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Concept: Aortic valve stenosis

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Background We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. Methods We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. Results A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. Conclusions In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902 .).

Concepts: Epidemiology, Mortality rate, Medical terms, Heart, Risk, Surgery, Physician, Aortic valve stenosis

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IMPORTANCE Aortic stenosis is the most common form of valvular heart disease. Progression of aortic stenosis is very slow and highly variable. Decisions about when to perform valve surgery are made by subjective assessment of patient symptoms and objective measures of the valve and ventricular function by transthoracic echocardiography. OBJECTIVE To review current concepts regarding the development, progression, and assessment of aortic stenosis; the appropriate monitoring intervals for transthoracic echocardiography; and the indications for valve procedures. EVIDENCE REVIEW Guidelines and literature search. FINDINGS Angina, exertional syncope, and heart failure are key symptoms indicating a need for intervention. The frequency of valvular monitoring by transthoracic echocardiography is guided by the disease severity. Despite evidence of severe disease, valve procedures can safely be deferred if patients experience no symptoms and have normal left ventricular ejection fraction. Asymptomatic patients with severe aortic stenosis may subconsciously curtail their activities to avoid symptoms. Apparently, asymptomatic patients can undergo a carefully monitored exercise stress test to confirm both their asymptomatic status and hemodynamic response to exercise. Bioprosthetic valves are a good replacement alternative for older patients who are good surgical candidates and who have no need for warfarin therapy. For patients who are at high or very high risk of cardiac surgery, transcutaneous aortic valve implantation is an increasing available and preferred over medical management. CONCLUSIONS AND RELEVANCE Asymptomatic patients with severe aortic stenosis require frequent monitoring of their subjective symptoms combined with objective measurement of aortic valve gradient and ventricular function by transthoracic echocardiography. Although conventional surgical replacement remains the mainstay of therapy for aortic stenosis, transcutaneous aortic valve implantation options are evolving.

Concepts: Myocardial infarction, Cardiology, Heart failure, Ejection fraction, Heart, Echocardiography, Left ventricle, Aortic valve stenosis

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Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients.

Concepts: Aortic valve stenosis

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Calcific aortic stenosis (AS) is the most common form of valve disease in the western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understanding of its causes. The CHARGE extra-coronary calcium consortium reported a genome-wide association study (GWAS) demonstrating that genetic variants in LPA are strongly associated with aortic valve (AV) calcium and clinical AS. Using a Mendelian randomization study design, it was demonstrated that the effect of this genetic variant is mediated by plasma lipoprotein(a) (Lp[a]), directly implicating elevations in Lp(a) as a cause of AV calcium and progression to AS. This discovery has sparked intense interest in Lp(a) as a modifiable cause for aortic valve disease. Herein, we will review the mounting epidemiological and genetic findings in support of Lp(a) mediated valve disease, discuss potential mechanisms underlying this observation and outline the steps to translate this discovery to a much needed novel preventive and/or therapeutic strategy for aortic valve disease.

Concepts: Medicine, Genetics, Epidemiology, Genome-wide association study, Aortic valve, Western world, Western culture, Aortic valve stenosis

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Up to 40% of patients with aortic stenosis (AS) harbor discordant Doppler-echocardiographic findings, the most common of which is the presence of a small aortic valve area (≤1.0 cm(2)) suggesting severe AS, but a low gradient (<40 mm Hg) suggesting nonsevere AS. The purpose of this paper is to present the role of multimodality imaging in the diagnostic and therapeutic management of this challenging entity referred to as low-gradient AS. Doppler-echocardiography is critical to determine the subtype of low-gradient AS: that is, classical low-flow, paradoxical low-flow, or normal-flow. Patients with low-flow, low-gradient AS generally have a worse prognosis compared with patients with high-gradient or with normal-flow, low-gradient AS. Patients with low-gradient AS and evidence of severe AS benefit from aortic valve replacement (AVR). However, confirmation of the presence of severe AS is particularly challenging in these patients and requires a multimodality imaging approach including low-dose dobutamine stress echocardiography and aortic valve calcium scoring by multidetector computed tomography. Transcatheter AVR using a transfemoral approach may be superior to surgical AVR in patients with low-flow, low-gradient AS. Further studies are needed to confirm the best valve replacement procedure and prosthetic valve for each category of low-gradient AS and to identify patients with low-gradient AS in whom AVR is likely to be futile.

Concepts: Valvular heart disease, Aortic valve stenosis, Aortic valve area calculation

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Background Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. Methods We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. Results After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. Conclusions The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509 .).

Concepts: Positive predictive value, Negative predictive value, Cardiology, Echocardiography, Platelet, Von Willebrand factor, Von Willebrand disease, Aortic valve stenosis

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The prognostic importance of left ventricular (LV) mass in nonsevere asymptomatic aortic stenosis has not been documented in a large prospective study.

Concepts: Medical terms, Prognosis, Left ventricle, Asymptomatic, Aortic valve, Valvular heart disease, Aortic valve stenosis, Aortic insufficiency

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The aim of this study was to evaluate the relationship between aortic valve area (AVA) obtained by Doppler echocardiography and outcome in patients with severe asymptomatic aortic stenosis and to define a specific threshold of AVA for identifying asymptomatic patients at very high risk based on their clinical outcome.

Concepts: Medical terms, Doppler echocardiography, Echocardiography, Medical ultrasound, Asymptomatic, Valvular heart disease, Aortic valve stenosis, Aortic valve area calculation

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Aims: Transcatheter aortic valve implantation (TAVI) has become a viable option for selected high-risk patients with severe and symptomatic aortic stenosis. First- and second-generation TAVI devices are either self- or balloon-expandable, and are often not repositionable or not fully retrievable, leading to suboptimal positioning in some cases. This may result in paravalvular regurgitation, AV conduction delay, or compromise of coronary perfusion. A broader application of TAVI requires advances in both valve and delivery systems. Therefore, in order to facilitate accurate positioning, to minimise paravalvular leakage, possibly to reduce the risk of AV conduction delay, and possibly to be able to abort the procedure, a “next-generation” TAVI system has been developed which is repositionable and retrievable, the TRINITY heart valve system. Methods and results: The TRINITY heart valve system was implanted in a first-in-human study using the transapical approach to demonstrate feasibility and procedural success. All endpoints were adjudicated according to VARC definitions at seven and 30 days. The TRINITY heart valve system was implanted in a 74-year-old patient with severe symptomatic aortic valve stenosis. In this case, repositioning of the TRINITY resulted in optimal position without paravalvular leakage and with perfect function. Conclusions: The TRINITY heart valve is a repositionable and retrievable TAVI system. Both the implantation result and short-term clinical and haemodynamic outcome were excellent.

Concepts: Cardiology, Heart, Tricuspid valve, Left ventricle, Valvular heart disease, Artificial heart valve, Aortic valve stenosis, Aortic insufficiency

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It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome.

Concepts: Aortic valve stenosis