Aortic Pulse Research Articles

Estudio de la asociación de marcadores de rigidez arterial central y periférica con la función renal en pacientes con hipertensión arterial, diabetes mellitus y enfermedad renal crónica

Rationale and objectivesIncreased aortic or central arterial stiffness (CAS) is a major factor in cardiovascular morbidity and mortality in patients with vascular risk factors. Decreased glomerular filtration rate (GFR) and increased urinary albumin excretion (uALB) are associated with lethal and non-lethal cardiovascular events. The pathophysiological mechanisms of this association are not fully defined.The aim of this study was: 1.- To analyze the CAS, comparing several markers, in subjects with arterial hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD) and their combination. 2.- To study the possible association of CAS with renal dysfunction (decrease in GFR and increase in uALB). Material and methodsA total of 286 subjects were included, divided into several groups: Control (n: 38); HTN (n:51); DM without CKD (n:26); CKD without DM (n:77); CKD with DM (n:94). Several indices obtained by applanation tonometry were used to determine the CAS: carotid-femoral pulse velocity (VPc-f); central pulse pressure (cPP); augmentation index standardized to a cardiac frequency of 75 l/min (IA75); peripheral / aortic arterial stiffness gradient (ASGp-a). As a marker of peripheral arterial stiffness, the carotid-radial pulse velocity (PVc-r) was determined. The ASGp-a was calculated from the PVc-r /PVc-f ratio. The subendocardial viability index (iBuckberg) was obtained from the aortic pulse wave.Multiple regression, binary logistic regression, and multinomial regression were used to study the association between arterial stiffness markers and renal function. ResultsThe adjusted values of the PVc-f [(median (interquartile range) (m/sec)] were significantly higher in subjects with DM [(9 (1.2)], CKD [(9.4 (0.7)] and DM with CKD [(10.9 (0.7)] than in the control group [(8.2 (1.3)] and group with HTN [(8.3 (0.9)], (p:0.001). Patients with DM with CKD had higher PVc-f values than all other groups (p: 0.001). The ASGp-a of the patients was significantly lower than that of the controls, and the group with DM with CKD had significantly lower values than the other groups. The cPP in the DM with CKD group was significantly higher than in the other groups. All patients had an AI75 higher than the control group.When all aortic stiffness markers were introduced together in the regression, PV c-f was the only one that, after multivariate adjustment, was independently and inversely associated with GFR (β; –4, p:0.001) and predicted the presence of GFR decrease (< 60mL/min/1.73 m2), [(OR (95%CI): 1.50 (1.17-1.92; p:0.001]. The PVc-f was the only index directly associated with albuminuria (β: 0.15, p: 0.02) and predicted the existence of abnormal albuminuria (> 30mg/g), [(OR; 1.66 (1.25-2.20), p:0.001)]. The PVc-f was also associated with the iBuckberg (β: -2.73, p: 0.01).Multinomial regression confirmed that PVc-f is a significant determinant of GFR and uALB. On the other hand, the increase in PVc-f and the presence of DM contribute significantly to the magnitude of albuminuria. ConclusionsAortic stiffness increases in the presence of vascular risk factors such as hypertension, DM and CKD. This increase is greater when DM and CKD coexist. Increased aortic stiffness is inversely associated with GFR and directly with uALB, and is predictive of decreased GFR and abnormal uALB. The VPc-f is the parameter of aortic stiffness that is most consistently associated with renal dysfunction. Increased aortic stiffness could be one of the pathomechanisms linking renal dysfunction to cardiovascular events.

Aortic calcification accelerates cardiac dysfunction via inducing apoptosis of cardiomyocytes.

Vascular calcification (VC) is a known predictor of cardiovascular events in patients with atherosclerosis and chronic renal disease. However, the exact relationship between VC and cardiovascular mortality remains unclear. Herein, we investigated the underlying mechanisms between VC progression, arterial stiffness, and cardiac dysfunction. C57BL/6 mice were administered intraperitoneally vitamin D3 (VD3) at a dosage of 35×104 IU/day for 14 days. At day 42, VC extent, artery elasticity, carotid artery blood flow, aorta pulse propagation velocity, cardiac function, and pathological changes were evaluated. Heart apoptosis was detected using TUNEL and immunohistochemistry staining. In vitro, rat cardiomyocytes H9C2 were exposed to media from calcified rat vascular smooth muscle cells (VSMCs) cultured in calcification medium, and then H9C2 apoptosis and gene expression related to cardiac function were assessed. VD3-treated mice displayed a significant aortic calcification, increased pulse propagation velocity of aortae, and reduced cardiac function. Aortae showed increased calcification and elastolysis, with increased heart apoptosis. Hearts demonstrated higher levels of ANP, BNP, MMP2, and lower levels of bcl2/bax. Moreover, calcified rat VSMC media induced H9C2 apoptosis and upregulated genes expression linked to cardiac dysfunction. Our data provide evidence that VC accelerates cardiac dysfunction, partially by inducing cardiomyocytes apoptosis.

Liensinine improves AngII-induced vascular remodeling via MAPK/TGF-β1/Smad2/3 signaling

Ethnopharmacological relevanceLiensinine(Lien, C37H42N2O6) is an alkaloid compound from plumula nelumbinis that demonstrates an antihypertensive effect. The protective effects of Lien on target organs during hypertension are still unclear.Aim of the study: This study aimed to understand the mechanism of Lien during the treatment of hypertension, with emphasis on vascular protection. Materials and methodsLien was extracted and isolated from plumula nelumbinis for further study. In vivo model of Ang II-induced hypertension, non-invasive sphygmomanometer was used to detect the blood pressure in and out of the context of Lien intervention. Ultrasound was used to detect the abdominal aorta pulse wave and media thickness of hypertensive mice, and RNA sequencing was used to detect the differential genes and pathways of blood vessels. The intersection of Lien and MAPK protein molecules was detected by molecular interconnecting technique. The pathological conditions of abdominal aorta vessels of mice were observed by HE staining. The expression of PCNA, α-SMA, Collagen Type Ⅰ and Collagen Type Ⅲ proteins were detected by IHC. The collagen expression in the abdominal aorta was detected by Sirius red staining. The MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA was detected by Western blot. In vitro, MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA were detected by Western blot, and the expression of α-SMA was detected by immunofluorescence; ELISA was used to detect the effect of ERK/MAPK inhibitor PD98059 on Ang Ⅱ-induced TGF-β1secrete; and the detection TGF-β1and α-SMA protein expression by Western blot; Western blot was used to detect the effect of ERK/MAPK stimulant12-O-tetradecanoyl phorbol-13-acetate (TPA) on the protein expression of TGF-β1 and α-SMA. ResultsLien displayed an antihypertensive effect on Ang Ⅱ-induced hypertension, reducing the pulse wave conduction velocity of the abdominal aorta and the thickness of the abdominal aorta vessel wall, ultimately improving the pathological state of blood vessels. RNA sequencing further indicated that the differential pathways expressed in the abdominal aorta of hypertensive mice were enriched in proliferation-related markers compared with the Control group. The profile of differentially expressed pathways was ultimately reversed by Lien. Particularly, MAPK protein demonstrated good binding with the Lien molecule. In vivo, Lien inhibited Ang Ⅱ-induced abdominal aorta wall thickening, reduced collagen deposition in the ventral aortic vessel, and prevented the occurrence of vascular remodeling by inhibiting MAPK/TGF-β1/Smad2/3 signaling activation. In addition, Lien inhibited the activation of Ang II-induced MAPK and TGF-β1/Smad2/3 signaling, attenuating the expression of PCNA and inhibiting the reduction of α-SMA, collectively playing a role in the inhibition of Ang Ⅱ-induced hypertensive vascular remodeling. PD98059 alone could inhibit Ang Ⅱ-induced elevation of TGF-β1 and the decrease of α-SMA expression. Further, PD98059 combined with Lien had no discrepancy with the inhibitors alone. Simultaneously TPA alone could significantly increase the expression of TGF-β1 and decrease the expression of α-SMA. Further, Lien could inhibit the effect of TPA. ConclusionThis study helped clarify the protective mechanism of Lien during hypertension, elucidating its role as an inhibitor of vascular remodeling and providing an experimental basis for the research and development of novel antihypertensive therapies.

P23: Preservation of Pulsatility with Universal Ventricular Assist Device: An In Vitro Assessment of Biventricular Support

Objective: The objective of this study was to assess the ability and performance of the Universal Ventricular Assist Device (UVAD) to maintain pulsatility when used as a biventricular assist device (BVAD) through an in vitro experiment utilizing a pulsatile biventricular mock circulatory loop. Methods: The UVAD pumps were evaluated in a dual configuration (BVAD) in the simulated circulatory model under conditions of left heart failure (HF), right HF, and moderate/severe biventricular HF. Measurements of total flow, pulse pressure in the aorta, pulse augmentation factor (PAF), energy-equivalent pressure (EEP), and surplus hemodynamic energy (SHE) were taken at various pump speeds to assess pulsatility. Results: The association between the maximum and minimum pressures and various parameters of the pump was determined during the cardiac cycle. It was observed that the pulse pressure increased across all heart conditions (Figure 1). The PAF ranged from 17-35% in healthy, LHF, RHF, and mild BHF conditions, with the highest PAF, 90%, being observed in the severe BHF condition. EEP correlated with LVAD flow in all groups (R2 = 0.87-0.97) and increased from baseline in all cases. SHE peaked at approximately 5-6 L/min of LVAD support and tended to dissipate surplus energy at higher LVAD pump flow. The greatest decrease in SHE from baseline, 53%, was observed in the mild BHF condition with the highest levels of left ventricular assist device (LVAD) and right ventricular assist device (RVAD) support. Conclusion: The UVAD successfully demonstrated the ability to preserve pulsatility in vitro, and to optimize cardiac output, as an isolated circulatory support device option (RVAD or LVAD), and when used for BVAD support.Figure 1. The relationships between LVAD/RVAD pump flow and aortic pulse pressure/PAF/EEP/SHE in each heart condition. LVAD, left ventricular assist device; RVAD, right ventricular assist device; AoP, aortic pressure; EEP, energy-equivalent pressure; SHE, surplus hemodynamic energy.

Methods of arterial stiffness calculation and cardiovascular disease events: the multiethnic study of atherosclerosis.

A wide variety of different formulae have been used to calculate local arterial stiffness with little external validation in relationship to cardiovascular events. We compared the associations of several arterial stiffness calculations in a large, multiethnic cohort. The multi-ethnic study of atherosclerosis (MESA) is a longitudinal study of 6814 adults without clinical cardiovascular disease (CVD) at enrollment. MESA participants with CVD surveillance through year 2018 and carotid ultrasound ( n = 5873) or aorta MRI ( n = 3175) at the baseline exam (2000-2002) were included. We analyzed 21 different calculations of local arterial stiffness. Cross-sectional and longitudinal statistical analyses were performed in addition to Cox hazard modeling for associations with CVD events (myocardial infarction, resuscitated cardiac arrest, stroke, adjudicated angina, and cardiovascular death). Carotid artery stiffness calculations had variable correlations with each other ( r = 0.56-0.99); aortic stiffness measures were similar ( r = 0.66-0.99). Nevertheless, for CVD events, the hazard ratio (HR) per standard deviation change were similar for all carotid stiffness calculations with HRs in the range of 1.00-1.10 (equivalence P < 0.001). For the aorta, aortic distensibility coefficient had a stronger association with CVD events (HR 1.18 [1.02-1.37]) compared to aorta Peterson's elastic modulus (HR 0.98 [0.89-1.07]) and aorta pulse wave velocity (HR 1.00 [0.90-1.11]). HRs between all other aortic stiffness calculations were equivalent ( P < 0.01). Different methods of calculating local arterial stiffness largely gave equivalent results, indicating that the variety of different arterial stiffness calculations in use do not cause inconsistent findings.

Berberine Improves Vascular Dysfunction by Inhibiting Trimethylamine-N-oxide via Regulating the Gut Microbiota in Angiotensin II-Induced Hypertensive Mice

Berberine (BBR) has been demonstrated to exert cardiovascular protective effects by regulating gut microbiota. However, few studies examine the effect of BBR on the gut microbiota in hypertension. This study aims to investigate the role of BBR in regulating microbial alterations and vascular function in hypertension. C57BL/6 J mice were infused with Ang II (0.8 mg/kg/day) via osmotic minipumps and treated with BBR (150 mg/kg/day) or choline (1%) for 4 weeks. Blood pressure was detected by tail-cuff measurement once a week. Abdominal aorta pulse wave velocity (PWV) and endothelium dependent vasodilatation were measured to evaluate vascular function. Vascular remodeling was assessed by histological staining of aortic tissue. The fecal microbiota was profiled using 16S ribosomal DNA (rDNA) sequencing. Plasma trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) and hepatic FMO3 expression were measured. We found that BBR treatment significantly alleviated the elevated blood pressure, vascular dysfunction, and pathological remodeling in Ang II-induced hypertensive mice, while choline treatment aggravated hypertension-related vascular dysfunction. 16S rDNA gene sequencing results showed that BBR treatment altered gut microbiota composition (reduced the Firmicutes/Bacteroidetes (F/B) ratio and increased the abundances of Lactobacillus). Moreover, BBR inhibited FMO3 expression and plasma TMA/TMAO production in hypertensive mice. TMAO treatment increased the apoptosis and oxidative stress of human aortic endothelial cells (HAECs) and aggravated Ang II-induced HAECs dysfunction in vitro. These results indicate that the protective effect of BBR in hypertension might be attributed (at least partially) to the inhibition of TMAO production via regulating the gut microbiota.

Артериальная ригидность у пациентов с острым коронарным синдромом без стойкого подъема сегмента ST в сочетании с хронической болезнью почек и артериальной гипертензией и ее коррекция на фоне антигипертензивной терапии

Objective: to study arterial stiffness in patients with acute coronary syndrome without ST elevation, who have hypertension (AH) and stage 2-3A chronic kidney disease (CKD) and to assess the ability of angiotensin-converting enzyme inhibitor perindopril and angiotensin receptor antagonist losartan to reduce arterial stiffness in these patients. Materials and Methods. We studied 44 patients with ACS without ST elevation combined with CKD stage 2-3A, AH (the 1st group). The comparison groups were the ACS without ST segment elevation, AH patients with normal renal function (the 2nd group, n=27) and the 3rd group (n=44) of patients with chronic CHD, AH and CKD. Group 1 patients were divided into 2 subgroups taking perindopril or losartan. The parameters of vascular wall stiffness (pulse wave velocity (PWV), cardio-ankle vascular index (CAVI), ankle brachial index (ABI), aortic augmentation index (AI), central systolic and pulse aortic pressure, peripheral blood pressure (BP), estimated glomerular filtration rate (GFR) were assessed.) Results. The patients with ACS without ST elevation combined with 2-3A stages of CKD and AH had a significantly higher cPAP, AI, PWV, and CAVI than the patients of the 2nd group. During 3 months of complex therapy with perindopril, a decrease in PWV, cSAP, cPAP, AI was observed. There were no significant differences in the effects of perindopril and losartan on peripheral and central blood pressure, on renal function, on arterial stiffness parameters. Conclusion. Patients with AH and CKD stage 2-3A have more pronounced arterial stiffness compared to similar patients with normal GFR. Antihypertensive therapy with perindopril and losartan allows to reach target levels of peripheral BP, significantly reduce central aortic pressure and improve elastic properties of the arterial vascular wall.

Aortic Root Dimensions and Pulse Wave Velocity in Young Competitive Athletes

The assessment of aortic root dimensions is a cornerstone in cardiac pre-participation screening as dilation can result in severe cardiac events. Moreover, it can be a hint for an underlying connective tissue disease, which needs individualized sports counseling. This study examines the prevalence of aortic root dilatation in a cohort and its relationship to arterial stiffness as an early marker of cardiovascular risk due to vascular aging. From May 2012 to March 2018, we examined 281 young male athletes (14.7 ± 2.1 years) for their aortic root dimension. Moreover, we noninvasively assessed arterial stiffness parameter during pre-participation screening. Mean aortic diameter was 25.9 ± 3.1 mm and 18 of the 281 (6.4%) athletes had aortic root dilation without other clinical evidence of connective tissue disease. After adjusting for BSA, there was no association of aortic root diameter to pulse wave velocity (p = −0.054 r = 0.368) nor to central blood pressure (p = −0.029 r = 0.634). Thus, although a significant proportion of young athletes had aortic root dilatation, which certainly needs regular follow up, no correlation with arterial stiffness was found. It could be suggested that a dilated aortic root in young athletes does not alter pulse waveform and pulse reflection, and thus there is no increased cardiovascular risk in those subjects.

Abstract 9538: Comparison of Central Aortic Pressures Obtained Using an Invasive Pressure Catheter and the Noninvasive Sphygmocor Device

Introduction: The SphygmoCor (ATCOR, Naperville, IL) device utilizes a generalized transfer function based on patient’s age and gender to derive the aortic pressure pulse from the brachial-cuff based pressure measurements. This study compared aortic pressures obtained using SphygmoCor with aortic pressures obtained during cardiac catheterization. Hypothesis: Mean differences in aortic pressures obtained using SphygmoCor and pressure catheters will be less than 5 mmHg. Methods: After IRB approval, 136 patients were enrolled. During standard-of-care catheterization procedure, aortic pressure measurements were obtained using fluid-filled catheters. In a subset of patients (n = 13) the aortic pressure values were also obtained using solid-state high-fidelity Millar catheters. Immediately after the catheterization procedure, while the patients were still in the catheterization laboratory (on the procedure table), central aortic pressures were estimated with the SphygmoCor device. The measured and estimated aortic pressures were compared using linear regression and Bland-Altman analysis. A linear fit was performed to derive an additional transfer function to convert SphygmoCor pressure values to catheter-based aortic pressures, and the resulting differences in pressure values were compared. A bootstrap analysis was performed to test the generalizability of this transfer function. Results: Mean differences in systolic, diastolic and pulse aortic pressures obtained using the two techniques ranged from 6.5 to 18.0 mmHg (p &lt; 0.001). In the subset with high-fidelity catheters, the differences ranged from 8.0 to 18.9 mmHg. With the linear-fit transfer function, the differences in systolic, diastolic and pulse aortic pressures were low (&lt; 1 mmHg) corresponding to a reduction in bias noted with Bland-Altman analysis. The bootstrap analysis of the transfer function (100 iterations) achieved a coefficient of variation for the root mean square error &lt; 8.4% for systolic, diastolic and pulse aortic pressures. Conclusions: The magnitude of the differences between the SphygmoCor-estimated and catheter-based systolic, diastolic and pulse aortic pressures reduced considerably after using the linear-fit transfer function derived in this study.

Vasoprotective effects hypotensive therapy in patients with coronary heart disease combined with chronic kidney disease stage 2-3 after coronary stenting

Aim To study the condition of coronary vasculature by data of coronarography (CG) in patients with chronic ischemic heart disease (IHD) and arterial hypertension (AH) associated with stage 2-4 chronic kidney disease (CKD) and to evaluate the effect of a 12-week complex treatment with perindopril or with a combination of perindopril/amlodipine on changes in vascular wall stiffness, endothelial function, and structure and function parameters in this patient category after coronary stenting.Material and methodsr This study included 87 patients with chronic IHD and AH associated with stage 2-3 CKD for whom CG was performed due to ineffectiveness of the antianginal therapy. The patients were divided into three subgroups: subgroup 1 included 28 patients who received a conservative treatment with perindopril 10 mg/day; subgroup 2 consisted of 25 patients who underwent coronary stenting and were prescribed perindopril; subgroup 3 consisted of 34 patients who underwent stenting and were prescribed the perindopril/amlodipine combination. The reference group included 47 patients with IHD and AH with preserved kidney function. Anatomic and functional parameters of the heart, arterial stiffness, pulse wave velocity, cardio-ankle vascular index, augmentation index, central aortic systolic and pulse pressure, endothelium-dependent vasodilation, plasma concentration of endothelin-1 (ET-1), and plasma concentration of nitric oxide metabolites were evaluated at baseline and after 12 weeks of treatment.Results In patients with IHD, AH, and stage 2-3 CKD, arterial stiffness was more pronounced than in patients with preserved kidney function. Concentrations of ET-1 were significantly higher and levels of nitric oxide were lower in CKD. Supplementing the complex therapy with perindopril resulted in a considerable hypotensive effect in all subgroups, improvement of the kidney function, and positive dynamics of arterial stiffness and endothelial function. Changes in these parameters were more pronounced in patients after coronary stenting than in patients receiving only a conservative treatment. The use of perindopril/amlodipine following stenting exerted the most significant angioprotective and cardioprotective effect.Conclusion Patients with IHD and AH in combination with early CKD have pronounced impairment of the condition of arterial blood vessels and the heart. Addition of perindopril to the treatment not only exerted a hypotensive effect but also beneficially influenced mechanisms of progression of this combined pathology.

Masked hypertension risk as condition of arterial stiffness in cardiovascular risk patients: a pilot single-stage screening observational study

Background. Masked arterial hypertension (MAH) is associated with asymptomatic injury of both heart and kidneys. Links between MAH and arterial stiffness are unclear, with debates ongoing on their mutual causative relation. Research into the arterial stiffness contribution to MAH development is a perspective area of cardiology.Objectives. The MAH risk assessment as a condition of arterial stiffness in patients at cardiovascular risk (CVR) without a verified cardiovascular disease (CVD).Methods. A single-stage screening observational study included a total of 92 CVR patients without a verified cardiovascular disease. The trial conducted general clinical examination, daily blood pressure monitoring (DBPM), volumetric sphygmoplethysmography with reading cardio-ankle vascular index (CAVI1), aortic and carotid artery pulse wave velocity (PWV), carotid-femoral PWV (CFV) and augmentation index.Results. Patients were assigned in two cohorts by MAH presence, the primary MAH (58; 63.0%) and normal BP in DBPM (34; 37.0% patients) cohorts. The cohorts did not discord by age, major CVR factors, comorbidity or clinical profile. Men prevailed over women in the MAH cohort (p = 0.028). The cohorts had similar CFV, aortic PWV and augmentation index. Carotid PWV was higher in the MAH cohort both in mean values and elevation rate (p = 0.002 and p = 0.035, respectively). OR and HR were 3.29 and 2.35 (95% CI for OR 1.08–10.49, HR 1.05– 6.02), respectively. MAH was associated with increased CAVI1 for mean values and CAVI1 &gt; 8 incidence rate (p = 0.010 and 0.049, respectively); OR 3.29 (95% CI 1.00–11.41), HR 2.46 (95% CI 1.00–7.10). Correlation analysis revealed a moderate direct dependence between the MAH presence and elevation rate of C-PWV (Q = 0.53) and CAVI1 &gt; 8 (Q = 0.53).Conclusion. The risk of MAH development in CVR patients is both gender and arterial stiffness-dependent. MAH development is associated with increased CAVI1 and carotid PWV.

Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

[Figure: see text].

Conductance artery stiffness impairs atrio-ventriculo-arterial coupling before manifestation of arterial hypertension or left ventricular hypertrophic remodelling

As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV.

Doxorubicin induces arterial stiffness: A comprehensive in vivo and ex vivo evaluation of vascular toxicity in mice

Arterial stiffness is an important predictor of cardiovascular risk. Clinical studies have demonstrated that arterial stiffness increases in cancer patients treated with the chemotherapeutic doxorubicin (DOX). However, the mechanisms of DOX-induced arterial stiffness remain largely unknown. This study aimed to evaluate artery stiffening in DOX-treated mice using in vivo and ex vivo techniques. Male C57BL/6J mice were treated for 2 weeks with 2 mg/kg (low dose) or 4 mg/kg (high dose) of DOX weekly. Arterial stiffness was assessed in vivo with ultrasound imaging (abdominal aorta pulse wave velocity (aaPWV)) and applanation tonometry (carotid-femoral PWV) combined with ex vivo vascular stiffness and reactivity evaluation. The high dose increased aaPWV, while cfPWV did not reach statistical significance. Phenylephrine (PE)-contracted aortic segments showed a higher Peterson’s modulus (Ep) in the high dose group, while Ep did not differ when vascular smooth muscle cells (VSMCs) were relaxed by a NO donor (DEANO). In addition, aortic rings of DOX-treated mice showed increased PE contraction, decreased basal nitric oxide (NO) index and impaired acetylcholine-induced endothelium-dependent relaxation. DOX treatment contributed to endothelial cell loss and reduced endothelial nitric oxide synthase (eNOS) expression in the aorta. In conclusion, we have replicated DOX-induced arterial stiffness in a murine model and this aortic stiffness is driven by impaired endothelial function, contributing to increased vascular tone.

Leaflets fusion length in bicuspid aortic valve is related to ascending and aortic root dilation and ascending aorta wall shear stress

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III Background Bicuspid aortic valve (BAV) is the most common congenital heart defect, consisting in the fusion of two aortic valve leaflets. Altered flow patterns have been related to aortic wall degeneration in BAV patients and may be responsible for the high prevalence of aortic disease in these patients. A number of studies on excised BAV or using advanced imaging modalities reported a wide variability of fusion extent between leaflet, but no previous study assessed whether leaflet fusion length may be used to stratify BAV patients. Purpose We aimed to test whether leaflet fusion extent can be quantified by cardiac magnetic resonance imaging (CMR) and whether it is related to aortic dilation and flow abnormalities in non-dysfunctional BAV. Methods One hundred and twenty BAV adults with no previous aortic or aortic valve surgery or significant valvular disease were consecutively enrolled. Patients with two sinuses of Valsalva (true BAV) or fusion of the left and non-coronary cusps, both being rare forms of BAV, were excluded. Twenty-eight healthy volunteers were also included for comparison. A 4D flow CMR sequence was acquired and circumferential wall shear stress and pulse wave velocity were assessed in the ascending aorta. A stack of double-oblique cine images of the aortic valve were used to quantify the length of the fusion between leaflets. Results The length of the fusion between leaflets was effectively measured in 112/120 patients (93%). Reproducibility was good (ICC = 0.826). Fusion length varied greatly (range 2.3 – 15.4 mm, 7.8 ± 3.2 mm, tertiles cut-off points were 6 and 9.3 mm). After correction for age, BSA, stroke volume and BAV fusion morphotype, fusion length was independently associated with diameter at the sinus of Valsalva (p = 0.002). Moreover, once corrected for age, stroke volume and ascending aorta pulse wave velocity, fusion length was positively related to ascending aorta diameter (p = 0.028). The comparison of maps of circumferential peak-systolic WSS in healthy volunteers (left) and BAV patients pertaining to the three leaflet fusion length tertiles is shown in Figure 1. Circumferential WSS progressively increase with larger fusion length. This trend was statistically significant (p &amp;lt; 0.05) in the right and outer regions of the proximal and mid ascending aorta. Conclusions Bicuspid aortic leaflet fusion length varies considerably and it is independently associated with ascending aorta and aortic root dilation, possibly through flow alterations. Abstract Figure 1

Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes.

Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). Pubertal youth (n = 284) aged 12-21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO2peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. In adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO2peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. Obesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.

Comprehensive assessment of local and regional aortic stiffness in patients with tricuspid or bicuspid aortic valve aortopathy using magnetic resonance imaging

BackgroundWe aimed to provide a comprehensive aortic stiffness description using magnetic resonance imaging (MRI) in patients with ascending thoracic aorta aneurysm and tricuspid (TAV-ATAA) or bicuspid (BAV) aortic valve. MethodsThis case-control study included 18 TAV-ATAA and 19 BAV patients, with no aortic valve stenosis/severe regurgitation, who were 1:1 age-, gender- and central blood pressures (BP)-matched to healthy volunteers. Each underwent simultaneous aortic MRI and BP measurements. 3D anatomical MRI provided aortic diameters. Stiffness indices included: regional ascending (AA) and descending (DA) aorta pulse wave velocity (PWV) from 4D flow MRI; local AA and DA strain, distensibility and theoretical Bramwell-Hill (BH) model-based PWV, as well as regional arch PWV from 2D flow MRI. ResultsPatient groups had significantly higher maximal AA diameter (median[interquartile range], TAV-ATAA: 47.5[42.0–51.3]mm, BAV: 45.0[41.0–47.0]mm) than their respective controls (29.1[26.8–31.8] and 28.1[26.0–32.0]mm, p < 0.0001), while BP were similar (p ≥ 0.25). Stiffness indices were significantly associated with age (ρ ≥ 0.33), mean BP (arch PWV: ρ = 0.25, p = 0.05; DA distensibility: ρ = −0.30, p = 0.02) or AA diameter (arch PWV: ρ = 0.28, p = 0.03; DA PWV: ρ = 0.32, p = 0.009). None of them, however, was significantly different between TAV-ATAA or BAV patients and their matched controls. Finally, while direct PWV measures were significantly correlated to BH-PWV estimates in controls (ρ ≥ 0.40), associations were non-significant in TAV-ATAA and BAV groups (p ≥ 0.18). ConclusionsThe overlap of MRI-derived aortic stiffness indices between patients with TAV or BAV aortopathy and matched controls highlights another heterogeneous feature of aortopathy, and suggests the urgent need for more sensitive indices which might help better discriminate such diseases.

Determinants of central aortic pressure and pulse pressure amplification changes in patients with aortic aneurysm: the role of aortic diameter and aortic aneurysm location level

Abstract Background The presence of aortic aneurysm can alters pulse wave propagation and reflection, causing changes in central aortic pressure and pulse pressure amplification (PPA) between the aorta and the brachial artery that might be associated with unfavorable hemodynamic effects for the central arteries and the heart. However, the impact of the location of the aneurysm and increase of the aortic diameter on central blood pressure (CBP) is not fully understood. Objective To investigate central aortic pressure and PPA regarding to association with arterial stiffness and aortic diameter in patients with ascending aortic aneurysm (AA), descending thoracic and abdominal aortic aneurysm (TAA and AAA). Methods 122 patients (96 males, 65±11 years) with aortic aneurysm were enrolled before aortic repair. The parameters of the aorta were evaluated by MSCT angiography: 44 patients (30 males, 55±13 years) had AA (the maximum diameter: 59.9±14.2 mm), 13 patients (11 males, 62±11 years) had TAA (the maximum diameter: 62.8±8.0 mm) and 65 patients (54 males, 69±8 years) had AAA (the maximum diameter: 52.3±17.2 mm). Brachial blood pressure (BBP) was measured by OMRON. CBP, augmentation index (AIx), carotid-femoral pulse wave velocity (PWV) were assessed by SphygmoCor. PPA was calculated as a difference between the values of central and brachial pulse pressure (CPP and BPP). Results Patients of the three groups did not differ in BPP (AA: 59.2±17.6; TAA 56.8±12.8; AAA: 59.3±11.4 mm Hg; P=0.5). Intergroup comparison revealed a difference in CPP between the three patients groups: CPP was higher in patients with AA and AAA, lower in patients with TAA (AA: 50.3±16.2; TAA 43.8±10.8; AAA: 50.0±11.2 mm Hg; P=0.05). PPA was lower in patients with AA and AAA than in patients with TAA (9.6±6.7 and 9.3±4.2 vs. 13.0±6.5 mm Hg; P=0.05 and P=0.04, respectively). IAx was higher in patients with AA and AAA than in patients with TAA (25.2±8.1 and 27.6±8.2 vs. 17.2±8.2 mm Hg; P=0.008 and P=0.001, respectively). A decrease of PPA across all patients correlated with an increase of IAx (r = - 0.268; P=0.003). CPP decreased with an increase of the aortic diameter for each level of the aneurysm (AA: r = - 0.460, P=0.016; TAA: r = - 0.833, P=0.003; AAA: r = - 0.275, P=0.05). PWV decreased with the expansion of the maximum aortic diameter at the level of the AA, TAA and AAA: (r = - 0.389, P=0.03; r = - 0.827, P=0.02 and r = - 0.350, P=0.01, respectively). Conclusion In patients with aortic aneurysm measurements of lower central pulse pressure and reduced PWV indicate an association with increased diameter of the aneurysm. An increase in augmentation index, early return of reflected waves, thus smaller PP amplification and higher CPP were identified in patients with ascending and abdominal aortic aneurysm compared by patients with descending thoracic aortic aneurysm. Funding Acknowledgement Type of funding source: None

Patients with blunt traumatic thoracic aortic injury treated with TEVAR present increased flow dynamics alterations and pulse wave velocity: a 4D flow CMR study

Abstract Background Thoracic endovascular aortic repair (TEVAR) is widely used for the treatment of blunt traumatic thoracic aortic injuries. Aortic flow dynamics and mechanical implications of this intervention are poorly investigated and may be of particular interest in the long-term follow-up of these mostly young patients. Purpose To assess whether the presence of TEVAR in a cohort of otherwise healthy subjects was related to dilation of the proximal aorta or increase in aortic stiffness and flow alterations. Methods Nineteen patients who underwent TEVAR implantation after a traumatic injury of the thoracic descending aorta (DAo) (10.0±6.1 years from intervention) and 44 healthy volunteers (HV) underwent 4D flow CMR to compute ascending aorta (AAo) pulse wave velocity (PWV), a marker of aortic stiffness, systolic flow reversal ratio (SFRR), quantifying backward flow during systole and in-plane rotational flow (IRF), measuring in-plane strength of helical flow. IRF and SFRR were assessed at 20 planes between the sinotubular junction and the mid thoracic DAo. Aortic diameters were measured using double-oblique cine CMR. Results Patients with TEVAR and HV did not differ in age, sex, body surface area, blood pressure and DAo diameter distal to TEVAR (Table). However, TEVAR patients presented larger diameters at the sinus of Valsalva and AAo, increased AAo PWV and strong flow alterations: IRF was reduced from the distal AAo to the proximal DAo, while SFRR was increased in the whole thoracic aorta (Figure). Conclusions In patients with blunt traumatic thoracic aortic injury treated with TEVAR the aorta proximal to TEVAR is dilated, stiffer and present potentially pathogenic flow conditions. Longitudinal studies are needed to assess whether these alterations have prognostic value and may improve clinical prevention and management of these patients. Figure 1. IRF and SFRR in healthy vs TEVAR Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study has been funded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI19/01480). Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I).

0550 Insomnia is Associated with Greater Arterial Stiffness and Cardiac Dysfunction

Abstract Introduction Insomnia is a novel and modifiable risk factor for incident cardiovascular disease (CVD). However, identification of early markers of subclinical CVD in diagnosed insomnia is understudied. Our aim for this ongoing study is to contrast markers of cardiovascular structure and function between people with insomnia and good-sleeping controls. Methods Persons with insomnia (met ICSD-III criteria) and good sleeping controls (&amp;lt;8 Insomnia Severity Index, mean 8-night SOL and WASO&amp;lt;31min) were recruited from the community. Twenty-two adults (21-39y; 55% women) with no history of CVD, diabetes, inflammatory conditions, significant hypertension, or current sleep-disordered breathing (WatchPat200, Itamar Medical) were enrolled and underwent fasting cardiovascular testing. Testing included: Central augmented aortic pressure (AP) and carotid-femoral pulse wave velocity (cfPWV) for vascular stiffness; brachial artery flow mediated dilation (FMD) to assess endothelial function; and 2D echocardiography to assess ejection fraction (EF%), left ventricular global longitudinal strain (LVGLS), left atrial volume index (LAVI), mitral valve E/e’ ratio (E/e’), and lateral e’. ANCOVA models, adjusting for age, comparing persons with insomnia (n=6) to good sleeping controls (n=16) on each cardiovascular measure were conducted. Results AP (range:-5,10mmHg), cfPWV (range: 4.8-7.6m/s), EF% (range:55.0-72.0%), LVGLS (range:-26,-19%) LAVI (range:14.1-26.7mL/m2), E/e’ (range:3.2-7.8), and lateral e’ (range:0.09-0.22cm/sec) were all within normal ranges according to age and sex normative standards. Mean FMD was 8.8% (SD=4.3, range:4.3-19.8%). Age adjusted ANCOVA models indicated that the insomnia group had significantly worse cardiovascular function than good sleeping controls on cfPWV (M=6.8±0.3 vs. M=5.7±0.2; p=0.004), EF% (M=60.0±1.7 vs. M=65.2±1.0; p=0.017), LVGLS (M=-21.6±0.6 vs. M=-24.3±0.4; p=0.001), and lateral e’ (M=0.12±0.01 vs. M=0.18±0.01; p=0.003). No group differences were found for AP, FMD, LAVI, and E/e’. Conclusion Among relatively healthy young adults, people with insomnia had greater arterial stiffness and worse left ventricular systolic and diastolic functioning. Support American Academy of Sleep Medicine Foundation Focused Projects Award for Junior Investigators 179-FP-18