Aortic Arch Pulse Wave Velocity Research Articles

Vascular Chemerin from PVAT contributes to Norepinephrine and Serotonin-Induced Vasoconstriction and Vascular Stiffness in a Sex-Dependent Manner.

The adipokine chemerin supports normal blood pressure and contributes to adiposity-associated hypertension, evidenced by falls in mean arterial pressure in Dahl SS rats given an antisense oligonucleotide against chemerin. In humans, circulating chemerin is positively associated with hypertension and aortic stiffness. Mechanisms of chemerin's influence on vascular health and disease remain unknown. We identified chemerin production in the vasculature-the blood vessel and its perivascular adipose tissue (PVAT). Here, using RNAScope®, QPCR, isometric contractility, high frequency ultrasound imaging, and western blot in the Dahl SS rat, we test the hypothesis that endogenous chemerin amplifies agonist-induced vasoconstriction through Chemerin1 and that chemerin drives aortic stiffness in the thoracic aorta. CMKLR1 (Chemerin1) expression was higher in the media, and Rarres2 (chemerin) expression was higher in the PVAT. Chemerin1 antagonism via selective inhibitor CCX832 reduced maximal contraction to norepinephrine (NE) and serotonin (5-HT), but not angiotensin II, in isolated thoracic aorta (PVAT intact) from male Dahl SS rat. In females, CCX832 did not alter contraction to NE or 5-HT. Male, but not female, genetic chemerin knockout Dahl SS rats had lower aortic arch pulse wave velocity than wild types, indicating chemerin's role in aortic stiffness. Aortic PVAT from females expressed less chemerin protein than males, suggesting PVAT as the primary source of active chemerin. We show that chemerin made by the PVAT amplifies NE and 5-HT-induced contraction and potentially induces aortic stiffening in a sex-dependent manner, highlighting the potential for chemerin to be a key factor in blood pressure control and aortic stiffening.

Abstract 13: Vascular Chemerin, Particularly from PVAT, contributes to Norepinephrine and Serotonin-Induced Vasoconstriction and Vascular Stiffness in a Sex-Dependent Manner

The adipokine chemerin has been implicated in healthy blood pressure maintenance and adiposity-associated hypertension, evidenced by falls in mean arterial pressure after administration of an antisense oligonucleotide against chemerin in Dahl SS rats. Circulating levels of chemerin are positively associated, in humans, with hypertension and aortic stiffening—a blood pressure-independent risk factor of cardiovascular disease. While chemerin’s role in blood pressure is observed in whole animals, mechanisms of chemerin’s influence on vascular health and disease remain unknown. Chemerin causes direct vasoconstriction through its main receptor Chemerin1 and indirect vasoconstriction by amplifying electrical field stimulation-induced contraction. We identified chemerin production at the vasculature—the blood vessel and its perivascular adipose tissue (PVAT)—and are working to discover the mechanistic role of vascular chemerin in blood vessel function and disease. Using RNAScope®, QPCR, isometric contractility, western blot, and in vivo imaging, we test the hypothesis that vascular chemerin increases arterial contractility through Chemerin1 and plays a role in aortic stiffening. RNAScope® probes detected CMKLR1 expression in the tunica media and PVAT of the thoracic aorta. QPCR revealed Rarres2 expression was higher in the PVAT, and CMKLR1 expression was higher in the media. Chemerin1 antagonism via the selective inhibitor CCX832 (1μM) significantly reduced maximal contraction to both norepinephrine (NE) and serotonin (5-HT) (see figure), but not angiotensin II, in the male rat +PVAT groups. This supports that PVAT-derived chemerin plays a role in sympathetic stimulation of the vasculature. Interestingly, in females, this change in contractile response to NE and 5-HT was not observed. Western blot showed that females express significantly lower levels of chemerin protein in PVAT, suggesting PVAT as the primary source of active chemerin. Finally, male, but not female, genetic chemerin knockout Dahl SS rats have lower aortic arch pulse wave velocity than wild types (M WT: 3.7 ± .7 M KO: 1.4 ± .3 F WT: 2.6 ± .5, F KO: 1.5 ± .3 m/s, N=4-6/group), highlighting a role of chemerin in aortic stiffening. Thus, chemerin, sourced by the PVAT, plays a significant role in vascular contractility and aortic stiffening in males. Future work will determine if chemerin’s influence is amplified in adiposity-associated hypertension, where chemerin levels are elevated in both sexes.

Abstract 18846: A Noninvasive Smartphone Assessment of Aortic Arch Pulse Wave Velocity and Total Arterial Compliance

Introduction: Several clinical studies including a large multiethnic population (Dallas Heart Study) have shown that total arterial compliance (TAC) and aortic arch pulse wave velocity (PWV aa ) are predictors of cardiovascular disease (CVD) events. Dallas Heart Study also showed that PWV aa predicts brain white matter hyperintensity volume independent of cardiovascular risk factors. Recently, Intrinsic Frequency (IF) analysis of carotid pressure waveform from the Framingham Heart Study was used to predict heart failure (HF) events and CVD (Hypertension, 2021 PMID: 33390053). Aim: Our goal was to show the IF method can determine PWV aa and TAC when applied on carotid pulse waveforms obtained from a standard iPhone camera. Methods: The clinical cohort consisted of 120 individuals (40% women) with ages from 20-92 yrs (mean 53 ± 18), including 54 healthy and 66 patients with CVD (22 HF). Phase-contrast magnetic resonance imaging (PC-MRI) and carotid pressure tonometry data were used to compute TAC. PWV aa values were obtained using PC-MRI flow in ascending and descending aorta (not achieved in 1 patients). A custom Apple iPhone 5S application was used to obtain carotid pulse waves by holding the camera against the neck. IF parameters of iPhone waveforms (calibrated by cuff brachial pressures) were used in machine learning algorithms (IF-iPhone). The models of TAC and PWV aa were developed using 100 participants (99 for PWV aa ) and blindly tested on an additional 20 individuals. Results: In blind tests, iPhone-IF models showed Pearson correlations of r=0.89 and r=0.84 with the measured values of TAC and PWV aa , respectively (Fig.1). Conclusions: Assessment of PWV aa and TAC can be accurately achieved using an unmodified smartphone (iPhone). PWV aa evaluation with an iPhone can be used to identify, predict, and quantify risk of vascular brain damage. A Noninvasive iPhone-based method can be used in a clinical or home setting to routinely assess TAC in the general population or in HF.

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.

Aortic stiffness and impairments in cerebrovascular function in cancer survivorship

An established consequence of anti-cancer treatment is increased aortic stiffness, which impairs the aortic damping of cardiac-generated pulsatile pressure and blood flow. These increased pulsations may result in vascular injury in the microcirculation of target end organs like the brain. The aim of the present study was to determine the ramifications of elevated aortic stiffness on cerebral macro- and microvascular pulsatility and autoregulatory function in cancer survivors. We hypothesized that cerebrovascular pulsatility would be enhanced, and cerebrovascular reactivity (CVR) to elevations in arterial CO 2 would be impaired, both in the large and small cerebral vessels in patients with a history of cancer and anti-cancer treatment versus healthy age- and sex-matched non-cancer controls. Aortic arch pulse wave velocity (aaPWV), a regional measure of stiffness in the proximal aorta, was calculated from echocardiographic views of the aortic valve and the descending aortic arch. Subjects then breathed room air for 60s followed by ~2 minutes of rebreathing with simultaneous collection of end-tidal pressure of CO 2 (P ET CO 2 ). Middle cerebral artery blood flow velocity (MCAv) was assessed using transcranial doppler. Oxygenated (oxy-[Hb]) and deoxygenated (deoxy-[Hb]) cerebral microvascular hemoglobin concentrations were monitored using two near-infrared spectroscopy probes placed over the prefrontal cortices. Pulsatility was assessed at baseline using Gosling’s Pulsatility Index (PI) for both the microvasculature and MCA. To account for changes in perfusion pressure, MAP was collected via finger plethysmography and cerebrovascular conductance indices were calculated for both oxy-[Hb] (CVCi oxy ) and MCAv (CVCi MCA ). CVR was calculated as the slope of CVCi oxy and CVCi MCA over P ET CO 2 during rebreathing. Six women were recruited (n = 3/group). Age was similar between the healthy non-cancer controls (HC) and patients with a history of cancer and anti-cancer treatment (CS) (31.0 ± 7 vs. 32.7 ± 13 years). Baseline ventilatory (P ET CO 2 ), central and cerebral hemodynamics were also similar (all p &gt; 0.05). aaPWV was significantly elevated in CS compared to HC (5.3 ± 0.6 vs. 3.1 ± 1.1 m/s, p = 0.04). Cerebral microcirculation PI in CS was significantly elevated (0.04 ± 0.01 vs. 0.02 ± 0.01, p = 0.02), but MCA PI was not different (p &gt; 0.05). CVR-CVCi oxy was impaired in CS (-3.6 ± 2.8 vs. 1.5 ± 0.5 nM·mmHg -1 /mmHg, p = 0.03), and CVR-CVCi MCA was similarly reduced (-0.05 ± 0.06 vs. 0.15 ± 0.01 mm/sec·mmHg -1 /mmHg, p &lt; 0.01). The increase in MAP during hypercapnia was similar between groups. Consistent with our hypothesis, both CVR-CVCi oxy and CVR-CVCi MCA were attenuated in patients with a history of anti-cancer treatment. Additionally, the microvascular pulsatility was greater in CS. This suggests an impaired cerebrovascular function, possibly related to increased transmission of pulsatility into the brain, in the years following cancer diagnoses and treatment. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract TP99: Non-invasive Aortic Pulse Wave Velocity Is Related To Gold Standard Carotid-femoral Pulse Wave Velocity: Implications For Monitoring Large Artery Stiffness In The Clinic

Introduction: Aortic stiffness is an independent predictor of fatal stroke in both hypertensive populations and healthy subjects, but traditional monitoring methods have had difficulty being incorporated into routine practice. The gold standard, carotid-femoral pulse wave velocity (cfPWV), poses methodological challenges as this method bypasses the most distensible vessel, the proximal aorta. We propose a new method, aortic arch pulse wave velocity (aaPWV) assessed via ultrasound, which encompasses the proximal aorta and can be performed during standard cardiac echocardiography. We sought to determine if the two methods were related. Methods: We recruited 44 healthy volunteers (38.1y [SEM: 2.39], range 20-62y, 80% female) for this study. Both aaPWV and cfPWV were measured by the wave-foot method using a commercial Logic S8 Ultrasound system (GE Healthcare) with synchronous electrocardiogram. cfPWV was calculated by determining the time delay between the two vessels and dividing by the measured distance between the two sites. aaPWV was calculated by determining the time delay between onset of aortic ejection from the apical 5-chamber view and the arrival of the pulse wave at the start of descending aorta in the suprasternal view. Distance for aaPWV was estimated using regression equation from the literature. Results: Paired t-tests revealed cfPWV was significantly greater than aaPWV (5.98 ± 0.17m/s vs. 4.7 ± 0.29m/s; P&lt;0.001). Pearson correlation revealed the two methods were related (r=0.35, P=0.01) and intraclass correlation coefficient revealed good agreement within and between raters (0.75, 0.85 respectively; 0.75-0.9 indicate good agreement). Conclusion: We report that while aaPWV and cfPWV are correlated, significant differences exist, which was expected given the proximal segment is the most elastic portion of the aorta. The findings from this study suggest aaPWV could be a more feasible method to measure large artery stiffness in routinely in the clinic, but future studies are needed to determine if aaPWV is similarly predictive of adverse cardiovascular outcomes.

Cross-Sectional Relationships of Proximal Aortic Stiffness and Left Ventricular Diastolic Function in Adults in the Community.

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)-vascular interactions and associated LV diastolic dysfunction. In a community-based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.5T CMR and transthoracic echocardiographic measures were included. Measures included proximal descending aortic strain and aortic arch pulse wave velocity by CMR (2002-2006) and diastolic function (mitral Doppler E and A wave velocity, E wave area, and LV tissue Doppler e' velocity) by echocardiography (2005-2008). Multivariable linear regression analysis was used to relate CMR aortic stiffness measures to measures of echocardiographic LV diastolic function. All continuous variables were standardized. In multivariable-adjusted regression analyses, aortic strain was inversely associated with E wave deceleration time (estimated β=-0.10±0.032, P=0.001), whereas aortic arch pulse wave velocity was inversely associated with E/A ratio (estimated β=-0.094±0.027, P=0.0006), E wave area (estimated β=-0.070±0.027, P=0.010), and e' (estimated β=-0.061±0.027, P=0.022), all indicating associations of higher aortic stiffness by CMR with less favorable LV diastolic function. Compared with men, women had a larger inverse relationship between pulse wave velocity and E/A ratio (interaction β=-0.085±0.031, P=0.0064). There was no significant effect modification by age or a U-shaped (quadratic) relation between aortic stiffness and LV diastolic function measures. Conclusions Higher proximal aortic stiffness is associated with less favorable LV diastolic function. Future studies may clarify temporal relations of aortic stiffness with varying patterns and progression of LV diastolic dysfunction.

Abstract P139: Association Of Thoracic Aorta Calcification And Aortic Arch Stiffness: The Multi-ethnic Study Of Atherosclerosis

Background: Arterial stiffness (AS) is a robust risk factor for HTN and CVD. It remains unclear how thoracic aortic calcification (TAC) presence, volume, and density relate to AS in the aortic arch. Improved understanding of central AS may provide insight to future mechanistic approaches to prevent and control CVD. Methods: We evaluated 1,385 participants from MESA Exam 5 with TAC data throughout the thoracic aorta via Chest CT and pulse wave velocity (PWV) as a measure of AS across the aortic arch via MRI. We used linear regression models to assess cross-sectional associations of TAC presence, volume, and density with aortic arch PWV with adjustment for 1) age, sex, and race; and 2) age, sex, race, BMI, diabetes, estimated glomerular filtration rate, HTN-medication use, SBP, DBP, total cholesterol/high-density lipoprotein ratio, smoking status, CAC volume, CAC density, education, physical activity, and sedentary behavior. Results: Participants were a mean age of 69 years (SD 9) [717 (52%) female; 509 (37%) White, 359 (26%) Black, 285 (21%) Hispanic/Latino, and 232 (17%) Chinese]. Calcification was present in 1,263 (91%) and 1,228 (89%) participants in the entire thoracic aorta and aortic arch, respectively, compared to 848 (61%) and 138 (10%) in the descending and ascending aorta segments. Calcium volume in the entire thoracic aorta and aortic arch were highly correlated (r=0.94) with respective means of 866 (SD 1,724) and 564 (1,014) mm 3 . Mean PWV across the aortic arch was 9 m/sec (SD 4). After full adjustment, the presence of aortic arch calcification, compared to no aortic arch calcification, was associated with a 0.76 m/sec higher mean PWV (95% CI: 0.34 - 1.18; p&lt;0.01), while a 1,000 mm 3 increment in aortic arch calcium volume was associated with 0.36 m/sec higher mean PWV (95% CI: 0.08-0.64; p=0.01). Results were similar when calcification in the entire thoracic aorta was the primary predictor variable. Conversely, there were no significant associations between mean or maximum calcium density measures and aortic arch PWV. Conclusion: TAC is highly prevalent in the thoracic aorta, especially the aortic arch. Calcification presence and higher calcification volume in the thoracic aorta, as well as the aortic arch itself, are associated with greater aortic arch AS.

Regional Vascular Changes and Aortic Dilatation in Pediatric Patients With Bicuspid Aortic Valve

BackgroundBicuspid aortic valve (BAV) is the most common congenital heart disease, often associated with valve dysfunction, coarctation of the aorta, and ascending aorta dilatation. Aortic dilatation might result from abnormal regional hemodynamics or inherent vascular disease. Vascular function in pediatric BAV remains poorly characterized. MethodsA cross-sectional study was performed to evaluate vascular function in 142 children with BAV aged 7-18 years compared with healthy control children. Echocardiography was performed to assess aortic dimensions, BAV function, and vascular function (aortic arch pulse wave velocity [PWV]), carotid intima media thickness, and aortic stiffness and distensibility). Carotid-femoral and carotid-radial PWV were assessed using tonometry. Vascular function was compared for 4 patient groups stratified according to aortic dilatation and a history of coarctation of the aorta. Multivariate regression analysis was performed to determine predictors of aortic dilatation. ResultsChildren with BAV had stiffer and less distensible ascending aortas with higher aortic arch PWV compared with control children. Carotid-femoral and carotid-radial PWV were not increased in patients with BAV, and the vascular assessment of the abdominal aorta was unremarkable. Multivariate regression revealed that aortic arch PWV was the only vascular function parameter that was associated with aortic dilatation. ConclusionsChildren with BAV have differences in vascular function that are confined to their proximal aorta, even in normal functioning BAV. The observed differences in vascular function are likely multifactorial, with contributions from abnormal regional flow and a potential localized primary aortopathy.

Effects of Exercise and Weight Loss on Proximal Aortic Stiffness in Older Adults With Obesity.

Obesity may accelerate age-related increases in aortic stiffness. Although aerobic exercise training generally has favorable effects on aortic structure and function, exercise alone may not be sufficient to improve aortic stiffness in older adults with obesity. We determined the effects of aerobic exercise training with and without moderate- to high-caloric restriction (CR) on the structure and function of the proximal aorta in 160 older (65-79 years) men and women with obesity (body mass index=30-45 kg/m2). Participants were randomly assigned to 1 of 3 groups: aerobic exercise training only (treadmill 4 days/week for 30 minutes at 65% to 70% of heart rate reserve; n=56), aerobic exercise training plus moderate CR (n=55), or aerobic exercise training plus more intensive CR (n=49) for 20 weeks. Aortic pulse wave velocity, aortic distensibility, and other measures of aortic structure and function were assessed by cardiovascular magnetic resonance imaging. Pearson correlation coefficients were examined to assess associations between changes in proximal aortic stiffness and changes in fitness, fatness, and other potential confounders. Weight loss in the aerobic exercise training plus moderate CR (-8.0 kg [95% CI, -9.17 to -6.87]) and aerobic exercise training plus more intensive CR (-8.98 kg [95% CI, -10.23 to -7.73) groups was significantly greater compared with the aerobic exercise training-only group (-1.66 kg [95% CI, -2.94 to -0.38]; P<0.017 for both). There were significant treatment effects for descending aorta distensibility (P=0.008) and strain (P=0.004) and aortic arch pulse wave velocity (P=0.01) with the aerobic exercise training plus moderate CR group having a 21% increase in distensibility (P=0.016) and an 8% decrease in pulse wave velocity (P=0.058). None of the aortic stiffness measures changed significantly in the aerobic exercise training-only or aerobic exercise training plus more intensive CR groups, and there were no significant changes in any other measure of aortic structure or function in these groups. Overall, increases in aortic distensibility were correlated with improvements in body weight and body fat distribution, but these associations were not statistically significant after adjustment for multiple comparisons. In older adults with obesity, combining aerobic exercise with moderate CR leads to greater improvements in proximal aortic stiffness than exercise alone. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01048736.

Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch

PurposeWall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement.MethodsFlow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE−/− mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification.Results4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE−/− mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m2 in wildtype mice and (1.27 ± 0.10) N/m2 in ApoE−/− mice.ConclusionThe post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements.

Abnormal Aortic Wall Properties in Women with Turner Syndrome.

Background Turner syndrome (TS) is associated with aortic dilatation and dissection, but the underlying process is unclear. The aim of this study was to investigate the elastic properties and composition of the aortic wall in women with TS. Methods In this cross-sectional study, 52 women with TS aged 35 ± 13 years (50% monosomy, 12 with bicuspid aortic valve [BAV] and 4 with coarctation) were investigated using carotid-femoral pulse wave velocity (CF-PWV) by echocardiography and ascending aortic distensibility (AAD) and aortic arch pulse wave velocity (AA-PWV) by magnetic resonance imaging (MRI). As control group, 13 women with BAV without TS and 48 healthy patients were included. Results Women with TS showed a higher AA-PWV (β = 1.08, confidence interval [CI]: 0.54–1.62) after correcting for age and comorbidities compared with controls. We found no significant difference in AAD and CF-PWV. In women with TS, the presence of BAV, coarctation of the aorta, or monosomy (45, X) was not associated with aortic stiffness. In addition, aortic tissue samples were investigated with routine and immunohistochemical stains in five additional women with TS who were operated. The tissue showed more compact smooth muscle cell layers with abnormal deposition and structure of elastin and diminished or absent expression of contractile proteins desmin, actin, and caldesmon, as well as the progesterone receptor. Conclusion Both aortic arch stiffness measurements on MRI and histomorphological changes point toward an inherent abnormal thoracic aortic wall in women with TS.

Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI: Pilot Study

Abnormal maternal vascular function during pregnancy stemming from systemic endothelial dysfunction (EDF) has a central role in the pathophysiology of preeclampsia (PE). To utilize quantitative MRI to investigate changes in physiological measures of vascular reactivity during normal pregnancy, and to explore EDF associated with preeclampsia. Prospective. Healthy pregnant (HP) (n = 14, mean GA = 26 ± 7 weeks) and nonpregnant women (NP; n = 14); newly postpartum (PP <48 hours) women with severe PE (PP-PE; n = 4) and normotensive pregnancy (PP-HP; n = 5). 1.5T/3T. RF spoiled multiecho gradient-recalled echo, 1D phase-contrast MRI, time-of-flight. The micro- and macrovascular function (vasodilatory capacity of arterioles and conduit arteries, respectively) of the femoral vascular bed was evaluated with MRI-based venous oximetry, arterial velocimetry, and luminal flow-mediated dilation quantification, during cuff-induced reactive hyperemia. Aortic arch pulse-wave velocity (aPWV) was quantified to assess arterial stiffness using an ungated 1D technique. Two-tailed unpaired t-tests were performed to address our two, primary a priori comparisons, HP vs. NP, and PP-PE vs. PP-HP. Given the pilot nature of this study, adjustments for multiple comparisons were not performed. In HP, microvascular function was attenuated compared to NP by a significant increase in the washout time (10 ± 2 vs. 8 ± 2 sec; P < 0.05) and reduced upslope (2.1 ± 0.5 vs. 3.2 ± 0.8%HbO2 /s; P < 0.05), time of forward flow (28 ± 5 vs. 33 ± 6 sec, P < 0.05), and hyperemic index (11 ± 3 vs. 16 ± 4 cm/s2 ; P < 0.05), but luminal flow-mediated dilatation (FMDL )was comparable between HP and NP. PP-PE exhibited significant vascular dysfunction compared to PP-HP, as evidenced by differences in upslope (2.2 ± 0.6 vs. 1.3 ± 0.2%HbO2 /s, P < 0.05), overshoot (16 ± 5 vs. 7 ± 3%HbO2 , P < 0.05), time of forward flow (28 ± 6 vs. 15 ± 7 s, P < 0.05), and aPWV (7 ± 1 vs. 8 ± 1 m/s, P < 0.05). Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.

The role of insulin resistance in the relation of visceral, abdominal subcutaneous and total body fat to cardiovascular function

Background and aimsThe separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling. Methods and resultsIn this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): −0.04 (−0.09;0.01) per SD (54 cm2) VAT; −0.05 (−0.10;0.00) per SD (94 cm2) aSAT; −0.09 (−0.16;-0.02) per SD (8%) TBF; −0.11 (−0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: −8.9 (−11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA-IR to the model to evaluate the mediating role of insulin resistance, change in E/A was −0.02 (−0.07;0.04) per SD VAT; −0.03 (−0.08;0.02) per SD aSAT; −0.06 (−0.13;0.01) per SD TBF, and change in LV end-diastolic volume was −7.0 (−9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity. ConclusionInsulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function.

Dynamic Effects of Aortic Arch Stiffening on Pulsatile Energy Transmission to Cerebral Vasculature as A Determinant of Brain-Heart Coupling

Aortic stiffness increases with age and is a robust predictor of brain pathology including Alzheimer’s and other dementias. Aging causes disproportionate stiffening of the aorta compared with the carotid arteries, reducing protective impedance mismatches at their interface and affecting transmission of destructive pulsatile energy to the cerebral circulation. Recent clinical studies have measured regional stiffness within the aortic arch using pulse wave velocity (PWV) and have found a stronger association with cerebrovascular events than global stiffness measures. However, effects of aortic arch PWV on the transmission of harmful excessive pulsatile energy to the brain is not well-understood. In this study, we use an energy-based analysis of hemodynamic waves to quantify the effect of aortic arch stiffening on transmitted pulsatility to cerebral vasculature, employing a computational approach using a one-dimensional model of the human vascular network. Results show there exists an optimum wave condition—occurring near normal human heart rates—that minimizes pulsatile energy transmission to the brain. This indicates the important role of aortic arch biomechanics on heart-brain coupling. Our results also suggest that energy-based indices of pulsatility combining pressure and flow data are more sensitive to increased stiffness than using flow or pressure pulsatility indices in isolation.

P1830 Single-beat aortic arch pulse wave velocity by dual-gate simultaneous Doppler technique: a novel method for arterial stiffness evaluation

Abstract Background Guidelines recommend increased aortic stiffness as a negative prognostic factor to be considered in primary and secondary prevention. Pulse wave velocity (PWV) is a frequently employed surrogate marker of aortic stiffness. Carotid-femoral PWV is the most common index in research and clinical practice, but recently several velocity-encoded magnetic resonance imaging (MRI) techniques have been used for the evaluation of regional aortic arch PWV, where the stiffness seems to be particularly relevant from a prognostic point of view. Purposes. We developed a new ultrasound method for the assessment of aortic arch PWV, using a single-beat dual-gate simultaneous pulsed wave Doppler tracing. The aim of the study is to evaluate the feasibility of this new technique in a group of healthy volunteers. Methods We examined 126 healthy volunteers (81 females, 45 males, mean age 42 + 15 years, range 13-83 years) using a commercially available machine equipped with simultaneous dual-gate pulsed Doppler. Using the suprasternal approach, the first sample volume was placed in ascending aorta and the second one in descending aorta. The distance between the two sites was directly measured with a curvilinear tracing in the middle of the vessel, following the shape of the aortic arch. PWV was calculated as the ratio of distance (in millimiters) and the transit time (in milliseconds) measured using the "foot-to-foot" method. The results are then easily transformed, simplifying in the commonly unit of meters/second. Results Feasibility was 99%; in one case it was not possible to measure accurately the aortic arch PWV due to unfavorable suprasternal acustic window. The procedure time was very fast, requiring 2 + 1 minutes. Intraobserver and interobserver variability were 7% and 9% respectively. Aortic arch PWV, as expected, showed a strong correlation with age in males as well as in females (r= 0.71 and r = 0.60 respectively, p &amp;lt; 0.001 for both); there was also a significant correlation with body mass index (r = 0.31; p &amp;lt; 0.001). Aortic arch PWV values ranged from 3.1 to 8.5 m/s, showing a substantial overlap with normal values reported in MRI studies. Conclusions The direct measurement of aortic arch PWV is feasible and reproducible with ultrasound, using the novel single-beat dual-gate simultaneous pulsed wave Doppler tracing. This technique could be implemented in a standard echo examination, that is much more available than MRI studies. Further studies are needed to evaluate if Doppler-derived aortic arch PWV could provide additional prognostic information. Abstract P1830 Figure. Aortic Arch PWV

Aortic elasticity after aortic coarctation relief: comparison of surgical and interventional therapy by cardiovascular magnetic resonance imaging

BackgroundPatients after aortic coarctation (CoA) repair show impaired aortic bioelasticity and altered left ventricular (LV) mechanics, predisposing diastolic dysfunction. Our purpose was to assess aortic bioelasticity and LV properties in CoA patients who underwent endovascular stenting or surgery using cardiovascular magnetic resonance (CMR) imaging.MethodsFifty CoA patients (20.5 ± 9.5 years) were examined by 3-Tesla CMR. Eighteen patients had previous stent implantation and 32 had surgical repair. We performed volumetric analysis of both ventricles (LV, RV) and left atrium (LA) to measure biventricular volumes, ejection fractions, left atrial (LA) volumes, and functional parameters (LAEFPassive, LAEFContractile, LAEFReservoir). Aortic distensibility and pulse wave velocity (PWV) were assessed. Native T1 mapping was applied to examine LV tissue properties. In twelve patients post-contrast T1 mapping was performed.ResultsLV, RV and LA parameters did not differ between the surgical and stent group. There was also no significant difference for aortic distensibility, PWV and T1 relaxation times. Aortic root distensibility correlated negatively with age, BMI, BSA and weight (p < 0.001). Native T1 values correlated negatively with age, weight, BSA and BMI (p < 0.001). Lower post-contrast T1 values were associated with lower aortic arch distensibility and higher aortic arch PWV (p < 0.001).ConclusionsCoA patients after surgery or stent implantation did not show significant difference of aortic elasticity. Thus, presumably other factors like intrinsic aortic abnormalities might have a greater impact on aortic elasticity than the approach of repair. Interestingly, our data suggest that native T1 values are influenced by demographic characteristics.

Non-invasive assessment of ventriculo-arterial coupling using aortic wave intensity analysis combining central blood pressure and phase-contrast cardiovascular magnetic resonance.

Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms. Two hundred and six healthy volunteers (age range 21-73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, -6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P < 0.01 for both). Increasing age decade and female sex were independently associated with decreased forward compression wave (-8.6 and -20.7 W/m2/cycle2, respectively, P < 0.01) and greater wave reflection index (0.02 and 0.03, respectively, P < 0.001). This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals.

Muscadine Grape Extract Treatment Improves Aortic Pulse Wave Velocity and Superior Mesenteric Artery Pulsatility Index in Hypertensive Transgenic (mRen2)27 Female Rats

Hypertension is a major risk factor for heart disease and stroke, the leading causes of death in the United States. Hypertension is characterized by changes in vascular hemodynamics including vascular stiffness of the elastic conduit arteries and increased peripheral vascular resistance of the smaller muscular arteries that are associated with tissue damage. Dietary phenolic compounds are linked to beneficial cardiovascular effects. In this study, we investigated the influence of a muscadine grape extract (MGE; Piedmont Research &amp; Development Corp.) on arterial stiffness and peripheral vascular resistance in hypertensive transgenic (mRen2)27 rats. We also investigated whether sex modulates MGE effects on arterial dysfunction in this rat model. MGE was administered in drinking water (0.2 mg polyphenolics/mL) starting at the age of 14 weeks, control animals were given regular water (n = 5 in each group, control and MGE‐treated female; n = 4 in each group, control and MGE‐treated male). After 6 weeks of treatment, noninvasive cardiovascular hemodynamic measurements were performed using a preclinical ultrasound system, Vevo LAZR (Fujifilm, Visual Sonics). Systolic blood pressure was measured using tail cuff plethysmography (NIBP‐8, Columbus instruments, Ohio). Aortic arch pulse wave velocity (PWV) was used as a measure of arterial stiffness and superior mesenteric artery (SMA) pulsatility index (PI), defined as PI = [(peak systolic velocity‐ end diastolic velocity)/mean flow velocity] was used as an indicator of peripheral vascular resistance. (mRen2)27 rats treated with MGE had lower aortic arch PWV compared with controls in both male (2.31 ± 0.33 vs. 3.79 ± 0.37 m/s, p &lt; 0.05) and female (2.44 ± 0.13 vs. 3.62 ± 0.37 m/s, p &lt; 0.05) rats. In addition, MGE‐treated female rats had lower SMA PI than control females (0.97 ± 0.07 vs. 1.27 ± 0.10, p &lt; 0.05). There were no significant effects of the extract on SMA PI in males (1.19 ± 0.05 vs. 1.34 ± 0.07). These MGE effects were independent of changes in body weight (508 ± 3 vs. 493 ± 9 g in males, 282 ± 5 vs. 280 ± 5 g in females), cardiac index (4.5 ± 0.1 vs. 4.6 ± 0.3 mg/g in males, 4.9 ± 0.3 vs. 4.5 ± 0.2 mg/g in females), systolic blood pressure (188 ± 5 vs. 199 ± 4 mm Hg in males, 191 ± 12 vs. 194 ± 12 mm Hg in females) or cardiac function. In conclusion, six weeks of MGE treatment improved arterial stiffness in both male and female hypertensive rats. More pronounced beneficial vascular effects in females suggest that MGE actions in the arterial vasculature are modulated by sex.Support or Funding InformationChronic Disease Fund Research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Thoracic Aortic Intima-Media Thickness in Preschool Children Born Small for Gestational Age

To assess thoracic aortic intima-media thickness (aIMT) as a marker of thoracic aortic remodeling in children born small for gestational age (SGA). We assessed thoracic aIMT, carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) in 239 patients (117 SGA; 122 appropriate for gestational age controls) age 6-8years. Each SGA participant was matched 1:1 based on sex, gestational age, and birth date. Thoracic aIMT was determined by 2-dimensional transthoracic echocardiography. SGA children showed a significant increase in both aIMT (0.89mm [0.12] vs 0.79mm [0.11], P<.001) and cIMT (.50mm [0.05] vs 0.49mm [0.04], P<.001) compared with appropriate for gestational age controls, but the magnitude of the difference in aIMT was greater than that in cIMT (standardized difference of the means: +84% vs +27%). aIMT was linearly correlated with aortic arch PWV as measured by echocardiography (r=0.211, P<.001) but not with carotid-femoral PWV (r=0.113, P=.111). Born SGA was independently associated with increased aIMT after controlling for perinatal, anthropometric, and biochemical determinants in linear regression models. SGA children exhibit increased thoracic aIMT and aortic arch PWV in early childhood that may suggest the presence of structural changes in the thoracic aorta wall architecture. Measurement of ascending aIMT by transthoracic echocardiography is feasible and reproducible and may be a useful marker of vascular disease.