A comparison of function lumen imaging probe measurements of anal sphincter function in fecal incontinence.

BACKGROUND: The functional lumen imaging probe (FLIP) is a test of anal sphincter distensibility under evaluation by specialist centers. Two measurement protocols termed "stepwise" and "ramp" are used, risking a lack of standardization. This study aims to compare the performance of these protocols to establish if there are differences between them. METHODS: Patients with fecal incontinence were recruited and underwent measurement with both protocols at a tertiary pelvic floor referral unit. Differences in minimum diameter, FLIP bag pressure, and distensibility index (DI) at rest and during squeeze were calculated at various FLIP bag volumes. KEY RESULTS: Twenty patients (19 female, mean age 61 [range: 38-78]) were included. The resting minimum diameter at 30 and 40 mL bag volumes were less in the stepwise protocol (mean bias: -0.55 mm and -1.18 mm, p < 0.05) along with the DI at the same bag volumes (mean bias: -0.37 mm2/mmHg and -0.55 mm2/mmHg, p < 0.05). There was also a trend towards greater bag pressures at 30 mL (mean bias: +2.08 mmHg, p = 0.114) and 40 mL (mean bias: +2.81 mmHg, p = 0.129) volumes in the stepwise protocol. There were no differences between protocols in measurements of minimum diameter, maximum bag pressure, or DI during voluntary squeeze (p > 0.05). CONCLUSION AND INFERENCES: There are differences between the two commonly described FLIP measurement protocols at rest, although there are no differences in the assessment of squeeze function. Consensus agreement is required to agree the most appropriate FLIP measurement protocol in assessing anal sphincter function.

B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

OBJECTIVES: During human pregnancy placental extravillous trophoblasts replace the vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling these arteries into distensible low resistance vessels to promote placental perfusion. The present study, determined whether B-flow/ spatio-temporal image correlation (STIC) M-mode ultrasonography provides an in vivo imaging method to digitally quantify spiral artery luminal distensibility, as a physiological index of spiral artery remodeling, during advancing stages of normal human pregnancy. METHODS: A prospective longitudinal observational study was conducted to quantify spiral artery distensibility, i.e. vessel luminal diameter at systole minus diameter at diastole, by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1), growth factors that modulate events important in spiral artery remodeling, were quantified in a subset of the subjects at the first, second and third semesters. RESULTS: Median [first quartile, third quartile] spiral artery distensibility progressively increased (P < 0.0001) between the first trimester (0.17 [0.14, 0.21]), second (0.23 [0.18, 0.28]) and third (0.26 [0.21, 0.35]) trimesters of pregnancy. Spiral artery volume flow (ml/cardiac cycle) progressively increased (P < 0.001) between the first 2.49 [1.38, 4.99], second 3.86 [2.06, 6.91] and third 7.79 [3.83, 14.98] trimesters. Coinciding with the elevation in spiral artery distensibility, the median ratio of serum PlGF/sFlt-1 levels increased (P < 0.001) between the first (7.2 [4.5, 10], second (22.7 [18.6, 42.2]) and third (56.2 [41.9, 92.5] trimesters. CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in vivo imaging technology to digitally quantify structural/physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. This article is protected by copyright. All rights reserved.

Arterial Health Markers in Relation to Behavior and Cognitive Outcomes at School Age.

BACKGROUND: Impaired arterial health is associated with a decline in cognitive function and psychopathology in adults. We hypothesized that these associations originate in early life. We examined the associations of blood pressure, common carotid artery intima media thickness, and carotid distensibility with behavior and cognitive outcomes during adolescence. METHODS AND RESULTS: This study was embedded in the Dutch Generation R Study, a population-based prospective cohort study from early fetal life onwards. Blood pressure, carotid intima media thickness, and carotid distensibility were measured at the age of 10 years. At the age of 13 years, total, internalizing and externalizing problems and attention-deficit hyperactivity disorder symptoms were measured using the parent-reported Child Behavior Checklist (CBCL/6-18), autistic traits were assessed by the Social Responsiveness Scale, and IQ was assessed using the Wechsler Intelligence Scale for Children-Fifth Edition. A 1-SD score higher mean arterial pressure was associated with lower odds of internalizing problems (odds ratio [OR], 0.92 [95% CI, 0.85-0.99]). However, this association was nonsignificant after correction for multiple testing. Carotid intima media thickness and carotid distensibility were not associated with behavior and cognitive outcomes at 13 years old. CONCLUSIONS: From our results, we cannot conclude that the associations of blood pressure, carotid intima media thickness, and carotid distensibility at age 10 years with behavior and cognitive outcomes are present in early adolescence. Further follow-up studies are needed to identify the critical ages for arterial health in relation to behavior and cognitive outcomes at older ages.

Predictive Value of Pulmonary Artery Distensibility for Short-Term Adverse Clinical Outcomes in Patients with Acute Pulmonary Embolism.

We aimed to explore the relationship between pulmonary artery distensibility obtained from computed tomography pulmonary angiography (CTPA) and short-term adverse clinical outcomes in patients with acute pulmonary embolism (APE). We included patients who underwent retrospective electrocardiogram-gated CTPA and were subsequently diagnosed with APE. Patients were categorized into good and poor outcome groups based on short-term clinical outcomes. Pulmonary artery distensibility (AD), right ventricle/left ventricle (RV/LV) ratio, and pulmonary artery obstruction index (PAOI) were measured, and the receiver operating characteristic curves were constructed. Sixty-four patients with APE (good outcome, 46; poor outcome, 18) were enrolled. AD, RV/LV ratio, and PAOI differed significantly between groups (P < 0.05). Pulmonary artery AD in the good outcome group was greater than that in the poor outcome group (P < 0.001). The poor outcome group exhibited a higher RV/LV ratio and PAOI than the good outcome group (P < 0.05). AD and PAOI were independent predictors of adverse clinical outcomes. Areas under the curve for AD and PAOI were 0.860 (95% confidence interval [CI]: 0.750-0.934) and 0.675 (95%CI: 0.546-0.786), and the combined curve of the AD and RV/LV ratio was 0.906 (95%CI: 0.806-0.965). The calibration curve showed a combined curve superior to the other curves. The decision curve showed high clinical application value of the combined curve. Retrospective electrocardiogram-gated CTPA-derived AD could serve as an indicator for predicting short-term adverse clinical outcomes in APE. Combining AD and PAOI has a high predictive value for short-term adverse clinical outcomes.

A New Method to Evaluate Lower Esophageal Distension Capacity in Eosinophilic Esophagitis by Using Functional Lumen Imaging Probe (EndoFLIP™).

Endoluminal functional lumen impedance planimetry (EndoFLIPTM) has become the gold standard to evaluate esophageal distensibility, although the study itself and its analysis present challenges. We propose here a new method to assess lower esophageal distension capacity that overcomes several limitations of prior approaches, including incomplete and corrupted EndoFLIPTM recordings. Esophageal distension capacity was evaluated with a 16-channel EndoFLIPTM in 10 controls and 14 patients with eosinophilic esophagitis (EoE). Controls were evaluated once. EoE patients were evaluated at baseline and after at least six weeks of treatment with orodispersible budesonide tablets, 1 mg bd. Balloon volumes were increased by 5 mL stepwise, either reaching a maximum volume of 60 mL or a maximum balloon pressure of 60 mmHg. Recordings were analyzed with a homemade R script. The mean esophageal diameter at 60 mL, D (60 mL), was calculated or extrapolated depending on whether the 60 mL volume was reached. By fitting a Michaelis-Menten curve across all measured diameters throughout all constant volume steps, the mean D (60 mL) was estimated. For control subjects, the mean ± SD value of D (60 mL) was 17.08 ± 1.69 mm, and for EoE patients at baseline, D (60 mL) was 14.51 ± 2.68 mm. After six weeks of treatment of EoE patients, D (60 mL) significantly increased to 16.22 ± 1.86 mm (paired Wilcoxon signed test: p = 0.0052), although the values for control subjects were not reached. The estimated mean esophageal diameter at 60 mL is a good proxy for esophageal distension capacity, which correlates with clinical outcomes in EoE. The method presented in this study overcomes difficulties encountered during the standard measurement protocol, allowing the analysis of recordings from incomplete and corrupted registries.

Functional lumen imaging probe topography identifies patients with normal acid exposure and esophageal hypervigilance amongst proton-pump inhibitor non-responders.

BACKGROUND: Multiple factors contribute to symptom generation and treatment response in proton-pump inhibitor non-responders (PPI-NRs). We aimed to test whether PPI-NRs with normal acid exposure have a higher degree of esophageal hypersensitivity and hypervigilance and can be identified using functional lumen imaging probe (FLIP) topography at the time of endoscopy. METHODS: Data from PPI-NRs whom underwent endoscopy, FLIP and wireless 96-h pH-metry were retrospectively analyzed. Patients were grouped according to acid exposure time (AET) as (a) 0 days abnormal (AET > 6%), (b) 1-2 days abnormal, or (c) 3-4 days abnormal. The esophageal hypervigilance and anxiety scale (EHAS) score and other symptom scores were compared between groups. The discriminatory ability of the esophagogastric junction (EGJ) distensibility index (DI) and max EGJ diameter in identifying patients with 0 days abnormal AET was tested via receiver-operating-characteristic (ROC) curve analysis. RESULTS: EHAS score was 38.6 in the 0 days abnormal AET group, 30.4 in the 1-2 days abnormal AET group (p = 0.073 when compared to 0 days abnormal) and 28.2 in the 3-4 days abnormal AET group (p = 0.031 when compared to 0 days abnormal). Area-under-the-curve (AUC) for the DI in association with 0 days AET > 6% was 0.629. A DI of < 2.8 mm2/mmHg had a sensitivity of 83.3%, and negative predictive value of 88% in classifying patients with 0 days abnormal acid exposure (p = 0.004). CONCLUSIONS: FLIP complements prolonged wireless pH-metry in distinguishing the subset of PPI-NRs with completely normal acid exposure and a higher burden of esophageal hypervigilance. Proper identification of patients along the functional heartburn spectrum can improve overall surgical outcomes.

Outcomes after per-oral endoscopic myotomy for Zenker's diverticula (Z-POEM) and correlation with impedance planimetry (FLIP).

INTRODUCTION: Zenker's diverticulum (ZD) is a false pulsion diverticulum of the cervical esophagus. It is typically found in older adults and manifests with dysphagia. The purpose of this study is to describe our experience with Per-oral endoscopic myotomy for Zenker's (Z-POEM) and intraoperative impedance planimetry (FLIP). METHODS: We performed a single institution retrospective review of patients undergoing Z-POEM in a prospective database between 2014 and 2022. Upper esophageal sphincter (UES) distensibility index (DI, mm2/mmHg) was measured by FLIP before and after myotomy. The primary outcome was clinical success. Secondary outcomes included technical failure, adverse events, and quality of life as assessed by the gastroesophageal health-related quality of life (GERD-HRQL), reflux severity index (RSI), and dysphagia score. A statistical analysis of DI was done with the paired t-test (p < 0.05). RESULTS: Fifty-four patients underwent Z-POEM, with FLIP measurements available in 30 cases. We achieved technical success and clinical success in 54/54 (100%) patients and 46/54 patients (85%), respectively. Three patients (6%) experienced contained leaks. Three patients were readmitted: one for aforementioned contained leak, one for dysphagia, and one post-operative pneumonia. Three patients with residual dysphagia underwent additional endoscopic procedures, all of whom had diverticula > 4 cm. Following myotomy, mean DI increased by 2.0 ± 1.7 mm2/mmHg (p < 0.001). In those with good clinical success, change in DI averaged + 1.6 ± 1.1 mm2/mmHg. Significant improvement was found in RSI and GERD-HRQL scores, but not dysphagia score. CONCLUSION: Z-POEM is a safe and feasible for treatment of ZD. We saw zero cases of intraoperative abandonment. We propose that large diverticula (> 4 cm) are a risk factor for poor outcomes and may require additional endoscopic procedures. An improvement in DI is expected after myotomy, however, the ideal range is still not known.

Biomecánica esofágica valorada mediante planimetría por impedancia (EndoFLIP™) en sujetos sanos y en pacientes con esofagitis eosinofílica. Valores de normalidad / Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values

Antecedentes: la esofagitis eosinofílica (EEo) activa se asocia a alteraciones en el calibre, la distensibilidad y la motilidad esofágica que podrían revertir con el tratamiento. Objetivos: estudiar el diámetro, la distensibilidad y la contractilidad esofágica en sujetos sanos comparándolos con pacientes con EEo antes y después del tratamiento. Métodos: estudio cuasiexperimental. Mediante EndoFLIP™, se analizaron el cuerpo esofágico y la unión esofagogástrica (UEG) de los tres grupos, y se diseñó un programa para obtener los valores de diámetro, distensibilidad y contractilidad esofágica. Resultados: incluimos diez voluntarios sanos (24-61 años, seis hombres) y nueve pacientes con EEo (21-52 años, siete hombres). El índice de distensibilidad de la UEG fue de 5,07 mm2/Hg en controles, 2,40 mm2/Hg en EEo antes del tratamiento y 2,46 mm2/Hg después; la meseta de distensibilidad fue de 20,02 mm, 15,43 mm y 17,41 mm, respectivamente; y el diámetro, de 21,90 mm, 17,73 mm y 18,30 mm, con diferencias significativas (p < 0,05) excepto entre los diámetros de controles y pacientes tratados (p = 0,079). Las contracciones anterógradas repetitivas aparecieron en el 90 % de los controles, en el 66,7 % de EEo a antes del tratamiento y en el 88,9 % después (p > 0,05). Conclusiones: el índice de distensibilidad de la UEG, la meseta de distensibilidad y el diámetro en controles son mayores que en pacientes, aunque seis semanas de tratamiento parece poco tiempo para ver cambios significativos en la biomecánica esofágica. Las contracciones anterógradas repetitivas son el patrón predominante en sanos y en EEo. Aportamos valores de normalidad de la biomecánica esofágica medida mediante planimetría por impedancia en nuestro entorno.(AU)

Background: active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. Objectives: to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. Methods: a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. Results: ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). Conclusions: esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.(AU)

A clinical strategy to improve the diagnostic performance of 3T non-contrast coronary MRA and noninvasively evaluate coronary distensibility: combination of diastole and systole imaging.

BACKGROUND: The clinical application of coronary MR angiography (MRA) combining diastole and systole imaging has never been described comprehensively in coronary artery disease (CAD) patients. We aimed to design an optimal non-contrast coronary MRA scan protocol combining diastolic and systolic imaging and to (1) evaluate its diagnostic performance for detecting significant coronary stenosis; (2) evaluate the feasibility of this protocol to noninvasively measure the coronary distensibility index (CDI). METHODS: From June 2021 to May 2022, 33 healthy volunteers and 91 suspected CAD patients scheduled for X-ray coronary angiography (CAG) were prospectively enrolled. 3T non-contrast water-fat coronary MRA was carried out twice at diastole and systole. Significant coronary stenosis was defined as a luminal diameter reduction of ≥ 50% using CAG as the reference and was evaluated as follows: (1) by coronary MRA in diastole alone; (2) by coronary MRA in systole alone; (3) by combined coronary MRA in diastole and systole. According to CAG, the patients were divided into significant CAD patients and non-significant CAD patients. The difference in CDI among participants was evaluated. RESULTS: Combined coronary MRA was completed in 31 volunteers and 76 patients. The per-patient sensitivity, specificity, and accuracy of combined coronary MRA were 97.5%, 83.3%, and 90.8%, respectively. Compared with single diastolic mode, combined coronary MRA showed equally high sensitivity but improved specificity on a per-patient basis (83.3% vs. 63.9%, adjusted P = 0.013). The CDI tested by coronary MRA decreased incrementally from healthy volunteers to non-significant and significant CAD patients. CONCLUSION: Compared with single-phase mode, 3 T non-contrast combined coronary MRA significantly improved specificity and may have potential to be a simple noninvasive method to measure CDI.

Echocardiographic reference intervals of the dimensions of the main pulmonary artery and the right pulmonary artery: a prospective study in 269 healthy dogs.

INTRODUCTION: No data are available on the echocardiographic reference intervals (RIs) for the main pulmonary artery (MPA) and right pulmonary artery (RPA) dimensions in a large sample of dogs. Therefore, we aimed to describe the echocardiographic RIs of the MPA and RPA dimensions in normal dogs. ANIMALS, MATERIALS, AND METHODS: Two hundred and sixty nine healthy dogs of different breeds, age and body weight (BW) were prospectively enrolled in this multicenter, observational study. The MPA diameter, RPA maximum diameter (RPAmax), and RPA minimum diameter (RPAmin) were measured from the right parasternal short axis view. Prediction intervals (PIs) for MPA, RPAmax and RPAmin were generated using allometric scales. Reference intervals (RI) of MPA indexed to the ascending aorta (MPA/AO), and RPAmax and RPAmin indexed to the aortic annulus (RPAmax/Aod and RPAmin/Aod), were defined. RESULTS: A positive linear relationship between MPA, RPAmax, RPAmin and BW was evident after logarithmic transformation (R2 = 0.859, R2 = 0.787 and R2 = 0.725, respectively; P<0.0001). According to allometric scales, the PI for the MPA normalized for BW (MPA_N) was between 5.50 and 8.07, the PI for the RPAmax normalized for BW (RPAmax_N) was between 3.23 and 5.62, while the PI for the RPAmin normalized for BW (RPAmin_N) was between 1.62 and 3.30. The median MPA/AO was 0.92 (RI, 0.78-1.01), the median RPAmax/Aod was 0.70 (RI, 0.53-0.98) and the median RPAmin/Aod was 0.40 (RI, 0.29-0.61). DISCUSSION AND CONCLUSIONS: The reported RIs of the MPA and RPA dimensions in normal dogs could increase the diagnostic accuracy of transthoracic echocardiography in the identification of pulmonary artery enlargement in dogs.

Intraoperative distensibility measurement in POEM for achalasia: impact on patient outcome and associations with other outcome variables at 1-year follow-up.

BACKGROUND AND AIMS: The functional luminal imaging probe (FLIP) can provide measurements of lower esophageal sphincter (LES) distensibility. Studies report that use of intraoperative FLIP examination during peroral endoscopic myotomy (POEM) for achalasia is associated with treatment success, but evidence is limited and inconsistent. The main aim of the present study was to assess associations between intraoperative FLIP values and 1-year outcomes. Additionally, associations between 1-year FLIP measurements and other 1-year outcome variables were studied. METHODS: We performed a single-center prospective study of consecutive achalasia patients treated with POEM with a standardized 1-year follow-up. The inclusion period was from June 2017 to January 2020. We compared 1-year outcomes (FLIP measurement values, Eckardt score (ES), reflux esophagitis, timed barium esophagogram (TBE), and lower esophageal sphincter resting pressure (LES-rp)) in patients with and without intraoperative FLIP examination. We also assessed associations between intraoperative FLIP values, 1-year FLIP values, and other 1-year outcomes. Results are given as median (IQR), and non-parametrical statistical analyses were applied. RESULTS: Sixty-two patients (27 females) with median age 45 years (35-54) were included. Baseline characteristics were similar in patients with (n = 32) and without (n = 30) intraoperative FLIP examination. In patients with intraoperative FLIP, ES was 2 (1-3) and LES distensibility index (DI) 3.7 (2.6-5.4) after 1 year, compared with ES 2 (1-3) and DI 4.0 (3.1-6.8)) in patients without intraoperative FLIP (ns). Intraoperative DI was not correlated with 1-year ES or DI. One-year DI correlated significantly with 1-year ES (rs - 0.42), TBE (rs - 0.34), and LES-rp (rs - 0.29). CONCLUSIONS: Use of intraoperative FLIP measurements in POEM for achalasia is not associated with improved 1-year outcome, and the clinical value of intraoperative FLIP in POEM for achalasia is questioned. Follow-up FLIP measurements are moderately associated with symptomatic outcome, and may serve as an additional diagnostic modality in post-treatment evaluation.

iCPET Calculator: A Web-Based Application to Standardize the Calculation of Alpha Distensibility in Patients With Pulmonary Arterial Hypertension.

Background Pulmonary vascular distensibility associates with right ventricular function and clinical outcomes in patients with unexplained dyspnea and pulmonary hypertension. Alpha distensibility coefficient is determined from a nonlinear fit to multipoint pressure-flow plots. Study aims were to (1) create and test a user-friendly tool to standardize analysis of exercise hemodynamics including distensibility, and (2) investigate changes in distensibility following treatment in patients with pulmonary arterial hypertension. Methods and Results Participants with an exercise right heart catherization were retrospectively identified from the University of Arizona Pulmonary Hypertension (UA PH) registry and split into a pulmonary arterial hypertension group, a comparator group, and a control group. Right ventricular function was quantified using the coupling ratio and diastolic stiffness. Prototypes of the invasive cardiopulmonary exercise testing (iCPET) calculator were developed using Matlab, Python, and RShiny to analyze exercise hemodynamics and alpha distensibility coefficient, α (%/mm Hg) from multipoint pressure flow plots. Interclass correlation coefficients were calculated for interplatform and interobserver variability in alpha. No significant bias in the intraplatform (Matlab versus RShiny; intraclass correlation coefficient: 0.996) or interobserver (intraclass correlation coefficient: 0.982) comparison of alpha values. Afterload significantly decreased (P<0.05) with no change in alpha distensibility in the pulmonary arterial hypertension group at follow-up. The comparator group had no change in pressure, resistance or alpha distensibility. There were no significant changes in RV diastolic stiffness at follow-up. Conclusions The interactive user interface in the iCPET calculator allows exploration of alpha distensibility using standardized methods. No significant change in alpha distensibility at follow-up suggests that alpha may be less modifiable in patients with long-standing pulmonary arterial hypertension.

Hemodynamic Determinants of Elevated Blood Pressure and Hypertension in the Middle to Older-Age UK Population: A UK Biobank Imaging Study.

BACKGROUND: Increased systemic vascular resistance and, in older people, reduced aortic distensibility, are thought to be the hemodynamic determinants of primary hypertension but cardiac output could also be important. We examined the hemodynamics of elevated blood pressure and hypertension in the middle to older-aged UK population participating in the UK Biobank imaging studies. METHODS: Cardiac output, systemic vascular resistance, and aortic distensibility were measured from cardiac magnetic resonance imaging in 31 112 (distensibility in 21 178) participants (46.3% male, mean age±SD 63±7 years). Body composition including visceral adipose tissue volume and abdominal subcutaneous adipose tissue volume were measured in 19 645 participants. RESULTS: Participants with higher blood pressure had higher cardiac output (higher by 17.9±26.6% in hypertensive compared with those with optimal blood pressure) and higher systemic vascular resistance (higher by 11.4±27.9% in hypertensive compared with those with optimal blood pressure). These differences were little changed after adjustment for body size and adiposity. The contribution of cardiac output relative to systemic vascular resistance was more marked in younger compared with older subjects. Aortic distensibility decreased with age and was lower in participants with higher compared with lower blood pressure but with a greater difference in younger compared with older subjects. CONCLUSIONS: In the middle to older-aged UK population, cardiac output plays an important role in contributing to elevated mean arterial blood pressure, particularly in younger compared with older subjects. Reduced aortic distensibility contributes to a rise in pulse pressure and systolic blood pressure at all ages.

One Step Back from Bedside to the Bench-How Do Different Arterial Stiffness Parameters Behave in Relation to Peripheral Resistance?

The investigation of arterial stiffening is a promising approach to estimating cardiovascular risk. Despite the widespread use of different methods, the dynamic nature of measured and calculated stiffness parameters is marginally investigated. We aimed to determine the stability of large artery elasticity parameters assessed via commonly used, ultrasound-based and oscillometric methods in relation to peripheral resistance modulation. A human experimental environment was composed, and fifteen young males were investigated at rest after extremity heating and external compression. Functional vascular parameters were monitored in each session, and several arterial stiffness parameters were analysed. The distensibility coefficient (DC) did not show significant changes during heat provocation and extremity compression, while DC's stability seemed to be acceptable. The same stability of carotid-femoral pulse wave velocity (PWV) was detected with ultrasound measurement (5.43 ± 0.79, 5.32 ± 0.86 and 5.28 ± 0.77, with p = 0.38, p = 0.27 and p = 0.76, respectively) with excellent intersession variability (intraclass correlation coefficient of 0.90, 0.88 and 0.91, respectively). However, the oscillometric PWV (oPWV) did change significantly between the heating and outer compression phase of the study (7.46 ± 1.37, 7.10 ± 1.18 and 7.60 ± 1.21, with p = 0.05, p = 0.68 and p < 0.001, respectively), the alteration of which is closely related to wave reflection, represented by the changes in reflection time. Our results indicate the good stability of directly measured elastic parameters such as DC and PWV, despite the extreme modulation of peripheral resistance. However, the oscillometric, indirectly detected PWV might be altered by physical interventions, which depend on wave reflection. The effective modulation of wave reflection was characterized by changes in the augmentation index, detected using both oscillometry and applanation tonometry. Thus, the environment during oscillometric measurement should be rigorously standardized. Furthermore, our results suggest the dynamic nature of the reflection point, rather than being a fixed anatomical point, proposed previously as aortic bifurcation.

Biomechanical remodeling of the murine descending thoracic aorta during late-gestation pregnancy.

With the rise in maternal mortality rates and the growing body of epidemiological evidence linking pregnancy history to maternal cardiovascular health, it is essential to comprehend the vascular remodeling that occurs during gestation. The maternal body undergoes significant hemodynamic alterations which are believed to induce structural remodeling of the cardiovascular system. Yet, the effects of pregnancy on vascular structure and function have not been fully elucidated. Such a knowledge gap has limited our understanding of the etiology of pregnancy-induced cardiovascular disease. Towards bridging this gap, we measured the biaxial mechanical response of the murine descending thoracic aorta during a normotensive late-gestation pregnancy. Non-invasive hemodynamic measurements confirmed a 50% increase in cardiac output in the pregnant group, with no changes in peripheral blood pressure. Pregnancy was associated with significant wall thickening ( ∼14%), an increase in luminal diameter ( ∼6%), and material softening in both circumferential and axial directions. This expansive remodeling of the tissue resulted in a reduction in tensile wall stress and intrinsic tissue stiffness. Collectively, our data indicate that an increase in the geometry of the vessel may occur to accommodate for the increase in cardiac output and blood flow that occurs in pregnancy. Similarly, wall thickening accompanied by increased luminal diameter, without a change in blood pressure may be a necessary mechanism to decrease the tensile wall stress, and avoid pathophysiological events following late gestation.

Internal jugular vein collapsibility does not predict fluid responsiveness in spontaneously breathing patients after cardiac surgery.

PURPOSE: The objective of our study was to evaluate the diagnostic accuracy of internal jugular vein (IJV) collapsibility as a predictor of fluid responsiveness in spontaneously breathing patients after cardiac surgery. METHODS: In this prospective observational study, spontaneously breathing patients were enrolled on the first postoperative day after coronary artery bypass grafting. Hemodynamic data coupled with simultaneous ultrasound assessment of the IJV were collected at baseline and after passive leg raising test (PLR). Continuous cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV) were assessed with FloTracTM/EV1000™. Fluid responsiveness was defined as an increase in CI ≥ 10% after PLR. We compared the differences in measured variables between fluid responders and non-responders and tested the ability of ultrasonographic IJV indices to predict fluid responsiveness. RESULTS: Fifty-four patients were included in the study. Seventeen (31.5%) were fluid responders. The responders demonstrated significantly lower inspiratory and expiratory diameters of the IJV at baseline, but IJV collapsibility was comparable (P = 0.7). Using the cut-off point of 20%, IJV collapsibility predicted fluid responsiveness with a sensitivity of 76.5% and specificity of 38.9%, ROC AUC 0.55. CONCLUSION: In spontaneously breathing patients after surgical coronary revascularisation, collapsibility of the internal jugular vein did not predict fluid responsiveness.

Association between Biomarkers of Inflammation and 10-Year Changes in Aortic Stiffness: The Multi-Ethnic Study of Atherosclerosis.

Background. Chronic inflammation is associated with incident cardiovascular events. We study the association between biomarkers of inflammation and subclinical vascular dysfunction measured as proximal aortic stiffness. Methods. MRI imaging was performed in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000) and at the 10-year follow-up. Aortic arch pulse wave velocity (PWV) and ascending and descending aorta distensibility (AAD, DAD) were measured in 1223 asymptomatic individuals at both exams. Linear regression was used to study the association of baseline inflammation-C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen (Fib)-with baseline and 10-year changes in aortic stiffness (PWV, AAD, DAD). Results. The mean age of the participants was 59 ± 9 years, 47.8% of them were men, 32.6% were hypertensive at baseline, and 7.6% were diabetic. At baseline and follow-up, the mean AAD values were, respectively, 1.73 × 10-3 mmHg-1 and 1.57 × 10-3 mmHg-1, the mean DAD values were 2.19 × 10-3 mmHg-1 and 1.99 × 10-3 mmHg-1, and the mean PWV values were 8.10 m/s and 8.99 m/s. At baseline, the AAD (in 10-3 mmHg-1) and DAD (in 10-3 mmHg-1) were inversely associated with CRP (in mg/L) (AAD coeff: -0.047, p-value: 0.011, DAD coeff: -0.068, p-value: <0.001) and IL6 (in pg/mL) (AAD coeff: -0.098, p-value: 0.003, DAD coeff: -0.14, p-value: <0.001) in a univariable analysis but not after adjustment for demographic variables or cardiovascular risk factors. The baseline DAD was inversely associated with Fib (in mg/dL) (coeff: -0.334, p-value: 0.001). The baseline PWV (in m/s) was positively associated with IL6 (in pg/mL) in a univariable analysis (coeff: 0.054, p-value: 0.014). In a longitudinal analysis, the 10-year changes in DAD were inversely associated with CRP, even after adjustment for demographics and risk factors (DAD coeff: -0.08, p-value 0.044). Conclusions. Higher CRP levels at baseline were independently associated with a 10-year increase in aortic stiffness, measured as decreased aortic distensibility.

Ascending Aorta 4D Time to Peak Distention Sexual Dimorphism and Association with Coronary Plaque Burden Severity in Women.

Coronary artery disease (CAD) risk and plaque scores are often subjective and biased, particularly in mid-age asymptomatic women, whose CAD risk assessment has been historically underestimated. In this study, a new automatic ascending aorta time-to-peak-distention (TPD) analysis was developed for fast screening and as an independent surrogate for subclinical atherosclerosis in asymptomatic women. CCTA was obtained in 50 asymptomatic adults. Plaque burden segment involvement score (SIS) and automatic TPD were obtained from all subjects. Logistic regression analyses were performed to investigate the association between CAD risk scores and TPD with severe coronary plaque burden (SIS>5). TPD, individually, was found to be a significant predictor of SIS>5. Additionally, sex was a significant effect modifier of TPD, with a stronger statistically significant association with women. Four-dimensional aortic time-to-peak distention could supplement conventional CCTA analysis and offer a quick objective screening tool for plaque burden severity and CAD risk stratification, especially in women.

Design and computational optimization of compliance-matching aortic grafts.

Introduction: Synthetic vascular grafts have been widely used in clinical practice for aortic replacement surgery. Despite their high rates of surgical success, they remain significantly less compliant than the native aorta, resulting in a phenomenon called compliance mismatch. This incompatibility of elastic properties may cause serious post-operative complications, including hypertension and myocardial hypertrophy. Methods: To mitigate the risk for these complications, we designed a multi-layer compliance-matching stent-graft, that we optimized computationally using finite element analysis, and subsequently evaluated in vitro. Results: We found that our compliance-matching grafts attained the distensibility of healthy human aortas, including those of young adults, thereby significantly exceeding the distensibility of gold-standard grafts. The compliant grafts maintained their properties in a wide range of conditions that are expected after the implantation. Furthermore, the computational model predicted the graft radius with enough accuracy to allow computational optimization to be performed effectively. Conclusion: Compliance-matching grafts may offer a valuable improvement over existing prostheses and they could potentially mitigate the risk for post-operative complications attributed to excessive graft stiffness.