Spontaneous Degenerative Aortic Valve Disease in New Zealand Obese Mice

Background Degenerative aortic valve (AoV) disease and resulting aortic stenosis are major clinical health problems. Murine models of valve disease are rare, resulting in a translational knowledge gap on underlying mechanisms, functional consequences, and potential therapies. Naïve New Zealand obese (NZO) mice were recently found to have a dramatic decline of left ventricular (LV) function at early age. Therefore, we aimed to identify the underlying cause of reduced LV function in NZO mice. Methods and Results Cardiac function and pulmonary hemodynamics of NZO and age‐matched C57BL/6J mice were monitored by serial echocardiographic examinations. AoVs in NZO mice demonstrated extensive thickening, asymmetric aortic leaflet formation, and cartilaginous transformation of the valvular stroma. Doppler echocardiography of the aorta revealed increased peak velocity profiles, holodiastolic flow reversal, and dilatation of the ascending aorta, consistent with aortic stenosis and regurgitation. Compensated LV hypertrophy deteriorated to decompensated LV failure and remodeling, as indicated by increased LV mass, interstitial fibrosis, and inflammatory cell infiltration. Elevated LV pressures in NZO mice were associated with lung congestion and cor pulmonale , evident as right ventricular dilatation, decreased right ventricular function, and increased mean right ventricular systolic pressure, indicative for the development of pulmonary hypertension and ultimately right ventricular failure. Conclusions NZO mice demonstrate as a novel murine model to spontaneously develop degenerative AoV disease, aortic stenosis, and the associated end organ damages of both ventricles and the lung. Closely mimicking the clinical scenario of degenerative AoV disease, the model may facilitate a better mechanistic understanding and testing of novel treatment strategies in degenerative AoV disease.

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Heart valve disease (aortic valve disease): aortic stenosis

10.1093/med/9780198726012.003.0032 ◽

2016 ◽

Author(s):

Helmut Baumgartner ◽

Stefan Orwat ◽

Elif Sade ◽

Javier Bermejo

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Systolic Function ◽

Integrated Approach ◽

Left Ventricular ◽

Valve Disease ◽

Low Flow ◽

Heart Valve Disease ◽

Lv Function ◽

Diagnostic Challenge

Echocardiography has become the gold standard for the assessment of patients with aortic stenosis (AS). It allows morphological assessment of the aortic valve and provides information on the aetiology of the disease. The quantification of AS includes primarily the measurement of transaortic jet velocities and gradients as well as the calculation of the valve area, thus combining flow-dependent and relatively flow-independent variables. Awareness of potential pitfalls is fundamental when assessing these variables. Haemodynamic consequences of AS on left ventricular (LV) size, wall thickness, and function as well as associated valve lesions and estimates of pulmonary artery pressure are required for the comprehensive evaluation of the disease. In the setting of classical low-flow–low-gradient AS with reduced LV systolic function, low-dose dobutamine echocardiography is of particular diagnostic and prognostic importance. The entity of severe low-flow–low-gradient AS in the presence of preserved LV function remains a particular diagnostic challenge. For accurate differentiation from pseudo-severe AS or misclassified moderate AS, an integrated approach including additional variables such as the extent of valve calcification by computed tomography may be required. In addition to the assessment of AS aetiology and quantification of its severity, echocardiography can provide predictors of outcome that may have a major impact on the decision for intervention.

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Comparative Analysis of the Kinetic Behavior of Systemic Inflammatory Markers in Patients with Depressed versus Preserved Left Ventricular Function Undergoing Transcatheter Aortic Valve Implantation

Journal of Clinical Medicine ◽

10.3390/jcm10184148 ◽

2021 ◽

Vol 10 (18) ◽

pp. 4148

Author(s):

Haitham Abu Khadija ◽

Gera Gandelman ◽

Omar Ayyad ◽

Lion Poles ◽

Michael Jonas ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Transcatheter Aortic Valve Implantation ◽

Left Ventricular ◽

Lv Function ◽

Transcatheter Aortic Valve ◽

Function Group ◽

Aortic Valve Implantation ◽

Inflammatory Profile ◽

Valve Implantation

Background: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study’s aim was to investigate periprocedural inflammatory responses after TAVI. Methods: Patients with severe symptomatic aortic stenosis and reduced LV function who underwent transfemoral TAVI were enrolled. A paired-matched analysis (1:2 ratio) was performed using patients with preserved LV function. Whole white blood cells (WBC) and subpopulation dynamics as well as the neutrophil to lymphocyte ratio (NLR) were evaluated at different times. Results: A total of 156 patients were enrolled, including 52 patients with LVEF < 40% 35.00 [30.00, 39.25] and 104 with LVEF > 50% 55.00 [53.75, 60.0], p < 0.001. Baseline NLR in the reduced LV function group was significantly higher compared to the preserved LV function group, 2.85 [2.07, 4.78] vs. 3.90 [2.67, 5.26], p < 0.04. After a six-month follow-up, the inflammatory profile was found to be similar in the two groups, NLR 2.94 [2.01, 388] vs. 3.30 [2.06, 5.35], p = 0.288. No significant mortality differences between the two groups were observed in the long-term outcome. Conclusions: TAVI for severe symptomatic aortic stenosis, with reduced LV function, was associated with an improvement in the inflammatory profile that may account for some of the observable benefits of the procedure in this subset of patients.

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P650Influence of fetunin-a level on progression of calcific aortic valve stenosis The COFRASA - GENERAC StudyP651Common carotid artery remodeling 1 year after aortic valve surgeryP652Low gradient aortic stenosis with preserved ejection fraction: reclassification of severity by 3D transesophageal echocardiography. P653Results of balloon aortic valvuloplasty in patients with impaired left ventricle ejection fraction.P654Burden of associated aortic regurgitation in patients with mitral regurgitationP655Differences in right ventricular mechanics in acute and chronic ischemic mitral regurgitation after inferoposterior myocardial infarctionP656Tricuspid regurgitation in patients operated for severe symptomatic native aortic stenosis: pre-operative determinantsP657Echocardiographic diagnosis in patients with prosthetic or annuloplasty ring dysfunction: correlation with surgical findingsP659Agreement analisys of different three-dimensional transoesophageal echocardiographic modalities and cardiac CT scan in aortic annulus sizing for transapical heart valve implantationP660Elevated gradients after TAVR are associated with increased rehospitalization, but have no impact on mortality and major adverse cardiac eventsP661Echocardiographic characteristics of post-TAVI thrombosis and endocarditis: single-centre experienceP662Impact of mixed aortic valve disease in long-term mortality after transcatheter aortic valve implantationP663Quantification of mitral regurgitation during interventional valve repair: correlation between haemodynamic parameters and 3D color Doppler echocardiographyP664Mitraclip in functional mitral regurgitation: are immediate results the same in ischemic and non ischemic etiology?P665Left ventricular contractile reserve by stress echocardiography as a predictor of response to cardiac resynchronization therapy in heart failure: a meta-analysisP666Regardless of the definition used, left ventricular reverse remodeling is not different in fibrosis positive and negative dilated cardiomyopathy patientsP667Heterogeneity of LV contractile function by multidimensional strain in patients with EF<35%: Insights for the hemodynamic burdenP668Ability of 99mTc-DPD scintigraphy to predict conduction disorders requiring permanent pacemaker in patients with transthyretin-related cardiac amyloidosisP669Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: relation to electromechanical delayP670Could echocardiographic features differentiate Fabry cardiomyopathy from sarcomeric forms of hypertrophic cardiomyopathy?P671Pregnancy is well tolerated in women with arrhythmogenic right ventricular cardiomyopathy P672Glycogen storage cardiomyopathy (PRKAG2): do particular echocardiography findings in established and advanced techniques are helpful in suggesting the diagnosis?P673Improvement of arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 after optimization of antidiabetic medication

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jew250.001 ◽

2016 ◽

Vol 17 (suppl 2) ◽

pp. ii130-ii136

Author(s):

N. Kubota ◽

J. Petrini ◽

A. Gonzalez Gomez ◽

DS. Sorysz ◽

JM. Monteagudo Ruiz ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Aortic Valve ◽

Mitral Regurgitation ◽

Aortic Stenosis ◽

Right Ventricular ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Functional Mitral Regurgitation ◽

Reverse Remodeling ◽

Ventricular Mechanics

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THE TELEMETERED EXERCISE ELECTROCARDIOGRAM IN CONGENITAL AORTIC STENOSIS

PEDIATRICS ◽

10.1542/peds.47.1.31 ◽

1971 ◽

Vol 47 (1) ◽

pp. 31-39

Author(s):

Katherine H. Halloran

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Valve Stenosis ◽

Systolic Pressure ◽

Left Ventricular ◽

Normal Children ◽

Congenital Aortic Stenosis ◽

Electrocardiographic Leads ◽

Response To Exercise ◽

Exercise Electrocardiogram

Since children with aortic valve stenosis, who are at risk of syncope or sudden death, cannot be identified by the resting electrocardiogram or vectorcardiogram, the exercise electrocardiogram was evaluated and compared with the hemodynamic data obtained during cardiac catheterization. Telemetered exercise electrocardiograms were obtained in 31 children, ages 8 to 18 years, with aortic valve stenosis and in 25 normal children of comparable age. Electrocardiographic leads V1, V5, and V6 were obtained prior to, during, and following exercise on a variable resistance bicycle ergometer. Subjects pedalled until a heart rate of 170 per minute or greater was attained and maintained for at least 2 minutes. An increase in T-wave amplitude was observed in both control children and in those with aortic stenosis. No S-T segment abnormalities were noted in the normal children. Of the 16 patients with peak systolic left ventricular to aortic pressure gradients of less than 50 mm Hg, only one showed a segmental S-T depression. Of the 15 children with aortic valve gradients of 50 to 100 mm Hg, however, all except one showed an S-T segment depression in lead V5 of 2 mm or greater. No correlation between the resting electrocardiogram or the vectorcardiogram and the aortic valve gradient or left ventricular peak systolic pressure could be made. In addition, the abnormal S-T segment response to exercise could not be predicted from or correlated with the resting electrocardiogram. Since an ischemic S-T segment response to exercise was found uniformly in those with the higher gradients, this test appears to have a high degree of specificity in the clinical evaluation of these patients.

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Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis

European Heart Journal ◽

10.1093/eurheartj/ehaa033 ◽

2020 ◽

Vol 41 (20) ◽

pp. 1903-1914 ◽

Cited By ~ 10

Author(s):

Miriam Puls ◽

Bo Eric Beuthner ◽

Rodi Topci ◽

Anja Vogelgesang ◽

Annalen Bleckmann ◽

...

Keyword(s):

Heart Failure ◽

Aortic Valve ◽

Aortic Stenosis ◽

Myocardial Fibrosis ◽

Transcatheter Aortic Valve Implantation ◽

Left Ventricular ◽

Lv Function ◽

Transcatheter Aortic Valve ◽

Aortic Valve Implantation ◽

Valve Implantation

Abstract Aims Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes. Methods and results One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson’s trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF−) median percentage MF (≥11% or <11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003). In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. 2% in MF− patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0–369), P = 0.01]. Conclusion Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI.

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Echocardiographic evaluation of cardiac function response to removal of aortic stenosis: Surgical and trans-catheter aortic valve implantation (TAVI)

International Cardiovascular Forum Journal ◽

10.17987/icfj.v1i1.9 ◽

2015 ◽

Vol 1 (1) ◽

pp. 16

Author(s):

Ying Zhao ◽

Yi-hua He

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Heart Surgery ◽

Open Heart Surgery ◽

Left Ventricular ◽

Lv Function ◽

Open Heart ◽

Echocardiographic Evaluation ◽

Aortic Valve Implantation ◽

Valve Implantation

Aortic stenosis (AS) is the commonest valve disease in theWest, with a prevalence varying between 0.02% in adultsunder 44 years and 3-9% in those over 80 years of age 1, 2. Thedisease may remain “silent” and hence unnoticed for years,particularly in the elderly with naturally limited exercise. With thedevelopment of symptoms, patients may carry a mortality of36-52%, 52-80% and 80-90% at 3, 5 and 10 years, respectivelyif left untreated, with a potential high risk of sudden death 3.Surgical aortic valve replacement (SAVR) used to be the onlyeffective treatment for severe AS, being the second indicationfor open heart surgery after coronary artery bypass grafting(CABG) 4. Trans-catheter aortic valve implantation (TAVI) is arecently developed procedure which aims at non-surgical AVRin patients with severe, symptomatic and calcified AS whoare at high surgical risk because of either poor left ventricular(LV) function, ejection fraction (EF) <50%, or other significantco-morbidities e.g. age >80 years, previous CABG surgery and/or aorta or other heart valve surgery, impaired kidney function,chronic obstructive pulmonary disease (COPD) or pulmonaryhypertension 5. Currently, this technique is not recommendedin bicuspid AS patients due to the risk of incomplete andsuboptimal deployment of the aortic prosthesis [6]. TAVIavoids open heart surgery and hence is likely to protectmyocardial function. The purpose of this paper is to review theechocardiographic evaluation of LV, right ventricular (RV), andleft atrial (LA) function response to SAVR and TAVI for AS.

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Genetic and Developmental Contributors to Aortic Stenosis

Circulation Research ◽

10.1161/circresaha.120.317978 ◽

2021 ◽

Vol 128 (9) ◽

pp. 1330-1343 ◽

Cited By ~ 1

Author(s):

Punashi Dutta ◽

Jeanne F. James ◽

Hail Kazik ◽

Joy Lincoln

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Bicuspid Aortic Valve ◽

Financial Burden ◽

Left Ventricular ◽

Valve Disease ◽

Outflow Obstruction ◽

Left Ventricular Outflow Obstruction ◽

Ventricular Outflow Obstruction ◽

Left Ventricular Outflow

Aortic stenosis (AS) remains one of the most common forms of valve disease, with significant impact on patient survival. The disease is characterized by left ventricular outflow obstruction and encompasses a series of stenotic lesions starting from the left ventricular outflow tract to the descending aorta. Obstructions may be subvalvar, valvar, or supravalvar and can be present at birth (congenital) or acquired later in life. Bicuspid aortic valve, whereby the aortic valve forms with two instead of three cusps, is the most common cause of AS in younger patients due to primary anatomic narrowing of the valve. In addition, the secondary onset of premature calcification, likely induced by altered hemodynamics, further obstructs left ventricular outflow in bicuspid aortic valve patients. In adults, degenerative AS involves progressive calcification of an anatomically normal, tricuspid aortic valve and is attributed to lifelong exposure to multifactoral risk factors and physiological wear-and-tear that negatively impacts valve structure-function relationships. AS continues to be the most frequent valvular disease that requires intervention, and aortic valve replacement is the standard treatment for patients with severe or symptomatic AS. While the positive impacts of surgical interventions are well documented, the financial burden, the potential need for repeated procedures, and operative risks are substantial. In addition, the clinical management of asymptomatic patients remains controversial. Therefore, there is a critical need to develop alternative approaches to prevent the progression of left ventricular outflow obstruction, especially in valvar lesions. This review summarizes our current understandings of AS cause; beginning with developmental origins of congenital valve disease, and leading into the multifactorial nature of AS in the adult population.

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Abstract 15011: Association of Pulmonary Hemodynamics and Right Ventricular Function With Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.142.suppl_3.15011 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Romil R Parikh ◽

Faye L Norby ◽

Wendy Wang ◽

Thenappan Thenappan ◽

Kurt W Prins ◽

...

Keyword(s):

Atrial Fibrillation ◽

Right Ventricular ◽

Systolic Pressure ◽

Left Ventricular ◽

Cox Proportional Hazards ◽

Volume Index ◽

Pulmonary Artery Systolic Pressure ◽

Pulmonary Hemodynamics ◽

Functional Remodeling ◽

Rv Function

Introduction: Higher pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction are associated with higher risk of heart failure (HF) and mortality. Whether higher PASP and lower RV function are associated with risk of atrial fibrillation (AF) is unclear. Hypothesis: Higher PASP, higher pulmonary vascular resistance (PVR), and lower RV function are associated with incident AF after accounting for left atrial (LA) size and function, and left ventricular (LV) systolic and diastolic function. Methods: ARIC participants free of prevalent coronary heart disease (CHD), HF, AF, and with LA volume index (LAVi) <34ml/m 2 and average E/e’ ratio <14 in 2011-13 were included. We measured PASP, PVR, RV fractional area change (RVFAC), and RV-PA coupling (defined as RVFAC/PASP ratio) from 2D-echocardiograms. Incident AF (through 2018) was ascertained from hospital discharge codes and death certificates. We used Cox proportional hazards regression in our analysis. Results: We included 1915 participants (mean age 75 years, 69% female, 24% black) of whom 176 developed AF over a median follow-up of 6.3 years. PASP, PVR, and RV-PA coupling were significantly associated with incident AF after adjusting for measures of LA and LV structural and functional remodeling. RVFAC was not significantly associated with incident AF. Conclusions: In persons without CHD, HF, and LA enlargement, higher PASP and lower RV-PA coupling are associated with higher risk of AF after accounting for LA and LV structural and functional remodeling. This finding, which suggests a possible etiological role of RV remodeling for AF, needs further confirmation.

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Ventricular mechanics in patients with aortic valve disease: longitudinal, radial, and circumferential components

Cardiology in the Young ◽

10.1017/s1047951112002326 ◽

2013 ◽

Vol 24 (1) ◽

pp. 105-112 ◽

Cited By ~ 7

Author(s):

Benedetta Leonardi ◽

Renee Margossian ◽

Stephen P. Sanders ◽

Marcello Chinali ◽

Steven D. Colan

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Regurgitation ◽

Aortic Valve Disease ◽

Longitudinal Strain ◽

Circumferential Strain ◽

Wall Stress ◽

Left Ventricular ◽

Valve Disease ◽

Mass Volume

AbstractBackgroundReduced long-axis shortening despite enhanced global function has been reported in aortic stenosis. We sought to improve the understanding of this phenomenon using multi-dimensional strain analysis in conjunction with the evaluation of left ventricular rotation and twist – ventricular torsion – using tissue Doppler techniques.MethodsA total of 57 patients with variable severity of aortic stenosis, aortic regurgitation, or mixed aortic valve disease, subdivided into six groups, were studied. Ventricular morphology was assessed using long-axis/short-axis and mass/volume ratios, afterload using end-systolic meridional wall stress, and global performance using ejection fraction. The circumferential and longitudinal strain was measured from two-dimensional images, and left ventricular rotation and twist were estimated as the difference in rotation between the base and apex of the ventricle.ResultsAortic stenosis was associated with higher mass/volume, ejection fraction, circumferential strain and left ventricular rotation and twist, significantly lower end-systolic wall stress, and a trend towards lower longitudinal strain compared with normal. Myocardial mechanics in aortic regurgitation were normal despite ventricular dilation. Mixed aortic valve disease showed findings similar to aortic stenosis. Left ventricular rotation and twist correlated with midwall circumferential strain (r = 0.62 and p < 0.0001), endocardial circumferential strain (r = 0.61 and p < 0.0001), and end-systolic wall stress (r = 0.48 and p < 0.0001), but not with longitudinal strain (r = 0.18 and p > 0.05).ConclusionsMyocardial mechanics are normal in patients with aortic regurgitation, independent of abnormalities in cardiac geometry. Conversely, in aortic stenosis and mixed aortic valve disease, significant alterations in the patterns of fibre shortening are found. The effects of stenosis on cardiac function seem to dominate the effect of ventricular remodelling.

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Abstract 9944: Bicuspid and Unicuspid Aortic Valve: Fate of Moderate/Severe Mixed Aortic Valve Disease

Circulation ◽

10.1161/circ.132.suppl_3.9944 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Alexander Egbe ◽

Joeseph Poterucha ◽

Carole Warnes

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Valve Disease ◽

Left Ventricular ◽

Valve Disease ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Aortic Replacement ◽

Mechanical Prostheses

Objectives: There is paucity of data about mixed aortic valve disease (MAVD) in patients with bicuspid/unicuspid aortic valve (BAV). This study sought to describe the natural history of moderate/severe MAVD in this population. Methods: We queried our database for patients with BAV and moderate/severe MAVD from 1994-2013. We excluded patients with NYHA III/IV symptoms, left ventricular ejection fraction <50%, aortic dimension >50 mm, and significant disease of other valves. Primary endpoint was freedom from adverse events (AE) defined as aortic valve replacement (AVR) or death. Secondary endpoint was freedom from developing NYHA III/IV symptoms, and to identify predictors of AE. Cox proportional hazard model was used. Results: There were 138 patients (age 51±12 years, males 81%) who were followed for 8.5±4 years. Ninety-two patients (67%) underwent AVR at a mean follow-up duration of 3.7±2.5 years. Mechanical prostheses were implanted in 79% and 52% had concomitant CABG and/or aortic replacement during AVR. No early surgical mortality. Event-free survival was 51%, and 20% at 5 and 10 years. Predictors of AE were age at presentation (hazard ratio [HR] 5.22 Confidence interval [CI] 3.10 to 6.64) for every decade increase in age and having severe stenosis or regurgitation at the time of presentation (HR 1.32; CI 1.05 to 3.16). Conclusion: Time (age and duration of follow-up) was the strongest predictor of AE in BAV population unlike in patients with trileaflet aortic valve stenosis where peak aortic velocity was prognostic. Figure Legend: pVel: peak velocity group 1: moderate aortic stenosis and regurgitation Group ≥2: severe aortic stenosis or regurgitation

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