Hemodynamic Control of Endothelial Cell Fates in Development.

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. From the onset of blood flow, the embryonic vasculature is continuously exposed to a variety of hemodynamic forces. These biomechanical stimuli are key determinants of vascular cell specification and remodeling and the establishment of vascular homeostasis. In recent years, major advances have been made in our understanding of mechano-activated signaling networks that control both spatiotemporal and structural aspects of vascular development. It has become apparent that a major site for mechanotransduction is situated at the interface of blood and the vessel wall and that this process is controlled by the vascular endothelium. In this review, we discuss the hemodynamic control of endothelial cell fates, focusing on arterial-venous specification, lymphatic development, and the endothelial-to-hematopoietic transition, and present some recent insights into the mechano-activated pathways driving these cell fate decisions in the developing embryo.

Whole-brain, gray, and white matter time-locked functional signal changes with simple tasks and model-free analysis.

Recent studies have revealed the production of time-locked blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. "Whole-brain" actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.

Toward precision brain health: accurate prediction of a cognitive index trajectory using neuroimaging metrics.

The goal of precision brain health is to accurately predict individuals' longitudinal patterns of brain change. We trained a machine learning model to predict changes in a cognitive index of brain health from neurophysiologic metrics. A total of 48 participants (ages 21-65) completed a sensorimotor task during 2 functional magnetic resonance imaging sessions 6 mo apart. Hemodynamic response functions (HRFs) were parameterized using traditional (amplitude, dispersion, latency) and novel (curvature, canonicality) metrics, serving as inputs to a neural network model that predicted gain on indices of brain health (cognitive factor scores) for each participant. The optimal neural network model successfully predicted substantial gain on the cognitive index of brain health with 90% accuracy (determined by 5-fold cross-validation) from 3 HRF parameters: amplitude change, dispersion change, and similarity to a canonical HRF shape at baseline. For individuals with canonical baseline HRFs, substantial gain in the index is overwhelmingly predicted by decreases in HRF amplitude. For individuals with non-canonical baseline HRFs, substantial gain in the index is predicted by congruent changes in both HRF amplitude and dispersion. Our results illustrate that neuroimaging measures can track cognitive indices in healthy states, and that machine learning approaches using novel metrics take important steps toward precision brain health.

Effects of an online mindfulness-based intervention on brain haemodynamics: a pilot randomized controlled trial using functional near-infrared spectroscopy.

Although many neuroimaging studies have evaluated changes in the prefrontal cortex during mindfulness-based interventions, most of these studies were cross-sectional studies of skilled participants or involved pre-post comparisons before and after a single session. While functional near-infrared spectroscopy is a useful tool to capture changes in the hemodynamic response of the prefrontal cortex during continuous mindfulness-based intervention, its ability to detect the accumulated effects of continuous mindfulness-based intervention is currently unclear. We investigated whether a 12-wk online mindfulness-based intervention changed the hemodynamic response of the prefrontal cortex during a verbal fluency task. Eighty-two healthy university students were randomly allocated to a 12-wk online mindfulness-based intervention group or a wait-list control group. The integral values of oxygenated hemoglobin measured using functional near-infrared spectroscopy before and after the intervention were compared to the values in the wait-list group. The intervention condition showed significantly greater functional near-infrared spectroscopy signal activation than the control condition; however, the effect sizes before and after the intervention were small. Thus, continuous mindfulness-based intervention could alter prefrontal cortex function, and functional near-infrared spectroscopy could be useful for measuring the accumulated effects of continuous mindfulness-based interventions. With a better understanding of the association between mindfulness and functional near-infrared spectroscopy signals, functional near-infrared spectroscopy can be used for biofeedback analyses.

Pathophysiology of Acute Kidney Frailty.

Acute kidney frailty is a premorbid condition of diminished renal functional reserve that predisposes to acute kidney injury; this condition results from subclinical wear or distortion of renal homeostatic responses that protect the renal excretory function. Knowledge of its pathophysiological basis is critical for the development of diagnostic and therapeutic strategies that allow for prophylactic intervention and disease prevention.

Refining hemodynamic correction in in vivo wide-field fluorescent imaging through linear regression analysis.

Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

An in silico study of the effects of cardiovascular aging on carotid flow waveforms and indexes in a virtual population.

Cardiovascular aging is strongly associated with increased risk of cardiovascular disease and mortality. Moreover, health and lifestyle factors may accelerate age-induced alterations, such as increased arterial stiffness and wall dilation, beyond chronological age, making the clinical assessment of cardiovascular aging an important prompt for preventative action. Carotid flow waveforms contain information about age-dependent cardiovascular properties, and their ease of measurement via noninvasive Doppler ultrasound (US) makes their analysis a promising tool for the routine assessment of cardiovascular aging. In this work, the impact of different aging processes on carotid waveform morphology and derived indexes is studied in silico, with the aim of establishing the clinical potential of a carotid US-based assessment of cardiovascular aging. One-dimensional (1-D) hemodynamic modeling was employed to generate an age-specific virtual population (VP) of N = 5,160 realistic carotid hemodynamic waveforms. The resulting VP was statistically validated against in vivo aging trends in waveforms and indexes from the literature, and simulated waveforms were studied in relation to age and underlying cardiovascular parameters. In our study, the carotid flow augmentation index (FAI) significantly increased with age (with a median increase of 50% from the youngest to the oldest age group) and was strongly correlated to local arterial stiffening (r = 0.94). The carotid pulsatility index (PI), which showed less pronounced age variation, was inversely correlated with the reflection coefficient at the carotid branching (r = -0.88) and directly correlated with carotid net forward wave energy (r = 0.90), corroborating previous literature where it was linked to increased risk of cerebrovascular damage in the elderly. There was a high correlation between corrected carotid flow time (ccFT) and cardiac output (CO) (r = 0.99), which was not affected by vascular age. This study highlights the potential of carotid waveforms as a valuable tool for the assessment of cardiovascular aging.NEW & NOTEWORTHY An age-specific virtual population was generated based on a 1-D model of the arterial circulation, including newly defined literature-based specific age variations in carotid vessel properties. Simulated carotid flow/velocity waveforms, indexes, and age trends were statistically validated against in vivo data from the literature. A comprehensive study of the impact of aging on carotid flow waveform morphology was performed, and the mechanisms influencing different carotid indexes were elucidated. Notably, flow augmentation index (FAI) was found to be a strong indicator of local carotid stiffness.

Age- and sex-dependent cardiovascular impact of maternal perinatal stress and altered dopaminergic metabolism in the medulla oblongata of the offspring.

Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance.NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.

Phase-encoded fMRI tracks down brainstorms of natural language processing with subsecond precision.

Natural language processing unfolds information overtime as spatially separated, multimodal, and interconnected neural processes. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed rapid phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured real-time information flows as coherent hemodynamic waves traveling over the cortical surface during listening, reading aloud, reciting, and oral cross-language interpreting tasks. We were able to observe the timing, location, direction, and surge of traveling waves in all language tasks, which were visualized as "brainstorms" on brain "weather" maps. The paths of hemodynamic traveling waves provide direct evidence for dual-stream models of the visual and auditory systems as well as logistics models for crossmodal and cross-language processing. Specifically, we have tracked down the step-by-step processing of written or spoken sentences first being received and processed by the visual or auditory streams, carried across language and domain-general cognitive regions, and finally delivered as overt speeches monitored through the auditory cortex, which gives a complete picture of information flows across the brain during natural language functioning. PRACTITIONER POINTS: Phase-encoded fMRI enables simultaneous imaging of high spatial and temporal resolution, capturing continuous spatiotemporal dynamics of the entire brain during real-time overt natural language tasks. Spatiotemporal traveling wave patterns provide direct evidence for constructing comprehensive and explicit models of human information processing. This study unlocks the potential of applying rapid phase-encoded fMRI to indirectly track the underlying neural information flows of sequential sensory, motor, and high-order cognitive processes.

Changes in choroidal hemodynamics of form-deprivation myopia in Guinea pigs.

PURPOSE: We studied changes in the choroid, particularly variation in blood flow, during the development of myopia. The hemodynamic mechanism in play remains unclear. We evaluated blood flow by quantitating indocyanine green (ICG) fluorescence in a guinea pig model of form-deprivation myopia. METHODS: Guinea pigs were divided into form-deprivation myopia (FDM) and normal control (NC) groups. Ocular biometric and choroidal hemodynamics parameters were quantitatively derived via ICG imaging, and included the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). RESULTS: Form deprivation was associated with significant interocular differences in terms of both refractive error and axial length. ICG fluorescence hemodynamic maps of fundal blood flow and vasculature density were evident. In deprived eyes, the fluorescence signals exhibited significantly longer Trising and MTT but lower Imax and BFI than fellow eyes and NC group. The interocular differences in terms of the ocular biometric and hemodynamic parameters were significantly correlated. Hemodynamic analysis of choriocapillaris lobules revealed weakened fluorescence intensity and prolonged arrival and filling times in deprived eyes. Form deprivation reduced the number of lobulated choriocapillaris structures. CONCLUSION: Form-deprivation myopia triggered changes in the hemodynamic and vascular network structures of the choroid and choriocapillaris. The ICG fluorescence imaging/analysis method provides a unique tool for further myopia research.

Remote ischemic conditioning improves cerebral hemodynamics in symptomatic intracranial atherosclerosis: A PET/CT-guided randomized controlled study.

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

Hemoglobin Threshold for Blood Transfusion in Young Children Hospitalized with Iron Deficiency Anemia.

Current recommendations advise against blood transfusion in hemodynamically stable children with iron deficiency anemia. In an observational study of 125 children aged 6 through 36 months, hospitalized with iron deficiency anemia, we found that hemoglobin level predicted red blood cell transfusion (area under the curve 0.8862). A hemoglobin of 39 g/L had sensitivity 92% and specificity 72% for transfusion.

Relationship between regional sympathetic vascular transduction and sympathetic transduction of blood pressure in young adults at rest.

A burst of muscle sympathetic nerve activity (MSNA) induces vasoconstriction that transiently reduces regional vascular conductance and increases systemic blood pressure (BP) over the subsequent 4-8 cardiac cycles. These responses are termed sympathetic neurovascular transduction and sympathetic transduction of BP, respectively. Sympathetic transduction of BP is commonly calculated and interpreted as a proxy measure for regional sympathetic neurovascular transduction, despite the systemic nature of BP regulation. The present analysis tested whether the peak change in signal-averaged sympathetic transduction of BP was correlated to the change in regional sympathetic vascular transduction at rest. Fourteen adults (5 females, 23±3 years) arrived at the laboratory, ate a standardized meal, and rested for 90-120 minutes. MSNA (fibular nerve microneurography), heart rate (electrocardiography), beat-to-beat BP (finger photoplethysmography), and superficial femoral artery blood flow (Doppler ultrasound) were obtained continuously for 10 minutes in the supine position. Femoral vascular conductance was calculated as blood flow divided by mean arterial BP. The peak change in diastolic BP following a burst of MSNA was correlated to the corresponding nadir change in femoral vascular conductance (r=-0.58 [-0.07 to -0.85], P=0.03) and superficial femoral artery blood flow (r=-0.54 [-0.17 to -0.83], P=0.04). The nadir change in diastolic BP in cardiac cycles not following a MSNA burst was correlated to the peak change in femoral vascular conductance (r=-0.42 [-0.83 to 0.00], p=0.05) but not superficial femoral artery blood flow (r=0.41 [-0.77 to 0.15], p=0.14). In conclusion, more commonly assessed sympathetic transduction of BP provides moderate insight into regional sympathetic neurovascular transduction.

Low Shear-induced Fibrillar Fibronectin: comparative analyses of morphologies and cellular effects on Bovine Aortic Endothelial Cell Adhesion and Proliferation.

Wall shear stress (WSS) is a critical factor in vascular biology, and both high and low WSS are implicated in atherosclerosis. Fibronectin (FN) is a key extracellular matrix protein that plays an important role in cell activities. Under high shear stress, plasma FN (pFN) undergoes fibrillogenesis; however, its behavior under low shear stress remains unclear. This study aimed to investigate the formation of in vitro cell-free fibrillar FN (FFN) under low shear rate conditions and its effect on bovine aortic endothelial cell behavior. FN (500 µg/ml) was perfused through slide chambers at three flow rates (0.16 ml/h, 0.25 ml/h, and 0.48 ml/h), corresponding to low shear rates of 0.35 s-1, 0.55 s-1, and 1.05 s-1, respectively, for 4 hours at room temperature. The formed FN matrices were observed using fluorescence microscopy and SEM. Under low shear rates, distinct FN matrix structures were observed. FFN0 .48 formed immense fibrils with smooth surfaces, FFN0.25 formed a matrix with a rough surface, and FFN16 exhibited nodular structures. FFN0.25 supported cell activities to a greater extent than native FN and other FFN surfaces. Our study suggests that abnormally low shear conditions impact FN structure and function and enhance the understanding of FN fibrillogenesis in vascular biology, particularly in atherosclerosis.

Safety and Feasibility of an Implanted Inferior Vena Cava Sensor for Accurate Volume Assessment: FUTURE-HF2 Trial.

BACKGROUND: A novel implantable sensor has been designed to accurately measure inferior vena cava (IVC) area to allow daily monitoring of IVC area and collapse to predict congestion in heart failure (HF). METHODS: A prospective, multicenter, single arm, Early Feasibility Study enrolled 15 HF patients (irrespective of ejection fraction) with a HF event in the previous 12 months, an elevated NT-proBNP, and receiving ≥40 mg of furosemide equivalent. Primary endpoints included successful deployment without procedure-related (30 days) or sensor-related complications (three months) and successful data transmission to a secure database (3 months). Accuracy of sensor-derived IVC area, patient adherence, NYHA classification, and KCCQ were assessed from baseline to three months. Patient-specific signal alterations were correlated with clinical presentation to guide interventions. RESULTS: Fifteen patients underwent implantation (66±12 years; 47% female; 27% HFpEF, NT-ProBNP 2569 (median, IQR: (1674-5187)) ng/L; 87% NYHA Class III). All patients met the primary safety and effectiveness endpoints. Sensor-derived IVC area showed excellent agreement with concurrent CT (R2=0.99, mean absolute error=11.15 mm2). Median adherence to daily readings was 98% (IQR: 86-100%) per patient-month. A significant improvement was seen in NYHA class and a non-significant improvement was observed for KCCQ. CONCLUSIONS: Implantation of a novel IVC sensor (FIRE1) was feasible, uncomplicated, and safe. Sensor outputs aligned with clinical presentation and improvements in clinical outcomes. Future investigation to establish the IVC sensor remote management of HF is strongly warranted.

The impact of revascularization strategy on clinical failure, hemodynamic failure, and chronic limb-threatening ischemia symptoms in the BEST-CLI Trial.

OBJECTIVE: Sustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial. METHODS: As planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created. RESULTS: In cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. CONCLUSIONS: Durable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

Association between cytokines, nitric oxide, hemodynamic and microcirculation in a porcine model of sepsis.

Systemic inflammation and hemodynamic or microvascular alterations are a hallmark of sepsis and play a role in organs hypoperfusion and dysfunction. Pimobendan, an inodilator agent, could be an interesting option for inotropic support and microcirculation preservation during shock. The objectives of this study were to evaluate effect of pimobendan on cytokine and nitric oxide (NO) release and investigate whether changes of macro and microcirculation parameters are associated with the release of cytokines and NO in pigs sepsis model. After circulatory failure, induced by intravenous inoculation of live Pseudomonas aeruginosa, eight animals were treated with pimobendan and eight with placebo. Pimobendan did not affect cytokines secretion (TNF-α, IL-6 and IL-10), but decreased time-dependently NO release. Data of macro and microcirculation parameters, NO and TNF- α recorded at the time of circulatory failure (Thypotension) and the time maximum of production cytokines was used for analyses. A positive correlation was observed between TNF-α and cardiac index (r = 0.55, p = 0.03) and a negative with systemic vascular resistance (r = -0.52, p = 0.04). Positive correlations were seen both between IL-10, 30 min after resuscitation (T30min), and systolic arterial pressure (r = 0.57, p = 0.03) and cardiac index (r = 0.67, p = 0.01), and also between IL-6, taken 2 h after resuscitation and systolic arterial pressure (r = 0.53, p = 0.04). Negative correlations were found between IL-10 and lactate, measured resuscitation time (r = -0.58, p = 0.03). Regarding microcirculation parameters, we observed a positive correlation between IL-6 and IL-10 with the microvascular flow index (r = 0.52, p = 0.05; r = 0.84, p = 0.0003) and a negative correlation with the heterogeneity index with TNF-α and IL-10 (r = -0.51, p = 0.05; r = -0.74, p = 0.003) respectively. NO derivatives showed a positive correlation with temperature gradient (r = 0.54, p = 0.04). Pimobendan did not show anti-inflammatory effects in cytokines release. Our results also, suggest changes of macro- and microcirculation are associated mainly with low levels of IL-10 in sepsis.