Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations

Anvesha Singh, Ian Ford, John P Greenwood, Jamal N Khan, Akhlaque Uddin, Colin Berry, Stefan Neubauer, Bernard Prendergast, Michael Jerosch-Herold, Bryan Williams, Nilesh J Samani, Gerry P McCann, Anvesha Singh, Ian Ford, John P Greenwood, Jamal N Khan, Akhlaque Uddin, Colin Berry, Stefan Neubauer, Bernard Prendergast, Michael Jerosch-Herold, Bryan Williams, Nilesh J Samani, Gerry P McCann

Abstract

Introduction: Aortic stenosis (AS) is the commonest valve disorder in the developed world requiring surgery. Surgery in patients with severe asymptomatic AS remains controversial. Exercise testing can identify asymptomatic patients at increased risk of death and symptom development, but with limited specificity, especially in older adults. Cardiac MRI (CMR), including myocardial perfusion reserve (MPR) may be a novel imaging biomarker in AS.

Aims: (1) To improve risk stratification in asymptomatic patients with AS and (2) to determine whether MPR is a better predictor of outcome than exercise testing and brain natriuretic peptide (BNP).

Method/design: Multicentre, prospective observational study in the UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for predicting outcome.

Population: 170 asymptomatic patients with moderate-to-severe AS, who would be considered for aortic valve replacement (AVR).

Primary outcome: Composite of: typical symptoms necessitating referral for AVR and major adverse cardiovascular events.

Follow-up: 12-30 months (minimum 12 months).

Primary hypothesis: MPR will be a better predictor of outcome than exercise testing and BNP.

Ethics/dissemination: The study has full ethical approval and is actively recruiting patients. Data collection will be completed in November 2014 and the study results will be submitted for publication within 6 months of completion.

Clinicaltrialsgov identifier: NCT01658345.

Figures

Figure 1
Figure 1
Flow chart demonstrating study plan.
Figure 2
Figure 2
MRI protocol used (4/2/3C, 4/2/3 chamber; LA, left atrial; LGE, late gadolinium enhancement; LV, left ventricular; LVOT, left ventricular outflow tract).

References

    1. Bridgewater B, Kinsman R, Walton P, et al. Demonstrating quality: the sixth National Adult Cardiac Surgery database report. Henley-on-Thames: Society for Cardiothoracic Surgery in Great Britain & Ireland 2008
    1. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on valvular heart disease. Eur Heart J 2003;24:1231–43
    1. Nkomo V, Gardin J, Skelton T, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005–11
    1. Varadarajan P, Kapoor N, Bansal RC, et al. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg 2006;82:2111–15
    1. Vahanian A, Baumgartner H, Bax J, et al. 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;28:230–68
    1. Bonow RO, Carabello BA, Chatterjee K, et al. 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. J Am Coll Cardiol 2008;52:e1–142
    1. Carabello BA. Aortic valve replacement should be operated on before symptom onset. Circulation 2012;126:112–17
    1. Shah PK. Severe aortic stenosis should not be operated on before symptom onset. Circulation 2012;126:118–25
    1. McCann GP, Steadman CD, Ray SG, et al. Managing the asymptomatic patient with severe aortic stenosis: randomised controlled trials of early surgery are overdue. Heart 2011;97:1119–21
    1. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000;343:611–17
    1. Kang DH, Park SJ, Rim JH, et al. Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. Circulation 2010;121:1502–9
    1. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation 2010;121:151–6
    1. Amato MC, Moffa PJ, Werner KE, et al. Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing. Heart 2001;86:381–6
    1. Lancellotti P, Lebois F, Simon M, et al. Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis. Circulation 2005;112(Suppl 9):I377–82
    1. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J 2005;26:1309–13
    1. Steadman CD, Ray S, Ng LL, et al. Natriuretic peptides in common valvular heart disease. J Am Coll Cardiol 2010;55:2034–48
    1. Das P. Determinants of symptoms and exercise capacity in aortic stenosis: a comparison of resting haemodynamics and valve compliance during dobutamine stress. Eur Heart J 2003;24:1254–63
    1. Rafique AM, Biner S, Ray I, et al. Meta-analysis of prognostic value of stress testing in patients with asymptomatic severe aortic stenosis. Am J Cardiol 2009;104:972–7
    1. Bonow RO, Carabello BA, Chatterjee K, et al. 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:e523–661
    1. Cioffi G, Faggiano P, Vizzardi E, et al. Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart 2011;97:301–7
    1. Kupari M, Turto H, Lommi J. Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure? Eur Heart J 2005;26:1790–6
    1. Rost C, Korder S, Wasmeier G, et al. Sequential changes in myocardial function after valve replacement for aortic stenosis by speckle tracking echocardiography. Eur J Echocardiogr 2010;11:584–9
    1. Dweck MR, Joshi S, Murigu T, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol 2011;58:1271–9
    1. Rajappan K, Rimoldi OE, Dutka DP, et al. Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries. Circulation 2002;105:470–6
    1. Rajappan K, Rimoldi OE, Camici PG, et al. Functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis. Circulation 2003;107:3170–5
    1. Flett AS, Sado DM, Quarta G, et al. Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging 2012;13:819–26
    1. Munt BI, Legget ME, Healy NL, et al. Effects of aortic valve replacement on exercise duration and functional status in adults with valvular aortic stenosis. Can J Cardiol 1997;13:346–50
    1. Krayenbuehl HP, Hess OM, Monrad ES, et al. Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement. Circulation 1989;79:744–55
    1. Azevedo CF, Nigri M, Higuchi ML, et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol 2010;56:278–87
    1. Debl K, Djavidani B, Buchner S, et al. Delayed hyperenhancement in magnetic resonance imaging of left ventricular hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy: visualisation of focal fibrosis. Heart 2006;92:1447–51
    1. Weidemann F, Herrmann S, Stork S, et al. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation 2009;120:577–84
    1. Shehata ML, Cheng S, Osman NF, et al. Myocardial tissue tagging with cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2009;11:55.
    1. Sandstede JJ, Johnson T, Harre K, et al. Cardiac systolic rotation and contraction before and after valve replacement for aortic stenosis: a myocardial tagging study using MR imaging. AJR Am J Roentgenol 2002;178:953–8
    1. Steadman CD, Jerosch-Herold M, Grundy B, et al. Determinants and functional significance of myocardial perfusion reserve in severe aortic stenosis. J Am Coll Cardiol Imaging 2012;5:182–9
    1. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 2009;10:1–25
    1. Das P, Rimington H, Smeeton N, et al. Determinants of symptoms and exercise capacity in aortic stenosis: a comparison of resting haemodynamics and valve compliance during dobutamine stress. Eur Heart J 2003;24:1254–63
    1. Wasserman K, Hanson J, Sue D, et al. Principles of exercise testing and interpretation. 3rd edn Lippincott Williams and Wilkins, 1999
    1. Jerosch-Herold M, Swingen C, Seethamraju RT. Myocardial blood flow quantification with MRI by model-independent deconvolution. Med Phys 2002;29:886–97
    1. Ugander M, Oki AJ, Hsu LY, et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J 2012;33:1268–78
    1. Monin JL, Lancellotti P, Monchi M, et al. Risk score for predicting outcome in patients with asymptomatic aortic stenosis. Circulation 2009;120:69–75

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