Computation of aortic pulse wave velocity and aortic pulse wave velocity and aortic extensibility from pressure gradient measurements.

This study is concerned with the computation of aortic pulse wave velocity based on simultaneous recordings of the aortic pressure gradient and first-time derivative of aortic pressure. These variables were recorded by means of a double-lumen catheter introduced in the aorta of four anesthetized closed chest dogs, and connected to critically damped manometer systems. Results of aortic pulse wave velocity were then compared: (i) to the true phase velocity obtained from spectra of apparent phase velocity, and (ii) to the pulse wave velocity computed from the time shift between maximum slopes of the pressure wave. From the aortic valves to 37 cm down the aortic trunk, pulse wave velocity increased from 410-460 cm/s to approximately 600-800 cm/s. Based on the wave propagation equation presented of Bramwell and Hill (Bramwell, J.C., and Hill, A. V. 1922. Proc. R. Soc. 93, 298-306), volumetric extensibility coefficients were computed from pulse wave velocity data. Results indicated that, from the aortic valves to 37 cm down to the aorta, the mean volumetric extensibility decreased from 0.43-0.56% deltaV/cm H2O to 0.16-0.25% deltaV/cm H2O (1 cm H2O = 94.1 N/m2).     

The extent of the raphe in bicuspid aortic valves is associated with aortic regurgitation and aortic root dilatation

Background

The clinical course of bicuspid aortic valves (BAVs) is variable. Data on predictors of aortopathy and valvular dysfunction mainly focus on valve morphology.

Aim

To determine whether the presence and extent of the raphe (fusion site of valve leaflets) is associated with the degree of aortopathy and valvular dysfunction in patients with isolated BAV and associated aortic coarctation (CoA).

Methods

Valve morphology and aortic dimensions of 255 BAV patients were evaluated retrospectively by echocardiography.

Results

BAVs with a complete raphe had a significantly higher prevalence of valve dysfunction (especially aortic regurgitation) than BAVs with incomplete raphes (82.9 vs. 66.7 %, p = 0.01). Type 1A BAVs (fusion of right and left coronary leaflets) and complete raphe had larger aortic sinus diameters compared with the rest of the population (37.74 vs. 36.01, p = 0.031). Patients with CoA and type 1A BAV had significantly less valve regurgitation (13.6 vs. 55.8 %, p < 0.001) and smaller diameters of the ascending aorta (33.7 vs. 37.8 mm, p < 0.001) and aortic arch (25.8 vs. 30.2 mm, p < 0.001) than patients with isolated BAV.

Conclusions

Type 1A BAV with complete raphe is associated with more aortic regurgitation and root dilatation. The majority of CoA patients have incomplete raphes, associated with smaller aortic root diameters and less valve regurgitation.     

Balloon dilatation of the aortic valve for inoperable aortic stenosis.

The place of balloon dilatation of the aortic valve in the treatment of calcific aortic stenosis is controversial. Thirty two patients (mean age 76) in whom valve replacement was contraindicated were followed up for three to 24 months (mean 8); 25 were in functional class III or IV according to the New York Heart Association''s classification. Major complications of the procedure occurred in four patients. Echocardiography and Doppler studies were performed before operation and before discharge in 28 patients, and the area of the valve was measured again six to 50 (mean 23) weeks after operation in 11 patients. The peak to peak aortic pressure gradient fell from a mean of 65 (SD 24) to 46 (20) mm Hg, but the area of the aortic valve, measured by Doppler echocardiography, in 18 patients showed a modest but significant increase, from 0.61 (0.16) to 0.74 (0.23) cm2. One month after dilatation, 29 patients were alive, of whom 17 had improved symptoms. Only two had lasting clinical benefit. Sixteen patients died, 12 of a cardiac cause. The estimated one year survival rate was 49%. Six patients underwent or required valve replacement because of persisting symptoms. In view of its limited long term efficacy balloon dilatation of the aortic valve should be used only for patients with severe symptoms whose life expectancy is limited by other disease or who are considered to be unsuitable for valve replacement. It may have a role in improving the condition of patients who present with cardiogenic shock or pulmonary oedema before valve replacement is undertaken.     

A mechanical device for aortic compliance modulation: in vitro simulation of aortic dissection treatment

Stanford type A aortic dissection often rapidly leads to death from aortic rupture. We considered the possibility of introducing a passive counterpulsating damper into the dissected aorta in order to limit the physical stress associated with ventricular ejection and increase the diastolic aorto-ventricular pressure gradient. We conceived a damping device comprising an intravascular balloon connected to an adjustable external reservoir to regulate the air pressure inside the balloon, and performed a simulation study using a mechanical model of the cardiovascular system, mimicking aortic dissection. When the balloon was completely deflated, the behavior of the aortic pressure signal was typical of low-compliance aortic dissection, as characterized by an augmented maximum systolic value, accentuated diastolic decay, and a very low end-diastolic value. Balloon inflation (at incremental steps to 90 mmHg) progressively restored the aorto-ventricular pressure gradient and reduced peak systolic pressure values, leading to progressive improvements in the characteristics of the aortic pressure curve in terms of reduction in the maximum systolic value and slower diastolic decay. The proposed mechanism might exert beneficial effects at two levels: (1) directly, by reducing mechanical stress on the arterial wall; (2) indirectly, by allowing safer use of pharmaceutical agents (beta-blockers etc.). In vivo animal simulation studies are warranted to verify the effects of the device and optimize balloon shape and volume in a realistic pathophysiological setting.     

Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation

The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE(-/-)) mice that overexpress catalase in vascular smooth muscle cells (apoE(-/-)xTg(SMC-Cat)). At baseline, aortas from apoE(-/-)xTg(SMC-Cat) exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE(-/-) mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE(-/-)xTg(SMC-Cat) after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H(2)O(2) is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.     

Prolapse of noncoronary aortic cusp with severe aortic regurgitation after a tear of the aortic root

A patient with acute aortic regurgitation, a dissecting aneurysm with a localized transverse tear just above the aortic valve, and an aortic noncoronary cusp eversion is discussed. The valvular defects were considered to be of recent etiology, and the patient underwent successful aortic valve replacement and repair of the dissection.     

Effects of aortic coarctation on aortic antioxidant enzymes and NADPH oxidase protein expression

Abdominal aortic coarctation above the renal arteries leads to severe hypertension above the stenotic site and provides a model for simultaneous testing of the effects of increased and decreased pressure and consequently shear stress in the same animal. The effects of increased pressure, per se, on oxidative stress and antioxidant enzyme expression is unknown. We studied the protein expressions of antioxidant enzymes and NADPH oxidase (gp91phox subunit) in the aortic segments above and below the stenosis site in sham-operated control and aortic-banded rats at four weeks postoperatively. Compared with the control group, the banded group showed significant up-regulation of NADPH oxidase, catalase (CAT), Cu/Zn superoxide dismutase (SOD) and Mn SOD protein content in the thoracic aorta. In contrast, Mn SOD, Cu/Zn SOD and NADPH oxidase protein abundance were unchanged in the abdominal aortic segment below the stricture where blood pressure is not elevated, whereas CAT protein abundance was also elevated in the abdominal aorta. No changes were noted for glutathione peroxidase (GPX) protein content either in the thoracic or abdominal aortic segments. Coarctation-induced hypertension is associated with increased aortic CAT, Cu/Zn SOD, Mn SOD and NADPH oxidase protein expression. The up-regulation of NADPH oxidase increases reactive oxygen species (ROS) generation noted in the present study and contributes to inactivation of nitric oxide (NO) as shown previously in this model. Upregulation of antioxidant enzymes may be a compensatory response in the face of elevated pressure and oxidative stress. The normality of protein abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors, as opposed to circulating humoral factors that were similar in both segments, as a mechanism responsible for increased antioxidant enzyme expression.     

GDF11 prevents the formation of thoracic aortic dissection in mice: Promotion of contractile transition of aortic SMCs

Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de-differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β-aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno-associated virus type 2 (AAV-2)-mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)-2, 3, 9 in aortic SMCs. The canonical TGF-β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de-differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD.     

Hyperlipidaemia and aortic valve disease

PURPOSE OF REVIEW: Degenerative aortic valve stenosis is a common disease in the elderly, and traditional risk factors for atherosclerotic disease including hyperlipidaemia have been associated with the condition in several studies. This review addresses the role of the various risk factors and the potential for intervention. RECENT FINDINGS: The association of lipid abnormalities such as high lipoprotein(a) levels and the presence of the apolipoprotein E4 allele with aortic stenosis, as well as the presence of several inflammatory markers both in plasma and in surgically excised valves, suggest that the stenotic process is driven by many of the same factors behind atherosclerosis. The aortic valves of animals fed a cholesterol-rich diet exhibit many characteristics in common with the early stages of aortic stenosis. This opens up the potential of retarding the process through intervention strategies. SUMMARY: Hyperlipidaemia is associated with degenerative aortic valve stenosis, and the disease resembles the inflammatory process of atherosclerosis. Randomized controlled clinical trials will be needed to demonstrate the role of lipid intervention in patients with this condition.     

Balloon aortic valvuloplasty as a bridge to aortic valve replacement in a patient with severe calcific aortic stenosis

This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high.     

21毫米人造心脏瓣膜泵的设计及研制

为了研究能够长期置入主动脉瓣环的左心室辅助装置,研制出直径21毫米重27克可植入的主动脉瓣膜泵.装置包括一个转子和一个定子.转子由驱动磁钢和叶轮组成;定子装有带铁心的电机线圈和出口导叶.装置被置於主动脉瓣位置,所以不占用额外的解剖空间.血泵能像自然心脏一样直接将血液由心室输送到主动脉,不需要连接管道和旁路,因此对自然生理循环的干扰可以减到最低.血泵流量由最大到零周期变化.血液动力学测试表明,当血泵转速为17500转/分钟时,可以产生流量5升/分钟、压力增益50毫米汞柱的血流;同一转速下,当流量为零时,血泵能保持主动脉舒张压为80毫米汞柱.     

Patient-specific modeling of biomechanical interaction in transcatheter aortic valve deployment

The objective of this study was to develop a patient-specific computational model to quantify the biomechanical interaction between the transcatheter aortic valve (TAV) stent and the stenotic aortic valve during TAV intervention. Finite element models of a patient-specific stenotic aortic valve were reconstructed from multi-slice computed tomography (MSCT) scans, and TAV stent deployment into the aortic root was simulated. Three initial aortic root geometries of this patient were analyzed: (a) aortic root geometry directly reconstructed from MSCT scans, (b) aortic root geometry at the rapid right ventricle pacing phase, and (c) aortic root geometry with surrounding myocardial tissue. The simulation results demonstrated that stress, strain, and contact forces of the aortic root model directly reconstructed from MSCT scans were significantly lower than those of the model at the rapid ventricular pacing phase. Moreover, the presence of surrounding myocardium slightly increased the mechanical responses. Peak stresses and strains were observed around the calcified regions in the leaflets, suggesting the calcified leaflets helped secure the stent in position. In addition, these elevated stresses induced during TAV stent deployment indicated a possibility of tissue tearing and breakdown of calcium deposits, which might lead to an increased risk of stroke. The potential of paravalvular leak and occlusion of coronary ostia can be evaluated from simulated post-deployment aortic root geometries. The developed computational models could be a valuable tool for pre-operative planning of TAV intervention and facilitate next generation TAV device design.     

Biological aortic age derived from the arterial pressure waveform

Indexes for arterial stiffness are, by their nature, influenced by the ambient blood pressure due to the curvilinear nature of arterial compliance. We developed a new concept of the "Modelflow aortic age," which is, theoretically, not influenced by the ambient blood pressure and provides an easily understood context (biological vs. chronological age) for measures of arterial stiffness. The purpose of the present study was to validate this pressure-independent index for aortic stiffness in humans. Twelve sedentary elderly (65-77 yr), 11 Masters athletes (65-73 yr), and 12 sedentary young individuals (20-42 yr) were studied. Modelflow aortic ages were comparable with chronological ages in both sedentary groups, indicating that healthy sedentary individuals have age-appropriate aortas. In contrast, Masters athletes showed younger Modelflow aortic ages than their chronological ages. The coefficient of variation of sedentary subjects was three times smaller with the Modelflow aortic age (21%) than with other indexes, such as static systemic arterial stiffness (61%), central pulse wave velocity (61%), or carotid β-stiffness index (58%). The typical error was very small and two times smaller in the Modelflow aortic age (<7%) than in static systemic arterial stiffness (>13%) during cardiac unloading by lower body negative pressure. The Modelflow aortic age can more precisely and reliably estimate aortic stiffening with aging and modifiers, such as life-long exercise training compared with the pressure-dependent index of static systemic arterial stiffness, and provides a physiologically relevant and clinically compelling context for such measurements.     

Family screening in patients with isolated bicuspid aortic valve

Netherlands Heart Journal - To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and...     

A ventricular-vascular coupling model in presence of aortic stenosis

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V(3)) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V(3) model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99x - 2.36 with a coefficient of determination r(2) = 0.98. There was also very good agreement between estimated and measured stroke volumes (y = 1.03x + 2.2, r(2) = 0.96, SEE = 2.8 ml). Hence, this mathematical V(3) model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.     

Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study

Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (<4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.     

Coupling between MRI-assessed regional aortic pulse wave velocity and diameters in patients with thoracic aortic aneurysm: a feasibility study

Aims

Thoracic aortic aneurysm (TAA) is potentially life-threatening and requires close follow-up to prevent aortic dissection. Aortic stiffness and size are considered to be coupled. Regional aortic stiffness in patients with TAA is unknown. We aimed to evaluate coupling between regional pulse wave velocity (PWV), a marker of vascular stiffness, and aortic diameter in TAA patients.

Methods

In 40 TAA patients (59 ± 13 years, 28 male), regional aortic diameters and regional PWV were assessed by 1.5 T MRI. The incidence of increased diameter and PWV were determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta; S4, suprarenal and S5, infrarenal abdominal aorta). In addition, coupling between regional PWV testing and aortic dilatation was evaluated and specificity and sensitivity were assessed.

Results

Aortic diameter was 44 ± 5 mm for the aortic root and 39 ± 5 mm for the ascending aorta. PWV was increased in 36 (19 %) aortic segments. Aortic diameter was increased in 28 (14 %) segments. Specificity of regional PWV testing for the prediction of increased regional diameter was ≥ 84 % in the descending thoracic to abdominal aorta and ≥ 68 % in the ascending aorta and aortic arch.

Conclusion

Normal regional PWV is related to absence of increased diameter, with high specificity in the descending thoracic to abdominal aorta and moderate results in the ascending aorta and aortic arch.     

Family screening in patients with isolated bicuspid aortic valve: Restriction to those with aortic dilatation is not justified

AimTo determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only.MethodsDuring follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening.ResultsFrom 2012–2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4–83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62–8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16–1.66).ConclusionScreening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.     

A quantitative histological study of the aortic nerve and the aortic body in the buffalo (Bubalus bubalis)

In the buffalo, the left aortic nerve ramifies in the periarterial connective tissue between the ventral surface of the aortic arch and the truncus pulmonalis. The right aortic nerve ramifies over the dorsal and right aspects of the aorta ascendens near its origin. The histograms of myelinated fibres of both left and right aortic nerve are distinctly unimodal with peak around 4-6 micron (64.2-67.8%). The left aortic body is situated in the periarterial connective tissue between the ventral surface of the aortic arch and the truncus pulmonalis, while the right aortic body is located in the tunica adventitia of the dorsal and right aspects of the aorta ascendens near its origin. The greatest sagittal section area of the left aortic body is 0.102 +/- 0.009 mm2 and that of the right aortic body is 0.041 +/- 0.002 mm2. The organ is highly vascular. The mean size of the glomus cells from the left aortic body is 7.68 +/- 0.9 micron x 9.37 +/- 0.13 micron (short diameter x long diameter), whereas the corresponding value for the right aortic body is 7.84 +/- 0.14 micron x 9.86 +/- 0.21 micron; and their density values are (11,417 +/- 301.7)/mm2 and (9,839 +/- 213.3)/mm2 respectively.     

Biomechanical characterization of the native porcine aortic root

A thorough understanding of the well-functioning, native aortic root is pivotal in an era, where valve sparing surgical techniques are developed and used with increasing frequency. The objective of this study was to characterize the local structural stiffness of the native aortic root, to create a baseline for understanding how different surgical interventions affect the dynamics of the aortic root. In this acute porcine study (N = 10), two dedicated force transducers were implanted to quantify the forces acting on both the annular plane and on the sinotubular junction (STJ). To assess the changes in geometry, eleven sonomicrometry crystals were implanted within the aortic root. The combination of force and length measurements yields the radial structural stiffness for each segment of the aortic root.The least compliant segment at the annular plane was the right-left interleaflet triangle with a stiffness modulus of 1.1 N mm⁻¹ (SD0.4). At the sinotubular junction the same segment (right-left) was most compliant, compared with the two other segments, however not statistically significant different.The elastic energy storage was derived from the aortic root pressure volume relationship; the mean elastic energy storage was 826 µJ (SD529). In conclusion, the aortic root has been characterized in terms of both segmental forces, segmental change in length and elastic energy storage. This study is the first to assess the radial structural stiffness of different segments of the aortic root. The presented data is reference for further studies regarding the impact of surgical interventions on the aortic root.