Calcific aortic stenosis

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Abstract

Calcific aortic stenosis (AS) is the most prevalent heart valve disorder in developed countries. It is characterized by progressive fibro-calcific remodelling and thickening of the aortic valve leaflets that, over years, evolve to cause severe obstruction to cardiac outflow. In developed countries, AS is the third-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension, with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old. Congenital abnormality (bicuspid valve) and older age are powerful risk factors for calcific AS. Metabolic syndrome and an elevated plasma level of lipoprotein(a) have also been associated with increased risk of calcific AS. The pathobiology of calcific AS is complex and involves genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteoblastic transition of cardiac valve interstitial cells and active leaflet calcification. Although no pharmacotherapy has proved to be effective in reducing the progression of AS, promising therapeutic targets include lipoprotein(a), the renin-angiotensin system, receptor activator of NF-κB ligand (RANKL; also known as TNFSF11) and ectonucleotidases. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe AS. The diagnosis and staging of AS are based on the assessment of stenosis severity and left ventricular systolic function by Doppler echocardiography, and the presence of symptoms. The introduction of transcatheter AVR in the past decade has been a transformative therapeutic innovation for patients at high or prohibitive risk for surgical valve replacement, and this new technology might extend to lower-risk patients in the near future.

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A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease.

Bernard Iung, Gabriel Baron, Eric G Butchart … (2003)

To identify the characteristics, treatment, and outcomes of contemporary patients with valvular heart disease (VHD) in Europe, and to examine adherence to guidelines. The Euro Heart Survey on VHD was conducted from April to July 2001 in 92 centres from 25 countries; it included prospectively 5001 adults with moderate to severe native VHD, infective endocarditis, or previous valve intervention. VHD was native in 71.9% of patients and 28.1% had had a previous intervention. Mean age was 64+/-14 years. Degenerative aetiologies were the most frequent in aortic VHD and mitral regurgitation while most cases of mitral stenosis were of rheumatic origin. Coronary angiography was used in 85.2% of patients before intervention. Of the 1269 patients who underwent intervention, prosthetic replacement was performed in 99.0% of aortic VHD, percutaneous dilatation in 33.9% of mitral stenosis, and valve repair in 46.5% of mitral regurgitation; 31.7% of patients had > or =1 associated procedure. Of patients with severe, symptomatic, single VHD, 31.8% did not undergo intervention, most frequently because of comorbidities. In asymptomatic patients, accordance with guidelines ranged between 66.0 and 78.5%. Operative mortality was <5% for single VHD. This survey provides unique contemporary data on characteristics and management of patients with VHD. Adherence to guidelines is globally satisfying as regards investigations and interventions.

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Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.

Martin Leon, Craig R Smith, Michael E Mack … (2010)

Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis. We randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or transfemoral transcatheter implantation of a balloon-expandable bovine pericardial valve. The primary end point was the rate of death from any cause. A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States). At 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7% with TAVI, as compared with 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001). The rate of the composite end point of death from any cause or repeat hospitalization was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs. 58.0%, P<0.001). At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%, P=0.06) and major vascular complications (16.2% vs. 1.1%, P<0.001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram. In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

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Burden of valvular heart diseases: a population-based study.

Vuyisile T Nkomo, Julius M Gardin, Thomas N Skelton … (2006)

Valvular heart diseases are not usually regarded as a major public-health problem. Our aim was to assess their prevalence and effect on overall survival in the general population. We pooled population-based studies to obtain data for 11 911 randomly selected adults from the general population who had been assessed prospectively with echocardiography. We also analysed data from a community study of 16 501 adults who had been assessed by clinically indicated echocardiography. In the general population group, moderate or severe valve disease was identified in 615 adults. There was no difference in the frequency of such diseases between men and women (p=0.90). Prevalence increased with age, from 0.7% (95% CI 0.5-1.0) in 18-44 year olds to 13.3% (11.7-15.0) in the 75 years and older group (p<0.0001). The national prevalence of valve disease, corrected for age and sex distribution from the US 2000 population, is 2.5% (2.2-2.7). In the community group, valve disease was diagnosed in 1505 (1.8% adjusted) adults and frequency increased considerably with age, from 0.3% (0.2-0.3) of the 18-44 year olds to 11.7% (11.0-12.5) of those aged 75 years and older, but was diagnosed less often in women than in men (odds ratio 0.90, 0.81-1.01; p=0.07). The adjusted mortality risk ratio associated with valve disease was 1.36 (1.15-1.62; p=0.0005) in the population and 1.75 (1.61-1.90; p<0.0001) in the community. Moderate or severe valvular diseases are notably common in this population and increase with age. In the community, women are less often diagnosed than are men, which could indicate an important imbalance in view of the associated lower survival. Valve diseases thus represent an important public-health problem.