Medical management of asymptomatic aortic stenosis in adults
- Catherine M Otto, MD
Catherine M Otto, MD
- Editor-in-Chief — Cardiovascular Medicine
- Section Editor — Cardiac Evaluation; Valvular Disease
- Professor of Medicine
- University of Washington
In individuals with normal aortic valves, the effective area of valve opening equals the cross-sectional area of the left ventricular outflow tract, which is about 3.0 to 4.0 cm2 in adults. As aortic stenosis (AS) develops, a minimal valve gradient is present until the orifice area becomes less than half of normal. The natural history of AS therefore begins with a prolonged asymptomatic period associated with minimal mortality.
Serial hemodynamic examinations in several studies show that progressive valve obstruction occurs in nearly all adults with calcific aortic valve disease once even mild valve obstruction is present (figure 1). Patients remain asymptomatic as aortic velocity increases and valve area decreases until the severity of obstruction results in an inadequate cardiac output with exercise leading to symptom onset. (See "Natural history, epidemiology, and prognosis of aortic stenosis", section on 'Risk factors for progression'.)
In general, symptoms in patients with AS and normal left ventricular systolic function rarely occur until the stenosis is severe as defined by valve area <1.0 cm2, aortic jet velocity over 4.0 m/sec, and/or mean transvalvular gradient exceeding 40 mmHg (table 1). However, many patients do not develop symptoms until even more severe valve obstruction is present, and some patients with less severe AS or with mixed stenosis and regurgitation are symptomatic. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Complications'.)
The only effective treatment for symptomatic severe AS is valve replacement (surgical aortic valve replacement [SAVR] or transcatheter aortic valve implantation [TAVI]). Choice of therapy in patients with symptomatic severe AS is discussed separately. (See "Choice of therapy for symptomatic severe aortic stenosis".)
Among asymptomatic patients, there are no medical therapies that have been proven to delay progression of the leaflet disease. Although retrospective studies of statin therapy were promising, a large randomized prospective study demonstrated that statin therapy does not prevent disease progression. However, many patients meet criteria for statin therapy based on standard risk factor evaluation and should be treated according to guidelines. In addition, most adults with AS have concurrent cardiac conditions that require therapy, including hypertension, coronary heart disease, atrial fibrillation, and left ventricular dysfunction.
- Nishimura RA, Otto CM, Bonow RO, et al. 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. J Am Coll Cardiol 2014; 63:e57.
- Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005; 111:3290.
- Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000; 343:611.
- Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation 2010; 121:151.
- Kang DH, Park SJ, Rim JH, et al. Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. Circulation 2010; 121:1502.
- Lindman BR, Clavel MA, Mathieu P, et al. Calcific aortic stenosis. Nat Rev Dis Primers 2016; 2:16006.
- Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009; 119:1541.
- Pohle K, Mäffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001; 104:1927.
- Palta S, Pai AM, Gill KS, Pai RG. New insights into the progression of aortic stenosis: implications for secondary prevention. Circulation 2000; 101:2497.
- Rallidis L, Naoumova RP, Thompson GR, Nihoyannopoulos P. Extent and severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia. Heart 1998; 80:583.
- Agmon Y, Khandheria BK, Meissner I, et al. Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study. J Am Coll Cardiol 2001; 38:827.
- Shavelle DM, Takasu J, Budoff MJ, et al. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet 2002; 359:1125.
- Novaro GM, Tiong IY, Pearce GL, et al. Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis. Circulation 2001; 104:2205.
- Bellamy MF, Pellikka PA, Klarich KW, et al. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol 2002; 40:1723.
- Rosenhek R, Rader F, Loho N, et al. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation 2004; 110:1291.
- Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol 2001; 88:693.
- Thiago L, Tsuji SR, Nyong J, et al. Statins for aortic valve stenosis. Cochrane Database Syst Rev 2016; 9:CD009571.
- Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005; 352:2389.
- Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359:1343.
- Otto CM. Calcific aortic stenosis--time to look more closely at the valve. N Engl J Med 2008; 359:1395.
- Chan KL, Teo K, Dumesnil JG, et al. Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 2010; 121:306.
- van der Linde D, Yap SC, van Dijk AP, et al. Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial). Am J Cardiol 2011; 108:265.
- O'Brien KD, Probstfield JL, Caulfield MT, et al. Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med 2005; 165:858.
- Nadir MA, Wei L, Elder DH, et al. Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis. J Am Coll Cardiol 2011; 58:570.
- Stewart RA, Kerr AJ, Cowan BR, et al. A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis. Am Heart J 2008; 156:348.
- Aurigemma GP, Keaney JF Jr. Renin-angiotensin system inhibition for aortic stenosis "A II, Bruté?". J Am Coll Cardiol 2011; 58:577.
- Skolnick AH, Osranek M, Formica P, Kronzon I. Osteoporosis treatment and progression of aortic stenosis. Am J Cardiol 2009; 104:122.
- Innasimuthu AL, Katz WE. Effect of bisphosphonates on the progression of degenerative aortic stenosis. Echocardiography 2011; 28:1.
- Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation 1993; 87:I121.
- Roberts WC, Oluwole BO, Fernicola DJ. Comparison of active infective endocarditis involving a previously stenotic versus a previously nonstenotic aortic valve. Am J Cardiol 1993; 71:1082.
- Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116:1736.
- Kadem L, Dumesnil JG, Rieu R, et al. Impact of systemic hypertension on the assessment of aortic stenosis. Heart 2005; 91:354.
- Zile MR, Gaasch WH. Heart failure in aortic stenosis - improving diagnosis and treatment. N Engl J Med 2003; 348:1735.
- Gosavi S, Channa R, Mukherjee D. Systemic Hypertension in Patients with Aortic Stenosis: Clinical Implications and Principles of Pharmacological Therapy. Cardiovasc Hematol Agents Med Chem 2015; 13:50.
- Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens 2001; 15:659.
- Badano L, Cassottano P, Bertoli D, et al. Changes in effective aortic valve area during ejection in adults with aortic stenosis. Am J Cardiol 1996; 78:1023.
- Bermejo J, García-Fernández MA, Torrecilla EG, et al. Effects of dobutamine on Doppler echocardiographic indexes of aortic stenosis. J Am Coll Cardiol 1996; 28:1206.
- Burwash IG, Forbes AD, Sadahiro M, et al. Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis. Am J Physiol 1993; 265:H1734.
- Chambers JB, Sprigings DC, Cochrane T, et al. Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves. Br Heart J 1992; 67:193.
- Shah SP, Kumar A, Draper TS, Gaasch WH. Hypertension in patients with severe aortic stenosis: emphasis on antihypertensive treatment and the risk of syncope. Curr Hypertens Rev 2014; 10:149.
- Kvidal P, Bergström R, Hörte LG, Ståhle E. Observed and relative survival after aortic valve replacement. J Am Coll Cardiol 2000; 35:747.
- Julius BK, Spillmann M, Vassalli G, et al. Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts. Circulation 1997; 95:892.
- Hasdai D, Lev EI, Behar S, et al. Acute coronary syndromes in patients with pre-existing moderate to severe valvular disease of the heart: lessons from the Euro-Heart Survey of acute coronary syndromes. Eur Heart J 2003; 24:623.
- Bonow RO, Nishimura RA, Thompson PD, Udelson JE. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 5: Valvular Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2385.
- Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. Circulation 2015; 132:624.
- Chockalingam A, Venkatesan S, Subramaniam T, et al. Safety and efficacy of angiotensin-converting enzyme inhibitors in symptomatic severe aortic stenosis: Symptomatic Cardiac Obstruction-Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS). Am Heart J 2004; 147:E19.
- Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005; 111:920.
- SERIAL EVALUATION
- PREVENTION OF DISEASE PROGRESSION
- Hypercholesterolemia and statin therapy
- - Rationale
- - Statin trials
- - Statin conclusion
- Other potential preventative therapies
- ENDOCARDITIS PROPHYLAXIS
- CORONARY ARTERY DISEASE
- Risk factor reduction
- Symptomatic CAD
- PHYSICAL ACTIVITY AND EXERCISE
- ATRIAL FIBRILLATION
- HEART FAILURE
- CONCURRENT DISEASE OF THE AORTA
- NONCARDIAC SURGERY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS