scholarly journals Titin isoform expression in aortic stenosis

2009 ◽  
Vol 117 (6) ◽  
pp. 237-242 ◽  
Author(s):  
Lynne WILLIAMS ◽  
Neil Howell ◽  
Domenico Pagano ◽  
Peter Andreka ◽  
Marton Vertesaljai ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Aortic Stenosis ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Normal Donor ◽  
Myocardial Stiffness ◽  
Hypertrophic Response ◽  
Cardiac Titin ◽  
Sarcomeric Protein ◽  
Artery Disease

Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that the expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from 13 donor hearts for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66±0.04 in the normal donor hearts compared with 0.48±0.03 in patients with aortic stenosis; P=0.02). However, total titin remained unchanged (0.28±0.02 compared with 0.24±0.02 respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B titin in response to pressure overload may result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.

Preserved heart function after left ventricular pressure overload in adult mice subjected to neonatal cardiac hypoplasia

2017 ◽  
Vol 9 (1) ◽  
pp. 112-124
Author(s):  
K. Heinecke ◽  
A. Heuser ◽  
F. Blaschke ◽  
C. Jux ◽  
L. Thierfelder ◽  
...  
Keyword(s):  
Mouse Model ◽  
Heart Function ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Cellular Level ◽  
Left Ventricular ◽  
P38 Map Kinase ◽  
Cross Sectional ◽  
Hypertrophic Response ◽  
Cardiomyocyte Number

Intrauterine growth restriction in animal models reduces heart size and cardiomyocyte number at birth. Such incomplete cardiomyocyte endowment is believed to increase susceptibility toward cardiovascular disease in adulthood, a phenomenon referred to as developmental programming. We have previously described a mouse model of impaired myocardial development leading to a 25% reduction of cardiomyocyte number in neonates. This study investigated the response of these hypoplastic hearts to pressure overload in adulthood, applied by abdominal aortic constriction (AAC). Echocardiography revealed a similar hypertrophic response in hypoplastic hearts compared with controls over the first 2 weeks. Subsequently, control mice develop mild left ventricular (LV) dilation, wall thinning and contractile dysfunction 4 weeks after AAC, whereas hypoplastic hearts fully maintain LV dimensions, wall thickness and contractility. At the cellular level, controls exhibit increased cardiomyocyte cross-sectional area after 4 weeks pressure overload compared with sham operated animals, but this hypertrophic response is markedly attenuated in hypoplastic hearts. AAC mediated induction of fibrosis, apoptosis or cell cycle activity was not different between groups. Expression of fetal genes, indicative of pathological conditions, was similar in hypoplastic and control hearts after AAC. Among various signaling pathways involved in cardiac hypertrophy, pressure overload induces p38 MAP-kinase activity in hypoplastic hearts but not controls compared with the respective sham operated animals. In summary, based on the mouse model used in this study, our data indicates that adult hearts after neonatal cardiac hypoplasia show an altered growth response to pressure overload, eventually resulting in better functional outcome compared with controls.

scholarly journals Left ventricular hypertrophy in patients treated with regular hemodialyses

2008 ◽  
Vol 61 (7-8) ◽  
pp. 369-374 ◽  
Author(s):  
Dejan Petrovic ◽  
Biljana Stojimirovic
Keyword(s):  
Risk Factors ◽  
Left Ventricle ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Concentric Hypertrophy ◽  
Cardiovascular Morbidity And Mortality

Left ventricular hypertrophy is the main risk factor for development of cardiovascular morbidity and mortality in patients on hemodialysis. Left ventricular hypertrophy is found in 75% of the patients treated with hemodialysis. Risk factors for left ventricular hypertrophy in patients on hemodialysis include: blood flow through arterial-venous fistula, anemia, hypertension, increased extracellular fluid volume, oxidative stress, microinflammation, hyperhomocysteinemia, secondary hyperpara- thyroidism, and disturbed calcium and phosphate homeostasis. Left ventricular pressure overload leads to parallel placement of new sarcomeres and development of concentric hypertrophy of left ventricle. Left ventricular hypertrophy advances in two stages. In the stage of adaptation, left ventricular hypertrophy occurs as a response to increased tension stress of the left ventricular wall and its action is protective. When volume and pressure overload the left ventricle chronically and without control, adaptive hypertrophy becomes maladaptive hypertrophy of the left ventricle, where myocytes are lost, systolic function is deranged and heart insufficiency is developed. Left ventricular mass index-LVMi greater than 131 g/m2 in men and greater than 100 g/m2 in women, and relative wall thickness of the left ventricle above 0.45 indicate concentric hypertrophy of the left ventricle. Eccentric hypertrophy of the left ventricle is defined echocardiographically as LVMi above 131 g/m2 in men and greater than 100 g/m2 in women, with RWT ?0.45. Identification of patients with increased risk for development of left ventricular hypertrophy and application of appropriate therapy to attain target values of risk factors lead to regression of left ventricular hypertrophy, reduced cardiovascular morbidity and mortality rates and improved quality of life in patients treated with regular hemodialyses.

scholarly journals FREQUENCY OF CORONARY ARTERY DISEASE IN VALVULAR AORTIC STENOSIS :EXPERIENCE OF THE CARDIOLOGY CENTER OF MOHAMED V MILITARY HOSPITAL ABOUT 148 CASES

2021 ◽  
Vol 9 (08) ◽  
pp. 487-491
Author(s):  
D. Massimbo ◽  
S. Nikiema ◽  
S. Ahchouch ◽  
I. Asfalou ◽  
A. Benyass
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Aortic Stenosis ◽  
Coronary Disease ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Military Hospital ◽  
Ventricular Ejection Fraction ◽  
Artery Disease

Introduction: The risk factors for aortic stenosis have been shown to be similar to those for atherosclerosis. Thus, coronary disease is often found simultaneously in patients with aortic stenosis. Our work aims to determine the frequency of coronary disease in a Moroccan population with aortic stenosis while recalling the causes and the prognostic and therapeutic impacts of this association. Materials and Methods: This is a retrospective study of 148 patients hospitalized at the cardiology center of the military hospital of Rabat over a period of 24 months, during which we analyzed clinical, electrocardiographic, echocardiographic and coronarographic data of the patients in order to evaluate the coronary involvement during aortic stenosis. Results: The mean age of the population was 65 [57, 74] years, the sex ratio was 1.21. Smoking reported in 38.5% of patients was the main modifiable cardiovascular risk factor, followed by hypertension in 35.8% of patients. Dyspnea on exertion was the most frequent reason for consultation at 81%, 64% of which were at least NYHA functional class III, followed by angina, which represented 33% of the series. The aortic stenosis was tight in the majority (mean SAo: 0.8 cm²) and the left ventricular ejection fraction was preserved overall. Coronary artery disease was associated with aortic stenosis in 24% of cases, with predominantly monotruncal involvement (53%) followed by tritruncal involvement (30%). 21.6% of these patients underwent coronary artery bypass grafting concomitantly with surgical replacement of the aortic valve. Conclusion: The incidence of coronary artery disease associated with aortic stenosis is variable according to age. It is higher in European series because of aging. In our relatively younger population, it is lower but not negligible.

Abstract 1581: Extension of Titin as a Function of Filling Pressure and Sarcomere Length in the Porcine Left Ventricle

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Martin M LeWinter ◽  
Joseph Popper ◽  
Lori Nyland ◽  
Stephen B Bell ◽  
Henk Granzier
Keyword(s):  
Left Ventricle ◽  
Sarcomere Length ◽  
Filling Pressure ◽  
Passive Tension ◽  
Large Mammals ◽  
Myocardial Stiffness ◽  
Sarcomeric Protein ◽  
Equilibrium Volume ◽  
Slack Length

The giant sarcomeric protein titin is a molecular spring that is the chief source of cardiomyocyte passive tension and a major determinant of myocardial stiffness. The spring portion is located in the I band and consists of PEVK, Ig repeat and N2B and N2A elements. Titin occurs as two isoforms. N2B is a smaller and stiffer isoform that contains only the N2B element and predominates in the left ventricle (LV) of rodents. N2BA titin contains both N2A and N2B elements. N2B and N2BA are co-expressed in the sarcomere of large mammals (~60:40 ratio). As a result, passive cardiomyocyte and myocardial stiffness in large mammals is less than in rodents. Details of titin extension as a function of sarcomere length (SL) have been elucidated in rodents but not in large mammals, where the presence of both isoforms would be expected to modify extension and passive tension. Accordingly, we studied titin extension in miniswine. We first established the relation between filling pressure and SL in the anterior LV wall of the in situ, freshly arrested (KCl) heart. SL was determined over a range of filling pressures using a light microscopic method that minimizes shrinkage. At equilibrium volume (transmural pressure 0 mmHg), SL was between 2.00–2.10 μm, longer than slack length of ~1.85 μm in muscle strips. SL reached a maximum of ~2.50 βm when the LV was over-distended (filling pressure >40 mmHg). We then examined extension of titin in myocardial strips using electron microscopy and immuno-labeling of selected epitopes. The chief difference between isoforms was that the N2B-Us epitope segment in N2B titin lengthened ~four times more than the N2B-Us segment in N2BA titin over SLs from ~1.80 to ~2.50 μm. This difference remained large over the SL range present in the in situ LV. Linear fits of the measured end-to-end length of N2B-Us segments were used to estimate the force-SL relation of single N2B and N2BA molecules. This analysis predicted a much steeper relation for N2B titin. Thus, over the range of SLs present in the in situ LV the most prominent difference in extension of N2B and N2BA titin is greater lengthening of the N2B segment of N2B titin. This predicts a much greater in situ stiffness for N2B titin and demonstrates how passive stiffness can be exquisitely controlled by varying isoform expression.

scholarly journals P959 Handheld echocardiography in a real world scenario: concordances compared to standard echo reports

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
L David Lechinewski ◽  
I P Vieira ◽  
N Clausell ◽  
L A Z Moura ◽  
M Barnes ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Aortic Stenosis ◽  
Right Ventricle ◽  
Pulmonary Regurgitation ◽  
Left Ventricular ◽  
K Value ◽  
Study Results ◽  
Hemodynamic Assessment ◽  
And Function ◽  
Experienced Echocardiographer

Abstract Background Handheld echocardiography devices(HH) arise as a common tool in clinical examination and screening for various cardiovascular disorders. Despite of it, studies with this method are small, with unselected patients and limited scope of diagnostic comparison. Purpose Assess the usefulness of the new miniaturized HH and compare its concordances with the standard high definition echocardiography study(STD). Methods Between April and May of 2016 adult patients who were scheduled to regular STD, were also submitted to a HH exam. Experienced sonographers performed and an experienced echocardiographer reviewed the STD exam, and an experienced echocardiographer performed and reviewed the HH study - reviewers were blinded to the other study results. STD exams included 2-dimensional images, Color Doppler and hemodynamics analysis. With the HH hemodynamic assessment was not performed as the machine does not include such technology. Agreement between the reports was analyzed. Results 110 patients were included. Mean age was 62.4 ± 16.7 years. The κ values(Table) show good correlation between HH and STD on the analysis of left ventricular global and segment functions, right ventricle size and function, mitral and aortic stenosis. On the evaluation of left ventricle hypertrophy, mitral and aortic regurgitations the correlation was modest, while poor correlation was found for pulmonary and tricuspid regurgitations. Conclusion In a daily practice scenario with experienced hands, HH demonstrates good results for the assessment of ventricles size and function, while the evaluation of right heart valves was the least reliable performance. Dissemination of HH should occur with considerations and caution. K Values for Echocardiography Analysis Echocardiography analysis K value Global estimated LV dysfunction 0.85 Wall motion abnormalities 0.78 LV hypertrophy 0.6 RV size 0.83 RV function 0.82 Mitral regurgitation 0.42 Aortic regurgitation 0.56 Mitral stenosis 0.96 Aortic stenosis 0.82 Tricuspid regurgitation 0.26 Pulmonary regurgitation 0.25 LV: left ventricle; RV: right ventricle.

Contractile function in chronic gradually developing subcoronary aortic stenosis

1981 ◽  
Vol 240 (1) ◽  
pp. H80-H84
Author(s):  
B. A. Carabello ◽  
R. Mee ◽  
J. J. Collins ◽  
R. A. Kloner ◽  
D. Levin ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Animal Studies ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Stroke Work ◽  
Group A ◽  
Group B

Whether hypertrophied cardiac muscle functions normally or abnormally is a point of controversy in the literature. Most animal studies showing depressed performance of hypertrophied cardiac muscle have used experimental methods in which hypertrophy was produced by acutely imposing a pressure overload on the left or right ventricle, which may cause myocardial injury. To assess the possibility that chronic, slowly developing hypertrophy is associated with normal myocardial function, we developed an experimental model in which increased afterload is imposed gradually on the left ventricle in the dog. A snug band was placed around the aorta beneath the left coronary artery in puppies without producing a stenosis. As the puppies grew, relative aortic stenosis developed as increased cardiac output flowed across that fixed outflow area. One group (group A) of six puppies was banded early, whereas a second group (group B, five puppies) was banded late and served as controls. Left ventricular weight (g) to body weight (kg) ratio remained normal in group B animals (3.9 +/- 0.14), whereas this ratio was increased to 5.3 +/- 0.24 (P < 0.001) in group A animals indicating development of moderate cardiac hypertrophy. Ejection fraction, dP/dt, Vcf, and stroke work per gram of myocardium were virtually identical in both groups. We conclude that moderate, gradually developing cardiac hypertrophy as produced by this model is associated with normal myocardial contractile performance.

scholarly journals Time course of left ventricular remodelling and mechanics after aortic valve surgery: aortic stenosis vs. aortic regurgitation

2019 ◽  
Vol 20 (10) ◽  
pp. 1105-1111
Author(s):  
E Mara Vollema ◽  
Gurpreet K Singh ◽  
Edgard A Prihadi ◽  
Madelien V Regeer ◽  
See Hooi Ewe ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Regurgitation ◽  
Time Course ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Valve Surgery ◽  
Aortic Valve Surgery ◽  
Lv Mass

Abstract Aims Pressure overload in aortic stenosis (AS) and both pressure and volume overload in aortic regurgitation (AR) induce concentric and eccentric hypertrophy, respectively. These structural changes influence left ventricular (LV) mechanics, but little is known about the time course of LV remodelling and mechanics after aortic valve surgery (AVR) and its differences in AS vs. AR. The present study aimed to characterize the time course of LV mass index (LVMI) and LV mechanics [by LV global longitudinal strain (LV GLS)] after AVR in AS vs. AR. Methods and results Two hundred and eleven (61 ± 14 years, 61% male) patients with severe AS (63%) or AR (37%) undergoing surgical AVR with routine echocardiographic follow-up at 1, 2, and/or 5 years were evaluated. Before AVR, LVMI was larger in AR patients compared with AS. Both groups showed moderately impaired LV GLS, but preserved LV ejection fraction. After surgery, both groups showed LV mass regression, although a more pronounced decline was seen in AR patients. Improvement in LV GLS was observed in both groups, but characterized by an initial decline in AR patients while LV GLS in AS patients remained initially stable. Conclusion In severe AS and AR patients undergoing AVR, LV mass regression and changes in LV GLS are similar despite different LV remodelling before AVR. In AR, relief of volume overload led to reduction in LVMI and an initial decline in LV GLS. In contrast, relief of pressure overload in AS was characterized by a stable LV GLS and more sustained LV mass regression.

Aortic stenosis

2018 ◽  
Author(s):  
Patrick Davey ◽  
Jim Newton
Keyword(s):  
Blood Flow ◽  
Aortic Valve ◽  
Left Ventricle ◽  
Left Ventricular Hypertrophy ◽  
Aortic Stenosis ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Aortic Valve Leaflets ◽  
Reduced Mobility

Aortic stenosis is characterized by thickening and reduced mobility of the aortic valve leaflets and results in restriction to the blood flow from the left ventricle to the aorta, and secondary left ventricular hypertrophy.

scholarly journals A ventricular-vascular coupling model in presence of aortic stenosis

2005 ◽  
Vol 288 (4) ◽  
pp. H1874-H1884 ◽  
Author(s):  
Damien Garcia ◽  
Paul J. C. Barenbrug ◽  
Philippe Pibarot ◽  
André L. A. J. Dekker ◽  
Frederik H. van der Veen ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Left Ventricle ◽  
Aortic Stenosis ◽  
Vascular System ◽  
Severe Aortic Stenosis ◽  
Left Ventricular ◽  
Arterial System ◽  
Coefficient Of Determination ◽  
Ventricular Afterload ◽  
Good Agreement

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 (V3) 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 V3 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 = 0.99 x − 2.36 with a coefficient of determination r2 = 0.98. There was also very good agreement between estimated and measured stroke volumes ( y = 1.03 x + 2.2, r2 = 0.96, SEE = 2.8 ml). Hence, this mathematical V3 model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.

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