Reduction In Aortic Valve Area Research Articles

Left ventricular hypertrophy, diastolic dysfunction and right ventricular load predict outcome in moderate aortic stenosis.

Predictors of progression of moderate aortic valve stenosis (AS) are incompletely understood. The objective of this study was to evaluate the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction, and right ventricular (RV) load in moderate AS. Moderate AS was defined by aortic valve area (AVA), peak transvalvular velocity (Vmax) or mean pressure gradient (PGmean). A total of 131 Patients were divided into two groups according to the number of pathophysiological changes (LVH, diastolic dysfunction with increased LV filling pressures and/or RV load): <2 (group 1); ≥2 (group 2). The primary outcome was survival without aortic valve replacement (AVR). After follow-up of 30 months, the reduction of AVA (-0.06 ± 0.16 vs. -0.24 ± 0.19 cm2, P < 0.001), the increase of PGmean (2.89 ± 6.35 vs 6.29 ± 7.13 mmHg, P < 0.001) and the decrease of the global longitudinal strain (0.8 ± 2.56 vs. 1.57 ± 3.42%, P < 0.001) from baseline to follow-up were significantly more pronounced in group 2. Survival without AVR was 82% (group 1) and 56% (group 2) [HR 3.94 (1.74-8.94), P < 0.001]. Survival without AVR or progression of AS was 77% (group 1) and 46% (group 2) [HR 3.80 (1.84-7.86), P < 0.001]. The presence of ≥2 pathophysiological changes predicted outcome whereas age, comorbidities, LDL-cholesterol did not. The presence of ≥2 pathophysiological changes is a strong predictor of outcome in moderate AS and may be useful for risk stratification, particularly for scheduling follow-up time intervals and deciding the timing of AVR.

Progression of Aortic Stenosis and Long-term Follow-Up in Women

Data on the rate of progression of aortic stenosis (AS) in women are limited. We retrospectively studied 95 female patients (age 75 ± 13 yrs) with aortic valve area (AVA) &lt;2.0 cm2 (mild AS 1.5-1.9 cm2, moderate AS 1.0-1.4 cm2, severe AS &lt;1.0 cm2). All patients underwent serial transthoracic echocardiography. We determined annual AVA decrease (rate of AS progression) by 3 approaches, each of which was applied to the entire cohort: 1) as a single group; 2) in the 3 subgroups of mild, moderate and severe AS; and 3) in the rapid and slower progressors. Study endpoints were aortic valve replacement (AVR) and all-cause mortality. The mean duration of follow-up was 4.5 ± 2.9 years. Mean rate of reduction in AVA for the total study group was 0.14 ± 0.16 cm2/yr and was directly related to presence of hypertension and baseline AVA, and inversely related to follow-up duration (all p&lt;0.05). The annualized decrease in AVA for each of the subgroups of mild, moderate and severe AS at baseline was 0.21±0.31 cm2, 0.13±0.11 cm2, 0.11±0.09 cm2, respectively (p&lt;0.0001). Rapid progression of AS (decrease in AVA ≥0.20 cm2/yr) occurred in 21% of patients (n=20) and was associated with baseline hypertension (p=0.03) and inversely related to follow-up duration (p=0.0007). Rapid progressors had shorter follow-up than slower progressors (20 vs. 42 mos, p=0.002). Event-free survival with end-points of death (n=65) or surgical/transcatheter AVR (n=24) at 1, 3, and 5 years, respectively, was 93%, 66% and 40% for mild AS; 96%, 72% and 48% for moderate AS; and 93%, 38% and 24% for severe AS. Thus, event-free survival at 5 years in patients with baseline severe AS was approximately half that of patients with AS of mild or moderate severity. In addition, event-free survival at 1 year in slower progressors was 92% and in rapid progressors was 70%.

Gout and Progression of Aortic Stenosis

BackgroundPatients with aortic stenosis are nearly twice as likely to have a diagnosis of gout compared with individuals without aortic valve disease. MethodsThis retrospective study evaluated consecutive adults age ≥65 years with aortic stenosis between December 2012 and November 2016 who underwent at least 2 transthoracic echocardiograms (TTEs) separated by at least 1 year. Severe aortic stenosis was defined as any combination of an aortic valve peak velocity ≥4.0 m/sec, mean gradient ≥40 mm Hg, aortic valve area ≤1 cm2, or decrease in left ventricular ejection fraction as a result of aortic stenosis. ResultsOf the 699 study patients, gout was present in 73 patients (10%) and not found in 626 patients (90%). Median follow-up was 903 days [552-1302] for patients with gout and 915 days [601-1303] for patients without gout (P = 0.60). The presence of severe aortic stenosis on follow-up transthoracic echocardiogram was more frequent in patients with gout compared to those without gout (74% vs 54%, P = 0.001; hazard ratio [HR] 1.45 [1.09-1.93]), even among the 502 patients without severe aortic stenosis at baseline (63% vs 39%, P = 0.003; hazard ratio 1.43 [1.07-1.91]). Gout remained associated with the development of severe aortic stenosis after multivariable adjustment (adjusted hazard ratio [aHR] 1.46 [1.03-2.08], P = 0.03). The annualized reduction in aortic valve area was numerically greater in the group with gout compared with the group without gout (−0.10 cm2/y [−0.18, −0.03] vs −0.08 cm2/y [−0.16, −0.01], P = 0.09); annualized change in peak velocity and mean gradient did not differ between groups. ConclusionsProgression to severe aortic stenosis was more frequent in patients with gout compared with those without gout, supporting the hypothesis that gout is a risk factor for aortic stenosis.

Effects of vitamin K antagonist on aortic valve degeneration in non-valvular atrial fibrillation patients: Prospective 4-year observational study

BackgroundThe prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients. MethodsOf enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group). ResultsDespite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p=0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p=0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p=0.002). The effects of ARB on AVA were obscure. ConclusionMajor bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Five-year echocardiographic follow-up after TAVI: structural and functional changes of a balloon-expandable prosthetic aortic valve.

Scarce data are available on the long-term structural and functional changes of prosthetic valves after transcatheter aortic valve implantation (TAVI). The objective was to evaluate with echocardiography the long-term structural and functional changes of prosthetic valves after TAVI. Structural valve deterioration (SVD) was defined as leaflet thickening ≥3mm, presence of calcification and abnormal leaflet motion. Five-year echocardiographic follow-up was available in 96 out of 318 patients who underwent TAVI with a balloon-expandable device between April 2008 and December 2011. At 1-year follow-up, no patient showed SVD. At 5-year follow-up, SVD were observed in 29 (30%) patients who showed also a significant reduction of aortic valve area (AVA) together with an increase of mean and peak aortic pressure gradients at the latest echocardiography evaluation. Moreover, rate of central aortic valve regurgitation ≥2 was higher in SVD patients as compared to those without SVD, while there was no difference in terms of paravalvular regurgitation. Despite SVD, one patient only reached the criteria for severe stenosis and no reintervention was needed at 5-year follow-up. Variables independently associated with SVD were female sex, small body surface area, use of a 23 mm valve, and small AVA at pre-discharge echocardiogram. At 5-year follow-up, 30% of patients who underwent TAVI with a balloon-expandable valve showed initial SVD. However, SVD was not associated with severe stenosis in most of the patients and had no significant impact on and clinical outcome.

Higher visit-to-visit intra-dialytic blood pressure is associated with the progression of aortic valve stenosis in chronic hemodialysis patients.

Aortic valve stenosis (AS) is a frequent complication contributing to poor prognosis in chronic hemodialysis (CHD) patients. High blood pressure (BP) is known to be associated with AS progression in the general population. In CHD patients, however, BP varies during and between hemodialysis sessions with ultrafiltration volume or inter-dialytic weight gain; therefore it is difficult to characterize the BP status with a conventional single measurement. Our purpose was to clarify the BP variables affecting AS progression in CHD patients. We retrospectively enrolled 32 consecutive CHD patients with AS [aortic valve area (AVA), 1.3±0.3cm(2); mean age 69±8years] who had serial transthoracic echocardiographic studies at least 6months apart (mean 23±9months). AS progression was evaluated using absolute reduction in AVA per year. Pre-dialytic and intra-dialytic (every hour during sessions) BPs throughout the 3 consecutive visits were used to determine each patient's BP status. We calculated the mean values of pre-dialytic and intra-dialytic BPs and their variability. In univariate analysis, mean visit-to-visit pre-dialytic and intra-dialytic BP were associated with AS progression, whereas all variables of BP variability were not. Multiple regression analysis indicated that only mean visit-to-visit intra-dialytic systolic and diastolic BP remained independently associated with AS progression after adjustment for age, sex, hypertension, hypercholesterolemia, diabetes mellitus, and serum parathyroid hormone (p<0.05). Although BP regulation in CHD patients is complex and multifactorial, mean visit-to-visit intra-dialytic BP was independently associated with AS progression. Prospective studies are necessary before considering intra-dialytic BP as a potential target for therapy.

Valvular endothelial cells: Guardians or destroyers of aortic valve integrity?

Atherosclerosis and calcific aortic valve disease (CAVD) are two distinct, morbid processes that share similar pathophysiological events. Both diseases are characterized by recruitment of immune cells, activation of inflammatory pathways, proliferation/differentiation of resident elements, remodeling of extracellular matrix and calcium deposition [ 1 Bentzon J.F. Otsuka F. Virmani R. Falk E. Mechanisms of plaque formation and rupture. Circ. Res. 2014; 114: 1852-1866 Crossref PubMed Scopus (1057) Google Scholar , 2 Yutzey K.E. et al. Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2387-2393 Crossref PubMed Scopus (180) Google Scholar ]. However, while the actual impact of intimal calcification on plaque stability is still controversial [ [3] Otsuka F. Sakakura K. Yahagi K. Joner M. Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed?. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 724-736 Crossref PubMed Scopus (281) Google Scholar ], no uncertainty exists about the clinical harmful consequences of calcium deposition within the aortic valve. As a matter of fact, progressive stiffness of calcified leaflets leads to reduction of aortic valve area, which results in chronic left ventricular pressure overload. Clinical manifestations of the advanced disease are syncope, angina and inevitable progression towards end-stage heart failure. Aging is the major risk factor for CAVD and this explains way the disease prevalence is growing in the countries with the highest life expectancy (about 3% of Americans aged 75 and over are affected) [ [4] Mozaffarian D. et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation. 2015; 131: e29-322 Crossref PubMed Scopus (5504) Google Scholar ]. Nevertheless, several basic and clinical science studies performed in the last two decades clearly demonstrated that arterial and valve calcification should be considered as an active, finely regulated biological process, which is mainly characterized by the activation of osteogenic programs and/or the lost of anti-calcific defense mechanisms within the vascular/valve tissue [ 2 Yutzey K.E. et al. Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2387-2393 Crossref PubMed Scopus (180) Google Scholar , 5 Demer L.L. Tintut Y. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 715-723 Crossref PubMed Scopus (240) Google Scholar ]. These new data are of great relevance since nowadays the only treatments available to cure CAVD consist of invasive therapeutic strategies (namely surgical or transcatheter aortic valve replacement) and there is a substantial need of new pharmacological targets. Valvular interstitial cells suppress calcification of valvular endothelial cellsAtherosclerosisVol. 242Issue 1PreviewCalcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Full-Text PDF Open Access

Parathyroid hormone and systolic blood pressure accelerate the progression of aortic valve stenosis in chronic hemodialysis patients

BackgroundAortic valve stenosis (AS) is a frequent complication contributing to poor prognosis in chronic hemodialysis (CHD) patients. However, little is known regarding the risk factors affecting AS progression. The purpose of this study was to define risk factors affecting AS progression in CHD patients. MethodsWe retrospectively investigated 34 consecutive CHD patients with asymptomatic AS (mild in 9, moderate in 20, severe in 5; aortic valve area (AVA), 1.31±0.31cm2; mean age, 69±8years) who underwent followed-up paired transthoracic echocardiography with period of at least six months apart (22±9months). AS progression was evaluated using the absolute reduction in AVA per year. ResultsCHD patients were divided into 20 patients with rapid progression (AVA reduction, >0.1cm2 per year) and 14 with slow progression (AVA reduction, ≦0.1cm2 per year). Serum parathyroid hormone (PTH) level was significantly higher in patients with rapid progression than in those with slow progression [343±489pg/ml vs. 76±80pg/ml, P<0.05]. In univariate analysis, AS progression by absolute AVA reduction per year was associated with age, PTH level, initial AVA, systolic blood pressure (SBP), diastolic blood pressure, total cholesterol, and left ventricular diameter at end-diastole and end-systole. Multiple regression analysis indicated that serum PTH level and SBP remained independently associated with AS progression. ConclusionsAS progression was accelerated in the presence of high PTH and SBP. Careful monitoring and intensive treatment of these parameters may have a beneficial effect on secondary prevention in CHD patients.

Rate of progression of valvular aortic stenosis in patients ≥60 years of age

A retrospective analysis of 171 women and 119 men, mean age 76 +/- 9 years, with aortic stenosis diagnosed by Doppler echocardiography, who had follow-up Doppler echocardiograms, showed that the reduction in aortic valve area per year was not significantly different in older persons with mild, moderate, and severe aortic stenosis. The decrease in aortic valve area per year was significantly greater in men 60 to 74 years old than in women 60 to 74 years old (p = 0.025), in women > or =75 years old than in women 60 to 74 years old (p = 0.006), and in persons with mitral annular calcium than in persons without mitral annular calcium (p = 0.046).

New insights into the progression of aortic stenosis: implications for secondary prevention.

The risk factors affecting aortic stenosis (AS) progression are not clearly defined. Insights into this may allow for its secondary prevention. We investigated predictors of AS progression in 170 consecutive patients with AS who had paired echocardiograms > or =3 months (23+/-11) apart. Various clinical, echocardiographic, and biochemical variables were related to the change in aortic valve area (AVA). The annual rate of reduction in AVA was 0.10+/-0.27 cm(2) or 7+/-18% per year. The reduction in AVA per year was significantly related to initial AVA (r = 0.46, P<0.0001), the mean aortic valve gradient (r = 0.27, P = 0.04), left ventricular (LV) outflow tract velocity (r = 0.26, P = 0.001), and LV end-diastolic diameter (r = 0.20, P = 0.04) and marginally to serum creatinine level (r = 0.15, P = 0.08). Patients with a rate of reduction in AVA faster than the mean had higher serum creatinine (P = 0.04) and calcium (P = 0.08) levels. Those with a serum cholesterol level >200 mg/dL had a rate of AVA reduction roughly twice that of those with a lower cholesterol level (P = 0.04). Stepwise multiple regression analysis identified initial AVA, current smoking, and serum calcium level as the independent predictors of amount of AVA reduction per year. Absolute and percentage reduction in AVA per year in those with AS is greater in those with milder degrees of stenosis and is accelerated in the presence of smoking, hypercholesterolemia, and elevated serum creatinine and calcium levels. These findings may have important implications in gaining further insights into the mechanism of AS progression and in formulating strategies to retard this process.

Rate of change in aortic valve area during a cardiac cycle can predict the rate of hemodynamic progression of aortic stenosis.

The ability to predict the rate of hemodynamic progression in an individual patient with valvular aortic stenosis has been elusive. The purpose of the present study was to evaluate whether the rate of change in aortic valve area (AVA) measured during the ejection phase of a cardiac cycle predicts the rate of hemodynamic progression in patients with asymptomatic aortic stenosis. In 84 adults with initially asymptomatic aortic stenosis and a baseline AVA of > or =0.9 cm(2), annual echocardiographic data were obtained prospectively (mean follow-up 2.8+/-1.3 years). With the initial echocardiogram, the ratio of AVA measured at mid-acceleration and mid-deceleration to the AVA at peak velocity was calculated. The primary outcome variable was the annual rate of change in AVA (rate of progression), with rate of progression classified as rapid (a reduction in AVA of > or =0.2 cm(2)/y) or slow (<0.2 cm(2)/y). Rapid progression was significantly associated with an AVA ratio of > or =1.25 (P=0.004, risk ratio 3.1, 95% CI 1.2 to 7.9). The sensitivity, specificity, and positive predictive value of AVA ratio of > or =1.25 for the prediction o rapid progression of valvar aortic stenosis was 64%, 72%, and 80% respectively. The decrease in ejection fraction measured from the initial to final echocardiogram was small but greater for patients with an AVA ratio of > or =1.25 (-4+/-7% versus +2+/-7%, P<0.001). A flow-dependent change in AVA can be measured during a routine transthoracic echocardiographic study. The rate of change in AVA is an additional measure of disease severity and may be used to predict an individual's risk for subsequent rapid disease progression.

Calcific degeneration of the aortic valve in old age: is the development of flow obstruction predictable?

Aortic valve calcification and stenosis become increasingly common with advancing age. This work aimed at assessing whether a time-dependent reduction of aortic valve area is detectable in an unselected elderly population and whether the rate of reduction can be predicted from clinical or biochemical characteristics. A population-based prospective echocardiographic follow-up study. A university hospital. In 1990, randomly selected persons born in 1904, 1909 and 1914 (total n = 501) underwent a Doppler echocardiographic study of aortic valve and biochemical tests of glucose, lipid and calcium metabolism. In 1993, echocardiography was repeated in 333 survivors of the original cohorts. These individuals constitute the present study population. Three-year changes in the aortic valve area and velocity ratio (peak outflow tract velocity/peak aortic jet velocity) determined by Doppler echocardiography. Aortic valve area decreased from a mean of 1.95 cm2 (95% confidence interval of mean, 1.88-2.03 cm2) to 1.78 cm2 (1.71-1.85 cm2) within 3 years (P < 0.001). Concomitantly, the velocity ratio decreased from 0.75 (0.73-0.77) to 0.68 (0.67-0.70) (P < 0.001). The changes in aortic valve area and velocity ratio were unrelated to age, sex, presence of hypertension, coronary artery disease or diabetes, and to all assessed biochemical characteristics. A weak positive statistical association was found between the decrease in aortic valve area and the body mass index at entry (r = 0.16, P < 0.01). A time-dependent reduction of the aortic valve flow orifice can be demonstrated in persons representing the general elderly population. The deterioration of aortic valve function within a span of 3 years is neither clinically nor biochemically predictable. A longer follow-up may be necessary to identify the risk factors of aortic valve stenosis in old age.

Progression of isolated aortic stenosis: Analysis of 29 patients having more than 1 cardiac catheterization

Factors related to progression of nonrheumatic aortic stenosis (AS) were analyzed in 29 adult patients who underwent serial hemodynamic studies over a mean of 71 months. AS was congenital in 8 patients and degenerative in 21. The patients were divided into 2 groups on the basis of the change in aortic valve area between the 2 studies. Twelve patients had a ≥ 25% reduction in aortic valve area (Group I) and 17 patients had < 25% decrease in aortic valve area (Group II). There were no significant differences between the 2 groups in age, interval between studies, cardiac output, left ventricular end-diastolic pressure, left ventricular peak systolic pressure and origin of AS (congenital or degenerative). Group I patients had significantly larger initial aortic valve areas than did Group II patients (1.3 ± 0.9 cm 2 versus 0.8 ± 0.4 cm 2, p = 0.02). Also, the initial peak transaortic pressure gradients were lower in Group I than in Group II (27 ±19 versus 58 ± 38 mm Hg, p = 0.01). Group I patients had a significantly greater increase in pressure gradient and a greater reduction in cardiac output than did Group II patients (24 ± 21 mm Hg in Group I versus−0.1 ± 24.5 mm Hg in Group II, p = 0.01, and −1.0 ± 1.3 liters/min in Group I versus 0.10 ± 1.4 liters/min in Group II, p = 0.03). Thus, AS progressed in 41 % of a selected group of patients who underwent repeated cardiac catheterization. The progression was not predictable. Although 10 patients (34%) had moderate aortic regurgitation (AR) in the second study, it was not related to the origin or rate of progression of AS. Mild AS tends to progress more than severe AS. Congenital AS appears to progress at the same rate as degenerative AS.