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Concept: Aortic valve stenosis


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 number, NCT01240902 .).

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


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


Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS).

Concepts: Male, Gender, Aortic valve stenosis, Aortic valve area calculation


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


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


Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS.

Concepts: Aortic valve stenosis


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


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; number, NCT02628509 .).

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


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


The American College of Cardiology collaborated with the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons to develop and evaluate Appropriate Use Criteria (AUC) for the treatment of patients with severe aortic stenosis (AS). This is the first AUC to address the topic of AS and its treatment options, including surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). A number of common patient scenarios experienced in daily practice were developed along with assumptions and definitions for those scenarios, which were all created using guidelines, clinical trial data, and expert opinion in the field of AS. The 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(1) and its 2017 focused update paper (2) were used as the primary guiding references in developing these indications. The writing group identified 95 clinical scenarios based on patient symptoms and clinical presentation, and up to 6 potential treatment options for those patients. A separate, independent rating panel was asked to score each indication from 1 to 9, with 1-3 categorized as “Rarely Appropriate,” 4-6 as “May Be Appropriate,” and 7-9 as “Appropriate.” After considering factors such as symptom status, left ventricular (LV) function, surgical risk, and the presence of concomitant coronary or other valve disease, the rating panel determined that either SAVR or TAVR is Appropriate in most patients with symptomatic AS at intermediate or high surgical risk; however, situations commonly arise in clinical practice in which the indications for SAVR or TAVR are less clear, including situations in which 1 form of valve replacement would appear reasonable when the other is less so, as do other circumstances in which neither intervention is the suitable treatment option. The purpose of this AUC is to provide guidance to clinicians in the care of patients with severe AS by identifying the reasonable treatment and intervention options available based on the myriad clinical scenarios with which patients present. This AUC document also serves as an educational and quality improvement tool to identify patterns of care and reduce the number of rarely appropriate interventions in clinical practice.

Concepts: Clinical trial, Cardiology, Heart, Surgery, Valvular heart disease, Thoracic surgery, Aortic valve stenosis, Aortic insufficiency