P5993Comprehensive characterization of experimental aortic valve stenosis by multiparametric MRI

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Quast ◽  
S Zimmer ◽  
F Boenner ◽  
C Jacoby ◽  
I Gyamfi-Poku ◽  
...  

Abstract Background Recently, we established an experimental model of moderate aortic valve stenosis (AS) aiming to mimic human disease progression closely. Functional and structural MRI of a mouse model in experimental aortic valve stenosis has not been accomplished so far. Purpose Here, we aimed at developing comprehensive MRI approach for simultaneous assessment of changes in valvular, left ventricular and aortic morphology and function. Methods Male 12-week-old wildtype mice (C57Bl/6) were subjected to wire injury of the aortic valve to induce aortic valve stenosis. High resolution MRI at 9.4T was used to monitor subsequent functional and structural changes in the aortic valve, the ascending aorta, the left ventricle and aortic flow patterns. Results MRI permits accurate planimetry of the orifice and the thickness of the aortic valve, allows a reliable three-dimensional mapping of transvalvular aortic flow, simultaneously depicts aortic regurgitation in 3D fashion and permits assessment of left ventricular changes due to AS. In our model we observed a reduced valve orifice and an increase in valve thickness. Homogenous flow pattern under control converted to heterogenous and turbulent flow with progression of AS associated with increased aortic strain, aortic wall and left ventricular wall thickness. Conclusions In a murine model of aortic valve stenosis MRI is capable to reliably display a three-dimensional transvalvular aortic flow profile with concomitant quantification of structural and functional changes in aortic valve, left ventricle, and ascending aorta. This comprehensive functional imaging at high resolution and distinct reproducibility offers for the first time serial assessment of disease progression in an experimental model of aortic valve stenosis.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S T Niepmann ◽  
E Steffen ◽  
A Zietzer ◽  
M Adam ◽  
J Nordsiek ◽  
...  

Abstract Background Aortic valve stenosis (AS) is the most common valve disease requiring therapeutic intervention. Even though the incidence of AS has been continuously rising and AS is associated with significant morbidity and mortality, to date, no medical treatments have been identified that can modify disease progression. In fact, only invasive interventional or surgical replacement of severely diseased valves is recommended. This unmet medical need is likely attributed to the lack of a clear understanding of the molecular mechanism driving disease development. To investigate the pathophysiology leading to AS, reliable and reproducible animal models that mimic human pathophysiology are needed. Hypothesis Induction of a graded wire-induced aortic valve stenosis model in mice is feasible to reflect and study pathophysiological mechanisms underlying the progression of aortic valve stenosis. Methods We have tested and expanded the protocols of a novel wire-injury induced aortic valve stenosis mouse model. A spring coronary guide wire or a bare metal wire was used to apply shear stress to the aortic valve cusps with increasing intensity with ultrasound-guided monitoring in male 10 to 12-week-old C57Bl/6j mice. These protocols allowed the induction of distinct models with soft, moderate and intense wire injury. Functional analysis including maximum flow velocity (Vmax), ejection fraction, fractional shortening, left ventricular volumes, diameters and wall thickness were assessed by echocardiography before, one and four weeks after induction of aortic valve stenosis. Immunohistological analysis were performed after eight weeks (hematoxylin and eosin, von-Kossa staining, anti-CD68-staining). Results Upon moderate or severe injury, AS developed with a significant increase in aortic valve peak blood flow velocity. While moderate injury promoted solitary AS, severe-injury induced mixed aortic valve disease with concomitant mild to moderate aortic regurgitation. Only 5% of the mice who received a moderate injury displayed a mild aortic regurgitation. In the group of mice with intense injury 50% of the mice had a mild and 18,75% had a moderate aortic insufficiency. The changes in aortic valve function were reflected by dilation and hypertrophy of the left ventricle, as well as a decreased left ventricular ejection fraction after intense injury, while moderate injury did not show significant dilation of the left ventricle. Histological analysis revealed the three classic hallmarks of human disease with aortic valve thickening, increased macrophage infiltration and calcification eight weeks after injury. Conclusion Hereby, we demonstrate that the induction of a graded wire induced aortic valve stenosis model in mice mimicking relevant pathophysiological mechanisms is feasible to study disease progression. We extended existing protocols to induce moderate stenosis allowing to solely study aortic valve stenosis without relevant aortic valve regurgitation. Acknowledgement/Funding S.N. was funded by Else-Kröner-Fresenius-Foundation of the Medical Faculty of the University of Bonn


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boris Barbarics ◽  
Katja Eildermann ◽  
Lars Kaderali ◽  
Lukas Cyganek ◽  
Uwe Plessmann ◽  
...  

AbstractAortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. To overcome these issues this study used high resolution mass spectrometry in combination with a stem cell-derived cardiac specific protein quantification-standard to profile the proteomes of 17 atrial and 29 left ventricular myocardial FFPE human myocardial tissue samples from AVS-patients. In our proteomic analysis we quantified a median of 1980 (range 1495–2281) proteins in every single sample and identified significant upregulation of 239 proteins in atrial and 54 proteins in ventricular myocardium. We compared the proteins with published data. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. In summary, we provide both a workflow for quantitative proteomics of human FFPE heart tissue and a comprehensive proteomic resource for AVS induced changes in the human myocardium.


2021 ◽  
Vol 46 (5) ◽  
pp. 100801
Author(s):  
João Abecasis ◽  
Daniel Gomes Pinto ◽  
Sância Ramos ◽  
Pier Giorgio Masci ◽  
Nuno Cardim ◽  
...  

2020 ◽  
Vol 22 (Supplement_N) ◽  
pp. N142-N145
Author(s):  
Alice Benedetti ◽  
Alvise Del Monte ◽  
Maurizio Rubino ◽  
Daniela Mancuso

Abstract A 36-year-old woman at 31 weeks’ gestation presented with exertional dyspnoea and palpitations. She had a history of bicuspid aortic valve treated with surgical aortic valvotomy for severe stenosis, followed by ascending aorta replacement for type A acute aortic dissection and Bentall operation with a mechanical valve for severe aortic regurgitation. Eight years after the last surgery, magnetic resonance angiography showed aortic arch aneurysm (49 mm) with a small intimal flap. Thereafter, the patient was lost to follow-up until the current admission. She was hemodynamically stable on presentation and physical examination was unremarkable apart from a mechanical second heart sound. The electrocardiogram showed sinus rhythm with left bundle branch block (Panel A). Transthoracic echocardiography revealed severe left ventricular dilation (EDV 90 ml/m2) with mild dysfunction (EF 50%), normal prosthetic aortic valve function, and aortic arch dilation (50 mm) (Panel B and C). After a multidisciplinary evaluation, elective cesarean section was performed at 34 weeks’ gestation. A post-delivery aortic computed tomography angiography revealed aortic arch aneurysm (52 mm) with intimal flap and two pseudoaneurysms of the anterior aortic wall causing sternal erosion (Panel D, E, F and G). Subsequently, the patient underwent ascending aorta and aortic arch replacement by Frozen Elephant Trunk technique with a 24 x130 mm prosthesis between the aortic root and the descending aorta. The postoperative course was uneventful, and the patient was discharged to a cardiac rehabilitation centre.


2005 ◽  
Vol 15 (S1) ◽  
pp. 27-36 ◽  
Author(s):  
Alfred Asante-Korang ◽  
Robert H. Anderson

The previous reviews in this section of our Supplement1,2 have summarized the anatomic components of the ventriculo-arterial junctions, and then assessed the echocardiographic approach to the ventriculo-arterial junction or junctions as seen in the morphologically right ventricle. In this complementary review, we discuss the echocardiographic assessment of the comparable components found in the morphologically left ventricle, specifically the outflow tract and the arterial root. We will address the echocardiographic anatomy of the aortic valvar complex, and we will review the causes of congenital arterial valvar stenosis, using the aortic valve as our example. We will also review the various lesions that, in the outflow of the morphologically left ventricle, can produce subvalvar and supravalvar stenosis. We will then consider the salient features of the left ventricular outflow tract in patients with discordant ventriculo-arterial connections, and double outlet ventricles. To conclude the review, we will briefly address some rarer anomalies that involve the left ventricular outflow tract, showing how the transesophageal echocardiogram is used to assist the surgeon preparing for repair. The essence of the approach will be to consider the malformations as seen at valvar, subvalvar, or supravalvar levels,1 but we should not lose sight of the fact that aortic coarctation or interruption, hypoplasia of the left heart, and malformations of the mitral valve are all part of the spectrum of lesions associated with obstruction to the left ventricular outflow tract. These additional malformations, however, are beyond the scope of this review.


2020 ◽  
Vol 87 (9-10) ◽  
pp. 40-43
Author(s):  
V. V. Popov ◽  
R. M. Vitovskyi ◽  
Yu. V. Bakhovska ◽  
O. O. Bolshak ◽  
K. Ye. Vakulenko ◽  
...  

Objective. To research of possibilities of reconstruction of aorta`s ostium and ascending aorta during aortic valve replacement and simultaneous correction of mitral valve defects at patients with narrow aorta`s ostium. Materials and methods. The study group consisted of 46 patients with mitral-aortic heart diseases and combination with a narrow aortic mouth, who were operated on at the A Amosov National Institute of Cardiovascular surgery for the period from January 1, 2006 to January 1, 2020. All patients underwent reconstruction of the aortic root and ascending aorta according to the original method of posterior aortoplasty. There were 26 men (56.5%) and 20 women (43.5%). The age of patients ranged from 23 to 72 years (average - 58.4±7.3 years). 8 (17.4%) patients belonged to class III NYHA, 38 (82.6%) - to class IV. Results. Of the 46 operated patients at the hospital stage (30 days after surgery), 4 died (hospital mortality 8.7%). No fatalities were associated with surgical technique. The dynamics of echocardiographic parameters at the hospital stage was as follows: the systolic gradient on the aortic valve was before surgery 112.1 ± 15.2 mm Hg, on the aortic prosthesis at discharge - 23.2 ± 6.4 mm Hg; end-systolic index (ESI) of the left ventricle (ml/m²) - 59.1 ± 7.6 (before surgery) and 48.3 ± 5.9 (after surgery); left ventricle ejection fraction (EF) - 0.45 ± 0.04 (before surgery) and 0.53 ± 0.04 (after surgery). Conclusions. The proposed original technique of posterior aortoplasty allows to effectively expand the mouth of the aorta for further implantation of an artificial heart valve of larger diameter. The technique is quite safe. At the hospital stage there are no complications directly related to the technique of operations. At the early postoperative period, the morphometric parameters of the left ventricle (EF and ESI) improved. The technique can be successfully used for the correction of combined mitral-aortic valve defects.


2021 ◽  
pp. 039139882110214
Author(s):  
Guang-Mao Liu ◽  
Fu-Qing Jiang ◽  
Jiang-Ping Song ◽  
Sheng-Shou Hu

The intraventricular blood flow changed by blood pump flow dynamics may correlate with thrombosis and ventricular suction. The flow velocity, distribution of streamlines, vorticity, and standard deviation of velocity inside a left ventricle failing to different extents throughout the cardiac cycle when supported by an axial blood pump were measured by particle image velocimetry (PIV) in this study. The results show slower and static flow velocities existed in the central region of the left ventricle near the mitral valve and aortic valve and that were not sensitive to left ventricular (LV) failure degree or LV pressure. Strong vorticity located near the inner LV wall around the LV apex and the blood pump inlet was not sensitive to LV failure degree or LV pressure. Higher standard deviation of the blood velocity at the blood pump inlet decreased with increasing LV failure degree, whereas the standard deviation of the velocity near the atrium increased with increasing intraventricular pressure. The experimental results demonstrated that the risk of thrombosis inside the failing left ventricle is not related to heart failure degree. The “washout” performance of the strong vorticity near the inner LV wall could reduce the thrombotic potential inside the left ventricle and was not related to heart failure degree. The vorticity near the aortic valve was sensitive to LV failure degree but not to LV pressure. We concluded that the risk of blood damage caused by adverse flow inside the left ventricle decreased with increasing LV pressure.


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