Meta-Analysis of Prognostic Value of Stress Testing in Patients With Asymptomatic Severe Aortic Stenosis

      The management strategy in asymptomatic patients with severe aortic stenosis (AS) is controversial. Aortic valve replacement has significant morbidity and mortality, while there is a risk for sudden cardiac death with conservative management. There is no consensus on the prognostic value of stress testing to stratify management. A pooled analysis of studies in patients with severe AS was performed to assess the prognostic value of stress testing for adverse events, including angina, dyspnea, acute heart failure, sudden death, and symptoms requiring aortic valve replacement. A search of published research was performed using the terms “stress test” and “asymptomatic aortic stenosis.” A random-effects model was used to calculate pooled odds ratios and 95% confidence intervals. Data from 7 studies were included (491 patients with asymptomatic severe AS). None of the patients experienced any complications during or after stress testing. There were no sudden deaths in the patients with normal stress test results after 1 year of follow-up, while 5% with abnormal stress test results had sudden cardiac death. Overall, 52 of 253 patients (21%) with normal stress test results had adverse cardiac events, compared with 156 of 238 (66%) with abnormal stress test results (odds ratio 0.12, 95% confidence interval 0.07 to 0.21, p <0.001). In conclusion, stress testing in asymptomatic patients with severe AS is safe and identifies patients at risk for adverse cardiac events and sudden cardiac death. These data suggest that stress tests can be used for risk stratification and for deciding on the timing of aortic valve replacement in asymptomatic patients with severe AS.
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        • Otto C.M.
        • Burwash I.G.
        • Legget M.E.
        • Munt B.I.
        • Fujioka M.
        • Healy N.L.
        • Kraft C.D.
        • Miyake-Hull C.Y.
        • Schwaegler R.G.
        Prospective study of asymptomatic valvular aortic stenosis.
        Circulation. 1997; 95: 2262-2270
        • Alborino D.
        • Hoffmann J.L.
        • Fournet P.C.
        • Bloch A.
        Value of exercise testing to evaluate the indication for surgery in asymptomatic patients with valvular aortic stenosis.
        J Heart Valve Dis. 2002; 11: 204-209
        • Amato M.C.
        • Moffa P.J.
        • Werner K.E.
        • Ramires J.A.
        Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing.
        Heart. 2001; 86: 381-386
        • Das P.
        • Rimington H.
        • Chambers J.
        Exercise testing to stratify risk in aortic stenosis.
        Eur Heart J. 2005; 26: 1309-1313
        • Lancellotti P.
        • Lebois F.
        • Simon M.
        • Tombeux C.
        • Chauvel C.
        • Pierard L.A.
        Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis.
        Circulation. 2005; 112: I-377-I-382
        • Maréchaux S.
        • Ennezat P.V.
        • LeJemtel T.H.
        • Polge A.S.
        • de Groote P.
        • Asseman P.
        • Nevière R.
        • Le Tourneau T.
        • Deklunder G.
        Left ventricular response to exercise in aortic stenosis: an exercise echocardiographic study.
        Echocardiography. 2007; 24: 955-959
        • Peidro R.
        • Brion G.
        • Angelino A.
        Exercise testing in asymptomatic aortic stenosis.
        Cardiology. 2007; 108: 258-264
        • Takeda S.
        • Rimington H.
        • Chambers J.
        Prediction of symptom-onset in aortic stenosis: a comparison of pressure drop/flow slope and haemodynamic measures at rest.
        Int J Cardiol. 2001; 81: 131-137
        • Weisenberg D.
        • Shapira Y.
        • Vaturi M.
        • Monakier D.
        • Iakobishvili Z.
        • Battler A.
        • Sagie A.
        Does exercise echocardiography have an added value over exercise testing alone in asymptomatic patients with severe aortic stenosis?.
        J Heart Valve Dis. 2008; 17: 376-380
        • Clyne C.A.
        • Arrighi J.A.
        • Maron B.J.
        • Dilsizian V.
        • Bonow R.O.
        • Cannon III, R.O.
        Systemic and left ventricular responses to exercise stress in asymptomatic patients with valvular aortic stenosis.
        Am J Cardiol. 1991; 68: 1469-1476
        • Van Pelt N.C.
        • Kerr A.J.
        • Legget M.E.
        • Pasupati S.
        • Whalley G.
        • Wong S.
        • Zeng I.
        • Stewart R.A.
        Increased B-type natriuretic peptide is associated with an abnormal blood pressure response to exercise in asymptomatic aortic stenosis.
        Int J Cardiol. 2008; 127: 313-320
        • Otto C.M.
        • Pearlman A.S.
        • Kraft C.D.
        • Miyake-Hull C.Y.
        • Burwash I.G.
        • Gardner C.J.
        Physiologic changes with maximal exercise in asymptomatic valvular aortic stenosis assessed by Doppler echocardiography.
        J Am Coll Cardiol. 1992; 20: 1160-1167
        • Iung B.
        • Baron G.
        • Butchart E.G.
        • Delahaye F.
        • Gohlke-Bärwolf C.
        • Levang O.W.
        • Tornos P.
        • Vanoverschelde J.L.
        • Vermeer F.
        • Boersma E.
        • Ravaud P.
        • Vahanian A.
        A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease.
        Eur Heart J. 2003; 24: 1231-1243
        • Bax L.
        • Yu L.M.
        • Ikeda N.
        • Tsuruta H.
        • Moons K.G.M.
        MIX: comprehensive free software for meta-analysis of causal research data.
        (Version 1.7. 2008) (Accessed October 1, 2008)
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Rosenhek R.
        • Maurer G.
        • Baumgartner H.
        Should early elective surgery be performed in patients with severe but asymptomatic aortic stenosis?.
        Eur Heart J. 2002; 23: 1417-1421
        • Dal-Bianco J.P.
        • Khandheria B.K.
        • Mookadam F.
        • Gentile F.
        • Sengupta P.P.
        Management of asymptomatic severe aortic stenosis.
        J Am Coll Cardiol. 2008; 52: 1279-1292
        • Bonow R.O.
        • Carabello B.A.
        • Chatterjee K.
        • de Leon Jr, A.C.
        • Faxon D.P.
        • Freed M.D.
        • Gaasch W.H.
        • Lytle B.W.
        • Nishimura R.A.
        • O'Gara P.T.
        • O'Rourke R.A.
        • Otto C.M.
        • Shah P.M.
        • Shanewise J.S.
        • 2006 Writing Committee MembersAmerican College of Cardiology/American Heart Association Task Force
        2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
        Circulation. 2008; 118: e523-e661
        • Vahanian A.
        • Baumgartner H.
        • Bax J.
        • Butchart E.
        • Dion R.
        • Filippatos G.
        • Flachskampf F.
        • Hall R.
        • Iung B.
        • Kasprzak J.
        • Nataf P.
        • Tornos P.
        • Torracca L.
        • Wenink A.
        • Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology
        • E.S.C. Committee for Practice Guidelines
        Guidelines on the management of valvular heart disease: the Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.
        Eur Heart J. 2007; 28: 230-268
      1. Society of Thoracic Surgery, National Database, Spring 2002, Executive Summary.
        • Edwards F.H.
        • Peterson E.D.
        • Coombs L.P.
        • DeLong E.R.
        • Jamieson W.R.
        • Shroyer A.L.W.
        • Grover F.L.
        Prediction of operative mortality after valve replacement surgery.
        J Am Coll Cardiol. 2001; 37: 885-892
        • Rosenhek R.
        • Binder T.
        • Porenta G.
        • Lang I.
        • Christ G.
        • Schemper M.
        • Maurer G.
        • Baumgartner H.
        Predictors of outcome in severe, asymptomatic aortic stenosis.
        N Engl J Med. 2000; 343: 611-617
        • Pellikka P.A.
        • Sarano M.E.
        • Nishimura R.A.
        • Malouf J.F.
        • Bailey K.R.
        • Scott C.G.
        • Barnes M.E.
        • Tajik A.J.
        Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up.
        Circulation. 2005; 111: 3290-3295
        • Kelly T.A.
        • Rothbart R.M.
        • Cooper C.M.
        • Kaiser D.L.
        • Smucker M.L.
        • Gibson R.S.
        Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis.
        Am J Cardiol. 1988; 61: 123-130
        • Ross Jr, J.
        • Braunwald E.
        Aortic stenosis.
        Circulation. 1968; 38: 61-67
        • Pai R.G.
        • Kapoor N.
        • Bansal R.C.
        • Varadarajan P.
        Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.
        Ann Thorac Surg. 2006; 82: 2116-2122
        • Brown M.L.
        • Pellikka P.A.
        • Schaff H.V.
        • Scott C.G.
        • Mullany C.J.
        • Sundt T.M.
        • Dearani J.A.
        • Daly R.C.
        • Orszulak T.A.
        The benefits of early valve replacement in asymptomatic patients with severe aortic stenosis.
        J Thorac Cardiovasc Surg. 2008; 135: 308-315
        • Rahimtoola S.H.
        The problem of valve prosthesis-patient mismatch.
        Circulation. 1978; 58: 20-24
        • Piérard L.A.
        • Lancellotti P.
        Stress testing in valve disease.
        Heart. 2007; 93: 766-772