Mitral Regurgitation and Aortic Stenosis: Prevalent and Progressive Valve Diseases


Aortic Valve Stenosis Overview

Aortic stenosis represents 34% of the native valvular diseases in industrialized nations, and is the most common primary valve disease requiring surgery or transcatheter intervention in Europe and North America.1,2

Degenerative calcification is the leading cause (81.9%) of aortic stenosis in older adults according to the Euro Heart Survey on Valvular Heart Disease.3 Due to aging populations its prevalence is growing: the number of elderly patients with calcific aortic stenosis is projected to more than double by 2050 in both Europe and the U.S.4

    Aortic Stenosis Statistics

    From the onset of symptoms, risk of mortality from aortic valve stenosis is approximately 25% at 1 year and 50% at 2 years if patients, who are already medically treated, do not undergo aortic valve replacement–this is because replacement is the only effective treatment.5,6

    Among this same patient subset, more than 50% of deaths are sudden cardiac deaths.5 It is theorized that the fatal arrhythmias that proceed aortic valve stenosis are secondary to inadequate blood flow through the aortic valve into the coronary arteries.7

    Each year, approximately 280,000 aortic valve prostheses are implanted worldwide, and that figure is expected to reach 850,000 annually by 2050.8

    Referrals for Aortic Stenosis

    If referring physicians determine that intervention is warranted, they should refer patients to heart valve centers with highly specialized multidisciplinary teams, comprehensive equipment, and sufficient procedural volumes to offer patients high-quality care.2

    CATEGORIES of Aortic Stenosis

    There are 4 categories of aortic stenosis:2

    1. Severe aortic stenosis: high-gradient stenosis regardless of left ventricular ejection fraction (LVEF), with valve area < 1 cm2 and
      mean gradient > 40 mmHg

    For the remaining 3 categories the valve area is < 1 cm2 and the mean gradient is < 40 mmHg.

    1. Low-flow, low-gradient aortic stenosis with LVEF < 50%—echocardiography can determine severity
    2. Low-flow, low-gradient aortic stenosis with LVEF ≥ 50%—echocardiography can determine severity
    3. Moderate aortic stenosis: normal-flow, low-gradient stenosis with LVEF ≥ 50%

    Pathophysiology of Aortic Stenosis

    Elevated left ventricular systolic blood pressure accompanies aortic stenosis, yet compensatory mechanisms include LV hypertrophy and atrial augmentation of preload—so cardiac output can be maintained for many years. As the disease worsens, these adaptations become inadequate and the patient may eventually develop symptoms of decreased cardiac output and heart failure.5


    Due to the often slow, progressive nature of aortic stenosis, patients may not recognize symptoms because they may have gradually limited their daily activity levels. Typical initial symptoms are dyspnea on exertion or decreased exercise tolerance.6

    Most patients with aortic stenosis are first diagnosed when cardiac auscultation reveals a systolic murmur. Patient symptoms which are late manifestations of the disease include:5

    • Angina pectoris typically upon physical exertion
    • Heart failure symptoms such as paroxysmal nocturnal dyspnea, orthopnea, dyspnea on exertion, and shortness of breath
    • Syncope, often upon exertion when systemic vasodilatation in the presence of a fixed forward stroke volume causes the arterial systolic blood pressure to drop
    • Systolic hypertension

    Asymptomatic patients with severe aortic stenosis should be re-evaluated at least every 6 months to determine if there is a change in symptoms such as exercise tolerance.2

    Considerations for Referring Physicians

    Primary care physicians should consider aortic stenosis in adults who present with any of the symptoms noted above and who also present with a systolic murmur. A low-intensity murmur alone does not exclude aortic stenosis, especially as left ventricular systolic function deteriorates.9

    Physicians are increasingly recommending aortic valve replacement even in asymptomatic patients with severe aortic stenosis, particularly if there is evidence of rapid disease progression.10

    Intervention: SAVR and TAVI

    The strongest indication for intervention is the presence of symptoms. Early intervention is strongly recommended in all symptomatic patients with severe aortic stenosis because of the high mortality rate.2

    The heart team should choose surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) by considering each patient’s cardiac characteristics, comorbidities, and the risks and benefits of both interventions.2 In the U.S., the first TAVI device approval occurred in late 2011 for patients with symptomatic, severe aortic stenosis deemed at extreme risk for surgical aortic valve replacement (SAVR). Subsequently, label expansion and new device approvals have extended access to TAVR to patients deemed to be at high risk (2012), intermediate risk (2016), and low risk (2019) for SAVR, as well as to patients with degenerated surgically implanted aortic tissue valves.11

    In Europe, intermediate risk approval was granted in 201613 and low risk approval was granted in 2019.14

    In asymptomatic patients, physicians need to carefully weigh the benefits vs risks for SAVR; TAVI is being studied in this population. If asymptomatic patients demonstrate predictors of rapid symptom development, physicians may perform surgery early, especially when surgical risk is low.

    The Increase in TAVI Procedures: Primarily Patients Otherwise Untreated

    Data from the U.S. revealed that the annual volume of TAVI have increased every year since 2011, and in 2019, TAVI volume (72,991) exceeded all forms of surgical AVR (57,626). For the first time, SAVR volume declined in 2019. The annual number of patients deemed high/extreme risk initially increased but then stabilized but remains substantial; this group accounts for approximately 31,000 to 33,000 procedures in each of the last 4 years. The volume of intermediate-risk patients steadily has increased to 32,697 procedures in 2019. The number of patients deemed low risk is starting to increase, with 8,395 patients treated in 2019 representing 11.5% of all TAVI patients. Procedures in 2019 were predominantly classified as elective (91.4%); procedures were considered urgent in 8.0%, emergent in 0.3%, and salvage in 0.07%. The year-by-year decline in mortality from the early TAVI experience to 2019 has been steady and dramatic, with in-hospital mortality falling from 5.4% to 1.3%, and 30-day mortality decreasing from 7.2% to 2.5%. The dramatic decrease in Length of Stay, the high percentage of patients being discharged directly to home, and 8 of 10 patients, including high-extreme risk patients, achieving at 1 year the “alive and well” patient reported outcome are all testaments to the on-going reduced burden of TAVI treatment and achievement of benefits to patients including those who are elderly with a heavy dose of comorbid conditions.11

    Medical Therapy for Aortic Stenosis

    For aortic stenosis patients, medical therapy cannot improve outcomes compared with the natural history of the disease.7

    2017 Updates to the European Society of Cardiology Valvular Heart Disease Guidelines

    Among the primary changes are the following:2

    Symptomatic Aortic Stenosis Patients

    • Recommending TAVI in patients not suitable for SAVR
    • Recommending SAVR in patient at low surgical risk and with no other contraindicating risk factors
    • Stating that intervention “should be” considered (vs “may be” per the 2012 Guidelines) in patients with low-flow, low-gradient aortic stenosis and reduced EF without flow reserve

    Asymptomatic Aortic Stenosis Patients

    • Stating that surgery is indicated when there are markedly high brain natriuretic peptide (BNP) levels confirmed by repeated measurements—increased pressure gradient and LV hypertrophy are no longer required
    • Adding an indication for surgery in patients with severe pulmonary hypertension

    Patients with Severe Aortic Regurgitation and Aortic Root Disease

    • Suggesting heart team discussion for patients in whom valve repair may be a good alternative to replacement
    • Stating that surgery should be considered in patients with aortic root disease with maximal ascending aortic diameter ≥ 45 mm, in patients with specific genetic mutations

    TAVI Valve-in-Valve

    • Stating that transcatheter aortic valve-in-valve implantation should be considered for patients with prosthetic valve dysfunction


    • Recommending that post-TAVI patients at high risk of bleeding should be considered for single antiplatelet therapy

    Choosing a Prosthetic Valve

    Physicians should choose between a mechanical and a biological valve primarily by taking into account:2

    • The possibility of anticoagulation-related bleeding and thromboembolism with a mechanical valve
    • The possibility of tissue valve deterioration
    • The patient’s preferences and lifestyle

    Bioprostheses should be considered in patients whose life expectancy is lower than the presumed durability of the bioprosthesis and in those with increased bleeding risk.2

    The Importance of Patient Involvement in Valve Choice

    A study in the Netherlands, examining patients with either bioprosthetic or mechanical valves, found that 89% of the patients said it is very important to be involved in prosthetic valve selection. However, only 64% agreed that they actually had been involved in the decision, and 40% reported that they did not receive enough information. A better patient experience in the decision-making process was associated with better mental health (p = 0.036).12

    Bicuspid Aortic Valve

    Most patients with a bicuspid aortic valve will develop aortic stenosis or aortic regurgitation over their lifetime. In 20%-30% of patients with bicuspid valves, other family members also have bicuspid valve disease and/or a related aortic abnormality. There are no proven drug therapies that have been shown to reduce the rate of progression of aortic dilation in patients with aortopathy associated with bicuspid aortic valve.6

    The information provided is not intended for medical diagnosis or treatment as a substitute for professional advice.  Consult with a physician or qualified healthcare provider for appropriate medical advices.

    MAT-2107049 V1.0 | Item approved for Global OUS use only.

    1. Capoulade R, et al. Assessment of aortic valve disease: role of imaging modalities. Curr Treat Options Cardio Med. 2015;17: 49. doi: 10.1007/s11936-015-0409-7.
    2. Baumgartner H, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739–2791. doi:10.1093/eurheartj/ehx391.
    3. Faggiano P, et al. Epidemiology and cardiovascular risk factors in aortic stenosis. Cardiovasc Ultrasound. 2006;4:27. doi: 10.1186/1476-7120-4-27.
    4. Benjamin EJ, et al. Heart disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67-e492. doi: 10.1161/CIR.0000000000000558.
    5. Ren X. Aortic stenosis. MedScape. Published March 23, 2017.
    6. Nishimura RA, et al. 2014 AHA/ACC Guideline for the management of patients with valvular heart disease. Circulation. 2014;129(23):2440-2492. doi: 10.1161/CIR.0000000000000029.
    7. Kulick DL. Aortic valve stenosis symptoms, treatment, types, and surgery. MedicineNet. Reviewed November 13, 2017.
    8. Zenses AS, et al. Prosthetic aortic valves. Encyclopedia of Biomedical Engineering. 2018. Accessed September 17, 2018.
    9. Grimard BH, et al. Aortic stenosis: diagnosis and treatment. Am Fam Physician. 2016;93(5):371-378.
    10. Bonow RO, et al. Management strategies and future challenges for aortic valve disease. Lancet. 2016;387:1312–1323.
    11. Carroll JD, et al. STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2020;76:2492–516. doi: 10.1016/j.jacc.2020.09.595.
    12. Korteland NM, et al. Quality of life and prosthetic aortic valve selection in non-elderly adult patients. Interact Cardiovasc Thorac Surg. 2016;22(6):723-728. doi: 10.1093/icvts/ivw021.

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