Development of aortic valve sclerosis or stenosis in rabbits: role of cholesterol and calcium

BACKGROUND AND AIM OF THE STUDY: Aortic valve sclerosis is fairly common and is currently seen as a marker of systemic atherosclerosis. For unclear reasons only a minority of those sclerotic valves will evolve to become stenotic suggesting that atherogenic factors alone are insufficient to explain the development of valve stenosis. We had reported in a model of cholesterol fed rabbits that a combination of high cholesterol with vitamin D supplementation was necessary to induce valve stenosis and significant calcium deposition whereas high cholesterol alone only induced a sclerosis of the valve. In this study, we further evaluated the role of vitamin D treatment in the development of aortic valve disease (sclerosis or stenosis) in this rabbit model. METHODS: Rabbits were divided in 4 groups followed for 12 weeks: 1) no treatment; 2) cholesterol-enriched diet, 3) cholesterol-enriched diet + vitamin D2 (VD; 50000IU, daily) 4) VD alone for 12 weeks. Echocardiographic assessment of the aortic valve was done at baseline, and every 4 weeks thereafter. Aortic valve area, maximal and mean transvalvular gradients were recorded and compared over time. Immunohistological study of the valves of AS rabbits was also realized for several classical atherosclerosis markers. RESULTS: Vitamin D2 treated animal did not develop any stenosis of the valve despite increased echogenicity due to diffuse calcium deposits on the leaflets without any atherosclerotic lesions. Only the combination of high cholesterol with VD resulted in a decrease of aortic valve area. Immunohistological analysis of aortic valves from VD rabbits showed the presence of calcium deposits, T-cell infiltration in addition to positive labeling for alpha-smooth muscle cell actin. We did not observe macrophage infiltration in aortic valve leaflets of VD rabbits. CONCLUSION: Hypercholesterolemia or vitamin D supplements alone could not induce aortic valve stenosis in our animal model whereas the combination resulted in a decreased aortic valve area. These findings support the hypothesis that a combination of atherosclerotic and calcifying factors is necessary to induce aortic valve stenosis in this model.     

A high fat/high carbohydrate diet induces aortic valve disease in C57BL/6J mice.

OBJECTIVES: The purpose of this study was to compare aortic valve function and morphology in adult wild-type (WT) mice and in low-density lipoprotein receptor-deficient (LDLr-/-) mice fed or not fed a high-fat/high-carbohydrate (HF/HC) diet. BACKGROUND: Observations suggest a link between degenerative aortic valve stenosis (AS) and atherosclerosis. Aortic valve stenosis has been successfully induced in animal models of extreme hypercholesterolemia, but these models are less relevant to humans. It is not known if a proatherogenic HF/HC diet without added cholesterol could have the same negative impacts. METHODS: Forty C57BL/6J mice were divided into four groups: WT + normal diet, WT + HF/HC diet, LDLr-/- with a normal diet, and LDLr-/- with a HF/HC diet. Aortic valve function and histology were evaluated by echocardiography after four months. RESULTS: Wild-type mice on a HF/HC diet became mildly hypercholesterolemic, obese, and hyperglycemic. As expected, LDLr-/- mice became severely hypercholesterolemic. Both WT and LDLr-/- mice on a HF/HC diet displayed smaller valve areas and higher transvalvular velocities (p < 0.01) after four months. Aortic valve leaflets were thicker and infiltrated with lipids and macrophages in both HF/HC groups. CONCLUSIONS: A HF/HC diet in mice results in significant aortic valve abnormalities. Putting WT mice on a HF/HC diet reproduced a combination of atherogenic factors (obesity, mild dyslipidemia, and hyperglycemia) more commonly encountered in humans than isolated severe hypercholesterolemia. Severe hypercholesterolemia was not a prerequisite in our model. This experimental model suggests that AS development is multifactorial and that hypercholesterolemia should not be the only target in this disease.     

Magnetic resonance to assess the aortic valve area in aortic stenosis: how does it compare to current diagnostic standards?

OBJECTIVES: The purpose of the present study was to evaluate whether magnetic resonance (MR) planimetry of the aortic valve area (AVA) may prove to be a reliable, non-invasive diagnostic tool in the assessment of aortic valve stenosis, and how the results compare with current diagnostic standards.BACKGROUND: Current standard techniques for assessing the severity of aortic stenosis include transthoracic and transesophageal echocardiography (TEE) as well as transvalvular pressure measurements during cardiac catheterization. METHODS: Forty consecutive patients underwent cardiac catheterization, TEE, and MR. The AVA was estimated by direct planimetry (MR, TEE) or calculated indirectly via the peak systolic transvalvular gradient (catheter). Pressure gradients from cardiac catheterization and Doppler echocardiography were also compared. RESULTS: By MR, the mean AVA(max) was 0.91 +/- 0.25 cm(2); by TEE, AVA(max) was 0.89 +/- 0.28 cm(2); and by catheter, the AVA was calculated as 0.64 +/- 0.26 cm(2). Mean absolute differences in AVA were 0.02 cm(2) for MR versus TEE, 0.27 cm(2) for MR versus catheter, and 0.25 cm(2) for TEE versus catheter. Correlations for AVA(max) were r = 0.96 between MR and TEE, r = 0.47 between TEE and catheter, and r = 0.44 between MR and catheter. The correlation between Doppler and catheter gradients was r = 0.71. CONCLUSIONS: Magnetic resonance planimetry of the AVA correlates well with TEE and less well with the catheter-derived AVA. Invasive and Doppler pressure correlated less well than those obtained from planimetric techniques. Magnetic resonance planimetry of the AVA may provide an accurate, non-invasive, well-tolerated alternative to invasive techniques and transthoracic echocardiography in the assessment of aortic stenosis.     

Development of mild aortic valve stenosis in a rabbit model of hypertension.

OBJECTIVES: This study was designed to investigate the association between hypertension and aortic valve stenosis (AVS) in a rabbit model. BACKGROUND: Degenerative AVS is a prevalent disease in elderly persons. Its molecular mechanisms remain unclear, in part because of the absence of experimental models. Epidemiologic data suggest a link between hypertension and AVS. However, there has been no evidence of a cause-effect relationship. METHODS: New Zealand White rabbits were divided into two groups: 1) animals (n = 20) instrumented according to one-kidney/one-clip hypertensive model; and 2) control animals (n = 10) sham operated. Echocardiography (S12 MHz) was used to assess aortic valve (AV) morphology and function as well as left ventricular mass at baseline and after two and four months of hypertension. RESULTS: Blood pressure and left ventricular mass increase were highly significant in the animal model but not in controls at two months, without noticeable AV function abnormalities. After 4 months, however, 14 hypertensive survived animals showed a 14.6% reduction of AV area (0.240 +/- 0.063 cm2 vs. 0.205 +/- 0.060 cm2, p < 0.05), a 19.6% increase of AV thickness (0.056 +/- 0.011 cm vs. 0.067 +/- 0.010 cm, p < 0.001), a 40.4% increase of transvalvular mean gradient (5.35 +/- 2.26 mm Hg vs. 7.51 +/- 3.73 mm Hg, p < 0.05) and a 63.6% increase of transvalvular maximal gradient (10.56 +/- 3.68 mm Hg vs. 17.28 +/- 10.95 mm Hg, p < 0.05). Control animals did not show significant changes. CONCLUSIONS: We report a novel experimental model of AVS in rabbits that may prove useful in studying the progression of the disease and the efficacy of new treatments. The present findings support the hypothesis of a causal link between hypertension and AVS.     

Relation of weights of operatively excised stenotic aortic valves to preoperative transvalvular peak systolic pressure gradients and to calculated aortic valve areas

OBJECTIVES: The purpose of this study was to correlate the weights of operatively excised stenotic aortic valves to preoperative transvalvular peak systolic gradients and to calculated aortic valve areas. BACKGROUND: No previous publication has correlated the weights of stenotic aortic valves to the transvalvular gradients or to the calculated aortic valve areas. METHODS: We weighed operatively excised stenotic aortic valves in 324 adults who had undergone preoperative left-sided cardiac catheterization. RESULTS: As the weights of the operatively excised stenotic aortic valves increased (from <1 g to >6 g), the average transvalvular peak systolic pressure gradients progressively increased. For any valve weight, in general, the women had higher average transvalvular gradients (p 相似文献   

In-vivo analysis of the instantaneous transvalvular pressure difference-flow relationship in aortic valve stenosis: implications of unsteady fluid-dynamics for the clinical assessment of disease severity

BACKGROUND AND AIM OF THE STUDY: Because the hemodynamic basis of aortic valve area (AVA) has never been validated in vivo, several alternative indices have been proposed to quantify the severity of aortic stenosis (AS). This study was designed to assess the fluid-dynamics of aortic valve stenosis in order to clarify which index best accounts for disease severity. The diagnostic implications of reversed deltaP during ejection were also investigated. METHODS: Chronic valvular AS characterized by stiff leaflets without commissural fusion was created surgically in eight adult mongrel dogs; three additional animals were used as controls. At two-week intervals (three studies per dog), simultaneous micromanometer pressure and transit-time Q measurements were collected under different hemodynamic conditions. Instantaneous deltaP and Q signals were processed digitally and fitted to a modified form of the unsteady Bernoulli equation in which AS is characterized by effective valve area. RESULTS: An unsteady Bernoulli equation accurately predicted measured instantaneous AP values (R = 0.97+/-0.06), and a quadratic correlation was observed between instantaneously fitted and Gorlin-derived AVA. Additionally, deltaP < 0 mmHg during late ejection was observed in the majority of AS datasets, with a normalized time to deltaP reversal of 93+/-13% for AS animals versus 69+/-36% for controls (p <0.0005). Time to deltaP reversal inversely correlated with the Strouhal number (R = -0.77), and was responsible for an overestimation of mean systolic transvalvular deltaP and Q that resulted in a significant bias in the Gorlin method. Error was highest in moderate stenosis with low transvalvular output. CONCLUSION: Unsteady fluid-dynamics supports AVA over other measures of AS such as aortic valve resistance. However importantly, late-ejection reversal of deltaP precludes estimating the systolic ejection period from pressure tracings, and accounts for an additional source of error when AS is quantified invasively.     

Development of aortic valve sclerosis in a rabbit model of atherosclerosis: an immunohistochemical and histological study

BACKGROUND AND AIM OF THE STUDY: It has been suggested that aortic valve sclerosis (AVS) is an atherosclerotic disease process that can proceed to aortic stenosis. The absence of reports studying an animal model of the early stages of this disease has precluded the development of preventive therapeutic strategies. A cholesterol-fed (0.25% cholesterol in chow) rabbit model of atherosclerosis that is characterized by a moderate level of hypercholesterolemia was studied to determine its efficacy as a model of early AVS. Cellular, structural and morphological changes in the aortic valves of these rabbits were studied. METHODS: Twenty rabbits were assigned randomly to four experimental groups: Group 1 received normal chow for 40 weeks; group 2 received 0.25% cholesterol-supplemented chow for 20 weeks; group 3 received 0.25% cholesterol-supplemented chow for 40 weeks; and group 4 received 0.25% cholesterol-supplemented chow for 20 weeks followed by normal chow for an additional 20 weeks. The aortas and aortic valves were analyzed using immunohistochemical and histological methods to detect cellular and structural components of the developing lesions. RESULTS: All rabbits in groups 2, 3 and 4 developed atherosclerotic lesions in their aortas. Aortic valves from these animals demonstrated thickening, lipid deposition, a change in collagen content and organization, a reorganization of elastin, and the presence of both macrophage infiltrate and osteopontin. CONCLUSION: These findings were consistent with the suggestion of a link between atherosclerosis and AVS. Results were also similar to changes reported in human sclerotic aortic valves, suggesting the suitability of this rabbit model of atherosclerosis as a model for AVS.     

Quantification of aortic valve area and left ventricular muscle mass in healthy subjects and patients with symptomatic aortic valve stenosis by MRI

MRI allows visualization and planimetry of the aortic valve orifice and accurate determination of left ventricular muscle mass, which are important parameters in aortic stenosis. In contrast to invasive methods, MRI planimetry of the aortic valve area (AVA) is flow independent. AVA is usually indexed to body surface area. Left ventricular muscle mass is dependent on weight and height in healthy individuals.We studied AVA, left ventricular muscle mass (LMM) and ejection fraction (EF) in 100 healthy individuals and in patients with symptomatic aortic valve stenosis (AS). All were examined by MRI (1.5 Tesla Siemens Sonate) and the AVA was visualized in segmented 2D flash sequences and planimetry of the performed AVA was manually.The aortic valve area in healthy individuals was 3.9+/-0.7 cm(2), and the LMM was 99+/-27 g. In a correlation analysis, the strongest correlation of AVA was to height (r=0.75, p<0.001) and for LMM to weight (r=0.64, p<0.001). In a multiple regression analysis, the expected AVA for healthy subjects can be predicted using body height: AVA=-2.64+0.04 x(height in cm) -0.47 x w (w=0 for man, w=1 for female).In patients with aortic valve stenosis, AVA was 1.0+/-0.35 cm(2), in correlation to cath lab r=0.72, and LMM was 172+/-56 g.We compared the AS patients results with the data of the healthy subjects, where the reduction of the AVA was 28+/-10% of the expected normal value, while LMM was 42% higher in patients with AS. There was no correlation to height, weight or BSA in patients with AS.With cardiac MRI, planimetry of AVA for normal subjects and patients with AS offered a simple, fast and non-invasive method to quantify AVA. In addition LMM and EF could be determined. The strong correlation between height and AVA documented in normal subjects offered the opportunity to integrate this relation between expected valve area and definitive orifice in determining the disease of the aortic valve for the individual patient. With diagnostic MRI in patients with AS, invasive measurements of the systolic transvalvular gradient does not seem to be necessary.     

Aortic valve calcification as quantified with multislice computed tomography predicts short-term clinical outcome in patients with asymptomatic aortic stenosis

BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification may be an independent risk factor for adverse clinical outcome. The study aim was to assess the predictive value of possible risk factors, including the severity of aortic valve calcification as quantified with 16-multislice computed tomography (MSCT) for adverse short-term clinical outcome in patients with asymptomatic, degenerative aortic stenosis (AS). METHODS: Possible risk factors for adverse short-term clinical outcome were prospectively tested in 34 consecutive patients with asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated with continuity equation, mean and maximal transvalvular pressure gradients, end-diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic peptide (BNP), C-reactive protein (CRP)). RESULTS: Within 18-24 months of follow up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients suffered from onset of symptoms accompanied by hemodynamic progression, and one patient died from sudden cardiac death. Six of these 10 patients underwent aortic valve replacement, one patient declined surgery, and three patients were not accepted for surgery (one of these died suddenly shortly afterwards). The aortic valve calcium score was the strongest predictor of a major adverse clinical event (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409 Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse clinical outcome. CONCLUSION: The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS. In patients with severe aortic valve calcification, close follow up examinations are mandatory, and early elective surgery may be considered even in the absence of symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS.     

New model of atherosclerosis in insulin resistant sand rats: hypercholesterolemia combined with D2 vitamin

To overcome the sand rats' resistance to cholesterol induced atherosclerosis, animals were given D2 vitamin at 2000 IU/rat per day associated with cholesterol-enriched diet for 45 days, following 45 days of high cholesterol diet alone. At days 0, 45 and 90, plasma parameters, aortic and heart morphology were examined. Other animals receiving a high cholesterol diet alone were used as a control group. Results showed at day 45 severe hypercholesterolemia, elevated plasma LDL and VLDL-cholesterol, oxidized LDL and calcium levels, a rise of lecithin cholesterol acyl transferase activity and moderate hyperinsulinemia. Lesions were characterized by widening of the first interlamellar spaces in the aorta, fibrosis of coronary arterial wall and recent foci of myocardial fibrosis. At day 90, plasma calcium level decreased and oxidized LDL were more enhanced. Insulin resistance development was associated with glucose intolerance and hyperinsulinemia. The D2 vitamin administration induced advanced atherosclerotic lesions in arterial wall, represented by the rupture of elastic lamellae, smooth muscle cell proliferation and lipid-calcic core. The complicated plaque frequently evolved into ulcerations. The ischaemic effects were represented by acute myocardial infarction. D2 vitamin is an atherogenic agent which, when associated with hypercholesterolemia, allows the development of advanced atherosclerotic lesions in sand rat which resembles human plaque.     

Does exercise echocardiography have an added value over exercise testing alone in asymptomatic patients with severe aortic stenosis?

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the clinical utility and added value of exercise stress echocardiography (ESE) over exercise testing alone in asymptomatic patients with severe aortic stenosis (AS). METHODS: The results of treadmill ESE in 101 consecutive patients (59 males, 42 females; mean age 69 +/- 10 years; range: 35-85 years) with asymptomatic severe AS (aortic valve area (AVA) <1 cm2 and/or mean transvalvular pressure gradient > or =50 mmHg) and normal left ventricular function, were analyzed. The test was considered abnormal if stopped prematurely because of limiting symptoms, a fall or small rise in systolic blood pressure, or complex ventricular arrhythmia. RESULTS: The mean resting AVA was 0.74 +/- 0.13 cm2, and peak and mean transvalvular gradients were 91 +/- 19 and 57 +/- 13 mmHg, respectively. In total, 69 patients (68%) developed an abnormal response, including symptoms (n = 48) and abnormal blood pressure response (n = 44). There were no cases of syncope or other major complications. Exercise transaortic pressure gradients could not be used to discriminate patients with otherwise normal and abnormal ESE or cardiac events. An abnormal contractile response was observed in 12 patients, in seven of whom it was the only ESE abnormal parameter. A total of 96 patients (95%) was followed up for a mean of 35 +/- 14 months. Aortic valve replacement-free survival was significantly lower in patients with an abnormal ESE result compared to those with a normal result. CONCLUSION: ESE has a limited added value to exercise testing alone in asymptomatic patients with severe AS. In a small percentage of these cases an abnormal contractile response, despite otherwise normal exercise parameters, constitutes a new finding that deserves further investigation.     

Preliminary experience in the assessment of aortic valve calcification by ECG-gated multislice spiral computed tomography

BACKGROUND: The aim was to correlate the degree of valvular calcification in patients with aortic stenosis determined by retrospectively electrocardiogram (ECG)-gated multislice spiral computed tomography with stenosis severity assessed by cardiac catheterization. METHODS: Prospective study on 41 patients (18 men, mean age 71+/-8 years) with aortic stenosis, who underwent four detector row multislice spiral computed tomography and cardiac catheterization. Severity of aortic stenosis was classified by cardiac catheterization. Aortic valve area, peak to peak and mean transvalvular gradients were correlated with the degree of calcification determined by multislice spiral computed tomography. Aortic valve calcification was assessed using aortic Agatston score, aortic mass score and aortic volume score. RESULTS: All measured aortic valve calcification scores were significantly higher in patients with severe aortic stenosis (n=29) than in patients with moderate (n=7) or mild aortic stenosis (n=5, p<0.001). Aortic valve calcification scores correlated significantly with aortic valve area (r=-0.49, p=0.001 for aortic mass score) and with peak to peak (r=0.68, p<0.001) and mean (r=0.60, p<0.001) transvalvular gradients. CONCLUSIONS: Severity of aortic valve calcification assessed by cardiac multislice spiral computed tomography is inversely related to aortic valve area and positively correlated with transvalvular gradients. Based on this preliminary data larger studies should be performed with echocardiography as a reference standard in order to validate this new information and its utility in the clinical management of the patient.     

Aortic valve area discrepancy by Gorlin equation and Doppler echocardiography continuity equation: relationship to flow in patients with valvular aortic stenosis

BACKGROUND: In vitro studies have shown a discrepancy between aortic valve area (AVA) measurements derived invasively by Gorlin equation (Gorlin AVA) and noninvasively by Doppler echocardiography (Doppler-echo) continuity equation (Doppler AVA) during low flow states. OBJECTIVE: To assess whether a flow-related discrepancy between Gorlin AVA and Doppler AVA occurs in the clinical setting in patients with isolated valvular aortic stenosis. PATIENTS AND METHODS: Seventy-five consecutive patients with isolated valvular aortic stenosis, who had AVA determined both invasively by Gorlin equation and noninvasively by Doppler-echo continuity equation, were retrospectively reviewed. RESULTS: Gorlin AVA and Doppler AVA correlated (r=0.68) over the narrow AVA range (Gorlin AVA 0.30 to 1.22 cm2); however, Doppler AVA was systematically larger than Gorlin AVA (0.80+/-0.21 versus 0.70+/-0.23 cm2, AVA difference = 0.10+/-0.17 cm2, P<0.0001). The AVA difference was inversely related to invasive cardiac index (r=-0.51) and was significantly greater at low flow states (cardiac index less than 2.5 L/min/m2) than at normal flow states (cardiac index 2.5 L/min/m2 or more) (0.16+/-0.15 versus -0.03+/-0.15 cm2, P<0.0001). Independent predictors of the AVA difference were the difference between Doppler-echo and invasive cardiac output (P<0.0001); the difference between Doppler-echo and invasive mean transvalvular pressure gradient (P=0.0002); and the average cardiac output (Doppler-echo plus invasive cardiac output/2, P=0.001) at the time of the hemodynamic assessments. The AVA difference was not related to average pressure gradient, average AVA or patient characteristics. CONCLUSIONS: A flow-related discrepancy between Gorlin AVA and Doppler AVA occurs in the clinical setting of patients with isolated valvular aortic stenosis. This discrepancy should be considered when assessing aortic stenosis severity during low flow states, where Gorlin AVA may be significantly smaller than Doppler AVA.     

Vitamin E does not slow the progression of hypercholesterolemic atherosclerosis

BACKGROUND:

Vitamin E suppresses the development of atherosclerosis but does not regress established hypercholesterolemic atherosclerosis.

OBJECTIVES:

To investigate whether vitamin E slows the progression of established atherosclerosis, and whether this effect is associated with reductions in serum lipids and oxidative stress.

METHODS:

The present study was performed in four groups of rabbits: group I, regular diet (control); group II, 0.25% cholesterol diet (two months); group III, 0.25% cholesterol diet (four months); and group IV, 0.25% cholesterol diet (two months) followed by 0.25% cholesterol and vitamin E (two months). Serum lipids and the chemiluminescent activity of white blood cells (WBC-CL), a measure of oxygen radical production by white blood cells, were measured before and at monthly intervals for the duration of the study. Aortas were removed at the end of the protocol for assessment of atherosclerosis and the chemiluminescent activity of aortic tissue (aortic-CL), a measure of antioxidant reserve.

RESULTS:

Atherosclerosis was associated with hyperlipidemia and increased oxidative stress, indicated by increased nonactivated WBC-CL and alteration of the aortic-CL. Significant areas of the intimal surfaces of the aortas from group II (26.54%±4.11%), group III (69.37%±5.34%) and group IV (65.96%±7.86%) were covered with atherosclerotic lesions. Vitamin E did not alter serum lipids, aortic antioxidant reserve or WBC-CL. Vitamin E was ineffective in slowing the progression of hypercholesterolemic atherosclerosis.

CONCLUSION:

Vitamin E did not slow the progression of hypercholesterolemic atherosclerosis, and this effect was associated with its ineffectiveness in reducing serum lipids and oxidative stress.     

Timing of surgery in aortic stenosis

Opinion statement Aortic valve stenosis (AVS) usually results from three distinct processes (degenerativecalcific, rheumatic, and congenital), with a final common pathway of significant aortic outflow tract obstruction. The stenotic lesion tends to progress slowly, but once symptoms develop clinical deterioration can ensue rapidly. Chest pain, dyspnea, and syncope are the most common symptoms of significant AVS. Detection of symptoms, subtle or obvious, is critical to the management of AVS because their presence portends a worse overall prognosis and is an indication for intervention. There are several special clinical scenarios that require added consideration, including individuals with concomitant coronary artery disease, the presence of a relatively small transvalvular pressure gradient in the setting of low cardiac output (so-called low-gradient AVS), and elderly with severe AVS. Surgical aortic valve replacement (AVR) is the mainstay treatment for relief of obstruction in patients with symptomatic AVS. Percutaneous balloon valvuloplasty is reserved for the small minority of patients who are not surgical candidates and is associated with a high restenosis rate. Percutaneous AVR is a new technology that is being tested in a few select centers on patients who are not operative candidates.     

Comparison of outcome of higher versus lower transvalvular gradients in patients with severe aortic stenosis and low (<40%) left ventricular ejection fraction

Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) is associated with poor outcome. This analysis was designed primarily to describe the clinical course of a large series of consecutive patients with severe AS and low ejection fraction (EF) (<40%) who, because of high surgical risk, were referred for transcatheter aortic valve implantation consideration. A cohort of 270 patients with severe AS and low EF (<40%) who were referred to participate in a clinical trial of transcatheter aortic valve implantation was studied. Clinical, hemodynamic, and periprocedural complications and follow-up mortality data were collected and compared between patients with low mean transvalvular gradients (≤40 mm Hg, n = 170 [63%]) and high transvalvular gradients (>40 mm Hg, n = 100 [37%]). Patients with low gradients were younger (mean age 79.8 ± 9.1 vs 83.8 ± 7.7 years, p <0.001) and had higher incidences of coronary artery disease and renal failure. Mean aortic valve area was larger (0.73 ± 0.23 vs 0.53 ± 0.18 cm(2), p <0.001), while mean EF (26.4 ± 6.9% vs 30.5% ± 6.6%, p <0.001), cardiac output (3.7 ± 1.1 vs 4.1 ± 1.3 L/min, p = 0.04), and cardiac index (1.9 ± 0.5 vs 2.1 ± 0.6 L/min/m(2), p = 0.04) were lower in patients with lower gradients compared to those with higher gradients, respectively. Mortality was higher in patients with low gradients (53.8%) at a mean follow-up of 151 days compared to those with high gradients (41%) at a mean follow-up of 256 days (p = 0.01). In conclusion, patients with severe AS and low EF with low transvalvular gradients are at higher risk for worse outcomes compared to patients with high transvalvular gradients. Surgery or transcatheter aortic valve implantation treatment and high baseline transvalvular gradient are associated with EF improvement.     

Accuracy of aortic stenosis severity assessment by Doppler echocardiography: importance of image quality

The aim of the present study was to investigate which factors could influence the accuracy of aortic stenosis severity assessment by Doppler echocardiography in an unselected population. Doppler echocardiographic determination of mean transvalvular pressure gradient and aortic valve area by continuity equation was performed in 101 patients before catheterization. According to the catheterization data, aortic stenosis was classified into 2 categories: mild to moderate (orifice area [Gorlin formula] > 0.75 cm², mean transvalvular gradient < 50 mmHg) and severe (orifice area < 0.75 cm², mean transvalvular gradient 50 mmHg). The influence of eight factors on the absolute difference in aortic valve area and mean transvalvular pressure gradient and on the concordant classification in the same category by both methods was investigated.Results. By multivariate analysis, the absolute difference in aortic valve area by both methods was significantly associated with poor image quality, absolute difference between mean catheterization and Doppler transvalvular gradient and inversely related to body mass index. Absolute difference in mean transvalvular gradients by both methods was significantly associated only with image quality. Poor image quality emerged as the only significant factor influencing the concordant classification between invasive and noninvasive studies according to orifice area (but not according to transvalvular pressure gradient).Conclusion. Echographic image quality significantly influences the accuracy of Doppler echocardiographic determination of aortic valve area and, to a lesser extent, of transvalvular pressure gradient. Therefore, the mere noninvasive approach is not suitable to every consecutive patient with aortic stenosis. Qualifications concerning overall image quality should identify patients most likely to benefit from catheterization.     

Factors influencing the mean postoperative gradients across stentless porcine valves

BACKGROUND: To study the preoperative and intraoperative variables influencing the mean post-operative transvalvular gradient across stentless porcine valves. METHODS: From 1995 to 2002, 84 patients underwent stentless valve insertion. The mean age was 73 years, and 63% were male. The valve pathology was aortic stenosis (AS) in 79%, aortic regurgitation (AR) in 12%, and mixed in 9%. Valve sizes ranged from 21 to 29 with size 27 being most frequent. 54% of patients had concomitant procedures. Patients had at least yearly clinical and echocardiographic follow-up. RESULTS: There was no operative mortality. 9.5% of the patients had significant postoperative complications. The average echo interval was 18.6 months (range 1-88). The overall mean transvalvular gradient was 9.88+/-5.67 (SD) mmHg. Variables associated with significantly reduced gradients were: larger valve sizes (p=0.002), younger age (p=0.05), pre-op AR (p=0.008), and increasing post-operative interval (p=0.05). The mean gradients decreased by 0.28 mmHg for each post-operative year. The method of implantation did not significantly affect gradients (p=0.26). CONCLUSIONS: Excellent mean transvalvular gradients were achieved with stentless valves studied, with a low operative risk. The gradients did not appear to be related to intra-operative factors, suggesting that insertion techniques can be tailored to suit patient conditions and surgeon preferences.     

Quantification of aortic valve area and left ventricular muscle mass in healthy subjects and patients with symptomatic aortic valve stenosis by MRI

MRI allows visualization and planimetry of the aortic valve orifice and accurate determination of left ventricular muscle mass, which are important parameters in aortic stenosis. In contrast to invasive methods, MRI planimetry of the aortic valve area (AVA) is flow independent. AVA is usually indexed to body surface area. Left ventricular muscle mass is dependent on weight and height in healthy individuals.We studied AVA, left ventricular muscle mass (LMM) and ejection fraction (EF) in 100 healthy individuals and in patients with symptomatic aortic valve stenosis (AS). All were examined by MRI (1.5 Tesla Siemens Sonate) and the AVA was visualized in segmented 2D flash sequences and planimetry of the performed AVA was manually.     

Serial Doppler Gradients Are Predictive of Future Bioprosthetic Valve Degeneration

Doppler echocardiography and color flow imaging are helpful techniques in evaluating the functional status of a bioprosthetic valve. The aim of this study was to determine whether serial Doppler gradients are predictive of future bioprosthetic valve degeneration. We performed serial echo-Doppler studies over a 6-year period (1988–1994) on 228 patients who had undergone mitral (n = 112) or aortic (n = 116) bioprosthetic valve implantation between 1973 and 1994. Thirtynine mitral prostheses and 30 aortic prostheses became dysfunctional and required reoperation. A serial rise in mean gradient of 5 mmHg or more across the mitral valve and 25 mmHg or more across the aortic valve was significantly associated with increased valve degeneration (odds ratio 3.40 and 16.11 and 95% confidence intervals 1.31 and 8.80 and 13.6 and 72.13 for the mitral and aortic valve, respectively). Both aortic and mitral valves began to degenerate after 8 years. Serial echo-Doppler studies showed a rise in transvalvular gradients around the same time. Closer evaluation for prosthetic valve dysfunction should be considered in patients 8 or more years status post surgery, especially those with high transvalvular gradients.