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      Diagnosis and Management of Valvular Aortic Stenosis

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          Abstract

          Valvular aortic stenosis (AS) is a progressive disease that affects 2% of the population aged 65 years or older. The major cause of valvular AS in adults is calcification and fibrosis of a previously normal tricuspid valve or a congenital bicuspid valve, with rheumatic AS being rare in the United States. Once established, the rate of progression of valvular AS is quite variable and impossible to predict for any particular patient. Symptoms of AS are generally insidious at onset, though development of any of the three cardinal symptoms of angina, syncope, or heart failure portends a poor prognosis. Management of symptomatic AS remains primarily surgical, though transcatheter aortic valve replacement (TAVR) is becoming an accepted alternative to surgical aortic valve replacement (SAVR) for patients at high or prohibitive operative risk.

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          Two-year outcomes after transcatheter or surgical aortic-valve replacement.

          Susheel Kodali, Mathew R Williams, Craig R Smith … (2012)
          The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).
          Article 0 comments Cited 372 times – based on 0 reviews     Review now
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            Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.

            Anne Rossebø, Terje R Pedersen, Kurt Boman … (2008)
            Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results. We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events. During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01). Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.) 2008 Massachusetts Medical Society
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              Mutations in NOTCH1 cause aortic valve disease.

              Vidu Garg, Alecia N. Muth, Joshua F Ransom … (2005)
              Calcification of the aortic valve is the third leading cause of heart disease in adults. The incidence increases with age, and it is often associated with a bicuspid aortic valve present in 1-2% of the population. Despite the frequency, neither the mechanisms of valve calcification nor the developmental origin of a two, rather than three, leaflet aortic valve is known. Here, we show that mutations in the signalling and transcriptional regulator NOTCH1 cause a spectrum of developmental aortic valve anomalies and severe valve calcification in non-syndromic autosomal-dominant human pedigrees. Consistent with the valve calcification phenotype, Notch1 transcripts were most abundant in the developing aortic valve of mice, and Notch1 repressed the activity of Runx2, a central transcriptional regulator of osteoblast cell fate. The hairy-related family of transcriptional repressors (Hrt), which are activated by Notch1 signalling, physically interacted with Runx2 and repressed Runx2 transcriptional activity independent of histone deacetylase activity. These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease.
              Article 0 comments Cited 295 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Med Insights Cardiol
                Journal ID (iso-abbrev): Clin Med Insights Cardiol
                Journal ID (publisher-id): Clinical Medicine Insights: Cardiology
                Title: Clinical Medicine Insights. Cardiology
                Publisher: Libertas Academica
                ISSN (Electronic): 1179-5468
                Publication date Collection: 2014
                Publication date (Electronic): 19 October 2014
                Volume: 8
                Issue: Suppl 1
                Pages: 15-24
                Affiliations
                Cardiology Division, Department of Medicine, The Johns Hopkins Hospital, Baltimore, MD, USA.
                Author notes
                Article
                Publisher ID: cmc-suppl.1-2014-015
                DOI: 10.4137/CMC.S15716
                PMC ID: 4213201
                PubMed ID: 25368539
                SO-VID: d7638e45-5013-42fc-b984-95fa9e222664
                Copyright © © 2014 the author(s), publisher and licensee Libertas Academica Ltd.
                License:

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                Date received : 14 April 2014
                Date revision received : 03 June 2014
                Date accepted : 10 June 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: valvular aortic stenosis,surgical aortic valve replacement,transcatheter aortic valve replacement,balloon aortic valvuloplasty,aortic stenosis therapy
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: valvular aortic stenosis, surgical aortic valve replacement, transcatheter aortic valve replacement, balloon aortic valvuloplasty, aortic stenosis therapy

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