger blood vessels may act as total absorbers of near-infrared light, so that NIRS measurements tend to reflect blood volume that is mostly associated with the microvasculature. Another important feature of NIRS is its capability to measure the concentration of both oxygenated and deoxygenated species of hemoglobin , defined as the ability of vascular smooth muscle to respond to changes in transmural pressure. For example, the hemoglobin volume index (HVx), defined as the correlation coefficient between fluctuations in [HbT] and ABP, has been proposed as a non-invasive alternative to a measure of CPR, the pressure reactivity index (PRx), which is given by the correlation coefficient between ICP and ABP –4. Both et al.  noted thet al. .A number of NIRS studies have assessed AR by co-registering dynamic traces of ABP and either TOI –11 or H,13, follet al. analyzed spontaneous oscillations and they found that the relative phase of [HbO2] and ABP decreased from slightly positive values  at ~0.02 Hz to slightly negative values  at 0.10 Hz  were studied in a group of newborn infants on life support , during seven levels of flow from the support system  in the Mayer waves range. Rowley et al. studied WCC, WPH and WPCOH between ABP and [HbO2] in patients suffering from autonomic failure during posture changes (head up tilt) [2] during posture change: ~11° at baseline, ~-34° during head up tilt, ~6° post tilt. On the contrary, the heathy controls, at frequencies in the range 0.07–0.13 Hz, showed an almost constant negative phase in the range -17°–-6° for the three blocks of the protocol. We recall that a positive phase between ABP and [HbO2] means that the oscillations of ABP are leading those of [HbO2]. It is also worth mentioning that except for patients during head up tilt, in all other cases the phase error bars were larger than the mean values. Tian et al. studied WCOH, WPH and WPCOH between ABP and tissue saturation on a cohort of infants suffering from hypoxic-ischemic encephalopathy  measured with NIRS) and systemic ABP. We measured 22 healthy subjects to characterize the relationship between [HbT] and ABP over multiple frequencies in the range 0.04–0.20 Hz. We used pneumatic thigh cuffs to induce controlled MAP oscillations to drive cerebral blood volume oscillations at a given frequency. We also implemented a time-varying approach for coherence analysis with a sliding short time Fourier transform (STFT). This enabled us to quantify coherence between [HbT] and ABP for thigh-cuff-induced oscillations as well as spontaneous oscillations, thus resulting in measurements of the transfer function at several frequencies beyond the ones specifically induced by the thigh cuffs.2], the approach described in this work may be more robust than methods that we have previously introduced to assess AR from dynamic measurements of [Hb] and [HbO2] [We propose an analytical model for the phase and amplitude relationships between [HbT] and ABP. This model results in a transfer function for [HbT] and ABP that consists of a constant term plus a frequency dependent term in the form of a first-order low pass filter. The physical interpretation of the constant term is an arterial compliance effect, which becomes dominant at high frequencies (>1 Hz), whereas the frequency-dependent term  is assigned to cerebral blood flow effects on the venous compartment. Importantly, the time constant of the low pass filter characterizes the AR response and can be used as an AR metric. This model provides a framework for measurements of AR that are based on [HbT] dynamics driven by ABP. Because dynamic NIRS measurements of [HbT] typically feature a better signal-to-noise ratio than measurements of [Hb] and [HbOd [HbO2] –28.Twenty-two healthy subjects  participated in the study. The Tufts University Institutional Review Board approved the experimental protocol, and the subjects provided written informed consent prior to the experiment. The data for nine of the female subjects (nn. 13–21) have been previously analyzed for a comparison of the relative phase and amplitude of oxyhemoglobin and deoxyhemoglobin concentration oscillations in brain and breast tissue .I690(t) and I830(t)) was collected at a distance of 3.5 cm from the illumination point on the subject’s forehead. The modified-Beer Lambert law was used to compute relative changes in oxyhemoglobin (Δ[HbO2]), deoxyhemoglobin (Δ[Hb]), and total hemoglobin concentrations (Δ[HbT]) in units of microMolar (μM). The relative differential path length factor and baseline optical properties at 690 and 830 nm were determined from frequency-domain data either by a multi-distance approach  . For details on the particular set up for each subject, see  3.5 cm) . Extinct 3.5 cm) .To induce MAP oscillations, pneumatic cuffs were placed around both subject’s thighs and were connected to a cuff inflation system . A microcontroller was connected to the regulator of the inflation system via a 1/4 inch stereo phone plug in order to set customized rates of inflation and deflation (Arduino Uno R3). Maximum inflation pressure of the cuffs was at least 180 mmHg, therefore greater than systolic blood pressure, in order to induce arterial occlusion. The air pressure in the thigh cuffs was continuously monitored with a digital manometer . Continuous arterial blood pressure (ABP) was recorded with a beat-to-beat blood pressure monitoring system . A pulse oximeter measured the heart rate . All signals were recorded synchronously with a sample rate of at least 6.25 Hz.The experiment duration was 20–60 minutes. In each experiment, the thigh cuffs were cyclically inflated and deflated at frequencies ranging from 0.04 Hz to 0.20 Hz in order to induce MAP oscillations that would drive coherent oscillations in cerebral hemodynamics. In one protocol, we induced oscillations at a set of frequencies with sequential 90 s epochs of oscillations at a given frequency followed by 90 s of baseline. Another protocol was a “chirp” like sequence where we also induced oscillations at a set of frequencies, but this time each frequency was applied for a duration of 6 periods of oscillation, without baseline periods in between each frequency. See t) and Δ[HbT](t) as a measure of their level of co-variation. Signals are coherent at a particular frequency when their relative amplitude and phase are stable at that frequency. The International Cerebral Autoregulation Research Network (CARNet) has developed guidelines for the standardization of coherence computation and transfer function analysis in this field , we considered the coherence of ΔABP, is obtained as follows:PABP,[HbT] is the cross power spectral density between ABP and [HbT], PABP,ABP is the power spectral density of ABP, and P[HbT],[HbT] is the power spectral density of [HbT]. Perfect linear coupling results in a coherence of 1, whereas absence of coupling results in a coherence of 0. We elected to perform the spectral analysis with the STFT based on Welch’s overlapped averaged periodogram method ). Another sequence of independent random numbers was generated to simulate ΔABP. Our approach for coherence analysis was applied to these independent sets of random numbers 1000 times to generate the null statistical distribution for coherence. We found that the 5% critical value of coherence between ABP and [HbT] was 0.79, so we selected this value as our threshold for significance. We applied this threshold to the image of coherence, and we defined a binary image, where the pixels above threshold were assigned the value of 1 and those below threshold were assigned the value of 0.To compute a threshold for significant coherence, we used the following approach . Two seqFollowing thresholding of the coherence image, we determined the connected components in the binary image (MATLAB function “bwconncomp”) which considers adjacent pixels as part of the same group. We computed the area of each separate group of connected pixels which we call clusters. We expected coherence between the two signals to be maintained for at least several seconds, so that single pixels or small clusters of pixels passing the threshold were assigned to noise. A second set of data for generating the null statistics for coherent cluster size was created with another run of 1000 random independent time traces of ΔABP and Δ[HbT]. Upon thresholding with the selected value of 0.79, the size of each coherence region within the image was recorded. We computed that regions greater than 13 (25) pixels had a 5% (0.2%) chance of being designated as coherent by chance. In the analysis of the experimental data, coherence was computed between ΔABP and Δ[HbT]. We created a binary image with 1’s indicating pixels that exceeded the coherence threshold. Then the size of coherent clusters was computed, and pixels in clusters whose size was less than 25 pixels were set to 0 in the binary image. We heuristically found that the threshold of 25 pixels, with a significance level of 0.2%, provided estimates of transfer functions with less variability than a threshold of 13 pixels without eliminating too many clusters. After the size thresholding, some single pixels protruded at the edges of clusters, and we assigned them to noise. A filter was applied to the binary coherence image to eliminate protruding pixels.The time-varying transfer function between ABP and [HbT] was computed with the same time resolution, frequency resolution, and windowing approach as the coherence computation. The MATLAB function “tfestimate” was used for this portion of the analysis. The transfer function over frequency and time is written as follows:The time-frequency transfer function, at pixels that passed the thresholding condition, was averaged over time with the assumption that each coherent pixel in time is a sample of the same transfer function. The time-averaged transfer function between ABP and [HbT] as a function of frequency is:Blood volume changes result from two possible effects: vascular dilation/constriction  and vascular recruitment/collapse (i.e. opening of new vessels or closing of existing ones). Vascular recruitment/collapse may occur at the capillary level, and it is a common occurrence in skeletal muscle but not in brain tissue , so thatt), and therefore in arterial transmural pressure, directly result in changes in arterial blood volume, ΔCBVa)((t), according to a factor, Ca) for the arterial compartment in this case). In the frequency domain, CBVa) the venous blood pressure is much lower than arterial blood pressure, so that we neglect direct effects of ABP on the venous transmural pressure, and thus onto venous blood volume. Instead, we consider venous blood volume dynamics resulting from cerebral blood flow changes, which are mostly driven by ABP changes in this study. Therefore, rather than being directly driven by ABP, we consider venous blood volume changes to be mediated by CBF changes. The arterial outflow acts as the capillary inflow (i.e. v)((t), defined as the venous blood volume per unit volume of tissue within the optically probed region, can change only for an imbalance between venous inflow, The venous cerebral blood volume, CBVt = 0, we have In a situation of equilibrium, at time If we make the further approximation that the venous compliance is large enough to accommodate any inflow changes through venous volume changes  and are attenuated by a factor 1/ω as frequency increases. We note that this result of a π/2 phase lag of CBV with respect to CBF refers to the case of ideal sinusoidal oscillations.Because in the frequency domain a time derivative becomes a product by k is a dimensional constant. Taking τAR)( (related to autoregulation), the impulse response function is As a result of dynamic cerebral autoregulation (AR), the temporal response of CBF to ABP changes can be described in terms of a high pass filter, through its impulse response function We can now consider the total blood volume phasor, which results from the sum of the arterial and venous blood volume phasors given in Eqs  and 12)12):CBV(Ka)( = ctHb Ca)( and Kv)( = ctHb kτ(AR). Because the total hemoglobin concentration, [HbT], measured with NIRS is given by the product ctHb CBV, where ctHb is the concentration of hemoglobin in blood, Ka) or left side (subjects nn. 13–22) of the subject’s forehead. For the subjects who wore the spatial mapping probe (subjects nn. 1–8), the left-most channel , the data were averaged over time to produce the spectra HABP,[HbT](ω), under the assumption of time invariance. The mean values and the standard error of the mean are indicated by the circles with error bars in ABP(ω) and [HbT](ω) amplitude ratios and phase differences at each frequency that featured coherent oscillations, averaged over all twenty-two subjects.Following the computation of Ka) ranged from 0.3 to 5.1 s with a mean value of 2.2 ± 1.3 s.The best fits of the data with the model of ω ≫ 1/τ(AR)), where cerebral autoregulation is not effective, [HbT] and ABP oscillations tend to be in phase with each other, and with a relative amplitude given by Ka) signifies that the condition ω ≫ 1/τ(AR) is satisfied at the heartbeat frequency of about 1 Hz (in this case ωτ(AR) ≈ 4π ≫ 1), consistent with the fact that cerebral autoregulation is not effective at the heartbeat frequency. In fact, the extension of the fit lines of Ka)( vs. ABP. The relative contributions of these two sources to the observed [HbT] dynamics depends on frequency: at high frequencies (ω ≫ 1/τAR)( ≈ 2.2 s), the arterial term dominates and accounts for the asymptotic values for amplitude and phase (Ka) that one can see in ω ≲ 1/τAR), the venous term dominates and the transfer function HABP,[HbT](ω) takes the form of a low-pass filter. According to this model, in this low-frequency range (≲ 0.1 Hz) the CBF phase is given by the [HbT] phase + π/2. This observation can be the basis for a novel NIRS-based approach to the dynamic study of CBF. Specifically, in this low-frequency range, this π/2 phase shift may be applied to measured [HbT] oscillations in order to determine the phase of CBF oscillations.Our results are consistent with the model of v), which we have not monitored in this study. ICP is relatively constant in healthy individuals, but the effect of ICP may become important in the case of patients with cerebrovascular pathologies.According to our interpretation, [HbT] dynamics measured with NIRS are mostly determined by passive arterial responses to ABP dynamics and passive venous responses to CBF dynamics. Therefore, active arteriolar responses to ABP changes would not be directly measurable with NIRS, but they would be indirectly measurable through the effects of CBF on CBVτd = 1 s) would contribute a frequency-dependent phase lag (ωτd) that takes a value of 18° at 0.1 Hz.While our interpretation of the phase lag of [HbT] vs. ABP is related to the CBF dynamics and the π/2 phase lag of venous blood volume with respect to CBF oscillations, one may also consider a potential role of the propagation time of arterial blood pressure and the blood transit time in the cerebral microvasculature. Even though we measure ABP on the subject’s finger, the propagation time of arterial pressure waves from the macrovasculature to the microvasculature is of the order of 10–100 μs ,48, indiKa)( (0.01 ± 0.01 μM/mmHg) was significantly lower than the mean value of Kv)( (0.09 ± 0.05 μM/mmHg), indicating a smaller change in arterial volume than in venous volume . The observed variability in Ka)( and Kv) with intra-subject variations . The relative arterial and venous contributions to hemodynamic changes associated with functional or physiological processes is an area of active research  and ABP oscillations on source-detector separation, thus supporting the validity of cortical measurements of [HbT] dynamics at a single source-detector distance of 3.5 cm .The chirp-like protocol for inducing cerebral hemodynamics with cyclic inflation and deflation of thigh cuffs can cover the same number of frequencies in less time than the spaced oscillation approach. Our initial results indicate a strong potential for the faster chirp-like experimental protocol, which has a number of practical advantages associated with its shorter duration. In this study, we assumed that the timing and duration of ABP oscillations in different protocols does not affect the transfer function between ABP and [HbT]. In our experience, [HbT] and ABP oscillations that are coherent with each other feature similar phase relationships under a variety of protocols, including spontaneous oscillations at baseline, and sequential or chirp-like induced oscillations. However, the insensitivity of the relative dynamics of coherent [HbT] and ABP oscillations is an important point that we intend to further validate and demonstrate in future studies.We have reported a human study of the dynamic relationship between cerebral hemoglobin concentration  and systemic arterial blood pressure (measured with finger plethysmography). Specifically, we generated a theoretical transfer function to describe the frequency-dependent relationship between [HbT] and ABP oscillations, and we validated it experimentally in the frequency range 0.04–0.20 Hz, as well as at the heart rate (~1 Hz). Our results are consistent with two mechanisms of [HbT] oscillations, one directly due to ABP oscillations  and one due to ABP-driven oscillations in CBF (affecting the venous compartment and dominating at low frequency below ~0.1 Hz). According to this interpretation, NIRS measurements of [HbT] reflect the autoregulatory CBF response, at least in the low-frequency range of about 0.1 Hz or below. Consequently, this study sets the stage for a new approach to optical measurements of cerebral autoregulation, on the basis of robust measurements of [HbT] and ABP dynamics.S1 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S2 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S3 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S4 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S5 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S6 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S7 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S8 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer functions for eight channels.(XLSX)Click here for additional data file.S9 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S10 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S11 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S12 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S13 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S14 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S15 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S16 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S17 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S18 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S19 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S20 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S21 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.S22 DatasetTime traces of pneumatic cuff pressure, heart rate, arterial blood pressure, Δ[HbT] and ABP-[HbT] transfer function for one channel.(XLSX)Click here for additional data file.


There are many risk factors contributing to glaucomatous optic neuropathy. Beside increased intraocular pressure, vascular factors play a prominent role, particularly low blood pressure (BP), and vascular dysregulation. Both of them are essential components of the Flammer syndrome. The aim of this retrospective study was to evaluate whether in glaucoma patients there is a relationship between vascular dysregulation and the BP.Medical records of 57 unselected glaucoma patients were retrospectively studied.p = 0.028) and diastolic BP (p = 0.036). The regression analysis revealed also a significant inverse relationship between the duration of blood flow cessation and the systolic (p = 0.025) and diastolic BP (p = 0.016). After adjustment for age, gender, use of antihypertensive therapy, and excluding patients taking calcium channel blockers, the relationship was still significant for systolic (p = 0.025) and diastolic BP (p = 0.003).Based on the outcome of the capillaroscopy, patients were divided in a group of patients with vascular dysregulation, also called long-stoppers (flow cessation for 13 s or more), and a group of patients with normal vascular regulation, also called short-stoppers (flow cessation for 12 s or less). BP was significantly lower in the group of long-stoppers than in the group of short-stoppers. This applies for both systolic  and low BP are statistically related. This is in line with the observation that Flammer syndrome subjects have both primary vascular dysregulation and low BP and that Flammer syndrome is a risk factor for glaucomatous optic neuropathy, at least in normal tension glaucoma patients. The detection of vascular factors in glaucoma patients may lead to a more efficient treatment, better tailored to the individual patient. There is growing evidence that besides intraocular pressure (IOP), vascular factors are also involved in the pathogenesis of glaucomatous optic neuropathy (GON) . Two vasPrimary vascular dysregulation mainly involves the microcirculation ; therefoThese vascular factors are becoming increasingly important as the proportion of NTG in glaucoma increases. A recent update on the prevalence, etiology, diagnosis, and monitoring of NTG revealed that the proportion of NTG varies between countries from 30 to 90% .The goal of this retrospective study was to test the relationship between vascular dysregulation and BP , 5, 13 iWe retrospectively studied the medical records of 57 glaucoma patients (35 women and 22 men) referred to the Department of Ophthalmology at University Hospital Basel, Switzerland, and aged between 17 and 92 years. Glaucoma was diagnosed if typical glaucomatous excavation of the optic nerve head and corresponding visual field defects were present. Each patient had a documented comprehensive ophthalmologic evaluation with the following examinations: slit lamp, funduscopy, best corrected visual acuity, and IOP, as well as a nailfold capillaroscopy and BP measurement.Ethical approval for the study project was obtained from the local medical ethics committee “Ethikkommission Nordwest- und Zentralschweiz/EKNZ” (EKNZ: BASEC 2016-00531). The study was designed and conducted in accordance with the tenets of the Declaration of Helsinki.The nailfold capillaries were studied using a light microscope  attached to a television monitor, which was coupled to a video recorder. The television pictures depicting blood flow in the capillaries were videotaped and analyzed afterwards. The examinations were performed in a room with a constant temperature of 23 °C. Before the examination, the patients were acclimatized in this room for 30 min.The skin of the nailfold was made transparent using a drop of oil. The blood flow in the capillaries running parallel to the skin surface was observed. After the baseline blood flow recording, the nailfold area was cooled for 60 s by blowing decompressed carbon dioxide of approximately − 15 °C over the nailfold  For clinical purposes, blood flow standstill between 0 and 12 s was considered normal , and theBP was measured directly before capillaroscopy using an Omron blood pressure monitor .p values correspond to the Kruskall-Wallis test (for median) and chi-squared test. In order to predict systolic or diastolic BP from mST or “stop-time group”, linear mixed-effects models were performed. mST was log-transformed to achieve more symmetric distribution. Mixed-effects models are suitable for analyzing repeated measurement data (here data from the left and right eyes). Results were adjusted for age, gender, use of antihypertensive therapy, and excluding patients under calcium channel blockers. Results are presented as mean differences between “stop-time groups” with 95% confidence intervals and p values. Using log (mST) as a predictor, only p values were reported. A p value < 0.05 was considered significant. All evaluations were conducted using the statistical software R version 3.1.1  for metric variables. Overall on 3.1.1 .p = 0.57). Glaucoma patients taking antihypertensive treatment had a significantly higher systolic BP  despite treatment (differences in diastolic BP were not significant).Among our glaucoma patients, 34 (60%) were short-stoppers and 23 (40%) were long-stoppers. Among the short-stoppers were 21 women (61.8%) and 13 men (38.2%). Among the long-stoppers were 14 women (60.9%) and 9 men (39.1%). The median IOP was 13.0  mmHg in long-stoppers and 13.5  mmHg in short-stoppers; the difference was not statistically significant  and diastolic BP . The results are depicted in Fig. p = 0.025) and diastolic (p = 0.016). The longer the standstill in the nailfold capillaries, the lower the systolic and diastolic BP. After adjustment for age, gender, use of antihypertensive therapy, and excluding patients taking calcium channel blockers, the relationship was still significant for systolic (p = 0.025) and diastolic BP (p = 0.003).BP was significantly lower in long-stoppers than in short-stoppers. This applies to both systolic  and low BP are statistically related. This is in line with the observation that subjects with Flammer syndrome have both primary vascular dysregulation and low BP and that Flammer syndrome is a risk factor for GON, at least in NTG patients. Examining vascular aspects in glaucoma patients, such as BP and quantification of regulation of blood flow, may lead to a more efficient treatment tailored to the patient and prevent progression of glaucoma damage, especially in NTG patients. Targeted predictive vascular diagnostics may lead to better recognition of patients with increased risk. This may ultimately lead to a more personalized treatment.


Arterial hypertension is a common finding in patients with neurofibromatosis (NF) type 1. Renovascular hypertension due to renal artery stenosis or midaortic syndrome could be the underlying cause. We report the case of a 4-year-old girl with NF type 1 and midaortic syndrome whose changes in blood pressure and pulse wave velocity suggested the evolution of vasculopathy, diagnosis of renovascular hypertension, and provided insights of response to treatment. Hypertension persisted after percutaneous transluminal angioplasty in the abdominal aorta, requiring escalation of antihypertensive treatment, while arterial stiffness demonstrated a mild decrease. Regular assessment of blood pressure using ambulatory blood pressure monitoring and noninvasive assessment of arterial stiffness may enhance the medical care of patients with NF type 1. Arterial hypertension is a common finding in patients with neurofibromatosis (NF) type 1 with a reported prevalence up to 20% . HyperteArterial stiffness is a general term used to describe the elasticity or compliance of the arteries . The patWe report a case of refractory hypertension accompanied with increased arterial stiffness in a female toddler with NF type 1 and midaortic. We describe changes in office, ambulatory blood pressure (BP), and cf-PWV during follow-up visits suggesting evolution of acquired vasculopathy, diagnosis of renovascular hypertension, and provided insights of response to treatment.We report the case of a 4-year-old girl, who was diagnosed with NF type 1 at the age of 14 days. Her mother and her older brother also suffer from NF type 1. During the annual follow-up at the age of 2.5 years, she had office BP levels below the 90th percentile (p.c.) for age, sex, and height . A routine ambulatory blood pressure monitoring (ABPM) showed a nondipping profile with normal mean BP levels  .One year later, at the age of 4 years, her office BP was greater than the 95th p.c., and a difference of 20 mm Hg between upper and lower extremities was documented . ClinicaOn her follow-up visit 4 months after PTA, there was no difference in BP between the upper and lower extremities, and pulses were present on both sides. Office BP levels presented a decrease but remained greater than the 95th percentile. Moreover, 24 h BP increased and cf-PWV was further increased, despite pharmacological treatment with amlodipine, furosemide, and atenolol. Clonidine was subsequently added to treatment. On the other hand, renal function was significantly improved. Both MRA and CTA showed a moderate improvement of the anatomical structures with abdominal aorta stenosis ranging between 0.35 and 0.5 cm, while other findings remained constant.During her next follow-up visit, 8 months after PTA, renal function was further improved, and the patient presented significant reduction of ambulatory BP levels and a reduction in cf-PWV values despite sustained office BP elevation . HoweverWe present a case of refractory hypertension in a toddler with NF type 1 and midaortic syndrome. The diagnosis of hypertension due to midaortic syndrome in our patient was an incidental finding. Severe symptoms associated with BP elevation have been reported in cases series of children with midaortic syndrome . The earNeurofibromatosis type 1 has been reported as being the most common genetic condition associated with midaortic syndrome . TummoloThe correlation between arterial BP and arterial stiffness has already been well documented in previous pediatric studies , 7. In tRegular BP assessment enables early diagnosis of hypertension in genetic conditions with high prevalence of midaortic syndrome, which recent studies show to present in younger ages than initially reported , 8. FurtIn conclusion, renovascular hypertension in NF type 1 may have significant adverse effect on arterial stiffness event with short duration of HTN. Regular assessment of BP using ABPM may enhance the medical care of patients with NF type 1 during regular assessment for the diagnosis of cardiovascular complications and guide further management. The use of more noninvasive techniques including cf-PWV could further add on the prognosis and evaluation of therapeutic outcome in patients with refractory hypertension.


Background: Hypertension is one of the most significant and common risk factors for cardiovascular disease, yet it remains poorly controlled in China. This study aims to examine trends and socioeconomic inequalities in the management of hypertension between 2011 and 2015 in China and to investigate the association between antihypertensive medication treatment and reduction of blood pressure, using nationally representative data. Methods: Concentration curve and concentration index were used to assess socioeconomic-related inequalities in hypertension care and health service utilisation. The fixed-effects analysis was performed to measure the impact of medication treatment on reduction of blood pressure among people with hypertension by using linear regression models. Results: Among hypertensive individuals, there were growing trends in the rates of awareness and treatment from 55.87% and 48.44% in 2011, to 68.31% in 2013 and 61.97% in 2015, respectively. The proportion of hypertension control was still below 30%. The fixed-effects models indicated that medication treatment was statistically significant and associated with the patients’ systolic blood pressure  and diastolic blood pressure . Conclusions: China has made good progress in the hypertension diagnosis, medication treatment and coverage of health services over the last 10 years; however, pro-rich inequalities in hypertension care still exist, and there is considerable progress to be made in the prevention, treatment and effective control of hypertension. In the era of sustainable development goals (SDG), advancing universal health coverage (UHC) has become the centrepiece of health policy in many countries . In thisPrevious studies reported the degree of diagnosis, treatment and control of hypertension in China ,6, but mIn this study, trends and socioeconomic inequalities were evaluated in healthcare and control of hypertension between 2011 and 2015 in China. Additionally, the association between antihypertensive medication treatment and reduction of blood pressure, using a nationally longitudinal dataset, was investigated, controlling for changes in treatment status for different periods.Data from baseline and follow-up surveys in the China Health and Retirement Longitudinal Study (CHARLS) undertaken in 2011, 2013 and 2015 was utilised. This study aimed to collect a nationally representative sample of Chinese residents aged 45 and over to inform scientific research on the elderly and to assess health trends. The CHARLS design, based on the Health and Retirement Study (HRS) and other related ageing surveys, has received funding support from Peking University, the Behavioural and Social Research Division of the National Institute on Aging, and the World Bank .The CHARLS’ questionnaires cover the following domains: demographics, health status and functioning, healthcare and insurance, income and consumption, and several important biomarkers including height, weight and blood pressure. In CHARLS, each respondent's systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded three times by a trained nurse using a HEM-7112 electronic monitor. The average value for each study participant was calculated, but only given to the subjects once the interviews were completed. The interviewees were asked if they had hypertension and whether they were receiving any form of antihypertensive treatment. Details on how blood pressure measurements were taken in the CHARLS survey can be found elsewhere .To ensure a representative sample, the CHARLS baseline survey covered 150 counties/districts and 450 villages/urban communities, across 28 provinces, by using multistage stratified probability-proportionate-to-size (PPS) sampling. A total of 17,708 individuals in 10,257 households were successfully interviewed for the baseline CHARLS survey. The response rate was over 80% in all age-eligible households. Ongoing follow-up surveys were conducted every two years [After excluding cases with missing demographic information and blood pressure measurements, complete data were available for 13,725 individuals in 2011, 10,893 individuals in 2013, and 11,675 individuals in 2015. The three rounds of the CHARLS datasets were used to calculate the prevalence of hypertension and healthcare indicators for the different years. To measure the impact of medication treatment on blood pressure (BP), this research also created a panel dataset including 8,486 hypertensive individuals who could be identified in all rounds of the CHARLS by excluding the loss to follow-up and the deceased in 2013 and 2015.In this study, hypertension was defined as survey participants having systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or their being on antihypertensive medication treatment for raised blood pressure ,12. AmonThe prevalence of hypertension and rates of awareness, treatment and control amongst Chinese adults were calculated. The Chi-square trend test was used to evaluate the difference in trends in the prevalence of hypertension, healthcare utilisation and blood pressure control from 2011 to 2015. Concentration Curve (CC) and Concentration Index (CI) were used to assess socioeconomic-related inequalities in hypertension care and service use. The further the CC lies from the equality line (45-degree line), the higher the degree of inequality in healthcare and health service utilisation .CI to measure socioeconomic inequalities in healthcare and control for hypertension according to the following equation:h refers to the variable in healthcare; μ is the mean of h; and r refers to the fractional rank of people according to the per capita household consumption expenditure (PCE), from the poorest to richest. A positive CI value shows that healthcare or service use is more likely in those in a higher socioeconomic group, and a negative CI value shows that underprivileged people are more likely to use health services or to be controlled well. Similar to the concentration curve, the higher the absolute value of CI, the worse for those with lower socioeconomic status. Zero indicates no socioeconomic inequality in hypertension care [The concentration index can quantitatively reflect the degree of equality. This study calculated ion care .p values less than 0.05 were considered statistically significant.Given that treatment adherence and the within-person blood pressure can easily change over time, fixed-effects models (FEM) were performed to measure the impact of medication treatment on the reduction of blood pressure among those with hypertension by using linear regression analysis. The patients’ SBP and DBP were included in regression models as outcome variables. The explanatory variables of interest were age, per capita household consumption expenditure, Body Mass Index (BMI), comorbidity, current smoking and alcohol consumption. Correlates of hypertension treatment were analysed using the FEM, after controlling for demographic characteristics. In addition to estimating the main effects of the treatment on blood pressure, interaction effects were examined by introducing the interaction term of treatment and some core variables, including PCE, BMI and comorbidity. Considering the potential systematic error caused by sampling design and missing values, both the weighted and unweighted proportions for key variables of hypertension management were reported in descriptive results, using the weighting codes created by the CHARLS team . All staOverall, the prevalence of hypertension among adults in China aged 45 and above was approximately 40.78% in 2011, 43.25% in 2013 and 41.81% in 2015 . Among pFor the utilisation of health services, The results of socioeconomic-related inequality analyses for healthcare among patients with hypertension are shown in The concentration curves for hypertension care were below the equality line, indicating that hypertension care and the use of health services were disproportionately higher among wealthy individuals in China in 2015. In terms of hypertension management, the worst indicator of pro-rich inequality was the control of blood pressure . RegardiThis study demonstrates that the utilisation of consistent and regular medical treatment has improved the effective control over individuals with hypertension over time. This pattern is likely to reflect the successful implementation of recent policies and the intended outcomes of new health system reform which aim to achieve universal health coverage with affordable and equitable primary healthcare ,16. SincThis study showed a relatively high and stable prevalence of hypertension among middle-aged and elderly Chinese, with a downward turning point appearing in 2015. Meanwhile, it also reported an increased rate of hypertension awareness, treatment and control. The effective management of hypertension among the middle-aged and elderly is generally attributed to the implementation of the NPHI, which started in 2009 and aims to offer equitable essential public health services for all Chinese people, including hypertension and diabetes screening, standard management and health education .At the same time, the essential medicine system (EMS) was also rolled out across the country. This aims to improve medication access, quality and appropriate use, and this policy has benefited the majority of patients with hypertension, diabetes and some other NCDs ,20. ThroOverall, a substantial upward trend in health service utilisation was observed among Chinese adults with hypertension between 2011 and 2015. The new health system reform in China played a significant role in promoting this trend . The natImprovements in health insurance policies over the past few years have also played a positive role in hypertension management. The health system reform resulted in a significant increase in insurance coverage, with 95.7% of the Chinese population being covered by public health insurance schemes in 2011 . Along wThe experiences of several developing and developed countries have demonstrated the relationship between insurance and healthcare ,30,31,32This study revealed that the blood pressure of hypertensive patients was higher in people without medication than among those who reported the use of antihypertensive medication. Although the performance of hypertension management has been reported in China on several occasions ,41,42,43The reality of two-thirds of hypertensive patients experiencing uncontrolled blood pressure is likely to be the result of inconsistent, inadequate treatment or insufficient quality of health service provision. Though the NPHI was developed to ensure optimal management of hypertension and diabetes for Chinese adults aged 35 and above, the inconsistent and uncoordinated primary care delivery system, lack of qualified physicians and public health workers and absence of effective surveillance system handicapped the implementation of the NPHI . A surveThis study suggested levels of hypertension awareness, treatment and control tended to be higher among wealthier individuals in China, while a similar pro-rich distribution of health service use was observed, particularly the inpatient visit. The economic-related inequalities were consistent with previous findings regarding hypertension detection and treatment in China ,46, BrazA good degree of hypertension care and control is unlikely to be achieved unless the universal healthcare and public insurance coverage can be further strengthened to improve access to both primary care and essential medications for all . In 2019This is the first study in China to apply fixed-effects models in examining the impact of antihypertensive medication on reductions in blood pressure, considering the change of treatment status in different periods. This research will contribute to a deeper understanding of reform policies related to primary healthcare and public health services, and further analysis of the effectiveness of NCD treatment. This study only considered the middle-aged and older population in China, however. The effectiveness of hypertension treatment for younger Chinese groups should be considered in future studies. Some 20% of respondents were missing information on blood pressure during the surveys from 2011 to 2015. To account for nonresponse bias, we adjusted the analysis by using the created weights for individuals.China has made good progress in the identification of people with hypertension, in medication treatment and in coverage of health services over the last 10 years. Between 2011 and 2015, China also saw a significant increase in the use of inpatient care services and access to health education related to lifestyle behaviours among hypertensive patients. This pattern reflects the implementation of recent policies. Despite these advances, fewer than a third of Chinese adults with hypertension were in control of their blood pressure, and pro-rich inequalities in the hypertension care and service use exist. China still needs to make more progress with respect to prevention, and to ensure more effective treatment and control of hypertension.


The prevalence of non-communicable diseases, and associated morbidity and mortality, is increasing rapidly in low and middle-income countries where health systems often have limited access and lower quality of care. The intervention was to decentralise uncomplicated non-communicable disease (NCD) care from a hospital to nurse practitioners in health centres in a poor rural district in Eswatini, southern Africa. The objective of this study was to assess the feasibility and impact of decentralised care for NCDs within nurse-led clinics in order improve access and inform healthcare planning in Eswatini and similar settings.In collaboration with the Eswatini Ministry of Health, we developed and implemented a package of interventions to support nurse-led delivery of care, including: clinical desk-guide for hypertension and diabetes, training modules, treatment cards and registries and patient leaflets. Ten community clinics in the Lubombo Region of Eswatini were randomly selected to be trained to deliver NCD care for a period of 18 months. Observational data on follow-up rates, blood pressure (BP), glucose etc. were recorded and evaluated. We compared blood pressure and blood glucose measurements between the first and fourth visits and fitted a linear mixed effects model.One thousand one hundred twenty-five patients were recruited to the study. Of these patients, 573 attended for at least 4 appointments. There was a significant reduction in mean BP among hypertensive patients after four visits of 9.9 mmHg systolic and 4.7 mmHg diastolic (p = 0.01), and a non-significant reduction in fasting blood glucose among diabetic patients of 1.2 mmol/l (p = 0.2). Key components of NCD care were completed consistently by nurses throughout the intervention period, including a trend towards patients progressing from monotherapy to dual therapy in accordance with prescribing guidelines.The findings suggest that management of diabetes and hypertension care in a rural district setting can be safely delivered by nurses in community clinics according to a shared care protocol. Improved access is likely to lead to improved patient compliance with treatment. Non-Communicable Diseases (NCDs) are responsible for 40.5 million deaths globally each year, equivalent to 71% of all deaths . NCD carEswatini (formerly Swaziland) is a country with a population of 1.1 million people in Southern Africa . SimilarTraditionally, NCD care in Eswatini has been provided using a centralised model, with the majority of care provided by hospitals. Patients have limited access and commonly present late with symptoms of complications. Hospital services are working at full capacity, with little room for expansion. With increasing burden on hospital resources caused by HIV and now the ‘double burden’ of NCDs, this model of care is no longer sustainable. Neighbouring South Africa has worked to control NCDs through health systems strengthening , moving The study was conducted within the Lubombo region of Eswatini, a recently drought-stricken area with a high rate of extreme poverty. Lubombo is a predominantly rural region with a population of 212,500 and one of the highest prevalence rates of HIV in the world with 29% of those aged 15 and over infected with HIV . The regCurrently GSH has one clinic specifically for diabetes/hypertension, run by a team of nurses and assistants. The community clinics provide hypertensive and diabetic services on an ad hoc basis. Some community clinics provide a refill service for these medications, though supplies are inconsistent and access for patients to NCD medication is unreliable. A few community clinics have a doctor visit once a month to attend to patients for diagnoses and complications. Prior to the study, community clinic staff had not received specific training/ guidance on the management of NCDs. GSH is currently responsible for supervision and support of 18 clinics in Lubombo. This pilot project and prospective cohort study was designed to decentralise NCD care from a regional hospital to nurse-led community clinics in the rural Lubombo region. The objective of this study is to assess the feasibility and impact of decentralised care for NCDs within nurse-led clinics in the Lubombo region, Eswatini, in order improve access and inform healthcare planning in Eswatini and similar settings.This observational study began with preparatory work to ensure the clinics were equipped with necessary equipment including a weight scale, BP machine and glucometer to diagnose and treat type II diabetes and hypertension, along with patient information leaflets. We developed a treatment guideline in the form of a desk guide for cardiovascular disease, diabetes and hypertension, which dealt with: primary prevention, identification and screening, diagnosis, education, treatment and referral. The desk guide describes different thresholds for blood pressure control for patients with only hypertension (140/90 mmHg) compared to patients who also have diabetes (130/80 mmHg). The desk guide states a target fasting blood glucose of 7 mmol/l for effective glycaemic control. We developed and administered a 3.5-day skill-based and interactive, training programme for clinic nurses, which covered all elements of the desk guide including data collection, and was based around a combination of lectures, demonstrations and interactive case study based clinical role-plays. The Chief Pharmacist and national pharmaceutical dispensary made provisions to allow distribution of anti-hypertensive and anti-diabetic medications by trained nurse-practitioners. Clinics were provided with the following data collection tools: patient-held heath record card, client-held health record card, enrolment register, and annual review card.The patients enrolled in the study were recruited from community clinics based on their health status; being diagnosed with Type II diabetes mellitus (DM), hypertension (HTN), or cardiovascular disease (CVD) in accordance with the International Classification of Diseases criteria. Patients with Type I or Type II diabetes requiring insulin were excluded from the study.The following information was collected at baseline and during each follow up visit as appropriate: demographics , weight, waist circumference, blood pressure (BP) readings, random/fasting blood glucose readings (RBG and FBG respectively), HIV and TB status, medicines prescribed, and any other conditions the patient may have.p-values and calculated confidence intervals via the profile likelihood method.We described the baseline characteristics and the trend in health indicators over time, specifically: mean and standard deviation (sd) of systolic and diastolic blood pressure, the proportion of blood pressure readings above diagnostic and safety thresholds, and fasting blood glucose, and completion of routine clinical tasks. We compared blood pressure and blood glucose measurements between the first and fourth visits and fitted a linear mixed effects model with the difference in magnitude between the first and fourth visit as the outcome (dependent) variable and a random intercept for the clinic, to assess whether any change was significant, while accounting for the clustered nature of the data. We used the Kenward-Roger approximation to get approximate degrees of freedom for the t-distribution to get Verbal consent for inclusion in the study was obtained from participants on enrolment. As an operational research study, the project was focused on the service outcomes and it was not proposed that written consent be requested from individual patients to secure their participation. This study was approved by the Leeds University Faculty of Medicine and Health Research Ethics Committee and the Eswatini National Health Research Review Board.A defined six-month period for enrolment allowed for recruitment of sufficient numbers and the establishment of decentralisation at intervention clinics. Data collection was complete 12 months after enrolment. The total study duration was therefore 18 months (6 months recruitment + 12 months’ follow-up). One thousand one hundred twenty-five patients were recruited to the intervention clinics in total 923 (82%) had hypertension alone, 68 (6%) had diabetes alone and 134 (12%) had both diabetes and hypertension  seen over four visits.Table p = 0.01) (Table The mean systolic BP for this cohort on enrollment was 149 mmHg (range 90–259 mmHg). By Visit 4 this had fallen to 139 mmHg (range 88–240 mmHg). Mean diastolic BP was 88 mmHg (range 41–134 mmHg) on enrolment and fell to 81 mmHg (range 50–123 mmHg) by Visit 4. The change in both systolic and diastolic blood pressure in this group was statistically significant  and seen for at least four scheduled visits.The treatment target for diabetic patients with hypertension is 130/80 mmHg. Table p = 0.04). At baseline, the proportion of diabetic patients failing to reach the target threshold for SBP (130 mmHg) was 75%, falling to 58% by Visit 4. The proportion having poor DBP control also improved from 63 to 47%. Only small numbers of diabetic patients exceeded the safety threshold (180/110 mmHg). The overall proportion with SBP greater than 180 fell from 10 to 3.9% between Visit 1 to 4.Average SBP readings were similar to those seen in the hypertension cohort; ranging from systolic 148 mmHg at Visit 1 (100–218 mmHg) to 139 mmHg at Visit 4 (108–194 mmHg) and diastolic 86 mmHg at visit 1 (41–131 mmHg) to 81 mmHg at visit 4 (59–109). Table n = 122 who attended four visits or more. The mean fasting blood glucose for this cohort on enrollment was 9.6 mmol/l (range 4.2–22 mmol/l). By Visit 4 this had fallen slightly to 8.9 mmol/l (range 4.4–25.3 mmol/l). This change was not statistically significant (p = 0.2). There were fewer observations for fasting blood glucose which was not assessed as regularly as blood pressure.Fasting blood glucose (FBG) was the diabetic parameter most frequently recorded in this intervention. Table Fasting blood glucose readings over 10 mmol/l indicate poor control. The proportion of these readings reduced from 40% at baseline to 31% after four visits.Studying the defined cohort of 573 patients who attended four or more visits allows patterns in the usage of medication for diabetes and hypertension to be analysed. The Desk Guide states that patients should be started on Metformin and have a Sulfonylurea  added if control is poor (or if Metformin cannot be tolerated). At baseline, 17 patients (17%) of diabetic patients on medication were on Metformin only, compared to 8.1% on Glibenclamide only and 79% taking both Metformin and Glibenclamide. The numbers on dual therapy increased slightly over the course of the intervention. By visit 4, 83 diabetic patients (82%) were on both Metformin and Glibenclamide.Data was also captured on process indicators describing how closely the delivery of the intervention met the standards outlined in the Desk Guide. The Desk Guide advised that patients should attend community clinics for monthly reviews. For each NCD visit nurses were expected to provide health education and to complete tasks including weight and BP checks  and blood glucose (diabetic patients).The completion of routine tasks required by the intervention is illustrated in Table Table A large cohort of patients were found to have improving trends on average with treatment in all physiological parameters  over four visits. A statistically significant reduction in blood pressure was observed between the first and fourth visits among hypertensive patients with and without diabetes, however no significant change in blood glucose was observed and a significant proportion of patients remained above targets at follow-up. BP was checked in nearly all patients at all visits. Glucose was checked at more than 2/3rds of diabetic patient visits (though a lower percentage in visit 3 for unknown reasons). Health education was given to the large majority of patients, especially at the first visit when care was initiated. Medication usage demonstrates that patients’ drug/doses and were ‘stepped-up’ during the period, as recommended by the Desk Guide, with a trend towards the combination regimes. The process indicators demonstrate the ability of nurses in community clinics to successfully deliver the components of NCD care.This study adds to the evidence base of similar health system interventions in low and middle-income countries. Recent experience in Pakistan developing case management packages played an important role in helping to prioritise diabetes, hypertension, CVD, asthma and chronic obstructive pulmonary disease prevention across Punjab Province, leading to better provincial planning and budgeting and demonstrating that primary and secondary public health facilities can effectively deliver integrated NCD care in a developing country context –13. ThosThere were several operational challenges that arose and lessons can be learned from these for future service developments. Despite the agreement to allow clinics to order drugs, there were still problems with organising distribution to the community clinics, which incurred long periods of stock outs. There were often issues with transportation, specifically availability of vehicles and accessibility as many community clinics are not located on roads that are well-paved, with greater difficulty after heavy rainfall. Community clinic nurses have many other duties, such as child health, limiting their attention to diabetes and hypertension care. Specialist nurse supervision from the hospital helped to maintain enthusiasm for the intervention among the stakeholders, but it was challenging to sustain these visits at the necessary frequency. Patients with abnormal parameters or poor response to treatment were required by the protocol to be reviewed by a hospital doctor. This was an access a barrier which resulted in some patients remaining on sub-optimal treatment. This barrier could be overcome if, as for HIV and TB services in Eswatini, doctors visit and see complex cases at the community clinics.The observational nature of the data means that no firm conclusion can be drawn as to whether care under the new model is better or worse than current practice. The change in blood pressure between the first and fourth visits was statistically significant, but regression to the mean cannot be ruled out. There were significant losses to follow up, which may have been due to patients declining further treatment or seeking treatment elsewhere or may have also been an apparent loss due to poor record keeping. There is a risk of bias due to differential loss to follow up, where the least healthy or compliant patients drop out or keep poorer records, meaning the final sample may not be representative of the general population. There was consistent rotation of nursing staff on the local level presenting challenges. The geographical remoteness of the clinics meant central monitoring of these processes was challenging. The style of recording patient information in Eswatini involves medical staff writing signs, symptoms, vital statistics, diagnoses, and prescriptions in a patient-held notebook, which the patient keeps together with any other clinical documents. These patient-held records may have been well utilised, along with the patient-held cards used in the study, however, because these were kept by the patient, it was not possible to include their data. Given the limitations of this study design, further studies would be necessary to provide stronger evidence of benefit, perhaps including a ‘routine care’ control group. That said, the model proved to be feasible and accessibility of care was improved, and these results add to the evidence base supporting the decentralisation of NCDs in similar settings.These findings suggest that decentralization of care for NCDs in low resource settings is feasible and associated with improvements in physiological parameters, though continued training and supervision are required to embed change. Nurses in participating community clinics in Lubombo are now better equipped to recognise and correctly diagnose hypertension and diabetes, and they can initiate treatment and follow up uncomplicated patients. They are also able to follow up and monitor more complex cases and provide refills of drugs normally only available in hospital. Finally, they are using a record keeping system that will help with follow-up care and identify loss to follow-up or treatment failure, though the quality of recording has deteriorated, and further support and supervision is needed to improve this.


General anesthesia induction with the initiation of positive pressure ventilation creates a vulnerable phase for patients. The impact of positive intrathoracic pressure on cardiac performance has been studied but remains controversial. 3D echocardiography is a valid and MRI-validated bed-side tool to evaluate the right ventricle (RV). The aim of this study was to assess the impact of anesthesia induction  with positive pressure ventilation  on 2D and 3D echocardiography derived parameters of RV function.A prospective observational study on fifty-three patients undergoing elective cardiac surgery in a tertiary care university hospital was designed. Transthoracic echocardiography exams were performed before and immediately after anesthesia induction and were recorded together with hemodynamic parameters and ventilator settings.p = 0.0013) as well as the Tissue Doppler derived tricuspid annulus peak velocity (TDITVs’) were significantly reduced , but global right ventricular ejection fraction  and right ventricular stroke volume  did not change.After anesthesia induction TAPSE (mean difference − 1.6 mm (95% CI − 2.6 mm to − 0.7 mm; This data shows a preserved right ventricular ejection fraction and right ventricular stroke volume after anesthesia induction and initiation of positive pressure ventilation. However, the baso-apical right ventricular function is significantly reduced. Larger studies are needed in order to determine the clinical impact of these findings especially in patients presenting with impaired right ventricular function before anesthesia induction.NCT02820727.Retrospecitvely registered, 6th June 2016, ClinicalTrials.gov Identifier  Anesthesia induction and initiation of intermittent positive pressure ventilation (IPPV) can lead to hemodynamic impairment due to several factors. IPPV is a key element of general anesthesia that is routinely used for major surgical procedures and as part of intensive care treatment provided to critically ill patients. The impact of positive intrathoracic pressure during IPPV and positive end expiratory pressure (PEEP) on the circulatory system has been studied and well described , 2. The Two-dimensional (2D) transthoracic echocardiography has been used as a standard imaging modality to evaluate both cardiac dimensions and functions as well as inferior vena cava (IVC) diameters during varying levels of intrathoracic pressure in different clinical settings , 8. Due To the best of our knowledge, this is the first study explicitly examining the effects of anesthesia induction and positive pressure ventilation on right ventricular function using 3D echocardiography. The specific aim of this prospective observational study was to examine the effects of anesthesia induction and IPPV on conventional 2D-echocardiography and 3D-echocardiography-derived determinants of right ventricular function in patients scheduled for cardiac surgery.n = 52. During the study period from 11/2015 to 11/2016, 554 adult patients above the age of 18 years who were scheduled for elective cardiac surgery at a tertiary care university hospital were screened for possible inclusion. The inclusion criteria were sinus rhythm and ability to give informed consent. Patients were only asked to give informed consent if an investigator capable of performing a comprehensive 3DE was available on the day of surgery. Right ventricular function was assessed by real time three-dimensional transthoracic echocardiography (TTE) immediately before anesthesia induction under spontaneous ventilation and as soon as possible after achieving hemodynamic stability after anesthesia induction and endotracheal intubation under controlled IPPV with constant PEEP. The study was performed according to the STROBE statement for observational studies [Approval of this prospective study  was given by the Institutional Review Board at the University Hospital Tübingen (IRB# 320/2015BO2). Sample size was calculated for comparing paired differences. The calculated sample size to achieve a power of 80% and a level of significance of 0.05 (two tailed), for detecting a 2 ± 5 mm change in TAPSE (effect size of 0.4) was 2O and a peak inspiratory pressure (Pinsp) to receive a tidal volume of 6-8 ml/kg was initiated, and the inspiratory oxygen fraction was titrated to individual demands to maintain a SpO2 between 95 and 99%. End-tidal carbon dioxide levels were maintained between 35 and 37 mmHg by adjusting the ventilation frequency. All hemodynamic parameters were recorded during the echocardiography studies.Standardized monitoring was applied in all patients. The patients were not premedicated. All patients received an arterial cannula for blood pressure monitoring before anesthesia induction. Midazolam (0.1–0.15 mg/kg), sufentanil (0.3–0.5 μg/kg) and rocuronium (0.5–1 mg/kg) were applied intravenously (i.v.) for anesthesia induction and endotracheal intubation and were followed by sevoflurane ) for anesthesia maintenance. As per institutional standard, intravenous volume was administered restrictively using isotonic crystalloid solutions with a maximum of 15 ml/kg prior to initiation of cardiopulmonary bypass in all patients. A target mean arterial blood pressure (MBP) of > 65 mmHg was maintained during anesthesia induction using a continuous i.v. infusion of noradrenaline as a first line agent to counteract hypotension based on the clinical requirements. Pressure controlled positive pressure ventilation with a standardized PEEP of 5 cm HA transthoracic real time 3DE study  was performed in all patients by two experienced echocardiographers, trained in performing 3D imaging of the right ventricle. Echocardiography loops were recorded before and after anesthesia induction from transapical windows. The study protocol consisted of a 2D transapical 4-chamber view and 3D full volume acquisitions including the whole right and left ventricle. The 3D full volume datasets were acquired using an ECG-gated 4 heart beats-technique with a short apnoeic phase maintaining PEEP. Hemodynamic parameters were allowed to stabilize prior to the TTE exam. Tricuspid annular plane systolic excursion (TAPSE) was measured in an apical 4-chamber view using M-mode on the lateral tricuspid annulus. Systolic apical movement velocity of the lateral tricuspid annulus (TDITVs’) was assessed using tissue Doppler imaging. All measurements were performed according to current ASE recommendations . All 3D p values < 0.05.The normal distribution of the variables was assessed using skewness, kurtosis and the Shapiro-Wilk’s tests. Continuous variables are reported as the mean values ± standard deviation. For echocardiographic and hemodynamic parameters, 95% confidence intervals of the mean are reported. Comparison of continuous variables between the different groups was performed using a Student’s t test. Variables that were not normally distributed are reported as median and interquartile ranges (IQR). Comparison of these variables was performed using the Wilcoxon Rank-Sum test. The values of the different time points were compared using a two-tailed paired T-test. Categorical variables are reported as percentages. Differences in the variables were interpreted as significant at To assess intra-observer reliability, 10 randomly selected datasets were analyzed by the initial investigator, blinded to the initial results, at a different time point. To calculate inter-observer reliability, 10 randomly selected datasets were assessed by a second investigator blinded for the results of the first investigator. Intraclass correlation coefficients (ICC) and corresponding 95% confidence intervals were calculated to assess intra-observer and inter-observer reliability.All statistical analyses were performed using the SAS JMP software  and IBM SPSS statistics .Fifty-nine patients gave informed consent to take part in this study. Three patients could not be studied due to changes in surgical planning, and three patients had a low imaging quality (stitching artefacts) insufficient for 3D volumetry. Fifty-three patients  were included into the final analysis.The median age of the patients was 64 years (IQR 55 to 75) having a median EuroSCORE II of 2.9% IQR 1.9 to 7.5). Further demographic data as weight, height, body-surface-area, body-mass-index (BMI), preoperative laboratory values  and the planned cardiac surgeries are given in Table .9 to 7.5The median level of the PEEP was 5 mbar, the median Pinsp was 15 (IQR 14 to 17) to obtain a TV of 7 ml/kg (IQR 6 to 8). Anesthesia induction agents are given in Table p = < 0.0001), systolic blood pressure  mmHg to 112 (SD 19) mmHg; p < 0.0001), diastolic blood pressure  mmHg to 57 (SD 11) mmHg; p < 0.0001) and mean blood pressure  mmHg to 78 (SD 12) mmHg; p < 0.0001).Hemodynamic variables are given in Table A summary of the echocardiographic parameters is given in Table p = 0.0013) . 3D-RVLS-fw also significantly decreased (− 22.9 (SD 6) % to − 21.4 (SD 5.9) %, p = 0.0366)  mm to 16 (SD 4) mm; 13) Fig.  b. The Tp = 0.4451), 3D-RVLS-fw , TAPSE  or TDITVs’ .There was no significant correlation between the noradrenaline dose and the change in RVEF  were categorized into the group with a normal RVEF, twelve patients with a median age of 72 (IWR 63 to 77) were categorized into the group with depressed RVEF.In both groups HR and MAP were significantly lower after anesthesia induction compared to the baseline values. RVEDV did not significantly change in either of the groups. In the group with a normal RVEF, all parameters reflecting RV function  worsened significantly (Table The ICC for the intra-observer reliability for the RVEDV was 0.924 (95% CI: 0.741–0.980), RVESV 0.847 (95% CI: 0.524–0.959), RVEF 0.984 (95% CI: 0.942–0.996), 3D-RVLS-fw 0.927 (95% CI: 0.749–0.981) and RVFAC 0.669 (95% CI: 0.143–0.905). The ICC for the inter-observer reliability for the RVEDV was 0.927 (95% CI: 0.737–0.981), RVESV 0.957 (95% CI: 0.839–0.989), RVEF 0.846 (95% CI: 0.497–0.959), 3D-RVLS-fw 0.834 (95% CI: 0.466–0.956) and RVFAC 0.662 (95% CI: 0.052–0.09.12).2O did not alter RV function [2O [Anesthesia induction with endotracheal intubation and consecutive positive pressure ventilation constitutes a vulnerable phase for the right ventricle. Increased pulmonary vascular resistance due to the formation of atelectasis, hypercapnia or hypoxia can lead to right ventricular afterload increases. Additionally, positive pressure ventilation is known to alter right ventricular filling pressures. One of the first reports in 1948 showed that intrathoracic pressure was inversely correlated with right ventricular filling pressures . Severalfunction . This fition [2O .In addition to the effect of mechanical ventilation, right ventricular function can be altered by hemodynamic changes, as well as the direct negative effects of anesthesia agents on right ventricular myocardial contractility. Propofol, for example, has been shown to alter systemic hemodynamic parameters without influencing the RVEDV or RVEF, measured by pulmonary artery catheter-based techniques , 25. MidTo date and to the best of our knowledge, no other study has comprehensively assessed established parameters of right ventricular mechanics and novel 3D echocardiographic parameters of right ventricular function during anesthesia induction and initiation of positive pressure ventilation. Right ventricular volume, quantified by the RVEDVI, and the RVEDAI did not change in our study. This is contrary to previously published results by Couture et al. that showed an increase in preload as measured by the RVEDA after anesthesia induction . PEEP ann = 12) additional larger studies in this specific patient collective are needed to confirm or falsify this finding.In a subgroup analysis we can show that patients with a normal RVEF at baseline experienced a significant decrease in the longitudinal myocardial contraction component accompanied by a small but significant reduction in RVEF. Interestingly, in the subgroup of patients with depressed RVEF (< 35%) no change of any of the RV parameters could be observed. This suggests that in patients with already reduced RVEF anesthesia and IPPV do not further worsen right ventricular myocardial function. Due to the small sample size of the subset , are significantly reduced despite stable loading conditions. The reduction in tricuspid annular movement might be directly associated with changes in intrathoracic pressures by the initiation of positive pressure ventilation. The longitudinal right ventricular myocardial contraction (3D-RVLS-fw) was also reduced in our patient population. In addition we showed that the ejection fraction assessed by 3DE also slightly decreased during anesthesia induction in a subgroup of patients presenting with a normal baseline RVEF but, however, stroke volume did not change.This study shows a decrease in longitudinal right ventricular function after anesthesia induction using sufentanil, midazolam and rocuronium and IPPV with currently recommended ventilator settings. In a group of patients with a normal baseline RVEF the RVEF also slightly decreased but RV stroke volume stayed stable. Despite the reduction in longitudinal function and the slight reduction in RVEF (mean − 3%) this effect seems not to be directly clinically relevant as the stroke volume remained stable. However, echocardiographers need to be aware that longitudinal RV function is depressed under anesthesia and intraoperative values should be cautiously compared to baseline measurements when judging RV function. Modern 3DE techniques especially 3D volumetry improve insights into right heart dimensions and function and enhance our understanding of anesthesia-related changes of ventricular function and physiology. Therefore, 3D echocardiography should be used to complement 2D echocardiographic examinations in the perioperative setting.Our data have several limitations. The patients included in our single-center study do not represent a healthy collective but a cross section through patients presenting in cardiac anesthesia with various underlying diseases. Unfortunately, we cannot report on the changes in right ventricular afterload in our patients. The results for the 2D echocardiography measurements of RV longitudinal function could be biased because some values were missing during data collection. Although overall changes are small, the sample size might have been too small to reach significance for some of the 3D-based echocardiography parameters. The assessment of different right ventricular contraction components – such as longitudinal and circumferential shortening - could not be performed but might have given further insights into complex alterations of the myocardial contraction patterns. We do acknowledge that we can only report on the initial changes in right ventricular function and cannot address if this effect is reversible after emergence from anesthesia. In addition, the 3D technology that we used is not yet available in a broad clinical setting.Our results suggest that tricuspid annular movement and longitudinal RV function decreases after anesthesia induction and positive pressure ventilation, while the stroke volume does not change. The latter finding questions the clinical relevance of the small changes seen. Further investigations are necessary to confirm this finding, especially in patients with a depressed baseline RVEF and during anesthesia induction with other anesthetics or different ventilator settings.